TCDB is operated by the Saier Lab Bioinformatics Group
TRANSPORTERS & DISEASES:
TCIDOMIM NameProtein NameAccessionOMIM
9.B.38.2.1 HYPERTENSION, ESSENTIAL The 8 TMS GP M6a homologue (577 aas) A0E9B5 145500
9.B.87.1.1 OSTEOPOROSIS-PSEUDOGLIOMA SYNDROME; OPPG

Low density lipoprotein receptor-related protein 2 precursor (Megalin - 4660aas; glycoprotein 330) [required for SelP uptake in kidney]. May take up cadmium-metallothionein complexes via receptor-mediated endocytosis (Thévenod, 2010).

A2ARV4 259770
9.B.87.1.1 LOW DENSITY LIPOPROTEIN RECEPTOR-RELATED PROTEIN 1; LRP1

Low density lipoprotein receptor-related protein 2 precursor (Megalin - 4660aas; glycoprotein 330) [required for SelP uptake in kidney]. May take up cadmium-metallothionein complexes via receptor-mediated endocytosis (Thévenod, 2010).

A2ARV4 107770
9.B.87.1.1 FIBRILLIN 2; FBN2

Low density lipoprotein receptor-related protein 2 precursor (Megalin - 4660aas; glycoprotein 330) [required for SelP uptake in kidney]. May take up cadmium-metallothionein complexes via receptor-mediated endocytosis (Thévenod, 2010).

A2ARV4 612570
9.B.87.1.1 CUTIS LAXA, AUTOSOMAL DOMINANT

Low density lipoprotein receptor-related protein 2 precursor (Megalin - 4660aas; glycoprotein 330) [required for SelP uptake in kidney]. May take up cadmium-metallothionein complexes via receptor-mediated endocytosis (Thévenod, 2010).

A2ARV4 123700
9.B.87.1.1 GELEOPHYSIC DYSPLASIA

Low density lipoprotein receptor-related protein 2 precursor (Megalin - 4660aas; glycoprotein 330) [required for SelP uptake in kidney]. May take up cadmium-metallothionein complexes via receptor-mediated endocytosis (Thévenod, 2010).

A2ARV4 231050
9.B.87.1.1 CUTIS LAXA, AUTOSOMAL RECESSIVE, TYPE I

Low density lipoprotein receptor-related protein 2 precursor (Megalin - 4660aas; glycoprotein 330) [required for SelP uptake in kidney]. May take up cadmium-metallothionein complexes via receptor-mediated endocytosis (Thévenod, 2010).

A2ARV4 219100
9.B.87.1.1 HEMICENTIN; HMCN1

Low density lipoprotein receptor-related protein 2 precursor (Megalin - 4660aas; glycoprotein 330) [required for SelP uptake in kidney]. May take up cadmium-metallothionein complexes via receptor-mediated endocytosis (Thévenod, 2010).

A2ARV4 608548
9.B.87.1.1 ALAGILLE SYNDROME 1; ALGS1

Low density lipoprotein receptor-related protein 2 precursor (Megalin - 4660aas; glycoprotein 330) [required for SelP uptake in kidney]. May take up cadmium-metallothionein complexes via receptor-mediated endocytosis (Thévenod, 2010).

A2ARV4 118450
9.B.87.1.1 ATRIOVENTRICULAR SEPTAL DEFECT; AVSD

Low density lipoprotein receptor-related protein 2 precursor (Megalin - 4660aas; glycoprotein 330) [required for SelP uptake in kidney]. May take up cadmium-metallothionein complexes via receptor-mediated endocytosis (Thévenod, 2010).

A2ARV4 600309
9.B.87.1.1 CYSTEINE-RICH PROTEIN WITH EGF-LIKE DOMAINS 1; CRELD1

Low density lipoprotein receptor-related protein 2 precursor (Megalin - 4660aas; glycoprotein 330) [required for SelP uptake in kidney]. May take up cadmium-metallothionein complexes via receptor-mediated endocytosis (Thévenod, 2010).

A2ARV4 607170
9.B.87.1.1 FRONTOTEMPORAL LOBAR DEGENERATION WITH UBIQUITIN-POSITIVE INCLUSIONS; FTLDU

Low density lipoprotein receptor-related protein 2 precursor (Megalin - 4660aas; glycoprotein 330) [required for SelP uptake in kidney]. May take up cadmium-metallothionein complexes via receptor-mediated endocytosis (Thévenod, 2010).

A2ARV4 607485
9.B.87.1.1 MEGALOBLASTIC ANEMIA 1

Low density lipoprotein receptor-related protein 2 precursor (Megalin - 4660aas; glycoprotein 330) [required for SelP uptake in kidney]. May take up cadmium-metallothionein complexes via receptor-mediated endocytosis (Thévenod, 2010).

A2ARV4 261100
9.B.87.1.1 ENTEROKINASE DEFICIENCY

Low density lipoprotein receptor-related protein 2 precursor (Megalin - 4660aas; glycoprotein 330) [required for SelP uptake in kidney]. May take up cadmium-metallothionein complexes via receptor-mediated endocytosis (Thévenod, 2010).

A2ARV4 226200
9.B.87.1.1 POLYCYSTIC LIVER DISEASE; PCLD

Low density lipoprotein receptor-related protein 2 precursor (Megalin - 4660aas; glycoprotein 330) [required for SelP uptake in kidney]. May take up cadmium-metallothionein complexes via receptor-mediated endocytosis (Thévenod, 2010).

A2ARV4 174050
9.B.87.1.1 CHONDROITIN SULFATE PROTEOGLYCAN 2; CSPG2

Low density lipoprotein receptor-related protein 2 precursor (Megalin - 4660aas; glycoprotein 330) [required for SelP uptake in kidney]. May take up cadmium-metallothionein complexes via receptor-mediated endocytosis (Thévenod, 2010).

A2ARV4 118661
9.B.87.1.1 MANNAN-BINDING LECTIN SERINE PROTEASE 2; MASP2

Low density lipoprotein receptor-related protein 2 precursor (Megalin - 4660aas; glycoprotein 330) [required for SelP uptake in kidney]. May take up cadmium-metallothionein complexes via receptor-mediated endocytosis (Thévenod, 2010).

A2ARV4 605102
9.B.87.1.1 COMPLEMENT COMPONENT C1r DEFICIENCY

Low density lipoprotein receptor-related protein 2 precursor (Megalin - 4660aas; glycoprotein 330) [required for SelP uptake in kidney]. May take up cadmium-metallothionein complexes via receptor-mediated endocytosis (Thévenod, 2010).

A2ARV4 216950
9.B.87.1.1 LYMPHOPROLIFERATIVE SYNDROME, X-LINKED, 1; XLP1

Low density lipoprotein receptor-related protein 2 precursor (Megalin - 4660aas; glycoprotein 330) [required for SelP uptake in kidney]. May take up cadmium-metallothionein complexes via receptor-mediated endocytosis (Thévenod, 2010).

A2ARV4 308240
9.B.87.1.1 EPIPHYSEAL DYSPLASIA, MULTIPLE, 1; EDM1

Low density lipoprotein receptor-related protein 2 precursor (Megalin - 4660aas; glycoprotein 330) [required for SelP uptake in kidney]. May take up cadmium-metallothionein complexes via receptor-mediated endocytosis (Thévenod, 2010).

A2ARV4 132400
1.B.12.5.2 PSEUDOACHONDROPLASIA; PSACH The Azorhizobial autotransporter AoaA, required for N- fixing activity of stem nodules (Suzuki et al., 2008).
A8IBA8 177170
9.B.38.1.2 SPASTIC PARAPLEGIA 2, X-LINKED; SPG2 The 2 TMS Pelizaeus-Merzbacher disease (spastic paraplegia 2) protein; 136 aas
B1B1G5 312920
9.B.38.1.2 PROTEOLIPID PROTEIN 1; PLP1 The 2 TMS Pelizaeus-Merzbacher disease (spastic paraplegia 2) protein; 136 aas
B1B1G5 300401
2.A.1.2.41 RHABDOMYOSARCOMA 1; RMS1 The tetracycline resistance determinant, TetA42 from a deep terrestrial subsurface bacterium (Brown et al., 2008).
B2YGG2 268210
1.B.40.1.5 G PROTEIN-COUPLED RECEPTOR 1; GPR1 The cryptic trimeric Haemophilus adhesin, Cha (Sheets et al., 2008).
B3FNS7 600239
2.A.1.25.1 SPASTIC PARAPLEGIA 42, AUTOSOMAL DOMINANT; SPG42 (Putative) Acetyl-CoA:CoA antiporter O00400 612539
3.A.20.1.1 HISTONE DEACETYLASE 1; HDAC1

The peroxisomal importing translocon with receptors: Pex5p and Pex7p; and receptor facilitator: Pex4p

O00628 601241
3.A.20.1.1 TAF4 RNA POLYMERASE II, TATA BOX-BINDING PROTEIN-ASSOCIATED FACTOR, 135-KD; TAF4

The peroxisomal importing translocon with receptors: Pex5p and Pex7p; and receptor facilitator: Pex4p

O00628 601796
3.A.20.1.1 SOLUTE CARRIER FAMILY 2 (FACILITATED GLUCOSE TRANSPORTER), MEMBER 9; SLC2A9

The peroxisomal importing translocon with receptors: Pex5p and Pex7p; and receptor facilitator: Pex4p

O00628 606142
3.A.20.1.1 TRANSDUCIN-BETA-LIKE 3; TBL3

The peroxisomal importing translocon with receptors: Pex5p and Pex7p; and receptor facilitator: Pex4p

O00628 605915
3.A.20.1.1 TELOMERASE RNA COMPONENT; TERC

The peroxisomal importing translocon with receptors: Pex5p and Pex7p; and receptor facilitator: Pex4p

O00628 602322
3.A.20.1.1 DNA METHYLTRANSFERASE 3B; DNMT3B

The peroxisomal importing translocon with receptors: Pex5p and Pex7p; and receptor facilitator: Pex4p

O00628 602900
1.A.1.9.2 BIRK-BAREL MENTAL RETARDATION DYSMORPHISM SYNDROME KcnK3 K+ channel (TASK1, OAT1, TBAK1) (the K+ leak conductance). TASK1 and 3 may play a role in nontumorigenic primary hyperaldosteronism (Davies et al., 2008). O14649 612292
8.A.24.1.1 V-ERB-B2 AVIAN ERYTHROBLASTIC LEUKEMIA VIRAL ONCOGENE HOMOLOG 4; ERBB4 EBP50 or NHERF-1 O14745 600543
8.A.24.1.1 TRAFFICKING PROTEIN, KINESIN-BINDING 1; TRAK1 EBP50 or NHERF-1 O14745 608112
8.A.24.1.1 CARDIOMYOPATHY, DILATED, 1C; CMD1C EBP50 or NHERF-1 O14745 601493
2.A.6.6.1 BODY MASS INDEX; BMI

Niemann-Pick C1 AND C2 disease proteins (together may form a possible lipid/cholesterol exporter from lysosomes to other cellular sites) (Sleat et al., 2004). NPC1 deficiency causes lysosomal retention of cholesterol, sphingolipids, phospholipids, and glycolipids (Infante et al. 2008 a). NPC1 binds cholesterol, 25-hydroxycholesterol and various oxysterols (Infante et al. 2008 b; Liu et al., 2009 ). Soluble NPC2 binds cholesterol, and then passes it to the N-terminal domain of membranous NPC1 (Abi-Mosleh et al., 2009). Cholesterol trafficking in Niemann-Pick C-deficient cells is reviewed by Peake and Vance (2010).

O15118 606641
9.A.36.1.1 SCOTT SYNDROME Erythrocyte Ca2+-dependent phospholipid scramblase 1 O15162 262890
1.A.1.16.2 POTASSIUM CHANNEL, CALCIUM-ACTIVATED, INTERMEDIATE/SMALL CONDUCTANCE, SUBFAMILY N, MEMBER 4; KCNN4

The intermediate conductance, Ca2+-activated K+ channel, hIK1 (inhibited by 1 μM arachidonate which binds in the pore (Hamilton et al., 2003). Nucleoside diphosphate kinase B (NDPK-B) activates KCa3.1 via histidine phosphorylation, resulting in receptor-stimulated Ca2+ flux and T cell activation (Di et al., 2010).

O15554 602754
2.A.1.4.5 SOLUTE CARRIER FAMILY 37 (GLUCOSE-6-PHOSPHATE TRANSPORTER), MEMBER 4; SLC37A4 Microsomal glucose-6-P:Pi antiporter (glycogen storage disease (GSD1b and 1c); Gierke's disease protein) (SLC37A2; in mice, associated with white adipose tissue obesity and expressed at high levels in macrophage) (4 isoforms present in humans; Chen et al., 2008) O43826 602671
3.A.20.1.1 PEROXISOME BIOGENESIS FACTOR 1; PEX1

The peroxisomal importing translocon with receptors: Pex5p and Pex7p; and receptor facilitator: Pex4p

O43933 602136
1.C.15.1.1 KALLMANN SYNDROME 3; KAL3 Putative porin TT95 (WSP) O44397 244200
8.A.21.2.1 PROHIBITIN; PHB Stomatin homologue (Yokoyama and Matsui, 2005) O59180 176705
9.B.25.2.1 OPTIC ATROPHY 1; OPA1

The mammalian mitochondrial membrane fusion complex, Mitofusin 1 (Mfn1)/Mfn2/Optical Atrophy Protein 1 (OPA1) complex (the equivalent of the yeast Ugo1 protein has not been identified). Mfn1 and Mfn2 are two very similar (60% identity) GTPases in the outer membrane while OPA1 is a sequence divergent GTPase in the inner membrane (Chen and Chan, 2010).

O60313 165500
3.A.20.1.1 PEROXISOME BIOGENESIS FACTOR 10; PEX10

The peroxisomal importing translocon with receptors: Pex5p and Pex7p; and receptor facilitator: Pex4p

O60683 602859
3.A.20.1.1 CAS-BR-M MURINE ECOTROPIC RETROVIRAL TRANSFORMING SEQUENCE B; CBLB

The peroxisomal importing translocon with receptors: Pex5p and Pex7p; and receptor facilitator: Pex4p

O60683 604491
3.A.20.1.1 TOPOISOMERASE I-BINDING ARGININE/SERINE-RICH PROTEIN; TOPORS

The peroxisomal importing translocon with receptors: Pex5p and Pex7p; and receptor facilitator: Pex4p

O60683 609507
3.A.20.1.1 BREAST-OVARIAN CANCER, FAMILIAL, SUSCEPTIBILITY TO, 1; BROVCA1

The peroxisomal importing translocon with receptors: Pex5p and Pex7p; and receptor facilitator: Pex4p

O60683 604370
2.A.48.2.1 THIAMINE-RESPONSIVE MEGALOBLASTIC ANEMIA SYNDROME; TRMA

Thiamine uptake transporter-1, THTR-1 (the thiamine-responsive megaloblastic anemia (TRMA) protein). Downregulated in Chronic Kidney Disease (CKD) in heart, liver, and brain causing malabsorption (Bukhari et al., 2011).

O60779 249270
1.A.1.11.11 NIGHT BLINDNESS, CONGENITAL STATIONARY, TYPE 2B; CSNB2B

The Cav1.4 Ca2+ channel (gene CACNA1F). Mutations resulting in increased activity cause x-linked incomplete congenital stationary night blindness (CSNB2) (Hemara-Wahanui et al., 2005; Peloquin et al., 2007).

O60840 610427
1.A.2.1.8 VITREORETINAL DEGENERATION, SNOWFLAKE TYPE; SVD The inward rectifier potassium channel 13, Kir 7.1 O60928 193230
9.A.25.1.1 CARBOXYL-ESTER LIPASE; CEL The RD1 protein secretion complex
O69740 114840
8.A.15.1.1 ONCOGENE DJ1 K+ channel auxiliary subunit (KChAP) O70260 602533
2.A.1.13.3 ALLAN-HERNDON-DUDLEY SYNDROME; AHDS

The thyroid hormone transporter, MCT8 (transports L- and D-isomers of thyroxine (T4), 3,3',5-triiodothyronine (T3), 3,3'5'-triiodothyronine (rT3) and 3,3'-diiodothyronine [Km values = 2-5 μM; Leu, Phe, Trp and Tyr were not transported]) (Friesema et al., 2003). Loss of function mutations in MCT8 leads to Allan-Herndon-Dudley syndrome, severe X-linked psychomotor retardation and elevated serum T3 levels (Jansen et al., 2008). Essential molecular determinants for thyroid hormone transport and their structural implications are presented by Kinne et al. (2010). Induced by retinoic acid (Kogai et al., 2010). Mediates energy-independent bidirectional transport. MCT8 is specific for L-iodothyronines and requires at least one iodine atom per aromatic ring. Thyronamines, decarboxylated metabolites of iodothyronines, triiodothyroacetic acid and tetraiodothyroacetic acid, TH derivatives lacking both chiral center and amino group, are not substrates (Kinne et al., 2010).

O70324 300523
3.A.1.210.4 ANEMIA, SIDEROBLASTIC, AND SPINOCEREBELLAR ATAXIA; ASAT ABC7 iron transporter (X-linked sideroblastis anemia protein) (also called ABCB7) O75027 301310
2.A.29.14.1 SOLUTE CARRIER FAMILY 25 (MITOCHONDRIAL CARRIER, ARALAR), MEMBER 12; SLC25A12 Mitochondrial Ca2+-activated aspartate/glutamate antiporter carrier with Ca2+-binding EF-hand domain, Aralar O75746 603667
1.A.46.1.1 MACULAR DYSTROPHY, VITELLIFORM, ADULT-ONSET

Bestrophin-1 anion channel; VMD2 gene product (NO3- > I- > Br- > Cl-; PNO3-/PCl- = 5.8) (Sun et al., 2002). Regulated by ceramide-induced dephosphorylation (Xiao et al., 2009).

O76090 608161
9.B.25.2.1 DYNAMIN 1-LIKE; DNM1L

The mammalian mitochondrial membrane fusion complex, Mitofusin 1 (Mfn1)/Mfn2/Optical Atrophy Protein 1 (OPA1) complex (the equivalent of the yeast Ugo1 protein has not been identified). Mfn1 and Mfn2 are two very similar (60% identity) GTPases in the outer membrane while OPA1 is a sequence divergent GTPase in the inner membrane (Chen and Chan, 2010).

O95140 603850
3.A.1.208.10 PSEUDOXANTHOMA ELASTICUM, FORME FRUSTE

Multidrug (anthracycline) resistance organic anion efflux pump (ABC-C6; MRP6; MOAT-E - the pseudoxanthoma elasticum disease protein) exports glutathione conjugates including lencotriene C4, DNP, and N-ethylmaleimide S-glutathione; also exports anthracyclines, epipodophyllotoxins, cisplatin, and probably exports probenecid, benzbromarone and indomethacin (Chen and Tiwari, 2011).

O95255 177850
3.A.1.201.2 CHOLESTASIS, PROGRESSIVE FAMILIAL INTRAHEPATIC, 2; PFIC2

Bile salt export pump, BSEP or SPGP (associated with progressive familial intrahepatic cholestasis-2 (also called ABCB11) and benign recurrent intrahepatic cholestasis (Kagawa et al., 2008)). Unconjugaged bile salts and glycine conjugates > taurine conjugates.

O95342 601847
3.D.3.2.1 CHLORAMPHENICOL TOXICITY

Ubiquinol:cytochrome c oxidoreductase

P00157 515000
3.D.4.11.1 TRANSFER RNA, MITOCHONDRIAL, LYSINE; MTTK Cytochrome oxidase (Cox) P00414 590060
1.C.92.1.2 C-REACTIVE PROTEIN, PENTRAXIN-RELATED; CRP Serum amyloid P component precursor, SAP (223aas) P02743 123260
3.D.1.6.1 ALZHEIMER DISEASE, SUSCEPTIBILITY TO, MITOCHONDRIAL The animal H+-translocating NADH dehydrogenase (NDH) complex (45 subunits) (Cardol et al., 2004) P03892 502500
3.D.1.6.1 MITOCHONDRIAL MYOPATHY, ENCEPHALOPATHY, LACTIC ACIDOSIS, AND STROKE-LIKE EPISODES; MELAS The animal H+-translocating NADH dehydrogenase (NDH) complex (45 subunits) (Cardol et al., 2004) P03924 540000
2.A.6.6.5 3-@HYDROXY-3-METHYLGLUTARYL-CoA REDUCTASE; HMGCR 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase P04035 142910
3.D.1.6.1 NADH-UBIQUINONE OXIDOREDUCTASE 1 BETA SUBCOMPLEX, 9; NDUFB9 The animal H+-translocating NADH dehydrogenase (NDH) complex (45 subunits) (Cardol et al., 2004) P04394 601445
3.A.3.1.1 ATPase, Na+/K+ TRANSPORTING, ALPHA-1 POLYPEPTIDE; ATP1A1

Na+-, K+-ATPase (Na+ efflux; K+ uptake) (Mutations in the γ-subunit causes renal hypomagnesemia, associated with hypocalciurea) (Cairo et al., 2008). The Na/K-ATPase is an important signal transducer that not only interacts and regulates protein kinases, but also functions as a scaffold (Li and Xie, 2009). Capsazepine, a synthetic vanilloid, converts the Na, K-ATPase to a Na-ATPase (Mahmmoud, 2008a). There are alternative α- and β-subunits, α1, α2,... β1, β2,... in muscle which form α1β1, α1β2, α2β1 and α2β2, heterodimers, each with differing Na+ affinities (4-13mM) (Kristensen and Juel, 2010). α3 and β3 isoforms have also been identified. The γ-subunit is the same as TC# 1.A.27.2.1. Poulsen et al. (2010) have proposed a second ion conduction pathway in the C-terminal part of the ATPase. The two C-terminal tyrosines stabilize the occluded Na/K pump conformations containing Na or K ions (Vedovato and Gadsby, 2010).

P05023 182310
1.A.1.11.2 HYPOKALEMIC PERIODIC PARALYSIS; HOKPP Muscle plasmalemma, voltage-gated, L-type dihydropyridine receptor Ca2+ channel, α-1 subunit (DHPR) (Ba2+ > Ca2+) P07293 170400
1.C.39.3.1 COMPLEMENT COMPONENT 8 DEFICIENCY, TYPE I Pore-forming, membrane attack, complement component 8, α-polypeptide precursor; C8α-MACPF (structure solved to 2.5 Å resolution; Hadders et al., 2007; Rosado et al., 2007).
P07357 120950
1.C.39.3.1 MATRIX METALLOPROTEINASE 9; MMP9 Pore-forming, membrane attack, complement component 8, α-polypeptide precursor; C8α-MACPF (structure solved to 2.5 Å resolution; Hadders et al., 2007; Rosado et al., 2007).
P07357 120361
1.C.39.3.1 A DISINTEGRIN-LIKE AND METALLOPROTEASE WITH THROMBOSPONDIN TYPE 1 MOTIF, 13; ADAMTS13 Pore-forming, membrane attack, complement component 8, α-polypeptide precursor; C8α-MACPF (structure solved to 2.5 Å resolution; Hadders et al., 2007; Rosado et al., 2007).
P07357 604134
1.C.39.3.1 A DISINTEGRIN-LIKE AND METALLOPROTEINASE WITH THROMBOSPONDIN TYPE 1 MOTIF, 5; ADAMTS5 Pore-forming, membrane attack, complement component 8, α-polypeptide precursor; C8α-MACPF (structure solved to 2.5 Å resolution; Hadders et al., 2007; Rosado et al., 2007).
P07357 605007
1.C.39.3.1 WEILL-MARCHESANI SYNDROME, AUTOSOMAL RECESSIVE Pore-forming, membrane attack, complement component 8, α-polypeptide precursor; C8α-MACPF (structure solved to 2.5 Å resolution; Hadders et al., 2007; Rosado et al., 2007).
P07357 277600
1.C.35.2.1 COMBINED SAPOSIN DEFICIENCY Cerebroside sulfate activator protein, CSAP P07602 611721
1.A.24.1.3 GAP JUNCTION PROTEIN, BETA-1; GJB1 Heteromeric connexin (Cx)32/Cx26) (transports cAMP, cGMP and all inositol phosphates with 1-4 esterified phosphate groups (homomeric Cx26(β2) or homomeric Cx32 do not transport the inositol phosphates as well) (Ayad et al., 2006) P08034 304040
1.A.33.1.3 HEAT-SHOCK 70-KD PROTEIN 1A; HSPA1A Heat shock protein 70(1B) P08107 140550
1.A.31.1.2 ANNEXIN A7; ANXA7 Annexin VI P08133 186360
3.A.1.201.1 MELANOMA, CUTANEOUS MALIGNANT; CMM

Broad specificity multidrug resistance (MDR) efflux pump (exports organic cations and amphiphilic compounds of unrelated chemical structure) (These include: anti-biotics, viral agents, cancer agents, hypertensives, depressants, histamines, emetics, and the protease inhibitor, lopinavir. Pgp also exports immunosuppressants, detergents, long-chain fatty acids, HIV protease inhibitors, synthetic tetramethylrosamine analogues, calcein M, etc.); peptide efflux pump; phospholipid (e.g., phosphatidyl serine), cholesterol and sterol flippase (also called ABCB1 and p-gp)). Binds and probably transports inhibitors and agonists of SUR (2.A.1.208.4) (Bessadok et al., 2011). The 3-d structure has been determined (Aller et al., 2009). It can pump from the cytoplasmic leaflet to either the outer leaflet or the outer medium (Katzir et al., 2010).

P08183 155600
1.C.50.1.1 CEREBRAL AMYLOID ANGIOPATHY, APP-RELATED Alzheimer’s disease amyloid β-protein (amino acids 1-42) (AβP) P08592 605714
3.A.1.204.1 ATP-BINDING CASSETTE, SUBFAMILY D, MEMBER 1; ABCD1 Eye pigment precursor transporter P10090 300371
2.A.1.1.28 SOLUTE CARRIER FAMILY 2 (FACILITATED GLUCOSE TRANSPORTER), MEMBER 1; SLC2A1

The erythrocyte/brain hexose facilitator,
Gtr1 or Glut1. Also transports D-glucose, dehydroascorbate, and the flavonone, quercetin, via one channel and water via a distinct channel. Sugar transport has been suggested to function via a sliding mechanism involving several sugar binding sites (Cunningham et al., 2006). (Receptor for human T-cell leukemia virus (HTLV)) (Manel et al., 2003). Regulated by stomatin to take up dehydroascorbate (Montel-Hagen et al., 2008). Mutations cause Glut1 deficiency syndrome, a human encephalopathy that results from decreased glucose flux through the blood brain barrier (Pascual et al., 2008). Mueckler and Makepeace (2009) have presented a model of the exofacial substrate-binding site and helical folding of Glut1. Glut 1, 2, 4 and 9 are functional both in the plasma membrane and the endoplasmic reticulum (Takanaga and Frommer, 2010). Down-regulated in the brains of Alzheimer's disease patients (Liu et al., 2008b). Metabolic stress rapidly stimulates blood-brain barrier endothelial cell sugar transport by acute up-regulation of plasma membrane GLUT1 levels, possibly involving an AMP-activated kinase activity (Cura and Carruthers, 2010).

P11166 138140
2.A.1.1.29 FANCONI-BICKEL SYNDROME; FBS

Glucosamine/glucose uniporter, Glut-2 (may also transport dehydroascorbate (Mardones et al., 2011Maulén et al., 2003), and cotransport water against an osmotic gradient (Naftalin, 2008))

P11168 227810
9.A.16.1.1 SIALURIA, FINNISH TYPE Lysosomal-associated membrane protein 2 precursor, lamp2a P13473 604369
9.A.16.1.1 LYSOSOME-ASSOCIATED MEMBRANE PROTEIN 2; LAMP2 Lysosomal-associated membrane protein 2 precursor, lamp2a P13473 309060
3.A.5.8.1 HEAT-SHOCK 70-KD PROTEIN 8; HSPA8

The general secretory pathway (Sec-SRP) complex. The Yet1 and Yet3 proteins interact directly with the Sec translocon (Wilson & Barlowe et al., 2010). The Sss1/Sec61γ protein (80aas) has two domains. The cytosolic domain is required for Sec61p interaction while the transmembrane clamp domain is required to complete activation of the translocon after precursor targeting to Sec61p (Wilkinson et al., 2010).

P14906 600816
3.D.1.6.1 NADH-UBIQUINONE OXIDOREDUCTASE FLAVOPROTEIN 1; NDUFV1 The animal H+-translocating NADH dehydrogenase (NDH) complex (45 subunits) (Cardol et al., 2004) P15690 161015
1.A.1.2.10 EPISODIC ATAXIA, TYPE 1; EA1

Voltage-gated K+ channel, chain A, Shaker-related, Kv1.2 (Crystal structure known, Long et al., 2007). Delemotte et al. (2010) described the effects of sensor domain mutations on molecular dynamics of Kv1.2.

P16389 160120
9.B.8.1.1 ONCOGENE JUN-D; JUND Canalicular bile acid transporter (C-BAT) ecto-ATPase (GP110) P16573 165162
9.B.8.1.1 CARCINOEMBRYONIC ANTIGEN-RELATED CELL ADHESION MOLECULE 6; CEACAM6 Canalicular bile acid transporter (C-BAT) ecto-ATPase (GP110) P16573 163980
9.B.8.1.1 COMPLEMENT COMPONENT 9; C9 Canalicular bile acid transporter (C-BAT) ecto-ATPase (GP110) P16573 120940
9.B.8.1.1 HYDROCEPHALUS DUE TO CONGENITAL STENOSIS OF AQUEDUCT OF SYLVIUS; HSAS Canalicular bile acid transporter (C-BAT) ecto-ATPase (GP110) P16573 307000
9.B.8.1.1 TITIN; TTN Canalicular bile acid transporter (C-BAT) ecto-ATPase (GP110) P16573 188840
9.B.8.1.1 Fc RECEPTOR-LIKE PROTEIN 3; FCRL3 Canalicular bile acid transporter (C-BAT) ecto-ATPase (GP110) P16573 606510
9.B.8.1.1 CONTACTIN 4; CNTN4 Canalicular bile acid transporter (C-BAT) ecto-ATPase (GP110) P16573 607280
9.B.8.1.1 THANATOPHORIC DYSPLASIA, TYPE I; TD1 Canalicular bile acid transporter (C-BAT) ecto-ATPase (GP110) P16573 187600
9.B.8.1.1 OPIOID-BINDING PROTEIN/CELL ADHESION MOLECULE-LIKE; OPCML Canalicular bile acid transporter (C-BAT) ecto-ATPase (GP110) P16573 600632
9.B.8.1.1 MUCOSA-ASSOCIATED LYMPHOID TISSUE LYMPHOMA TRANSLOCATION GENE 1; MALT1 Canalicular bile acid transporter (C-BAT) ecto-ATPase (GP110) P16573 604860
9.B.8.1.1 PLATELET-ENDOTHELIAL CELL ADHESION MOLECULE 1; PECAM1 Canalicular bile acid transporter (C-BAT) ecto-ATPase (GP110) P16573 173445
9.B.8.1.1 TREACHER COLLINS-FRANCESCHETTI SYNDROME; TCOF Canalicular bile acid transporter (C-BAT) ecto-ATPase (GP110) P16573 154500
9.B.8.1.1 POLIOVIRUS RECEPTOR-LIKE 1; PVRL1 Canalicular bile acid transporter (C-BAT) ecto-ATPase (GP110) P16573 600644
9.B.8.1.1 BASAL CELL ADHESION MOLECULE; BCAM Canalicular bile acid transporter (C-BAT) ecto-ATPase (GP110) P16573 612773
9.B.8.1.1 SLAM FAMILY, MEMBER 6; SLAMF6 Canalicular bile acid transporter (C-BAT) ecto-ATPase (GP110) P16573 606446
1.A.1.2.2 POTASSIUM CHANNEL, VOLTAGE-GATED, SUBFAMILY V, MEMBER 2; KCNV2

Voltage-sensitive K+ channel

P17972 607604
1.A.1.2.2 SPINOCEREBELLAR ATAXIA 13; SCA13

Voltage-sensitive K+ channel

P17972 605259
2.A.6.6.2 BASAL CELL NEVUS SYNDROME; BCNS Patched (Ptc) segmentation polarity protein P18502 109400
1.A.10.1.1 GLUTAMATE RECEPTOR, IONOTROPIC, AMPA 3; GRIA3 Glutamate ionotropic channel receptor (GIC), kainate-subtype, GluR-K1; GluR1; GluR-A (preferentially monovalent cation selective). Contributes to amygdala-dependent emotional learning and fear conditioning (Humeau et al., 2007). P19490 305915
3.D.4.8.1 SCO1, S. CEREVISIAE, HOMOLOG OF; SCO1 Cytochrome oxidase (Cox) P19516 603644
3.A.1.201.3 ATP-BINDING CASSETTE, SUBFAMILY B, MEMBER 4; ABCB4 Short chain fatty acid phosphatidylcholine translocase (phospholipid flippase), MDR3 (associated with progressive familial intrahepatic cholestasis-3). (Narrow drug specificity relative to MDR1. Exports digoxin, paclitaxel, vinblastin and bile acids.) (also called ABCB4) P21439 171060
3.D.4.8.1 COQ2, S. CEREVISIAE, HOMOLOG OF; COQ2 Cytochrome oxidase (Cox) P21592 609825
1.A.3.1.2 CENTRAL CORE DISEASE OF MUSCLE

The Ryanodine receptor Ca2+/K+ release tetrameric channel, RyR1, present in skeletal muscle, is 5038 aas long. Mutants are linked to core myopathies such as Central Core Disease and Multiple Minicore Disease) (Xu et al., 2008). RyR1 interacts with CLIC2 to modulate its channel activity (Meng et al., 2009).

P21817 117000
1.A.1.2.4 ATRIAL FIBRILLATION, FAMILIAL, 7; ATFB7

Margatoxin-sensitive voltage-gated K+ channel, Kv1.3 (in plasma and mitochondrial membranes of T lymphocytes) (Szabò et al., 2005). Kv1.3 associates with the sequence similar (>80%) Kv1.5 protein in macrophage forming heteromers that like Kv1.3 homomers are r-margatoxin sensitive (Vicente et al., 2006). However, the heteromers have different biophysical and pharmacological properties. The Kv1.3 mitochondrial potassium channel is involved in apoptotic signalling in lymphocytes (Gulbins et al., 2010).

P22460 612240
1.C.40.1.3 HYPERALPHALIPOPROTEINEMIA CETP (cholesterylester transfer protein) precursor P22687 143470
1.A.9.3.1 GLYCINE RECEPTOR, ALPHA-1 SUBUNIT; GLRA1

Adult glycine-inhibited chloride (anion selective) heteropentameric channel (GlyR) consisting of α1- and β-subunits (Cascio, 2004; Sivilotti, 2010). Ivermectin potentiates glycine-induced channel activation (Wang and Lynch, 2012).

P23415 138491
1.G.7.1.1 DYSTROPHIA MYOTONICA 2; DM2

GAG polyprotein; contains matrix proteins p16, capsid protein p25 and nucleocapsid protein p14 (442aas).

P23425 602668
1.C.48.1.1 FATAL FAMILIAL INSOMNIA; FFI Major prion protein precursor PrP (yielding peptide PrP[106-126]) P23907 600072
1.C.48.1.1 SPONGIFORM ENCEPHALOPATHY WITH NEUROPSYCHIATRIC FEATURES Major prion protein precursor PrP (yielding peptide PrP[106-126]) P23907 606688
3.D.1.6.1 ALEXANDER DISEASE The animal H+-translocating NADH dehydrogenase (NDH) complex (45 subunits) (Cardol et al., 2004) P25708 203450
8.A.25.1.1 NEUROFIBROMATOSIS, TYPE II; NF2 Ezrin P26040 101000
8.A.25.1.1 MYOSIN, HEAVY CHAIN 9, NONMUSCLE; MYH9 Ezrin P26040 160775
8.A.21.1.1 STOMATOCYTOSIS I Erythrocyte stomatin (Band 7) P27105 185000
8.A.21.1.1 PODOCIN; NPHS2 Erythrocyte stomatin (Band 7) P27105 604766
3.A.1.203.1 ATP-BINDING CASSETTE, SUBFAMILY D, MEMBER 3; ABCD3 Peroxysomal long chain fatty acyl (LCFA) transporter associated with Zellweger Syndrome P28288 170995
3.A.20.1.1 CEREBROHEPATORENAL SYNDROME, VARIANT TYPES

The peroxisomal importing translocon with receptors: Pex5p and Pex7p; and receptor facilitator: Pex4p

P28328 214110
1.A.24.1.3 DEAFNESS, AUTOSOMAL RECESSIVE 1A; DFNB1A Heteromeric connexin (Cx)32/Cx26) (transports cAMP, cGMP and all inositol phosphates with 1-4 esterified phosphate groups (homomeric Cx26(β2) or homomeric Cx32 do not transport the inositol phosphates as well) (Ayad et al., 2006) P29033 220290
1.A.24.1.3 ECTODERMAL DYSPLASIA, HIDROTIC, AUTOSOMAL DOMINANT Heteromeric connexin (Cx)32/Cx26) (transports cAMP, cGMP and all inositol phosphates with 1-4 esterified phosphate groups (homomeric Cx26(β2) or homomeric Cx32 do not transport the inositol phosphates as well) (Ayad et al., 2006) P29033 129500
1.A.1.5.3 ACHROMATOPSIA 2; ACHM2 Heterotetrameric (3A:1B) rod photoreceptor cyclic GMP-gated cation channel, CNG (Zhong et al., 2002). Defects produce channelopathies (Biel& Michalakis, 2007). P29973 216900
9.B.25.1.1 DYNAMIN 2; DNM2

The mitochondrial inner/outer membrane fusion complex, Fzo/Mgm1/Ugo1. Only the Ugo1 protein is a member of the MC superfamily.

P32266 602378
9.B.25.1.1 LEUKOCYTE ADHESION DEFICIENCY, TYPE I; LAD

The mitochondrial inner/outer membrane fusion complex, Fzo/Mgm1/Ugo1. Only the Ugo1 protein is a member of the MC superfamily.

P32266 116920
9.A.50.1.1 LEUCYL-CYSTINYL AMINOPEPTIDASE; LNPEP The tRNA nuclear export machinery, t-Exporter. Includes UTP8, a tRNA-binding protein, Los1 and Msn5/ two tRNA export receptors (Strub et al., 2007) P32835 151300
9.A.50.1.1 CARPENTER SYNDROME The tRNA nuclear export machinery, t-Exporter. Includes UTP8, a tRNA-binding protein, Los1 and Msn5/ two tRNA export receptors (Strub et al., 2007) P32835 201000
9.A.50.1.1 GRISCELLI SYNDROME, TYPE 2; GS2 The tRNA nuclear export machinery, t-Exporter. Includes UTP8, a tRNA-binding protein, Los1 and Msn5/ two tRNA export receptors (Strub et al., 2007) P32835 607624
9.A.50.1.1 TRANSFORMING GROWTH FACTOR-BETA RECEPTOR, TYPE I; TGFBR1 The tRNA nuclear export machinery, t-Exporter. Includes UTP8, a tRNA-binding protein, Los1 and Msn5/ two tRNA export receptors (Strub et al., 2007) P32835 190181
9.A.50.1.1 PARKINSON DISEASE 8; PARK8 The tRNA nuclear export machinery, t-Exporter. Includes UTP8, a tRNA-binding protein, Los1 and Msn5/ two tRNA export receptors (Strub et al., 2007) P32835 607060
9.A.50.1.1 RAS-ASSOCIATED PROTEIN RAB1; RAB1 The tRNA nuclear export machinery, t-Exporter. Includes UTP8, a tRNA-binding protein, Los1 and Msn5/ two tRNA export receptors (Strub et al., 2007) P32835 179508
3.A.1.203.3 CONTIGUOUS ABCD1/DXS1375E DELETION SYNDROME

The peroxysomal long chain fatty acid (LCFA) half transporter, ABCD1 (ALD, the adrenoleukodystrophy protein) (functions as a homodimer and accepts acyl-CoA esters (van Roermund et al. 2008)). Transports C24:0 and C26:0 as substrates (van Roermund et al., 2011).

P33897 300475
3.D.1.6.1 DEOXYGUANOSINE KINASE; DGUOK The animal H+-translocating NADH dehydrogenase (NDH) complex (45 subunits) (Cardol et al., 2004) P34942 601465
1.A.24.1.6 GAP JUNCTION PROTEIN, ALPHA-3; GJA3 Connexin37 (Cx37). The N-terminus contains an α-helix that is required for channel function (Kyle et al., 2009).
P35212 121015
1.A.1.10.7 SODIUM CHANNEL, NEURONAL TYPE I, ALPHA SUBUNIT; SCN1A Voltage-sensitive Na+ channel, Nav1.1 or SCN1A (causes epilepsy when mutated) (Rusconi et al., 2007). P35498 182389
1.A.1.10.4 PARAMYOTONIA CONGENITA OF VON EULENBURG; PMC

The skeletal muscle Na+ channel, NaV1.4 (mutations in the S4 segment cause hypokalemic periodic paralysis; Sokolov et al., 2007). Also causes myotonia; regulated by calmodulin which binds to the C-terminus of Nav1.4 (Biswas et al., 2008). NaV1.4 gating pores are permeable to guanidine (Sokolov et al., 2010).

P35499 168300
2.A.49.2.1 CHLORIDE CHANNEL 1, SKELETAL MUSCLE; CLCN1 Voltage and (possibly) ATP-gated Cl- channel, ClC-1 (Bennetts et al., 2005; Zifarelli and Pusch, 2008). When mutant, it causes dominant and recessive myotonia. It has a large cytoplasmic C-terminal domain bearing two CBS (cystathionine-β-synthase) domains. P35523 118425
2.A.49.2.6 EPILEPSY, IDIOPATHIC GENERALIZED, SUSCEPTIBILITY TO, 11; EIG11

The ClC-2 chloride channel/carrier expressed in many tissues (Cl- ≥ Br- > I-) (Thiemann et al., 1992). Regulated in the retina by Cereblon (Q96SW2) (Hohberger and Enz, 2009). A toxin, GaTx2, is a potent and specific inhibitor of ClC-2, binding with a Ki of 20pM (Thompson et al., 2009). ClC-2 channels constitute part of the background conductance and assist chloride extrusion (Rinke et al., 2010). ClC-2 channels regulate neuronal excitability, not intracellular chloride levels (Ratté and Prescott, 2011).

P35525 607628
3.A.3.5.3 ATPase, Cu(2+)-TRANSPORTING, BETA POLYPEPTIDE; ATP7B Cu+-, Ag+-ATPase (efflux from the cytosol into the secretory pathway) (Barnes et al., 2005); ATP7B (Wilson's disease protein, α-chain) (continuously expressed in Purkinje neurons). It delivers Cu+ to the ferroxidase, ceruloplasmin, in liver. May also transport Fe2+ (Takeda et al., 2005). P35670 606882
3.A.8.1.1 DENTIN SIALOPHOSPHOPROTEIN; DSPP

Mitochondrial protein translocase (MPT) (Chacinska et al., 2005; Mokranjac et al., 2005; Bihlmaier et al., 2007). The crystal structure of the intermembrane space domain of yeast Tim50 has been solved to 1.83 Å resolution (Qian et al., 2011). A protruding beta-hairpin of Tim50 is crucial for interaction with Tim23, providing a molecular basis for the cooperation of Tim50 and Tim23 in preprotein translocation to the protein-conducting channel of the mitochondrial inner membrane (Qian et al., 2011). 

P36046 125485
3.A.5.8.1 ADP-RIBOSYLATION FACTOR-LIKE 11; ARL11

The general secretory pathway (Sec-SRP) complex. The Yet1 and Yet3 proteins interact directly with the Sec translocon (Wilson & Barlowe et al., 2010). The Sss1/Sec61γ protein (80aas) has two domains. The cytosolic domain is required for Sec61p interaction while the transmembrane clamp domain is required to complete activation of the translocon after precursor targeting to Sec61p (Wilkinson et al., 2010).

P36057 609351
3.A.5.8.1 SAR1, S. CEREVISIAE, HOMOLOG OF, A; SAR1A

The general secretory pathway (Sec-SRP) complex. The Yet1 and Yet3 proteins interact directly with the Sec translocon (Wilson & Barlowe et al., 2010). The Sss1/Sec61γ protein (80aas) has two domains. The cytosolic domain is required for Sec61p interaction while the transmembrane clamp domain is required to complete activation of the translocon after precursor targeting to Sec61p (Wilkinson et al., 2010).

P36057 607691
1.A.9.1.1 SCHIZOPHRENIA 13; SCZD13

Nicotinic acetylcholine-activated cation-selective channel, pentameric α2βγδ (immature muscle) nα2βγε (mature muscle). Acetylcholine receptor δ subunit mutations underlie a fast-channel myasthenic syndrome and arthrogryposis multiplex congenita (Brownlow et al., 2001). Residues in TMS2 and the cytoplasmic loop linking TMSs 3 and 4 influence conductance, selectivity, gating and desensitization (Peters et al., 2010). nAChR and TRPC channel proteins (1.A.4) mediate nicotine addiction in many animals from humans to worms (Feng et al., 2006).

P36544 613025
1.A.6.1.1 BRONCHIECTASIS WITH OR WITHOUT ELEVATED SWEAT CHLORIDE 2; BESC2 Epithelial Na+ channel, ENaC (regulates salt and fluid homeostasis and blood pressure; regulated by Nedd4 isoforms) (Henry et al., 2003) (Cd2+ inhibits α-ENaC by binding to the internal pore where it interacts with residues in TMS2 (Takeda et al., 2007). P37088 613021
1.C.77.1.1 SYNUCLEIN, BETA; SNCB α-synuclein (140 aas) P37840 602569
1.C.77.1.1 SYNUCLEIN, GAMMA; SNCG α-synuclein (140 aas) P37840 602998
3.A.18.1.1 SMN-INTERACTING PROTEIN 1; SIP1

The nuclear mRNA Export Complex (mRNA-E also called TREX) (including the exon junction complex) [TAP+p15 interact as a complex with the nuclear pore to facilitate mRNA transport to the cytoplasm] (Nojimma et al. 2007; Cheng et al., 2006)

P38919 602595
3.A.18.1.1 DEAD/H BOX 21; DDX21

The nuclear mRNA Export Complex (mRNA-E also called TREX) (including the exon junction complex) [TAP+p15 interact as a complex with the nuclear pore to facilitate mRNA transport to the cytoplasm] (Nojimma et al. 2007; Cheng et al., 2006)

P38919 606357
3.A.18.1.1 POLYMERASE, DNA, GAMMA; POLG

The nuclear mRNA Export Complex (mRNA-E also called TREX) (including the exon junction complex) [TAP+p15 interact as a complex with the nuclear pore to facilitate mRNA transport to the cytoplasm] (Nojimma et al. 2007; Cheng et al., 2006)

P38919 174763
3.A.18.1.1 DIABETES MELLITUS, INSULIN-DEPENDENT, 19; IDDM19

The nuclear mRNA Export Complex (mRNA-E also called TREX) (including the exon junction complex) [TAP+p15 interact as a complex with the nuclear pore to facilitate mRNA transport to the cytoplasm] (Nojimma et al. 2007; Cheng et al., 2006)

P38919 610155
3.A.18.1.1 PLEUROPULMONARY BLASTOMA; PPB

The nuclear mRNA Export Complex (mRNA-E also called TREX) (including the exon junction complex) [TAP+p15 interact as a complex with the nuclear pore to facilitate mRNA transport to the cytoplasm] (Nojimma et al. 2007; Cheng et al., 2006)

P38919 601200
3.A.18.1.1 PROCOLLAGEN-PROLINE, 2-OXOGLUTARATE-4-DIOXYGENASE, BETA SUBUNIT; P4HB

The nuclear mRNA Export Complex (mRNA-E also called TREX) (including the exon junction complex) [TAP+p15 interact as a complex with the nuclear pore to facilitate mRNA transport to the cytoplasm] (Nojimma et al. 2007; Cheng et al., 2006)

P38919 176790
3.A.1.211.1 TANGIER DISEASE; TGD

The cholesterol/phospholipid flippase, ABC1 (called ABCA1 in humans; Tangier disease proteins; 2261 aas; sp: O95477). An amphipathic helical region of the N-terminal barrel of the phospholipid transfer protein (PLTP) is critical for ABCA1-dependent cholesterol efflux (Oram et al., 2008). PLTP helix 144-163 removes lipid domains formed by ABCA1, stabilizing ABCA1, interacting with phospholipids, and promoting phospholipid transfer by direct interactions with ABCA1. May transport sphingosine-1-phosphate (Kobayashi et al., 2009). May protect from cardiovascular disease and diabetes (Tang and Oram, 2009).

P41233 205400
3.A.1.211.1 ICHTHYOSIS CONGENITA, HARLEQUIN FETUS TYPE

The cholesterol/phospholipid flippase, ABC1 (called ABCA1 in humans; Tangier disease proteins; 2261 aas; sp: O95477). An amphipathic helical region of the N-terminal barrel of the phospholipid transfer protein (PLTP) is critical for ABCA1-dependent cholesterol efflux (Oram et al., 2008). PLTP helix 144-163 removes lipid domains formed by ABCA1, stabilizing ABCA1, interacting with phospholipids, and promoting phospholipid transfer by direct interactions with ABCA1. May transport sphingosine-1-phosphate (Kobayashi et al., 2009). May protect from cardiovascular disease and diabetes (Tang and Oram, 2009).

P41233 242500
3.A.1.211.1 ATP-BINDING CASSETTE, SUBFAMILY A, MEMBER 1; ABCA1

The cholesterol/phospholipid flippase, ABC1 (called ABCA1 in humans; Tangier disease proteins; 2261 aas; sp: O95477). An amphipathic helical region of the N-terminal barrel of the phospholipid transfer protein (PLTP) is critical for ABCA1-dependent cholesterol efflux (Oram et al., 2008). PLTP helix 144-163 removes lipid domains formed by ABCA1, stabilizing ABCA1, interacting with phospholipids, and promoting phospholipid transfer by direct interactions with ABCA1. May transport sphingosine-1-phosphate (Kobayashi et al., 2009). May protect from cardiovascular disease and diabetes (Tang and Oram, 2009).

P41233 600046
3.A.1.211.1 ICHTHYOSIS CONGENITA, HARLEQUIN FETUS TYPE

The cholesterol/phospholipid flippase, ABC1 (called ABCA1 in humans; Tangier disease proteins; 2261 aas; sp: O95477). An amphipathic helical region of the N-terminal barrel of the phospholipid transfer protein (PLTP) is critical for ABCA1-dependent cholesterol efflux (Oram et al., 2008). PLTP helix 144-163 removes lipid domains formed by ABCA1, stabilizing ABCA1, interacting with phospholipids, and promoting phospholipid transfer by direct interactions with ABCA1. May transport sphingosine-1-phosphate (Kobayashi et al., 2009). May protect from cardiovascular disease and diabetes (Tang and Oram, 2009).

P41233 242500
3.D.1.6.1 NADH-UBIQUINONE OXIDOREDUCTASE Fe-S PROTEIN 7; NDUFS7 The animal H+-translocating NADH dehydrogenase (NDH) complex (45 subunits) (Cardol et al., 2004) P42026 601825
4.C.2.1.1 CHOLINE ACETYLTRANSFERASE; CHAT Peroxisomal carnitine O-acetyl transferase (carnitine acylase (CAT or CrAT)) P43155 118490
4.C.2.1.1 CARNITINE PALMITOYLTRANSFERASE I DEFICIENCY Peroxisomal carnitine O-acetyl transferase (carnitine acylase (CAT or CrAT)) P43155 255120
4.C.2.1.1 CARNITINE PALMITOYLTRANSFERASE II DEFICIENCY, LETHAL NEONATAL Peroxisomal carnitine O-acetyl transferase (carnitine acylase (CAT or CrAT)) P43155 608836
2.A.53.2.2 SOLUTE CARRIER FAMILY 26 (ANION TRANSPORTER), MEMBER 6: SLC26A6 Canicular sulfate:HCO3- antiporter (Slc26a1)
P45380 610068
9.A.48.1.1 SYNAPTOTAGMIN 7; SYT7 The Unconventional Protein Secretion System, UPSS P46096 604146
9.A.48.1.1 BCL6 COREPRESSOR; BCOR The Unconventional Protein Secretion System, UPSS P46096 300485
9.A.48.1.1 CONE-ROD DYSTROPHY 7; CORD7 The Unconventional Protein Secretion System, UPSS P46096 603649
9.A.48.1.1 HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS, FAMILIAL, 3; FHL3 The Unconventional Protein Secretion System, UPSS P46096 608898
9.A.48.1.1 COPINE VII; CPNE7 The Unconventional Protein Secretion System, UPSS P46096 605689
9.A.48.1.1 MUSCULAR DYSTROPHY, LIMB-GIRDLE, TYPE 2B; LGMD2B The Unconventional Protein Secretion System, UPSS P46096 253601
1.A.9.2.1 5-@HYDROXYTRYPTAMINE RECEPTOR 3A; HTR3A

Serotonin (5-hydroxytryptamine)-activated cation-selective channel. Residues in TMS2 and the cytoplasmic loop linking TMSs 3 and 4 influence conductance, selectivity, gating and desensitization (Peters et al., 2010; McKinnon et al., 2011).

P46098 182139
1.A.9.5.2 GAMMA-AMINOBUTYRIC ACID RECEPTOR, ALPHA-1; GABRA1

γ-aminobutyric acid (GABA)-inhibited Cl- channel, type A (α-, β- γ-subunit precursors), regulated by GABA receptor accessory protein, GABARAP (Luu et al., 2006). The major central endocannabinoid, 2-Arachidonoyl glycerol (2-AG), directly acts at GABA(A) receptors. It potentiates the receptor at low GABA concentrations (Sigel et al., 2011).

P47869 137160
1.A.9.5.2 GAMMA-AMINOBUTYRIC ACID RECEPTOR, BETA-3; GABRB3

γ-aminobutyric acid (GABA)-inhibited Cl- channel, type A (α-, β- γ-subunit precursors), regulated by GABA receptor accessory protein, GABARAP (Luu et al., 2006). The major central endocannabinoid, 2-Arachidonoyl glycerol (2-AG), directly acts at GABA(A) receptors. It potentiates the receptor at low GABA concentrations (Sigel et al., 2011).

P47869 137192
1.A.24.1.5 CATARACT, ZONULAR PULVERULENT 1; CZP1 Heteromeric (or homomeric) Connexin46/Connexin50 junction (Cx46/Cx50) (mutations in Cx50 cause cataracts) (Derosa et al., 2007). P48165 116200
2.A.19.3.1 FEBRILE CONVULSIONS, FAMILIAL, 4; FEB4

The 9 TMS cardiac Ca2+:3 Na+ antiporter, NCX1 (The Ca2+ sensor (residues 371-508) binds cytoplasmic Ca2+ allosterically to activate exchange activity) (Nicoll et al., 2006; Ren et al., 2006) NCX1 forms homodimers (Ren et al., 2008). It is present in mitochondria where it catalyzes Ca2+ efflux. TMS packing has been analyzed by Ren et al. (2010). Cytoplasmic Ca2+ regulates the dimeric NCX by binding to two adjacent Ca2+-binding domains (CBD1 and CBD2) located in the large intracellular loop between transmembrane segments 5 and 6. John et al. (2011) showed that Ca2+ decreases the distance between the cytoplasmic loops of NCX pairs, thereby activating transport.

P48765 604352
9.B.88.2.1 PLACENTAL GROWTH FACTOR; PGF Vascular endothelial growth factor, VEGF (419aas) P49767 601121
9.B.88.2.1 PLATELET-DERIVED GROWTH FACTOR C; PDGFC Vascular endothelial growth factor, VEGF (419aas) P49767 608452
1.A.54.1.1 ALZHEIMER DISEASE 2 Presenilin-1 (PS-1; STM-1; E5-1; AD) Ca2+ leak channel (part of the γ-secretase complex; expression alters the lipid raft composition in neuronal membranes (Eckert and Müller, 2009)).
P49768 104310
1.A.54.1.2 ALZHEIMER DISEASE 4 Presenilin-2 (PS-2; STM-2; E5-2; AD3 LP; AD5 PSN-2) Ca2+ leak channel P49810 606889
1.B.33.3.1 SECRETORY CARRIER MEMBRANE PROTEIN 3; SCAMP3

The mitochondrial Sorting and Assembly Machinery (SAM) includes Tom37 (Mas37; Sam37) and Tom13 (Mim1), see 3.A.8 (Paschen et al., 2005). Can assemble C-terminal α-helical anchor proteins as well as β-barrel proteins in the outer mitochondrial membrane (Stojanovski et al., 2007). Mim1 is required for the biogenesis of the beta-barrel protein Tom40 and also for membrane insertion and assembly of signal-anchored Tom receptors (Becker et al., 2008; 2011). Tom7 regulates Mdm10-mediated assembly of the mitochondrial import channel protein Tom40 (Yamano et al., 2010).

P50110 606913
2.A.53.2.1 DIASTROPHIC DYSPLASIA

Sulfate/anion transporter (diastrophic dysplasia protein) (SLC26A2). It catalyzes electroneutral SO4-, OH- and Cl- exchange regulated by extracellular Cl- (Ohana et al., 2011).

P50443 222600
1.A.6.1.1 LIDDLE SYNDROME Epithelial Na+ channel, ENaC (regulates salt and fluid homeostasis and blood pressure; regulated by Nedd4 isoforms) (Henry et al., 2003) (Cd2+ inhibits α-ENaC by binding to the internal pore where it interacts with residues in TMS2 (Takeda et al., 2007). P51168 177200
1.A.1.15.6 JERVELL AND LANGE-NIELSEN SYNDROME 1; JLNS1

K+ voltage-gated channel, KQT-like subfamily; Kv7.1; KCNQ1 (regulated by KCNE peptides which affect voltage sensor equilibrium; Rocheleau and Kobertz, 2007). Almost 300 mutations of KCNQ1 have been identified in patients, and most are linked to the long QT syndrome (Peroz et al., 2008). KCNQ1-KCNE1 complexes may interact intermittently with the actin cytoskeleton via the C-terminal region (Mashanov et al., 2010). The stoichiometry of the KCNQ1 - KCNE1 complex is flexible, with up to four KCNE1 subunits associating with the four KCNQ1 subunits of the channel (Nakajo et al., 2010).

P51787 220400
2.A.49.3.3 CHLORIDE CHANNEL 7; CLCN7 CLC-7 chloride:H+ antiporter; provides the primary Cl- permeation pathway in the lysosome (Graves et al., 2008) P51798 602727
2.A.49.2.5 CHLORIDE CHANNEL, KIDNEY, A; CLCNKA The kidney thick ascending limb of Henle's loop and collecting duct chloride channel/carrier, ClC-K2 (Br- > I- > Cl- >> cyclamate) (Adachi et al., 1994). P51802 602024
9.B.5.1.1 KELL BLOOD GROUP PRECURSOR; XK KX antigen P51811 314850
8.A.17.1.1 BRUGADA SYNDROME 5 Sodium channel ß1 subunit P53788 612838
1.B.33.3.1 ALKALINE PHOSPHATASE, PLASMA LEVEL OF, QUANTITATIVE TRAIT LOCUS 1

The mitochondrial Sorting and Assembly Machinery (SAM) includes Tom37 (Mas37; Sam37) and Tom13 (Mim1), see 3.A.8 (Paschen et al., 2005). Can assemble C-terminal α-helical anchor proteins as well as β-barrel proteins in the outer mitochondrial membrane (Stojanovski et al., 2007). Mim1 is required for the biogenesis of the beta-barrel protein Tom40 and also for membrane insertion and assembly of signal-anchored Tom receptors (Becker et al., 2008; 2011). Tom7 regulates Mdm10-mediated assembly of the mitochondrial import channel protein Tom40 (Yamano et al., 2010).

P53969 171720
2.A.1.13.1 SOLUTE CARRIER FAMILY 16 (MONOCARBOXYLIC ACID TRANSPORTER), MEMBER 1; SLC16A1

The proton-linked monocarboxylate (lactate, pyruvate, mevalonate, branched chain oxo acids, β-hydroxybutyrate, γ-hydroxybutyrate, butyrate, acetoacetate and acetate) uptake/efflux porter. Activity is stimulated by direct interaction with carbonic anhydrase isoform II (Becker et al., 2005). [This transporter interacts physically with the chaperone protein Basigin (CD147; TC #8.A.23.1.1) which is required both for targetting to the plasma membrane and for activity. Mct-2 uses a different chaperone protein, GP70. Mct-1 also transports the methionine hydroxy analogue 2-hydroxy (4-methylthio) butanate (Martin-Venegas et al., 2007). Activity is stimulated by binding of carbonic anhydrase II (Becker and Deitmer, 2008). MCT1, 3 and 4 require the ancillary protein, basigin (P35613; 8.A.23.1.1) for plasma membrane localization (Ovens et al., 2010).

P53985 600682
1.A.1.11.8 EPISODIC ATAXIA, TYPE 2; EA2 Voltage-dependent Ca2+ channel α-1A subunit (2212 aas), Cav2.1 (P/Q-type) (when mutated, leads to a human channelopathy (episodic ataxia type-2 (EA2) due to protein misfolding and retention in the E.R. (Mezghrani et al., 2008) P54282 108500
1.A.1.11.8 MIGRAINE, FAMILIAL HEMIPLEGIC, 1; FHM1 Voltage-dependent Ca2+ channel α-1A subunit (2212 aas), Cav2.1 (P/Q-type) (when mutated, leads to a human channelopathy (episodic ataxia type-2 (EA2) due to protein misfolding and retention in the E.R. (Mezghrani et al., 2008) P54282 141500
8.A.16.3.1 CRYSTALLIN, BETA-A1; CRYBA1 Tetrameric tetraspanin MP20 (4 TMS scaffold protein; Gonen et al., 2007) P54825 123610
2.A.30.3.1 PSORIASIS SUSCEPTIBILITY 5; PSORS5

NaCl/KCl symporter (basolateral), NKCC1 (may also transport NH4+ and water); (Worrell et al., 2008; Hamann et al., 2010).

P55011 604316
2.A.30.1.1 BARTTER SYNDROME, ANTENATAL, TYPE 1 NaCl/KCl symporter; the ortholog in humans when mutated can be responsible for Bartter syndrome, an autosomal recessive disease (Stechman et al., 2007). P55016 601678
3.A.16.1.1 SPASTIC PARAPLEGIA 7, AUTOSOMAL RECESSIVE; SPG7 ER retrotranslocon P55072 607259
3.A.16.1.1 MITOCHONDRIAL COMPLEX III DEFICIENCY ER retrotranslocon P55072 124000
1.A.1.15.4 POTASSIUM CHANNEL, VOLTAGE-GATED, KQT-LIKE SUBFAMILY, MEMBER 4; KCNQ4    6 TMS cell volume sensitive, voltage-gated K+ channel, KCNQ4 (mutations cause DFNA2, an autosomal dominant form of progressive hearing loss) (forms homomers or heteromers with KCNQ3) (localized to the basal membrane of cochlear outer hair cells and in several nuclei of the central auditory pathway in the brainstem). Four splice variants form heterotetramers; each subunit has different voltage and calmodulin-sensitivities (Xu et al., 2007) P56696 603537
1.C.85.1.1 DEFENSIN, BETA, 1; DEFB1 β-defensin-1 P60022 602056
3.A.5.9.1 RNA-BINDING PROTEIN S1; RNPS1

Sec-SRP translocase complex. The BAP29 and BAP31 proteins interact directly with the Sec translocon (Wilson & Barlowe et al., 2010).

P61011 606447
9.A.48.1.1 LACRIMOAURICULODENTODIGITAL SYNDROME; LADD The Unconventional Protein Secretion System, UPSS P61148 149730
2.A.6.6.1 NIEMANN-PICK DISEASE, TYPE C2

Niemann-Pick C1 AND C2 disease proteins (together may form a possible lipid/cholesterol exporter from lysosomes to other cellular sites) (Sleat et al., 2004). NPC1 deficiency causes lysosomal retention of cholesterol, sphingolipids, phospholipids, and glycolipids (Infante et al. 2008 a). NPC1 binds cholesterol, 25-hydroxycholesterol and various oxysterols (Infante et al. 2008 b; Liu et al., 2009 ). Soluble NPC2 binds cholesterol, and then passes it to the N-terminal domain of membranous NPC1 (Abi-Mosleh et al., 2009). Cholesterol trafficking in Niemann-Pick C-deficient cells is reviewed by Peake and Vance (2010).

P61916 607625
1.F.1.1.1 MYASTHENIA, FAMILIAL INFANTILE, 1

The SNARE fusion complex, fusing neurotransmitter vesicles with the presynaptic membrane. Ca2+ acts on the synaptic vesicle synaptotagmin1 to trigger rapid exocytosis (Chapman, 2008).

P63027 605809
1.A.2.1.2 SHORT QT SYNDROME 1; SQT1

G-protein enhanced inward rectifier K channel 2, IRK2 (Kir2.1)(Andersen-Tawil Syndrome (ATS-1) protein; the V302M mutation causing the syndrome, alters the G-loop cytoplasmic K conduction pathway) (Bendahhou et al., 2003; Ma et al., 2007). (Blocked by chloroquine which binds in the cytoplasmic pore domain (Rodriguez-Menchaca et al., 2008)). Forms heteromultimers with Kir3.1 and Kir3.4 (Ishihara et al., 2009). A C-terminal domain is critical for the sensitivity of Kir2.1 to cholesterol (Epshtein et al., 2009). Flecainide increases Kir2.1 currents by interacting with cysteine 311, decreasing the polyamine-induced rectification (Caballero et al., 2010).

P63252 609620
1.A.2.1.2 PIERRE ROBIN SYNDROME

G-protein enhanced inward rectifier K channel 2, IRK2 (Kir2.1)(Andersen-Tawil Syndrome (ATS-1) protein; the V302M mutation causing the syndrome, alters the G-loop cytoplasmic K conduction pathway) (Bendahhou et al., 2003; Ma et al., 2007). (Blocked by chloroquine which binds in the cytoplasmic pore domain (Rodriguez-Menchaca et al., 2008)). Forms heteromultimers with Kir3.1 and Kir3.4 (Ishihara et al., 2009). A C-terminal domain is critical for the sensitivity of Kir2.1 to cholesterol (Epshtein et al., 2009). Flecainide increases Kir2.1 currents by interacting with cysteine 311, decreasing the polyamine-induced rectification (Caballero et al., 2010).

P63252 261800
9.B.88.1.1 SELENOPROTEIN P, PLASMA, 1; SEPP1 Selenoprotein P (SelP) precursor (probably mediates transport of the reduced form, hydrogen selenide (380aas) (Ganyc and Self, 2007). P70274 601484
1.A.28.1.3 BLOOD GROUP--KIDD SYSTEM; JK Kidney urea transporter, UT-A1 (mediates transepithelial urea transport in the inner medullary collecting duct for urinary concentration. Interacts with the C-terminus of Snapin (O95295) and SNARE-associated protein) (Mistry et al., 2007). Also transports formamide, acetamide, methylurea, methylformamide, ammonium carbamate, and acrylamide, and possibly dimethylurea and thiourea as well (Zhao et al., 2007). Also the erythrocyte urea transporter, UTB (Bagnasco, 2006). P70633 111000
2.A.49.6.1 IMP DEHYDROGENASE 1; IMPDH1 Putative Cl- channel P74477 146690
2.A.3.8.15 CYSTINURIA The b0,+ amino acid (cystine) transporter associated with the cystinuria-related type II membrane glycoprotein, BAT1 which forms a heterodimer with rBAT (TC# 8.A.9.1.1). Present in the apical membrane of renal proximal tubules (Chairoungdua et al., 1999) P82252 220100
2.A.6.6.4 TRANSMEMBRANE PROTEIN 1; TMEM1 SREBP cleavage-activating protein, SCAP P97260 602103
2.A.6.6.4 CMT1A DUPLICATED REGION TRANSCRIPT 1; CDRT1 SREBP cleavage-activating protein, SCAP P97260 604596
9.B.9.1.1 LECTIN, GALACTOSIDE-BINDING, SOLUBLE, 3; LGALS3 Urate transporter (UAT) P97840 153619
1.A.5.1.1 POLYCYSTIC KIDNEY DISEASE, INFANTILE SEVERE, WITH TUBEROUS SCLEROSIS; PKDTS

Polycystin 1 (PKD1) assembles with TRPP2 (Q86VP3) in a stoichiometry of 3TRPP2: 1PKD1, forming the receptor/ion channel complex (Yu et al., 2009). The C-terminal coiled-coil complex is critical for proper assembly (Zhu et al., 2011).

P98161 600273
1.A.5.1.1 POLYCYSTIN 1-LIKE 1; PKD1L1

Polycystin 1 (PKD1) assembles with TRPP2 (Q86VP3) in a stoichiometry of 3TRPP2: 1PKD1, forming the receptor/ion channel complex (Yu et al., 2009). The C-terminal coiled-coil complex is critical for proper assembly (Zhu et al., 2011).

P98161 609721
1.A.5.1.1 EPILEPSY, LATERAL TEMPORAL LOBE, AUTOSOMAL DOMINANT; ADLTE

Polycystin 1 (PKD1) assembles with TRPP2 (Q86VP3) in a stoichiometry of 3TRPP2: 1PKD1, forming the receptor/ion channel complex (Yu et al., 2009). The C-terminal coiled-coil complex is critical for proper assembly (Zhu et al., 2011).

P98161 600512
1.A.5.1.1 MYELOID DIFFERENTIATION PRIMARY RESPONSE GENE 88; MYD88

Polycystin 1 (PKD1) assembles with TRPP2 (Q86VP3) in a stoichiometry of 3TRPP2: 1PKD1, forming the receptor/ion channel complex (Yu et al., 2009). The C-terminal coiled-coil complex is critical for proper assembly (Zhu et al., 2011).

P98161 602170
1.A.5.1.1 TREMOR, HEREDITARY ESSENTIAL, 1; ETM1

Polycystin 1 (PKD1) assembles with TRPP2 (Q86VP3) in a stoichiometry of 3TRPP2: 1PKD1, forming the receptor/ion channel complex (Yu et al., 2009). The C-terminal coiled-coil complex is critical for proper assembly (Zhu et al., 2011).

P98161 190300
1.A.5.1.1 REGENERATING ISLET-DERIVED 3-ALPHA; REG3A

Polycystin 1 (PKD1) assembles with TRPP2 (Q86VP3) in a stoichiometry of 3TRPP2: 1PKD1, forming the receptor/ion channel complex (Yu et al., 2009). The C-terminal coiled-coil complex is critical for proper assembly (Zhu et al., 2011).

P98161 167805
1.A.5.1.1 PHOSPHOLIPASE A2 RECEPTOR 1; PLA2R1

Polycystin 1 (PKD1) assembles with TRPP2 (Q86VP3) in a stoichiometry of 3TRPP2: 1PKD1, forming the receptor/ion channel complex (Yu et al., 2009). The C-terminal coiled-coil complex is critical for proper assembly (Zhu et al., 2011).

P98161 604939
3.A.3.2.5 ATPase, Ca(2+)-TRANSPORTING, TYPE 2C, MEMBER 1; ATP2C1

The Golgi Ca2+ , Mn2+ -ATPase, hSPCA1 (efflux) (the Hailey-Hailey disease protein). Involved in responses to golgi stress, apoptosis and midgestational death (Okunade et al., 2007). SPCA1 transports Mn2+ from the cytosol into the Golgi. Increasing Golgi Mn2+ transport increased cell viability upon Mn2+ exposure, supporting a role in the management of Mn2+ -induced neurotoxicity (Mukhopadhyay and Linstedt, 2011).

P98194 604384
2.A.29.4.2 SOLUTE CARRIER FAMILY 25 (CARNITINE/ACYLCARNITINE TRANSLOCASE), MEMBER 20; SLC25A20 Phosphate carrier protein (PiC); mitochondrial precursor (PTP) (SLC25A3) Q00325 212138
8.A.33.1.1 FATTY ACID-BINDING PROTEIN 4; FABP4 The epidermal (psoriasis-associated) fatty acid binding protein, FABP (Wang et al., 2007) Q01469 600434
8.A.33.1.1 ANDROGEN INSENSITIVITY SYNDROME; AIS The epidermal (psoriasis-associated) fatty acid binding protein, FABP (Wang et al., 2007) Q01469 300068
8.A.28.1.1 ANKYRIN 2; ANK2 Ankyrin-B Q01484 106410
8.A.28.1.1 SPHEROCYTOSIS, TYPE 1; SPH1 Ankyrin-B Q01484 182900
8.A.28.1.1 NEPHRONOPHTHISIS 2; NPHP2 Ankyrin-B Q01484 602088
8.A.28.1.1 DEATH-ASSOCIATED PROTEIN KINASE 1; DAPK1 Ankyrin-B Q01484 600831
8.A.28.1.1 PHOSPHOLIPASE A2, GROUP VI; PLA2G6 Ankyrin-B Q01484 603604
8.A.28.1.1 MAJOR HISTOCOMPATIBILITY COMPLEX, CLASS I, B; HLA-B Ankyrin-B Q01484 142830
8.A.28.1.1 NUCLEAR FACTOR KAPPA-B, SUBUNIT 2; NFKB2 Ankyrin-B Q01484 164012
8.A.28.1.1 MELANOMA, CUTANEOUS MALIGNANT, SUSCEPTIBILITY TO, 3; CMM3 Ankyrin-B Q01484 609048
8.A.28.1.1 TUMOR NECROSIS FACTOR RECEPTOR SUPERFAMILY, MEMBER 6; TNFRSF6 Ankyrin-B Q01484 134637
2.A.29.12.1 SOLUTE CARRIER FAMILY 25 (MITOCHONDRIAL CARRIER, GRAVES DISEASE AUTOANTIGEN), MEMBER 16; SLC25A16 Grave’s disease carrier (GDC) protein (may transport coenzyme A or a coenzyme A precursor) (SLC25A16 for the human orthologue) Q01888 139080
1.A.11.4.3 RHESUS BLOOD GROUP-ASSOCIATED GLYCOPROTEIN; RHAG

Rhesus (Rh) complex (tetramer: RhAG2, RhCE1, RhD1) (Exports ammonia from human red blood cells) (Conroy et al., 2005)

Q02094 180297
1.A.11.4.3 RHESUS BLOOD GROUP, D ANTIGEN; RHD

Rhesus (Rh) complex (tetramer: RhAG2, RhCE1, RhD1) (Exports ammonia from human red blood cells) (Conroy et al., 2005)

Q02161 111680
1.C.63.1.2 MICROPHTHALMIA, SYNDROMIC 2; MCOPS2 α-latroinsectotoxin precursor (α-LIT) (1411aas) (Shatursky et al., 2007) Q02989 300166
3.A.1.209.1 TRANSPORTER, ATP-BINDING CASSETTE, MAJOR HISTOCOMPATIBILITY COMPLEX, 2; TAP2

MHC heterodimeric peptide exporter (TAP) (from cytoplasm to the endoplasmic reticulum) (TAP1=ABCB2; TAP2=ABCB3) (defects in TAP1 or TAP2 cause immunodeficiency) (TAP1/TAP2 is stabilized by tapasin isoforms 1, 2 and 3) (Raghuraman et al., 2002). TAP1 has 10 TMSs, 4 unique N-terminal TMSs and 6 TMSs that form the translocation pore with N- and C-termini in the cytosol (Schrodt et al., 2006). The TAP2 nucleotide binding site appears to be the main catalytic active site driving transport suggesting asymmetry in the transporter (Perria et al., 2006). The TAP complex shows strict coupling between peptide binding and ATP hydrolysis, revealing no basal ATPase activity in the absence of peptides (Herget et al., 2009).

The transporter associated with antigen processing (TAP) plays a key role in the adaptive immune defense against infected or malignantly transformed cells by translocating proteasomal degradation products into the lumen of the endoplasmic reticulum for loading onto MHC class I molecules. TAP transports peptides from 8 to 40 residues, including even branched or modified molecules, suggestive of structural flexibility of the substrate-binding pocket. The bound peptides in side-chains' mobility was strongly restricted at the ends of the peptide, whereas the central region was flexible. Peptides bind to TAP in an extended kinked structure, analogous to those bound to MHC class I proteins (Herget et al., 2011).

Q03518 170261
3.A.3.5.6 CUTIS LAXA, X-LINKED Cu+-ATPase, ATP7A (MNK or Mc1) (efflux from the cytosol into the secretory pathway) (Menkes disease protein, α-chain). Expressed in Purkinje cells early in development and later in Bergmann glia. In melanocytes, it delivers Cu2+ to tyrosinase (Barnes et al., 2005). ATP7A has dual functions: 1) it incorporates copper into copper-dependent enzymes; and 2) it maintains intracellular copper levels by removing excess copper from the cytosol. To accomplish both functions, the protein traffics between different cellular locations, depending on copper levels (Bertini and Rosato, 2008). Q04656 304150
2.A.45.2.1 ALBINISM, OCULOCUTANEOUS, TYPE IA; OCA1A P-protein; possible tyrosine transporter (also called "melanocyte-specific transporter", "oculocutaneous albinism-related protein" and "pink-eyed dilution gene product") Q04671 203100
8.A.9.1.1 SOLUTE CARRIER FAMILY 3 (CYSTINE, DIBASIC, AND NEUTRAL AMINO ACID TRANSPORTER), MEMBER 1; SLC3A1 rBAT Q05839 104614
2.A.49.2.4 BSND GENE The kidney medulla chloride channel/carrier ClC-K1 (regulated by dehydration; functions in urinary concentration) (Uchida et al., 1993). Q06393 606412
2.A.58.1.1 SOLUTE CARRIER FAMILY 34 (SODIUM/PHOSPHATE COTRANSPORTER), MEMBER 3; SLC34A3

Renal Na+-dependent phosphate transport protein 2 (NPT2). Catalyzes 3Na+:1Pi symport (Ghezzi et al., 2009).

Q06496 609826
1.A.21.1.2 MYELOID CELL LEUKEMIA 1; MCL1 The mitochondrial apoptosis-inducing channel-forming protein, BAX
Q07812 159552
1.A.21.1.1 B-CELL CLL/LYMPHOMA 2; BCL2 Apoptosis regulator Bcl-X(L) Q07817 151430
3.A.8.1.1 3-@METHYLGLUTACONIC ACIDURIA, TYPE I

Mitochondrial protein translocase (MPT) (Chacinska et al., 2005; Mokranjac et al., 2005; Bihlmaier et al., 2007). The crystal structure of the intermembrane space domain of yeast Tim50 has been solved to 1.83 Å resolution (Qian et al., 2011). A protruding beta-hairpin of Tim50 is crucial for interaction with Tim23, providing a molecular basis for the cooperation of Tim50 and Tim23 in preprotein translocation to the protein-conducting channel of the mitochondrial inner membrane (Qian et al., 2011). 

Q07914 250950
9.B.39.1.1 ACTION MYOCLONUS-RENAL FAILURE SYNDROME; AMRF CD36 antigen Q08857 254900
9.B.39.1.1 SCAVENGER RECEPTOR CLASS B, MEMBER 2; SCARB2 CD36 antigen Q08857 602257
3.A.1.208.4 POTASSIUM CHANNEL, INWARDLY RECTIFYING, SUBFAMILY J, MEMBER 11; KCNJ11

SUR1 sulfonylurea receptor; subunit and regulator of α-cell ATP-sensitive K+ channel (TC #1.A.2); determines ATP sensitivity; no inherent transport function known; associated with persistent hyperinsulinemic hypoglycemia of infancy due to focal adenomatous hyperplasia (also called ABCC8). Gain-of-function mutations in the genes encoding the ATP-sensitive potassium (K(ATP)) channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) cause neonatal diabetes mellitus. Because mutant channels are inhibited less strongly by MgATP, this increases K(ATP) currents in pancreatic beta cells, thus reducing insulin secretion and producing diabetes (de Wet et al., 2007). Binds ligands (blockers): glibenclamide, tolbutamide, and meglitinide as well as agonists, SR47063 (a cromakalim analog), P1075 (a pinacidil analog), and diazoxide (Bessadok et al., 2011).

Q09428 600937
1.A.31.1.4 HYPERTROPHIC NEUROPATHY OF DEJERINE-SOTTAS

Annexin 2 (forms a tetrameric complex with the S100A10 protein and binds the C-terminus of the AHNAK protein via the N-terminus of annexin 2 (De Seranno et al., 2006)

Q09666 145900
3.A.2.1.3 ATP SYNTHASE, H+ TRANSPORTING, MITOCHONDRIAL F1 COMPLEX, GAMMA SUBUNIT 1; ATP5C1 H+-translocating F-type ATPase Q12165 108729
1.A.1.20.1 POTASSIUM CHANNEL, VOLTAGE-GATED, SUBFAMILY H, MEMBER 2; KCNH2

K+ voltage-gated ether-a-go-go-related channel, H-ERG (Erg1) subunit Kv11.1 (long QT syndrome type 2) (Gong et al., 2006) (forms a heteromeric K+ channel regulating cardiac repolarization, neuronal firing frequency and neoplastic cell growth. Oligomerization is due to N-terminal interactions between two splice variants, hERG1a and hERG1b (Phartiyal et al., 2007)).Structure funtion relationships of ERG channel activation and inhibition have been reviewed (Durdagi et al., 2010). Interactions between the N-terminal domain and the transmembrane core modulate hERG K+ channel gating (Fernández-Trillo et al., 2011).

Q12809 152427
1.A.5.2.1 POLYCYSTIN 2-LIKE 2; PKD2L2

Polycystin 2 (PKD2) (Anyatonwu and Ehrlich, 2005). Regulated by α-actinin (AAC17470) by direct binding (Li et al., 2007). Regulated by diaphanous-related formin 1 (mDia1) (Bai et al., 2008). Has 6 TMSs with N- and C- termini inside (Hoffmeister et al., 2010).

Q13563 604669
3.A.20.1.1 PEROXISOME BIOGENESIS FACTOR 6; PEX6

The peroxisomal importing translocon with receptors: Pex5p and Pex7p; and receptor facilitator: Pex4p

Q13608 601498
1.A.1.11.4 BRUGADA SYNDROME 1

The voltage-dependent L-type Ca2+ channel α-subunit-1C (L-type Cav1.2), CACNA1C (mutations cause Timothy's syndrome, a disorder associated with autism) (Splawski et al., 2006). The C-terminus of Cav1.2 encodes a transcription factor (Gomez-Ospina et al., 2006). Cav1.2 associates with the α-2, δ-1, β and γ subunits (Yang et al., 2011). The CRAC channel activator STIM1 binds and inhibits L-type voltage-gated calcium channel, Cav1.2 (Park et al., 2010).

Q13936 601144
1.A.1.5.3 CYCLIC NUCLEOTIDE-GATED CHANNEL, BETA-1; CNGB1 Heterotetrameric (3A:1B) rod photoreceptor cyclic GMP-gated cation channel, CNG (Zhong et al., 2002). Defects produce channelopathies (Biel& Michalakis, 2007). Q14028 600724
1.A.1.10.3 POTASSIUM CHANNEL, VOLTAGE-GATED, ISK-RELATED SUBFAMILY, MEMBER 1; KCNE1 Ca2+-regulated heart Na+ channel, Nav1.5 (COOH terminus functions in the control of channel inactivation and in pathologies caused by inherited mutations that disrupt it (Glaaser et al., 2006)); regulated by ProTx-II Toxin (Smith et al., 2007), telethonin, the titin cap protein; 167aas; secreted protein; O15273) (Mazzone et al., 2008), and the Mog1 protein, a central component of the channel complex (Wu et al., 2008). Nav1.5, the principal Na+ channel in the heart, possesses an ankyrin binding site; direct interaction with ankyrin-G is required for the expression of Nav1.5 at the cardiomyocyte cell surface (Bennett and Healy, 2008; Lowe et al., 2008). Mutations cause type 3 long QT syndrome and type 1 Brugada syndrome, two distinct heritable arrhythmia syndromes (Mazzone et al., 2008). Q14524 176261
1.A.1.10.3 LONG QT SYNDROME 1; LQT1 Ca2+-regulated heart Na+ channel, Nav1.5 (COOH terminus functions in the control of channel inactivation and in pathologies caused by inherited mutations that disrupt it (Glaaser et al., 2006)); regulated by ProTx-II Toxin (Smith et al., 2007), telethonin, the titin cap protein; 167aas; secreted protein; O15273) (Mazzone et al., 2008), and the Mog1 protein, a central component of the channel complex (Wu et al., 2008). Nav1.5, the principal Na+ channel in the heart, possesses an ankyrin binding site; direct interaction with ankyrin-G is required for the expression of Nav1.5 at the cardiomyocyte cell surface (Bennett and Healy, 2008; Lowe et al., 2008). Mutations cause type 3 long QT syndrome and type 1 Brugada syndrome, two distinct heritable arrhythmia syndromes (Mazzone et al., 2008). Q14524 192500
1.A.1.2.11 RETINAL CONE DYSTROPHY 3A; RCD3A

Voltage-gated K+ channel, Shab-related, Kv2.1 (858aas) (Crystal structure known, Long et al., 2007). Rat Kv2.1 and Kv2.2 (long) are colocalized in the somata and proximal dendrites of cortical pyramidal neurons and are capable of forming functional heteromeric delayed rectifier channels. The delayed rectifer currents, which regulate action potential firing, are encoded by heteromeric Kv2 channels in cortical neurons (Kihira et al., 2010). Phosphorylation by AMP-activated protein kinase regulates membrane excitability (Ikematsu et al., 2011).

Q14721 610024
9.B.64.1.1 START DOMAIN-CONTAINING PROTEIN 3; STARD3 The metastatic lymph node-64 (MLN-64) protein Q14849 607048
3.A.18.1.1 SPLICING FACTOR, ARGININE/SERINE-RICH, 9; SFRS9

The nuclear mRNA Export Complex (mRNA-E also called TREX) (including the exon junction complex) [TAP+p15 interact as a complex with the nuclear pore to facilitate mRNA transport to the cytoplasm] (Nojimma et al. 2007; Cheng et al., 2006)

Q15287 601943
3.A.18.1.1 CD44 ANTIGEN; CD44

The nuclear mRNA Export Complex (mRNA-E also called TREX) (including the exon junction complex) [TAP+p15 interact as a complex with the nuclear pore to facilitate mRNA transport to the cytoplasm] (Nojimma et al. 2007; Cheng et al., 2006)

Q15287 107269
9.A.1.1.1 MILLER-DIEKER LISSENCEPHALY SYNDROME; MDLS The RalA binding protein 1 (RalBP1 or RLIP76) multidrug exporter (Awasthi et al., 2000; Sharma et al., 2001; Awasthi et al., 2007) Q15311 247200
9.A.1.1.1 DUANE RETRACTION SYNDROME 2 The RalA binding protein 1 (RalBP1 or RLIP76) multidrug exporter (Awasthi et al., 2000; Sharma et al., 2001; Awasthi et al., 2007) Q15311 604356
9.A.1.1.1 LEUKEMIA, ACUTE LYMPHOBLASTIC; ALL The RalA binding protein 1 (RalBP1 or RLIP76) multidrug exporter (Awasthi et al., 2000; Sharma et al., 2001; Awasthi et al., 2007) Q15311 613065
9.A.1.1.1 RAS-ASSOCIATED PROTEIN RAB8A; RAB8A The RalA binding protein 1 (RalBP1 or RLIP76) multidrug exporter (Awasthi et al., 2000; Sharma et al., 2001; Awasthi et al., 2007) Q15311 165040
1.A.1.10.5 ERYTHERMALGIA, PRIMARY

Voltage-sensitive Na channel, type 9, α-subunit, Nav1.7 or SCN9A (orthologous to 1.A.1.10.1). Loss of function results in a channelopathy that causes the congenital inability to experience pain (Cregg et al., 2010). An S241T mutation causes inherited erythromelalgia IEM; erythermalgia, an autosomal dominant neuropathy characterized by burning pain in the extremities in response to mild warmth (due to altered gating) (Lampert et al., 2006; Drenth and Waxman, 2007). Gain-of-function mutations in the Na(v)1.7 channel lead to DRG neuron hyperexcitability associated with severe pain, whereas loss of the Na(v)1.7 channel in patients leads to indifference to pain (Dib-Hajj et al., 2007). Blocked by 1-benzazepin-2-one (Kd = 1.6 nM) (Williams et al., 2007). Mutations in the Nav1.7 Na channel α-subunit give rise to familial pain syndromes (Catterall et al., 2008; Fischer and Waxman, 2010 ).

Q15858 133020
1.F.1.1.1 COMPLEXIN 2; CPLX2

The SNARE fusion complex, fusing neurotransmitter vesicles with the presynaptic membrane. Ca2+ acts on the synaptic vesicle synaptotagmin1 to trigger rapid exocytosis (Chapman, 2008).

Q16623 605033
1.F.1.1.1 HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS, FAMILIAL, 4; FHL4

The SNARE fusion complex, fusing neurotransmitter vesicles with the presynaptic membrane. Ca2+ acts on the synaptic vesicle synaptotagmin1 to trigger rapid exocytosis (Chapman, 2008).

Q16623 603552
1.F.1.1.1 PSEUDOHYPOPARATHYROIDISM, TYPE IB; PHP1B

The SNARE fusion complex, fusing neurotransmitter vesicles with the presynaptic membrane. Ca2+ acts on the synaptic vesicle synaptotagmin1 to trigger rapid exocytosis (Chapman, 2008).

Q16623 603233
1.A.9.1.2 CHOLINERGIC RECEPTOR, NEURONAL NICOTINIC, ALPHA POLYPEPTIDE 5; CHRNA5

The nicotinic acetylcholine activated cation selective channel precursor, Acr-2 or Acr-3/Unc-38 (both β and α-type chains are required for activity; levamisole-gated; activity reduced by antagonists mecamylamine and d-tubocurarine) (Squire et al., 1995; Baylis et al., 1997). nAChR and TRPC channel proteins (1.A.4) mediate nicotine addiction in many animals from humans to worms (Feng et al., 2006).

Q23022 118505
1.A.9.1.2 EPILEPSY, NOCTURNAL FRONTAL LOBE, TYPE 1

The nicotinic acetylcholine activated cation selective channel precursor, Acr-2 or Acr-3/Unc-38 (both β and α-type chains are required for activity; levamisole-gated; activity reduced by antagonists mecamylamine and d-tubocurarine) (Squire et al., 1995; Baylis et al., 1997). nAChR and TRPC channel proteins (1.A.4) mediate nicotine addiction in many animals from humans to worms (Feng et al., 2006).

Q23022 600513
1.A.9.1.2 MYASTHENIC SYNDROME, CONGENITAL, SLOW-CHANNEL; SCCMS

The nicotinic acetylcholine activated cation selective channel precursor, Acr-2 or Acr-3/Unc-38 (both β and α-type chains are required for activity; levamisole-gated; activity reduced by antagonists mecamylamine and d-tubocurarine) (Squire et al., 1995; Baylis et al., 1997). nAChR and TRPC channel proteins (1.A.4) mediate nicotine addiction in many animals from humans to worms (Feng et al., 2006).

Q23022 601462
3.A.3.8.1 CHOLESTASIS, INTRAHEPATIC, OF PREGNANCY; ICP

Golgi Aminophospholipid (phosphatidyl serine and phosphatidyl ethanolamine) translocase (flipping from the exofacial to the cytosolic leaflet of membranes to generate phospholipid asymmetry), required for vesicle-mediated protein transport from the Golgi and endosomes. The system has been reconstituted after purification in proteoliposomes. It flips phosphatidyl serine but not phosphatidylcholine or sphinogomyelin (Zhou and Graham, 2009).

Q29449 147480
9.A.40.3.1 UROFACIAL SYNDROME; UFS

Broad specificity heavy metal transporter, ACDP2 (ancient conserved domain-containing protein-2), CNNM2 or Cyclin2. Transports Mg2+ (Quamme, 2009).

Q3TWN3 236730
9.A.40.3.1 JALILI SYNDROME

Broad specificity heavy metal transporter, ACDP2 (ancient conserved domain-containing protein-2), CNNM2 or Cyclin2. Transports Mg2+ (Quamme, 2009).

Q3TWN3 217080
4.C.1.1.7 ATP-BINDING CASSETTE, SUBFAMILY D, MEMBER 4; ABCD4 4-Coumarate CoA synthase (ligase 2) (EC 6.2.1.12) Q42524 603214
4.C.1.1.7 SAETHRE-CHOTZEN SYNDROME; SCS 4-Coumarate CoA synthase (ligase 2) (EC 6.2.1.12) Q42524 101400
1.B.12.2.2 COLLAGEN, TYPE IX, ALPHA-3; COL9A3 Autoexporter of tracheal colonization factor Q45343 120270
3.A.1.14.18 TRANSCRIPTION ELONGATION FACTOR B, POLYPEPTIDE 2; TCEB2 Heme acquisition ABC uptake transporter, IsdDEF (Liu et al., 2008) Q5HGV2 600787
2.A.1.2.39 TETRACYCLINE TRANSPORTER-LIKE PROTEIN Tetracycline-specific exporter, TetA41 (most like 2.A.1.2.4) (Thompson et al., 2007). Q5JAK9 610977
1.A.1.11.13 SKIN/HAIR/EYE PIGMENTATION, VARIATION IN, 9; SHEP9 Two-pore Ca2+ channel protein 1, TPC1 (Km(Ca2+))=50 µM; voltage gated; 461 aas; 6TMSs) (Hashimoto et al., 2004; Kurusu et al, 2004; 2005) Q5QM84 611742
1.A.17.1.1 SIX-TRANSMEMBRANE EPITHELIAL ANTIGEN OF PROSTATE 2; STEAP2

The plasma membrane Ca2+-dependent chloride channel, TMEM16A (Anoctamin 1a). The mouse orthologue (Q8BHY3), TMEM16A (956aas), is localized to the apical membranes of epithelia as well as intracellular membranes in many cell types. Knockout mice show diminished rhythmic contraction of gastric smooth muscle (Huang et al., 2009). ANO1 is also required for normal tracheal development (Ousingsawat et al., 2009).

Q5XXA6 605094
2.A.43.3.1 CONGENITAL DISORDER OF GLYCOSYLATION, TYPE If; CDG1F The Lec15/Lec35 suppressor, SL15 Q60441 609180
8.A.34.1.1 SORBIN AND SH3-DOMAINS CONTAINING 1; SORBS1 Endophilin A1 (BAR-domain, SH3-domain containing GRB2-like protein 2 (Endophilin 1 or A1; SH3-domain protein 2A)) Q62420 605264
8.A.34.1.1 HCLS1-ASSOCIATED PROTEIN X1; HAX1 Endophilin A1 (BAR-domain, SH3-domain containing GRB2-like protein 2 (Endophilin 1 or A1; SH3-domain protein 2A)) Q62420 605998
8.A.34.1.1 CORTACTIN; CTTN Endophilin A1 (BAR-domain, SH3-domain containing GRB2-like protein 2 (Endophilin 1 or A1; SH3-domain protein 2A)) Q62420 164765
8.A.34.1.1 NEBULETTE Endophilin A1 (BAR-domain, SH3-domain containing GRB2-like protein 2 (Endophilin 1 or A1; SH3-domain protein 2A)) Q62420 605491
8.A.34.1.1 TUMOR NECROSIS FACTOR LIGAND SUPERFAMILY, MEMBER 6; TNFSF6 Endophilin A1 (BAR-domain, SH3-domain containing GRB2-like protein 2 (Endophilin 1 or A1; SH3-domain protein 2A)) Q62420 134638
8.A.34.1.1 NEUTROPHIL CYTOSOLIC FACTOR 2; NCF2 Endophilin A1 (BAR-domain, SH3-domain containing GRB2-like protein 2 (Endophilin 1 or A1; SH3-domain protein 2A)) Q62420 608515
8.A.34.1.1 CATENIN, BETA-1; CTNNB1 Endophilin A1 (BAR-domain, SH3-domain containing GRB2-like protein 2 (Endophilin 1 or A1; SH3-domain protein 2A)) Q62420 116806
8.A.34.1.1 PYOGENIC STERILE ARTHRITIS, PYODERMA GANGRENOSUM, AND ACNE Endophilin A1 (BAR-domain, SH3-domain containing GRB2-like protein 2 (Endophilin 1 or A1; SH3-domain protein 2A)) Q62420 604416
2.A.30.5.2 SOLUTE CARRIER FAMILY 12 (SODIUM/CHLORIDE TRANSPORTER), MEMBER 6; SLC12A6

KCl symporter KCC2. It influences postsynaptic AMPA receptor content and lateral diffusion in dendritic spines (Gauvain et al., 2011).

Q63633 604878
1.B.12.12.1 MUCIN 4, TRACHEOBRONCHIAL; MUC4 The acidic repeat AT protein, ARP (1441 aas) (Litwin et al., 2007) (shows N-terminal sequence similarity to 1.B.12.2.3 and C-terminal similarity to 1.B.12.8.2). Q6G2D1 158372
4.C.3.1.1 HYPERCHOLANEMIA, FAMILIAL; FHCA Peroxisomal Acyl-CoA thioesterase 5, Acot5 (2-4 putative TMSs) (two domains: N-terminal Bile Acid-CoA:amino acid N-acetyl transferase domain and a C-terminal Acyl-CoA thioester hydrolase domain) Q6Q2Z6 607748
1.A.6.1.6 PAROXYSMAL NONKINESIGENIC DYSKINESIA 1; PNKD1 Acid sensing cation channel ASIC4.1 (senses and gated by extracellular pH) (forms homomers and heteromers with ASIC4.2) (Chen et al., 2007) Q708S4 118800
2.A.28.1.3 GLUCOSE-6-PHOSPHATE DEHYDROGENASE; G6PD The organic anion:Na+ symporter, SOAT (transports estrone-3-sulfate (Km= 31 μM) and dehydropiandrosterone sulfate (Km = 30 μM) but not taurocholate, estradiol-17β-glucuronide or ouabain) (Geyer et al., 2004) Q70EX6 305900
1.C.46.2.1 NATRIURETIC PEPTIDE PRECURSOR A; NPPA Cardiac Peptide (145aas)
Q78AW6 108780
1.A.4.7.1 NOTCH, DROSOPHILA, HOMOLOG OF, 2; NOTCH2 The mechanically gated hearing and balance ion channel in sensory hair cells of the vertebrate inner ear, NompC (Sidi et al., 2003) Q7T1G6 600275
1.A.4.7.1 ADVANCED GLYCOSYLATION END PRODUCT-SPECIFIC RECEPTOR; AGER The mechanically gated hearing and balance ion channel in sensory hair cells of the vertebrate inner ear, NompC (Sidi et al., 2003) Q7T1G6 600214
1.A.4.7.1 T-CELL ACTIVATION GTPase-ACTIVATING PROTEIN; TAGAP The mechanically gated hearing and balance ion channel in sensory hair cells of the vertebrate inner ear, NompC (Sidi et al., 2003) Q7T1G6 609667
1.A.4.7.1 DEMENTIA, LEWY BODY; DLB The mechanically gated hearing and balance ion channel in sensory hair cells of the vertebrate inner ear, NompC (Sidi et al., 2003) Q7T1G6 127750
1.A.4.7.1 SYNUCLEIN-ALPHA-INTERACTING PROTEIN; SNCAIP The mechanically gated hearing and balance ion channel in sensory hair cells of the vertebrate inner ear, NompC (Sidi et al., 2003) Q7T1G6 603779
1.A.4.7.1 PULMONARY HYPERTENSION, CHRONIC THROMBOEMBOLIC, WITHOUT DEEP VEIN THROMBOSIS, SUSCEPTIBILITY TO The mechanically gated hearing and balance ion channel in sensory hair cells of the vertebrate inner ear, NompC (Sidi et al., 2003) Q7T1G6 612862
2.A.1.14.15 SOLUTE CARRIER FAMILY 17 (SODIUM PHOSPHATE COTRANSPORTER), MEMBER 1; SLC17A1 Apical membrane renal proximal tubule. Voltage-driven but Na+-independent organic anion transporter, OATv1 (transports p-aminohippurate; probably transports organic anions but not cations and not inorganic phosphate. It may catalyze excretion of various drugs, xenobiotics, and their metabolites) (Jutabha et al., 2003) Q7YQJ7 182308
1.A.1.5.4 ACHROMATOPSIA 3; ACHM3 Olfactory heteromeric cyclic nucleotide-gated cation (mainly Na+, Ca2+) channel CNGA2/CNGA4/CNGB1b (present in sensory cilia of olfactory receptor neurons; activated by odorant-induced increases in cAMP concentration) (Michalakis et al., 2006). Q80XL8 262300
1.A.24.2.1 LEUKODYSTROPHY, HYPOMYELINATING, 3 Connexin 47 gap junction (catalyzes intercellular diffusion of neurobiotin, Lucifer yellow and 4',6-diamidino-2-phenylindole; expressed in brain and spinal cord neurons) (Teubner et al., 2001). Possesses sequences between TMSs 2 and 3 and following TMS 4 that differ from these regions in most other connexins. Q8BQU6 260600
8.A.30.1.1 UBIQUITIN-CONJUGATING ENZYME E2L 3; UBE2L3 Nedd4-2 (1004 aas, 0 TMSs: Ubiquitin protein ligase, E3)/Nedd4 interacting protein-2 (311 aas; 3 TMSs: ww domain binding protein 5 (N4WBP5A)) (Zhou, et al., 2007) Q8CFI0 603721
8.A.30.1.1 SUPEROXIDE DISMUTASE 1; SOD1 Nedd4-2 (1004 aas, 0 TMSs: Ubiquitin protein ligase, E3)/Nedd4 interacting protein-2 (311 aas; 3 TMSs: ww domain binding protein 5 (N4WBP5A)) (Zhou, et al., 2007) Q8CFI0 147450
8.A.30.1.1 UBIQUITIN-PROTEIN LIGASE E3A; UBE3A Nedd4-2 (1004 aas, 0 TMSs: Ubiquitin protein ligase, E3)/Nedd4 interacting protein-2 (311 aas; 3 TMSs: ww domain binding protein 5 (N4WBP5A)) (Zhou, et al., 2007) Q8CFI0 601623
8.A.30.1.1 ESOPHAGEAL CANCER Nedd4-2 (1004 aas, 0 TMSs: Ubiquitin protein ligase, E3)/Nedd4 interacting protein-2 (311 aas; 3 TMSs: ww domain binding protein 5 (N4WBP5A)) (Zhou, et al., 2007) Q8CFI0 133239
1.A.10.1.10 HYPOPARATHYROIDISM, FAMILIAL ISOLATED; FIH

The homo- and heteromeric glutamate receptor, GLR3.3/3.4 (Desensitized in 3 patterns: (1) by Glu alone; (2) by Ala, Cys, Glu or Gly; (3) by Ala, Cys, Glu, Gly, Ser or Asn (Stephens et al., 2008).

Q8GXJ4 146200
3.A.18.1.1 MCCUNE-ALBRIGHT SYNDROME; MAS

The nuclear mRNA Export Complex (mRNA-E also called TREX) (including the exon junction complex) [TAP+p15 interact as a complex with the nuclear pore to facilitate mRNA transport to the cytoplasm] (Nojimma et al. 2007; Cheng et al., 2006)

Q8IYB3 174800
3.A.18.1.1 BRITTLE CORNEA SYNDROME; BCS

The nuclear mRNA Export Complex (mRNA-E also called TREX) (including the exon junction complex) [TAP+p15 interact as a complex with the nuclear pore to facilitate mRNA transport to the cytoplasm] (Nojimma et al. 2007; Cheng et al., 2006)

Q8IYB3 229200
8.A.18.3.1 CALCIUM CHANNEL, VOLTAGE-DEPENDENT, ALPHA-2/DELTA SUBUNIT 3; CACNA2D3 Ca2+ channel, voltage-dependent, α2δ subunit 3, CACNA2D3 Q8IZS8 606399
8.B.9.1.1 PROSTATE CANCER, HEREDITARY, 13; HPC13 Triflin Q8JI39 611928
2.A.58.1.3 HYPOPHOSPHATEMIC RICKETS WITH HYPERCALCIURIA, HEREDITARY; HHRH

Renal Na+/phosphate electroneutral symporter, NPTIIc or NaPi-IIc; responsible for hypophosphatemic hypercalciuric nephrolithiasis associated with rickets (Stechman et al., 2007). Catalyzes 2Na+:1Pi symport (Ghezzi et al., 2009).

Q8N130 241530
1.H.1.1.5 CLAUDIN 19; CLDN19 Claudin-19 (Cldn19) (interacts with Cldn16 to form cation-selective tight junctions; mutations in both proteins can give rise to hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC), an inherited disorder (Hou et al., 2008). (Belongs to the PMP22-Claudin subfamily) Q8N6F1 610036
2.A.31.4.1 CORNEAL ENDOTHELIAL DYSTROPHY 2; CHED2 Boron transporter, NcBC1 (in the absence of borate, it functions as a Na+ and OH- (H+) channel; in the presence of borate, it functions as an electrogenic Na+-coupled borate cotransporter) (Park et al., 2004) Q8NBS3 217700
2.A.4.4.5 SOLUTE CARRIER FAMILY 30 (ZINC TRANSPORTER), MEMBER 8; SLC30A8 Golgi/secretory granule Zn2+ uptake (into Golgi or granules) permease, ZnT7 (Ishihara et al., 2006) Q8NEW0 611145
3.D.4.11.1 NASOPHARYNGEAL CARCINOMA 1 Cytochrome oxidase (Cox) Q8TF08 607107
4.C.3.1.2 EPILEPSY, FAMILIAL TEMPORAL LOBE; ETL2 Peroxisomal Acyl-CoA thioesterase-12, Acot12 (2-4 putative TMSs) Q8WYK0 608096
3.A.1.4.6 GLUTAMATE RECEPTOR, METABOTROPIC, 6; GRM6 The neutral amino acid permease, N-1 (transports pro, phe, leu, gly, ala, ser, gln and his, but gln and his are not transported via NatB) (Picossi et al., 2005) Q8YVY4 604096
9.B.87.2.1 CEREBELLAR HYPOPLASIA AND MENTAL RETARDATION WITH OR WITHOUT QUADRUPEDAL LOCOMOTION; CHMRQ1 Low density lipoprotein receptor, Apolipoprotein E receptor 2 (ApoER2; 996aas) [required for SelP uptake in brain and testis, but not kidney]. Q924X6 224050
9.B.87.2.1 LOW DENSITY LIPOPROTEIN RECEPTOR-RELATED PROTEIN 8; LRP8 Low density lipoprotein receptor, Apolipoprotein E receptor 2 (ApoER2; 996aas) [required for SelP uptake in brain and testis, but not kidney]. Q924X6 602600
9.B.87.2.1 PROPROTEIN CONVERTASE, SUBTILISIN/KEXIN-TYPE, 9; PCSK9 Low density lipoprotein receptor, Apolipoprotein E receptor 2 (ApoER2; 996aas) [required for SelP uptake in brain and testis, but not kidney]. Q924X6 607786
9.B.87.2.1 HEPARAN SULFATE PROTEOGLYCAN OF BASEMENT MEMBRANE; HSPG2 Low density lipoprotein receptor, Apolipoprotein E receptor 2 (ApoER2; 996aas) [required for SelP uptake in brain and testis, but not kidney]. Q924X6 142461
9.B.87.2.1 TENASCIN C; TNC Low density lipoprotein receptor, Apolipoprotein E receptor 2 (ApoER2; 996aas) [required for SelP uptake in brain and testis, but not kidney]. Q924X6 187380
9.B.87.2.1 PROTEIN S; PROS1 Low density lipoprotein receptor, Apolipoprotein E receptor 2 (ApoER2; 996aas) [required for SelP uptake in brain and testis, but not kidney]. Q924X6 176880
9.B.87.2.1 OSTEOARTHRITIS SUSCEPTIBILITY 2; OS2 Low density lipoprotein receptor, Apolipoprotein E receptor 2 (ApoER2; 996aas) [required for SelP uptake in brain and testis, but not kidney]. Q924X6 140600
9.B.87.2.1 HYPERURICEMIC NEPHROPATHY, FAMILIAL JUVENILE; HNFJ Low density lipoprotein receptor, Apolipoprotein E receptor 2 (ApoER2; 996aas) [required for SelP uptake in brain and testis, but not kidney]. Q924X6 162000
9.B.87.2.1 UROMODULIN; UMOD Low density lipoprotein receptor, Apolipoprotein E receptor 2 (ApoER2; 996aas) [required for SelP uptake in brain and testis, but not kidney]. Q924X6 191845
9.B.87.2.1 NANOPHTHALMOS 2; NNO2 Low density lipoprotein receptor, Apolipoprotein E receptor 2 (ApoER2; 996aas) [required for SelP uptake in brain and testis, but not kidney]. Q924X6 609549
9.B.87.2.1 INTERLEUKIN 8; IL8 Low density lipoprotein receptor, Apolipoprotein E receptor 2 (ApoER2; 996aas) [required for SelP uptake in brain and testis, but not kidney]. Q924X6 146930
9.B.87.2.1 THROMBOSPONDIN IV; THBS4 Low density lipoprotein receptor, Apolipoprotein E receptor 2 (ApoER2; 996aas) [required for SelP uptake in brain and testis, but not kidney]. Q924X6 600715
2.A.5.4.3 17-@BETA-HYDROXYSTEROID DEHYDROGENASE VIII; HSD17B8 Zip7 golgi Zn2+ uptake (into the cytoplasm) transporter (Ke4, Slc39a7) (Huang et al., 2005). This protein can substitute for Iar1, the indole acetic acid-alanine resistance protein, of A. thaliana (Lasswell et al., 2000) Q92504 601417
1.A.3.1.1 ARRHYTHMOGENIC RIGHT VENTRICULAR DYSPLASIA, FAMILIAL, 2; ARVD2

Ryanodine receptor Ca2+ release channel, RyR2 (causes Ca2+ release from the E.R. and causes cardiac arrhythmia) (Chelu and Wehrens, 2007). (Associates with FKBP12.6, but phosphorylation by protein kinase A on serine-2030 causes dissociation (Jones et al., 2008)).

Q92736 600996
3.A.2.2.4 CUTIS LAXA, AUTOSOMAL RECESSIVE, TYPE IIA;

The Ubiquitous Vacuolar H+ ATPase, V1/V0, has been implicated in various human diseases including osteopetrosis, renal tubule acidosis, and cancer (Hinton et al., 2009).

Q93050 219200
3.D.1.6.1 THYROID CARCINOMA, HURTHLE CELL The animal H+-translocating NADH dehydrogenase (NDH) complex (45 subunits) (Cardol et al., 2004) Q95KV7 607464
3.D.1.6.1 NADH-UBIQUINONE OXIDOREDUCTASE 1 ALPHA SUBCOMPLEX, 13; NDUFA13 The animal H+-translocating NADH dehydrogenase (NDH) complex (45 subunits) (Cardol et al., 2004) Q95KV7 609435
2.A.7.16.1 CONGENITAL DISORDER OF GLYCOSYLATION, TYPE IIc; CDG2C The GDP fucose transporter (GFT) (defective in human leukocyte adhesion disease II) Q96A29 266265
2.A.22.6.4 SOLUTE CARRIER FAMILY 6 (NEUROTRANSMITTER TRANSPORTER), MEMBER 19; SLC6A19

The neutral amino acid transporter, B0AT3 (Slc6a18); XT2 (55% identical to 2.A.22.6.3)

Q96N87 608893
2.A.1.50.1 FOLATE MALABSORPTION, HEREDITARY

The apical intestinal proton coupled, high affinity folate transporter, the hereditary folate malabsorption protein, PCFT/HCP1 (Also reported to mediate heme-iron uptake from the gut lumen with duodenal epithelial cells (Shayeghi et al., 2005; Latunde-Dada et al., 2006; Subramanian et al., 2008), but it shows a higher affinity for folate than heme) (Qiu et al., 2006). Responsible for folate uptake by choroid plexus epithelial cells (Wollack et al., 2007) and placenta (Yasuda et al., 2008). The rat orthologue (Q5EBA8) catalyzes H+-dependent folate uptake in the intestine (Inoue et al., 2008). Responsible for the rare autosomal recessive disorder, hereditary folate malabsorption (Zhao and Goldman, 2007). PCFT/ICP1, when mutated, is the cause of Hereditary Folate Malabsorption in humans (Qiu et al., 2006). Evidence for a 12 TMS topology has been presented (Zhao et al., 2010Qiu et al., 2006Zhao et al., 2011). Downregulated in Chronic Kidney Disease (CKD) in heart, liver, and brain causing malabsorption (Bukhari et al., 2011).

Q96NT5 229050
1.A.4.5.1 AMYOTROPHIC LATERAL SCLEROSIS-PARKINSONISM/DEMENTIA COMPLEX 1 Non-selective channel kinase-1; Mg2+-ATP-regulated divalent cation channel, LTRPC7 Q96QT4 105500
1.A.1.25.1 REARRANGED DURING TRANSFECTION PROTOONCOGENE; RET

The 6TMS bacterial cyclic nucleotide-regulated, voltage independent channel, MlotiK1 (Clayton et al., 2008). Gating involves large rearrangements of the cyclic nucleotide-binding domains (Mari et al., 2011).

Q98GN8 164761
3.A.1.211.5 ATP-BINDING CASSETTE, SUBFAMILY A, MEMBER 3; ABCA3

The surfactant-secreting porter, ABCA3 (exports lipids and proteins into lamellar bodies). Fatal surfactant deficiency (FSD) can result from mutations in ABCA3, causing abnormal intracellular localization (type I) or decreased ATP hydrolysis (type II). ABCA3 is found in lamellar bodies of lung alveolar type II cells where it probably secretes surfactants (mixture of lipids; e.g., PC) and proteins (e.g., surfactant proteins A, B, C and D) stored in lamellar bodies and exocytosed (Matsumura et al., 2006). ABCA3 plays an essential role in pulmonary surfactant lipid metabolism and lamellar body biogenesis, probably by transporting these lipids as substrates (Ban et al., 2007). Cheong et al., 2007 have shown that ABCA3 is critical for lamellar body biogenesis in mice. They suggest it functions in surfactant-protein B processing and lung development late in gestation. Lymphoma exosomes shield target cells from antibody attack, and exosome biogenesis is modulated by lysosome-associated ABCA3 which mediates resistance to chemotherapy. Silencing ABCA3 enhances susceptability of target cells to antibody-mediated lysis. Mechanisms of cancer cell resistance to drugs and antibodies are linked in an ABCA3-dependent pathway of exosome secretion (Aung et al., 2011).

Q99758 601615
3.A.16.1.1 DER1-LIKE DOMAIN FAMILY, MEMBER 1; DERL1 ER retrotranslocon Q9BUN8 608813
1.F.1.1.1 VESICLE-ASSOCIATED MEMBRANE PROTEIN 7: VAMP7

The SNARE fusion complex, fusing neurotransmitter vesicles with the presynaptic membrane. Ca2+ acts on the synaptic vesicle synaptotagmin1 to trigger rapid exocytosis (Chapman, 2008).

Q9BV40 300053
2.A.29.19.1 HYPERORNITHINEMIA-HYPERAMMONEMIA-HOMOCITRULLINURIA SYNDROME

Mitochondrial ornithine carrier 2 (ORC2 or OrnT2) (transports ornithine, citrulline, lysine, arginine, histidine); HHH syndrome (SLC25A2). Catalyzes ornithine:citrulline antiport and ornithine:H+ antiport (Tonazzi and Indiveri, 2011).

Q9BXI2 238970
2.A.57.1.6 HYPERPIGMENTATION, CUTANEOUS, WITH HYPERTRICHOSIS, HEPATOSPLENOMEGALY, HEART ANOMALIES, HEARING LOSS, AND HYPOGONADISM

Equilibrative (Na+-independent) low affinity nucleoside transporter, hENT3 (transports nucleosides with broad selectivity and low affinity; also transports adenine). Relatively low sensitivity to classical nucleoside transport inhibitors, nitrobenzylthioinosine, dipyridamole, and dilazep. pH optimum=5.5; present in acidic intracellular compartments (Baldwin et al., 2005). (Present largely in the lysosomes). May cause histiocytosis, perturb lysosome function and upset macrophage homeostasis when defective (Hsu et al., 2012).

Q9BZD2 612391
8.A.31.1.1 SECRETED LY6/PLAUR DOMAIN-CONTAINING PROTEIN 1; SLURP1 The Ly-6/neurotoxin-like protein1 precursor, Lynx1 Q9BZG9 606119
9.B.47.1.1 ANTERIOR PHARYNX DEFECTIVE 1, C. ELEGANS, HOMOLOG OF, B; APH1B Presenilin 1 of the γ-Secretase complex
Q9DCZ9 607630
1.A.4.2.5 SPONDYLOMETAPHYSEAL DYSPLASIA, KOZLOWSKI TYPE; SMDK

Vanilloid receptor-related, osmotically activated channel, VR-OAC (also called TRPV4 and Trp12); required for bladder voiding in mice (Gevaert et al., 2007). Regulated by Pacsin3 via its SH3 domain which affects its subcellular localization and inhibits its activity in a stimulus-specific fashion (D'hoedt et al., 2008). Responsible for autosomal dominant brachyolmia (Rock et al., 2008). Multiple gating mechanisms have been demonstrated for TRPV4 (Loukin et al., 2010).

Q9ERZ8 184252
2.A.49.2.2 PROTEINURIA, LOW MOLECULAR WEIGHT, WITH HYPERCALCIURIA AND NEPHROCALCINOSIS

Intracellular (endosomal) outward rectifying kidney Cl-:H (2:1) antiporter ClC5 (nitrate > Cl- = Br- > I- > acetate > gluconate) (Picollo and Pusch, 2005; Scheel et al., 2005); responsible for Dent''s disease, an X-linked disorder characterized by low molecular weight proteinuria, hypercalciuria, and nephrolithiasis (Stechman et al., 2007; Zifarelli and Pusch, 2009). Plays a role by facilitating endosomal acidification through neutralization of proton pump currents (Novarino et al., 2010; Rickheit et al., 2010). The carrier is regulated by protons as studied by Picollo et al., (2010). CLC-5 and KIF3B interact to facilitate CLC-5 plasma membrane expression, endocytosis, and microtubular transport (Reed et al., 2010).

Q9GKE7 308990
1.A.5.3.1 MUCOLIPIDOSIS IV The lysosomal monovalent cation/Ca2+ channel, TRP-ML1 (Mucolipin-1) (associated with the human lipid storage disorder, mucolipidosis type IV (MLIV)) (Kiselyov et al., 2005; Luzio et al., 2007). TRPML1 is an endolysosomal iron release channel (Dong et al., 2008).
Q9GZU1 252650
3.A.18.1.1 ICHTHYOSIS VULGARIS

The nuclear mRNA Export Complex (mRNA-E also called TREX) (including the exon junction complex) [TAP+p15 interact as a complex with the nuclear pore to facilitate mRNA transport to the cytoplasm] (Nojimma et al. 2007; Cheng et al., 2006)

Q9H307 146700
3.A.2.2.4 T CELL IMMUNE REGULATOR 1; TCIRG1

The Ubiquitous Vacuolar H+ ATPase, V1/V0, has been implicated in various human diseases including osteopetrosis, renal tubule acidosis, and cancer (Hinton et al., 2009).

Q9HBG4 604592
2.A.66.9.1 CHONDROCALCINOSIS 2; CCAL2

The progressive ankylosis (ANK) protein homologue (AnkH) gives rise to craniometaphyseal bone dysplasia in man. It has 12 putative TMSs (Nürnberg et al., 2001)

Q9HCJ1 118600
8.A.17.1.2 SODIUM CHANNEL, VOLTAGE-GATED, TYPE I, BETA SUBUNIT; SCN1B Sodium channel ß3 subunit Q9JK00 600235
8.A.11.1.1 ARYL HYDROCARBON RECEPTOR-INTERACTING PROTEIN; AIP The immunophilin-like prolyl-peptidyl isomerase TWISTED DWARF1 direct regulator of auxin efflux mediated by Pgp1 (3.A.1.201.5) and Pgp19 (3.A.1.201.6), Twd1 (shows significant sequence similarity with Toc64, 3.A.9.1.1) Q9LDC0 605555
8.A.11.1.1 LEBER CONGENITAL AMAUROSIS 1; LCA1 The immunophilin-like prolyl-peptidyl isomerase TWISTED DWARF1 direct regulator of auxin efflux mediated by Pgp1 (3.A.1.201.5) and Pgp19 (3.A.1.201.6), Twd1 (shows significant sequence similarity with Toc64, 3.A.9.1.1) Q9LDC0 204000
1.A.1.4.5 SPASTIC PARAPLEGIA 39, AUTOSOMAL RECESSIVE; SPG39 Root stelar K+ outward rectifying channel, SKOR (involved in K+ release into the xylem sap; part of the plant water stress response) (Gaymard et al., 1998). Q9M8S6 612020
3.A.3.13.1 KUFOR-RAKEB SYNDROME; KRS Functionally uncharacterized P-type ATPase family 13 (FUPA13) (5 members; 1150-1230 aas). (Families 3.A.13-16 (FUPA 13-16) are more closely related to each other than they are to other P-type ATPases. They may comprise a single family from distantly related eukaryotic organisms). Q9NQ11 606693
5.B.1.2.2 ASPIRIN RESISTANCE Thyroid NADPH oxidase/peroxidase 2 (Dual oxidase 2; Duox2) with two EF band domains, responsive to Ca2+ regulation (De Deken et al., 2000; Edens et al., 2001) Q9NRD8 608223
5.B.1.2.1 THYROID PEROXIDASE; TPO Thyroid NADPH oxidase/peroxidase 1 (Dual oxidase 1; Duox1) with two EF band domains, responsive to Ca2+ regulation (De Deken et al., 2000; Edens et al., 2001) Q9NRD9 606765
5.B.1.2.1 CONE DYSTROPHY 3; COD3 Thyroid NADPH oxidase/peroxidase 1 (Dual oxidase 1; Duox1) with two EF band domains, responsive to Ca2+ regulation (De Deken et al., 2000; Edens et al., 2001) Q9NRD9 602093
5.B.1.2.1 GUANYLATE CYCLASE ACTIVATOR 1B; GUCA1B Thyroid NADPH oxidase/peroxidase 1 (Dual oxidase 1; Duox1) with two EF band domains, responsive to Ca2+ regulation (De Deken et al., 2000; Edens et al., 2001) Q9NRD9 602275
1.G.6.1.1 INTERCELLULAR ADHESION MOLECULE 1; ICAM1

The human poliovirus 2B viroporin (from the polyprotein). The 97 residue 2B viroporin consists of residues 1031-1127 in the polyprotein.

Q9Q280 147840
2.A.31.2.1 SOLUTE CARRIER FAMILY 4 (SODIUM BICARBONATE COTRANSPORTER), MEMBER 7; SLC4A7 Electroneutral Na+:HCO3- cotransporter (NBC) Q9R1N3 603353
8.B.13.1.1 DIARRHEA 3, SECRETORY SODIUM, CONGENITAL; DIAR3 Kalicludine 3 toxin (59 aas) There are three types, AsKCl-3, which block Kv1.2 K+ channels. Shows 48% identity (e-11) with a central region of an Alzheimer's disease amyloid A4 homologue (1.C.50.1.1).
Q9TWF8 270420
8.B.13.1.1 BETHLEM MYOPATHY Kalicludine 3 toxin (59 aas) There are three types, AsKCl-3, which block Kv1.2 K+ channels. Shows 48% identity (e-11) with a central region of an Alzheimer's disease amyloid A4 homologue (1.C.50.1.1).
Q9TWF8 158810
1.A.48.1.1 HNF1 HOMEOBOX A; HNF1A Tweety maxi-Cl- anion channel Q9U6L4 142410
8.A.16.2.3 TRANSMEMBRANE PROTEIN 114; TMEM114 Voltage-dependent Ca2+ channel γ4 subunit, CACNG4 Q9UBN1 611579
9.B.43.2.1 SIX-TRANSMEMBRANE EPITHELIAL ANTIGEN OF PROSTATE; STEAP The 6 TMS epithelial plasma membrane antigen of the prostate (STEAP) (Hubert et al., 1999; Yang et al., 2001) Q9UHE8 604415
2.A.29.14.2 SOLUTE CARRIER FAMILY 25 (CITRIN), MEMBER 13; SLC25A13 Mitochondrial Ca2+-activated aspartate/glutamate antiporter carrier with Ca2+-binding EF-hand domain, Citrin (defects in humans cause type II citrullinemia) Q9UJS0 603859
4.C.2.1.2 CARNITINE ACETYLTRANSFERASE; CRAT Peroxisomal carnitine O-octanoyl transferase (CrOT) Q9UKG9 600184
1.A.4.1.7 TRANSIENT RECEPTOR POTENTIAL CATION CHANNEL, SUBFAMILY C, MEMBER 3; TRPC3

Short transient receptor channel 5 (TrpC5 or Htrp5) (transports Ca2+ and Sr2+ in the presence of Orai1 and STIM1 (TC# 1.A.52.1.1) (Ma et al., 2008). It is a cold-transducer in the peripheral nervous system (Zimmermann et al., 2011).

Q9UL62 602345
8.A.10.4.1 POTASSIUM CHANNEL, VOLTAGE-GATED, ISK-RELATED SUBFAMILY, MEMBER 3; KCNE3 MinK-related peptide 3 (MiRK3) or KCNE4 (β-subunit) Q9WTW3 604433
2.A.53.2.3 DIARRHEA 1, SECRETORY CHLORIDE, CONGENITAL; DIAR1 Intestinal down-regulated in adenoma (DRA) protein; HCO3-/Cl- antiporter, SLC26a3 (responsible for congenital chloride-losing diarrhea in humans) (Schweinfest et al., 2006). DRA has 12 putative TMSs and a C-terminal STAS domain required for function and activation of CFTR by DRA (Dorwart et al., 2008). Catalyzes 2Cl-/1HCO3- antiport, Cl-/OH- exchange and sulfate transport (Shcheynikov et al., 2006; Moseley et al., 1999).
Q9WVC8 214700
3.A.3.8.6 HYPOPARATHYROIDISM, X-LINKED; HYPX Golgi phospholipid transporting (flipping) ATPase3 (1213aas; 10TMSs). Involved in growth of roots and shoots. Uses a β-ATPase3 subunit, ALIS1 (TC#8.A.27.4) (Paulsen et al., 2008). Q9XIE6 307700
1.A.4.1.5 FOCAL SEGMENTAL GLOMERULOSCLEROSIS 2; FSGS2 TRPC6 cation channel (mutation causes familial focal segmental glomerulosclerosis) (Winn et al., 2005; Mukerji et al., 2007). Q9Y210 603965
1.H.1.1.1 HYPOMAGNESEMIA 3, RENAL; HOMG3

Claudin 16 (CLDN16; Paracellin) (defects in CLDN16 are the cause of familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) (primary hypomagnesemia) (Hou et al., 2007; Ikari et al., 2008).

Q9Y5I7 248250
5.B.1.1.3 NADPH OXIDASE 1; NOX1 Multiple tissue mitogenic oxidase, subunit 65 (Mox1 or Nox1) (alternative splicing yields a 191 aa protein with H+ channel activity) (Bánfi et al., 2000; Suh et al., 1999) Q9Y5S8 300225
3.A.18.1.1 SPLICING FACTOR, ARGININE/SERINE-RICH, 10; SFRS10

The nuclear mRNA Export Complex (mRNA-E also called TREX) (including the exon junction complex) [TAP+p15 interact as a complex with the nuclear pore to facilitate mRNA transport to the cytoplasm] (Nojimma et al. 2007; Cheng et al., 2006)

Q9Y5S9 602719
3.A.18.1.1 PARKINSON DISEASE 10; PARK10

The nuclear mRNA Export Complex (mRNA-E also called TREX) (including the exon junction complex) [TAP+p15 interact as a complex with the nuclear pore to facilitate mRNA transport to the cytoplasm] (Nojimma et al. 2007; Cheng et al., 2006)

Q9Y5S9 606852
3.A.18.1.1 TAR DNA-BINDING PROTEIN; TARDBP

The nuclear mRNA Export Complex (mRNA-E also called TREX) (including the exon junction complex) [TAP+p15 interact as a complex with the nuclear pore to facilitate mRNA transport to the cytoplasm] (Nojimma et al. 2007; Cheng et al., 2006)

Q9Y5S9 605078
3.A.18.1.1 HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN R; HNRNPR

The nuclear mRNA Export Complex (mRNA-E also called TREX) (including the exon junction complex) [TAP+p15 interact as a complex with the nuclear pore to facilitate mRNA transport to the cytoplasm] (Nojimma et al. 2007; Cheng et al., 2006)

Q9Y5S9 607201
1.A.24.1.5 CATARACT, ZONULAR PULVERULENT 3; CZP3 Heteromeric (or homomeric) Connexin46/Connexin50 junction (Cx46/Cx50) (mutations in Cx50 cause cataracts) (Derosa et al., 2007). Q9Y6H8 601885
1.H.1.8.1 CLAUDIN 1; CLDN1 Claudin 10a (anion selective; Angelow et al., 2008)
Q9Z0S6 603718
3.B.1.1.3 PROPIONYL-CoA CARBOXYLASE, BETA SUBUNIT; PCCB Na+-transporting glutaconyl-CoA decarboxylase Q9ZAA7 232050
1.A.27.2.1 HYPOMAGNESEMIA 2, RENAL; HOMG2 γ-subunit (proteolipid) of Na+,K+-ATPase P54710 154020
2.A.1.19.2 SOLUTE CARRIER FAMILY 22 (ORGANIC CATION TRANSPORTER), MEMBER 4; SLC22A4

The ergothionine/organic cation porter, OctN1 (SLC22A4). Associated with rheumatoid arthritis (Barton et al., 2005).

O14546 604190
8.A.22.1.4 CALCIUM CHANNEL, VOLTAGE-DEPENDENT, BETA-4 SUBUNIT; CACNB4

Ca2+ channel, voltage-dependent, β4-subunit, CACNB4

O00305 601949
1.I.1.1.1 CARDIOMYOPATHY, FAMILIAL HYPERTROPHIC, 10; CMH10

NPC (Tran and Wente, 2006)

P06704 608758
1.I.1.1.1 MYOSIN, LIGHT CHAIN 5, REGULATORY; MYL5

NPC (Tran and Wente, 2006)

P06704 160782
1.I.1.1.1 CARDIOMYOPATHY, DILATED, 1Z; CMD1Z

NPC (Tran and Wente, 2006)

P06704 611879
1.I.1.1.1 CALCIUM-BINDING PROTEIN 1; CABP1

NPC (Tran and Wente, 2006)

P06704 605563
1.I.1.1.1 LETHAL CONGENITAL CONTRACTURE SYNDROME 1; LCCS1

NPC (Tran and Wente, 2006)

Q12315 253310
1.I.1.1.1 SET DOMAIN-CONTAINING PROTEIN 2; SETD2

NPC (Tran and Wente, 2006)

Q02455 612778
1.I.1.1.1 ARTHROGRYPOSIS, DISTAL, TYPE 2B; DA2B

NPC (Tran and Wente, 2006)

Q02455 601680
1.I.1.1.1 FIBROBLAST GROWTH FACTOR RECEPTOR 1; FGFR1

NPC (Tran and Wente, 2006)

Q02455 136350
1.I.1.1.1 CARDIOMYOPATHY, DILATED, 1D; CMD1D

NPC (Tran and Wente, 2006)

Q02455 601494
1.I.1.1.1 COLLAGEN, TYPE XVII, ALPHA-1; COL17A1

NPC (Tran and Wente, 2006)

Q02455 113811
1.I.1.1.1 INCLUSION BODY MYOPATHY 3, AUTOSOMAL DOMINANT; IBM3

NPC (Tran and Wente, 2006)

Q02455 605637
1.I.1.1.1 AROMATASE EXCESS SYNDROME; AEXS

NPC (Tran and Wente, 2006)

Q02455 139300
1.I.1.1.1 EMERY-DREIFUSS MUSCULAR DYSTROPHY, AUTOSOMAL DOMINANT; EDMD2

NPC (Tran and Wente, 2006)

Q02455 181350
1.I.1.1.1 PEUTZ-JEGHERS SYNDROME; PJS

NPC (Tran and Wente, 2006)

Q02455 175200
1.I.1.1.1 CARDIOMYOPATHY, DILATED, 3B; CMD3B

NPC (Tran and Wente, 2006)

Q02455 302045
1.I.1.1.1 CARDIOMYOPATHY, FAMILIAL HYPERTROPHIC; CMH

NPC (Tran and Wente, 2006)

Q02455 192600
1.I.1.1.1 MYOSIN, HEAVY CHAIN 6, CARDIAC MUSCLE, ALPHA; MYH6

NPC (Tran and Wente, 2006)

Q02455 160710
1.I.1.1.1 MICROCEPHALY, PRIMARY AUTOSOMAL RECESSIVE, 3; MCPH3

NPC (Tran and Wente, 2006)

Q02455 604804
1.I.1.1.1 MECKEL SYNDROME, TYPE 5; MKS5

NPC (Tran and Wente, 2006)

Q02455 611561
1.I.1.1.1 NEURONOPATHY, DISTAL HEREDITARY MOTOR, TYPE IIB; HMN2B

NPC (Tran and Wente, 2006)

Q02455 608634
1.I.1.1.1 ESTROGEN-RELATED RECEPTOR-BETA-LIKE 1; ESRRBL1

NPC (Tran and Wente, 2006)

Q02455 606621
1.I.1.1.1 COAGULATION FACTOR V; F5

NPC (Tran and Wente, 2006)

Q02455 612309
1.I.1.1.1 SPECTRIN, BETA, ERYTHROCYTIC; SPTB

NPC (Tran and Wente, 2006)

Q02455 182870
1.I.1.1.1 CUT-LIKE 1; CUTL1

NPC (Tran and Wente, 2006)

Q02455 116896
1.I.1.1.1 PERRY SYNDROME

NPC (Tran and Wente, 2006)

Q02455 168605
1.I.1.1.1 LAMININ, ALPHA-3; LAMA3

NPC (Tran and Wente, 2006)

Q02455 600805
1.I.1.1.1 GRISCELLI SYNDROME, TYPE 1; GS1

NPC (Tran and Wente, 2006)

Q02455 214450
1.I.1.1.1 ICHTHYOSIS, BULLOUS TYPE

NPC (Tran and Wente, 2006)

Q02455 146800
1.I.1.1.1 NEUROFILAMENT 3; NEF3

NPC (Tran and Wente, 2006)

Q02455 162250
1.I.1.1.1 DIARRHEA 2, WITH MICROVILLOUS ATROPHY; DIAR2

NPC (Tran and Wente, 2006)

Q02455 251850
1.I.1.1.1 PREMATURE OVARIAN FAILURE 1; POF1

NPC (Tran and Wente, 2006)

Q02455 311360
1.I.1.1.1 GLIAL FIBRILLARY ACIDIC PROTEIN; GFAP

NPC (Tran and Wente, 2006)

Q02455 137780
1.I.1.1.1 TSC2 GENE; TSC2

NPC (Tran and Wente, 2006)

Q02455 191092
1.I.1.1.1 ICHTHYOSIS, CYCLIC, WITH EPIDERMOLYTIC HYPERKERATOSIS

NPC (Tran and Wente, 2006)

Q02455 607602
1.I.1.1.1 KERATIN 15; KRT15

NPC (Tran and Wente, 2006)

Q02455 148030
1.I.1.1.1 PANIC DISORDER 1; PAND1

NPC (Tran and Wente, 2006)

Q02455 167870
1.I.1.1.1 LAMININ, GAMMA-1; LAMC1

NPC (Tran and Wente, 2006)

Q02455 150290
1.I.1.1.1 MONILETHRIX

NPC (Tran and Wente, 2006)

Q02455 158000
1.I.1.1.1 PACHYONYCHIA CONGENITA, TYPE 2; PC2

NPC (Tran and Wente, 2006)

Q02455 167210
1.I.1.1.1 KERATIN 13; KRT13

NPC (Tran and Wente, 2006)

Q02455 148065
1.I.1.1.1 LAMININ, ALPHA-1; LAMA1

NPC (Tran and Wente, 2006)

Q02455 150320
1.I.1.1.1 PAIRED-LIKE HOMEOBOX 2B; PHOX2B

NPC (Tran and Wente, 2006)

Q02455 603851
1.I.1.1.1 ALPHA-B CRYSTALLINOPATHY

NPC (Tran and Wente, 2006)

Q02455 608810
1.I.1.1.1 PANCREATIC CARCINOMA

NPC (Tran and Wente, 2006)

Q02455 260350
1.I.1.1.1 NIJMEGEN BREAKAGE SYNDROME

NPC (Tran and Wente, 2006)

Q02455 251260
1.I.1.1.1 COLLECTIN 12; COLEC12

NPC (Tran and Wente, 2006)

Q02455 607621
1.I.1.1.1 STRIATONIGRAL DEGENERATION, INFANTILE; SNDI

NPC (Tran and Wente, 2006)

P14907 271930
1.I.1.1.1 ENCEPHALOPATHY, ACUTE NECROTIZING 1, SUSCEPTIBILITY TO; ANE1

NPC (Tran and Wente, 2006)

P32499 608033
1.I.1.1.1 HOMEOBOX A9; HOXA9

NPC (Tran and Wente, 2006)

P49687 142956
1.I.1.1.1 CHLORIDE CHANNEL 6; CLCN6

NPC (Tran and Wente, 2006)

P40477 602726
1.I.1.1.1 SEC13-LIKE PROTEIN 1; SEC13L1

NPC (Tran and Wente, 2006)

P53011 600152