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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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

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

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

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

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

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

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).

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).

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

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).

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

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

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

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

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).

The Ca_v1.4 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).

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).

Bestrophin-1 anion channel; VMD2 gene product (NO₃^- > I^- > Br^- > Cl^-; P_NO3^-/P_Cl^- = 5.8) (Sun et al., 2002). Regulated by ceramide-induced dephosphorylation (Xiao et al., 2009).

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).

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).

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.

Ubiquinol:cytochrome c oxidoreductase

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, β_2,... 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).

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).

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).

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

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).

Voltage-gated K⁺ channel, chain A, Shaker-related, K_v1.2 (Crystal structure known, Long et al., 2007). Delemotte et al. (2010) described the effects of sensor domain mutations on molecular dynamics of Kv1.2.

Voltage-sensitive K⁺ channel

Voltage-sensitive K⁺ channel

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).

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).

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).

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

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

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

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

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).

The skeletal muscle Na⁺ channel, Na_V1.4 (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 Na_v1.4 (Biswas et al., 2008). Na_V1.4 gating pores are permeable to guanidine (Sokolov et al., 2010).

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).

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). 

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).

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).

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).

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)

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)

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)

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)

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)

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)

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).

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).

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).

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).

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).

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).

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).

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.

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).

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

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).

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).

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).

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

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

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).

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

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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

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

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).

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

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). 

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).

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)

K⁺ voltage-gated ether-a-go-go-related channel, H-ERG (Erg1) subunit K_v11.1 (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).

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).

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

The voltage-dependent L-type Ca²⁺ channel α-subunit-1C (L-type Ca_v1.2), CACNA1C (mutations cause Timothy's syndrome, a disorder associated with autism) (Splawski et al., 2006). The C-terminus of Ca_v1.2 encodes a transcription factor (Gomez-Ospina et al., 2006). Ca_v1.2 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, Ca_v1.2 (Park et al., 2010).

Voltage-gated K⁺ channel, Shab-related, K_v2.1 (858aas) (Crystal structure known, Long et al., 2007). Rat K_v2.1 and K_v2.2 (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 K_v2 channels in cortical neurons (Kihira et al., 2010). Phosphorylation by AMP-activated protein kinase regulates membrane excitability (Ikematsu et al., 2011).

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)

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)

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 ).

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

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

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

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).

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).

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).

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).

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

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

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).

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

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).

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)

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)

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).

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)).

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).

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

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., 2010; Qiu et al., 2006; Zhao et al., 2011). Downregulated in Chronic Kidney Disease (CKD) in heart, liver, and brain causing malabsorption (Bukhari et al., 2011).

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).

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).

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

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).

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).

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).

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).

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)

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).

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

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

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).

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).

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)

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)

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)

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)

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

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

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