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2.A.1.19.3
The polyspecific organic cation (L- and D-carnitine, butyryl-L-carnitine, acetyl carnitine, γ-butyro-betaine, glycinebetaine, β-lactam antibiotics with a quaternary nitrogen such as cephaloridine, and others):Na+ symporter, OctN2 (SLC22A5). Carnitine is transporter with high affinity (2 - 20 μM0 (Ingoglia et al. 2015). Associated with Crohn''s disease (Barton et al., 2005) as well as primary carnitine deficiency.  The protein is glycosylated on extracytoplasmic asparagines, and these residues are in a region important for function and turnover (Filippo et al. 2011).  OCTN2 maintains the carnitine homeostasis, resulting from intestinal absorption, distribution to tissues, and renal excretion/reabsorption (Pochini et al. 2013).  OCTN1 and OCTN2 are associated with several pathologies, such as inflammatory bowel disease, primary carnitine deficiency, diabetes, neurological disorders, and cancer.  OctN2 is activated in a process dependent on Caveolin1 (Q03135)which interacts directly with OctN2 and by protein kinase C which does not phosphorylate OctN2 directly (Czeredys et al. 2013).

Accession Number:O76082
Protein Name:OCN2 aka OctN2 aka SLC22A5
Length:557
Molecular Weight:62752.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:11
Location1 / Topology2 / Orientation3: Membrane1 / Multi-pass membrane protein2
Substrate Carnitine, Butyryl-L-carnitine, Acetyl carnitine, Gamma-butryo-betaine, Glycine betaine, Beta-lactam antibiotics, Na+

Cross database links:

HOG000234570
Genevestigator: O76082 O76082
eggNOG: prNOG18524 COG0477
RefSeq: NP_003051.1   
Entrez Gene ID: 6584   
Pfam: PF00083   
Drugbank: Drugbank Link   
OMIM: 212140  phenotype
266600  phenotype
603377  gene
KEGG: hsa:6584    hsa:6584   

Gene Ontology

GO:0016324 C:apical plasma membrane
GO:0031526 C:brush border membrane
GO:0016021 C:integral to membrane
GO:0005524 F:ATP binding
GO:0015226 F:carnitine transporter activity
GO:0015238 F:drug transmembrane transporter activity
GO:0030165 F:PDZ domain binding
GO:0015293 F:symporter activity
GO:0015879 P:carnitine transport
GO:0015893 P:drug transport
GO:0060731 P:positive regulation of intestinal epithelia...
GO:0052106 P:quorum sensing during interaction with host
GO:0006814 P:sodium ion transport
GO:0070715 P:sodium-dependent organic cation transport
GO:0016323 C:basolateral plasma membrane
GO:0042895 F:antibiotic transporter activity
GO:0060731 P:positive regulation of intestinal epithelial structure maintenance
GO:0052106 P:quorum sensing involved in interaction with host

References (44)

[1] “cDNA sequence, transport function, and genomic organization of human OCTN2, a new member of the organic cation transporter family.”  Wu X.et.al.   9618255
[2] “Molecular and functional identification of sodium ion-dependent, high affinity human carnitine transporter OCTN2.”  Tamai I.et.al.   9685390
[3] “Primary systemic carnitine deficiency is caused by mutations in a gene encoding sodium ion-dependent carnitine transporter.”  Nezu J.et.al.   9916797
[4] “Complete sequencing and characterization of 21,243 full-length human cDNAs.”  Ota T.et.al.   14702039
[5] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[6] “Functional characteristics and tissue distribution pattern of organic cation transporter 2 (OCTN2), an organic cation/carnitine transporter.”  Wu X.et.al.   10454528
[7] “Mass-spectrometric identification and relative quantification of N-linked cell surface glycoproteins.”  Wollscheid B.et.al.   19349973
[8] “Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.”  Mayya V.et.al.   19690332
[9] “Carnitine transporter OCTN2 mutations in systemic primary carnitine deficiency: a novel Arg169Gln mutation and a recurrent Arg282ter mutation associated with an unconventional splicing abnormality.”  Burwinkel B.et.al.   10425211
[10] “Identification of two novel mutations in OCTN2 of three patients with systemic carnitine deficiency.”  Vaz F.M.et.al.   10480371
[11] “Mutations of OCTN2, an organic cation/carnitine transporter, lead to deficient cellular carnitine uptake in primary carnitine deficiency.”  Tang N.L.et.al.   10072434
[12] “Genetic epidemiology of the carnitine transporter OCTN2 gene in a Japanese population and phenotypic characterization in Japanese pedigrees with primary systemic carnitine deficiency.”  Koizumi A.et.al.   10545605
[13] “Mutations in novel organic cation transporter (OCTN2), an organic cation/carnitine transporter, with differential effects on the organic cation transport function and the carnitine transport function.”  Seth P.et.al.   10559218
[14] “Two novel missense mutations of the OCTN2 gene (W283R and V446F) in a patient with primary systemic carnitine deficiency.”  Mayatepek E.et.al.   10612840
[15] “A missense mutation in the OCTN2 gene associated with residual carnitine transport activity.”  Wang Y.et.al.   10679939
[16] “Functional variants of OCTN cation transporter genes are associated with Crohn disease.”  Peltekova V.D.et.al.   15107849
[17] “Functional genetic diversity in the high-affinity carnitine transporter OCTN2 (SLC22A5).”  Urban T.J.et.al.   16931768
[18] “cDNA sequence, transport function, and genomic organization of human OCTN2, a new member of the organic cation transporter family.”  Wu X.et.al.   9618255
[19] “Molecular and functional identification of sodium ion-dependent, high affinity human carnitine transporter OCTN2.”  Tamai I.et.al.   9685390
[20] “Primary systemic carnitine deficiency is caused by mutations in a gene encoding sodium ion-dependent carnitine transporter.”  Nezu J.et.al.   9916797
[21] “OCTN2VT, a splice variant of OCTN2, does not transport carnitine because of the retention in the endoplasmic reticulum caused by insertion of 24 amino acids in the first extracellular loop of OCTN2.”  Maekawa S.et.al.   17509700
[22] “Complete sequencing and characterization of 21,243 full-length human cDNAs.”  Ota T.et.al.   14702039
[23] “The DNA sequence and comparative analysis of human chromosome 5.”  Schmutz J.et.al.   15372022
[24] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[25] “Functional characteristics and tissue distribution pattern of organic cation transporter 2 (OCTN2), an organic cation/carnitine transporter.”  Wu X.et.al.   10454528
[26] “Mass-spectrometric identification and relative quantification of N-linked cell surface glycoproteins.”  Wollscheid B.et.al.   19349973
[27] “Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.”  Mayya V.et.al.   19690332
[28] “Carnitine transporter OCTN2 mutations in systemic primary carnitine deficiency: a novel Arg169Gln mutation and a recurrent Arg282ter mutation associated with an unconventional splicing abnormality.”  Burwinkel B.et.al.   10425211
[29] “Identification of two novel mutations in OCTN2 of three patients with systemic carnitine deficiency.”  Vaz F.M.et.al.   10480371
[30] “Mutations of OCTN2, an organic cation/carnitine transporter, lead to deficient cellular carnitine uptake in primary carnitine deficiency.”  Tang N.L.et.al.   10072434
[31] “Genetic epidemiology of the carnitine transporter OCTN2 gene in a Japanese population and phenotypic characterization in Japanese pedigrees with primary systemic carnitine deficiency.”  Koizumi A.et.al.   10545605
[32] “Mutations in novel organic cation transporter (OCTN2), an organic cation/carnitine transporter, with differential effects on the organic cation transport function and the carnitine transport function.”  Seth P.et.al.   10559218
[33] “Two novel missense mutations of the OCTN2 gene (W283R and V446F) in a patient with primary systemic carnitine deficiency.”  Mayatepek E.et.al.   10612840
[34] “A missense mutation in the OCTN2 gene associated with residual carnitine transport activity.”  Wang Y.et.al.   10679939
[35] “Functional analysis of mutations in the OCTN2 transporter causing primary carnitine deficiency: lack of genotype-phenotype correlation.”  Wang Y.et.al.   11058897
[36] “Phenotype and genotype variation in primary carnitine deficiency.”  Wang Y.et.al.   11715001
[37] “Carnitine transporter defect due to a novel mutation in the SLC22A5 gene presenting with peripheral neuropathy.”  Makhseed N.et.al.   15617188
[38] “Validation of dye-binding/high-resolution thermal denaturation for the identification of mutations in the SLC22A5 gene.”  Dobrowolski S.F.et.al.   15714519
[39] “Functional genetic diversity in the high-affinity carnitine transporter OCTN2 (SLC22A5).”  Urban T.J.et.al.   16931768
[40] “Expanded newborn screening identifies maternal primary carnitine deficiency.”  Schimmenti L.A.et.al.   17126586
[41] “Maternal systemic primary carnitine deficiency uncovered by newborn screening: clinical, biochemical, and molecular aspects.”  El-Hattab A.W.et.al.   20027113
[42] “Molecular spectrum of SLC22A5 (OCTN2) gene mutations detected in 143 subjects evaluated for systemic carnitine deficiency.”  Li F.-Y.et.al.   20574985
[43] “Diagnoses of newborns and mothers with carnitine uptake defects through newborn screening.”  Lee N.-C.et.al.   20074989
[44] “Genotype-phenotype correlation in primary carnitine deficiency.”  Rose E.C.et.al.   21922592

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FASTA formatted sequence
1:	MRDYDEVTAF LGEWGPFQRL IFFLLSASII PNGFTGLSSV FLIATPEHRC RVPDAANLSS 
61:	AWRNHTVPLR LRDGREVPHS CRRYRLATIA NFSALGLEPG RDVDLGQLEQ ESCLDGWEFS 
121:	QDVYLSTIVT EWNLVCEDDW KAPLTISLFF VGVLLGSFIS GQLSDRFGRK NVLFVTMGMQ 
181:	TGFSFLQIFS KNFEMFVVLF VLVGMGQISN YVAAFVLGTE ILGKSVRIIF STLGVCIFYA 
241:	FGYMVLPLFA YFIRDWRMLL VALTMPGVLC VALWWFIPES PRWLISQGRF EEAEVIIRKA 
301:	AKANGIVVPS TIFDPSELQD LSSKKQQSHN ILDLLRTWNI RMVTIMSIML WMTISVGYFG 
361:	LSLDTPNLHG DIFVNCFLSA MVEVPAYVLA WLLLQYLPRR YSMATALFLG GSVLLFMQLV 
421:	PPDLYYLATV LVMVGKFGVT AAFSMVYVYT AELYPTVVRN MGVGVSSTAS RLGSILSPYF 
481:	VYLGAYDRFL PYILMGSLTI LTAILTLFLP ESFGTPLPDT IDQMLRVKGM KHRKTPSHTR 
541:	MLKDGQERPT ILKSTAF