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O76082 (S22A5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 133. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Solute carrier family 22 member 5
Alternative name(s):
High-affinity sodium-dependent carnitine cotransporter
Organic cation/carnitine transporter 2
Gene names
Name:SLC22A5
Synonyms:OCTN2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length557 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Sodium-ion dependent, high affinity carnitine transporter. Involved in the active cellular uptake of carnitine. Transports one sodium ion with one molecule of carnitine. Also transports organic cations such as tetraethylammonium (TEA) without the involvement of sodium. Also relative uptake activity ratio of carnitine to TEA is 11.3. Ref.9

Subunit structure

Interacts with PDZK1 By similarity.

Subcellular location

Membrane; Multi-pass membrane protein Ref.18.

Tissue specificity

Strongly expressed in kidney, skeletal muscle, heart and placenta. Highly expressed in intestinal cell types affected by Crohn disease, including epithelial cells. Expressed in CD68 macrophage and CD43 T-cells but not in CD20 B-cells. Ref.9

Involvement in disease

Systemic primary carnitine deficiency (CDSP) [MIM:212140]: Autosomal recessive disorder of fatty acid oxidation caused by defective carnitine transport. Present early in life with hypoketotic hypoglycemia and acute metabolic decompensation, or later in life with skeletal myopathy or cardiomyopathy.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 Ref.22 Ref.24 Ref.25 Ref.26 Ref.27 Ref.28

Miscellaneous

Inhibited by emetine, quinidine and verapamil. The IC50 of emetine is 4.2 µM. Not inhibited by valproic acid.

Sequence similarities

Belongs to the major facilitator (TC 2.A.1) superfamily. Organic cation transporter (TC 2.A.1.19) family. [View classification]

Ontologies

Keywords
   Biological processIon transport
Sodium transport
Symport
Transport
   Cellular componentMembrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDisease mutation
   DomainTransmembrane
Transmembrane helix
   LigandATP-binding
Nucleotide-binding
Sodium
   PTMGlycoprotein
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcarnitine transmembrane transport

Inferred from direct assay Ref.2. Source: GOC

carnitine transport

Inferred from direct assay Ref.2. Source: BHF-UCL

drug transmembrane transport

Inferred by curator PubMed 15238359. Source: GOC

drug transport

Inferred by curator PubMed 15238359. Source: BHF-UCL

positive regulation of intestinal epithelial structure maintenance

Inferred from mutant phenotype PubMed 18005709. Source: BHF-UCL

quaternary ammonium group transport

Inferred from direct assay Ref.1. Source: BHF-UCL

quorum sensing involved in interaction with host

Inferred from mutant phenotype PubMed 18005709. Source: BHF-UCL

sodium ion transport

Inferred from electronic annotation. Source: UniProtKB-KW

sodium-dependent organic cation transport

Inferred from direct assay PubMed 15238359Ref.2. Source: BHF-UCL

transmembrane transport

Traceable author statement. Source: Reactome

   Cellular_componentapical plasma membrane

Inferred from direct assay PubMed 17274673PubMed 18641280. Source: BHF-UCL

basolateral plasma membrane

Inferred from electronic annotation. Source: Ensembl

brush border membrane

Inferred from direct assay PubMed 15238359. Source: BHF-UCL

extracellular vesicular exosome

Inferred from direct assay PubMed 19056867. Source: UniProt

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

plasma membrane

Inferred by curator Ref.1. Source: BHF-UCL

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

PDZ domain binding

Inferred from physical interaction PubMed 15523054. Source: BHF-UCL

antibiotic transporter activity

Inferred from electronic annotation. Source: Ensembl

carnitine transmembrane transporter activity

Inferred from direct assay Ref.2. Source: BHF-UCL

drug transmembrane transporter activity

Inferred by curator PubMed 15238359. Source: BHF-UCL

quaternary ammonium group transmembrane transporter activity

Inferred from direct assay Ref.1. Source: BHF-UCL

symporter activity

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O76082-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: O76082-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-336: Missing.
     337-351: TWNIRMVTIMSIMLW → MWILLFQLSSALCFR
Note: No experimental confirmation available.
Isoform 3 (identifier: O76082-3)

Also known as: OCTN2VT;

The sequence of this isoform differs from the canonical sequence as follows:
     131-131: E → EQDSGAYNAMKNRMGKKPALCLPAQ
Note: Retained in the ER, unable to perform carnitine uptake.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 557557Solute carrier family 22 member 5
PRO_0000220500

Regions

Topological domain1 – 2020Cytoplasmic Potential
Transmembrane21 – 4121Helical; Name=1; Potential
Topological domain42 – 142101Extracellular Potential
Transmembrane143 – 16321Helical; Name=2; Potential
Topological domain164 – 1729Cytoplasmic Potential
Transmembrane173 – 19321Helical; Name=3; Potential
Topological domain194 – 1974Extracellular Potential
Transmembrane198 – 21821Helical; Name=4; Potential
Topological domain219 – 23214Cytoplasmic Potential
Transmembrane233 – 25321Helical; Name=5; Potential
Topological domain254 – 2574Extracellular Potential
Transmembrane258 – 27821Helical; Name=6; Potential
Topological domain279 – 34163Cytoplasmic Potential
Transmembrane342 – 36221Helical; Name=7; Potential
Topological domain363 – 37311Extracellular Potential
Transmembrane374 – 39421Helical; Name=8; Potential
Topological domain395 – 40612Cytoplasmic Potential
Transmembrane407 – 42721Helical; Name=9; Potential
Topological domain428 – 4303Extracellular Potential
Transmembrane431 – 45121Helical; Name=10; Potential
Topological domain452 – 46211Cytoplasmic Potential
Transmembrane463 – 48321Helical; Name=11; Potential
Topological domain484 – 4885Extracellular Potential
Transmembrane489 – 50921Helical; Name=12; Potential
Nucleotide binding218 – 2258ATP Potential

Amino acid modifications

Modified residue4861Phosphotyrosine Ref.11
Modified residue5501Phosphothreonine By similarity
Glycosylation571N-linked (GlcNAc...) Ref.10
Glycosylation641N-linked (GlcNAc...) Potential
Glycosylation911N-linked (GlcNAc...) Ref.10

Natural variations

Alternative sequence1 – 336336Missing in isoform 2.
VSP_011120
Alternative sequence1311E → EQDSGAYNAMKNRMGKKPAL CLPAQ in isoform 3.
VSP_043904
Alternative sequence337 – 35115TWNIR…SIMLW → MWILLFQLSSALCFR in isoform 2.
VSP_011121
Natural variant121G → S in CDSP. Ref.26
Corresponds to variant rs139203363 [ dbSNP | Ensembl ].
VAR_064109
Natural variant151G → W in CDSP. Ref.25 Ref.26 Ref.28
VAR_064110
Natural variant171F → L in CDSP. Ref.23 Ref.26 Ref.27
VAR_020347
Natural variant191R → P in CDSP; carnitine transport is reduced to less than 5% of normal. Ref.20 Ref.22 Ref.28
VAR_064111
Natural variant221Missing in CDSP; reduces carnitine transport. Ref.28
VAR_066842
Natural variant261S → N in CDSP; reduces carnitine transport. Ref.28
VAR_066843
Natural variant321N → S in CDSP; reduces carnitine transport. Ref.24 Ref.26 Ref.28
VAR_064112
Natural variant461P → S in CDSP; carnitine transport is reduced to less than 5% of normal. Ref.24 Ref.25 Ref.26 Ref.28
VAR_064113
Natural variant661T → P Associated with CDSP; unclassified missense variant. Ref.26
VAR_064114
Natural variant751R → P Associated with CDSP; unclassified missense variant. Ref.26
VAR_064115
Natural variant831R → L in CDSP; reduces carnitine transport. Ref.21 Ref.22 Ref.25 Ref.26 Ref.28
VAR_064116
Natural variant961G → A Associated with CDSP; unclassified missense variant. Ref.26
VAR_064117
Natural variant1221D → Y in CDSP. Ref.26
VAR_064118
Natural variant1231V → G Associated with CDSP; unclassified missense variant. Ref.26
VAR_064119
Natural variant1421A → S in CDSP. Ref.25 Ref.26 Ref.28
VAR_064120
Natural variant1431P → L Associated with CDSP; unclassified missense variant. Ref.26 Ref.27
VAR_064121
Natural variant1441L → F. Ref.23
Corresponds to variant rs10040427 [ dbSNP | Ensembl ].
VAR_020348
Natural variant1691R → Q in CDSP; reduces carnitine transport. Ref.12 Ref.26 Ref.28
VAR_009252
Natural variant1691R → W in CDSP; abolishes carnitine transport. Ref.19 Ref.22 Ref.26 Ref.28
VAR_064122
Natural variant1771M → V Associated with CDSP; unclassified missense variant. Ref.26
Corresponds to variant rs145068530 [ dbSNP | Ensembl ].
VAR_064123
Natural variant1791M → L in CDSP. Ref.15
VAR_022564
Natural variant1861L → P in CDSP. Ref.26
VAR_064124
Natural variant2111Y → C in CDSP. Ref.13
VAR_009253
Natural variant2141A → V in CDSP; reduces carnitine transport. Ref.25 Ref.26 Ref.28
VAR_064125
Natural variant2271R → H in CDSP. Ref.26
Corresponds to variant rs185551386 [ dbSNP | Ensembl ].
VAR_064126
Natural variant2301F → L Associated with CDSP; unclassified missense variant. Ref.26
VAR_064127
Natural variant2321T → M in CDSP; markedly reduced carnitine transport compared to the wild-type protein. Ref.22 Ref.25 Ref.26 Ref.28
Corresponds to variant rs114269482 [ dbSNP | Ensembl ].
VAR_064128
Natural variant2341G → R in CDSP. Ref.27
VAR_064129
Natural variant2401A → T Associated with CDSP; unclassified missense variant. Ref.26
VAR_064130
Natural variant2421G → V in CDSP; abolishes carnitine transport. Ref.19 Ref.22
VAR_064131
Natural variant2571R → W in CDSP. Ref.26
VAR_064132
Natural variant2641T → R in CDSP. Ref.26
VAR_064133
Natural variant2801S → F in CDSP; reduces carnitine transport. Ref.28
VAR_066844
Natural variant2821R → Q in CDSP; reduces carnitine transport. Ref.26 Ref.27 Ref.28
VAR_064134
Natural variant2831W → C in CDSP; reduces L-carnitine uptake. Ref.15
VAR_022565
Natural variant2831W → R in CDSP; reduces carnitine transport. Ref.17 Ref.28
VAR_009254
Natural variant3011A → D in CDSP; has 2-3% residual carnitine transport of the value measured in cells expressing the wild-type protein. Ref.19 Ref.22
VAR_064135
Natural variant3121I → V Associated with CDSP; unclassified missense variant. Ref.26
Corresponds to variant rs77300588 [ dbSNP | Ensembl ].
VAR_064136
Natural variant3511W → R in CDSP; abolishes carnitine transport. Ref.19 Ref.22 Ref.28
VAR_064137
Natural variant3551S → L in CDSP. Ref.26
VAR_064138
Natural variant3581Y → N Associated with CDSP; unclassified missense variant. Ref.26
VAR_064139
Natural variant3621S → L in CDSP. Ref.27
VAR_064140
Natural variant3981P → L in CDSP. Ref.26
VAR_064141
Natural variant3991R → Q in CDSP; carnitine transport is reduced to less than 5% of normal. Ref.20 Ref.22
VAR_064142
Natural variant3991R → W in CDSP. Ref.25 Ref.26
VAR_064143
Natural variant4401T → M in CDSP; reduces carnitine transport. Ref.26 Ref.28
VAR_064144
Natural variant4421A → I in CDSP; requires 2 nucleotide substitutions; reduces carnitine transport. Ref.25 Ref.26 Ref.28
VAR_064145
Natural variant4431F → V in CDSP. Ref.26
VAR_064146
Natural variant4461V → F in CDSP; reduces carnitine transport. Ref.17 Ref.28
VAR_009255
Natural variant4471Y → C in CDSP; reduces carnitine transport. Ref.22 Ref.28
VAR_064147
Natural variant4491Y → D in CDSP. Ref.22 Ref.23 Ref.26
Corresponds to variant rs11568514 [ dbSNP | Ensembl ].
VAR_029315
Natural variant4521E → K in CDSP. Ref.18 Ref.22 Ref.26
VAR_009256
Natural variant4551P → R in CDSP. Ref.26
VAR_064148
Natural variant4671S → C in CDSP; reduces L-carnitine uptake. Ref.15 Ref.24 Ref.26 Ref.27 Ref.28
Corresponds to variant rs60376624 [ dbSNP | Ensembl ].
VAR_022566
Natural variant4681T → R in CDSP; markedly reduced carnitine transport compared to the wild-type protein. Ref.22
VAR_064149
Natural variant4711R → C in CDSP. Ref.27
VAR_064150
Natural variant4711R → P in CDSP; reduces carnitine transport. Ref.28
VAR_066845
Natural variant4781P → L in CDSP; loss of carnitine transport but stimulated organic cation transport. Ref.14 Ref.16
VAR_009257
Natural variant4811V → F. Ref.23
Corresponds to variant rs11568513 [ dbSNP | Ensembl ].
VAR_020349
Natural variant4811V → I. Ref.23
Corresponds to variant rs11568513 [ dbSNP | Ensembl ].
VAR_036816
Natural variant4881R → C in CDSP. Ref.24 Ref.26
VAR_064151
Natural variant4881R → H in CDSP; reduces carnitine transport. Ref.28
Corresponds to variant rs28383481 [ dbSNP | Ensembl ].
VAR_066846
Natural variant5071L → S in CDSP. Ref.26
VAR_064152
Natural variant5081F → L. Ref.23
VAR_029316
Natural variant5301M → V. Ref.23
VAR_029317
Natural variant5491P → S Associated with CDSP; unclassified missense variant. Ref.23 Ref.26
Corresponds to variant rs11568525 [ dbSNP | Ensembl ].
VAR_020350

Experimental info

Mutagenesis3521M → R: Loss of both carnitine and organic cation transport functionalities.
Sequence conflict1141L → P in AAH12325. Ref.8

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 1, 1998. Version 1.
Checksum: 928B1F6EFF63C48D

FASTA55762,752
        10         20         30         40         50         60 
MRDYDEVTAF LGEWGPFQRL IFFLLSASII PNGFTGLSSV FLIATPEHRC RVPDAANLSS 

        70         80         90        100        110        120 
AWRNHTVPLR LRDGREVPHS CRRYRLATIA NFSALGLEPG RDVDLGQLEQ ESCLDGWEFS 

       130        140        150        160        170        180 
QDVYLSTIVT EWNLVCEDDW KAPLTISLFF VGVLLGSFIS GQLSDRFGRK NVLFVTMGMQ 

       190        200        210        220        230        240 
TGFSFLQIFS KNFEMFVVLF VLVGMGQISN YVAAFVLGTE ILGKSVRIIF STLGVCIFYA 

       250        260        270        280        290        300 
FGYMVLPLFA YFIRDWRMLL VALTMPGVLC VALWWFIPES PRWLISQGRF EEAEVIIRKA 

       310        320        330        340        350        360 
AKANGIVVPS TIFDPSELQD LSSKKQQSHN ILDLLRTWNI RMVTIMSIML WMTISVGYFG 

       370        380        390        400        410        420 
LSLDTPNLHG DIFVNCFLSA MVEVPAYVLA WLLLQYLPRR YSMATALFLG GSVLLFMQLV 

       430        440        450        460        470        480 
PPDLYYLATV LVMVGKFGVT AAFSMVYVYT AELYPTVVRN MGVGVSSTAS RLGSILSPYF 

       490        500        510        520        530        540 
VYLGAYDRFL PYILMGSLTI LTAILTLFLP ESFGTPLPDT IDQMLRVKGM KHRKTPSHTR 

       550 
MLKDGQERPT ILKSTAF 

« Hide

Isoform 2 [UniParc].

Checksum: B66DFBC13A50BDAF
Show »

FASTA22124,688
Isoform 3 (OCTN2VT) [UniParc].

Checksum: C4DB6274B866DBF9
Show »

FASTA58165,327

References

« Hide 'large scale' references
[1]"cDNA sequence, transport function, and genomic organization of human OCTN2, a new member of the organic cation transporter family."
Wu X., Prasad P.D., Leibach F.H., Ganapathy V.
Biochem. Biophys. Res. Commun. 246:589-595(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"Molecular and functional identification of sodium ion-dependent, high affinity human carnitine transporter OCTN2."
Tamai I., Ohashi R., Nezu J., Yabuuchi H., Oku A., Shimane M., Sai Y., Tsuji A.
J. Biol. Chem. 273:20378-20382(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Kidney.
[3]"Primary systemic carnitine deficiency is caused by mutations in a gene encoding sodium ion-dependent carnitine transporter."
Nezu J., Tamai I., Oku A., Ohashi R., Yabuuchi H., Hashimoto N., Nikaido H., Sai Y., Koizumi A., Shoji Y., Takada G., Matsuishi T., Yashino M., Kato H., Ohura T., Tsujimoto G., Hayakawa J., Shimane M., Tsuji A.
Nat. Genet. 21:91-94(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
[4]"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., Mori D., Nishiya T., Takikawa O., Horinouchi T., Nishimoto A., Kajita E., Miwa S.
Biochim. Biophys. Acta 1773:1000-1006(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
[5]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
Tissue: Trachea.
[6]"The DNA sequence and comparative analysis of human chromosome 5."
Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S. expand/collapse author list , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.
Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Lung.
[9]"Functional characteristics and tissue distribution pattern of organic cation transporter 2 (OCTN2), an organic cation/carnitine transporter."
Wu X., Huang W., Prasad P.D., Seth P., Rajan D.P., Leibach F.H., Chen J., Conway S.J., Ganapathy V.
J. Pharmacol. Exp. Ther. 290:1482-1492(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY.
[10]"Mass-spectrometric identification and relative quantification of N-linked cell surface glycoproteins."
Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M., Schiess R., Aebersold R., Watts J.D.
Nat. Biotechnol. 27:378-386(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-57 AND ASN-91.
Tissue: Leukemic T-cell.
[11]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-486, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[12]"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., Kreuder J., Schweitzer S., Vorgerd M., Gempel K., Gerbitz K.-D., Kilimann M.W.
Biochem. Biophys. Res. Commun. 261:484-487(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CDSP GLN-169.
[13]"Identification of two novel mutations in OCTN2 of three patients with systemic carnitine deficiency."
Vaz F.M., Scholte H.R., Ruiter J., Hussaarts-Odijk L.M., Rodrigues Pereira R., Schweitzer S., de Klerk J.B.C., Waterham H.R., Wanders R.J.A.
Hum. Genet. 105:157-161(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CDSP CYS-211.
[14]"Mutations of OCTN2, an organic cation/carnitine transporter, lead to deficient cellular carnitine uptake in primary carnitine deficiency."
Tang N.L., Ganapathy V., Wu X., Hui J., Seth P., Yuen P.M., Wanders R.J., Fok T.F., Hjelm N.M.
Hum. Mol. Genet. 8:655-660(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CDSP LEU-478.
[15]"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., Nozaki J., Ohura T., Kayo T., Wada Y., Nezu J., Ohashi R., Tamai I., Shoji Y., Takada G., Kibira S., Matsuishi T., Tsuji A.
Hum. Mol. Genet. 8:2247-2254(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CDSP LEU-179; CYS-283 AND CYS-467, CHARACTERIZATION OF VARIANTS CDSP LEU-179; CYS-283 AND CYS-467.
[16]"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., Wu X., Huang W., Leibach F.H., Ganapathy V.
J. Biol. Chem. 274:33388-33392(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANT CDSP LEU-478, MUTAGENESIS.
[17]"Two novel missense mutations of the OCTN2 gene (W283R and V446F) in a patient with primary systemic carnitine deficiency."
Mayatepek E., Nezu J., Tamai I., Oku A., Katsura M., Shimane M., Tsuji A.
Hum. Mutat. 15:118-118(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CDSP ARG-283 AND PHE-446.
[18]"A missense mutation in the OCTN2 gene associated with residual carnitine transport activity."
Wang Y., Kelly M.A., Cowan T.M., Longo N.
Hum. Mutat. 15:238-245(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, VARIANT CDSP LYS-452.
[19]"Functional analysis of mutations in the OCTN2 transporter causing primary carnitine deficiency: lack of genotype-phenotype correlation."
Wang Y., Taroni F., Garavaglia B., Longo N.
Hum. Mutat. 16:401-407(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CDSP TRP-169; VAL-242; ASP-301 AND ARG-351, CHARACTERIZATION OF VARIANTS CDSP TRP-169; VAL-242; ASP-301 AND ARG-351.
[20]"Phenotype and genotype variation in primary carnitine deficiency."
Wang Y., Korman S.H., Ye J., Gargus J.J., Gutman A., Taroni F., Garavaglia B., Longo N.
Genet. Med. 3:387-392(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CDSP PRO-19 AND GLN-399, CHARACTERIZATION OF VARIANTS CDSP PRO-19 AND GLN-399.
[21]"Carnitine transporter defect due to a novel mutation in the SLC22A5 gene presenting with peripheral neuropathy."
Makhseed N., Vallance H.D., Potter M., Waters P.J., Wong L.T.K., Lillquist Y., Pasquali M., Amat di San Filippo C., Longo N.
J. Inherit. Metab. Dis. 27:778-780(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CDSP LEU-83.
[22]"Validation of dye-binding/high-resolution thermal denaturation for the identification of mutations in the SLC22A5 gene."
Dobrowolski S.F., McKinney J.T., Amat di San Filippo C., Giak Sim K., Wilcken B., Longo N.
Hum. Mutat. 25:306-313(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CDSP PRO-19; LEU-83; TRP-169; MET-232; VAL-242; ASP-301; ARG-351; GLN-399; CYS-447; ASP-449; LYS-452 AND ARG-468, CHARACTERIZATION OF VARIANTS MET-232 AND ARG-468.
[23]"Functional genetic diversity in the high-affinity carnitine transporter OCTN2 (SLC22A5)."
Urban T.J., Gallagher R.C., Brown C., Castro R.A., Lagpacan L.L., Brett C.M., Taylor T.R., Carlson E.J., Ferrin T.E., Burchard E.G., Packman S., Giacomini K.M.
Mol. Pharmacol. 70:1602-1611(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS LEU-17; PHE-144; ASP-449; ILE-481; PHE-481; LEU-508; VAL-530 AND SER-549.
[24]"Expanded newborn screening identifies maternal primary carnitine deficiency."
Schimmenti L.A., Crombez E.A., Schwahn B.C., Heese B.A., Wood T.C., Schroer R.J., Bentler K., Cederbaum S., Sarafoglou K., McCann M., Rinaldo P., Matern D., di San Filippo C.A., Pasquali M., Berry S.A., Longo N.
Mol. Genet. Metab. 90:441-445(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CDSP SER-32; SER-46; CYS-467 AND CYS-488, CHARACTERIZATION OF VARIANT CDSP SER-46.
[25]"Maternal systemic primary carnitine deficiency uncovered by newborn screening: clinical, biochemical, and molecular aspects."
El-Hattab A.W., Li F.-Y., Shen J., Powell B.R., Bawle E.V., Adams D.J., Wahl E., Kobori J.A., Graham B., Scaglia F., Wong L.-J.
Genet. Med. 12:19-24(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CDSP TRP-15; SER-46; LEU-83; SER-142; VAL-214; MET-232; TRP-399 AND ILE-442.
[26]"Molecular spectrum of SLC22A5 (OCTN2) gene mutations detected in 143 subjects evaluated for systemic carnitine deficiency."
Li F.-Y., El-Hattab A.W., Bawle E.V., Boles R.G., Schmitt E.S., Scaglia F., Wong L.-J.
Hum. Mutat. 31:E1632-E1651(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CDSP SER-12; TRP-15; LEU-17; SER-32; SER-46; LEU-83; TYR-122; SER-142; TRP-169; GLN-169; PRO-186; VAL-214; HIS-227; MET-232; TRP-257; ARG-264; GLN-282; LEU-355; LEU-398; TRP-399; MET-440; ILE-442; VAL-443; ASP-449; LYS-452; ARG-455; CYS-467; CYS-488 AND SER-507, VARIANTS PRO-66; PRO-75; ALA-96; GLY-123; LEU-143; VAL-177; LEU-230; THR-240; VAL-312; ASN-358 AND SER-549.
[27]"Diagnoses of newborns and mothers with carnitine uptake defects through newborn screening."
Lee N.-C., Tang N.-L., Chien Y.-H., Chen C.-A., Lin S.-J., Chiu P.-C., Huang A.-C., Hwu W.-L.
Mol. Genet. Metab. 100:46-50(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CDSP LEU-17; ARG-234; GLN-282; LEU-362; CYS-467 AND CYS-471, VARIANT LEU-143.
[28]"Genotype-phenotype correlation in primary carnitine deficiency."
Rose E.C., di San Filippo C.A., Ndukwe Erlingsson U.C., Ardon O., Pasquali M., Longo N.
Hum. Mutat. 33:118-123(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CDSP TRP-15; PRO-19; PHE-22 DEL; ASN-26; SER-32; SER-46; LEU-83; SER-142; GLN-169; TRP-169; VAL-214; MET-232; PHE-280; GLN-282; ARG-283; ARG-351; MET-440; ILE-442; PHE-446; CYS-447; CYS-467; PRO-471 AND HIS-488, CHARACTERIZATION OF VARIANTS CDSP TRP-15; PRO-19; PHE-22 DEL; ASN-26; SER-32; SER-46; LEU-83; GLN-169; TRP-169; VAL-214; MET-232; PHE-280; GLN-282; ARG-283; ARG-351; MET-440; ILE-442; PHE-446; CYS-447; CYS-467 AND PRO-471.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF057164 mRNA. Translation: AAC24828.1.
AB015050 mRNA. Translation: BAA29023.1.
AB016625 Genomic DNA. Translation: BAA36712.1.
AB291606 mRNA. Translation: BAF45812.1.
AK128610 mRNA. Translation: BAC87527.1.
AK313230 mRNA. Translation: BAG36041.1.
AC118464 Genomic DNA. No translation available.
CH471062 Genomic DNA. Translation: EAW62337.1.
CH471062 Genomic DNA. Translation: EAW62338.1.
BC012325 mRNA. Translation: AAH12325.1.
PIRJW0089.
RefSeqNP_003051.1. NM_003060.3.
XP_005272112.1. XM_005272055.2.
UniGeneHs.443572.

3D structure databases

ProteinModelPortalO76082.
SMRO76082. Positions 144-514.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112471. 3 interactions.
STRING9606.ENSP00000245407.

Chemistry

ChEMBLCHEMBL2073693.
DrugBankDB00583. L-Carnitine.

Protein family/group databases

TCDB2.A.1.19.3. the major facilitator superfamily (mfs).

PTM databases

PhosphoSiteO76082.

Proteomic databases

PaxDbO76082.
PRIDEO76082.

Protocols and materials databases

DNASU6584.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000245407; ENSP00000245407; ENSG00000197375. [O76082-1]
ENST00000435065; ENSP00000402760; ENSG00000197375. [O76082-3]
GeneID6584.
KEGGhsa:6584.
UCSCuc003kww.4. human. [O76082-1]
uc003kwx.4. human. [O76082-3]
uc010jdr.1. human. [O76082-2]

Organism-specific databases

CTD6584.
GeneCardsGC05P131733.
HGNCHGNC:10969. SLC22A5.
MIM212140. phenotype.
603377. gene.
neXtProtNX_O76082.
Orphanet158. Carnitine uptake deficiency.
PharmGKBPA333.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0477.
HOGENOMHOG000234570.
HOVERGENHBG061545.
InParanoidO76082.
KOK08202.
OMAGMKHRKT.
OrthoDBEOG7C8GH9.
PhylomeDBO76082.
TreeFamTF315847.

Enzyme and pathway databases

ReactomeREACT_15518. Transmembrane transport of small molecules.

Gene expression databases

ArrayExpressO76082.
BgeeO76082.
CleanExHS_SLC22A5.
GenevestigatorO76082.

Family and domain databases

InterProIPR020846. MFS_dom.
IPR016196. MFS_dom_general_subst_transpt.
IPR004749. Orgcat_transp.
IPR005828. Sub_transporter.
IPR005829. Sugar_transporter_CS.
[Graphical view]
PfamPF00083. Sugar_tr. 1 hit.
[Graphical view]
SUPFAMSSF103473. SSF103473. 1 hit.
TIGRFAMsTIGR00898. 2A0119. 1 hit.
PROSITEPS50850. MFS. 1 hit.
PS00216. SUGAR_TRANSPORT_1. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiSLC22A5.
GenomeRNAi6584.
NextBio25621.
PROO76082.
SOURCESearch...

Entry information

Entry nameS22A5_HUMAN
AccessionPrimary (citable) accession number: O76082
Secondary accession number(s): A2Q0V1 expand/collapse secondary AC list , B2R844, D3DQ87, Q6ZQZ8, Q96EH6
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: November 1, 1998
Last modified: April 16, 2014
This is version 133 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM