O76082 (S22A5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	557 AA.
Sequence status	Complete.
Protein existence	Evidence 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 process	Ion transport Sodium transport Symport Transport
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Domain	Transmembrane Transmembrane helix
Ligand	ATP-binding Nucleotide-binding Sodium
PTM	Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	positive regulation of intestinal epithelial structure maintenance Inferred from mutant phenotype PubMed 18005709. 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
Cellular_component	apical plasma membrane Inferred from direct assay PubMed 17274673PubMed 18641280. Source: BHF-UCL basolateral plasma membrane Inferred from electronic annotation. Source: Compara brush border membrane Inferred from direct assay PubMed 15238359. Source: BHF-UCL integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW antibiotic transporter activity Inferred from electronic annotation. Source: Compara 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 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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 557	557	Solute carrier family 22 member 5		PRO_0000220500
Regions
	Topological domain	1 – 20	20	Cytoplasmic Potential
	Transmembrane	21 – 41	21	Helical; Name=1; Potential
	Topological domain	42 – 142	101	Extracellular Potential
	Transmembrane	143 – 163	21	Helical; Name=2; Potential
	Topological domain	164 – 172	9	Cytoplasmic Potential
	Transmembrane	173 – 193	21	Helical; Name=3; Potential
	Topological domain	194 – 197	4	Extracellular Potential
	Transmembrane	198 – 218	21	Helical; Name=4; Potential
	Topological domain	219 – 232	14	Cytoplasmic Potential
	Transmembrane	233 – 253	21	Helical; Name=5; Potential
	Topological domain	254 – 257	4	Extracellular Potential
	Transmembrane	258 – 278	21	Helical; Name=6; Potential
	Topological domain	279 – 341	63	Cytoplasmic Potential
	Transmembrane	342 – 362	21	Helical; Name=7; Potential
	Topological domain	363 – 373	11	Extracellular Potential
	Transmembrane	374 – 394	21	Helical; Name=8; Potential
	Topological domain	395 – 406	12	Cytoplasmic Potential
	Transmembrane	407 – 427	21	Helical; Name=9; Potential
	Topological domain	428 – 430	3	Extracellular Potential
	Transmembrane	431 – 451	21	Helical; Name=10; Potential
	Topological domain	452 – 462	11	Cytoplasmic Potential
	Transmembrane	463 – 483	21	Helical; Name=11; Potential
	Topological domain	484 – 488	5	Extracellular Potential
	Transmembrane	489 – 509	21	Helical; Name=12; Potential
	Nucleotide binding	218 – 225	8	ATP Potential
Amino acid modifications
	Modified residue	486	1	Phosphotyrosine Ref.11
	Glycosylation	57	1	N-linked (GlcNAc...) Ref.10
	Glycosylation	64	1	N-linked (GlcNAc...) Potential
	Glycosylation	91	1	N-linked (GlcNAc...) Ref.10
Natural variations
	Alternative sequence	1 – 336	336	Missing in isoform 2.		VSP_011120
	Alternative sequence	131	1	E → EQDSGAYNAMKNRMGKKPAL CLPAQ in isoform 3.		VSP_043904
	Alternative sequence	337 – 351	15	TWNIR…SIMLW → MWILLFQLSSALCFR in isoform 2.		VSP_011121
	Natural variant	12	1	G → S in CDSP. Ref.26		VAR_064109
	Natural variant	15	1	G → W in CDSP. Ref.25 Ref.26 Ref.28		VAR_064110
	Natural variant	17	1	F → L in CDSP. Ref.23 Ref.26 Ref.27		VAR_020347
	Natural variant	19	1	R → P in CDSP; carnitine transport is reduced to less than 5% of normal. Ref.20 Ref.22 Ref.28		VAR_064111
	Natural variant	22	1	Missing in CDSP; reduces carnitine transport. Ref.28		VAR_066842
	Natural variant	26	1	S → N in CDSP; reduces carnitine transport. Ref.28		VAR_066843
	Natural variant	32	1	N → S in CDSP; reduces carnitine transport. Ref.24 Ref.26 Ref.28		VAR_064112
	Natural variant	46	1	P → S in CDSP; carnitine transport is reduced to less than 5% of normal. Ref.24 Ref.25 Ref.26 Ref.28		VAR_064113
	Natural variant	66	1	T → P Associated with CDSP; unclassified missense variant. Ref.26		VAR_064114
	Natural variant	75	1	R → P Associated with CDSP; unclassified missense variant. Ref.26		VAR_064115
	Natural variant	83	1	R → L in CDSP; reduces carnitine transport. Ref.21 Ref.22 Ref.25 Ref.26 Ref.28		VAR_064116
	Natural variant	96	1	G → A Associated with CDSP; unclassified missense variant. Ref.26		VAR_064117
	Natural variant	122	1	D → Y in CDSP. Ref.26		VAR_064118
	Natural variant	123	1	V → G Associated with CDSP; unclassified missense variant. Ref.26		VAR_064119
	Natural variant	142	1	A → S in CDSP. Ref.25 Ref.26 Ref.28		VAR_064120
	Natural variant	143	1	P → L Associated with CDSP; unclassified missense variant. Ref.26 Ref.27		VAR_064121
	Natural variant	144	1	L → F. Ref.23 Corresponds to variant rs10040427 [ dbSNP | Ensembl ].		VAR_020348
	Natural variant	169	1	R → Q in CDSP; reduces carnitine transport. Ref.12 Ref.26 Ref.28		VAR_009252
	Natural variant	169	1	R → W in CDSP; abolishes carnitine transport. Ref.19 Ref.22 Ref.26 Ref.28		VAR_064122
	Natural variant	177	1	M → V Associated with CDSP; unclassified missense variant. Ref.26		VAR_064123
	Natural variant	179	1	M → L in CDSP. Ref.15		VAR_022564
	Natural variant	186	1	L → P in CDSP. Ref.26		VAR_064124
	Natural variant	211	1	Y → C in CDSP. Ref.13		VAR_009253
	Natural variant	214	1	A → V in CDSP; reduces carnitine transport. Ref.25 Ref.26 Ref.28		VAR_064125
	Natural variant	227	1	R → H in CDSP. Ref.26		VAR_064126
	Natural variant	230	1	F → L Associated with CDSP; unclassified missense variant. Ref.26		VAR_064127
	Natural variant	232	1	T → M in CDSP; markedly reduced carnitine transport compared to the wild-type protein. Ref.22 Ref.25 Ref.26 Ref.28		VAR_064128
	Natural variant	234	1	G → R in CDSP. Ref.27		VAR_064129
	Natural variant	240	1	A → T Associated with CDSP; unclassified missense variant. Ref.26		VAR_064130
	Natural variant	242	1	G → V in CDSP; abolishes carnitine transport. Ref.19 Ref.22		VAR_064131
	Natural variant	257	1	R → W in CDSP. Ref.26		VAR_064132
	Natural variant	264	1	T → R in CDSP. Ref.26		VAR_064133
	Natural variant	280	1	S → F in CDSP; reduces carnitine transport. Ref.28		VAR_066844
	Natural variant	282	1	R → Q in CDSP; reduces carnitine transport. Ref.26 Ref.27 Ref.28		VAR_064134
	Natural variant	283	1	W → C in CDSP; reduces L-carnitine uptake. Ref.15		VAR_022565
	Natural variant	283	1	W → R in CDSP; reduces carnitine transport. Ref.17 Ref.28		VAR_009254
	Natural variant	301	1	A → 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 variant	312	1	I → V Associated with CDSP; unclassified missense variant. Ref.26		VAR_064136
	Natural variant	351	1	W → R in CDSP; abolishes carnitine transport. Ref.19 Ref.22 Ref.28		VAR_064137
	Natural variant	355	1	S → L in CDSP. Ref.26		VAR_064138
	Natural variant	358	1	Y → N Associated with CDSP; unclassified missense variant. Ref.26		VAR_064139
	Natural variant	362	1	S → L in CDSP. Ref.27		VAR_064140
	Natural variant	398	1	P → L in CDSP. Ref.26		VAR_064141
	Natural variant	399	1	R → Q in CDSP; carnitine transport is reduced to less than 5% of normal. Ref.20 Ref.22		VAR_064142
	Natural variant	399	1	R → W in CDSP. Ref.25 Ref.26		VAR_064143
	Natural variant	440	1	T → M in CDSP; reduces carnitine transport. Ref.26 Ref.28		VAR_064144
	Natural variant	442	1	A → I in CDSP; requires 2 nucleotide substitutions; reduces carnitine transport. Ref.25 Ref.26 Ref.28		VAR_064145
	Natural variant	443	1	F → V in CDSP. Ref.26		VAR_064146
	Natural variant	446	1	V → F in CDSP; reduces carnitine transport. Ref.17 Ref.28		VAR_009255
	Natural variant	447	1	Y → C in CDSP; reduces carnitine transport. Ref.22 Ref.28		VAR_064147
	Natural variant	449	1	Y → D in CDSP. Ref.22 Ref.23 Ref.26 Corresponds to variant rs11568514 [ dbSNP | Ensembl ].		VAR_029315
	Natural variant	452	1	E → K in CDSP. Ref.18 Ref.22 Ref.26		VAR_009256
	Natural variant	455	1	P → R in CDSP. Ref.26		VAR_064148
	Natural variant	467	1	S → C in CDSP; reduces L-carnitine uptake. Ref.15 Ref.24 Ref.26 Ref.27 Ref.28		VAR_022566
	Natural variant	468	1	T → R in CDSP; markedly reduced carnitine transport compared to the wild-type protein. Ref.22		VAR_064149
	Natural variant	471	1	R → C in CDSP. Ref.27		VAR_064150
	Natural variant	471	1	R → P in CDSP; reduces carnitine transport. Ref.28		VAR_066845
	Natural variant	478	1	P → L in CDSP; loss of carnitine transport but stimulated organic cation transport. Ref.14 Ref.16		VAR_009257
	Natural variant	481	1	V → F. Ref.23		VAR_020349
	Natural variant	481	1	V → I. Ref.23		VAR_036816
	Natural variant	488	1	R → C in CDSP. Ref.24 Ref.26		VAR_064151
	Natural variant	488	1	R → H in CDSP; reduces carnitine transport. Ref.28		VAR_066846
	Natural variant	507	1	L → S in CDSP. Ref.26		VAR_064152
	Natural variant	508	1	F → L. Ref.23		VAR_029316
	Natural variant	530	1	M → V. Ref.23		VAR_029317
	Natural variant	549	1	P → S Associated with CDSP; unclassified missense variant. Ref.23 Ref.26 Corresponds to variant rs11568525 [ dbSNP | Ensembl ].		VAR_020350
Experimental info
	Mutagenesis	352	1	M → R: Loss of both carnitine and organic cation transport functionalities.
	Sequence conflict	114	1	L → P in AAH12325. Ref.8

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1998. Version 1. Checksum: 928B1F6EFF63C48D	FASTA	557	62,752
	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
	Isoform 2 [UniParc]. Checksum: B66DFBC13A50BDAF	FASTA	221	24,688
	10 20 30 40 50 60 MWILLFQLSS ALCFRMTISV GYFGLSLDTP NLHGDIFVNC FLSAMVEVPA YVLAWLLLQY 70 80 90 100 110 120 LPRRYSMATA LFLGGSVLLF MQLVPPDLYY LATVLVMVGK FGVTAAFSMV YVYTAELYPT 130 140 150 160 170 180 VVRNMGVGVS STASRLGSIL SPYFVYLGAY DRFLPYILMG SLTILTAILT LFLPESFGTP 190 200 210 220 LPDTIDQMLR VKGMKHRKTP SHTRMLKDGQ ERPTILKSTA F
	Isoform 3 (OCTN2VT) [UniParc]. Checksum: C4DB6274B866DBF9	FASTA	581	65,327
	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 EQDSGAYNAM KNRMGKKPAL CLPAQWNLVC EDDWKAPLTI SLFFVGVLLG 190 200 210 220 230 240 SFISGQLSDR FGRKNVLFVT MGMQTGFSFL QIFSKNFEMF VVLFVLVGMG QISNYVAAFV 250 260 270 280 290 300 LGTEILGKSV RIIFSTLGVC IFYAFGYMVL PLFAYFIRDW RMLLVALTMP GVLCVALWWF 310 320 330 340 350 360 IPESPRWLIS QGRFEEAEVI IRKAAKANGI VVPSTIFDPS ELQDLSSKKQ QSHNILDLLR 370 380 390 400 410 420 TWNIRMVTIM SIMLWMTISV GYFGLSLDTP NLHGDIFVNC FLSAMVEVPA YVLAWLLLQY 430 440 450 460 470 480 LPRRYSMATA LFLGGSVLLF MQLVPPDLYY LATVLVMVGK FGVTAAFSMV YVYTAELYPT 490 500 510 520 530 540 VVRNMGVGVS STASRLGSIL SPYFVYLGAY DRFLPYILMG SLTILTAILT LFLPESFGTP 550 560 570 580 LPDTIDQMLR VKGMKHRKTP SHTRMLKDGQ ERPTILKSTA F

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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, MASS SPECTROMETRY. 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, MASS SPECTROMETRY. 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.

Web resources

GeneReviews

The SLC22A5 database

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.
IPI	IPI00435872. IPI00435873. IPI00829886.
PIR	JW0089.
RefSeq	NP_003051.1. NM_003060.3.
UniGene	Hs.443572.
3D structure databases
ProteinModelPortal	O76082.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000245407.
Protein family/group databases
TCDB	2.A.1.19.3. major facilitator superfamily (MFS).
PTM databases
PhosphoSite	O76082.
Proteomic databases
PaxDb	O76082.
PRIDE	O76082.
Protocols and materials databases
DNASU	6584.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000245407; ENSP00000245407; ENSG00000197375. ENST00000435065; ENSP00000402760; ENSG00000197375.
GeneID	6584.
KEGG	hsa:6584.
UCSC	uc003kww.4. human. uc010jdr.1. human.
Organism-specific databases
CTD	6584.
GeneCards	GC05P131733.
HGNC	HGNC:10969. SLC22A5.
MIM	212140. phenotype. 603377. gene.
neXtProt	NX_O76082.
Orphanet	158. Carnitine uptake deficiency.
PharmGKB	PA333.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0477.
HOGENOM	HOG000234570.
HOVERGEN	HBG061545.
InParanoid	O76082.
KO	K08202.
OMA	EVIIRRA.
OrthoDB	EOG4WDDBH.
PhylomeDB	O76082.
Enzyme and pathway databases
Reactome	REACT_15518. Transmembrane transport of small molecules.
Gene expression databases
ArrayExpress	O76082.
Bgee	O76082.
CleanEx	HS_SLC22A5.
Genevestigator	O76082.
GermOnline	ENSG00000197375. Homo sapiens.
Family and domain databases
InterPro	IPR020846. MFS_dom. IPR016196. MFS_dom_general_subst_transpt. IPR004749. Orgcat_transp. IPR005828. Sub_transporter. IPR005829. Sugar_transporter_CS. [Graphical view]
Pfam	PF00083. Sugar_tr. 1 hit. [Graphical view]
SUPFAM	SSF103473. MFS_gen_substrate_transporter. 1 hit.
TIGRFAMs	TIGR00898. 2A0119. 1 hit.
PROSITE	PS50850. MFS. 1 hit. PS00216. SUGAR_TRANSPORT_1. 1 hit. [Graphical view]
ProtoNet	Search...
Other
DrugBank	DB00583. L-Carnitine.
GenomeRNAi	6584.
NextBio	25621.
SOURCE	Search...

Entry information

Entry name

S22A5_HUMAN

Accession

Primary (citable) accession number: O76082
Secondary accession number(s): A2Q0V1 , B2R844, D3DQ87, Q6ZQZ8, Q96EH6

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	November 1, 1998
Last modified:	May 1, 2013
This is version 122 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.