Solute carrier family 22 member 4

Details

Name
Solute carrier family 22 member 4
Synonyms
  • Ergothioneine transporter
  • ET transporter
  • ETT
  • ETTh
  • OCTN1
  • Organic cation/carnitine transporter 1
  • UT2H
Gene Name
SLC22A4
UniProtKB Entry
Q9H015Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0010533|Solute carrier family 22 member 4
MRDYDEVIAFLGEWGPFQRLIFFLLSASIIPNGFNGMSVVFLAGTPEHRCRVPDAANLSS
AWRNNSVPLRLRDGREVPHSCSRYRLATIANFSALGLEPGRDVDLGQLEQESCLDGWEFS
QDVYLSTVVTEWNLVCEDNWKVPLTTSLFFVGVLLGSFVSGQLSDRFGRKNVLFATMAVQ
TGFSFLQIFSISWEMFTVLFVIVGMGQISNYVVAFILGTEILGKSVRIIFSTLGVCTFFA
VGYMLLPLFAYFIRDWRMLLLALTVPGVLCVPLWWFIPESPRWLISQRRFREAEDIIQKA
AKMNNIAVPAVIFDSVEELNPLKQQKAFILDLFRTRNIAIMTIMSLLLWMLTSVGYFALS
LDAPNLHGDAYLNCFLSALIEIPAYITAWLLLRTLPRRYIIAAVLFWGGGVLLFIQLVPV
DYYFLSIGLVMLGKFGITSAFSMLYVFTAELYPTLVRNMAVGVTSTASRVGSIIAPYFVY
LGAYNRMLPYIVMGSLTVLIGILTLFFPESLGMTLPETLEQMQKVKWFRSGKKTRDSMET
EENPKVLITAF
Number of residues
551
Molecular Weight
62154.48
Theoretical pI
7.27
GO Classification
Functions
acetylcholine transmembrane transporter activity / amino acid transmembrane transporter activity / amino-acid betaine transmembrane transporter activity
Processes
amino acid import across plasma membrane / xenobiotic transport
Components
basal plasma membrane / mitochondrial membrane
General Function
Transporter that mediates the transport of endogenous and microbial zwitterions and organic cations (PubMed:10215651, PubMed:15107849, PubMed:15795384, PubMed:16729965, PubMed:20601551, PubMed:22206629, PubMed:22569296, PubMed:29530864). Functions as a Na(+)-dependent and pH-dependent high affinity microbial symporter of potent food-derived antioxidant ergothioeine (PubMed:15795384, PubMed:29530864, PubMed:33124720). Transports one sodium ion with one ergothioeine molecule (By similarity). Involved in the absorption of ergothioneine from the luminal/apical side of the small intestine and renal tubular cells, and into non-parenchymal liver cells, thereby contributing to maintain steady-state ergothioneine level in the body (PubMed:20601551). Also mediates the bidirectional transport of acetycholine, although the exact transport mechanism has not been fully identified yet (PubMed:22206629). Most likely exports anti-inflammatory acetylcholine in non-neuronal tissues, thereby contributing to the non-neuronal cholinergic system (PubMed:22206629, PubMed:22569296). Displays a general physiological role linked to better survival by controlling inflammation and oxidative stress, which may be related to ergothioneine and acetycholine transports (PubMed:15795384, PubMed:22206629). May also function as a low-affinity Na(+)-dependent transporter of L-carnitine through the mitochondrial membrane, thereby maintaining intracellular carnitine homeostasis (PubMed:10215651, PubMed:15107849, PubMed:16729965). May contribute to regulate the transport of cationic compounds in testis across the blood-testis-barrier (PubMed:35307651)
Specific Function
Acetylcholine transmembrane transporter activity
Pfam Domain Function
Signal Regions
Not Available
Transmembrane Regions
21-41 142-162 172-192 198-218 233-253 258-278 338-358 372-392 400-420 427-447 461-481 487-507
Cellular Location
Apical cell membrane
Gene sequence
>lcl|BSEQ0010534|Solute carrier family 22 member 4 (SLC22A4)
ATGCGGGACTACGACGAGGTGATCGCCTTCCTGGGCGAGTGGGGGCCCTTCCAGCGCCTC
ATCTTCTTCCTGCTCAGCGCCAGCATCATCCCCAATGGCTTCAATGGTATGTCAGTCGTG
TTCCTGGCGGGGACCCCGGAGCACCGCTGTCGAGTGCCGGACGCCGCGAACCTGAGCAGC
GCCTGGCGCAACAACAGTGTCCCGCTGCGGCTGCGGGACGGCCGCGAGGTGCCCCACAGC
TGCAGCCGCTACCGGCTCGCCACCATCGCCAACTTCTCGGCGCTCGGGCTGGAGCCGGGG
CGCGACGTGGACCTGGGGCAGCTGGAGCAGGAGAGCTGCCTGGATGGCTGGGAGTTCAGC
CAGGACGTCTACCTGTCCACCGTCGTGACCGAGTGGAATCTGGTGTGTGAGGACAACTGG
AAGGTGCCCCTCACCACCTCCCTGTTCTTCGTAGGCGTGCTCCTCGGCTCCTTCGTGTCC
GGGCAGCTGTCAGACAGGTTTGGCAGGAAGAACGTTCTCTTCGCAACCATGGCTGTACAG
ACTGGCTTCAGCTTCCTGCAGATTTTCTCCATCAGCTGGGAGATGTTCACTGTGTTATTT
GTCATCGTGGGCATGGGCCAGATCTCCAACTATGTGGTAGCCTTCATACTAGGAACAGAA
ATTCTTGGCAAGTCAGTTCGTATTATATTCTCTACATTAGGAGTGTGCACATTTTTTGCA
GTTGGCTATATGCTGCTGCCACTGTTTGCTTACTTCATCAGAGACTGGCGGATGCTGCTG
CTGGCGCTGACGGTGCCGGGAGTGCTGTGTGTCCCGCTGTGGTGGTTCATTCCTGAATCT
CCCCGATGGCTGATATCCCAGAGAAGATTTAGAGAGGCTGAAGATATCATCCAAAAAGCT
GCAAAAATGAACAACATAGCTGTACCAGCAGTGATATTTGATTCTGTGGAGGAGCTAAAT
CCCCTGAAGCAGCAGAAAGCTTTCATTCTGGACCTGTTCAGGACTCGGAATATTGCCATA
ATGACCATTATGTCTTTGCTGCTATGGATGCTGACCTCAGTGGGTTACTTTGCTCTGTCT
CTGGATGCTCCTAATTTACATGGAGATGCCTACCTGAACTGTTTCCTCTCTGCCTTGATT
GAAATTCCAGCTTACATTACAGCCTGGCTGCTATTGCGAACCCTGCCCAGGCGTTATATC
ATAGCTGCAGTACTGTTCTGGGGAGGAGGTGTGCTTCTCTTCATTCAACTGGTACCTGTG
GATTATTACTTCTTATCCATTGGTCTGGTCATGCTGGGAAAATTTGGGATCACCTCTGCT
TTCTCCATGCTGTATGTCTTCACTGCTGAGCTCTACCCAACCCTGGTCAGGAACATGGCG
GTGGGGGTCACATCCACGGCCTCCAGAGTGGGCAGCATCATTGCCCCCTACTTTGTTTAC
CTCGGTGCTTACAACAGAATGCTGCCCTACATCGTCATGGGTAGTCTGACTGTCCTGATT
GGAATCCTCACCCTTTTTTTCCCTGAAAGTTTGGGAATGACTCTTCCAGAAACCTTAGAG
CAGATGCAGAAAGTGAAATGGTTCAGATCTGGGAAAAAAACAAGAGACTCAATGGAGACA
GAAGAAAATCCCAAGGTTCTAATAACTGCATTCTGA
Chromosome Location
5
Locus
5q31.1
External Identifiers
ResourceLink
UniProtKB IDQ9H015
UniProtKB Entry NameS22A4_HUMAN
GenBank Protein ID2605501
GenBank Gene IDAB007448
GeneCard IDSLC22A4
GenAtlas IDSLC22A4
HGNC IDHGNC:10968
KEGG IDhsa:6583
NCBI Gene ID6583
General References
  1. Tamai I, Yabuuchi H, Nezu J, Sai Y, Oku A, Shimane M, Tsuji A: Cloning and characterization of a novel human pH-dependent organic cation transporter, OCTN1. FEBS Lett. 1997 Dec 8;419(1):107-11. [Article]
  2. Grundemann D, Harlfinger S, Golz S, Geerts A, Lazar A, Berkels R, Jung N, Rubbert A, Schomig E: Discovery of the ergothioneine transporter. Proc Natl Acad Sci U S A. 2005 Apr 5;102(14):5256-61. Epub 2005 Mar 28. [Article]
  3. Schmutz J, Martin J, Terry A, Couronne O, Grimwood J, Lowry S, Gordon LA, 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 JF, Chan YM, Denys M, Detter JC, 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 JP, 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 JF, Eichler EE, Olsen A, Pennacchio LA, Rokhsar DS, Richardson P, Lucas SM, Myers RM, Rubin EM: The DNA sequence and comparative analysis of human chromosome 5. Nature. 2004 Sep 16;431(7006):268-74. [Article]
  4. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  5. Yabuuchi H, Tamai I, Nezu J, Sakamoto K, Oku A, Shimane M, Sai Y, Tsuji A: Novel membrane transporter OCTN1 mediates multispecific, bidirectional, and pH-dependent transport of organic cations. J Pharmacol Exp Ther. 1999 May;289(2):768-73. [Article]
  6. Tokuhiro S, Yamada R, Chang X, Suzuki A, Kochi Y, Sawada T, Suzuki M, Nagasaki M, Ohtsuki M, Ono M, Furukawa H, Nagashima M, Yoshino S, Mabuchi A, Sekine A, Saito S, Takahashi A, Tsunoda T, Nakamura Y, Yamamoto K: An intronic SNP in a RUNX1 binding site of SLC22A4, encoding an organic cation transporter, is associated with rheumatoid arthritis. Nat Genet. 2003 Dec;35(4):341-8. Epub 2003 Nov 9. [Article]
  7. Saito S, Iida A, Sekine A, Ogawa C, Kawauchi S, Higuchi S, Nakamura Y: Catalog of 238 variations among six human genes encoding solute carriers ( hSLCs) in the Japanese population. J Hum Genet. 2002;47(11):576-84. [Article]
  8. Kawasaki Y, Kato Y, Sai Y, Tsuji A: Functional characterization of human organic cation transporter OCTN1 single nucleotide polymorphisms in the Japanese population. J Pharm Sci. 2004 Dec;93(12):2920-6. [Article]
  9. Peltekova VD, Wintle RF, Rubin LA, Amos CI, Huang Q, Gu X, Newman B, Van Oene M, Cescon D, Greenberg G, Griffiths AM, St George-Hyslop PH, Siminovitch KA: Functional variants of OCTN cation transporter genes are associated with Crohn disease. Nat Genet. 2004 May;36(5):471-5. Epub 2004 Apr 11. [Article]

Associated Data

Bio-Entities
Bio-EntityType
Solute carrier family 22 member 4 (Humans)protein
primary
Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
Levocarnitineapproved, investigationalunknowntargetDetails
VerapamilapprovedunknowntransporterinhibitorDetails
Spermineexperimental, nutraceuticalunknowntransporterinhibitorDetails
SpermidineexperimentalunknowntransporterinhibitorDetails
QuinineapprovedunknowntransporterinhibitorDetails
Quinidineapproved, investigationalunknowntransporterinhibitorDetails
PutrescineexperimentalunknowntransporterinhibitorDetails
ProcainamideapprovedunknowntransporterinhibitorDetails
Benzylpenicillinapproved, vet_approvedunknowntransporterinhibitorDetails
Aminohippuric acidapproved, investigationalunknowntransporterinhibitorDetails
OfloxacinapprovedunknowntransporterinhibitorDetails
NicotineapprovedunknowntransporterinhibitorDetails
Lysineapproved, nutraceuticalunknowntransporterinhibitorDetails
Levofloxacinapproved, investigationalunknowntransporterinhibitorDetails
GuanidineapprovedunknowntransporterinhibitorDetails
ClonidineapprovedunknowntransporterinhibitorDetails
Cimetidineapproved, investigationalunknowntransporterinhibitorDetails
Cholineapproved, nutraceuticalunknowntransporterinhibitorDetails
Levocarnitineapproved, investigationalunknowntransportersubstrateinhibitorDetails
Arginineinvestigational, nutraceuticalunknowntransporterinhibitorDetails
AmilorideapprovedunknowntransporterinhibitorDetails
ImipramineapprovedunknowntransporterinhibitorDetails
Desipramineapproved, investigationalunknowntransporterinhibitorDetails
Cytarabineapproved, investigationalunknowntransportersubstrateDetails
Ipratropiumapproved, experimentalunknowntransportersubstrateDetails
TiotropiumapprovedunknowntransportersubstrateDetails
Tetraethylammoniumexperimental, investigationalunknowntransporterDetails
Mepyramineapproved, vet_approvedunknowntransporterDetails
Testosterone cypionateapprovedunknowntransportersubstrateDetails
Testosterone enanthateapprovedunknowntransportersubstrateDetails
Testosterone undecanoateapproved, investigationalunknowntransportersubstrateDetails
Choline salicylateapproved, nutraceuticalunknowntransporterinhibitorDetails
SolriamfetolapprovedunknowntransporterDetails
Memantineapproved, investigationalunknowntransporterDetails
Formoterolapproved, investigationalunknowntransportersubstrateDetails
HydroxyureaapprovednotransportersubstrateDetails