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Protein

Solute carrier family 22 member 4

Gene

SLC22A4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Sodium-ion dependent, low affinity carnitine transporter. Probably transports one sodium ion with one molecule of carnitine. Also transports organic cations such as tetraethylammonium (TEA) without the involvement of sodium. Relative uptake activity ratio of carnitine to TEA is 1.78. A key substrate of this transporter seems to be ergothioneine (ET).2 Publications

Caution

PubMed:9426230 reported that this protein does not transport carnitine, however, experiments were done with the Phe-503 variant, which affects the ability to transport carnitine. PubMed:15459889 showed that, although weakly, it can also transport carnitine at some level. Its function in carnitine transport is therefore unclear.Curated

Kineticsi

  1. KM=0.470 mM for TEA (at 37 degrees Celsius and pH 7.4)2 Publications
  1. Vmax=0.974 nmol/min/mg enzyme toward TEA (at 37 degrees Celsius and pH 7.4)2 Publications

pH dependencei

More active at neutral and alkaline pHs than at acidic pHs.2 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi218 – 225ATPSequence analysis8

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • carnitine transmembrane transporter activity Source: MGI
  • cation:cation antiporter activity Source: BHF-UCL
  • nucleotide binding Source: ProtInc
  • organic anion transmembrane transporter activity Source: GO_Central
  • PDZ domain binding Source: BHF-UCL
  • quaternary ammonium group transmembrane transporter activity Source: BHF-UCL
  • secondary active organic cation transmembrane transporter activity Source: Reactome
  • symporter activity Source: UniProtKB-KW

GO - Biological processi

  • body fluid secretion Source: ProtInc
  • carnitine metabolic process Source: GO_Central
  • carnitine transport Source: MGI
  • organic cation transport Source: ProtInc
  • quaternary ammonium group transport Source: BHF-UCL
  • sodium ion transport Source: UniProtKB-KW
  • triglyceride metabolic process Source: Ensembl

Keywordsi

Biological processIon transport, Sodium transport, Symport, Transport
LigandATP-binding, Nucleotide-binding, Sodium

Enzyme and pathway databases

ReactomeiR-HSA-549127 Organic cation transport

Protein family/group databases

TCDBi2.A.1.19.2 the major facilitator superfamily (mfs)

Names & Taxonomyi

Protein namesi
Recommended name:
Solute carrier family 22 member 4
Alternative name(s):
Ergothioneine transporter
Short name:
ET transporter
Organic cation/carnitine transporter 1
Gene namesi
Name:SLC22A4
Synonyms:ETT, OCTN1, UT2H
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

EuPathDBiHostDB:ENSG00000197208.5
HGNCiHGNC:10968 SLC22A4
MIMi604190 gene
neXtProtiNX_Q9H015

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 20CytoplasmicSequence analysisAdd BLAST20
Transmembranei21 – 41Helical; Name=1Sequence analysisAdd BLAST21
Topological domaini42 – 141ExtracellularSequence analysisAdd BLAST100
Transmembranei142 – 162Helical; Name=2Sequence analysisAdd BLAST21
Topological domaini163 – 171CytoplasmicSequence analysis9
Transmembranei172 – 192Helical; Name=3Sequence analysisAdd BLAST21
Topological domaini193 – 197ExtracellularSequence analysis5
Transmembranei198 – 218Helical; Name=4Sequence analysisAdd BLAST21
Topological domaini219 – 232CytoplasmicSequence analysisAdd BLAST14
Transmembranei233 – 253Helical; Name=5Sequence analysisAdd BLAST21
Topological domaini254 – 257ExtracellularSequence analysis4
Transmembranei258 – 278Helical; Name=6Sequence analysisAdd BLAST21
Topological domaini279 – 337CytoplasmicSequence analysisAdd BLAST59
Transmembranei338 – 358Helical; Name=7Sequence analysisAdd BLAST21
Topological domaini359 – 371ExtracellularSequence analysisAdd BLAST13
Transmembranei372 – 392Helical; Name=8Sequence analysisAdd BLAST21
Topological domaini393 – 399CytoplasmicSequence analysis7
Transmembranei400 – 420Helical; Name=9Sequence analysisAdd BLAST21
Topological domaini421 – 426ExtracellularSequence analysis6
Transmembranei427 – 447Helical; Name=10Sequence analysisAdd BLAST21
Topological domaini448 – 460CytoplasmicSequence analysisAdd BLAST13
Transmembranei461 – 481Helical; Name=11Sequence analysisAdd BLAST21
Topological domaini482 – 486ExtracellularSequence analysis5
Transmembranei487 – 507Helical; Name=12Sequence analysisAdd BLAST21
Topological domaini508 – 551CytoplasmicSequence analysisAdd BLAST44

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Involvement in diseasei

Rheumatoid arthritis (RA)1 Publication
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionAn inflammatory disease with autoimmune features and a complex genetic component. It primarily affects the joints and is characterized by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures.
See also OMIM:180300

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi6583
MalaCardsiSLC22A4
MIMi180300 phenotype
OpenTargetsiENSG00000197208
PharmGKBiPA332

Chemistry databases

ChEMBLiCHEMBL2073668
DrugBankiDB00594 Amiloride
DB00345 Aminohippuric acid
DB01053 Benzylpenicillin
DB00122 Choline
DB00501 Cimetidine
DB00575 Clonidine
DB01151 Desipramine
DB00536 Guanidine
DB00458 Imipramine
DB00332 Ipratropium bromide
DB00125 L-Arginine
DB00583 L-Carnitine
DB00123 L-Lysine
DB01137 Levofloxacin
DB06691 Mepyramine
DB00184 Nicotine
DB01165 Ofloxacin
DB01035 Procainamide
DB01917 Putrescine
DB00908 Quinidine
DB00468 Quinine
DB03566 Spermidine
DB00127 Spermine
DB00624 Testosterone
DB08837 Tetraethylammonium
DB01409 Tiotropium
DB00661 Verapamil

Polymorphism and mutation databases

BioMutaiSLC22A4
DMDMi146345508

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002204971 – 551Solute carrier family 22 member 4Add BLAST551

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi57N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi64N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi91N-linked (GlcNAc...) asparagineSequence analysis1

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiQ9H015
PeptideAtlasiQ9H015
PRIDEiQ9H015
ProteomicsDBi80197

PTM databases

iPTMnetiQ9H015
PhosphoSitePlusiQ9H015

Expressioni

Tissue specificityi

Widely expressed. Highly expressed in whole blood, bone marrow, trachea and fetal liver. Weakly expressed in kidney, skeletal muscle, prostate, lung, pancreas, placenta, heart, uterus, spleen and spinal cord. 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. Predominantly expressed in CD14 cells in peripheral blood mononuclear cells.3 Publications

Inductioni

Overexpressed upon TNF treatment.1 Publication

Gene expression databases

BgeeiENSG00000197208
CleanExiHS_SLC22A4
GenevisibleiQ9H015 HS

Organism-specific databases

HPAiCAB015468
HPA036974

Interactioni

Subunit structurei

Interacts with PDZK1.By similarity

GO - Molecular functioni

  • PDZ domain binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi112470, 1 interactor
STRINGi9606.ENSP00000200652

Structurei

3D structure databases

ProteinModelPortaliQ9H015
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IRIE Eukaryota
ENOG410XSRI LUCA
GeneTreeiENSGT00760000118852
HOGENOMiHOG000234570
HOVERGENiHBG061545
InParanoidiQ9H015
KOiK08202
OMAiSWEMFTV
OrthoDBiEOG091G05AC
PhylomeDBiQ9H015
TreeFamiTF315847

Family and domain databases

CDDicd06174 MFS, 1 hit
InterProiView protein in InterPro
IPR020846 MFS_dom
IPR005828 MFS_sugar_transport-like
IPR036259 MFS_trans_sf
IPR004749 Orgcat_transp/SVOP
IPR005829 Sugar_transporter_CS
PfamiView protein in Pfam
PF00083 Sugar_tr, 1 hit
SUPFAMiSSF103473 SSF103473, 1 hit
TIGRFAMsiTIGR00898 2A0119, 1 hit
PROSITEiView protein in PROSITE
PS50850 MFS, 1 hit
PS00216 SUGAR_TRANSPORT_1, 1 hit

Sequencei

Sequence statusi: Complete.

Q9H015-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRDYDEVIAF LGEWGPFQRL IFFLLSASII PNGFNGMSVV FLAGTPEHRC
60 70 80 90 100
RVPDAANLSS AWRNNSVPLR LRDGREVPHS CSRYRLATIA NFSALGLEPG
110 120 130 140 150
RDVDLGQLEQ ESCLDGWEFS QDVYLSTVVT EWNLVCEDNW KVPLTTSLFF
160 170 180 190 200
VGVLLGSFVS GQLSDRFGRK NVLFATMAVQ TGFSFLQIFS ISWEMFTVLF
210 220 230 240 250
VIVGMGQISN YVVAFILGTE ILGKSVRIIF STLGVCTFFA VGYMLLPLFA
260 270 280 290 300
YFIRDWRMLL LALTVPGVLC VPLWWFIPES PRWLISQRRF REAEDIIQKA
310 320 330 340 350
AKMNNIAVPA VIFDSVEELN PLKQQKAFIL DLFRTRNIAI MTIMSLLLWM
360 370 380 390 400
LTSVGYFALS LDAPNLHGDA YLNCFLSALI EIPAYITAWL LLRTLPRRYI
410 420 430 440 450
IAAVLFWGGG VLLFIQLVPV DYYFLSIGLV MLGKFGITSA FSMLYVFTAE
460 470 480 490 500
LYPTLVRNMA VGVTSTASRV GSIIAPYFVY LGAYNRMLPY IVMGSLTVLI
510 520 530 540 550
GILTLFFPES LGMTLPETLE QMQKVKWFRS GKKTRDSMET EENPKVLITA

F
Length:551
Mass (Da):62,155
Last modified:May 1, 2007 - v3
Checksum:iC827A99AA78C9443
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_019528306I → T2 PublicationsCorresponds to variant dbSNP:rs272893Ensembl.1
Natural variantiVAR_019529462G → E Abrogates TEA transport activity. 2 PublicationsCorresponds to variant dbSNP:rs4646201Ensembl.1
Natural variantiVAR_019530503L → F Reduces the ability to transport carnitine. 2 PublicationsCorresponds to variant dbSNP:rs1050152EnsemblClinVar.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB007448 mRNA Translation: BAA23356.1
Y09881 mRNA Translation: CAA71007.1
AC008599 Genomic DNA No translation available.
AC034220 Genomic DNA No translation available.
BC028313 mRNA Translation: AAH28313.1
CCDSiCCDS4153.1
RefSeqiNP_003050.2, NM_003059.2
UniGeneiHs.310591

Genome annotation databases

EnsembliENST00000200652; ENSP00000200652; ENSG00000197208
GeneIDi6583
KEGGihsa:6583
UCSCiuc003kwq.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiS22A4_HUMAN
AccessioniPrimary (citable) accession number: Q9H015
Secondary accession number(s): O14546
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 19, 2004
Last sequence update: May 1, 2007
Last modified: June 20, 2018
This is version 148 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

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