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Protein

Solute carrier family 22 member 2

Gene

SLC22A2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creatinine, amantadine, memantine, acriflavine, 4-[4-(dimethylamino)-styryl]-N-methylpyridinium ASP, amiloride, metformin, N-1-methylnicotinamide (NMN), tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, cisplatin and oxaliplatin. Cisplatin may develop a nephrotoxic action. Transport of creatinine is inhibited by fluoroquinolones such as DX-619 and LVFX. This transporter is a major determinant of the anticancer activity of oxaliplatin and may contribute to antitumor specificity.14 Publications

Kineticsi

  1. KM=1 mM for agmatine8 Publications
  2. KM=95 µM for amiloride8 Publications
  3. KM=24 µM for ASP8 Publications
  4. KM=34 µM for memantine8 Publications
  5. KM=27 µM for amantadine8 Publications
  6. KM=1.38 mM for metformin8 Publications
  7. KM=1.9 mM for noradrenaline8 Publications
  8. KM=1.9 mM for norepinephrine8 Publications
  9. KM=1.3 mM for histamine8 Publications
  10. KM=0.39 mM for dopamine8 Publications
  11. KM=0.08 mM for serotonine8 Publications
  12. KM=72.6 µM for cimetidine (at pH 7.4 and 37 degrees Celsius)8 Publications
  13. KM=56.1 µM for famotidine8 Publications
  14. KM=65.2 µM for ranitidine8 Publications
  15. KM=431 µM for TEA (isoform 1)8 Publications
  16. KM=63 µM for TEA (isoform 2)8 Publications
  1. Vmax=3770 pmol/min/mg enzyme for TEA uptake (isoform 1)8 Publications
  2. Vmax=314 pmol/min/mg enzyme for TEA uptake (isoform 2)8 Publications
  3. Vmax=11.9 nmol/min/mg enzyme for metformin uptake8 Publications
  4. Vmax=2170 pmol/min/mg enzyme for cimetidine uptake8 Publications
  5. Vmax=204 pmol/min/mg enzyme for famotidine uptake8 Publications
  6. Vmax=265 pmol/min/mg enzyme for ranitidine uptake8 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei451Involved in recognition of organic cations and participates in structural changes that occur during translocation of organic cationsBy similarity1

GO - Molecular functioni

GO - Biological processi

  • body fluid secretion Source: ProtInc
  • choline transport Source: GO_Central
  • dopamine transport Source: GO_Central
  • drug transmembrane transport Source: Reactome
  • neurotransmitter biosynthetic process Source: Reactome
  • neurotransmitter secretion Source: Reactome
  • organic cation transport Source: MGI
Complete GO annotation...

Keywords - Biological processi

Ion transport, Transport

Enzyme and pathway databases

ReactomeiR-HSA-112311. Neurotransmitter Clearance In The Synaptic Cleft.
R-HSA-181430. Norepinephrine Neurotransmitter Release Cycle.
R-HSA-2161517. Abacavir transmembrane transport.
R-HSA-442660. Na+/Cl- dependent neurotransmitter transporters.
R-HSA-549127. Organic cation transport.

Protein family/group databases

TCDBi2.A.1.19.30. the major facilitator superfamily (mfs).

Names & Taxonomyi

Protein namesi
Recommended name:
Solute carrier family 22 member 2
Alternative name(s):
Organic cation transporter 2
Short name:
hOCT2
Gene namesi
Name:SLC22A2
Synonyms:OCT2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

HGNCiHGNC:10966. SLC22A2.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 22CytoplasmicSequence analysisAdd BLAST22
Transmembranei23 – 43HelicalSequence analysisAdd BLAST21
Topological domaini44 – 150ExtracellularSequence analysisAdd BLAST107
Transmembranei151 – 171HelicalSequence analysisAdd BLAST21
Topological domaini172 – 177CytoplasmicSequence analysis6
Transmembranei178 – 198HelicalSequence analysisAdd BLAST21
Topological domaini199 – 208ExtracellularSequence analysis10
Transmembranei209 – 229HelicalSequence analysisAdd BLAST21
Topological domaini230 – 238CytoplasmicSequence analysis9
Transmembranei239 – 259HelicalSequence analysisAdd BLAST21
Topological domaini260 – 263ExtracellularSequence analysis4
Transmembranei264 – 284HelicalSequence analysisAdd BLAST21
Topological domaini285 – 348CytoplasmicSequence analysisAdd BLAST64
Transmembranei349 – 369HelicalSequence analysisAdd BLAST21
Topological domaini370 – 375ExtracellularSequence analysis6
Transmembranei376 – 396HelicalSequence analysisAdd BLAST21
Topological domaini397 – 414CytoplasmicSequence analysisAdd BLAST18
Transmembranei415 – 435HelicalSequence analysisAdd BLAST21
Topological domaini436 – 441ExtracellularSequence analysis6
Transmembranei442 – 462HelicalSequence analysisAdd BLAST21
Topological domaini463 – 464CytoplasmicSequence analysis2
Transmembranei465 – 485HelicalSequence analysisAdd BLAST21
Topological domaini486 – 494ExtracellularSequence analysis9
Transmembranei495 – 515HelicalSequence analysisAdd BLAST21
Topological domaini516 – 555CytoplasmicSequence analysisAdd BLAST40

GO - Cellular componenti

  • extracellular exosome Source: UniProtKB
  • integral component of plasma membrane Source: ProtInc
  • membrane Source: ProtInc
  • plasma membrane Source: Reactome
  • presynapse Source: GOC
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi6582.
OpenTargetsiENSG00000112499.
PharmGKBiPA331.

Chemistry databases

ChEMBLiCHEMBL1743122.
DrugBankiDB00915. Amantadine.
DB00594. Amiloride.
DB00345. Aminohippurate.
DB01114. Chlorphenamine.
DB00122. Choline.
DB00501. Cimetidine.
DB00515. Cisplatin.
DB00242. Cladribine.
DB00907. Cocaine.
DB00987. Cytarabine.
DB00694. Daunorubicin.
DB01151. Desipramine.
DB01160. Dinoprost Tromethamine.
DB00917. Dinoprostone.
DB01075. Diphenhydramine.
DB00280. Disopyramide.
DB00988. Dopamine.
DB00668. Epinephrine.
DB00783. Estradiol.
DB00927. Famotidine.
DB00690. Flurazepam.
DB00536. Guanidine.
DB00667. Histamine Phosphate.
DB00619. Imatinib.
DB00458. Imipramine.
DB00709. Lamivudine.
DB01137. Levofloxacin.
DB01043. Memantine.
DB00331. Metformin.
DB00264. Metoprolol.
DB00184. Nicotine.
DB00368. Norepinephrine.
DB00526. Oxaliplatin.
DB01580. Oxprenolol.
DB01337. Pancuronium.
DB00914. Phenformin.
DB00925. Phenoxybenzamine.
DB00413. Pramipexole.
DB00457. Prazosin.
DB01032. Probenecid.
DB01035. Procainamide.
DB00396. Progesterone.
DB00571. Propranolol.
DB01103. Quinacrine.
DB00908. Quinidine.
DB00468. Quinine.
DB00206. Reserpine.
DB00152. Thiamine.
DB01199. Tubocurarine.
DB00570. Vinblastine.
DB00495. Zidovudine.
GuidetoPHARMACOLOGYi1020.

Polymorphism and mutation databases

BioMutaiSLC22A2.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003209571 – 555Solute carrier family 22 member 2Add BLAST555

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi72N-linked (GlcNAc...)Sequence analysis1

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiO15244.
PeptideAtlasiO15244.
PRIDEiO15244.

PTM databases

iPTMnetiO15244.
PhosphoSitePlusiO15244.

Expressioni

Tissue specificityi

Mainly expressed in kidney. Localized at the luminal membrane and basolateral membrane of kidney distal tubule and proximal tubules. To a lower extent, expressed in neurons of the cerebral cortex and in various subcortical nuclei (at protein levels). Also detected in secretory phase endometrium; in scattered cells in the stroma.4 Publications

Inductioni

May be down-regulated in diabetic patients.1 Publication

Gene expression databases

BgeeiENSG00000112499.
CleanExiHS_SLC22A2.
ExpressionAtlasiO15244. baseline and differential.
GenevisibleiO15244. HS.

Organism-specific databases

HPAiCAB068236.
CAB068237.
HPA008567.

Interactioni

Protein-protein interaction databases

BioGridi112469. 8 interactors.
IntActiO15244. 8 interactors.
STRINGi9606.ENSP00000355920.

Chemistry databases

BindingDBiO15244.

Structurei

3D structure databases

ProteinModelPortaliO15244.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0255. Eukaryota.
COG0477. LUCA.
GeneTreeiENSGT00760000118852.
HOGENOMiHOG000234568.
HOVERGENiHBG061545.
InParanoidiO15244.
KOiK08199.
OMAiPWAASNM.
OrthoDBiEOG091G05AC.
PhylomeDBiO15244.
TreeFamiTF315847.

Family and domain databases

CDDicd06174. MFS. 1 hit.
InterProiIPR020846. MFS_dom.
IPR005828. MFS_sugar_transport-like.
IPR004749. Orgcat_transp/SVOP.
IPR005829. Sugar_transporter_CS.
[Graphical view]
PfamiPF00083. Sugar_tr. 1 hit.
[Graphical view]
SUPFAMiSSF103473. SSF103473. 1 hit.
TIGRFAMsiTIGR00898. 2A0119. 1 hit.
PROSITEiPS50850. MFS. 1 hit.
PS00216. SUGAR_TRANSPORT_1. 2 hits.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O15244-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MPTTVDDVLE HGGEFHFFQK QMFFLLALLS ATFAPIYVGI VFLGFTPDHR
60 70 80 90 100
CRSPGVAELS LRCGWSPAEE LNYTVPGPGP AGEASPRQCR RYEVDWNQST
110 120 130 140 150
FDCVDPLASL DTNRSRLPLG PCRDGWVYET PGSSIVTEFN LVCANSWMLD
160 170 180 190 200
LFQSSVNVGF FIGSMSIGYI ADRFGRKLCL LTTVLINAAA GVLMAISPTY
210 220 230 240 250
TWMLIFRLIQ GLVSKAGWLI GYILITEFVG RRYRRTVGIF YQVAYTVGLL
260 270 280 290 300
VLAGVAYALP HWRWLQFTVS LPNFFFLLYY WCIPESPRWL ISQNKNAEAM
310 320 330 340 350
RIIKHIAKKN GKSLPASLQR LRLEEETGKK LNPSFLDLVR TPQIRKHTMI
360 370 380 390 400
LMYNWFTSSV LYQGLIMHMG LAGDNIYLDF FYSALVEFPA AFMIILTIDR
410 420 430 440 450
IGRRYPWAAS NMVAGAACLA SVFIPGDLQW LKIIISCLGR MGITMAYEIV
460 470 480 490 500
CLVNAELYPT FIRNLGVHIC SSMCDIGGII TPFLVYRLTN IWLELPLMVF
510 520 530 540 550
GVLGLVAGGL VLLLPETKGK ALPETIEEAE NMQRPRKNKE KMIYLQVQKL

DIPLN
Length:555
Mass (Da):62,581
Last modified:November 30, 2010 - v2
Checksum:i06528F9519CE211E
GO
Isoform 2 (identifier: O15244-2) [UniParc]FASTAAdd to basket
Also known as: OCT2-A

The sequence of this isoform differs from the canonical sequence as follows:
     427-483: DLQWLKIIIS...CDIGGIITPF → GKFQVKLESY...SEQIHMASLL
     484-555: Missing.

Show »
Length:483
Mass (Da):54,475
Checksum:i0AD53D9697B4E7B2
GO
Isoform 3 (identifier: O15244-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     225-242: ITEFVGRRYRRTVGIFYQ → SKNVCACNCENKATSLPK
     243-555: Missing.

Note: No experimental confirmation available.
Show »
Length:242
Mass (Da):26,685
Checksum:i510EAB0C05C06B43
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03932254P → S.1 PublicationCorresponds to variant rs8177504dbSNPEnsembl.1
Natural variantiVAR_039323165M → I Lower Vmax. 1 PublicationCorresponds to variant rs8177507dbSNPEnsembl.1
Natural variantiVAR_039324201T → M.1 PublicationCorresponds to variant rs145450955dbSNPEnsembl.1
Natural variantiVAR_039325270S → A Increased Ki value for TBA inhibition of MPP. 6 PublicationsCorresponds to variant rs316019dbSNPEnsembl.1
Natural variantiVAR_039326297A → G.Corresponds to variant rs8177513dbSNPEnsembl.1
Natural variantiVAR_039327400R → C Lower Vmax and reduced Ki value for TBA inhibition of MPP. 1 PublicationCorresponds to variant rs8177516dbSNPEnsembl.1
Natural variantiVAR_039328432K → Q Lower Km value for MPP and reduced Ki value for TBA inhibition of MPP. 1 PublicationCorresponds to variant rs8177517dbSNPEnsembl.1
Natural variantiVAR_039329463R → K.Corresponds to variant rs3907239dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_031771225 – 242ITEFV…GIFYQ → SKNVCACNCENKATSLPK in isoform 3. 1 PublicationAdd BLAST18
Alternative sequenceiVSP_031772243 – 555Missing in isoform 3. 1 PublicationAdd BLAST313
Alternative sequenceiVSP_031773427 – 483DLQWL…IITPF → GKFQVKLESYLQDPGERECH GPLIGKPCNLSSKSIWKDKL EGSIWDPSEQIHMASLL in isoform 2. 1 PublicationAdd BLAST57
Alternative sequenceiVSP_031774484 – 555Missing in isoform 2. 1 PublicationAdd BLAST72

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X98333 mRNA. Translation: CAA66978.1.
AB075951 mRNA. Translation: BAC02720.1.
AK290787 mRNA. Translation: BAF83476.1.
AL162582 Genomic DNA. Translation: CAI20003.1.
CH471051 Genomic DNA. Translation: EAW47602.1.
BC030978 mRNA. Translation: AAH30978.1.
BC039899 mRNA. Translation: AAH39899.1.
AJ251885 Genomic DNA. Translation: CAB96133.1.
CCDSiCCDS5276.1. [O15244-1]
RefSeqiNP_003049.2. NM_003058.3. [O15244-1]
UniGeneiHs.436385.

Genome annotation databases

EnsembliENST00000366953; ENSP00000355920; ENSG00000112499. [O15244-1]
GeneIDi6582.
KEGGihsa:6582.
UCSCiuc003qtf.4. human. [O15244-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X98333 mRNA. Translation: CAA66978.1.
AB075951 mRNA. Translation: BAC02720.1.
AK290787 mRNA. Translation: BAF83476.1.
AL162582 Genomic DNA. Translation: CAI20003.1.
CH471051 Genomic DNA. Translation: EAW47602.1.
BC030978 mRNA. Translation: AAH30978.1.
BC039899 mRNA. Translation: AAH39899.1.
AJ251885 Genomic DNA. Translation: CAB96133.1.
CCDSiCCDS5276.1. [O15244-1]
RefSeqiNP_003049.2. NM_003058.3. [O15244-1]
UniGeneiHs.436385.

3D structure databases

ProteinModelPortaliO15244.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112469. 8 interactors.
IntActiO15244. 8 interactors.
STRINGi9606.ENSP00000355920.

Chemistry databases

BindingDBiO15244.
ChEMBLiCHEMBL1743122.
DrugBankiDB00915. Amantadine.
DB00594. Amiloride.
DB00345. Aminohippurate.
DB01114. Chlorphenamine.
DB00122. Choline.
DB00501. Cimetidine.
DB00515. Cisplatin.
DB00242. Cladribine.
DB00907. Cocaine.
DB00987. Cytarabine.
DB00694. Daunorubicin.
DB01151. Desipramine.
DB01160. Dinoprost Tromethamine.
DB00917. Dinoprostone.
DB01075. Diphenhydramine.
DB00280. Disopyramide.
DB00988. Dopamine.
DB00668. Epinephrine.
DB00783. Estradiol.
DB00927. Famotidine.
DB00690. Flurazepam.
DB00536. Guanidine.
DB00667. Histamine Phosphate.
DB00619. Imatinib.
DB00458. Imipramine.
DB00709. Lamivudine.
DB01137. Levofloxacin.
DB01043. Memantine.
DB00331. Metformin.
DB00264. Metoprolol.
DB00184. Nicotine.
DB00368. Norepinephrine.
DB00526. Oxaliplatin.
DB01580. Oxprenolol.
DB01337. Pancuronium.
DB00914. Phenformin.
DB00925. Phenoxybenzamine.
DB00413. Pramipexole.
DB00457. Prazosin.
DB01032. Probenecid.
DB01035. Procainamide.
DB00396. Progesterone.
DB00571. Propranolol.
DB01103. Quinacrine.
DB00908. Quinidine.
DB00468. Quinine.
DB00206. Reserpine.
DB00152. Thiamine.
DB01199. Tubocurarine.
DB00570. Vinblastine.
DB00495. Zidovudine.
GuidetoPHARMACOLOGYi1020.

Protein family/group databases

TCDBi2.A.1.19.30. the major facilitator superfamily (mfs).

PTM databases

iPTMnetiO15244.
PhosphoSitePlusiO15244.

Polymorphism and mutation databases

BioMutaiSLC22A2.

Proteomic databases

PaxDbiO15244.
PeptideAtlasiO15244.
PRIDEiO15244.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000366953; ENSP00000355920; ENSG00000112499. [O15244-1]
GeneIDi6582.
KEGGihsa:6582.
UCSCiuc003qtf.4. human. [O15244-1]

Organism-specific databases

CTDi6582.
DisGeNETi6582.
GeneCardsiSLC22A2.
H-InvDBHIX0025014.
HGNCiHGNC:10966. SLC22A2.
HPAiCAB068236.
CAB068237.
HPA008567.
MIMi602608. gene.
neXtProtiNX_O15244.
OpenTargetsiENSG00000112499.
PharmGKBiPA331.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0255. Eukaryota.
COG0477. LUCA.
GeneTreeiENSGT00760000118852.
HOGENOMiHOG000234568.
HOVERGENiHBG061545.
InParanoidiO15244.
KOiK08199.
OMAiPWAASNM.
OrthoDBiEOG091G05AC.
PhylomeDBiO15244.
TreeFamiTF315847.

Enzyme and pathway databases

ReactomeiR-HSA-112311. Neurotransmitter Clearance In The Synaptic Cleft.
R-HSA-181430. Norepinephrine Neurotransmitter Release Cycle.
R-HSA-2161517. Abacavir transmembrane transport.
R-HSA-442660. Na+/Cl- dependent neurotransmitter transporters.
R-HSA-549127. Organic cation transport.

Miscellaneous databases

GeneWikiiSLC22A2.
GenomeRNAii6582.
PROiO15244.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000112499.
CleanExiHS_SLC22A2.
ExpressionAtlasiO15244. baseline and differential.
GenevisibleiO15244. HS.

Family and domain databases

CDDicd06174. MFS. 1 hit.
InterProiIPR020846. MFS_dom.
IPR005828. MFS_sugar_transport-like.
IPR004749. Orgcat_transp/SVOP.
IPR005829. Sugar_transporter_CS.
[Graphical view]
PfamiPF00083. Sugar_tr. 1 hit.
[Graphical view]
SUPFAMiSSF103473. SSF103473. 1 hit.
TIGRFAMsiTIGR00898. 2A0119. 1 hit.
PROSITEiPS50850. MFS. 1 hit.
PS00216. SUGAR_TRANSPORT_1. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiS22A2_HUMAN
AccessioniPrimary (citable) accession number: O15244
Secondary accession number(s): Q5T7Q6
, Q6PIQ8, Q8NG62, Q9NQB9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 26, 2008
Last sequence update: November 30, 2010
Last modified: November 30, 2016
This is version 146 of the entry and version 2 of the sequence. [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

Documents

  1. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.