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Protein

Solute carrier family 22 member 2

Gene

SLC22A2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Caution

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 serotonin8 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

Keywordsi

Biological processIon transport, Transport

Enzyme and pathway databases

ReactomeiR-HSA-112311 Neurotransmitter clearance
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

EuPathDBiHostDB:ENSG00000112499.12
HGNCiHGNC:10966 SLC22A2
MIMi602608 gene
neXtProtiNX_O15244

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 – 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

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi6582
OpenTargetsiENSG00000112499
PharmGKBiPA331

Chemistry databases

ChEMBLiCHEMBL1743122
DrugBankiDB08838 Agmatine
DB00915 Amantadine
DB00594 Amiloride
DB02533 Aminoguanidine
DB00345 Aminohippuric acid
DB01114 Chlorphenamine
DB00122 Choline
DB00501 Cimetidine
DB00515 Cisplatin
DB00242 Cladribine
DB00907 Cocaine
DB00987 Cytarabine
DB00694 Daunorubicin
DB01151 Desipramine
DB09555 Dexchlorpheniramine maleate
DB01160 Dinoprost Tromethamine
DB00917 Dinoprostone
DB01075 Diphenhydramine
DB00280 Disopyramide
DB00988 Dopamine
DB00668 Epinephrine
DB00783 Estradiol
DB00927 Famotidine
DB00690 Flurazepam
DB00365 Grepafloxacin
DB00536 Guanidine
DB05381 Histamine
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
DB08837 Tetraethylammonium
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...) asparagineSequence 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

BioGridi11246942 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
OMAiKAGWLIG
OrthoDBiEOG091G05AC
PhylomeDBiO15244
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, 2 hits

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 → S1 PublicationCorresponds to variant dbSNP:rs8177504Ensembl.1
Natural variantiVAR_039323165M → I Lower Vmax. 1 PublicationCorresponds to variant dbSNP:rs8177507Ensembl.1
Natural variantiVAR_039324201T → M1 PublicationCorresponds to variant dbSNP:rs145450955Ensembl.1
Natural variantiVAR_039325270S → A Increased Ki value for TBA inhibition of MPP. 6 PublicationsCorresponds to variant dbSNP:rs316019Ensembl.1
Natural variantiVAR_039326297A → G. Corresponds to variant dbSNP:rs8177513Ensembl.1
Natural variantiVAR_039327400R → C Lower Vmax and reduced Ki value for TBA inhibition of MPP. 1 PublicationCorresponds to variant dbSNP:rs8177516Ensembl.1
Natural variantiVAR_039328432K → Q Lower Km value for MPP and reduced Ki value for TBA inhibition of MPP. 1 PublicationCorresponds to variant dbSNP:rs8177517Ensembl.1
Natural variantiVAR_039329463R → K. Corresponds to variant dbSNP:rs3907239Ensembl.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 No translation available.
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

Similar proteinsi

Entry informationi

Entry nameiS22A2_HUMAN
AccessioniPrimary (citable) accession number: O15244
Secondary accession number(s): Q5T7Q6
, Q6PIQ8, Q8NG62, Q9NQB9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 26, 2008
Last sequence update: November 30, 2010
Last modified: March 28, 2018
This is version 156 of the entry and version 2 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