O70577 · S22A2_MOUSE
- ProteinSolute carrier family 22 member 2
- GeneSlc22a2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids553 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Electrogenic voltage-dependent transporter that mediates the transport of a variety of organic cations such as endogenous bioactive amines, cationic drugs and xenobiotics (PubMed:23458604).
Functions as a Na+-independent, bidirectional uniporter (By similarity).
Cation cellular uptake or release is driven by the electrochemical potential, i.e. membrane potential and concentration gradient (By similarity).
However, may also engage electroneutral cation exchange when saturating concentrations of cation substrates are reached (By similarity).
Predominantly expressed at the basolateral membrane of hepatocytes and proximal tubules and involved in the uptake and disposition of cationic compounds by hepatic and renal clearance from the blood flow. Implicated in monoamine neurotransmitters uptake such as histamine, dopamine, adrenaline/epinephrine, noradrenaline/norepinephrine, serotonin and tyramine, thereby supporting a physiological role in the central nervous system by regulating interstitial concentrations of neurotransmitters. Also capable of transporting dopaminergic neuromodulators cyclo(his-pro), salsolinol and N-methyl-salsolinol, thereby involved in the maintenance of dopaminergic cell integrity in the central nervous system. Mediates the bidirectional transport of acetylcholine (ACh) at the apical membrane of ciliated cell in airway epithelium, thereby playing a role in luminal release of ACh from bronchial epithelium. Also transports guanidine and endogenous monoamines such as vitamin B1/thiamine, creatinine and N-1-methylnicotinamide (NMN). Mediates the uptake and efflux of quaternary ammonium compound choline (By similarity).
Mediates the bidirectional transport of polyamine agmatine and the uptake of polyamines putrescine and spermidine (PubMed:23458604).
Able to transport non-amine endogenous compounds such as prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha). Also involved in the uptake of xenobiotic 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP). May contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (By similarity).
Functions as a Na+-independent, bidirectional uniporter (By similarity).
Cation cellular uptake or release is driven by the electrochemical potential, i.e. membrane potential and concentration gradient (By similarity).
However, may also engage electroneutral cation exchange when saturating concentrations of cation substrates are reached (By similarity).
Predominantly expressed at the basolateral membrane of hepatocytes and proximal tubules and involved in the uptake and disposition of cationic compounds by hepatic and renal clearance from the blood flow. Implicated in monoamine neurotransmitters uptake such as histamine, dopamine, adrenaline/epinephrine, noradrenaline/norepinephrine, serotonin and tyramine, thereby supporting a physiological role in the central nervous system by regulating interstitial concentrations of neurotransmitters. Also capable of transporting dopaminergic neuromodulators cyclo(his-pro), salsolinol and N-methyl-salsolinol, thereby involved in the maintenance of dopaminergic cell integrity in the central nervous system. Mediates the bidirectional transport of acetylcholine (ACh) at the apical membrane of ciliated cell in airway epithelium, thereby playing a role in luminal release of ACh from bronchial epithelium. Also transports guanidine and endogenous monoamines such as vitamin B1/thiamine, creatinine and N-1-methylnicotinamide (NMN). Mediates the uptake and efflux of quaternary ammonium compound choline (By similarity).
Mediates the bidirectional transport of polyamine agmatine and the uptake of polyamines putrescine and spermidine (PubMed:23458604).
Able to transport non-amine endogenous compounds such as prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha). Also involved in the uptake of xenobiotic 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP). May contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (By similarity).
Miscellaneous
Mediates the renal secretion of many clinically used cationic drugs (By similarity) (PubMed:23458604).
Transports drugs such as diabetes treatment medicine metformin and neurotoxins 1-methyl-4-phenylpyridinium (MPP+), famotidine, ranitidine, amantadine, acriflavine, amiloride, memantine, cimetidine, cisplatin, oxaliplatin, platinum-based drugs cisplatin and oxaliplatin, 3'-azido-3'-deoxythymidine (AZT) and tetraethylammonium (TEA) (PubMed:23458604).
Mediates the bidirectional transport of MPP+. Metformin competitively inhibits OCT1-mediated thiamine uptake, leading to a decrease in hepatic steatosis. Plays a predominant role in the anticancer activity of cisplatin and oxaliplatin and may contribute to antitumor specificity (By similarity).
Involved in cisplatin-induced nephrotoxicity (By similarity).
Transports drugs such as diabetes treatment medicine metformin and neurotoxins 1-methyl-4-phenylpyridinium (MPP+), famotidine, ranitidine, amantadine, acriflavine, amiloride, memantine, cimetidine, cisplatin, oxaliplatin, platinum-based drugs cisplatin and oxaliplatin, 3'-azido-3'-deoxythymidine (AZT) and tetraethylammonium (TEA) (PubMed:23458604).
Mediates the bidirectional transport of MPP+. Metformin competitively inhibits OCT1-mediated thiamine uptake, leading to a decrease in hepatic steatosis. Plays a predominant role in the anticancer activity of cisplatin and oxaliplatin and may contribute to antitumor specificity (By similarity).
Involved in cisplatin-induced nephrotoxicity (By similarity).
Catalytic activity
- (R)-noradrenaline(out) = (R)-noradrenaline(in)
- (R)-adrenaline(out) = (R)-adrenaline(in)
- serotonin(out) = serotonin(in)
- dopamine(out) = dopamine(in)
- histamine(out) = histamine(in)
- thiamine(in) = thiamine(out)
- creatinine(in) = creatinine(out)
- 1-methylnicotinamide(out) = 1-methylnicotinamide(in)
- guanidine(out) = guanidine(in)
- choline(out) = choline(in)
- agmatine(out) = agmatine(in)This reaction proceeds in the forward and the backward directions.
- putrescine(out) = putrescine(in)
- spermidine(in) = spermidine(out)
- tyramine(in) = tyramine(out)
- L-histidyl-L-proline diketopiperazine(in) = L-histidyl-L-proline diketopiperazine(out)
- (R)-salsolinol(in) = (R)-salsolinol(out)
- N-methyl-(R)-salsolinol(in) = N-methyl-(R)-salsolinol(out)
- acetylcholine(in) = acetylcholine(out)
- prostaglandin F2alpha(out) = prostaglandin F2alpha(in)
- prostaglandin E2(out) = prostaglandin E2(in)
Activity regulation
Tyrosine phosphorylation of the transporter leads to activation of the transport activity (PubMed:26979622).
TEA uptake is activated by tyrosine phosphorylation (PubMed:26979622).
Inhibited by cGMP, most likely through a cGMP-binding protein that interacts with OCT2 (By similarity).
TEA uptake is activated by tyrosine phosphorylation (PubMed:26979622).
Inhibited by cGMP, most likely through a cGMP-binding protein that interacts with OCT2 (By similarity).
Features
Showing features for site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Site | 451 | Involved in recognition of organic cations and participates in structural changes that occur during translocation of organic cations | ||||
Sequence: C |
GO annotations
Keywords
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameSolute carrier family 22 member 2
- Alternative names
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionO70577
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Basolateral cell membrane ; Multi-pass membrane protein
Basal cell membrane ; Multi-pass membrane protein
Apical cell membrane ; Multi-pass membrane protein
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-21 | Cytoplasmic | ||||
Sequence: MPTVDDILEHIGEFHLFQKQT | ||||||
Transmembrane | 22-42 | Helical | ||||
Sequence: FFLLALLSGAFTPIYVGIVFL | ||||||
Topological domain | 43-150 | Extracellular | ||||
Sequence: GFTPNHHCRSPGVAELSQRCGWSPAEELNYTVPGLGSAGEVSFLSQCMRYEVDWNQSTLDCVDPLSSLAANRSHLPLSPCEHGWVYDTPGSSIVTEFNLVCAHSWMLD | ||||||
Transmembrane | 151-171 | Helical | ||||
Sequence: LFQSLVNVGFFIGAVGIGYLA | ||||||
Topological domain | 172-177 | Cytoplasmic | ||||
Sequence: DRFGRK | ||||||
Transmembrane | 178-198 | Helical | ||||
Sequence: FCLLVTILINAISGVLMAISP | ||||||
Topological domain | 199-210 | Extracellular | ||||
Sequence: NYAWMLVFRFLQ | ||||||
Transmembrane | 211-231 | Helical | ||||
Sequence: GLVSKAGWLIGYILITEFVGL | ||||||
Topological domain | 232-238 | Cytoplasmic | ||||
Sequence: GYRRTVG | ||||||
Transmembrane | 239-259 | Helical | ||||
Sequence: ICYQIAFTVGLLILAGVAYAL | ||||||
Topological domain | 260-263 | Extracellular | ||||
Sequence: PNWR | ||||||
Transmembrane | 264-284 | Helical | ||||
Sequence: WLQFAVTLPNFCFLLYFWCIP | ||||||
Topological domain | 285-348 | Cytoplasmic | ||||
Sequence: ESPRWLISQNKNAKAMKIIKHIAKKNGKSVPVSLQSLTADEDTGMKLNPSFLDLVRTPQIRKHT | ||||||
Transmembrane | 349-369 | Helical | ||||
Sequence: LILMYNWFTSSVLYQGLIMHM | ||||||
Topological domain | 370-375 | Extracellular | ||||
Sequence: GLAGDN | ||||||
Transmembrane | 376-396 | Helical | ||||
Sequence: IYLDFFYSALVEFPAAFIIIL | ||||||
Topological domain | 397-404 | Cytoplasmic | ||||
Sequence: TIDRIGRR | ||||||
Transmembrane | 405-425 | Helical | ||||
Sequence: YPWAVSNMVAGAACLASVFIP | ||||||
Topological domain | 426-432 | Extracellular | ||||
Sequence: DDLQWLK | ||||||
Transmembrane | 433-453 | Helical | ||||
Sequence: ITVACLGRMGITIAYEMVCLV | ||||||
Topological domain | 454-464 | Cytoplasmic | ||||
Sequence: NAELYPTYIRN | ||||||
Transmembrane | 465-485 | Helical | ||||
Sequence: LAVLVCSSMCDIGGIVTPFLV | ||||||
Topological domain | 486-494 | Extracellular | ||||
Sequence: YRLTDIWLE | ||||||
Transmembrane | 495-515 | Helical | ||||
Sequence: FPLVVFAVVGLVAGGLVLLLP | ||||||
Topological domain | 516-553 | Cytoplasmic | ||||
Sequence: ETKGKALPETIEDAEKMQRPRKKKEKRIYLQVKKAELS |
Keywords
- Cellular component
Phenotypes & Variants
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 27 variants from UniProt as well as other sources including ClinVar and dbSNP.
Chemistry
PTM/Processing
Features
Showing features for chain, glycosylation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000320958 | 1-553 | Solute carrier family 22 member 2 | |||
Sequence: MPTVDDILEHIGEFHLFQKQTFFLLALLSGAFTPIYVGIVFLGFTPNHHCRSPGVAELSQRCGWSPAEELNYTVPGLGSAGEVSFLSQCMRYEVDWNQSTLDCVDPLSSLAANRSHLPLSPCEHGWVYDTPGSSIVTEFNLVCAHSWMLDLFQSLVNVGFFIGAVGIGYLADRFGRKFCLLVTILINAISGVLMAISPNYAWMLVFRFLQGLVSKAGWLIGYILITEFVGLGYRRTVGICYQIAFTVGLLILAGVAYALPNWRWLQFAVTLPNFCFLLYFWCIPESPRWLISQNKNAKAMKIIKHIAKKNGKSVPVSLQSLTADEDTGMKLNPSFLDLVRTPQIRKHTLILMYNWFTSSVLYQGLIMHMGLAGDNIYLDFFYSALVEFPAAFIIILTIDRIGRRYPWAVSNMVAGAACLASVFIPDDLQWLKITVACLGRMGITIAYEMVCLVNAELYPTYIRNLAVLVCSSMCDIGGIVTPFLVYRLTDIWLEFPLVVFAVVGLVAGGLVLLLPETKGKALPETIEDAEKMQRPRKKKEKRIYLQVKKAELS | ||||||
Glycosylation | 71 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N |
Post-translational modification
Tyrosine phosphorylated by tyrosine-protein kinase YES1.
Keywords
- PTM
Proteomic databases
PTM databases
Structure
Family & Domains
Features
Showing features for motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Motif | 284-288 | Proline-rich sequence | ||||
Sequence: PESPR |
Domain
Contains one proline-rich sequence (Pro-Glu-Ser-Pro-Arg) that may be involved in tyrosine-protein kinase YES1 binding and is required for the activation of substrate transport.
Sequence similarities
Belongs to the major facilitator (TC 2.A.1) superfamily. Organic cation transporter (TC 2.A.1.19) family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
O70577-1
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.
- Name1
- Length553
- Mass (Da)61,831
- Last updated1998-08-01 v1
- Checksum1E9744F0D5415483
O70577-2
- Name2
Features
Showing features for alternative sequence.
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AJ006036 EMBL· GenBank· DDBJ | CAA06827.1 EMBL· GenBank· DDBJ | mRNA | ||
AK052658 EMBL· GenBank· DDBJ | BAC35086.1 EMBL· GenBank· DDBJ | mRNA | ||
BC015250 EMBL· GenBank· DDBJ | AAH15250.1 EMBL· GenBank· DDBJ | mRNA | ||
BC069911 EMBL· GenBank· DDBJ | AAH69911.1 EMBL· GenBank· DDBJ | mRNA | ||
AF481054 EMBL· GenBank· DDBJ | AAM22158.1 EMBL· GenBank· DDBJ | Genomic DNA |