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solute carrier family 22 member 2; organic cation transporter 2; hOCT2 (SLC22A2, OCT2)
Function:
- mediates tubular uptake of organic compounds from circulation
- mediates influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamine, 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 & oxaliplatin.
- cisplatin may develop a nephrotoxic action
- transport of creatinine is inhibited by fluoroquinolones such as DX-619 & LVFX
- this transporter is a major determinant of the anticancer activity of oxaliplatin & may contribute to antitumor specificity
Kinetic parameters:
- KM=1 mM for agmatine
- KM=95 uM for amiloride
- KM=24 uM for ASP
- KM=34 uM for memantine
- KM=27 uM for amantadine
- KM=1.38 mM for metformin
- KM=1.9 mM for noradrenaline
- KM=1.9 mM for norepinephrine
- KM=1.3 mM for histamine
- KM=0.39 mM for dopamine
- KM=0.08 mM for serotonine
- KM=72.6 uM for cimetidine (at pH 7.4 & 37 degrees celsius)
- KM=56.1 uM for famotidine
- KM=65.2 uM for ranitidine
- KM=431 uM for TEA (isoform 1)
- KM=63 uM for TEA (isoform 2)
- Vmax=3770 pmol/min/mg enzyme for TEA uptake (isoform 1)
- Vmax=314 pmol/min/mg enzyme for TEA uptake (isoform 2)
- Vmax=11.9 nmol/min/mg enzyme for metformin uptake
- Vmax=2170 pmol/min/mg enzyme for cimetidine uptake
- Vmax=204 pmol/min/mg enzyme for famotidine uptake
- Vmax=265 pmol/min/mg enzyme for ranitidine uptake
Structure:
- belongs to the major facilitator superfamily, organic cation transporter family
Compartment: membrane (putative)
Alternative splicing: named isoforms=3
Expression:
- mainly expressed in kidney
- localized at the luminal membrane & basolateral membrane of kidney distal tubule & proximal tubules
- to a lesser extent, expressed in neurons of cerebral cortex & in various subcortical nuclei (at protein level)
- also detected in secretory phase endometrium; in scattered cells in the stroma
Pathology: may be down-regulated in diabetic patients
General
glycoprotein
major facilitator superfamily (MFS)
solute carrier family 22 (SLC22, SLC22A)
transmembrane 12 protein
Properties
SIZE: entity length = 555 aa
MW = 63 kD
COMPARTMENT: cellular membrane
MOTIF: cytoplasmic domain {1-22}
transmembrane domain {23-43}
exoplasmic loop {44-150}
MOTIF: N-glycosylation site {N72}
transmembrane domain {151-171}
cytoplasmic loop {172-177}
transmembrane domain {178-198}
exoplasmic loop {199-208}
transmembrane domain {209-229}
cytoplasmic loop {230-238}
transmembrane domain {239-259}
exoplasmic loop {260-263}
transmembrane domain {264-284}
cytoplasmic loop {285-348}
transmembrane domain {349-369}
exoplasmic loop {370-375}
transmembrane domain {376-396}
cytoplasmic loop {397-414}
transmembrane domain {415-435}
exoplasmic loop {436-441}
transmembrane domain {442-462}
MOTIF: binding site
SITE: 451-451
FOR-BINDING-OF: cation
cytoplasmic loop {463-464}
transmembrane domain {465-485}
exoplasmic loop {486-494}
transmembrane domain {495-515}
cytoplasmic domain {516-555}
Database Correlations
OMIM 602608
UniProt O15244
Pfam PF07690
Kegg hsa:6582
References
UniProt :accession O15244