Electrogenic voltage-dependent transporter that mediates the transport of a variety of organic cations such as endogenous bioactive amines, cationic drugs and xenobiotics (       , ). Functions as a pH- and Na(+)-independent, bidirectional transporter (By similarity). Cation cellular uptake or release is driven by the electrochemical potential (i.e. membrane potential and concentration gradient) and substrate selectivity (By similarity). Hydrophobicity is a major requirement for recognition in polyvalent substrates and inhibitors (By similarity). Primarily 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 (By similarity). Most likely functions as an uptake carrier in enterocytes contributing to the intestinal elimination of organic cations from the systemic circulation . Transports endogenous monoamines such as N-1-methylnicotinamide (NMN), guanidine, histamine, neurotransmitters dopamine, serotonin and adrenaline ( , ). Also transports natural polyamines such as spermidine, agmatine and putrescine at low affinity, but relatively high turnover . Involved in the hepatic uptake of vitamin B1/thiamine, hence regulating hepatic lipid and energy metabolism . 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 . Transports dopaminergic neuromodulators cyclo(his-pro) and salsolinol with lower efficency . Also capable of transporting non-amine endogenous compounds such as prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) . May contribute to the transport of cationic compounds in testes across the blood-testis-barrier (Probable). Also involved in the uptake of xenobiotics tributylmethylammonium (TBuMA), quinidine, N-methyl-quinine (NMQ), N-methyl-quinidine (NMQD) N-(4,4-azo-n-pentyl)-quinuclidine (APQ), azidoprocainamide methoiodide (AMP), N-(4,4-azo-n-pentyl)-21-deoxyajmalinium (APDA) and 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP) ( , ).
Mediates the uptake of 1-methyl-4-phenylpyridinium (MPP(+)).
Not able to uptake 1-methyl-4-phenylpyridinium (MPP(+)).
Not able to uptake 1-methyl-4-phenylpyridinium (MPP(+)).
Not able to uptake 1-methyl-4-phenylpyridinium (MPP(+)).
Subcellular locations: Basolateral cell membrane, Apical cell membrane, Lateral cell membrane, Basal cell membrane, Cell membrane
Localized to the sinusoidal/basolateral membrane of hepatocytes (By similarity). Mainly localized to the basolateral membrane of renal proximal tubular cells (By similarity). However, also identified at the apical side of proximal tubular cells . Mainly expressed at the lateral membrane of enterocytes . Also observed at the apical side of enterocytes . Localized to the luminal/apical membrane of ciliated epithelial cells in bronchi . Localized to the basal membrane of Sertoli cells .
Widely expressed with high level in liver ( , ). In liver, expressed around the central vein . Expressed in kidney (, ). Expressed in small intestine enterocytes (, ). Localized to peritubular myoid cells, Leydig cells and moderately to the basal membrane of Sertoli cells in testes . Expressed in tracheal and bronchial ciliated epithelium in the respiratory tract . Also expressed in skeletal muscle, stomach, spleen, heart, placentacolon, brain, granulycytes and lympohocytes (, ).
Expressed in liver and in glial cell lines.
Expressed in liver and in glial cell lines.
Expressed in glial cell lines. Not expressed in liver.
Expressed in glial cell lines. Not expressed in liver.