SLC22A3

Protein-coding gene in the species Homo sapiens

SLC22A3

Identifiers

Aliases

SLC22A3, EMT, EMTH, OCT3, solute carrier family 22 member 3

External IDs

OMIM: 604842; MGI: 1333817; HomoloGene: 22630; GeneCards: SLC22A3; OMA:SLC22A3 - orthologs

Gene location (Human)

Chr.	Chromosome 6 (human)^[1]

Band	6q25.3	Start	160,348,378 bp^[1]
Band	6q25.3	End	160,452,577 bp^[1]

Gene location (Mouse)

Chr.	Chromosome 17 (mouse)^[2]

Band	17 A1\|17 8.52 cM	Start	12,637,847 bp^[2]
Band	17 A1\|17 8.52 cM	End	12,726,591 bp^[2]

RNA expression pattern

Bgee

Human

Mouse (ortholog)

Top expressed in

thoracic aorta

ascending aorta

tibial nerve

right coronary artery

gastrocnemius muscle

left coronary artery

popliteal artery

right lobe of liver

left uterine tube

prostate

Top expressed in

gallbladder

utricle

white adipose tissue

brown adipose tissue

subcutaneous adipose tissue

submandibular gland

mammary gland

secondary oocyte

conjunctival fornix

sciatic nerve

More reference expression data

BioGPS


More reference expression data

Gene ontology
Molecular function	protein binding toxin transmembrane transporter activity transporter activity quaternary ammonium group transmembrane transporter activity organic cation transmembrane transporter activity organic anion transmembrane transporter activity dopamine:sodium symporter activity
Cellular component	integral component of membrane membrane integral component of plasma membrane plasma membrane
Biological process	dopamine transport histamine transport monoamine transport histamine uptake xenobiotic transmembrane transport toxin transport ion transport quaternary ammonium group transport organic cation transport regulation of appetite transmembrane transport organic anion transport dopamine uptake
Sources:Amigo / QuickGO

Orthologs

Species

Human

Mouse

Entrez


6581


20519

Ensembl


ENSG00000146477


ENSMUSG00000023828

UniProt


O75751


Q9WTW5

RefSeq (mRNA)


NM_021977


NM_011395

RefSeq (protein)


NP_068812


NP_035525

Location (UCSC)

Chr 6: 160.35 – 160.45 Mb

Chr 17: 12.64 – 12.73 Mb

PubMed search

^[3]

^[4]

Wikidata

View/Edit Human

View/Edit Mouse

Solute carrier family 22 member 3 (SLC22A3) also known as the organic cation transporter 3 (OCT3) or extraneuronal monoamine transporter (EMT) is a protein that in humans is encoded by the SLC22A3 gene.^[5]^[6]^[7]

Polyspecific organic cation transporters in the liver, kidney, intestine, and other organs are critical for elimination of many endogenous small organic cations as well as a wide array of drugs and environmental toxins. This gene is one of three similar cation transporter genes located in a cluster on chromosome 6. The encoded protein contains twelve putative transmembrane domains and is a plasma integral membrane protein.^[7]

Distribution

OCT3 is widely distributed in brain tissue. It is not yet completely clear whether its location is primarily neuronal or glial. Areas of the brain in which it has been reported include: hippocampus, retrosplenial cortex, visual cortex, hypothalamus, amygdala, nucleus accumbens, thalamus, raphe nucleus, subiculum, superior and inferior colliculi, and islands of Calleja.^[8]^[9]

Pharmacology

Organic cation transporter 3 is a polyspecific transporter whose transport is independent of sodium. Known substrates for transport include: histamine, serotonin, norepinephrine, dopamine and MPP⁺. Capacity for transport and affinity for these substrates may vary between rat and human isoforms however.^[9]

Transport activity of OCT3 is inhibited by recreational and pharmaceutical drugs, including MDMA, phencyclidine (PCP), MK-801, amphetamine, methamphetamine and cocaine.^[9] Transport is also inhibited by the chemical decynium-22 and physiological concentrations of corticosterone and cortisol. K_i values for decynium-22 and corticosterone inhibition of OCT3 transport are respectively 10 and 100 times lower than K_i values of OCT1 and OCT2.^[10] This effect of glucocorticoids is believed to explain the phenomenon of stress-induced relapse in recovering addicts, where dopamine transport inhibition causes reactivation of hypersensitive dopamine pathways involved in drug-seeking behavior and incentive salience.

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000146477 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000023828 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Kekuda R, Prasad PD, Wu X, Wang H, Fei YJ, Leibach FH, Ganapathy V (Aug 1998). "Cloning and functional characterization of a potential-sensitive, polyspecific organic cation transporter (OCT3) most abundantly expressed in placenta". J Biol Chem. 273 (26): 15971–15979. doi:10.1074/jbc.273.26.15971. PMID 9632645.
^ Verhaagh S, Schweifer N, Barlow DP, Zwart R (Sep 1999). "Cloning of the mouse and human solute carrier 22a3 (Slc22a3/SLC22A3) identifies a conserved cluster of three organic cation transporters on mouse chromosome 17 and human 6q26-q27". Genomics. 55 (2): 209–218. doi:10.1006/geno.1998.5639. PMID 9933568.
^ ^a ^b "Entrez Gene: SLC22A3 solute carrier family 22 (extraneuronal monoamine transporter), member 3".
^ Gasser PJ, Orchinik M, Raju I, Lowry CA (Feb 2009). "Distribution of organic cation transporter 3, a corticosterone-sensitive monoamine transporter, in the rat brain". J Comp Neurol. 512 (4): 529–555. doi:10.1002/cne.21921. PMID 19025979. S2CID 33389900.
^ ^a ^b ^c Amphoux A, Vialou V, Drescher E, Brüss M, Mannoury La Cour C, Rochat C, Millan MJ, Giros B, Bönisch H, Gautron S (Jun 2006). "Differential pharmacological in vitro properties of organic cation transporters and regional distribution in rat brain". Neuropharmacology. 50 (8): 941–952. doi:10.1016/j.neuropharm.2006.01.005. PMID 16581093. S2CID 42204368.
^ Hayer-Zillgen M, Brüss M, Bönisch H (Jul 2002). "Expression and pharmacological profile of the human organic cation transporters hOCT1, hOCT2 and hOCT3". Br J Pharmacol. 136 (6): 829–836. doi:10.1038/sj.bjp.0704785. PMC 1573414. PMID 12110607.

Wu X, Kekuda R, Huang W, et al. (1999). "Identity of the organic cation transporter OCT3 as the extraneuronal monoamine transporter (uptake2) and evidence for the expression of the transporter in the brain". J. Biol. Chem. 273 (49): 32776–32786. doi:10.1074/jbc.273.49.32776. PMID 9830022.
Gründemann D, Schechinger B, Rappold GA, Schömig E (1999). "Molecular identification of the corticosterone-sensitive extraneuronal catecholamine transporter". Nat. Neurosci. 1 (5): 349–351. doi:10.1038/1557. PMID 10196521. S2CID 8355270.
Gründemann D, Schömig E (2000). "Gene structures of the human non-neuronal monoamine transporters EMT and OCT2". Hum. Genet. 106 (6): 627–635. doi:10.1007/s004390000309. PMID 10942111. S2CID 28444495.
Wu X, Huang W, Ganapathy ME, et al. (2000). "Structure, function, and regional distribution of the organic cation transporter OCT3 in the kidney". Am. J. Physiol. Renal Physiol. 279 (3): F449–58. doi:10.1152/ajprenal.2000.279.3.F449. PMID 10966924. S2CID 12385921.
Wieland A, Hayer-Zillgen M, Bönisch H, Brüss M (2001). "Analysis of the gene structure of the human (SLC22A3) and murine (Slc22a3) extraneuronal monoamine transporter". Journal of Neural Transmission. 107 (10): 1149–1157. doi:10.1007/s007020070028. PMID 11129104. S2CID 9706545.
Wessler I, Roth E, Deutsch C, et al. (2001). "Release of non-neuronal acetylcholine from the isolated human placenta is mediated by organic cation transporters". Br. J. Pharmacol. 134 (5): 951–956. doi:10.1038/sj.bjp.0704335. PMC 1573028. PMID 11682442.
Martel F, Keating E, Calhau C, et al. (2002). "Regulation of human extraneuronal monoamine transporter (hEMT) expressed in HEK293 cells by intracellular second messenger systems". Naunyn-Schmiedeberg's Arch. Pharmacol. 364 (6): 487–495. doi:10.1007/s002100100476. PMID 11770002. S2CID 21499579.
Hayer-Zillgen M, Brüss M, Bönisch H (2003). "Expression and pharmacological profile of the human organic cation transporters hOCT1, hOCT2 and hOCT3". Br. J. Pharmacol. 136 (6): 829–836. doi:10.1038/sj.bjp.0704785. PMC 1573414. PMID 12110607.
Gründemann D, Hahne C, Berkels R, Schömig E (2003). "Agmatine is efficiently transported by non-neuronal monoamine transporters extraneuronal monoamine transporter (EMT) and organic cation transporter 2 (OCT2)". J. Pharmacol. Exp. Ther. 304 (2): 810–817. doi:10.1124/jpet.102.044404. PMID 12538837. S2CID 11496882.
Lazar A, Gründemann D, Berkels R, et al. (2003). "Genetic variability of the extraneuronal monoamine transporter EMT (SLC22A3)". J. Hum. Genet. 48 (5): 226–230. doi:10.1007/s10038-003-0015-5. PMID 12768439.
Haag C, Berkels R, Gründemann D, et al. (2004). "The localisation of the extraneuronal monoamine transporter (EMT) in rat brain". J. Neurochem. 88 (2): 291–297. doi:10.1111/j.1471-4159.2004.02180.x. PMID 14690517. S2CID 45854898.
Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–45. doi:10.1038/ng1285. PMID 14702039.
Bottalico B, Larsson I, Brodszki J, et al. (2004). "Norepinephrine transporter (NET), serotonin transporter (SERT), vesicular monoamine transporter (VMAT2) and organic cation transporters (OCT1, 2 and EMT) in human placenta from pre-eclamptic and normotensive pregnancies". Placenta. 25 (6): 518–529. doi:10.1016/j.placenta.2003.10.017. PMID 15135235.
Jiang W, Prokopenko O, Wong L, et al. (2005). "IRIP, a new ischemia/reperfusion-inducible protein that participates in the regulation of transporter activity". Mol. Cell. Biol. 25 (15): 6496–6508. doi:10.1128/MCB.25.15.6496-6508.2005. PMC 1190334. PMID 16024787.
Bourdet DL, Pritchard JB, Thakker DR (2006). "Differential substrate and inhibitory activities of ranitidine and famotidine toward human organic cation transporter 1 (hOCT1; SLC22A1), hOCT2 (SLC22A2), and hOCT3 (SLC22A3)". J. Pharmacol. Exp. Ther. 315 (3): 1288–1297. doi:10.1124/jpet.105.091223. PMID 16141367. S2CID 1633259.
Aoyama N, Takahashi N, Kitaichi K, et al. (2006). "Association between gene polymorphisms of SLC22A3 and methamphetamine use disorder". Alcohol. Clin. Exp. Res. 30 (10): 1644–1649. doi:10.1111/j.1530-0277.2006.00215.x. PMID 17010131.
Bottalico B, Noskova V, Pilka R, et al. (2007). "The organic cation transporters (OCT1, OCT2, EMT) and the plasma membrane monoamine transporter (PMAT) show differential distribution and cyclic expression pattern in human endometrium and early pregnancy decidua". Mol. Reprod. Dev. 74 (10): 1303–1311. doi:10.1002/mrd.20697. PMID 17393420. S2CID 25378552.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

Membrane proteins, carrier proteins: membrane transport proteins solute carrier (TC 2A)

By group

SLC1–10

(1):	high affinity glutamate and neutral amino-acid transporter SLC1A1 2 3 4 5 6 7
(2):	facilitative GLUT transporter SLC2A1 2 3 4 5 6 7 8 9 10 11 12 13 14
(3):	heavy subunits of heterodimeric amino-acid transporters SLC3A1 2
(4):	bicarbonate transporter SLC4A1 2 3 4 5 6 7 8 9 10 11
(5):	sodium glucose cotransporter SLC5A1 2 3 4 5 6 7 8 9 10 11 12
(6):	sodium- and chloride- dependent sodium:neurotransmitter symporters SLC6A1 SLC6A2 SLC6A3 SLC6A4 SLC6A5 SLC6A6 SLC6A7 SLC6A8 SLC6A9 SLC6A10 SLC6A11 SLC6A12 SLC6A13 SLC6A14 SLC6A15 SLC6A16 SLC6A17 SLC6A18 SLC6A19 SLC6A20
(7):	cationic amino-acid transporter/glycoprotein-associated SLC7A1 SLC7A2 SLC7A3 SLC7A4 glycoprotein-associated/light or catalytic subunits of heterodimeric amino-acid transporters SLC7A5 SLC7A6 SLC7A7 SLC7A8 SLC7A9 SLC7A10 SLC7A11 SLC7A13 SLC7A14
(8):	Na⁺/Ca²⁺ exchanger SLC8A1 SLC8A2 SLC8A3
(9):	Na⁺/H⁺ exchanger SLC9A1 SLC9A2 SLC9A3 SLC9A4 SLC9A5 SLC9A6 SLC9A7 SLC9A8 SLC9A9 SLC9A10 SLC9A11
(10):	sodium bile salt cotransport SLC10A1 SLC10A2 SLC10A3 SLC10A4 SLC10A5 SLC10A6 SLC10A7 10A1 10A2 10A3 10A7

SLC11–20

(11):	proton coupled metal ion transporter SLC11A1 SLC11A2 11A3
(12):	electroneutral cation-Cl cotransporter SLC12A1 SLC12A2 SLC12A3 SLC12A4 SLC12A5 SLC12A6 SLC12A7 SLC12A8 SLC12A9
(13):	human Na⁺-sulfate/carboxylate cotransporter SLC13A1 SLC13A2 SLC13A3 SLC13A4 SLC13A5
(14):	urea transporter SLC14A1 SLC14A2
(15):	proton oligopeptide cotransporter SLC15A1 SLC15A2 SLC15A3 SLC15A4
(16):	monocarboxylate transporter SLC16A1 SLC16A2 SLC16A3 SLC16A4 SLC16A5 SLC16A6 SLC16A7 SLC16A8 SLC16A9 SLC16A10 SLC16A11 SLC16A12 SLC16A13 SLC16A14
(17):	Vesicular glutamate transporter 1 SLC17A1 SLC17A2 SLC17A3 SLC17A4 SLC17A5 SLC17A6 SLC17A7 SLC17A8 SLC17A9
(18):	vesicular monoamine transporter SLC18A1 SLC18A2 SLC18A3
(19):	folate/thiamine transporter SLC19A1 SLC19A2 SLC19A3
(20):	type III Na⁺-phosphate cotransporter SLC20A1 SLC20A2

SLC21–30

(21):	Organic anion-transporting polypeptide SLCO1A2 SLCO1B1 SLCO1B3 SLCO1B4 SLCO1C1 SLCO2A1 SLCO2B1 SLCO3A1 SLCO4A1 SLCO4C1 SLCO5A1(SLCO6A1)
(22):	organic cation/anion/zwitterion transporter SLC22A1 SLC22A2 SLC22A3 SLC22A4 SLC22A5 SLC22A6 SLC22A7 SLC22A8 SLC22A9 SLC22A10 SLC22A11 SLC22A12 SLC22A13 SLC22A14 SLC22A15 SLC22A16 SLC22A17 SLC22A18 SLC22A19 SLC22A20
(23):	Na+-dependent ascorbic acid transporter SLC23A1 SLC23A2 SLC23A3 SLC23A4
(24):	Na⁺/(Ca²⁺-K⁺) exchanger SLC24A1 SLC24A2 SLC24A3 SLC24A4 SLC24A5 SLC24A6
(25):	mitochondrial carrier SLC25A1 SLC25A2 SLC25A3 SLC25A4 SLC25A5 SLC25A6 SLC25A7 SLC25A8 SLC25A9 SLC25A10 SLC25A11 SLC25A12 SLC25A13 SLC25A14 SLC25A15 SLC25A16 SLC25A17 SLC25A18 SLC25A19 SLC25A20 SLC25A21 SLC25A22 SLC25A23 SLC25A24 SLC25A25 SLC25A26 SLC25A27 SLC25A28 SLC25A29 SLC25A30 SLC25A31 SLC25A32 SLC25A33 SLC25A34 SLC25A35 SLC25A36 SLC25A37 SLC25A38 SLC25A39 SLC25A40 SLC25A41 SLC25A42 SLC25A43 SLC25A44 SLC25A45 SLC25A46
(26):	multifunctional anion exchanger SLC26A1 SLC26A2 SLC26A3 SLC26A4 SLC26A5 SLC26A6 SLC26A7 SLC26A8 SLC26A9 SLC26A10 SLC26A11
(27):	fatty acid transport proteins SLC27A1 SLC27A2 SLC27A3 SLC27A4 SLC27A5 SLC27A6
(28):	Na⁺-coupled nucleoside transport (SLC28A1 SLC28A2 SLC28A3
(29):	facilitative nucleoside transporter SLC29A1 SLC29A2 SLC29A3 SLC29A4
(30):	zinc efflux SLC30A1 SLC30A2 SLC30A3 SLC30A4 SLC30A5 SLC30A6 SLC30A7 SLC30A8 SLC30A9 SLC30A10

SLC31–40

(31):	copper transporter SLC31A1
(32):	Vesicular glutamate transporter 1 SLC32A1
(33):	Acetyl-CoA transporter SLC33A1
(34):	type II Na⁺-phosphate cotransporter SLC34A1 SLC34A2 SLC34A3
(35):	nucleoside-sugar transporter SLC35A1 SLC35A2 SLC35A3 SLC35A4 SLC35A5 SLC35B1 SLC35B2 SLC35B3 SLC35B4 SLC35C1 SLC35C2 SLC35D1 SLC35D2 SLC35D3 SLC35E1 SLC35E2 SLC35E3 SLC35E4
(36):	proton-coupled amino-acid transporter SLC36A1 SLC36A2 SLC36A3 SLC36A436A2
(37):	sugar-phosphate/phosphate exchanger SLC37A1 SLC37A2 SLC37A3 SLC37A4
(38):	System A & N, sodium-coupled neutral amino-acid transporter SLC38A1 SLC38A2 SLC38A3 SLC38A4 SLC38A5 SLC38A6 SLC38A10
(39):	metal ion transporter SLC39A1 SLC39A2 SLC39A3 SLC39A4 SLC39A5 SLC39A6 SLC39A7 SLC39A8 SLC39A9 SLC39A10 SLC39A11 SLC39A12 SLC39A13 SLC39A14
(40):	basolateral iron transporter SLC40A1

SLC41–48

(41):	Magnesium transporter E SLC41A1 SLC41A2 SLC41A3
(42):	Ammonia transporter RhAG RhBG RhCG
(43):	Na⁺-independent, system-L like amino-acid transporter SLC43A1 SLC43A2 SLC43A3
(44):	Choline-like transporter SLC44A1 SLC44A2 SLC44A3 SLC44A4 SLC44A5
(45):	Putative sugar transporter SLC45A1 SLC45A2 SLC54A3 SLC45A4
(46):	Folate transporter SLC46A1 SLC46A2
(47):	multidrug and toxin extrusion SLC47A1 SLC47A2
(48):	Heme transporter

SLCO1–4
O1A2 O1B1 O1B3 O2B1 O431 O4A1

Ion pumps

Symporter, Cotransporter	Na⁺/K⁺,Cl⁻ Na⁺/P_i3 Na⁺/Cl⁻ Na⁺/glucose Na⁺/I⁻ Cl⁻/K⁺ 4 5
Antiporter (exchanger)	Na⁺/H⁺ Na⁺/Ca²⁺ Na⁺/(Ca²⁺-K⁺) - Cl⁻/HCO⁻ ₃ (Band 3) Cl⁻-formate Cl⁻-oxalate