Solute carrier family 22 member 3

Details

Name
Solute carrier family 22 member 3
Kind
protein
Synonyms
  • EMT
  • EMTH
  • Extraneuronal monoamine transporter
  • OCT3
  • Organic cation transporter 3
Gene Name
SLC22A3
UniProtKB Entry
O75751Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0012537|Solute carrier family 22 member 3
MPSFDEALQRVGEFGRFQRRVFLLLCLTGVTFAFLFVGVVFLGTQPDHYWCRGPSAAALA
ERCGWSPEEEWNRTAPASRGPEPPERRGRCQRYLLEAANDSASATSALSCADPLAAFPNR
SAPLVPCRGGWRYAQAHSTIVSEFDLVCVNAWMLDLTQAILNLGFLTGAFTLGYAADRYG
RIVIYLLSCLGVGVTGVVVAFAPNFPVFVIFRFLQGVFGKGTWMTCYVIVTEIVGSKQRR
IVGIVIQMFFTLGIIILPGIAYFIPNWQGIQLAITLPSFLFLLYYWVVPESPRWLITRKK
GDKALQILRRIAKCNGKYLSSNYSEITVTDEEVSNPSFLDLVRTPQMRKCTLILMFAWFT
SAVVYQGLVMRLGIIGGNLYIDFFISGVVELPGALLILLTIERLGRRLPFAASNIVAGVA
CLVTAFLPEGIAWLRTTVATLGRLGITMAFEIVYLVNSELYPTTLRNFGVSLCSGLCDFG
GIIAPFLLFRLAAVWLELPLIIFGILASICGGLVMLLPETKGIALPETVDDVEKLGSPHS
CKCGRNKKTPVSRSHL
Number of residues
556
Molecular Weight
61279.485
Theoretical pI
8.64
GO Classification
Functions
monoamine transmembrane transporter activity / neurotransmitter transmembrane transporter activity / organic anion transmembrane transporter activity / spermidine transmembrane transporter activity / toxin transmembrane transporter activity
Processes
cellular detoxification / dopamine uptake / epinephrine transport / epinephrine uptake / histamine metabolic process / histamine transport / monoamine transport / monoatomic ion transport / monocarboxylic acid transport / neurotransmitter transport / norepinephrine transport / norepinephrine uptake / organic anion transport / purine-containing compound transmembrane transport / serotonin transport / serotonin uptake / spermidine transport / transport across blood-brain barrier / xenobiotic transport
Components
apical plasma membrane / basolateral plasma membrane / endomembrane system / mitochondrial membrane / neuronal cell body / nuclear outer membrane / presynapse
General 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:10196521, PubMed:10966924, PubMed:12538837, PubMed:17460754, PubMed:20858707). Cation cellular uptake or release is driven by the electrochemical potential, i.e. membrane potential and concentration gradient (PubMed:10966924). Functions as a Na(+)- and Cl(-)-independent, bidirectional uniporter (PubMed:12538837). Implicated in monoamine neurotransmitters uptake such as dopamine, adrenaline/epinephrine, noradrenaline/norepinephrine, histamine, serotonin and tyramine, thereby supporting a role in homeostatic regulation of aminergic neurotransmission in the brain (PubMed:10196521, PubMed:16581093, PubMed:20858707). Transports dopaminergic neuromodulators cyclo(his-pro) and salsolinol with low efficiency (PubMed:17460754). May be involved in the uptake and disposition of cationic compounds by renal clearance from the blood flow (PubMed:10966924). May contribute to regulate the transport of cationic compounds in testis across the blood-testis-barrier (Probable). Mediates the transport of polyamine spermidine and putrescine (By similarity). Mediates the bidirectional transport of polyamine agmatine (PubMed:12538837). Also transports guanidine (PubMed:10966924). May also mediate intracellular transport of organic cations, thereby playing a role in amine metabolism and intracellular signaling (By similarity)
Specific Function
Monoamine transmembrane transporter activity
Pfam Domain Function
Signal Regions
Not Available
Transmembrane Regions
21-41 182-202 241-261 269-289 381-401 468-488 498-518
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0012538|Solute carrier family 22 member 3 (SLC22A3)
ATGCCCTCCTTCGACGAGGCGCTGCAGCGGGTGGGCGAGTTCGGGCGCTTCCAGAGGCGC
GTGTTTTTGCTGCTGTGCCTGACGGGCGTCACCTTCGCCTTCCTCTTCGTCGGCGTGGTC
TTCCTGGGCACGCAGCCCGACCACTACTGGTGCCGCGGGCCAAGTGCCGCGGCGCTGGCC
GAGCGCTGCGGCTGGAGCCCGGAGGAGGAGTGGAACCGCACGGCGCCCGCCTCCCGCGGC
CCAGAGCCCCCCGAGCGCCGCGGCCGCTGCCAGCGCTACCTCCTGGAGGCGGCCAACGAC
AGCGCCTCCGCCACTAGCGCTCTCAGCTGCGCGGACCCACTCGCCGCCTTCCCCAACCGC
TCGGCTCCCCTTGTGCCGTGCCGCGGCGGCTGGCGCTACGCCCAGGCCCACTCCACCATC
GTCAGCGAGTTTGACCTTGTCTGTGTCAATGCGTGGATGCTGGACCTCACCCAAGCCATC
CTGAACCTCGGCTTCCTGACTGGAGCATTCACCTTAGGCTATGCAGCAGACAGGTATGGC
AGGATCGTCATTTACTTGCTATCCTGCCTTGGTGTTGGCGTCACTGGGGTTGTGGTGGCC
TTTGCACCAAACTTCCCTGTGTTTGTGATCTTCCGCTTCCTGCAAGGTGTATTTGGAAAG
GGGACGTGGATGACTTGCTACGTGATTGTGACAGAAATAGTAGGTTCGAAACAAAGGAGG
ATTGTGGGAATCGTGATTCAAATGTTCTTTACCCTTGGAATCATAATTCTCCCTGGAATT
GCCTACTTCATCCCCAACTGGCAAGGAATCCAGTTAGCCATCACGCTGCCCAGCTTTCTC
TTCCTCCTTTATTACTGGGTGGTCCCTGAGTCTCCCCGTTGGCTGATTACTCGGAAGAAA
GGAGATAAAGCATTACAGATCCTGAGACGCATTGCTAAGTGCAATGGGAAATACCTCTCA
TCAAATTACTCAGAGATCACTGTTACAGATGAGGAAGTTAGTAATCCATCCTTTTTAGAT
CTGGTGAGAACTCCCCAAATGAGGAAATGCACACTTATTCTTATGTTTGCTTGGTTCACA
AGCGCAGTGGTGTATCAAGGACTTGTCATGCGCCTGGGAATTATAGGGGGCAACCTCTAT
ATAGACTTTTTCATCTCGGGCGTGGTGGAACTGCCAGGAGCTCTCTTGATCTTACTAACC
ATTGAGCGCCTTGGACGACGCCTCCCCTTTGCGGCAAGCAATATAGTGGCAGGGGTGGCA
TGCCTTGTCACTGCGTTCTTACCAGAAGGAATAGCATGGTTGAGGACCACAGTGGCTACA
TTGGGAAGACTAGGGATAACCATGGCCTTTGAAATTGTTTATTTGGTAAATTCAGAATTG
TACCCAACAACATTACGAAATTTCGGAGTTTCGCTCTGTTCAGGTCTGTGTGATTTTGGG
GGAATCATAGCCCCATTTCTGCTCTTTCGGCTAGCAGCCGTGTGGCTAGAACTACCTCTG
ATCATCTTTGGTATCCTGGCATCCATCTGTGGTGGCCTTGTGATGCTTTTGCCTGAAACC
AAGGGTATTGCCTTGCCAGAGACAGTGGATGATGTAGAAAAACTTGGCAGTCCACATTCC
TGTAAATGTGGCAGGAATAAGAAAACCCCAGTTTCCCGCTCTCACCTTTGA
Chromosome Location
6
Locus
6q25.3
External Identifiers
ResourceLink
UniProtKB IDO75751
UniProtKB Entry NameS22A3_HUMAN
GenBank Protein ID3581982
GenBank Gene IDAJ001417
GeneCard IDSLC22A3
HGNC IDHGNC:10967
PDB ID(s)7ZH0, 7ZH6, 7ZHA
KEGG IDhsa:6581
IUPHAR/Guide To Pharmacology ID1021
NCBI Gene ID6581
General References
  1. Grundemann D, Schechinger B, Rappold GA, Schomig E: Molecular identification of the corticosterone-sensitive extraneuronal catecholamine transporter. Nat Neurosci. 1998 Sep;1(5):349-51. [Article]
  2. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [Article]
  3. Mungall AJ, Palmer SA, Sims SK, Edwards CA, Ashurst JL, Wilming L, Jones MC, Horton R, Hunt SE, Scott CE, Gilbert JG, Clamp ME, Bethel G, Milne S, Ainscough R, Almeida JP, Ambrose KD, Andrews TD, Ashwell RI, Babbage AK, Bagguley CL, Bailey J, Banerjee R, Barker DJ, Barlow KF, Bates K, Beare DM, Beasley H, Beasley O, Bird CP, Blakey S, Bray-Allen S, Brook J, Brown AJ, Brown JY, Burford DC, Burrill W, Burton J, Carder C, Carter NP, Chapman JC, Clark SY, Clark G, Clee CM, Clegg S, Cobley V, Collier RE, Collins JE, Colman LK, Corby NR, Coville GJ, Culley KM, Dhami P, Davies J, Dunn M, Earthrowl ME, Ellington AE, Evans KA, Faulkner L, Francis MD, Frankish A, Frankland J, French L, Garner P, Garnett J, Ghori MJ, Gilby LM, Gillson CJ, Glithero RJ, Grafham DV, Grant M, Gribble S, Griffiths C, Griffiths M, Hall R, Halls KS, Hammond S, Harley JL, Hart EA, Heath PD, Heathcott R, Holmes SJ, Howden PJ, Howe KL, Howell GR, Huckle E, Humphray SJ, Humphries MD, Hunt AR, Johnson CM, Joy AA, Kay M, Keenan SJ, Kimberley AM, King A, Laird GK, Langford C, Lawlor S, Leongamornlert DA, Leversha M, Lloyd CR, Lloyd DM, Loveland JE, Lovell J, Martin S, Mashreghi-Mohammadi M, Maslen GL, Matthews L, McCann OT, McLaren SJ, McLay K, McMurray A, Moore MJ, Mullikin JC, Niblett D, Nickerson T, Novik KL, Oliver K, Overton-Larty EK, Parker A, Patel R, Pearce AV, Peck AI, Phillimore B, Phillips S, Plumb RW, Porter KM, Ramsey Y, Ranby SA, Rice CM, Ross MT, Searle SM, Sehra HK, Sheridan E, Skuce CD, Smith S, Smith M, Spraggon L, Squares SL, Steward CA, Sycamore N, Tamlyn-Hall G, Tester J, Theaker AJ, Thomas DW, Thorpe A, Tracey A, Tromans A, Tubby B, Wall M, Wallis JM, West AP, White SS, Whitehead SL, Whittaker H, Wild A, Willey DJ, Wilmer TE, Wood JM, Wray PW, Wyatt JC, Young L, Younger RM, Bentley DR, Coulson A, Durbin R, Hubbard T, Sulston JE, Dunham I, Rogers J, Beck S: The DNA sequence and analysis of human chromosome 6. Nature. 2003 Oct 23;425(6960):805-11. [Article]
  4. Verhaagh S, Schweifer N, Barlow DP, Zwart R: 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. 1999 Jan 15;55(2):209-18. [Article]
  5. Wu X, Huang W, Ganapathy ME, Wang H, Kekuda R, Conway SJ, Leibach FH, Ganapathy V: Structure, function, and regional distribution of the organic cation transporter OCT3 in the kidney. Am J Physiol Renal Physiol. 2000 Sep;279(3):F449-58. [Article]
  6. Van Damme P, Lasa M, Polevoda B, Gazquez C, Elosegui-Artola A, Kim DS, De Juan-Pardo E, Demeyer K, Hole K, Larrea E, Timmerman E, Prieto J, Arnesen T, Sherman F, Gevaert K, Aldabe R: N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB. Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12449-54. doi: 10.1073/pnas.1210303109. Epub 2012 Jul 18. [Article]

Associated Data

Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
ProcainamideapprovedunknowntransporterinhibitorDetails
ImipramineapprovedunknowntransporterinhibitorDetails
GuanidineapprovedunknowntransportersubstrateinhibitorDetails
Desipramineapproved, investigationalunknowntransporterinhibitorDetails
ClonidineapprovedunknowntransporterinhibitorDetails
Progesteroneapproved, vet_approvedunknowntransporterinhibitorDetails
PrazosinapprovedunknowntransporterinhibitorDetails
PhenoxybenzamineapprovedunknowntransporterinhibitorDetails
Estradiolapproved, investigational, vet_approvedunknowntransporterinhibitorDetails
Cimetidineapproved, investigationalunknowntransportersubstrateinhibitorDetails
Histamineapproved, investigationalunknowntransporterinhibitorDetails
DopamineapprovedunknowntransporterinhibitorDetails
Cholineapproved, nutraceuticalunknowntransporterinhibitorDetails
NicotineapprovedunknowntransporterinhibitorDetails
NorepinephrineapprovedunknowntransportersubstrateinhibitorDetails
Metamfetamineapproved, illicit, withdrawnunknowntransporterinhibitorDetails
Amphetamineapproved, illicit, investigationalunknowntransportersubstrateDetails
Irinotecanapproved, investigationalunknowntransporterinhibitorDetails
MelphalanapprovedunknowntransporterinhibitorDetails
Vincristineapproved, investigationalunknowntransporterinhibitorDetails
Adefovir dipivoxilapproved, investigationalunknowntransportersubstrateDetails
Oxaliplatinapproved, investigationalnotransportersubstrateDetails
AgmatineexperimentalunknowntransportersubstrateDetails
Tetraethylammoniumexperimental, investigationalunknowntransporterDetails
Tyramineinvestigational, nutraceuticalunknowntransporterDetails
Lamivudineapproved, investigationalunknowntransportersubstrateDetails
MetforminapprovedunknowntransportersubstrateDetails
Testosterone cypionateapprovedunknowntransportersubstrateDetails
Testosterone enanthateapprovedunknowntransportersubstrateDetails
Estradiol acetateapproved, investigational, vet_approvedunknowntransporterinhibitorDetails
Estradiol benzoateapproved, investigational, vet_approvedunknowntransporterinhibitorDetails
Estradiol cypionateapproved, investigational, vet_approvedunknowntransporterinhibitorDetails
Estradiol dienanthateapproved, investigational, vet_approvedunknowntransporterinhibitorDetails
Estradiol valerateapproved, investigational, vet_approvedunknowntransporterinhibitorDetails
Choline salicylateapproved, nutraceuticalunknowntransporterinhibitorDetails
Pramipexoleapproved, investigationalunknowntransporterDetails
LinagliptinapprovedunknowntransporterinhibitorDetails
Lansoprazoleapproved, investigationalunknowntransporterDetails
Formoterolapproved, investigationalunknowntransporterinhibitorDetails
SalmeterolapprovedunknowntransporterinhibitorDetails
Sulpirideapproved, investigationalunknowntransportersubstrateDetails
MirabegronapprovednotransportersubstrateDetails
ClozapineapprovednotransportersubstrateDetails