ATP-binding cassette sub-family C member 3

Details

Name
ATP-binding cassette sub-family C member 3
Kind
protein
Synonyms
  • 7.6.2.-
  • 7.6.2.2
  • 7.6.2.3
  • Canalicular multispecific organic anion transporter 2
  • CMOAT2
  • MLP2
  • MOAT-D
  • MRP3
  • Multi-specific organic anion transporter D
  • Multidrug resistance-associated protein 3
Gene Name
ABCC3
UniProtKB Entry
O15438Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0002113|ATP-binding cassette sub-family C member 3
MDALCGSGELGSKFWDSNLSVHTENPDLTPCFQNSLLAWVPCIYLWVALPCYLLYLRHHC
RGYIILSHLSKLKMVLGVLLWCVSWADLFYSFHGLVHGRAPAPVFFVTPLVVGVTMLLAT
LLIQYERLQGVQSSGVLIIFWFLCVVCAIVPFRSKILLAKAEGEISDPFRFTTFYIHFAL
VLSALILACFREKPPFFSAKNVDPNPYPETSAGFLSRLFFWWFTKMAIYGYRHPLEEKDL
WSLKEEDRSQMVVQQLLEAWRKQEKQTARHKASAAPGKNASGEDEVLLGARPRPRKPSFL
KALLATFGSSFLISACFKLIQDLLSFINPQLLSILIRFISNPMAPSWWGFLVAGLMFLCS
MMQSLILQHYYHYIFVTGVKFRTGIMGVIYRKALVITNSVKRASTVGEIVNLMSVDAQRF
MDLAPFLNLLWSAPLQIILAIYFLWQNLGPSVLAGVAFMVLLIPLNGAVAVKMRAFQVKQ
MKLKDSRIKLMSEILNGIKVLKLYAWEPSFLKQVEGIRQGELQLLRTAAYLHTTTTFTWM
CSPFLVTLITLWVYVYVDPNNVLDAEKAFVSVSLFNILRLPLNMLPQLISNLTQASVSLK
RIQQFLSQEELDPQSVERKTISPGYAITIHSGTFTWAQDLPPTLHSLDIQVPKGALVAVV
GPVGCGKSSLVSALLGEMEKLEGKVHMKGSVAYVPQQAWIQNCTLQENVLFGKALNPKRY
QQTLEACALLADLEMLPGGDQTEIGEKGINLSGGQRQRVSLARAVYSDADIFLLDDPLSA
VDSHVAKHIFDHVIGPEGVLAGKTRVLVTHGISFLPQTDFIIVLADGQVSEMGPYPALLQ
RNGSFANFLCNYAPDEDQGHLEDSWTALEGAEDKEALLIEDTLSNHTDLTDNDPVTYVVQ
KQFMRQLSALSSDGEGQGRPVPRRHLGPSEKVQVTEAKADGALTQEEKAAIGTVELSVFW
DYAKAVGLCTTLAICLLYVGQSAAAIGANVWLSAWTNDAMADSRQNNTSLRLGVYAALGI
LQGFLVMLAAMAMAAGGIQAARVLHQALLHNKIRSPQSFFDTTPSGRILNCFSKDIYVVD
EVLAPVILMLLNSFFNAISTLVVIMASTPLFTVVILPLAVLYTLVQRFYAATSRQLKRLE
SVSRSPIYSHFSETVTGASVIRAYNRSRDFEIISDTKVDANQRSCYPYIISNRWLSIGVE
FVGNCVVLFAALFAVIGRSSLNPGLVGLSVSYSLQVTFALNWMIRMMSDLESNIVAVERV
KEYSKTETEAPWVVEGSRPPEGWPPRGEVEFRNYSVRYRPGLDLVLRDLSLHVHGGEKVG
IVGRTGAGKSSMTLCLFRILEAAKGEIRIDGLNVADIGLHDLRSQLTIIPQDPILFSGTL
RMNLDPFGSYSEEDIWWALELSHLHTFVSSQPAGLDFQCSEGGENLSVGQRQLVCLARAL
LRKSRILVLDEATAAIDLETDNLIQATIRTQFDTCTVLTIAHRLNTIMDYTRVLVLDKGV
VAEFDSPANLIAARGIFYGMARDAGLA
Number of residues
1527
Molecular Weight
169341.14
Theoretical pI
7.2
GO Classification
Functions
ABC-type bile acid transporter activity / ABC-type glutathione S-conjugate transporter activity / ABC-type transporter activity / ABC-type xenobiotic transporter activity / ATP hydrolysis activity / ATPase-coupled inorganic anion transmembrane transporter activity / ATPase-coupled transmembrane transporter activity / glucuronoside transmembrane transporter activity / icosanoid transmembrane transporter activity / xenobiotic transmembrane transporter activity
Processes
leukotriene transport / transport across blood-brain barrier / xenobiotic metabolic process / xenobiotic transmembrane transport / xenobiotic transport
Components
basal plasma membrane / basolateral plasma membrane
General Function
ATP-dependent transporter of the ATP-binding cassette (ABC) family that binds and hydrolyzes ATP to enable active transport of various substrates including many drugs, toxicants and endogenous compound across cell membranes (PubMed:10359813, PubMed:11581266, PubMed:15083066). Transports glucuronide conjugates such as bilirubin diglucuronide, estradiol-17-beta-o-glucuronide and GSH conjugates such as leukotriene C4 (LTC4) (PubMed:11581266, PubMed:15083066). Transports also various bile salts (taurocholate, glycocholate, taurochenodeoxycholate-3-sulfate, taurolithocholate- 3-sulfate) (By similarity). Does not contribute substantially to bile salt physiology but provides an alternative route for the export of bile acids and glucuronides from cholestatic hepatocytes (By similarity). May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Can confer resistance to various anticancer drugs, methotrexate, tenoposide and etoposide, by decreasing accumulation of these drugs in cells (PubMed:10359813, PubMed:11581266)
Specific Function
Abc-type bile acid transporter activity
Pfam Domain Function
Signal Regions
Not Available
Transmembrane Regions
33-53 74-94 100-120 133-153 172-192 303-323 350-370 427-447 451-471 534-554 577-597 964-984 1022-1042 1086-1106 1108-1128 1200-1220 1223-1243
Cellular Location
Basolateral cell membrane
Gene sequence
>lcl|BSEQ0010744|Canalicular multispecific organic anion transporter 2 (ABCC3)
ATGGACGCCCTGTGCGGTTCCGGGGAGCTCGGCTCCAAGTTCTGGGACTCCAACCTGTCT
GTGCACACAGAAAACCCGGACCTCACTCCCTGCTTCCAGAACTCCCTGCTGGCCTGGGTG
CCCTGCATCTACCTGTGGGTCGCCCTGCCCTGCTACTTGCTCTACCTGCGGCACCATTGT
CGTGGCTACATCATCCTCTCCCACCTGTCCAAGCTCAAGATGGTCCTGGGTGTCCTGCTG
TGGTGCGTCTCCTGGGCGGACCTTTTTTACTCCTTCCATGGCCTGGTCCATGGCCGGGCC
CCTGCCCCTGTTTTCTTTGTCACCCCCTTGGTGGTGGGGGTCACCATGCTGCTGGCCACC
CTGCTGATACAGTATGAGCGGCTGCAGGGCGTACAGTCTTCGGGGGTCCTCATTATCTTC
TGGTTCCTGTGTGTGGTCTGCGCCATCGTCCCATTCCGCTCCAAGATCCTTTTAGCCAAG
GCAGAGGGTGAGATCTCAGACCCCTTCCGCTTCACCACCTTCTACATCCACTTTGCCCTG
GTACTCTCTGCCCTCATCTTGGCCTGCTTCAGGGAGAAACCTCCATTTTTCTCCGCAAAG
AATGTCGACCCTAACCCCTACCCTGAGACCAGCGCTGGCTTTCTCTCCCGCCTGTTTTTC
TGGTGGTTCACAAAGATGGCCATCTATGGCTACCGGCATCCCCTGGAGGAGAAGGACCTC
TGGTCCCTAAAGGAAGAGGACAGATCCCAGATGGTGGTGCAGCAGCTGCTGGAGGCATGG
AGGAAGCAGGAAAAGCAGACGGCACGACACAAGGCTTCAGCAGCACCTGGGAAAAATGCC
TCCGGCGAGGACGAGGTGCTGCTGGGTGCCCGGCCCAGGCCCCGGAAGCCCTCCTTCCTG
AAGGCCCTGCTGGCCACCTTCGGCTCCAGCTTCCTCATCAGTGCCTGCTTCAAGCTTATC
CAGGACCTGCTCTCCTTCATCAATCCACAGCTGCTCAGCATCCTGATCAGGTTTATCTCC
AACCCCATGGCCCCCTCCTGGTGGGGCTTCCTGGTGGCTGGGCTGATGTTCCTGTGCTCC
ATGATGCAGTCGCTGATCTTACAACACTATTACCACTACATCTTTGTGACTGGGGTGAAG
TTTCGTACTGGGATCATGGGTGTCATCTACAGGAAGGCTCTGGTTATCACCAACTCAGTC
AAACGTGCGTCCACTGTGGGGGAAATTGTCAACCTCATGTCAGTGGATGCCCAGCGCTTC
ATGGACCTTGCCCCCTTCCTCAATCTGCTGTGGTCAGCACCCCTGCAGATCATCCTGGCG
ATCTACTTCCTCTGGCAGAACCTAGGTCCCTCTGTCCTGGCTGGAGTCGCTTTCATGGTC
TTGCTGATTCCACTCAACGGAGCTGTGGCCGTGAAGATGCGCGCCTTCCAGGTAAAGCAA
ATGAAATTGAAGGACTCGCGCATCAAGCTGATGAGTGAGATCCTGAACGGCATCAAGGTG
CTGAAGCTGTACGCCTGGGAGCCCAGCTTCCTGAAGCAGGTGGAGGGCATCAGGCAGGGT
GAGCTCCAGCTGCTGCGCACGGCGGCCTACCTCCACACCACAACCACCTTCACCTGGATG
TGCAGCCCCTTCCTGGTGAGGCTTGGCACAGGGCTGGGTCCCTGCCTCCAGGGCTCTGGG
TGCCCAGGCATGGCCAGGGCTCATTGGACTCTACCCTGA
Chromosome Location
17
Locus
17q21.33
External Identifiers
ResourceLink
UniProtKB IDO15438
UniProtKB Entry NameMRP3_HUMAN
GenBank Protein ID3132270
GenBank Gene IDAB010887
GeneCard IDABCC3
GenAtlas IDABCC3
HGNC IDHGNC:54
PDB ID(s)8HVH, 8HW2, 8HW4, 8IZP
KEGG IDhsa:8714
NCBI Gene ID8714
General References
  1. Uchiumi T, Hinoshita E, Haga S, Nakamura T, Tanaka T, Toh S, Furukawa M, Kawabe T, Wada M, Kagotani K, Okumura K, Kohno K, Akiyama S, Kuwano M: Isolation of a novel human canalicular multispecific organic anion transporter, cMOAT2/MRP3, and its expression in cisplatin-resistant cancer cells with decreased ATP-dependent drug transport. Biochem Biophys Res Commun. 1998 Nov 9;252(1):103-10. [Article]
  2. Kiuchi Y, Suzuki H, Hirohashi T, Tyson CA, Sugiyama Y: cDNA cloning and inducible expression of human multidrug resistance associated protein 3 (MRP3). FEBS Lett. 1998 Aug 14;433(1-2):149-52. [Article]
  3. Belinsky MG, Bain LJ, Balsara BB, Testa JR, Kruh GD: Characterization of MOAT-C and MOAT-D, new members of the MRP/cMOAT subfamily of transporter proteins. J Natl Cancer Inst. 1998 Nov 18;90(22):1735-41. [Article]
  4. Fromm MF, Leake B, Roden DM, Wilkinson GR, Kim RB: Human MRP3 transporter: identification of the 5'-flanking region, genomic organization and alternative splice variants. Biochim Biophys Acta. 1999 Jan 8;1415(2):369-74. [Article]
  5. Konig J, Rost D, Cui Y, Keppler D: Characterization of the human multidrug resistance protein isoform MRP3 localized to the basolateral hepatocyte membrane. Hepatology. 1999 Apr;29(4):1156-63. [Article]
  6. Zody MC, Garber M, Adams DJ, Sharpe T, Harrow J, Lupski JR, Nicholson C, Searle SM, Wilming L, Young SK, Abouelleil A, Allen NR, Bi W, Bloom T, Borowsky ML, Bugalter BE, Butler J, Chang JL, Chen CK, Cook A, Corum B, Cuomo CA, de Jong PJ, DeCaprio D, Dewar K, FitzGerald M, Gilbert J, Gibson R, Gnerre S, Goldstein S, Grafham DV, Grocock R, Hafez N, Hagopian DS, Hart E, Norman CH, Humphray S, Jaffe DB, Jones M, Kamal M, Khodiyar VK, LaButti K, Laird G, Lehoczky J, Liu X, Lokyitsang T, Loveland J, Lui A, Macdonald P, Major JE, Matthews L, Mauceli E, McCarroll SA, Mihalev AH, Mudge J, Nguyen C, Nicol R, O'Leary SB, Osoegawa K, Schwartz DC, Shaw-Smith C, Stankiewicz P, Steward C, Swarbreck D, Venkataraman V, Whittaker CA, Yang X, Zimmer AR, Bradley A, Hubbard T, Birren BW, Rogers J, Lander ES, Nusbaum C: DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage. Nature. 2006 Apr 20;440(7087):1045-9. [Article]
  7. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  8. Kool M, de Haas M, Scheffer GL, Scheper RJ, van Eijk MJ, Juijn JA, Baas F, Borst P: Analysis of expression of cMOAT (MRP2), MRP3, MRP4, and MRP5, homologues of the multidrug resistance-associated protein gene (MRP1), in human cancer cell lines. Cancer Res. 1997 Aug 15;57(16):3537-47. [Article]
  9. Hillman RT, Green RE, Brenner SE: An unappreciated role for RNA surveillance. Genome Biol. 2004;5(2):R8. Epub 2004 Feb 2. [Article]
  10. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [Article]
  11. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [Article]

Associated Data

Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
Omeprazoleapproved, investigational, vet_approvedunknowntransporterinducerDetails
CisplatinapprovedunknowntransporterinducerDetails
Phenobarbitalapproved, investigationalunknowntransporterinducerDetails
RifampinapprovedunknowntransporterinducerDetails
NifedipineapprovedunknowntransporterinducerDetails
Metyraponeapproved, investigationalunknowntransporterinducerDetails
SulfinpyrazoneapprovedunknowntransporterinhibitorDetails
Probenecidapproved, investigationalunknowntransporterinhibitorDetails
Indomethacinapproved, investigationalunknowntransporterinhibitorDetails
Vincristineapproved, investigationalunknowntransporterinhibitorDetails
VerapamilapprovedunknowntransporterinhibitorDetails
Taurocholic acidapproved, experimentalunknowntransportersubstrateinhibitorDetails
EtoposideapprovedunknowntransportersubstrateinhibitorDetails
Doxorubicinapproved, investigationalunknowntransporterinhibitorDetails
MethotrexateapprovedunknowntransportersubstrateinhibitorDetails
GlyburideapprovedunknowntransporterinhibitorDetails
Conjugated estrogensapprovedunknowntransporterinhibitorDetails
Cholic AcidapprovedunknowntransporterinhibitorDetails
Glutathioneapproved, investigational, nutraceuticalunknowntransportersubstrateDetails
Folic acidapproved, nutraceutical, vet_approvedunknowntransportersubstrateDetails
Gadoxetic acidapprovednotransportersubstrateDetails
EzetimibeapprovedunknowntransportersubstrateDetails
FluorouracilapprovedunknowntransportersubstrateDetails
Lamivudineapproved, investigationalunknowntransportersubstrateDetails
DovitinibinvestigationalunknowntransporterDetails
Raloxifeneapproved, investigationalunknowntransportersubstrateDetails
Fexofenadineapproved, investigationalunknowntransportersubstrateDetails
Promethazineapproved, investigationalunknowntransporterinhibitorDetails
Bempedoic acidapproved, investigationalunknowntransporterinhibitorDetails
Belantamab mafodotinapprovedunknowntransportersubstrateDetails
Pralatrexateapproved, investigationalnotransportersubstrateinhibitorDetails
Elafibranorapproved, investigationalunknowntransporterinhibitorDetails