ATP-binding cassette sub-family C member 4

Details

Name
ATP-binding cassette sub-family C member 4
Kind
protein
Synonyms
  • 7.6.2.-
  • 7.6.2.2
  • 7.6.2.3
  • MOAT-B
  • MOATB
  • MRP/cMOAT-related ABC transporter
  • MRP4
  • Multi-specific organic anion transporter B
  • Multidrug resistance-associated protein 4
Gene Name
ABCC4
UniProtKB Entry
O15439Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0037136|ATP-binding cassette sub-family C member 4
MLPVYQEVKPNPLQDANLCSRVFFWWLNPLFKIGHKRRLEEDDMYSVLPEDRSQHLGEEL
QGFWDKEVLRAENDAQKPSLTRAIIKCYWKSYLVLGIFTLIEESAKVIQPIFLGKIINYF
ENYDPMDSVALNTAYAYATVLTFCTLILAILHHLYFYHVQCAGMRLRVAMCHMIYRKALR
LSNMAMGKTTTGQIVNLLSNDVNKFDQVTVFLHFLWAGPLQAIAVTALLWMEIGISCLAG
MAVLIILLPLQSCFGKLFSSLRSKTATFTDARIRTMNEVITGIRIIKMYAWEKSFSNLIT
NLRKKEISKILRSSCLRGMNLASFFSASKIIVFVTFTTYVLLGSVITASRVFVAVTLYGA
VRLTVTLFFPSAIERVSEAIVSIRRIQTFLLLDEISQRNRQLPSDGKKMVHVQDFTAFWD
KASETPTLQGLSFTVRPGELLAVVGPVGAGKSSLLSAVLGELAPSHGLVSVHGRIAYVSQ
QPWVFSGTLRSNILFGKKYEKERYEKVIKACALKKDLQLLEDGDLTVIGDRGTTLSGGQK
ARVNLARAVYQDADIYLLDDPLSAVDAEVSRHLFELCICQILHEKITILVTHQLQYLKAA
SQILILKDGKMVQKGTYTEFLKSGIDFGSLLKKDNEESEQPPVPGTPTLRNRTFSESSVW
SQQSSRPSLKDGALESQDTENVPVTLSEENRSEGKVGFQAYKNYFRAGAHWIVFIFLILL
NTAAQVAYVLQDWWLSYWANKQSMLNVTVNGGGNVTEKLDLNWYLGIYSGLTVATVLFGI
ARSLLVFYVLVNSSQTLHNKMFESILKAPVLFFDRNPIGRILNRFSKDIGHLDDLLPLTF
LDFIQTLLQVVGVVSVAVAVIPWIAIPLVPLGIIFIFLRRYFLETSRDVKRLESTTRSPV
FSHLSSSLQGLWTIRAYKAEERCQELFDAHQDLHSEAWFLFLTTSRWFAVRLDAICAMFV
IIVAFGSLILAKTLDAGQVGLALSYALTLMGMFQWCVRQSAEVENMMISVERVIEYTDLE
KEAPWEYQKRPPPAWPHEGVIIFDNVNFMYSPGGPLVLKHLTALIKSQEKVGIVGRTGAG
KSSLISALFRLSEPEGKIWIDKILTTEIGLHDLRKKMSIIPQEPVLFTGTMRKNLDPFNE
HTDEELWNALQEVQLKETIEDLPGKMDTELAESGSNFSVGQRQLVCLARAILRKNQILII
DEATANVDPRTDELIQKKIREKFAHCTVLTIAHRLNTIIDSDKIMVLDSGRLKEYDEPYV
LLQNKESLFYKMVQQLGKAEAAALTETAKQVYFKRNYPHIGHTDHMVTNTSNGQPSTLTI
FETAL
Number of residues
1325
Molecular Weight
149525.33
Theoretical pI
8.39
GO Classification
Functions
15-hydroxyprostaglandin dehydrogenase (NAD+) activity / ATP binding
Processes
platelet degranulation / transmembrane transport
Components
basolateral plasma membrane / membrane / plasma membrane / platelet dense granule membrane
General Function
ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes physiological compounds and xenobiotics from cells. Transports a range of endogenous molecules that have a key role in cellular communication and signaling, including cyclic nucleotides such as cyclic AMP (cAMP) and cyclic GMP (cGMP), bile acids, steroid conjugates, urate, and prostaglandins (PubMed:11856762, PubMed:12523936, PubMed:12835412, PubMed:12883481, PubMed:15364914, PubMed:15454390, PubMed:16282361, PubMed:17959747, PubMed:18300232, PubMed:26721430). Mediates the ATP-dependent efflux of glutathione conjugates such as leukotriene C4 (LTC4) and leukotriene B4 (LTB4) too. The presence of GSH is necessary for the ATP-dependent transport of LTB4, whereas GSH is not required for the transport of LTC4 (PubMed:17959747). Mediates the cotransport of bile acids with reduced glutathione (GSH) (PubMed:12523936, PubMed:12883481, PubMed:16282361). Transports a wide range of drugs and their metabolites, including anticancer, antiviral and antibiotics molecules (PubMed:11856762, PubMed:12105214, PubMed:15454390, PubMed:17344354, PubMed:18300232). Confers resistance to anticancer agents such as methotrexate (PubMed:11106685)
Specific Function
15-hydroxyprostaglandin dehydrogenase (nad+) activity
Pfam Domain Function
Signal Regions
Not Available
Transmembrane Regions
93-113 136-156 207-227 228-248 328-348 351-371 440-460 710-730 771-791 836-856 858-878 954-974 977-997 1038-1058
Cellular Location
Basolateral cell membrane
Gene sequence
>lcl|BSEQ0010828|Multidrug resistance-associated protein 4 (ABCC4)
ATGCTGCCCGTGTACCAGGAGGTGAAGCCCAACCCGCTGCAGGACGCGAACCTCTGCTCA
CGCGTGTTCTTCTGGTGGCTCAATCCCTTGTTTAAAATTGGCCATAAACGGAGATTAGAG
GAAGATGATATGTATTCAGTGCTGCCAGAAGACCGCTCACAGCACCTTGGAGAGGAGTTG
CAAGGGTTCTGGGATAAAGAAGTTTTAAGAGCTGAGAATGACGCACAGAAGCCTTCTTTA
ACAAGAGCAATCATAAAGTGTTACTGGAAATCTTATTTAGTTTTGGGAATTTTTACGTTA
ATTGAGGAAAGTGCCAAAGTAATCCAGCCCATATTTTTGGGAAAAATTATTAATTATTTT
GAAAATTATGATCCCATGGATTCTGTGGCTTTGAACACAGCGTACGCCTATGCCACGGTG
CTGACTTTTTGCACGCTCATTTTGGCTATACTGCATCACTTATATTTTTATCACGTTCAG
TGTGCTGGGATGAGGTTACGAGTAGCCATGTGCCATATGATTTATCGGAAGGCACTTCGT
CTTAGTAACATGGCCATGGGGAAGACAACCACAGGCCAGATAGTCAATCTGCTGTCCAAT
GATGTGAACAAGTTTGATCAGGTGACAGTGTTCTTACACTTCCTGTGGGCAGGACCACTG
CAGGCGATTGCAGTGACTGCCCTACTCTGGATGGAGATAGGAATATCGTGCCTTGCTGGG
ATGGCAGTTCTAATCATTCTCCTGCCCTTGCAAAGCTGTTTTGGGAAGTTGTTCTCATCA
CTGAGGAGTAAAACTGCAACTTTCACGGATGCCAGGATCAGGACCATGAATGAAGTTATA
ACTGGTATAAGGATAATAAAAATGTACGCCTGGGAAAAGTCATTTTCAAATCTTATTACC
AATTTGAGAAAGAAGGAGATTTCCAAGATTCTGAGAAGTTCCTGCCTCAGAGGGATGAAT
TTGGCTTCATTTTTCAGTGCAAGCAAAATCATCGTGTTTGTGACCTTCACCACCTACGTG
CTCCTCGGCAGTGTGATCACAGCCAGCCGCGTGTTCGTGGCAGTGACGCTGTATGGGGCT
GTGCGGCTGACGGTTACCCTCTTCTTCCCCTCAGCCATTGAGAGGGTGTCAGAGGCAATC
GTCAGCATCCGAAGAATCCAGACCTTTTTGCTACTTGATGAGATATCACAGCGCAACCGT
CAGCTGCCGTCAGATGGTAAAAAGATGGTGCATGTGCAGGATTTTACTGCTTTTTGGGAT
AAGGCATCAGAGACCCCAACTCTACAAGGCCTTTCCTTTACTGTCAGACCTGGCGAATTG
TTAGCTGTGGTCGGCCCCGTGGGAGCAGGGAAGTCATCACTGTTAAGTGCCGTGCTCGGG
GAATTGGCCCCAAGTCACGGGCTGGTCAGCGTGCATGGAAGAATTGCCTATGTGTCTCAG
CAGCCCTGGGTGTTCTCGGGAACTCTGAGGAGTAATATTTTATTTGGGAAGAAATACGAA
AAGGAACGATATGAAAAAGTCATAAAGGCTTGTGCTCTGAAAAAGGATTTACAGCTGTTG
GAGGATGGTGATCTGACTGTGATAGGAGATCGGGGAACCACGCTGAGTGGAGGGCAGAAA
GCACGGGTAAACCTTGCAAGAGCAGTGTATCAAGATGCTGACATCTATCTCCTGGACGAT
CCTCTCAGTGCAGTAGATGCGGAAGTTAGCAGACACTTGTTCGAACTGTGTATTTGTCAA
ATTTTGCATGAGAAGATCACAATTTTAGTGACTCATCAGTTGCAGTACCTCAAAGCTGCA
AGTCAGATTCTGATATTGAAAGATGGTAAAATGGTGCAGAAGGGGACTTACACTGAGTTC
CTAAAATCTGGTATAGATTTTGGCTCCCTTTTAAAGAAGGATAATGAGGAAAGTGAACAA
CCTCCAGTTCCAGGAACTCCCACACTAAGGAATCGTACCTTCTCAGAGTCTTCGGTTTGG
TCTCAACAATCTTCTAGACCCTCCTTGAAAGATGGTGCTCTGGAGAGCCAAGATACAGAG
AATGTCCCAGTTACACTATCAGAGGAGAACCGTTCTGAAGGAAAAGTTGGTTTTCAGGCC
TATAAGAATTACTTCAGAGCTGGTGCTCACTGGATTGTCTTCATTTTCCTTATTCTCCTA
AACACTGCAGCTCAGGTTGCCTATGTGCTTCAAGATTGGTGGCTTTCATACTGGGCAAAC
AAACAAAGTATGCTAAATGTCACTGTAAATGGAGGAGGAAATGTAACCGAGAAGCTAGAT
CTTAACTGGTACTTAGGAATTTATTCAGGTTTAACTGTAGCTACCGTTCTTTTTGGCATA
GCAAGATCTCTATTGGTATTCTACGTCCTTGTTAACTCTTCACAAACTTTGCACAACAAA
ATGTTTGAGTCAATTCTGAAAGCTCCGGTATTATTCTTTGATAGAAATCCAATAGGAAGA
ATTTTAAATCGTTTCTCCAAAGACATTGGACACTTGGATGATTTGCTGCCGCTGACGTTT
TTAGATTTCATCCAGAGATGGGATCTCGCTGTGTTGTCCTGGCTGGTCTCAAACTCCTAG
Chromosome Location
13
Locus
13q32.1
External Identifiers
ResourceLink
UniProtKB IDO15439
UniProtKB Entry NameMRP4_HUMAN
GenBank Protein ID3335173
GenBank Gene IDAF071202
GeneCard IDABCC4
GenAtlas IDABCC4
HGNC IDHGNC:55
PDB ID(s)8BJF, 8BWO, 8BWP, 8BWQ, 8BWR, 8I4A, 8I4B, 8I4C, 8IZ7, 8IZ8, 8IZ9, 8IZA, 8J3W, 8J3Z
KEGG IDhsa:10257
IUPHAR/Guide To Pharmacology ID782
NCBI Gene ID10257
General References
  1. Lee K, Belinsky MG, Bell DW, Testa JR, Kruh GD: Isolation of MOAT-B, a widely expressed multidrug resistance-associated protein/canalicular multispecific organic anion transporter-related transporter. Cancer Res. 1998 Jul 1;58(13):2741-7. [Article]
  2. Adachi M, Sampath J, Lan LB, Sun D, Hargrove P, Flatley R, Tatum A, Edwards MZ, Wezeman M, Matherly L, Drake R, Schuetz J: Expression of MRP4 confers resistance to ganciclovir and compromises bystander cell killing. J Biol Chem. 2002 Oct 11;277(41):38998-9004. Epub 2002 Jun 24. [Article]
  3. 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]
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  5. 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]
  6. 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]
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Associated Data

Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
MethotrexateapprovedunknowntransportersubstrateinhibitorDetails
Cyclic adenosine monophosphateexperimentalunknowntransportersubstrateinhibitorDetails
Probenecidapproved, investigationalunknowntransporterinhibitorDetails
DipyridamoleapprovedunknowntransporterinhibitorDetails
VerapamilapprovedunknowntransporterinhibitorDetails
SulfinpyrazoneapprovedunknowntransporterinhibitorDetails
Sildenafilapproved, investigationalunknowntransporterinhibitorDetails
Folic acidapproved, nutraceutical, vet_approvedunknowntransporterinhibitorDetails
Taurocholic acidapproved, experimentalunknowntransporterinhibitorDetails
Conjugated estrogensapprovedunknowntransporterinhibitorDetails
Ursodeoxycholic acidapproved, investigationalunknowntransporterinhibitorDetails
Cholic AcidapprovedunknowntransporterinhibitorDetails
Rofecoxibapproved, investigational, withdrawnunknowntransporterinhibitorDetails
Ketoprofenapproved, vet_approvedunknowntransporterinhibitorDetails
Indomethacinapproved, investigationalunknowntransporterinhibitorDetails
IbuprofenapprovedunknowntransporterinhibitorDetails
Flurbiprofenapproved, investigationalunknowntransporterinhibitorDetails
Diclofenacapproved, vet_approvedunknowntransporterinhibitorDetails
Celecoxibapproved, investigationalunknowntransporterinhibitorDetails
TioguanineapprovedunknowntransporterinhibitorDetails
Sorafenibapproved, investigationalunknowntransporterinhibitorDetails
Sunitinibapproved, investigationalunknowntransporterinhibitorDetails
MercaptopurineapprovedunknowntransportersubstrateDetails
Glutathioneapproved, investigational, nutraceuticalunknowntransportersubstrateDetails
DinoprostoneapprovedunknowntransportersubstrateDetails
Alprostadilapproved, investigationalunknowntransportersubstrateDetails
Adefovir dipivoxilapproved, investigationalunknowntransportersubstrateDetails
AtorvastatinapprovednotransportersubstrateDetails
RosuvastatinapprovedunknowntransportersubstrateDetails
OseltamivirapprovedunknowntransportersubstrateDetails
Meloxicamapproved, vet_approvedunknowntransporterbinderDetails
CefazolinapprovedunknowntransportersubstrateDetails
Nateglinideapproved, investigationalunknowntransportersubstrateDetails
ZidovudineapprovedunknowntransportersubstrateDetails
FluorouracilapprovedunknowntransportersubstrateDetails
Lamivudineapproved, investigationalunknowntransportersubstrateDetails
Tenofovir disoproxilapproved, investigationalunknowntransportersubstrateDetails
ATPinvestigational, nutraceuticalunknowntargetDetails
Rucaparibapproved, investigationalnotransporterinhibitorDetails
Fluciclovine (18F)approvednotransportersubstrateDetails
Dexibuprofenapproved, investigationalunknowntransporterDetails
Tenofovir alafenamideapprovednotransportersubstrateDetails
Tenofovirexperimental, investigationalnotransportersubstrateDetails
Raloxifeneapproved, investigationalunknowntransportersubstrateDetails
Hydrochlorothiazideapproved, vet_approvedunknowntransportersubstrateDetails
Promethazineapproved, investigationalunknowntransporterinhibitorDetails
Prasteroneapproved, investigational, nutraceuticalunknowntransportersubstrateDetails
Remdesivirapproved, investigationalunknowntransporterinhibitorDetails
ImatinibapprovednotransportersubstrateDetails
Gadoxetic acidapprovednotransportersubstrateDetails