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Multidrug resistance-associated protein 4 (ATP-binding cassette sub-family C member 4) (MRP/cMOAT-related ABC transporter) (Multi-specific organic anion transporter B) (MOAT-B)

 MRP4_HUMAN              Reviewed;        1325 AA.
O15439; A9Z1Z7; B7Z3Q7; Q8IVZ4; Q8IZN6; Q8NEW8; Q9Y6J2;
15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
23-SEP-2008, sequence version 3.
25-OCT-2017, entry version 176.
RecName: Full=Multidrug resistance-associated protein 4;
AltName: Full=ATP-binding cassette sub-family C member 4;
AltName: Full=MRP/cMOAT-related ABC transporter;
AltName: Full=Multi-specific organic anion transporter B;
Short=MOAT-B;
Name=ABCC4; Synonyms=MRP4;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT ILE-18.
PubMed=9661885;
Lee K., Belinsky M.G., Bell D.W., Testa J.R., Kruh G.D.;
"Isolation of MOAT-B, a widely expressed multidrug resistance-
associated protein/canalicular multispecific organic anion
transporter-related transporter.";
Cancer Res. 58:2741-2747(1998).
[2]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT ILE-18.
PubMed=12105214; DOI=10.1074/jbc.M203262200;
Adachi M., Sampath J., Lan L.B., Sun D., Hargrove P., Flatley R.,
Tatum A., Edwards M.Z., Wezeman M., Matherly L., Drake R., Schuetz J.;
"Expression of MRP4 confers resistance to ganciclovir and compromises
bystander cell killing.";
J. Biol. Chem. 277:38998-39004(2002).
[3]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
TISSUE=Kidney;
Kato R., Ishikawa T.;
Submitted (DEC-2002) to the EMBL/GenBank/DDBJ databases.
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
TISSUE=Thalamus;
PubMed=14702039; DOI=10.1038/ng1285;
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 T.-O., 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. 36:40-45(2004).
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
PubMed=15057823; DOI=10.1038/nature02379;
Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L.,
Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E.,
Griffiths-Jones S., Jones M.C., Keenan S.J., Oliver K., Scott C.E.,
Ainscough R., Almeida J.P., Ambrose K.D., Andrews D.T.,
Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Bannerjee R.,
Barlow K.F., Bates K., Beasley H., Bird C.P., Bray-Allen S.,
Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P.,
Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M.,
Clegg S.C., Cobley V., Collins J.E., Corby N., Coville G.J.,
Deloukas P., Dhami P., Dunham I., Dunn M., Earthrowl M.E.,
Ellington A.G., Faulkner L., Frankish A.G., Frankland J., French L.,
Garner P., Garnett J., Gilbert J.G.R., Gilson C.J., Ghori J.,
Grafham D.V., Gribble S.M., Griffiths C., Hall R.E., Hammond S.,
Harley J.L., Hart E.A., Heath P.D., Howden P.J., Huckle E.J.,
Hunt P.J., Hunt A.R., Johnson C., Johnson D., Kay M., Kimberley A.M.,
King A., Laird G.K., Langford C.J., Lawlor S., Leongamornlert D.A.,
Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., Martin S.,
Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S.,
Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I.,
Pelan S., Phillimore B., Porter K.M., Rice C.M., Searle S.,
Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Steward C.A.,
Sycamore N., Tester J., Thomas D.W., Tracey A., Tromans A., Tubby B.,
Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L.,
Wilming L., Wray P.W., Wright M.W., Young L., Coulson A., Durbin R.M.,
Hubbard T., Sulston J.E., Beck S., Bentley D.R., Rogers J., Ross M.T.;
"The DNA sequence and analysis of human chromosome 13.";
Nature 428:522-528(2004).
[6]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
Venter J.C.;
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
[7]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
TISSUE=Brain;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[8]
NUCLEOTIDE SEQUENCE [MRNA] OF 1155-1316 (ISOFORMS 1/2).
TISSUE=Brain;
PubMed=9270026;
Kool M., de Haas M., Scheffer G.L., Scheper R.J., van Eijk M.J.,
Juijn J.A., 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. 57:3537-3547(1997).
[9]
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Cervix carcinoma;
PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
Mann M.;
"Global, in vivo, and site-specific phosphorylation dynamics in
signaling networks.";
Cell 127:635-648(2006).
[10]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-646, AND IDENTIFICATION
BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Cervix carcinoma;
PubMed=18669648; DOI=10.1073/pnas.0805139105;
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
Elledge S.J., Gygi S.P.;
"A quantitative atlas of mitotic phosphorylation.";
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
[11]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-646, AND IDENTIFICATION
BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Leukemic T-cell;
PubMed=19690332; DOI=10.1126/scisignal.2000007;
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
Rodionov V., Han D.K.;
"Quantitative phosphoproteomic analysis of T cell receptor signaling
reveals system-wide modulation of protein-protein interactions.";
Sci. Signal. 2:RA46-RA46(2009).
[12]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-646, AND IDENTIFICATION
BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Cervix carcinoma;
PubMed=20068231; DOI=10.1126/scisignal.2000475;
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
Mann M.;
"Quantitative phosphoproteomics reveals widespread full
phosphorylation site occupancy during mitosis.";
Sci. Signal. 3:RA3-RA3(2010).
[13]
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
PubMed=21269460; DOI=10.1186/1752-0509-5-17;
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
"Initial characterization of the human central proteome.";
BMC Syst. Biol. 5:17-17(2011).
[14]
INTERACTION WITH SNX27.
PubMed=22411990; DOI=10.1074/jbc.M111.337931;
Hayashi H., Naoi S., Nakagawa T., Nishikawa T., Fukuda H.,
Imajoh-Ohmi S., Kondo A., Kubo K., Yabuki T., Hattori A., Hirouchi M.,
Sugiyama Y.;
"Sorting nexin 27 interacts with multidrug resistance-associated
protein 4 (MRP4) and mediates internalization of MRP4.";
J. Biol. Chem. 287:15054-15065(2012).
[15]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-646; THR-648; SER-664
AND SER-668, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
ANALYSIS].
TISSUE=Cervix carcinoma, and Erythroleukemia;
PubMed=23186163; DOI=10.1021/pr300630k;
Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
Mohammed S.;
"Toward a comprehensive characterization of a human cancer cell
phosphoproteome.";
J. Proteome Res. 12:260-271(2013).
[16]
VARIANTS CYS-556; ILE-776; ILE-820; PHE-854 AND VAL-866, AND
CHARACTERIZATION OF VARIANTS TRP-187; ASN-304; GLU-487; CYS-556;
LYS-757; ILE-776; ILE-820; PHE-854; VAL-866 AND MET-1142.
PubMed=18300232; DOI=10.1002/humu.20694;
Janke D., Mehralivand S., Strand D., Goedtel-Armbrust U.,
Habermeier A., Gradhand U., Fischer C., Toliat M.R., Fritz P.,
Zanger U.M., Schwab M., Fromm M.F., Nuernberg P., Wojnowski L.,
Closs E.I., Lang T.;
"6-mercaptopurine and 9-(2-phosphonyl-methoxyethyl) adenine (PMEA)
transport altered by two missense mutations in the drug transporter
gene ABCC4.";
Hum. Mutat. 29:659-669(2008).
[17]
VARIANT LYS-757.
PubMed=20547088; DOI=10.1016/j.legalmed.2010.04.001;
Yuasa I., Umetsu K., Matsusue A., Nishimukai H., Harihara S.,
Fukumori Y., Saitou N., Jin F., Chattopadhyay P.K., Henke L.,
Henke J.;
"A Japanese-specific allele in the GALNT11 gene.";
Leg. Med. 12:208-211(2010).
-!- FUNCTION: May be an organic anion pump relevant to cellular
detoxification.
-!- SUBUNIT: Interacts (via PDZ-binding motif) with SNX27 (via PDZ
domain). {ECO:0000269|PubMed:22411990}.
-!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=4;
Name=1;
IsoId=O15439-1; Sequence=Displayed;
Name=2;
IsoId=O15439-2; Sequence=VSP_035426;
Name=3;
IsoId=O15439-3; Sequence=VSP_043283, VSP_043284;
Note=No experimental confirmation available.;
Name=4;
IsoId=O15439-4; Sequence=VSP_057413, VSP_043283, VSP_043284;
Note=No experimental confirmation available.;
-!- TISSUE SPECIFICITY: Widely expressed, with particularly high
levels in prostate, but is barely detectable in liver.
-!- SIMILARITY: Belongs to the ABC transporter superfamily. ABCC
family. Conjugate transporter (TC 3.A.1.208) subfamily.
{ECO:0000305}.
-!- WEB RESOURCE: Name=ABCMdb; Note=Database for mutations in ABC
proteins;
URL="http://abcmutations.hegelab.org/proteinDetails?uniprot_id=O15439";
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EMBL; AF071202; AAC27076.1; -; mRNA.
EMBL; AY081219; AAL88745.1; -; mRNA.
EMBL; AY207008; AAO37649.1; -; mRNA.
EMBL; AF541977; AAN17334.1; -; mRNA.
EMBL; AK296247; BAH12293.1; -; mRNA.
EMBL; AL157818; CAC36037.2; -; Genomic_DNA.
EMBL; AL139381; CAC36037.2; JOINED; Genomic_DNA.
EMBL; AL356257; CAC36037.2; JOINED; Genomic_DNA.
EMBL; AL139381; CAI16589.1; -; Genomic_DNA.
EMBL; AL157818; CAI16589.1; JOINED; Genomic_DNA.
EMBL; AL356257; CAI16589.1; JOINED; Genomic_DNA.
EMBL; AL356257; CAI16722.1; -; Genomic_DNA.
EMBL; AL139381; CAI16722.1; JOINED; Genomic_DNA.
EMBL; AL157818; CAI16722.1; JOINED; Genomic_DNA.
EMBL; AL359750; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; CH471085; EAX08951.1; -; Genomic_DNA.
EMBL; CH471085; EAX08950.1; -; Genomic_DNA.
EMBL; BC041560; AAH41560.1; -; mRNA.
EMBL; U83660; AAB71757.1; -; mRNA.
CCDS; CCDS45061.1; -. [O15439-3]
CCDS; CCDS76643.1; -. [O15439-4]
CCDS; CCDS9474.1; -. [O15439-1]
RefSeq; NP_001098985.1; NM_001105515.2. [O15439-3]
RefSeq; NP_001288758.1; NM_001301829.1. [O15439-2]
RefSeq; NP_001288759.1; NM_001301830.1. [O15439-4]
RefSeq; NP_005836.2; NM_005845.4. [O15439-1]
UniGene; Hs.508423; -.
ProteinModelPortal; O15439; -.
SMR; O15439; -.
BioGrid; 115551; 23.
IntAct; O15439; 6.
STRING; 9606.ENSP00000366084; -.
BindingDB; O15439; -.
ChEMBL; CHEMBL1743128; -.
DrugBank; DB00718; Adefovir Dipivoxil.
DrugBank; DB00770; Alprostadil.
DrugBank; DB01076; Atorvastatin.
DrugBank; DB01327; Cefazolin.
DrugBank; DB00482; Celecoxib.
DrugBank; DB02659; Cholic Acid.
DrugBank; DB00286; Conjugated Equine Estrogens.
DrugBank; DB02527; Cyclic Adenosine Monophosphate.
DrugBank; DB00586; Diclofenac.
DrugBank; DB00917; Dinoprostone.
DrugBank; DB00975; Dipyridamole.
DrugBank; DB00544; Fluorouracil.
DrugBank; DB00712; Flurbiprofen.
DrugBank; DB00158; Folic Acid.
DrugBank; DB08884; Gadoxetic acid.
DrugBank; DB00143; Glutathione.
DrugBank; DB01050; Ibuprofen.
DrugBank; DB00328; Indomethacin.
DrugBank; DB01009; Ketoprofen.
DrugBank; DB00709; Lamivudine.
DrugBank; DB00814; Meloxicam.
DrugBank; DB01033; Mercaptopurine.
DrugBank; DB00563; Methotrexate.
DrugBank; DB00731; Nateglinide.
DrugBank; DB00198; Oseltamivir.
DrugBank; DB01032; Probenecid.
DrugBank; DB00533; Rofecoxib.
DrugBank; DB01098; Rosuvastatin.
DrugBank; DB00203; Sildenafil.
DrugBank; DB00398; Sorafenib.
DrugBank; DB01138; Sulfinpyrazone.
DrugBank; DB01268; Sunitinib.
DrugBank; DB04348; Taurocholic Acid.
DrugBank; DB00300; Tenofovir.
DrugBank; DB00352; Tioguanine.
DrugBank; DB01586; Ursodeoxycholic acid.
DrugBank; DB00661; Verapamil.
DrugBank; DB00495; Zidovudine.
GuidetoPHARMACOLOGY; 782; -.
TCDB; 3.A.1.208.7; the atp-binding cassette (abc) superfamily.
iPTMnet; O15439; -.
PhosphoSitePlus; O15439; -.
SwissPalm; O15439; -.
BioMuta; ABCC4; -.
EPD; O15439; -.
MaxQB; O15439; -.
PaxDb; O15439; -.
PeptideAtlas; O15439; -.
PRIDE; O15439; -.
Ensembl; ENST00000376887; ENSP00000366084; ENSG00000125257. [O15439-1]
Ensembl; ENST00000536256; ENSP00000442024; ENSG00000125257. [O15439-4]
Ensembl; ENST00000629385; ENSP00000487081; ENSG00000125257. [O15439-3]
GeneID; 10257; -.
KEGG; hsa:10257; -.
UCSC; uc001vmd.5; human. [O15439-1]
UCSC; uc010tih.2; human.
CTD; 10257; -.
DisGeNET; 10257; -.
EuPathDB; HostDB:ENSG00000125257.13; -.
GeneCards; ABCC4; -.
HGNC; HGNC:55; ABCC4.
HPA; HPA002476; -.
MalaCards; ABCC4; -.
MIM; 605250; gene.
neXtProt; NX_O15439; -.
OpenTargets; ENSG00000125257; -.
PharmGKB; PA397; -.
eggNOG; KOG0054; Eukaryota.
eggNOG; COG1132; LUCA.
GeneTree; ENSGT00880000137856; -.
HOVERGEN; HBG108314; -.
InParanoid; O15439; -.
KO; K05673; -.
OMA; REKMIGI; -.
OrthoDB; EOG091G00IN; -.
PhylomeDB; O15439; -.
TreeFam; TF105202; -.
Reactome; R-HSA-114608; Platelet degranulation.
Reactome; R-HSA-382556; ABC-family proteins mediated transport.
ChiTaRS; ABCC4; human.
GeneWiki; ABCC4; -.
GenomeRNAi; 10257; -.
PRO; PR:O15439; -.
Proteomes; UP000005640; Chromosome 13.
Bgee; ENSG00000125257; -.
CleanEx; HS_ABCC4; -.
Genevisible; O15439; HS.
GO; GO:0016323; C:basolateral plasma membrane; IDA:CACAO.
GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
GO; GO:0016020; C:membrane; IDA:UniProtKB.
GO; GO:0005886; C:plasma membrane; IDA:MGI.
GO; GO:0031088; C:platelet dense granule membrane; IDA:MGI.
GO; GO:0016404; F:15-hydroxyprostaglandin dehydrogenase (NAD+) activity; NAS:UniProtKB.
GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
GO; GO:0015662; F:ATPase activity, coupled to transmembrane movement of ions, phosphorylative mechanism; TAS:Reactome.
GO; GO:0042626; F:ATPase activity, coupled to transmembrane movement of substances; IBA:GO_Central.
GO; GO:0043225; F:ATPase-coupled anion transmembrane transporter activity; TAS:Reactome.
GO; GO:0060271; P:cilium assembly; IMP:MGI.
GO; GO:0002576; P:platelet degranulation; TAS:Reactome.
GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; IEA:Ensembl.
GO; GO:0032310; P:prostaglandin secretion; IDA:MGI.
GO; GO:0042493; P:response to drug; IEA:Ensembl.
GO; GO:0014070; P:response to organic cyclic compound; IEA:Ensembl.
GO; GO:0010243; P:response to organonitrogen compound; IEA:Ensembl.
GO; GO:0055085; P:transmembrane transport; IBA:GO_Central.
Gene3D; 1.20.1560.10; -; 2.
InterPro; IPR003593; AAA+_ATPase.
InterPro; IPR011527; ABC1_TM_dom.
InterPro; IPR036640; ABC1_TM_sf.
InterPro; IPR003439; ABC_transporter-like.
InterPro; IPR017871; ABC_transporter_CS.
InterPro; IPR030240; ABCC4.
InterPro; IPR027417; P-loop_NTPase.
PANTHER; PTHR24223:SF237; PTHR24223:SF237; 1.
Pfam; PF00664; ABC_membrane; 2.
Pfam; PF00005; ABC_tran; 2.
SMART; SM00382; AAA; 2.
SUPFAM; SSF52540; SSF52540; 2.
SUPFAM; SSF90123; SSF90123; 2.
PROSITE; PS50929; ABC_TM1F; 2.
PROSITE; PS00211; ABC_TRANSPORTER_1; 2.
PROSITE; PS50893; ABC_TRANSPORTER_2; 2.
1: Evidence at protein level;
Alternative splicing; ATP-binding; Complete proteome; Glycoprotein;
Membrane; Nucleotide-binding; Phosphoprotein; Polymorphism;
Reference proteome; Repeat; Transmembrane; Transmembrane helix;
Transport.
CHAIN 1 1325 Multidrug resistance-associated protein
4.
/FTId=PRO_0000093362.
TRANSMEM 93 113 Helical. {ECO:0000255|PROSITE-
ProRule:PRU00441}.
TRANSMEM 136 156 Helical. {ECO:0000255|PROSITE-
ProRule:PRU00441}.
TRANSMEM 207 227 Helical. {ECO:0000255|PROSITE-
ProRule:PRU00441}.
TRANSMEM 228 248 Helical. {ECO:0000255|PROSITE-
ProRule:PRU00441}.
TRANSMEM 328 348 Helical. {ECO:0000255|PROSITE-
ProRule:PRU00441}.
TRANSMEM 351 371 Helical. {ECO:0000255|PROSITE-
ProRule:PRU00441}.
TRANSMEM 440 460 Helical. {ECO:0000255|PROSITE-
ProRule:PRU00441}.
TRANSMEM 710 730 Helical. {ECO:0000255|PROSITE-
ProRule:PRU00441}.
TRANSMEM 771 791 Helical. {ECO:0000255|PROSITE-
ProRule:PRU00441}.
TRANSMEM 836 856 Helical. {ECO:0000255|PROSITE-
ProRule:PRU00441}.
TRANSMEM 858 878 Helical. {ECO:0000255|PROSITE-
ProRule:PRU00441}.
TRANSMEM 954 974 Helical. {ECO:0000255|PROSITE-
ProRule:PRU00441}.
TRANSMEM 977 997 Helical. {ECO:0000255|PROSITE-
ProRule:PRU00441}.
TRANSMEM 1038 1058 Helical. {ECO:0000255|PROSITE-
ProRule:PRU00441}.
DOMAIN 92 377 ABC transmembrane type-1 1.
{ECO:0000255|PROSITE-ProRule:PRU00441}.
DOMAIN 410 633 ABC transporter 1. {ECO:0000255|PROSITE-
ProRule:PRU00434}.
DOMAIN 714 1005 ABC transmembrane type-1 2.
{ECO:0000255|PROSITE-ProRule:PRU00441}.
DOMAIN 1041 1274 ABC transporter 2. {ECO:0000255|PROSITE-
ProRule:PRU00434}.
NP_BIND 445 452 ATP 1. {ECO:0000255|PROSITE-
ProRule:PRU00434}.
NP_BIND 1075 1082 ATP 2. {ECO:0000255|PROSITE-
ProRule:PRU00434}.
MOTIF 1322 1325 PDZ-binding.
MOD_RES 646 646 Phosphothreonine.
{ECO:0000244|PubMed:18669648,
ECO:0000244|PubMed:19690332,
ECO:0000244|PubMed:20068231,
ECO:0000244|PubMed:23186163}.
MOD_RES 648 648 Phosphothreonine.
{ECO:0000244|PubMed:23186163}.
MOD_RES 664 664 Phosphoserine.
{ECO:0000244|PubMed:23186163}.
MOD_RES 668 668 Phosphoserine.
{ECO:0000244|PubMed:23186163}.
CARBOHYD 651 651 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 690 690 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 746 746 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 754 754 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 792 792 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 1176 1176 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 1309 1309 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
VAR_SEQ 103 177 Missing (in isoform 4).
{ECO:0000303|PubMed:14702039}.
/FTId=VSP_057413.
VAR_SEQ 679 725 Missing (in isoform 2).
{ECO:0000303|Ref.3}.
/FTId=VSP_035426.
VAR_SEQ 846 859 TLLQVVGVVSVAVA -> RWDLAVLSWLVSNS (in
isoform 3 and isoform 4).
{ECO:0000303|PubMed:14702039,
ECO:0000303|PubMed:15489334}.
/FTId=VSP_043283.
VAR_SEQ 860 1325 Missing (in isoform 3 and isoform 4).
{ECO:0000303|PubMed:14702039,
ECO:0000303|PubMed:15489334}.
/FTId=VSP_043284.
VARIANT 18 18 L -> I (in dbSNP:rs11568681).
{ECO:0000269|PubMed:12105214,
ECO:0000269|PubMed:9661885}.
/FTId=VAR_046445.
VARIANT 78 78 P -> A (in dbSNP:rs11568689).
/FTId=VAR_029121.
VARIANT 171 171 C -> G (in dbSNP:rs4148460).
/FTId=VAR_046446.
VARIANT 184 184 M -> T (in dbSNP:rs45454092).
/FTId=VAR_020241.
VARIANT 187 187 G -> W (transport properties comparable
to wild-type; dbSNP:rs11568658).
{ECO:0000269|PubMed:18300232}.
/FTId=VAR_020242.
VARIANT 293 293 K -> E (in dbSNP:rs11568684).
/FTId=VAR_046447.
VARIANT 304 304 K -> N (transport properties comparable
to wild-type; dbSNP:rs2274407).
{ECO:0000269|PubMed:18300232}.
/FTId=VAR_022072.
VARIANT 356 356 T -> M (in dbSNP:rs11568701).
/FTId=VAR_046448.
VARIANT 403 403 P -> L (in dbSNP:rs11568705).
/FTId=VAR_029122.
VARIANT 487 487 G -> E (transport properties comparable
to wild-type; dbSNP:rs11568668).
{ECO:0000269|PubMed:18300232}.
/FTId=VAR_029123.
VARIANT 498 498 K -> E (in dbSNP:rs11568669).
/FTId=VAR_020243.
VARIANT 556 556 Y -> C (40% reduced expression level
compared to wild-type; higher transport
of 9-(2-phosphonyl-methoxyethyl) adenine
than wild-type; dbSNP:rs753414892).
{ECO:0000269|PubMed:18300232}.
/FTId=VAR_045684.
VARIANT 625 625 I -> M (in dbSNP:rs11568699).
/FTId=VAR_029124.
VARIANT 667 667 P -> L (in dbSNP:rs11568697).
/FTId=VAR_029125.
VARIANT 744 744 M -> V (in dbSNP:rs9282570).
/FTId=VAR_020244.
VARIANT 757 757 E -> K (10% reduced expression level
compared to wild-type; transport
properties comparable to wild-type;
dbSNP:rs3765534).
{ECO:0000269|PubMed:18300232,
ECO:0000269|PubMed:20547088}.
/FTId=VAR_022073.
VARIANT 776 776 V -> I (20% reduced expression level
compared to wild-type; significant lower
activity in 6-mercaptopurine transport
than wild-type; dbSNP:rs146708960).
{ECO:0000269|PubMed:18300232}.
/FTId=VAR_045685.
VARIANT 820 820 R -> I (transport properties comparable
to wild-type; dbSNP:rs11568659).
{ECO:0000269|PubMed:18300232}.
/FTId=VAR_045686.
VARIANT 854 854 V -> F (transport properties comparable
to wild-type; dbSNP:rs11568694).
{ECO:0000269|PubMed:18300232}.
/FTId=VAR_045687.
VARIANT 860 860 V -> M (in dbSNP:rs45477596).
/FTId=VAR_020245.
VARIANT 866 866 I -> V (transport properties comparable
to wild-type; dbSNP:rs139970608).
{ECO:0000269|PubMed:18300232}.
/FTId=VAR_045688.
VARIANT 900 900 V -> L (in dbSNP:rs45504892).
/FTId=VAR_020246.
VARIANT 1142 1142 T -> M (10% reduced expression level
compared to wild-type; transport
properties comparable to wild-type;
dbSNP:rs11568644).
{ECO:0000269|PubMed:18300232}.
/FTId=VAR_029126.
CONFLICT 703 703 N -> S (in Ref. 2; AAL88745).
{ECO:0000305}.
CONFLICT 757 757 E -> G (in Ref. 2; AAL88745).
{ECO:0000305}.
CONFLICT 893 893 E -> G (in Ref. 2; AAL88745).
{ECO:0000305}.
CONFLICT 1139 1139 N -> K (in Ref. 1; AAC27076).
{ECO:0000305}.
CONFLICT 1302 1302 H -> D (in Ref. 8; AAB71757).
{ECO:0000305}.
SEQUENCE 1325 AA; 149527 MW; BF2D53136B78C0BA CRC64;
MLPVYQEVKP NPLQDANLCS RVFFWWLNPL FKIGHKRRLE EDDMYSVLPE DRSQHLGEEL
QGFWDKEVLR AENDAQKPSL TRAIIKCYWK SYLVLGIFTL IEESAKVIQP IFLGKIINYF
ENYDPMDSVA LNTAYAYATV LTFCTLILAI LHHLYFYHVQ CAGMRLRVAM CHMIYRKALR
LSNMAMGKTT TGQIVNLLSN DVNKFDQVTV FLHFLWAGPL QAIAVTALLW MEIGISCLAG
MAVLIILLPL QSCFGKLFSS LRSKTATFTD ARIRTMNEVI TGIRIIKMYA WEKSFSNLIT
NLRKKEISKI LRSSCLRGMN LASFFSASKI IVFVTFTTYV LLGSVITASR VFVAVTLYGA
VRLTVTLFFP SAIERVSEAI VSIRRIQTFL LLDEISQRNR QLPSDGKKMV HVQDFTAFWD
KASETPTLQG LSFTVRPGEL LAVVGPVGAG KSSLLSAVLG ELAPSHGLVS VHGRIAYVSQ
QPWVFSGTLR SNILFGKKYE KERYEKVIKA CALKKDLQLL EDGDLTVIGD RGTTLSGGQK
ARVNLARAVY QDADIYLLDD PLSAVDAEVS RHLFELCICQ ILHEKITILV THQLQYLKAA
SQILILKDGK MVQKGTYTEF LKSGIDFGSL LKKDNEESEQ PPVPGTPTLR NRTFSESSVW
SQQSSRPSLK DGALESQDTE NVPVTLSEEN RSEGKVGFQA YKNYFRAGAH WIVFIFLILL
NTAAQVAYVL QDWWLSYWAN KQSMLNVTVN GGGNVTEKLD LNWYLGIYSG LTVATVLFGI
ARSLLVFYVL VNSSQTLHNK MFESILKAPV LFFDRNPIGR ILNRFSKDIG HLDDLLPLTF
LDFIQTLLQV VGVVSVAVAV IPWIAIPLVP LGIIFIFLRR YFLETSRDVK RLESTTRSPV
FSHLSSSLQG LWTIRAYKAE ERCQELFDAH QDLHSEAWFL FLTTSRWFAV RLDAICAMFV
IIVAFGSLIL AKTLDAGQVG LALSYALTLM GMFQWCVRQS AEVENMMISV ERVIEYTDLE
KEAPWEYQKR PPPAWPHEGV IIFDNVNFMY SPGGPLVLKH LTALIKSQEK VGIVGRTGAG
KSSLISALFR LSEPEGKIWI DKILTTEIGL HDLRKKMSII PQEPVLFTGT MRKNLDPFNE
HTDEELWNAL QEVQLKETIE DLPGKMDTEL AESGSNFSVG QRQLVCLARA ILRKNQILII
DEATANVDPR TDELIQKKIR EKFAHCTVLT IAHRLNTIID SDKIMVLDSG RLKEYDEPYV
LLQNKESLFY KMVQQLGKAE AAALTETAKQ VYFKRNYPHI GHTDHMVTNT SNGQPSTLTI
FETAL


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