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3.A.1.208.7
MRP4 (ABCC4); exporter of cyclic nucleotides (cAMP, cGMP and other nucleotide analogues, particularly purine analogues, methotrexate, bile acids, prostaglandins E1 and E2, reduced folates, 9-(2-phosphonylmethyoxyethyl)adenine, leukotrienes, estradiol 17-β-D-glucuronide) and drug sulfate conjugates (inhibited by nonsteroidal antiinflammatory drugs Reid et al., 2003; Rius et al., 2008)). When overexpressed, it can lower the intracellular concentration of nucleoside/nucleotide analogs, such as the antiviral compounds PMEA (9-(2-phosphonylmethoxyethyl)adenine) or ganciclovir, and of anticancer nucleobase analogs, such as 6-mercaptopurine, after their conversion into the respective nucleotides. MRP4 interacts directly with CFTR (3.A.1.202.1) to control Cl- secretion (Li et al., 2007). It also functions in urate elimination across the renal tubule apical membrane (Prestin et al. 2014). Thus, MRP4 is a broad specificity organic anion exporter (Ritter et al., 2005). MRP4 and CFTR together function in the regulation of cAMP and beta-adrenergic contraction in cardiac myocytes (Sellers et al., 2012). Amino acid changes can alter the uptake of drugs such as 6-mercaptopurine (6-MP) and 9-(2-phosphonyl methoxyethyl) adenine (PMEA) (Janke et al. 2008).

Accession Number:O15439
Protein Name:MRP4 aka ABCC4
Length:1325
Molecular Weight:149527.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:10
Location1 / Topology2 / Orientation3: Membrane1 / Multi-pass membrane protein2
Substrate Cyclic nucleotides, Nucleotide analogues, methotrexate, bile acids, Prostagland E1, Prostaglandin E2, Reduced folates, 9-(2-phosphonylmethyoxyethyl)adenine, Leukotrienes, Estradiol 17-beta-D-glucuronides, Drug sulfate conjugates

Cross database links:

Genevestigator: O15439
eggNOG: prNOG12442
HEGENOM: HBG758042
RefSeq: NP_001098985.1    NP_005836.2   
Entrez Gene ID: 10257   
Pfam: PF00664    PF00005   
OMIM: 605250  gene
KEGG: hsa:10257   

Gene Ontology

GO:0016021 C:integral to membrane
GO:0005624 C:membrane fraction
GO:0005886 C:plasma membrane
GO:0031088 C:platelet dense granule membrane
GO:0016404 F:15-hydroxyprostaglandin dehydrogenase (NAD+...
GO:0005524 F:ATP binding
GO:0042626 F:ATPase activity, coupled to transmembrane m...
GO:0005254 F:chloride channel activity
GO:0006811 P:ion transport
GO:0055085 P:transmembrane transport

References (8)

[1] “Isolation of MOAT-B, a widely expressed multidrug resistance-associated protein/canalicular multispecific organic anion transporter-related transporter.”  Lee K.et.al.   9661885
[2] “Expression of MRP4 confers resistance to ganciclovir and compromises bystander cell killing.”  Adachi M.et.al.   12105214
[3] “The DNA sequence and analysis of human chromosome 13.”  Dunham A.et.al.   15057823
[4] “Analysis of expression of cMOAT (MRP2), MRP3, MRP4, and MRP5, homologues of the multidrug resistance-associated protein gene (MRP1), in human cancer cell lines.”  Kool M.et.al.   9270026
[5] “Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.”  Olsen J.V.et.al.   17081983
[6] “A quantitative atlas of mitotic phosphorylation.”  Dephoure N.et.al.   18669648
[7] “Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.”  Mayya V.et.al.   19690332
[8] “6-mercaptopurine and 9-(2-phosphonyl-methoxyethyl) adenine (PMEA) transport altered by two missense mutations in the drug transporter gene ABCC4.”  Janke D.et.al.   18300232

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MLPVYQEVKP NPLQDANLCS RVFFWWLNPL FKIGHKRRLE EDDMYSVLPE DRSQHLGEEL 
61:	QGFWDKEVLR AENDAQKPSL TRAIIKCYWK SYLVLGIFTL IEESAKVIQP IFLGKIINYF 
121:	ENYDPMDSVA LNTAYAYATV LTFCTLILAI LHHLYFYHVQ CAGMRLRVAM CHMIYRKALR 
181:	LSNMAMGKTT TGQIVNLLSN DVNKFDQVTV FLHFLWAGPL QAIAVTALLW MEIGISCLAG 
241:	MAVLIILLPL QSCFGKLFSS LRSKTATFTD ARIRTMNEVI TGIRIIKMYA WEKSFSNLIT 
301:	NLRKKEISKI LRSSCLRGMN LASFFSASKI IVFVTFTTYV LLGSVITASR VFVAVTLYGA 
361:	VRLTVTLFFP SAIERVSEAI VSIRRIQTFL LLDEISQRNR QLPSDGKKMV HVQDFTAFWD 
421:	KASETPTLQG LSFTVRPGEL LAVVGPVGAG KSSLLSAVLG ELAPSHGLVS VHGRIAYVSQ 
481:	QPWVFSGTLR SNILFGKKYE KERYEKVIKA CALKKDLQLL EDGDLTVIGD RGTTLSGGQK 
541:	ARVNLARAVY QDADIYLLDD PLSAVDAEVS RHLFELCICQ ILHEKITILV THQLQYLKAA 
601:	SQILILKDGK MVQKGTYTEF LKSGIDFGSL LKKDNEESEQ PPVPGTPTLR NRTFSESSVW 
661:	SQQSSRPSLK DGALESQDTE NVPVTLSEEN RSEGKVGFQA YKNYFRAGAH WIVFIFLILL 
721:	NTAAQVAYVL QDWWLSYWAN KQSMLNVTVN GGGNVTEKLD LNWYLGIYSG LTVATVLFGI 
781:	ARSLLVFYVL VNSSQTLHNK MFESILKAPV LFFDRNPIGR ILNRFSKDIG HLDDLLPLTF 
841:	LDFIQTLLQV VGVVSVAVAV IPWIAIPLVP LGIIFIFLRR YFLETSRDVK RLESTTRSPV 
901:	FSHLSSSLQG LWTIRAYKAE ERCQELFDAH QDLHSEAWFL FLTTSRWFAV RLDAICAMFV 
961:	IIVAFGSLIL AKTLDAGQVG LALSYALTLM GMFQWCVRQS AEVENMMISV ERVIEYTDLE 
1021:	KEAPWEYQKR PPPAWPHEGV IIFDNVNFMY SPGGPLVLKH LTALIKSQEK VGIVGRTGAG 
1081:	KSSLISALFR LSEPEGKIWI DKILTTEIGL HDLRKKMSII PQEPVLFTGT MRKNLDPFNE 
1141:	HTDEELWNAL QEVQLKETIE DLPGKMDTEL AESGSNFSVG QRQLVCLARA ILRKNQILII 
1201:	DEATANVDPR TDELIQKKIR EKFAHCTVLT IAHRLNTIID SDKIMVLDSG RLKEYDEPYV 
1261:	LLQNKESLFY KMVQQLGKAE AAALTETAKQ VYFKRNYPHI GHTDHMVTNT SNGQPSTLTI 
1321:	FETAL