ABCC4 (ATP binding cassette subfamily C member 4)

Gene

• Entrez ID: 10257
• Gene name: ATP binding cassette subfamily C member 4
• Gene symbol: ABCC4
• Synonyms: MOAT-B, MOATB, MRP4
• Chromosome: 13
• Chromosome location: 13q32.1
• Summary: The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MRP subfamily which is involved in multi-drug resistance. This family member plays a role in cellular detoxification as a pump for its substrate, organic anions. It may also function in prostaglandin-mediated cAMP signaling in ciliogenesis. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Sep 2014]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs1751034	C>G,T	Drug-response	Coding sequence variant, genic downstream transcript variant, synonymous variant, missense variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT004989	hsa-miR-125b-5p	Microarray	17891175
MIRT020794	hsa-miR-155-5p	Proteomics	18668040
MIRT023897	hsa-miR-1-3p	Proteomics	18668040
MIRT031811	hsa-miR-16-5p	Proteomics	18668040
MIRT043124	hsa-miR-324-5p	CLASH	23622248
MIRT046379	hsa-miR-23b-3p	CLASH	23622248
MIRT527066	hsa-miR-3924	PAR-CLIP	22012620
MIRT527067	hsa-miR-98-3p	PAR-CLIP	22012620
MIRT527068	hsa-let-7f-1-3p	PAR-CLIP	22012620
MIRT527069	hsa-let-7b-3p	PAR-CLIP	22012620
MIRT527070	hsa-let-7a-3p	PAR-CLIP	22012620
MIRT527071	hsa-miR-8064	PAR-CLIP	22012620
MIRT527072	hsa-miR-7853-5p	PAR-CLIP	22012620
MIRT527073	hsa-miR-105-5p	PAR-CLIP	22012620
MIRT527074	hsa-miR-4666a-3p	PAR-CLIP	22012620
MIRT527075	hsa-miR-381-3p	PAR-CLIP	22012620
MIRT527076	hsa-miR-300	PAR-CLIP	22012620
MIRT527077	hsa-miR-1277-5p	PAR-CLIP	22012620
MIRT527078	hsa-miR-7-2-3p	PAR-CLIP	22012620
MIRT527079	hsa-miR-7-1-3p	PAR-CLIP	22012620

Transcription factors

Transcription factor	Regulation	Reference
NR1H4	Repression	22291955

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0002576	Process	Platelet degranulation	TAS
GO:0005515	Function	Protein binding	IPI	29146910
GO:0005524	Function	ATP binding	IEA
GO:0005886	Component	Plasma membrane	IBA	21873635
GO:0005886	Component	Plasma membrane	IDA	15297306, 18619525, 23137377, 25173977, 28112518
GO:0005886	Component	Plasma membrane	TAS
GO:0010243	Process	Response to organonitrogen compound	IEA
GO:0014070	Process	Response to organic cyclic compound	IEA
GO:0015216	Function	Purine nucleotide transmembrane transporter activity	IMP	25986174
GO:0015431	Function	ABC-type glutathione S-conjugate transporter activity	IDA	17959747
GO:0015562	Function	Efflux transmembrane transporter activity	IMP	25986174
GO:0015662	Function	Ion transmembrane transporter activity, phosphorylative mechanism	TAS
GO:0016020	Component	Membrane	HDA	19946888
GO:0016020	Component	Membrane	IBA	21873635
GO:0016020	Component	Membrane	IDA	15297306
GO:0016021	Component	Integral component of membrane	IEA
GO:0016323	Component	Basolateral plasma membrane	IDA	24130369, 25986174, 31791063
GO:0016323	Component	Basolateral plasma membrane	ISS	18619525
GO:0016324	Component	Apical plasma membrane	IDA	11856762, 25986174, 31791063
GO:0016404	Function	15-hydroxyprostaglandin dehydrogenase (NAD+) activity	NAS	7557451
GO:0016887	Function	ATPase activity	IEA
GO:0031088	Component	Platelet dense granule membrane	IDA	15297306
GO:0031088	Component	Platelet dense granule membrane	TAS
GO:0032310	Process	Prostaglandin secretion	IDA	25173977
GO:0038183	Process	Bile acid signaling pathway	IEA
GO:0042493	Process	Response to drug	IEA
GO:0042626	Function	ATPase-coupled transmembrane transporter activity	IBA	21873635
GO:0042626	Function	ATPase-coupled transmembrane transporter activity	IDA	15364914
GO:0042908	Process	Xenobiotic transport	IEA
GO:0042910	Function	Xenobiotic transmembrane transporter activity	IDA	11856762
GO:0042910	Function	Xenobiotic transmembrane transporter activity	IMP	25986174
GO:0048661	Process	Positive regulation of smooth muscle cell proliferation	IEA
GO:0055085	Process	Transmembrane transport	IBA	21873635
GO:0055085	Process	Transmembrane transport	TAS
GO:0060271	Process	Cilium assembly	IMP	25173977
GO:0070730	Process	CAMP transport	IDA	11856762
GO:0070730	Process	CAMP transport	IMP	25986174
GO:0071716	Process	Leukotriene transport	IDA	17959747
GO:0098591	Component	External side of apical plasma membrane	ISS	18619525
GO:0098656	Process	Anion transmembrane transport	IEA
GO:0140115	Process	Export across plasma membrane	IMP	25986174
GO:0150104	Process	Transport across blood-brain barrier	NAS	26590417, 30280653

Other IDs

• MIM: 605250
• HGNC: 55
• e!Ensembl: ENSG00000125257

Protein

• UniProt ID: O15439
• Protein name: ATP-binding cassette sub-family C member 4 (EC 7.6.2.-) (EC 7.6.2.2) (EC 7.6.2.3) (MRP/cMOAT-related ABC transporter) (Multi-specific organic anion transporter B) (MOAT-B) (Multidrug resistance-associated protein 4)
• Protein 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:12883481, PubMed:12523936, PubMed:12835412, 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:12883481, PubMed:12523936, PubMed:16282361). Transports a wide range of drugs and their metabolites, including anticancer, antiviral and antibiotics molecules (PubMed:11856762, PubMed:12105214, PubMed:15454390, PubMed:18300232, PubMed:17344354). Confers resistance to anticancer agents such as methotrexate (PubMed:11106685).
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00664	ABC_membrane	92 → 365	ABC transporter transmembrane region	Family
  PF00005	ABC_tran	428 → 563	ABC transporter	Domain
  PF00664	ABC_membrane	714 → 993	ABC transporter transmembrane region	Family
  PF00005	ABC_tran	1058 → 1205	ABC transporter	Domain

• Sequence:

  MLPVYQEVKPNPLQDANLCSRVFFWWLNPLFKIGHKRRLEEDDMYSVLPEDRSQHLGEEL
  QGFWDKEVLRAENDAQKPSLTRAIIKCYWKSYLVLGIFTLIEESAKVIQPIFLGKIINYF
  ENYDPMDSVALNTAYAYATVLTFCTLILAILHHLYFYHVQCAGMRLRVAMCHMIYRKALR
  LSNMAMGKTTTGQIVNLLSNDVNKFDQVTVFLHFLWAGPLQAIAVTALLWMEIGISCLAG
  MAVLIILLPLQSCFGKLFSSLRSKTATFTDARIRTMNEVITGIRIIKMYAWEKSFSNLIT
  NLRKKEISKILRSSCLRGMNLASFFSASKIIVFVTFTTYVLLGSVITASRVFVAVTLYGA
  VRLTVTLFFPSAIERVSEAIVSIRRIQTFLLLDEISQRNRQLPSDGKKMVHVQDFTAFWD
  KASETPTLQGLSFTVRPGELLAVVGPVGAGKSSLLSAVLGELAPSHGLVSVHGRIAYVSQ
  QPWVFSGTLRSNILFGKKYEKERYEKVIKACALKKDLQLLEDGDLTVIGDRGTTLSGGQK
  ARVNLARAVYQDADIYLLDDPLSAVDAEVSRHLFELCICQILHEKITILVTHQLQYLKAA
  SQILILKDGKMVQKGTYTEFLKSGIDFGSLLKKDNEESEQPPVPGTPTLRNRTFSESSVW
  SQQSSRPSLKDGALESQDTENVPVTLSEENRSEGKVGFQAYKNYFRAGAHWIVFIFLILL
  NTAAQVAYVLQDWWLSYWANKQSMLNVTVNGGGNVTEKLDLNWYLGIYSGLTVATVLFGI
  ARSLLVFYVLVNSSQTLHNKMFESILKAPVLFFDRNPIGRILNRFSKDIGHLDDLLPLTF
  LDFIQTLLQVVGVVSVAVAVIPWIAIPLVPLGIIFIFLRRYFLETSRDVKRLESTTRSPV
  FSHLSSSLQGLWTIRAYKAEERCQELFDAHQDLHSEAWFLFLTTSRWFAVRLDAICAMFV
  IIVAFGSLILAKTLDAGQVGLALSYALTLMGMFQWCVRQSAEVENMMISVERVIEYTDLE
  KEAPWEYQKRPPPAWPHEGVIIFDNVNFMYSPGGPLVLKHLTALIKSQEKVGIVGRTGAG
  KSSLISALFRLSEPEGKIWIDKILTTEIGLHDLRKKMSIIPQEPVLFTGTMRKNLDPFNE
  HTDEELWNALQEVQLKETIEDLPGKMDTELAESGSNFSVGQRQLVCLARAILRKNQILII
  DEATANVDPRTDELIQKKIREKFAHCTVLTIAHRLNTIIDSDKIMVLDSGRLKEYDEPYV
  LLQNKESLFYKMVQQLGKAEAAALTETAKQVYFKRNYPHIGHTDHMVTNTSNGQPSTLTI
  FETAL

• Sequence length: 1325