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    ABCC4 ATP binding cassette subfamily C member 4 (PEL blood group) [ Homo sapiens (human) ]

    Gene ID: 10257, updated on 2-Nov-2024

    Summary

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    Official Symbol
    ABCC4provided by HGNC
    Official Full Name
    ATP binding cassette subfamily C member 4 (PEL blood group)provided by HGNC
    Primary source
    HGNC:HGNC:55
    See related
    Ensembl:ENSG00000125257 MIM:605250; AllianceGenome:HGNC:55
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    MRP4; MOATB; MOAT-B
    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]
    Expression
    Broad expression in prostate (RPKM 22.4), urinary bladder (RPKM 9.3) and 16 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See ABCC4 in Genome Data Viewer
    Location:
    13q32.1
    Exon count:
    35
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 13 NC_000013.11 (95019835..95301451, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 13 NC_060937.1 (94223430..94506029, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 13 NC_000013.10 (95672089..95953705, complement)

    Chromosome 13 - NC_000013.11Genomic Context describing neighboring genes Neighboring gene VISTA enhancers hs189 and hs341 Neighboring gene long intergenic non-protein coding RNA 557 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr13:95648475-95649263 Neighboring gene RNA, U6 small nuclear 62, pseudogene Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7867 Neighboring gene NANOG hESC enhancer GRCh37_chr13:95826697-95827198 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7868 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr13:95845687-95846187 Neighboring gene H3K27ac hESC enhancer GRCh37_chr13:95856177-95856677 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr13:95861642-95862841 Neighboring gene Sharpr-MPRA regulatory region 4491 Neighboring gene small nucleolar RNA, C/D box 13G Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7869 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7870 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7871 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7872 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5436 Neighboring gene uncharacterized LOC124903192 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7873 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7874 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7875 Neighboring gene uncharacterized LOC102724149 Neighboring gene H3K27ac hESC enhancer GRCh37_chr13:95953650-95954424 Neighboring gene RNY3 pseudogene 8 Neighboring gene RNY4 pseudogene 27

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Multidrug Resistance Protein-4 Influences Aspirin Toxicity in Human Cell Line. Massimi I, et al. Mediators Inflamm, 2015. PMID 26491233, Free PMC Article
    2. A novel pathway for arsenic elimination: human multidrug resistance protein 4 (MRP4/ABCC4) mediates cellular export of dimethylarsinic acid (DMAV) and the diglutathione conjugate of monomethylarsonous acid (MMAIII). Banerjee M, et al. Mol Pharmacol, 2014 Aug. PMID 24870404
    3. Aspirin influences megakaryocytic gene expression leading to up-regulation of multidrug resistance protein-4 in human platelets. Massimi I, et al. Br J Clin Pharmacol, 2014 Dec. PMID 24902864, Free PMC Article
    4. Celecoxib induces MRP-4 in lung cancer cells: therapeutic implications. Gradilone A, et al. J Clin Oncol, 2007 Sep 20. PMID 17878487
    5. Role of multidrug resistance-associated protein 4 in the basolateral efflux of hepatically derived enalaprilat. Ferslew BC, et al. Drug Metab Dispos, 2014 Sep. PMID 24958844, Free PMC Article

    See all (237) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. ABCC4 impacts megakaryopoiesis and protects megakaryocytes against 6-mercaptopurine induced cytotoxicity.
      Title: ABCC4 impacts megakaryopoiesis and protects megakaryocytes against 6-mercaptopurine induced cytotoxicity.
    2. Structural and mechanistic basis of substrate transport by the multidrug transporter MRP4.
      Title: Structural and mechanistic basis of substrate transport by the multidrug transporter MRP4.
    3. m6A-modified circABCC4 promotes stemness and metastasis of prostate cancer by recruiting IGF2BP2 to increase stability of CCAR1.
      Title: m6A-modified circABCC4 promotes stemness and metastasis of prostate cancer by recruiting IGF2BP2 to increase stability of CCAR1.
    4. Specific inhibition of the transporter MRP4/ABCC4 affects multiple signaling pathways and thrombus formation in human platelets.
      Title: Specific inhibition of the transporter MRP4/ABCC4 affects multiple signaling pathways and thrombus formation in human platelets.
    5. Founder genetic variants of ABCC4 and ABCC11 in the Japanese population are not associated with the development of subacute myelo-optico-neuropathy (SMON).
      Title: Founder genetic variants of ABCC4 and ABCC11 in the Japanese population are not associated with the development of subacute myelo-optico-neuropathy (SMON).
    6. Drug resistance biomarker ABCC4 of selinexor and immune feature in multiple myeloma.
      Title: Drug resistance biomarker ABCC4 of selinexor and immune feature in multiple myeloma.
    7. IL-10 contributes to gemcitabine resistance in extranodal NK/T-cell lymphoma cells via ABCC4.
      Title: IL-10 contributes to gemcitabine resistance in extranodal NK/T-cell lymphoma cells via ABCC4.
    8. ABCC4 single-nucleotide polymorphisms as markers of tenofovir disoproxil fumarate-induced kidney impairment.
      Title: ABCC4 single-nucleotide polymorphisms as markers of tenofovir disoproxil fumarate-induced kidney impairment.
    9. In-vitro characterization of coding variants with predicted functional implications in the efflux transporter multidrug resistance protein 4 (MRP4, ABCC4).
      Title: In-vitro characterization of coding variants with predicted functional implications in the efflux transporter multidrug resistance protein 4 (MRP4, ABCC4).
    10. The Daily Expression of ABCC4 at the BCSFB Affects the Transport of Its Substrate Methotrexate.
      Title: The Daily Expression of ABCC4 at the BCSFB Affects the Transport of Its Substrate Methotrexate.
    Submit: New GeneRIF Correction See all GeneRIFs (169)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    EBI GWAS Catalog

    Description
    A genome-wide association study of breast and prostate cancer in the NHLBI's Framingham Heart Study.
    EBI GWAS Catalog
    A genome-wide association study of survival in small-cell lung cancer patients treated with irinotecan plus cisplatin chemotherapy.
    EBI GWAS Catalog
    An atlas of genetic influences on human blood metabolites.
    EBI GWAS Catalog
    Genome-wide association analyses of child genotype effects and parent-of-origin effects in specific language impairment.
    EBI GWAS Catalog
    Joint influence of small-effect genetic variants on human longevity.
    EBI GWAS Catalog
    New gene functions in megakaryopoiesis and platelet formation.
    EBI GWAS Catalog

    Variation

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    See Variation Viewer (GRCh37.p13)

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • EST170205

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables 15-hydroxyprostaglandin dehydrogenase (NAD+) activity NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    enables ABC-type bile acid transporter activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables ABC-type glutathione S-conjugate transporter activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables ABC-type transporter activity TAS
    Traceable Author Statement
    more info
    		  
    enables ABC-type xenobiotic transporter activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables ATP binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables ATP hydrolysis activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables ATPase-coupled inorganic anion transmembrane transporter activity TAS
    Traceable Author Statement
    more info
    		  
    enables ATPase-coupled transmembrane transporter activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables ATPase-coupled transmembrane transporter activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables ATPase-coupled transmembrane transporter activity TAS
    Traceable Author Statement
    more info
    		  
    enables efflux transmembrane transporter activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables glutathione transmembrane transporter activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables guanine nucleotide transmembrane transporter activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables prostaglandin transmembrane transporter activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables purine nucleotide transmembrane transporter activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables urate transmembrane transporter activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables xenobiotic transmembrane transporter activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables xenobiotic transmembrane transporter activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in bile acid and bile salt transport IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in cAMP transport IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in cAMP transport IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    acts_upstream_of_or_within cilium assembly IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in export across plasma membrane IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in glutathione transmembrane transport IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in guanine nucleotide transmembrane transport IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in leukotriene transport IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in monoatomic anion transmembrane transport IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in platelet degranulation TAS
    Traceable Author Statement
    more info
    		  
    acts_upstream_of_or_within prostaglandin secretion IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in prostaglandin transport IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in transmembrane transport IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in transmembrane transport TAS
    Traceable Author Statement
    more info
    		  
    involved_in transport across blood-brain barrier NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in urate transport IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in xenobiotic metabolic process TAS
    Traceable Author Statement
    more info
    		  
    involved_in xenobiotic transmembrane transport TAS
    Traceable Author Statement
    more info
    		  
    Component Evidence Code Pubs
    located_in Golgi apparatus IDA
    Inferred from Direct Assay
    more info
    		  
    located_in apical plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in basolateral plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in external side of apical plasma membrane ISS
    Inferred from Sequence or Structural Similarity
    more info
    		 PubMed 
    located_in membrane HDA PubMed 
    located_in membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in nucleolus IDA
    Inferred from Direct Assay
    more info
    		  
    is_active_in plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
    		  
    located_in platelet dense granule membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in platelet dense granule membrane TAS
    Traceable Author Statement
    more info
    		  

    General protein information

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    Preferred Names
    ATP-binding cassette sub-family C member 4
    Names
    MRP/cMOAT-related ABC transporter
    bA464I2.1 (ATP-binding cassette, sub-family C (CFTR/MRP), member 4)
    canalicular multispecific organic anion transporter (ABC superfamily)
    multi-specific organic anion transporter B
    multidrug resistance-associated protein 4
    NP_001098985.1
    NP_001288758.1
    NP_001288759.1
    NP_005836.2
    XP_016875809.1
    XP_047285990.1
    XP_047285991.1
    XP_054229974.1
    XP_054229975.1
    XP_054229976.1

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_050651.2 RefSeqGene

      Range
      4996..286612
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_1183

    mRNA and Protein(s)

    1. NM_001105515.3 → NP_001098985.1  ATP-binding cassette sub-family C member 4 isoform 2

      See identical proteins and their annotated locations for NP_001098985.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks several 3' exons but contains an alternate 3' terminal exon, and it thus differs in the 3' coding region and 3' UTR, compared to variant 1. The encoded isoform (2) has a distinct and shorter C-terminus, compared to isoform 1.
      Source sequence(s)
      AK290317, AL356257, BC041560, BX113883, CN410193
      Consensus CDS
      CCDS45061.1
      UniProtKB/TrEMBL
      A8K2Q2
      Related
      ENSP00000487081.1, ENST00000629385.1
      Conserved Domains (3) summary
      cd03250
      Location:410 → 610
      ABCC_MRP_domain1; ATP-binding cassette domain 1 of multidrug resistance-associated protein, subfamily C
      COG1132
      Location:90 → 633
      MdlB; ABC-type multidrug transport system, ATPase and permease component [Defense mechanisms]
      cl00549
      Location:96 → 365
      ABC_membrane; ABC transporter transmembrane region

    2. NM_001301829.2 → NP_001288758.1  ATP-binding cassette sub-family C member 4 isoform 3

      See identical proteins and their annotated locations for NP_001288758.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks an alternate in-frame exon in the central coding region, compared to variant 1, resulting in an isoform (3) that is shorter than isoform 1.
      Source sequence(s)
      AL139381, AL157818, AL356257
      Consensus CDS
      CCDS86356.1
      UniProtKB/Swiss-Prot
      O15439
      UniProtKB/TrEMBL
      A8K2Q2
      Related
      ENSP00000494751.1, ENST00000646439.1
      Conserved Domains (5) summary
      cd03244
      Location:992 → 1211
      ABCC_MRP_domain2; ATP-binding cassette domain 2 of multidrug resistance-associated protein
      cd03250
      Location:410 → 610
      ABCC_MRP_domain1; ATP-binding cassette domain 1 of multidrug resistance-associated protein, subfamily C
      TIGR01271
      Location:11 → 1222
      CFTR_protein; cystic fibrosis transmembrane conductor regulator (CFTR)
      pfam00664
      Location:677 → 944
      ABC_membrane; ABC transporter transmembrane region
      cl00549
      Location:96 → 365
      ABC_membrane; ABC transporter transmembrane region

    3. NM_001301830.2 → NP_001288759.1  ATP-binding cassette sub-family C member 4 isoform 4

      See identical proteins and their annotated locations for NP_001288759.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) lacks an alternate in-frame exon in the 5' coding region, and also lacks several 3' exons but contains an alternate 3' terminal exon, and it thus differs in the 3' coding region and 3' UTR, compared to variant 1. The encoded isoform (4) has a distinct and shorter C-terminus, compared to isoform 1.
      Source sequence(s)
      AK290317, AK296247, AL356257, BX113883, CN410193
      Consensus CDS
      CCDS76643.1
      UniProtKB/TrEMBL
      A8K2Q2
      Related
      ENSP00000442024.1, ENST00000536256.3
      Conserved Domains (4) summary
      cd03250
      Location:335 → 535
      ABCC_MRP_domain1; ATP-binding cassette domain 1 of multidrug resistance-associated protein, subfamily C
      COG1131
      Location:353 → 596
      CcmA; ABC-type multidrug transport system, ATPase component [Defense mechanisms]
      COG1132
      Location:639 → 771
      MdlB; ABC-type multidrug transport system, ATPase and permease component [Defense mechanisms]
      cl00549
      Location:643 → 770
      ABC_membrane; ABC transporter transmembrane region

    4. NM_005845.5 → NP_005836.2  ATP-binding cassette sub-family C member 4 isoform 1

      See identical proteins and their annotated locations for NP_005836.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
      Source sequence(s)
      AL139381, AL157818, AL356257
      Consensus CDS
      CCDS9474.1
      UniProtKB/Swiss-Prot
      A9Z1Z7, B7Z3Q7, O15439, Q8IVZ4, Q8IZN6, Q8NEW8, Q9Y6J2
      Related
      ENSP00000494609.1, ENST00000645237.2
      Conserved Domains (5) summary
      cd03244
      Location:1039 → 1258
      ABCC_MRP_domain2; ATP-binding cassette domain 2 of multidrug resistance-associated protein
      cd03250
      Location:410 → 610
      ABCC_MRP_domain1; ATP-binding cassette domain 1 of multidrug resistance-associated protein, subfamily C
      TIGR01271
      Location:11 → 1269
      CFTR_protein; cystic fibrosis transmembrane conductor regulator (CFTR)
      pfam00664
      Location:718 → 991
      ABC_membrane; ABC transporter transmembrane region
      cl00549
      Location:96 → 365
      ABC_membrane; ABC transporter transmembrane region

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000013.11 Reference GRCh38.p14 Primary Assembly

      Range
      95019835..95301451 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047430034.1 → XP_047285990.1  ATP-binding cassette sub-family C member 4 isoform X1

    2. XM_047430035.1 → XP_047285991.1  ATP-binding cassette sub-family C member 4 isoform X2

    3. XM_017020320.3 → XP_016875809.1  ATP-binding cassette sub-family C member 4 isoform X3

      UniProtKB/TrEMBL
      A8K2Q2

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060937.1 Alternate T2T-CHM13v2.0

      Range
      94223430..94506029 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054373999.1 → XP_054229974.1  ATP-binding cassette sub-family C member 4 isoform X1

    2. XM_054374000.1 → XP_054229975.1  ATP-binding cassette sub-family C member 4 isoform X2

    3. XM_054374001.1 → XP_054229976.1  ATP-binding cassette sub-family C member 4 isoform X3

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O15439.3 GenPept UniProtKB/Swiss-Prot:O15439

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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