ABCC2 ATP binding cassette subfamily C member 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: ABCC2provided by HGNC
Official Full Name: ATP binding cassette subfamily C member 2provided by HGNC
Primary source: HGNC:HGNC:53
See related: Ensembl:ENSG00000023839 MIM:601107; Vega:OTTHUMG00000018895
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: DJS; MRP2; cMRP; ABC30; CMOAT
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 protein is expressed in the canalicular (apical) part of the hepatocyte and functions in biliary transport. Substrates include anticancer drugs such as vinblastine; therefore, this protein appears to contribute to drug resistance in mammalian cells. Several different mutations in this gene have been observed in patients with Dubin-Johnson syndrome (DJS), an autosomal recessive disorder characterized by conjugated hyperbilirubinemia. [provided by RefSeq, Jul 2008]
Orthologs: mouse all

Genomic context

See ABCC2 in Genome Data Viewer Map Viewer

Location:: 10q24.2

Exon count:: 34

Annotation release	Status	Assembly	Chr	Location
108	current	GRCh38.p7 (GCF_000001405.33)	10	NC_000010.11 (99782598..99853741)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	10	NC_000010.10 (101542457..101611662)

Chromosome 10 - NC_000010.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: 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 Jun 15 11:32:44 2016

Bibliography

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GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

genetic association studies in a population in France: Data that SNPs in ABCC2 are associated with regulation of secretion of endogenous organic anions; the 3 SNPs investigated (-24C>T, exon 1, rs717620; c.3972C>T, exon 28, rs3740066; c.1249G>A, exon 10, rs2273697) are associated with differential excretion of 35 of the 108 metabolites analyzed.
Title: Single nucleotide polymorphisms of ABCC2 modulate renal secretion of endogenous organic anions.
BCRP and MRP2 can mediate elimination of ochratoxin A from cells, reducing OTA toxicity.
Title: Ochratoxin A transport by the human breast cancer resistance protein (BCRP), multidrug resistance protein 2 (MRP2), and organic anion-transporting polypeptides 1A2, 1B1 and 2B1.
Four SNPs within the APOE cluster (rs7412, rs4420638), ABCC2 (rs2002042) and CELSR/SORT1/PSRC1 (rs646776), displayed a major impact on statin efficacy. The wGRS was significantly associated with lower LDL-C at age 75 and 80
Title: A genetic risk score is significantly associated with statin therapy response in the elderly population.
We analyzed 150 SNPs in eight key genes involved in vincristine pharmacokinetics and in 13 miRNAs that regulate them. We studied their correlation with neurotoxicity during induction phase in 152 ALL patients treated with LAL/SHOP protocols. The strongest associations with neurotoxicity were observed for two SNPs in ABCC2.
Title: Vincristine pharmacokinetics pathway and neurotoxicity during early phases of treatment in pediatric acute lymphoblastic leukemia.
In the present review we focus on the role of MRP2 in the apical membrane of the enterocytes, as an important component of this intestinal barrier, as well as on its regulation and provide a detailed compilation of significant contributions demonstrating that MRP2 expression and function vary under relevant physiological and pathophysiological conditions
Title: Physiological and pathophysiological factors affecting the expression and activity of the drug transporter MRP2 in intestine. Impact on its function as membrane barrier.
ABCC2 polymorphisms were associated with hematological toxicity in non-small cell lung cancer patients.
Title: Associations of genetic polymorphisms of the transporters organic cation transporter 2 (OCT2), multidrug and toxin extrusion 1 (MATE1), and ATP-binding cassette subfamily C member 2 (ABCC2) with platinum-based chemotherapy response and toxicity in non-small cell lung cancer patients.
Meta-analysis. The ABCC2 c.-24C>T polymorphism increases the risk of resistance to antiepileptic drugs.
Title: The ABCC2 c.-24C>T polymorphism increases the risk of resistance to antiepileptic drugs: A meta-analysis.
we have investigated the role of ABCB1 rs1045642 and rs2032582 and ABCC2 rs2273697 and rs717620 in antiepileptic drug-resistance. Our study suggests that the ABCC2 rs717620 polymorphism is associated with resistance to antiepileptic drugs in Chinese patients with epilepsy.
Title: Association between the polymorphisms in the ATP-binding cassette genes ABCB1 and ABCC2 and the risk of drug-resistant epilepsy in a Chinese Han population.
A novel deletion in ABCC2 gene was identified in families with dual hereditary jaundice.
Title: Genetic and biochemical study of dual hereditary jaundice: Dubin-Johnson and Gilbert's syndromes. Haplotyping and founder effect of deletion in ABCC2.
Resveratrol-3-O-sulfate reduced in both MRP2-overexpressing MDCKII-UGT1A1 cells and Human UGT1A9-overexpressing HeLa cells.
Title: Curcumin Affects Phase II Disposition of Resveratrol Through Inhibiting Efflux Transporters MRP2 and BCRP.

Submit: New GeneRIF Correction See all GeneRIFs (208)

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

Associated conditions

Description	Tests
Dubin-Johnson syndrome MedGen: C0022350 OMIM: 237500 GeneReviews: Not available	Compare labs

NHGRI GWAS Catalog

Description
Identification of susceptibility loci for colorectal cancer in a genome-wide meta-analysis. NHGRI GWA Catalog NHGRI GWA CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Pathways from BioSystems

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ABC transporters, organism-specific biosystem (from KEGG)
ABC transporters, organism-specific biosystemThe ATP-binding cassette (ABC) transporters form one of the largest known protein families, and are widespread in bacteria, archaea, and eukaryotes. They couple ATP hydrolysis to active transport of ...
ABC transporters, conserved biosystem (from KEGG)
ABC transporters, conserved biosystemThe ATP-binding cassette (ABC) transporters form one of the largest known protein families, and are widespread in bacteria, archaea, and eukaryotes. They couple ATP hydrolysis to active transport of ...
ABC-family proteins mediated transport, organism-specific biosystem (from REACTOME)
ABC-family proteins mediated transport, organism-specific biosystemThe ATP-binding cassette (ABC) superfamily of active transporters involves a large number of functionally diverse transmembrane proteins. They transport a variety of compounds through membranes agai...
Antifolate resistance, organism-specific biosystem (from KEGG)
Antifolate resistance, organism-specific biosystemSince the 1940s, antifolates have played a pivotal role in drug treatment of malignant, microbial, parasitic and chronic inflammatory diseases. The molecular basis of the anti-proliferative activity ...
Antifolate resistance, conserved biosystem (from KEGG)
Antifolate resistance, conserved biosystemSince the 1940s, antifolates have played a pivotal role in drug treatment of malignant, microbial, parasitic and chronic inflammatory diseases. The molecular basis of the anti-proliferative activity ...
Bile secretion, organism-specific biosystem (from KEGG)
Bile secretion, organism-specific biosystemBile is a vital secretion, essential for digestion and absorption of fats and fat-soluble vitamins in the small intestine. Moreover, bile is an important route of elimination for excess cholesterol a...
Bile secretion, conserved biosystem (from KEGG)
Bile secretion, conserved biosystemBile is a vital secretion, essential for digestion and absorption of fats and fat-soluble vitamins in the small intestine. Moreover, bile is an important route of elimination for excess cholesterol a...
Codeine and Morphine Metabolism, organism-specific biosystem (from WikiPathways)
Codeine and Morphine Metabolism, organism-specific biosystemThe principal pathways for metabolism of codeine occur in the liver, although some metabolism occurs in the intestine and brain. Approximately 50-70% of codeine is converted to codeine-6-glucuronide ...
Constitutive Androstane Receptor Pathway, organism-specific biosystem (from WikiPathways)
Constitutive Androstane Receptor Pathway, organism-specific biosystemThe Constitutive Androstane Receptor (CAR) is a nuclear receptor and functions as a sensor for xenobiotics. It regulates transcription of genes encoding proteins in metabolism and excretion of xenobi...
Drug Induction of Bile Acid Pathway, organism-specific biosystem (from WikiPathways)
Drug Induction of Bile Acid Pathway, organism-specific biosystem
Drug Induction of Bile Acid Pathway
Irinotecan Pathway, organism-specific biosystem (from WikiPathways)
Irinotecan Pathway, organism-specific biosystemThis pathway shows the biotransformation of the chemotherapy prodrug irinotecan to form the active metabolite SN-38, an inhibitor of DNA topoisomerase I. SN-38 is primarily metabolized to the inactiv...
NRF2 pathway, organism-specific biosystem (from WikiPathways)
NRF2 pathway, organism-specific biosystemNRF2 is part of a group of transcription factors called nuclear receptors. It is activated under oxidative stress conditions and subsequently activates several antioxidative genes and proteins.
Nuclear Receptors in Lipid Metabolism and Toxicity, organism-specific biosystem (from WikiPathways)
Nuclear Receptors in Lipid Metabolism and Toxicity, organism-specific biosystemNuclear receptors are transcription factors that are activated upon binding to its ligands. Initially, they had been classified as classic endocrine nuclear hormone receptors and orphan receptors. Ho...
Photodynamic therapy-induced NFE2L2 (NRF2) survival signaling, organism-specific biosystem (from WikiPathways)
Photodynamic therapy-induced NFE2L2 (NRF2) survival signaling, organism-specific biosystemPhotodynamic therapy may induce an antioxidant response mediated by NFE2L2.
Platinum drug resistance, organism-specific biosystem (from KEGG)
Platinum drug resistance, organism-specific biosystemPlatinum-based drugs cisplatin, carboplatin and oxaliplatin are widely used in the therapy of solid malignancies, including testicular, ovarian, head and neck, colorectal, bladder and lung cancers. T...
Platinum drug resistance, conserved biosystem (from KEGG)
Platinum drug resistance, conserved biosystemPlatinum-based drugs cisplatin, carboplatin and oxaliplatin are widely used in the therapy of solid malignancies, including testicular, ovarian, head and neck, colorectal, bladder and lung cancers. T...
Transmembrane transport of small molecules, organism-specific biosystem (from REACTOME)
Transmembrane transport of small molecules, organism-specific biosystem
Transmembrane transport of small molecules

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D10S2421 (e-PCR)
- UniSTS:43031

ABCC2 (e-PCR)
- UniSTS:480048

RH119574 (e-PCR)
- UniSTS:132657

SHGC-154232 (e-PCR)
- UniSTS:178029

G49565 (e-PCR)
- UniSTS:109234

D10S2172 (e-PCR)
- UniSTS:28638

Homology

Homologs of the ABCC2 gene: The ABCC2 gene is conserved in Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, A.thaliana, and frog.
Orthologs from Annotation Pipeline: 208 organisms have orthologs with human gene ABCC2
The Hierarchical Catalog of Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
ATP binding	IEA Inferred from Electronic Annotation more info
ATPase activity, coupled to transmembrane movement of substances	TAS Traceable Author Statement more info	PubMed
ATPase-coupled anion transmembrane transporter activity	TAS Traceable Author Statement more info
bilirubin transmembrane transporter activity	TAS Traceable Author Statement more info
organic anion transmembrane transporter activity	TAS Traceable Author Statement more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein domain specific binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
ATP hydrolysis coupled anion transmembrane transport	IEA Inferred from Electronic Annotation more info
benzylpenicillin metabolic process	IEA Inferred from Electronic Annotation more info
bilirubin transport	IEA Inferred from Electronic Annotation more info
canalicular bile acid transport	IEA Inferred from Electronic Annotation more info
cellular chloride ion homeostasis	IEA Inferred from Electronic Annotation more info
cellular response to dexamethasone stimulus	IEA Inferred from Electronic Annotation more info
cellular response to hormone stimulus	IBA Inferred from Biological aspect of Ancestor more info
cellular response to interleukin-1	IEA Inferred from Electronic Annotation more info
cellular response to interleukin-6	IEA Inferred from Electronic Annotation more info
cellular response to lipopolysaccharide	IEA Inferred from Electronic Annotation more info
cellular response to tumor necrosis factor	IEA Inferred from Electronic Annotation more info
drug transmembrane transport	IEA Inferred from Electronic Annotation more info
female pregnancy	IEA Inferred from Electronic Annotation more info
mercury ion transport	IEA Inferred from Electronic Annotation more info
prostaglandin transport	IEA Inferred from Electronic Annotation more info
response to antineoplastic agent	IEA Inferred from Electronic Annotation more info
response to arsenic-containing substance	IEA Inferred from Electronic Annotation more info
response to estrogen	IEA Inferred from Electronic Annotation more info
response to heat	IEA Inferred from Electronic Annotation more info
response to methotrexate	IEA Inferred from Electronic Annotation more info
response to oxidative stress	IEA Inferred from Electronic Annotation more info
thyroid hormone transport	IEA Inferred from Electronic Annotation more info
transmembrane transport	TAS Traceable Author Statement more info
transport	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
apical plasma membrane	IDA Inferred from Direct Assay more info	PubMed
brush border membrane	IEA Inferred from Electronic Annotation more info
cell surface	IDA Inferred from Direct Assay more info	PubMed
integral component of plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
intercellular canaliculus	IEA Inferred from Electronic Annotation more info
plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: canalicular multispecific organic anion transporter 1

Names: ATP-binding cassette, sub-family C (CFTR/MRP), member 2; canalicular multidrug resistance protein; multidrug resistance-associated protein 2

NCBI Reference Sequences (RefSeq)

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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

NG_011798.1 RefSeqGene

Range

4893..74487

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000392.4 → NP_000383.1 canalicular multispecific organic anion transporter 1

See identical proteins and their annotated locations for NP_000383.1

Status: REVIEWED

Source sequence(s)

AL133353, U49248, U63970

Consensus CDS

CCDS7484.1

UniProtKB/Swiss-Prot

Q92887

Related

ENSP00000359478.4, OTTHUMP00000020267, ENST00000370449.8, OTTHUMT00000049825

Conserved Domains (5) summary

TIGR00957
Location:8 → 1537

MRP_assoc_pro; multi drug resistance-associated protein (MRP)

cd03244
Location:1298 → 1518

ABCC_MRP_domain2; ATP-binding cassette domain 2 of multidrug resistance-associated protein

cd03250
Location:637 → 838

ABCC_MRP_domain1; ATP-binding cassette domain 1 of multidrug resistance-associated protein, subfamily C

pfam00664
Location:983 → 1249

ABC_membrane; ABC transporter transmembrane region

cl00549
Location:326 → 593

ABC_membrane; ABC transporter transmembrane region

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 108 details...

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

Reference GRCh38.p7 Primary Assembly

Genomic

NC_000010.11 Reference GRCh38.p7 Primary Assembly

Range

99782598..99853741

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006717631.3 → XP_006717694.1 canalicular multispecific organic anion transporter 1 isoform X3

Conserved Domains (3) summary

cd03250
Location:637 → 838

ABCC_MRP_domain1; ATP-binding cassette domain 1 of multidrug resistance-associated protein, subfamily C

COG1132
Location:310 → 857

MdlB; ABC-type multidrug transport system, ATPase and permease component [Defense mechanisms]

cl00549
Location:326 → 593

ABC_membrane; ABC transporter transmembrane region
XM_017015675.1 → XP_016871164.1 canalicular multispecific organic anion transporter 1 isoform X4
XM_011539291.2 → XP_011537593.1 canalicular multispecific organic anion transporter 1 isoform X2

Conserved Domains (3) summary

cd03250
Location:637 → 838

ABCC_MRP_domain1; ATP-binding cassette domain 1 of multidrug resistance-associated protein, subfamily C

COG1132
Location:310 → 857

MdlB; ABC-type multidrug transport system, ATPase and permease component [Defense mechanisms]

cl00549
Location:326 → 593

ABC_membrane; ABC transporter transmembrane region
XM_006717630.3 → XP_006717693.1 canalicular multispecific organic anion transporter 1 isoform X1

Conserved Domains (5) summary

cd03244
Location:1066 → 1286

ABCC_MRP_domain2; ATP-binding cassette domain 2 of multidrug resistance-associated protein

cd03250
Location:405 → 606

ABCC_MRP_domain1; ATP-binding cassette domain 1 of multidrug resistance-associated protein, subfamily C

TIGR01271
Location:78 → 1290

CFTR_protein; cystic fibrosis transmembrane conductor regulator (CFTR)

pfam00664
Location:751 → 1017

ABC_membrane; ABC transporter transmembrane region

cl00549
Location:94 → 361

ABC_membrane; ABC transporter transmembrane region