ABCC2 (ATP binding cassette subfamily C member 2)

Gene

• Entrez ID: 1244
• Gene name: ATP binding cassette subfamily C member 2
• Gene symbol: ABCC2
• Synonyms: ABC30, CMOAT, DJS, MRP2, cMRP
• Chromosome: 10
• Chromosome location: 10q24.2
• 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]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs17222547	C>A	Pathogenic	Coding sequence variant, non coding transcript variant, genic downstream transcript variant, stop gained, 3 prime UTR variant
rs17222674	A>G	Conflicting-interpretations-of-pathogenicity	Missense variant, coding sequence variant, non coding transcript variant
rs17222716	G>C	Conflicting-interpretations-of-pathogenicity	Intron variant, genic downstream transcript variant
rs34937870	G>A,T	Pathogenic	Splice donor variant, genic downstream transcript variant, intron variant
rs56131651	G>A	Conflicting-interpretations-of-pathogenicity, likely-benign	Missense variant, coding sequence variant, non coding transcript variant
rs56199535	C>A,G,T	Pathogenic	Missense variant, coding sequence variant, non coding transcript variant, synonymous variant
rs72558199	C>T	Pathogenic, likely-pathogenic	Coding sequence variant, non coding transcript variant, genic downstream transcript variant, downstream transcript variant, stop gained
rs72558200	G>A	Pathogenic	Missense variant, coding sequence variant, non coding transcript variant, genic downstream transcript variant
rs72558201	A>G,T	Pathogenic	Missense variant, coding sequence variant, non coding transcript variant, genic downstream transcript variant
rs72558202	A>G	Pathogenic	Missense variant, coding sequence variant, non coding transcript variant, genic downstream transcript variant
rs139082536	G>A,C	Conflicting-interpretations-of-pathogenicity	Genic downstream transcript variant, 3 prime UTR variant, synonymous variant, non coding transcript variant, coding sequence variant
rs139800035	C>T	Conflicting-interpretations-of-pathogenicity, uncertain-significance	Intron variant
rs144192700	C>T	Conflicting-interpretations-of-pathogenicity, uncertain-significance	Genic downstream transcript variant, synonymous variant, non coding transcript variant, coding sequence variant
rs146405172	G>A	Likely-pathogenic	Splice donor variant
rs146575217	C>G	Uncertain-significance, conflicting-interpretations-of-pathogenicity	Coding sequence variant, genic downstream transcript variant, non coding transcript variant, synonymous variant
rs183923599	C>T	Pathogenic	Coding sequence variant, genic downstream transcript variant, non coding transcript variant, stop gained
rs371866713	C>A,G	Pathogenic	Coding sequence variant, stop gained, non coding transcript variant
rs387906395	T>A,G	Pathogenic	Splice donor variant
rs387906396	T>C	Pathogenic	Splice donor variant
rs559137047	C>T	Pathogenic	Non coding transcript variant, genic downstream transcript variant, stop gained, coding sequence variant
rs559908064	C>A,G	Conflicting-interpretations-of-pathogenicity	Genic upstream transcript variant, non coding transcript variant, synonymous variant, coding sequence variant
rs577353173	G>A,T	Pathogenic	Coding sequence variant, genic downstream transcript variant, stop gained, non coding transcript variant, missense variant
rs756707816	G>A,C	Pathogenic	Splice acceptor variant
rs761406918	C>T	Pathogenic	Non coding transcript variant, coding sequence variant, genic downstream transcript variant, stop gained
rs762243203	G>A	Pathogenic	Downstream transcript variant, splice donor variant, genic downstream transcript variant
rs762291612	CC>-	Pathogenic	Non coding transcript variant, coding sequence variant, genic downstream transcript variant, frameshift variant
rs762346634	->TC	Pathogenic	Non coding transcript variant, coding sequence variant, downstream transcript variant, genic downstream transcript variant, frameshift variant
rs762914474	TT>-	Pathogenic	Non coding transcript variant, coding sequence variant, genic downstream transcript variant, frameshift variant
rs764958537	T>C	Pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs765580991	T>-	Pathogenic	Non coding transcript variant, coding sequence variant, frameshift variant
rs769798659	A>-	Pathogenic	Coding sequence variant, genic upstream transcript variant, non coding transcript variant, frameshift variant
rs771652807	->T	Pathogenic	Downstream transcript variant, stop gained, coding sequence variant, genic downstream transcript variant, non coding transcript variant
rs772673105	CT>-	Uncertain-significance, pathogenic	Coding sequence variant, frameshift variant, non coding transcript variant
rs773850184	C>T	Pathogenic	Coding sequence variant, stop gained, non coding transcript variant
rs774778158	AT>-	Pathogenic	Coding sequence variant, frameshift variant, genic downstream transcript variant, non coding transcript variant
rs775771081	C>-	Pathogenic	Coding sequence variant, frameshift variant, genic downstream transcript variant, non coding transcript variant
rs776087856	G>A	Uncertain-significance, pathogenic	Coding sequence variant, stop gained, non coding transcript variant
rs777325157	ACAACAC>-	Pathogenic	Coding sequence variant, downstream transcript variant, frameshift variant, genic downstream transcript variant, non coding transcript variant
rs777902199	C>G,T	Likely-pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs864309675	TG>-	Pathogenic	Non coding transcript variant, coding sequence variant, frameshift variant
rs919078015	A>-	Pathogenic	Frameshift variant, coding sequence variant, non coding transcript variant, genic downstream transcript variant
rs1158274146	CT>-	Pathogenic	Frameshift variant, non coding transcript variant, coding sequence variant
rs1161530285	G>A	Pathogenic	Genic upstream transcript variant, splice donor variant
rs1208873596	C>-	Pathogenic	Coding sequence variant, non coding transcript variant, frameshift variant
rs1257076487	C>A	Pathogenic	Non coding transcript variant, stop gained, coding sequence variant
rs1314486961	->A	Pathogenic	Coding sequence variant, initiator codon variant, frameshift variant, non coding transcript variant
rs1333544687	->T	Pathogenic	Frameshift variant, non coding transcript variant, coding sequence variant, genic downstream transcript variant
rs1554845888	T>A	Pathogenic	Non coding transcript variant, stop gained, coding sequence variant, genic upstream transcript variant
rs1554849397	C>T	Pathogenic	Non coding transcript variant, stop gained, coding sequence variant
rs1554850241	C>T	Conflicting-interpretations-of-pathogenicity	Non coding transcript variant, synonymous variant, coding sequence variant
rs1554851699	->T	Pathogenic	Non coding transcript variant, frameshift variant, coding sequence variant
rs1554853026	TTAA>-	Pathogenic	Downstream transcript variant, intron variant, frameshift variant, non coding transcript variant, coding sequence variant, genic downstream transcript variant
rs1554854612	->TC	Pathogenic	Downstream transcript variant, coding sequence variant, non coding transcript variant, frameshift variant, genic downstream transcript variant
rs1564674618	GAGT>-	Pathogenic	Non coding transcript variant, frameshift variant, coding sequence variant
rs1564687941	A>-	Pathogenic	Non coding transcript variant, frameshift variant, coding sequence variant
rs1564688595	C>-	Pathogenic	Non coding transcript variant, frameshift variant, coding sequence variant
rs1564702358	A>T	Pathogenic	Downstream transcript variant, non coding transcript variant, stop gained, coding sequence variant, genic downstream transcript variant
rs1590192032	G>A	Pathogenic	Genic downstream transcript variant, coding sequence variant, non coding transcript variant, stop gained

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT731994	hsa-miR-490-3p	Immunohistochemistry, Luciferase reporter assay, qRT-PCR, Western blot	28386339

Transcription factors

Transcription factor	Regulation	Reference
IRF3	Activation	15185298

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005515	Function	Protein binding	IPI	17825285, 21988832
GO:0005524	Function	ATP binding	IEA
GO:0005886	Component	Plasma membrane	TAS
GO:0005887	Component	Integral component of plasma membrane	IEA
GO:0006855	Process	Drug transmembrane transport	IMP	18245269
GO:0006954	Process	Inflammatory response	IEA
GO:0006979	Process	Response to oxidative stress	IEA
GO:0007565	Process	Female pregnancy	IEA
GO:0008514	Function	Organic anion transmembrane transporter activity	TAS	7559771
GO:0008559	Function	ABC-type xenobiotic transporter activity	IMP	18245269
GO:0009408	Process	Response to heat	IEA
GO:0009986	Component	Cell surface	HDA	19581412
GO:0009986	Component	Cell surface	IDA	17825285
GO:0010629	Process	Negative regulation of gene expression	ISS
GO:0015127	Function	Bilirubin transmembrane transporter activity	TAS
GO:0015694	Process	Mercury ion transport	IEA
GO:0015721	Process	Bile acid and bile salt transport	IMP	16332456
GO:0015722	Process	Canalicular bile acid transport	IEA
GO:0015723	Process	Bilirubin transport	IEA
GO:0015732	Process	Prostaglandin transport	IEA
GO:0016020	Component	Membrane	IBA	21873635
GO:0016324	Component	Apical plasma membrane	IBA	21873635
GO:0016324	Component	Apical plasma membrane	IDA	11093739, 17825285
GO:0016887	Function	ATPase activity	IEA
GO:0019904	Function	Protein domain specific binding	IEA
GO:0030644	Process	Cellular chloride ion homeostasis	IEA
GO:0031427	Process	Response to methotrexate	IEA
GO:0031526	Component	Brush border membrane	IEA
GO:0032355	Process	Response to estradiol	IEA
GO:0033762	Process	Response to glucagon	IEA
GO:0035690	Process	Cellular response to drug	IEA
GO:0038183	Process	Bile acid signaling pathway	IEA
GO:0042178	Process	Xenobiotic catabolic process	IEA
GO:0042626	Function	ATPase-coupled transmembrane transporter activity	IBA	21873635
GO:0042626	Function	ATPase-coupled transmembrane transporter activity	IDA	11500505
GO:0042910	Function	Xenobiotic transmembrane transporter activity	IDA	11500505
GO:0043627	Process	Response to estrogen	IEA
GO:0046581	Component	Intercellular canaliculus	IEA
GO:0046618	Process	Drug export	IMP	18245269
GO:0046685	Process	Response to arsenic-containing substance	IEA
GO:0046691	Component	Intracellular canaliculus	IEA
GO:0055085	Process	Transmembrane transport	IBA	21873635
GO:0055085	Process	Transmembrane transport	TAS
GO:0070327	Process	Thyroid hormone transport	IEA
GO:0070633	Process	Transepithelial transport	ISS
GO:0071222	Process	Cellular response to lipopolysaccharide	IEA
GO:0071347	Process	Cellular response to interleukin-1	IEA
GO:0071354	Process	Cellular response to interleukin-6	IEA
GO:0071356	Process	Cellular response to tumor necrosis factor	IEA
GO:0071549	Process	Cellular response to dexamethasone stimulus	IEA
GO:0071716	Process	Leukotriene transport	IEA
GO:0097327	Process	Response to antineoplastic agent	IEA
GO:0120188	Process	Regulation of bile acid secretion	IEA
GO:0150104	Process	Transport across blood-brain barrier	NAS	26590417, 30280653
GO:1901086	Process	Benzylpenicillin metabolic process	IEA
GO:1904486	Process	Response to 17alpha-ethynylestradiol	IEA
GO:1990961	Process	Xenobiotic detoxification by transmembrane export across the plasma membrane	IEA
GO:1990962	Process	Xenobiotic transport across blood-brain barrier	ISS

Other IDs

• MIM: 601107
• HGNC: 53
• e!Ensembl: ENSG00000023839

Protein

• UniProt ID: Q92887
• Protein name: ATP-binding cassette sub-family C member 2 (EC 7.6.2.-) (EC 7.6.2.2) (EC 7.6.2.3) (Canalicular multidrug resistance protein) (Canalicular multispecific organic anion transporter 1) (Multidrug resistance-associated protein 2)
• Protein function: ATP-dependent transporter of the ATP-binding cassette (ABC) family that binds and hydrolyzes ATP to enable active transport of various substrates including many drugs, toxicants and endogenous compound across cell membranes. Transports a wide variety of conjugated organic anions such as sulfate-, glucuronide- and glutathione (GSH)-conjugates of endo- and xenobiotics substrates (PubMed:10220572, PubMed:10421658, PubMed:11500505, PubMed:16332456). Mediates hepatobiliary excretion of mono- and bis-glucuronidated bilirubin molecules and therefore play an important role in bilirubin detoxification (PubMed:10421658). Mediates also hepatobiliary excretion of others glucuronide conjugates such as 17beta-estradiol 17-glucosiduronic acid and leukotriene C4 (PubMed:11500505). Transports sulfated bile salt such as taurolithocholate sulfate (PubMed:16332456). Transport various anticancer drugs, such as anthracycline, vinca alkaloid and methotrexate and HIV-drugs such as protease inhibitors (PubMed:10220572, PubMed:11500505, PubMed:12441801). Confers resistance to several anti-cancer drugs including cisplatin, doxorubicin, epirubicin, methotrexate, etoposide and vincristine (PubMed:10220572, PubMed:11500505).
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00664	ABC_membrane	322 → 593	ABC transporter transmembrane region	Family
  PF00005	ABC_tran	654 → 789	ABC transporter	Domain
  PF00664	ABC_membrane	979 → 1251	ABC transporter transmembrane region	Family
  PF00005	ABC_tran	1317 → 1465	ABC transporter	Domain

• Sequence:

  MLEKFCNSTFWNSSFLDSPEADLPLCFEQTVLVWIPLGYLWLLAPWQLLHVYKSRTKRSS
  TTKLYLAKQVFVGFLLILAAIELALVLTEDSGQATVPAVRYTNPSLYLGTWLLVLLIQYS
  RQWCVQKNSWFLSLFWILSILCGTFQFQTLIRTLLQGDNSNLAYSCLFFISYGFQILILI
  FSAFSENNESSNNPSSIASFLSSITYSWYDSIILKGYKRPLTLEDVWEVDEEMKTKTLVS
  KFETHMKRELQKARRALQRRQEKSSQQNSGARLPGLNKNQSQSQDALVLEDVEKKKKKSG
  TKKDVPKSWLMKALFKTFYMVLLKSFLLKLVNDIFTFVSPQLLKLLISFASDRDTYLWIG
  YLCAILLFTAALIQSFCLQCYFQLCFKLGVKVRTAIMASVYKKALTLSNLARKEYTVGET
  VNLMSVDAQKLMDVTNFMHMLWSSVLQIVLSIFFLWRELGPSVLAGVGVMVLVIPINAIL
  STKSKTIQVKNMKNKDKRLKIMNEILSGIKILKYFAWEPSFRDQVQNLRKKELKNLLAFS
  QLQCVVIFVFQLTPVLVSVVTFSVYVLVDSNNILDAQKAFTSITLFNILRFPLSMLPMMI
  SSMLQASVSTERLEKYLGGDDLDTSAIRHDCNFDKAMQFSEASFTWEHDSEATVRDVNLD
  IMAGQLVAVIGPVGSGKSSLISAMLGEMENVHGHITIKGTTAYVPQQSWIQNGTIKDNIL
  FGTEFNEKRYQQVLEACALLPDLEMLPGGDLAEIGEKGINLSGGQKQRISLARATYQNLD
  IYLLDDPLSAVDAHVGKHIFNKVLGPNGLLKGKTRLLVTHSMHFLPQVDEIVVLGNGTIV
  EKGSYSALLAKKGEFAKNLKTFLRHTGPEEEATVHDGSEEEDDDYGLISSVEEIPEDAAS
  ITMRRENSFRRTLSRSSRSNGRHLKSLRNSLKTRNVNSLKEDEELVKGQKLIKKEFIETG
  KVKFSIYLEYLQAIGLFSIFFIILAFVMNSVAFIGSNLWLSAWTSDSKIFNSTDYPASQR
  DMRVGVYGALGLAQGIFVFIAHFWSAFGFVHASNILHKQLLNNILRAPMRFFDTTPTGRI
  VNRFAGDISTVDDTLPQSLRSWITCFLGIISTLVMICMATPVFTIIVIPLGIIYVSVQMF
  YVSTSRQLRRLDSVTRSPIYSHFSETVSGLPVIRAFEHQQRFLKHNEVRIDTNQKCVFSW
  ITSNRWLAIRLELVGNLTVFFSALMMVIYRDTLSGDTVGFVLSNALNITQTLNWLVRMTS
  EIETNIVAVERITEYTKVENEAPWVTDKRPPPDWPSKGKIQFNNYQVRYRPELDLVLRGI
  TCDIGSMEKIGVVGRTGAGKSSLTNCLFRILEAAGGQIIIDGVDIASIGLHDLREKLTII
  PQDPILFSGSLRMNLDPFNNYSDEEIWKALELAHLKSFVASLQLGLSHEVTEAGGNLSIG
  QRQLLCLGRALLRKSKILVLDEATAAVDLETDNLIQTTIQNEFAHCTVITIAHRLHTIMD
  SDKVMVLDNGKIIECGSPEELLQIPGPFYFMAKEAGIENVNSTKF

• Sequence length: 1545