ABCC6 ATP binding cassette subfamily C member 6 [Homo sapiens (human)] - Gene

Summary

Official Symbol: ABCC6provided by HGNC
Official Full Name: ATP binding cassette subfamily C member 6provided by HGNC
Primary source: HGNC:HGNC:57
See related: Ensembl:ENSG00000091262 MIM:603234; Vega:OTTHUMG00000129967
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: ARA; PXE; MLP1; MRP6; PXE1; URG7; ABC34; GACI2; MOATE; MOAT-E; EST349056
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). The encoded protein, a member of the MRP subfamily, is involved in multi-drug resistance. Mutations in this gene cause pseudoxanthoma elasticum. Alternatively spliced transcript variants that encode different proteins have been described for this gene. [provided by RefSeq, Jul 2008]
Expression: Biased expression in liver (RPKM 16.7), kidney (RPKM 9.5) and 9 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 16p13.11

Exon count:: 34

Annotation release	Status	Assembly	Chr	Location
109	current	GRCh38.p12 (GCF_000001405.38)	16	NC_000016.10 (16149565..16223617, complement)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	16	NC_000016.9 (16243422..16318083, complement)

Chromosome 16 - NC_000016.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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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?

Serum levels of MRP8/MRP14 and MRP6 were up-regulated in patients with Graves' disease (GD) and Hashimoto's thyroiditis (HT). In addition, mRNA expression of MRP proteins in PBMCs and the thyroid gland was markedly elevated in these patients.
Title: Myeloid related proteins are up-regulated in autoimmune thyroid diseases and activate toll-like receptor 4 and pro-inflammatory cytokines in vitro.
High URG7 reduces the ER stress by decreasing the amount of unfolded proteins, by increasing both the total protein ubiquitination and the AKT activation and reducing Caspase 3 activation.
Title: New insights on the functional role of URG7 in the cellular response to ER stress.
Two compound heterozygous ABCC6 loss-of-function mutations, c.4182_4182delG (p.Lys1394Asnfs*9) and c.2900G > A (p.Trp967*), were found
Title: ABCC6 mutations and early onset stroke: Two cases of a typical Pseudoxanthoma Elasticum.
Genetic analysis revealed three nonsense, four frame-shift, one exon deletion and 13 missense mutations in 73 Japanese pseudoxanthoma elasticum patients.
Title: Analysis of clinical symptoms and ABCC6 mutations in 76 Japanese patients with pseudoxanthoma elasticum.
in a French cohort with pseudoxanthoma elasticum, study identified 538 mutational events with 142 distinct variants, of which 66 were novel
Title: Mutation spectrum in the ABCC6 gene and genotype-phenotype correlations in a French cohort with pseudoxanthoma elasticum.
ABCC6 overexpression may also contribute to nilotinib and dasatinib resistance in vitro. With nilotinib and dasatinib now front line therapy options in the treatment of CML, concomitant administration of ABCC6 inhibitors may present an attractive option to enhance TKI efficacy
Title: ABCC6 plays a significant role in the transport of nilotinib and dasatinib, and contributes to TKI resistance in vitro, in both cell lines and primary patient mononuclear cells.
Using an integrated pathway-based approach, we identified polymorphisms in ABCC6, ABCB1 and CYP2C8 associated with overall survival. These associations were replicated in a large independent cohort, highlighting the importance of pharmacokinetic genes as prognostic markers in Ewing sarcoma
Title: Identification of genetic variants in pharmacokinetic genes associated with Ewing Sarcoma treatment outcome.
ABCC6 knockdown HepG2 cells show: 1) intracellular reductive stress; 2) cell cycle arrest in G1 phase; 3) upregulation of p21Cip p53 independent; and 4) downregulation of lamin A/C. the absence of ABCC6 profoundly changes the HepG2 phenotype, suggesting that Pseudoxanthoma elasticum syndrome is a complex metabolic disease that is not exclusively related to the absence of pyrophosphate in the bloodstream.
Title: <i>ABCC6</i> knockdown in HepG2 cells induces a senescent-like cell phenotype.
ABCC6 deficiency can be rescued by 4-phenylbutyrate therapy in a mouse model expressing human variants
Title: Functional Rescue of ABCC6 Deficiency by 4-Phenylbutyrate Therapy Reduces Dystrophic Calcification in Abcc6<sup>-/-</sup> Mice.
Biochemical and cell biological analyses demonstrate these mutations influence multiple steps in the biosynthetic pathway, minimally altering local domain structure but adversely impacting ABCC6 assembly and trafficking. The differential impacts on local and global protein structure are consistent with hierarchical folding and assembly of ABCC6.
Title: Stabilization of Nucleotide Binding Domain Dimers Rescues ABCC6 Mutants Associated with Pseudoxanthoma Elasticum.

Submit: New GeneRIF Correction See all GeneRIFs (85)

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
Generalized arterial calcification of infancy 2 MedGen: C3276161 OMIM: 614473 GeneReviews: Generalized Arterial Calcification of Infancy	Compare labs
Pseudoxanthoma elasticum MedGen: C0033847 OMIM: 264800 GeneReviews: Pseudoxanthoma Elasticum	Compare labs
Pseudoxanthoma elasticum, forme fruste MedGen: C1867450 OMIM: 177850 GeneReviews: Pseudoxanthoma Elasticum	Compare labs

NHGRI GWAS Catalog

Description
Loci associated with N-glycosylation of human immunoglobulin G show pleiotropy with autoimmune diseases and haematological cancers. 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...
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.
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

STS-X95715 (e-PCR)
- UniSTS:26409

D8S2279 (e-PCR)
- UniSTS:473907

G67881 (e-PCR)
- UniSTS:225592

99-4448 (e-PCR)
- UniSTS:240819

A007L01 (e-PCR)
- UniSTS:58824

RH103419 (e-PCR)
- UniSTS:97744

RH70947 (e-PCR)
- UniSTS:3042

Homology

Homologs of the ABCC6 gene: The ABCC6 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, and chicken.
Orthologs from Annotation Pipeline: 136 organisms have orthologs with human gene ABCC6
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	IBA Inferred from Biological aspect of Ancestor more info	PubMed
ATPase-coupled anion transmembrane transporter activity	TAS Traceable Author Statement more info
transporter activity	TAS Traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
ATP hydrolysis coupled anion transmembrane transport	IEA Inferred from Electronic Annotation more info
response to drug	TAS Traceable Author Statement more info	PubMed
transmembrane transport	IBA Inferred from Biological aspect of Ancestor more info	PubMed
transmembrane transport	TAS Traceable Author Statement more info
visual perception	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
apical plasma membrane	IEA Inferred from Electronic Annotation more info
basolateral plasma membrane	IBA Inferred from Biological aspect of Ancestor more info	PubMed
endoplasmic reticulum membrane	IEA Inferred from Electronic Annotation more info
integral component of membrane	IEA Inferred from Electronic Annotation more info
lateral plasma membrane	IEA Inferred from Electronic Annotation more info
membrane	IBA Inferred from Biological aspect of Ancestor more info	PubMed
nucleus	IDA Inferred from Direct Assay more info
plasma membrane	IDA Inferred from Direct Assay more info
plasma membrane	TAS Traceable Author Statement more info
vacuolar membrane	IBA Inferred from Biological aspect of Ancestor more info	PubMed

General protein information

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Preferred Names: multidrug resistance-associated protein 6; URG7 protein

Names: ATP-binding cassette, sub-family C (CFTR/MRP), member 6; anthracycline resistance-associated protein; multi-specific organic anion transporter E

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_007558.2 RefSeqGene

Range

5001..78907

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001079528.4 → NP_001072996.1 URG7 protein isoform 2

See identical proteins and their annotated locations for NP_001072996.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks much of the coding region and represents a distinct 3' UTR compared to variant 1. The encoded protein (isoform 2) is much shorter and has a distinct C-terminus compared to isoform 1. The encoded protein is not a transporter, but is thought to play a role in protecting hepatocytes during chronic hepatitis B virus infection.

Source sequence(s)

AY078405, BC050733

Consensus CDS

CCDS58430.1

UniProtKB/Swiss-Prot

O95255

Related

ENSP00000461686.1, OTTHUMP00000256353, ENST00000575728.1

Conserved Domains (1) summary

TIGR00957
Location:14 → 74

MRP_assoc_pro; multi drug resistance-associated protein (MRP)
NM_001171.5 → NP_001162.4 multidrug resistance-associated protein 6 isoform 1

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longest isoform (1).

Source sequence(s)

AF076622, AI074459, BC131732, DC361874

Consensus CDS

CCDS10568.1

UniProtKB/Swiss-Prot

O95255

Related

ENSP00000205557.7, OTTHUMP00000160427, ENST00000205557.11, OTTHUMT00000252232

Conserved Domains (5) summary

TIGR00957
Location:14 → 1502

MRP_assoc_pro; multi drug resistance-associated protein (MRP)

cd03244
Location:1263 → 1483

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

cd03250
Location:629 → 829

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

pfam16185
Location:27 → 146

MTABC_N; Mitochondrial ABC-transporter N-terminal five TM region

cl00549
Location:951 → 1216

ABC_membrane; ABC transporter transmembrane region
NM_001351800.1 → NP_001338729.1 multidrug resistance-associated protein 6 isoform 3

Status: REVIEWED

Source sequence(s)

AC136624, AF076622, AI074459, BC131732

Conserved Domains (1) summary

cl26602
Location:1 → 1388

SunT; ABC-type bacteriocin/lantibiotic exporters, contain an N-terminal double-glycine peptidase domain [Defense mechanisms]

RNA

NR_147784.1 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC136624, AF076622, AI074459, AM711638

Related

ENST00000456970.6

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109 details...

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

Reference GRCh38.p12 Primary Assembly

Genomic

NC_000016.10 Reference GRCh38.p12 Primary Assembly

Range

16149565..16223617 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_024450261.1 → XP_024306029.1 multidrug resistance-associated protein 6 isoform X6

Conserved Domains (1) summary

cl26602
Location:14 → 1514

SunT; ABC-type bacteriocin/lantibiotic exporters, contain an N-terminal double-glycine peptidase domain [Defense mechanisms]
XM_017023212.1 → XP_016878701.1 multidrug resistance-associated protein 6 isoform X2
XM_011522479.2 → XP_011520781.1 multidrug resistance-associated protein 6 isoform X1

Conserved Domains (5) summary

TIGR00957
Location:14 → 1491

MRP_assoc_pro; multi drug resistance-associated protein (MRP)

cd03244
Location:1252 → 1472

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

cd03250
Location:629 → 818

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

pfam16185
Location:27 → 146

MTABC_N; Mitochondrial ABC-transporter N-terminal five TM region

cl00549
Location:940 → 1205

ABC_membrane; ABC transporter transmembrane region
XM_011522480.1 → XP_011520782.1 multidrug resistance-associated protein 6 isoform X3

See identical proteins and their annotated locations for XP_011520782.1

Conserved Domains (4) summary

TIGR00957
Location:1 → 1388

MRP_assoc_pro; multi drug resistance-associated protein (MRP)

cd03244
Location:1149 → 1369

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

cd03250
Location:515 → 715

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

cl00549
Location:837 → 1102

ABC_membrane; ABC transporter transmembrane region
XM_011522481.3 → XP_011520783.1 multidrug resistance-associated protein 6 isoform X3

See identical proteins and their annotated locations for XP_011520783.1

Conserved Domains (4) summary

TIGR00957
Location:1 → 1388

MRP_assoc_pro; multi drug resistance-associated protein (MRP)

cd03244
Location:1149 → 1369

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

cd03250
Location:515 → 715

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

cl00549
Location:837 → 1102

ABC_membrane; ABC transporter transmembrane region
XM_017023214.1 → XP_016878703.1 multidrug resistance-associated protein 6 isoform X4
XM_011522482.3 → XP_011520784.1 multidrug resistance-associated protein 6 isoform X5

Related

ENSP00000483331.1, OTTHUMP00000256351, ENST00000622290.4

Conserved Domains (4) summary

cd03250
Location:629 → 829

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

COG1132
Location:296 → 845

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

pfam16185
Location:27 → 146

MTABC_N; Mitochondrial ABC-transporter N-terminal five TM region

cl00549
Location:315 → 578

ABC_membrane; ABC transporter transmembrane region