ABCC10 (ATP-binding cassette, sub-family C (CFTR/MRP), member 10)

2014-04-01   Elizabeth Hopper-Borge , Natalya Domanitskaya 

Fox Chase Cancer Center, Developmental Therapeutics Program, Philadelphia, PA, USA

Identity

HGNC
LOCATION
6p21.1
LOCUSID
ALIAS
EST182763,MRP7,SIMRP7
FUSION GENES

DNA/RNA

Note

Contains 22 exons and 21 introns (Kao et al., 2003).

Description

The gene encompasses 23065 bases.

Transcription

Transcript is 744 bps, and has 10 splice variants.

In normal tissue
A study of the ABCC10 promoter revealed that the presence of E2F and Sp1 sites are required for maximum transcription. In addition other elements were found in the promoter including: cAMP-responsive element binding protein, estrogen receptor binding site, hepatic nuclear factor, progesterone receptor binding site, and sterol regulatory element binding protein (Dabrowska and Sirotnak, 2004).
ABCC10 transcript is widespread at low levels (Hopper et al., 2001; Maher et al., 2005) with highest expression in the pancreas. Decreased expression is observed in activated resting T and B cells (Takayanagi et al., 2004).

In cancer
In cell lines: In terms of cancer, the ABCC10 gene is expressed in human tumor cell lines, HepG2, CWR22RV1 and TSU-PR1 at greater or equal levels than ABCC1, ABCC2 and ABCC3. Novel ABCC10 transcripts have been identified in HepG2, and CWR22RV1 cells. These transcripts are heterogeneic and imply complexity in the exons and introns of this region (Dabrowska and Sirotnak, 2004).
In breast cancer: ABCC10 transcript is upregulated in breast tumors treated with 5-fluorouracil, anthracycline, cyclophosphamide or taxane based neoadjuvant chemotherapy in comparison with normal tissue. Further, ABCC10 transcript expression is associated with ER positive breast cancer (Hlavac et al., 2013).
In acute myeloid leukemia: ABCC10 transcript is also expressed in acute myeloid leukemia (Hu et al., 2011).
In hepatocellular carcinoma: Transcripts from ABCC10 and various other transporters including: ABCB6, ABCC1, ABCC4, ABCC5, and ABCC12 are upregulated in over 50% hepatocellular carcinoma in untreated patients. It was also observed that microRNA let-7a/e is able to downregulate ABCC10 transcript (Borel et al., 2012).

Proteins

Atlas Image

Description

Unglycosylated ABCC10 is ~158 kDa (Hopper et al., 2001).
ABCC10, like ABCC1, 2, 3 and 6 (see figure above A) has an N-terminal membrane spanning domain (MSD) that is not present in ABCC4, 5, 11 or 12 (figure above B). All ABCC subfamily members contain two Nucleotide Binding Domains (NBD).

Expression

ABCC10 has been detected in various human occular-absorption barrier tissues including, the iris ciliary body, corneal epithelium, conjuntive epithelium, and retina (Chen et al., 2013).
ABCC10 is expressed in cell lines derived from acute myeloid leukemia (Hu et al., 2011).

Localisation

Localizes basolaterally in ABCC10-transfected LLC-pK1 cells (Malofeeva et al., 2012).

Function

In vitro
ABCC10 transports estrogen β glucuronide, and exhibits modest transport of leukotrienes. Similar to other subfamily members ABCC10 can efflux lipophilic anions (Chen et al., 2003).
ABCC10 is a drug efflux pump that is able to mediate transport of taxanes in vivo. In vitro studies have shown that ABCC10 confers resistance to a variety of hydrophobic drugs, including paclitaxel, docetaxel, vincristine, vinblastine, epothilone B, cytarabine, in a glutathione independent manner (Hopper-Borge et al., 2004; Hopper-Borge et al., 2009)
Prior work has shown that ABCC10 may have a role in natural killer cell mediated lysis. A report demonstrated that a peptide derived from ABCC10 binds to HLA-E and inhibits NK cell-mediated lysis in a CD94 and class I-dependent fashion (Wooden et al., 2005).
ABCC10 ATPase activity is stimulated by estradiol glucuronide, leukotriene, tamoxifen, docetaxel and ARA-C (Malofeeva et al., 2012).

In vivo
Abcc10 protects thymus, spleen and bone marrow when exposed to paclitaxel in vivo. Abcc10 loss promotes loss of white blood cells, increased weight loss and increased lethality in mice exposed to high doses of paclitaxel (Hopper-Borge et al., 2011).

Homology

ABCC10 exhibits structural and/or functional homology with other ABC transporters: CFTR, ABCC1, ABCC2, ABCC3, ABCC6. However, ABCC10 shares the lowest amino acid identity (33.8%) to ABCC1 compared to ABCC2, ABCC3, ABCC4, ABCC5 and ABCC6 (Hopper et al., 2001).
ABCC10 is present in many species including: drosophila melanogaster, xenopus, saccharomyces cerevisiae, danio rerio, sus scrofa, mus musculus, latimeria chalumnae, felis catus, bos taurus, tetranychus urticae (Schippert et al., 2008; Dermauw et al., 2013). ABCC10 is present in all placental mammals, similar to other subfamily members, ABCC1, ABCC3, ABCC4-7, and ABCC9 (Moitra and Dean, 2011).

Implicated in

Entity name
Non small cell lung cancer
Note
In vitro cellular resistance in non small cell lung cancer. ABCC10 expression is a predictive biomarker for the resistance to paclitaxel in non-small cell lung cancer (Oguri et al., 2008). ABCC10/MRP7 expression is associated with vinorelbine resistance in non-small cell lung cancer (Bessho et al., 2009). Another study implicated ABCC10 in gemcitabine resistance mechanisms in non small cell carcinoma cell lines (Ikeda et al., 2011).
ABCC10 is overexpressed in NSCLC. The expression of ABCC10 in adenocarcinoma is higher than in squamous cell carcinoma. ABCC10 expression in adenocarcinoma correlates with pathological grades and TNM stages (Wang et al., 2009).
Entity name
Head and neck cancer
Note
Multidrug resistance protein 7 expression is involved in cross-resistance to docetaxel in salivary gland adenocarcinoma cell lines (Naramoto et al., 2007).
Entity name
Ovarian cancer
Note
A ovarian carcinoma xenograft model demonstrated that intermittant docetaxel dosing of tumors promotes upregulation of MRP7 and other drug resistance genes including btubulin III, Akt2, and thioredoxin. However, when the dosing was continuous the various resistance genes did not upregulate (De Souza et al., 2011).
Note
ABCC10 may play a role in Ara-C resistance mechanisms in acute myeloid leukemia (Hu et al., 2011). ABCC10 transcript is more highly expressed in childhood AML than in many normal samples (Steinbach et al., 2006).
Entity name
Breast cancer
Note
In metastatic breast cancer, a difference in progression-free survival (PFS) was found between circulating stem cells (CTCs) positive and CTCs-negative patients. PFS was shorter in patients whose CTCs expressed two or more ABCC subfamilies, including ABCC10 (Gradilone et al., 2011).
ABCC10 expression may confer therapeutic resistance in solid breast tumors (submitted, Domanitskaya et al.).
Entity name
Colorectal cancer
Note
An inverse correlation between ABCC10 transcript and tumor aggressiveness and tumor grade severity was found in colorectal cancer (Hlavata et al., 2012).
Entity name
Human immunodeficiency virus
Note
ABCC10 polymorphisms contribute to the development of kidney tubular dysfunction (KTD) in some HIV patients (Giacomet et al., 2013). ABCC10 polymorphisms modulate blood levels of the anti HIV drugs tenofivir, and nevapirine (Pushpakom et al., 2011; Liptrott et al., 2012).
Entity name
Parkinsons disease
Note
ABCC10 inhibits methylmercury-associated animal toxicity and dopaminergic neurodegeneration in Caenorhabditis elegans (Vanduyn and Nass, 2014).

Bibliography

Pubmed IDLast YearTitleAuthors
190824712009ABCC10/MRP7 is associated with vinorelbine resistance in non-small cell lung cancer.Bessho Y et al
223144242012Diagnostic and therapeutic potential of miRNA signatures in patients with hepatocellular carcinoma.Borel F et al
239799162013Expression of efflux transporters in human ocular tissues.Chen P et al
125278062003Characterization of the transport properties of human multidrug resistance protein 7 (MRP7, ABCC10).Chen ZS et al
154742962004Regulation of transcription of the human MRP7 gene. Characteristics of the basal promoter and identification of tumor-derived transcripts encoding additional 5' end heterogeneity.Dabrowska M et al
215512632011Chemotherapy dosing schedule influences drug resistance development in ovarian cancer.De Souza R et al
236633082013A burst of ABC genes in the genome of the polyphagous spider mite Tetranychus urticae.Dermauw W et al
240675622013Tenofovir-induced renal tubular dysfunction in vertically HIV-infected patients associated with polymorphisms in ABCC2, ABCC4 and ABCC10 genes.Giacomet V et al
206034322011Circulating tumor cells (CTCs) in metastatic breast cancer (MBC): prognosis, drug resistance and phenotypic characterization.Gradilone A et al
235564492013The expression profile of ATP-binding cassette transporter genes in breast carcinoma.Hlaváč V et al
222947662012The role of ABC transporters in progression and clinical outcome of colorectal cancer.Hlavata I et al
111462242001Analysis of the structure and expression pattern of MRP7 (ABCC10), a new member of the MRP subfamily.Hopper E et al
215760882011Contribution of Abcc10 (Mrp7) to in vivo paclitaxel resistance as assessed in Abcc10(-/-) mice.Hopper-Borge EA et al
214871002011Activity of the multikinase inhibitor sorafenib in combination with cytarabine in acute myeloid leukemia.Hu S et al
211528612011Isolation and characterization of gemcitabine-resistant human non-small cell lung cancer A549 cells.Ikeda R et al
125669912003Genomic structure, gene expression, and promoter analysis of human multidrug resistance-associated protein 7.Kao HH et al
220826522012Association of ABCC10 polymorphisms with nevirapine plasma concentrations in the German Competence Network for HIV/AIDS.Liptrott NJ et al
158023882005Tissue distribution and hepatic and renal ontogeny of the multidrug resistance-associated protein (Mrp) family in mice.Maher JM et al
230870552012Modulation of the ATPase and transport activities of broad-acting multidrug resistance factor ABCC10 (MRP7).Malofeeva EV et al
211943602011Evolution of ABC transporters by gene duplication and their role in human disease.Moitra K et al
172032212007Multidrug resistance-associated protein 7 expression is involved in cross-resistance to docetaxel in salivary gland adenocarcinoma cell lines.Naramoto H et al
184456592008MRP7/ABCC10 expression is a predictive biomarker for the resistance to paclitaxel in non-small cell lung cancer.Oguri T et al
216286692011Genetic variants of ABCC10, a novel tenofovir transporter, are associated with kidney tubular dysfunction.Pushpakom SP et al
187695602008Microarray analysis of retinal gene expression in chicks during imposed myopic defocus.Schippert R et al
168578112006ABCA3 as a possible cause of drug resistance in childhood acute myeloid leukemia.Steinbach D et al
190593762009The high turnover Drosophila multidrug resistance-associated protein shares the biochemical features of its human orthologues.Szeri F et al
157248432004Human ATP-binding cassette transporter ABCC10: expression profile and p53-dependent upregulation.Takayanagi S et al
242666392014The putative multidrug resistance protein MRP-7 inhibits methylmercury-associated animal toxicity and dopaminergic neurodegeneration in Caenorhabditis elegans.VanDuyn N et al
207191742009[Expression and Clinical Significance of ABCC10 in the Patients with Non-small Cell Lung Cancer.].Wang P et al
160340732005Cutting edge: HLA-E binds a peptide derived from the ATP-binding cassette transporter multidrug resistance-associated protein 7 and inhibits NK cell-mediated lysis.Wooden SL et al

Other Information

Locus ID:

NCBI: 89845
MIM: 612509
HGNC: 52
Ensembl: ENSG00000124574

Variants:

dbSNP: 89845
ClinVar: 89845
TCGA: ENSG00000124574
COSMIC: ABCC10

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000124574ENST00000244533Q5T3U5
ENSG00000124574ENST00000372515D6R9B3
ENSG00000124574ENST00000372530Q5T3U5
ENSG00000124574ENST00000372530A0A024RD21
ENSG00000124574ENST00000505344H0Y904

Expression (GTEx)

0
5
10
15
20
25
30

Pathways

PathwaySourceExternal ID
ABC transportersKEGGko02010
ABC transportersKEGGhsa02010
Transmembrane transport of small moleculesREACTOMER-HSA-382551
ABC-family proteins mediated transportREACTOMER-HSA-382556

Protein levels (Protein atlas)

Not detected
Low
Medium
High

PharmGKB

Entity IDNameTypeEvidenceAssociationPKPDPMIDs
PA10204tenofovirChemicalClinicalAnnotation, PathwayassociatedPD21628669
PA447230HIVDiseaseClinicalAnnotationassociatedPKPD22082652
PA450616nevirapineChemicalClinicalAnnotationassociatedPKPD22082652
PA451879vincristineChemicalPathwayassociated

References

Pubmed IDYearTitleCitations
125278062003Characterization of the transport properties of human multidrug resistance protein 7 (MRP7, ABCC10).41
125278062003Characterization of the transport properties of human multidrug resistance protein 7 (MRP7, ABCC10).41
191180012009Human multidrug resistance protein 7 (ABCC10) is a resistance factor for nucleoside analogues and epothilone B.41
152564652004Analysis of the drug resistance profile of multidrug resistance protein 7 (ABCC10): resistance to docetaxel.38
216286692011Genetic variants of ABCC10, a novel tenofovir transporter, are associated with kidney tubular dysfunction.30
111462242001Analysis of the structure and expression pattern of MRP7 (ABCC10), a new member of the MRP subfamily.28
198417392009Imatinib and nilotinib reverse multidrug resistance in cancer cells by inhibiting the efflux activity of the MRP7 (ABCC10).27
190824712009ABCC10/MRP7 is associated with vinorelbine resistance in non-small cell lung cancer.24
215760882011Contribution of Abcc10 (Mrp7) to in vivo paclitaxel resistance as assessed in Abcc10(-/-) mice.23
230870552012Modulation of the ATPase and transport activities of broad-acting multidrug resistance factor ABCC10 (MRP7).18

Citation

Elizabeth Hopper-Borge ; Natalya Domanitskaya

ABCC10 (ATP-binding cassette, sub-family C (CFTR/MRP), member 10)

Atlas Genet Cytogenet Oncol Haematol. 2014-04-01

Online version: http://atlasgeneticsoncology.org/gene/47655/abcc10