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ATP-BINDING CASSETTE, SUBFAMILY C, MEMBER 5; ABCC5

ATP-BINDING CASSETTE, SUBFAMILY C, MEMBER 5; ABCC5

Alternative titles; symbolsMULTIDRUG RESISTANCE-ASSOCIATED PROTEIN 5; MRP5MOATCHGNC Approved Gene Symbol: ABCC5Cytogenetic location: 3q27.1 Genomic coordinat...

Alternative titles; symbols

  • MULTIDRUG RESISTANCE-ASSOCIATED PROTEIN 5; MRP5
  • MOATC

HGNC Approved Gene Symbol: ABCC5

Cytogenetic location: 3q27.1 Genomic coordinates (GRCh38): 3:183,919,933-184,018,009 (from NCBI)

▼ Description
Multidrug resistance (MDR) proteins (MRPs), such as MRP5, mediate the extrusion of drugs from normal cells and tumors (summary by Wijnholds et al., 2000) . MDR/ATP-binding cassette (ABC) membrane proteins are involved in energy-dependent transport of a wide variety of substrates. (summary by Allikmets et al., 1996).

▼ Cloning and Expression
Allikmets et al. (1996) and Kool et al. (1997) used EST database searching to identify partial cDNAs encoding ABCC5 (see ABCC4, 605250). Using RT-PCR with degenerate primers, Suzuki et al. (1997) isolated a cDNA encoding short MRP, an apparent splice variant of ABCC5 (Suzuki et al., 2000). By EST database searching, followed by 5-prime RACE, Belinsky et al. (1998) obtained a cDNA encoding full-length ABCC5, which they termed MOATC (multispecific organic anion transporter C). Sequence analysis predicted that the 1,437-amino acid protein, like other ABC transporters, contains Walker A, B and C motifs, nucleotide-binding folds, and 12 transmembrane spanning helices in 2 hydrophobic domains. Kool et al. (1997), Suzuki et al. (1997), and Belinsky et al. (1998) performed Northern blot analysis which revealed ubiquitous expression of a 6.6-kb ABCC5 transcript with highest levels in skeletal muscle followed by brain, kidney, testis, and heart.

McAleer et al. (1999) found differential expression of at least 3 different ABCC5 transcripts of approximately 10, 6.0 and 5.5 kb. Immunofluorescence analysis revealed predominant plasma membrane expression with some intracellular punctate staining. Overexpression of ABCC5 did not increase resistance to various classes of anticancer drugs.

▼ Gene Function
Wijnholds et al. (2000) reported the functional characterization of human MRP5. They found resistance against the thiopurine anticancer drugs 6-mercaptopurine (6-MP) and thioguanine, and the anti-HIV drug 9-(2-phosphonylmethoxyethyl)adenine (PMEA). This resistance was due to an increased extrusion of PMEA and 6-thioinosine monophosphate from the cells that overproduce MRP5. The authors speculated that MRP5 may play a role in some cases of unexplained resistance to thiopurines in acute lymphoblastic leukemia and/or to antiretroviral nucleoside analogs in HIV-affected patients.

Oguri et al. (2000) noted that the effectiveness of platinum drugs in lung cancer is limited by the development of drug resistance to them. Quantitative RT-PCR analysis showed that expression of ABCC5, like that of ABCC1 (158343) and gamma-glutamylcysteine synthetase (see 606857), is increased in normal and tumor lung tissue from patients with previous platinum exposure. However, in vitro exposure of lung cancer cells to the platinum drug cisplatin, or of mononuclear cells to carboplatin, does not cause increased expression of ABCC5.

▼ Mapping
By radiation hybrid analysis, Kool et al. (1997) mapped the ABCC5 gene to chromosome 3. Using FISH, Suzuki et al. (1997) and Belinsky et al. (1998) refined the localization to 3q27.

Tags: 3q27.1