Multidrug resistance-associated protein 5 (ABCC5)
The protein contains 1437 amino acids for an estimated molecular weight of 160660 Da.
Acts as a multispecific organic anion pump which can transport nucleotide analogs. Heme transporter required for the translocation of cytosolic heme to the secretory pathway (PubMed:24836561). (updated: April 22, 2020)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt, is predicted to be membranous by TOPCONS.
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Biological Process
CAMP transport
Carbohydrate metabolic process
CGMP transport
Export across plasma membrane
Folate transmembrane transport
Glutathione transmembrane transport
Glycosaminoglycan metabolic process
Heme transmembrane transport
Hyaluronan biosynthetic process
Hyaluronan metabolic process
Pathogenesis
Purine nucleotide transport
Small molecule metabolic process
Transmembrane transport
Transport
Transport across blood-brain barrier
Xenobiotic transport
Cellular Component
Apical plasma membrane
Basolateral plasma membrane
Cell surface
Endosome membrane
Golgi lumen
Integral component of plasma membrane
Membrane
Plasma membrane
Molecular Function
ABC-type xenobiotic transporter activity
ATP binding
ATPase
ATPase-coupled anion transmembrane transporter activity
ATPase-coupled transmembrane transporter activity
Efflux transmembrane transporter activity
Glutathione transmembrane transporter activity
Heme transmembrane transporter activity
Organic anion transmembrane transporter activity
Purine nucleotide transmembrane transporter activity
Xenobiotic transmembrane transporter activity
The reference OMIM entry for this protein is 605251
Atp-binding cassette, subfamily c, member 5; abcc5
Multidrug resistance-associated protein 5; mrp5
Moatc
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
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. ... More on the omim web site
April 25, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 605251 was added.