Common Name:	MRP5
HGNC Symbol:	ABCC5
HGNC Description:	ATP-binding cassette, sub-family C (CFTR/MRP), member 5
HGNC ID:	56
Chromosome:	Chr.3(-): 185120416-185218421
Location:	3q27
OMIM:	605251
OMIM Phenotype:	None
Accessions:	AF104942
Nucleotide RefSeq:	NM_005688
Protein RefSeq:	NP_005679
Entrez:	10057
Isoforms:	2
Evidence:	Substrate In Vitro Evidence: 1. MRP5 retrovirus-overproducing HEK293 and MDCKII cells were generated. Cytotoxicity assays using HEK293 cells showed that MRP5 caused resistance to 6-mercaptopurine, its prodrug azathioprine, thioguanine, 5-HP, and PMEA, but not to etoposide or teniposide. Wijnholds, J et al. PNAS 2000 Jun 20, 97(13):7476-81. 2. MRP5 is a GS-X pump because it transports DNP-GS and is inhibited by typical OAT inhibitors such as sulfinpyrazone. Wijnholds, J et al. PNAS 2000 Jun 20, 97(13):7476-81. 3. MRP5 expressed in inside-out membrane vesicles was used to test transport of cGMP and camp. Data indicate that MRP5 is a low-affinity cyclic nucleotide transporter that may function as an overflow pump. Wielinga, PR et al. JBC 2003 May 16, 278(20):17664-71 PMID 12637526. 4. Inside-out vesicles derived from MRP5-overexpressing cells accumulated alaninyl-d4TMP. Based on inhibitor screening, the affinity of MRP5 for nucleotide-based substrates is low. Reid, G et al. Mol Pharm 2003 May, 63(5):1094-103 PMID 12695538. Substrate In Vivo Evidence: 1. MRP5 expression in matched normal lung and lung cancer biopsies was examined by RT-PCR. Results suggest that exposure to platinum drugs in lung cancer and/or the chronic stress response to xenobiotics increased MRP5 expression levels. Oguri, T et al. Int J Cancer 2000 Apr 1, 86(1):95-100 PMID 10728601. 2. MRP5 knockout mice are healthy and fertile. Wijnholds, J et al. PNAS 2000 Jun 20, 97(13):7476-81. Tissue Distribution Evidence: 1. EST database screening demonstrates MRP5 expression in almost every tissue tested. MRP5 is overexpressed in a few cell lines, and RNA levels don't correlate with doxorubicin or cisplatin resistance. Kool, M et al. Cancer Res 1997 Aug 15, 57(16):3537-47 PMID 9270026. 2. In polarized MDCKII/MRP5 cells, MRP5 is localized to the basolateral plasma membranes. In non-polarized HEK293/MRP5 cells, MRP5 was predominantly intracellular with some membrane staining. Wijnholds, J et al. PNAS 2000 Jun 20, 97(13):7476-81. 3. MRP5 is localized in cardiac and cardiovascular myocytes as well as endothelial cells with increased expression in ischemic cardiomyopathy. MRP5-mediated cellular export my be a novel, disease-dependent pathway for cGMP removal from cardiac cells. Dazert, P et al. Am J Path 2003 Oct, 163(4):1567-77 PMID 14507663.
Tissues:	ubiquitous, increased expression in cardiac tissue in ischemic cardiomyopathy
Type:	protein coding
Sets:	II,IV
PharmGKB ID:	PA395
HPRD ID:	06898
Substrates:	6-MP, PMEA, low affinity for cyclic nucleotides
Trivial Names:	MRP5, SMRP, ABC33, MOATC, MOAT-C, pABC11, EST277145, DKFZp686C1782
Transcripts:	NM_001023587 [Chr.3(-): 185184235-185218421] NM_005688 [Chr.3(-): 185120416-185218421]

ABCC5 Resequencing

Transmembrane prediction:

Non-synonymous amino acid changes shown in red, indels (insertions and deletions) in blue, and synonymous changes in green. Exon(s) indicated by black outlines.