Species Human Entrez 368 | Human Mouse Ensembl n/a | |
Aliases ABCC6, ABC34, ARA, EST349056, GACI2, MLP1, MOAT-E, MOATE, MRP6, PXE, PXE1, URG7, ATP binding cassette subfamily C member 6 External IDs OMIM: 603234 MGI: 1351634 HomoloGene: 55559 GeneCards: ABCC6 | ||
Multidrug resistance-associated protein 6 (MRP6) also known as ATP-binding cassette sub-family C member 6 (ABCC6) and multi-specific organic anion transporter E (MOAT-E) is a protein that in humans is encoded by the ABCC6 gene. The protein encoded by the ABCC6 gene is a member of the superfamily of ATP-binding cassette (ABC) transporters.
Contents
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). This protein is a member of the MRP subfamily which is involved in multidrug resistance.
Pathology
Mutations in this protein cause pseudoxanthoma elasticum (PXE). The most common mutations, R1141X and 23-29del, account for about 25% of the found mutations.
Premature atherosclerosis is also associated with mutations in the ABCC6 gene, even in those without PXE.
Deficiency of Abcc6 in mouse models of ischemia leads to larger infarcts, which can be rescued by Abcc6 overexpression.
Location
Abcc6 gene encodes an intracellular transporter associated with mitochondrial function, located in the mitochondrial-associated membrane (MAM), whereas its substrate can be located in either MAM, cytosol or ER. Abcc6 is primarily expressed in liver and kidney,.
Signaling Pathways
It has been observed less Smad1/5/8 activation in the presence of Abcc6 than in mice lacking that gene in liver, kidney, heart, muscle, aorta and lungs. ALK1, ALK2 and ALK3 expression are higher in kidneys, but lower in liver, with functional Abcc6 and its presence causes higher expression of BMP2 in kidney and a decrease in its expression in liver. In the presence of Abcc6, BMP-4, BMP-6 and BMP-7 expression is increased in kidney and decreased in liver. Abcc6 deficient mice show higher BMP activation in the heart.