AP5M1
Protein-coding gene in the species Homo sapiens
From Wikipedia, the free encyclopedia
AP-5 complex subunit mu (AP5M1), otherwise known as MUDENG (MuD), is a protein that is encoded by the AP5M1 gene.[4] The AP5M1 gene was originally discovered when screening for genes which helped to promote death in Fas-mediated apoptosis.[5][6] It is a highly conserved gene.[5][7][6]
| AP5M1 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Aliases | AP5M1, C14orf108, MUDENG, Mu5, MuD, adaptor related protein complex 5 mu 1 subunit, adaptor related protein complex 5 subunit mu 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 614368; MGI: 1921635; HomoloGene: 10081; GeneCards: AP5M1; OMA:AP5M1 - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
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MuD is the medium-sized subunit of the AP5 adaptor complex.[8] MuD is expressed throughout the body and is located within both the mitochondria as well as the endoplasmic reticulum (ER) of cells.[5][7][6]
MuD has been shown to have the ability to induce apoptosis; however, there is evidence that it plays an anti-apoptotic role in apoptosis mediated by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL).[5][7][6][9][10]
Structure
MuD consists of 490 amino acids that interact to form a tertiary structure with three domains.[11][12]
The overall structure shares similarities with adaptor protein (AP) complexes that are related to clathrin-mediated endocytosis; amino acids 197 through 417 are a shared adaptin domain found in AP μ subunits.[13][14]
Within the adaptin domain are two aspartic acids, D276 and D290, which serve as binding sites for caspase-3.[14]
Function
The overall function of MuD remains unclear.[15] It is known, however, that MuD regulates the expression of BAX, a pro-apoptotic member of the Bcl-2 family of proteins.[16][15] Due to— and dependent upon— this relationship, MuD has been able to induce cell death in tumor cells.[17][16][15]
Additionally, MuD has been suggested to be involved in endosomal trafficking.[17][16][18][15]
TRAIL and MuD
TRAIL, an apoptosis-inducing ligand, activates caspase-8 and caspase-3, which initiate the intrinsic pathway of apoptosis by cleaving BH3 interacting-domain death agonist (Bid) into tBid, another pro-apoptotic member of the Bl-2 protein family.[19][20][21][22] MuD interferes with this process because D276 and D290 act as alternative binding sites for caspase-3, decreasing the amount of Bid that gets cleaved.[20][19][21] Tumor cells being treated with TRAIL are 32% more likely to survive when MuD is being expressed.[19]