AP5M1
Identifiers
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
Gene location (Human) Chr. Chromosome 14 (human)[1] Band 14q22.3 Start 57,268,924 bp[1] End 57,298,742 bp[1]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in jejunal mucosa endothelial cell retinal pigment epithelium palpebral conjunctiva rectum right ventricle duodenum kidney tubule Brodmann area 23 biceps brachii n/a More reference expression data BioGPS n/a
Gene ontology Molecular function protein binding Cellular component cytoplasm lysosomal membrane cytosol endosome late endosome lysosome AP-type membrane coat adaptor complex membrane late endosome membrane Biological process protein transport endosomal transport Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 55745 74385 Ensembl ENSG00000053770 n/a UniProt Q9H0R1 Q8BJ63 RefSeq (mRNA) NM_018229 NM_144535 NM_001360070 RefSeq (protein) NP_060699 NP_653118 NP_001346999 Location (UCSC) Chr 14: 57.27 – 57.3 Mb n/a PubMed search [2] [3]
Wikidata
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The 3D structure of the protein AP5M1. The alpha fold structure was obtained from Uniprot (AF-Q9H0R1-F1) and modeled using ChimeraX. The three domains are emphasized with color. The first domain is yellow, the second domain is teal, and the third domain is pink.

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]

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]   

References