AP5M1

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
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; OMA:AP5M1 - orthologs
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 Epithelium of choroid plexus endothelial cell mucosa of sigmoid colon retinal pigment epithelium palpebral conjunctiva rectum right ventricle duodenum kidney tubule 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.

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]