TMED10

TMED10 is a member of the EMP24/GP25L/p24 family and encodes a protein with a GOLD domain. TMED10 is localized to the plasma membrane and golgi cisternae and is involved in vesicular protein trafficking. TMED10 is also a member of a heteromeric secretase complex and regulates the complex's gamma-secretase activity without affecting its epsilon-secretase activity. Mutations in TMED10 have been associated with early-onset familial Alzheimer's disease.

Transmembrane P24 Trafficking Protein 10

Cargo receptor involved in protein vesicular trafficking and quality control in the endoplasmic reticulum (ER) and Golgi (PubMed:10052452, PubMed:11726511, PubMed:16641999, PubMed:17288597, PubMed:19296914, PubMed:20427317, PubMed:21219331, PubMed:27569046).
The p24 protein family is a group of transmembrane proteins that bind coat protein complex I/COPI and coat protein complex II/COPII involved in vesicular trafficking between the membranes (PubMed:10052452).
Acts at the lumenal side for incorporation of secretory cargo molecules into transport vesicles and involved in vesicle coat formation at the cytoplasmic side (PubMed:20427317, PubMed:27569046).
Mainly functions in the early secretory pathway and cycles between the ER, ER-Golgi intermediate compartment (ERGIC) and Golgi, mediating cargo transport through COPI and COPII-coated vesicles (PubMed:10052452, PubMed:10852829, PubMed:12237308).
In COPII vesicle-mediated anterograde transport, involved in the transport of GPI-anchored proteins by acting together with TMED2 as their cargo receptor; the function specifically implies SEC24C and SEC24D of the COPII vesicle coat and lipid raft-like microdomains of the ER (PubMed:20427317, PubMed:27569046).
Recognizes GPI anchors structural remodeled in the ER by the GPI inositol-deacylase/PGAP1 and the metallophosphoesterase MPPE1/PGAP5 (By similarity).
In COPI vesicle-mediated retrograde transport, involved in the biogenesis of COPI vesicles and vesicle coat recruitment (PubMed:11726511).
Involved in trafficking of amyloid beta A4 protein and soluble APP-beta release (independent from the modulation of gamma-secretase activity) (PubMed:17288597).
Involved in the KDELR2-mediated retrograde transport of the toxin A subunit (CTX-A-K63)together with COPI and the COOH terminus of KDELR2 (By similarity).
On Golgi membranes, acts as primary receptor for ARF1-GDP, a GTP-binding protein involved in COPI-vesicle formation (PubMed:11726511).
Increases coatomer-dependent GTPase-activating activity of ARFGAP2 which mediates the hydrolysis of ARF1-bound GTP and therefore modulates protein trafficking from the Golgi apparatus (PubMed:19296914).
Involved in the exocytic trafficking of G protein-coupled receptors F2LR1/PAR2 (trypsin and tryspin-like enzyme receptor), OPRM1 (opioid receptor) and P2RY4 (UTD and UDP receptor) from the Golgi to the plasma membrane, thus contributing to receptor resensitization (PubMed:21219331).
In addition to its cargo receptor activity, may also act as a protein channel after oligomerization, facilitating the post-translational entry of leaderless cytoplasmic cargo into the ERGIC (PubMed:32272059).
Involved in the translocation into ERGIC, the vesicle entry and the secretion of leaderless cargos (lacking the secretion signal sequence), including the mature form of interleukin 1/IL-1 family members, the alpha-crystallin B chain HSPB5, the carbohydrate-binding proteins galectin-1/LGALS1 and galectin-3/LGALS3, the microtubule-associated protein Tau/MAPT, and the annexin A1/ANXA1; the translocation process is dependent on cargo protein unfolding and enhanced by chaperones HSP90AB1 and HSP90B1/GRP9 (PubMed:32272059).
Could also associates with the presenilin-dependent gamma-secretase complex in order to regulate gamma-cleavages of the amyloid beta A4 protein to yield amyloid-beta 40/Abeta40 (PubMed:16641999).

Biological Process COPI coating of Golgi vesicleSource:UniProtKB1 Publication
Biological Process COPI-coated vesicle buddingSource:UniProtKB1 Publication
Biological Process COPII vesicle coatingSource:UniProtKB1 Publication
Biological Process cytosol to ERGIC protein transportSource:UniProtKB1 Publication
Biological Process endoplasmic reticulum to Golgi vesicle-mediated transportSource:GO_Central1 Publication
Biological Process Golgi organizationSource:GO_Central1 Publication
Biological Process intracellular protein transportSource:UniProtKB1 Publication
Biological Process negative regulation of aspartic-type endopeptidase activity involved in amyloid precursor protein catabolic processSource:Ensembl
Biological Process positive regulation of interleukin-1 productionSource:UniProtKB1 Publication
Biological Process positive regulation of protein secretionSource:UniProtKB1 Publication
Biological Process protein localization to ERGICSource:UniProtKB1 Publication
Biological Process regulated exocytosisSource:HGNC-UCL
Biological Process regulation of amyloid-beta formationSource:UniProtKB1 Publication
Biological Process retrograde vesicle-mediated transport, Golgi to endoplasmic reticulumSource:UniProtKB
Biological Process vesicle cargo loadingSource:UniProtKB1 Publication
Biological Process vesicle targeting, to, from or within GolgiSource:HGNC-UCL

Endoplasmic reticulum membrane
Endoplasmic reticulum-Golgi intermediate compartment membrane Analysis
Golgi apparatus membrane
Golgi apparatus, cis-Golgi network membrane
Golgi apparatus, trans-Golgi network membrane
Cytoplasmic vesicle, secretory vesicle membrane
Cell membrane
Melanosome
Identified by mass spectrometry in melanosome fractions from stage I to stage IV.

Lumenal: 32-185
Helical: 186-206
Cytoplasmic: 207-219