TMED10

Description

The TMED10 (transmembrane p24 trafficking protein 10) is a protein-coding gene located on chromosome 14.

Transmembrane emp24 domain-containing protein 10 is a protein that in humans is encoded by the TMED10 gene. This gene is a member of the EMP24/GP25L/p24 family and encodes a protein with a GOLD domain. This type I membrane protein is localized to the plasma membrane and golgi cisternae and is involved in vesicular protein trafficking. The protein 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 this gene have been associated with early-onset familial Alzheimer's disease. This gene has a pseudogene on chromosome 8.

TMED10 is a cargo receptor that plays a crucial role in protein vesicular trafficking and quality control within the endoplasmic reticulum (ER) and Golgi apparatus. It belongs to the p24 protein family, which are transmembrane proteins that bind coat protein complex I/COPI and coat protein complex II/COPII, facilitating vesicle transport between membranes. TMED10 acts on the lumenal side for the incorporation of secretory cargo molecules into transport vesicles and participates in vesicle coat formation on the cytoplasmic side. It primarily functions in the early secretory pathway, cycling between the ER, ER-Golgi intermediate compartment (ERGIC), and Golgi, mediating cargo transport via COPI and COPII-coated vesicles. In COPII vesicle-mediated anterograde transport, TMED10 collaborates with TMED2 as a cargo receptor for GPI-anchored proteins, particularly involving SEC24C and SEC24D of the COPII vesicle coat and lipid raft-like microdomains of the ER. It recognizes GPI anchors structurally remodeled in the ER by the GPI inositol-deacylase/PGAP1 and the metallophosphoesterase MPPE1/PGAP5. In COPI vesicle-mediated retrograde transport, TMED10 contributes to COPI vesicle biogenesis and vesicle coat recruitment. It participates in the trafficking of amyloid beta A4 protein and soluble APP-beta release, independent of gamma-secretase activity modulation. It also takes part in KDELR2-mediated retrograde transport of the toxin A subunit (CTX-A-K63) with COPI and the COOH terminus of KDELR2. On Golgi membranes, TMED10 acts as a primary receptor for ARF1-GDP, a GTP-binding protein involved in COPI-vesicle formation. It increases coatomer-dependent GTPase-activating activity of ARFGAP2, mediating the hydrolysis of ARF1-bound GTP, thereby modulating protein trafficking from the Golgi apparatus. TMED10 facilitates the exocytic trafficking of G protein-coupled receptors, such as F2LR1/PAR2 (trypsin and trypsin-like enzyme receptor), OPRM1 (opioid receptor), and P2RY4 (UTD and UDP receptor), from the Golgi to the plasma membrane, contributing to receptor resensitization. In addition to its cargo receptor function, TMED10 can act as a protein channel after oligomerization, facilitating the post-translational entry of leaderless cytoplasmic cargo into the ERGIC. It plays a role in the translocation into ERGIC, vesicle entry, and secretion of leaderless cargos, including mature forms of interleukin 1/IL-1 family members, the alpha-crystallin B chain HSPB5, carbohydrate-binding proteins galectin-1/LGALS1 and galectin-3/LGALS3, the microtubule-associated protein Tau/MAPT, and the annexin A1/ANXA1. This translocation process relies on cargo protein unfolding and is enhanced by chaperones HSP90AB1 and HSP90B1/GRP9. TMED10 can also associate with the presenilin-dependent gamma-secretase complex, regulating gamma-cleavages of the amyloid beta A4 protein to produce amyloid-beta 40/Abeta40.

TMED10 is also known as P24(DELTA), S31I125, S31III125, TMP21, Tmp-21-I, p23, p24d1.

Associated Diseases

WES Whole Exome Sequencing