9.B.188 The Transmembrane Emp24 Domain-containing Protein (TMED) Family 

Members of this family are involved in vesicular protein trafficking and mainly function in the early secretory pathway, but also in post-Golgi membranes. Thought to act as cargo receptor at the lumenal side for incorporation of secretory cargo molecules into transport vesicles and to be involved in vesicle coat formation at the cytoplasmic side. In COPII vesicle-mediated anterograde transport, involved in the transport of GPI-anchored proteins and proposed to act together with TMED10 as their cargo receptor; the function specifically implies SEC24C and SEC24D of the COPII vesicle coat and lipid raft-like microdomains of the ER. Recognizes GPI anchors structural remodeled in the ER by PGAP1 and MPPE1. COPI vesicle-mediated retrograde transport inhibits the GTPase-activating activity of ARFGAP1 towards ARF1 thus preventing immature uncoating and allowing cargo selection to take place. Involved in trafficking of G protein-coupled receptors (GPCRs). Regulates F2RL1, OPRM1 and P2RY4 exocytic trafficking from the Golgi to the plasma membrane, thus contributing to receptor resensitization. Facilitates CASR maturation and stabilization in the early secretory pathway and increases CASR plasma membrane targeting. Proposed to be involved in the organization of intracellular membranes such as the maintenance of the Golgi apparatus. May also play a role in the biosynthesis of secreted cargo such as eventual processing (Beck et al. 2009).



This family belongs to the .

 

References:

Hou, W., S. Gupta, M.C. Beauchamp, L. Yuan, and L.A. Jerome-Majewska. (2017). Non-alcoholic fatty liver disease in mice with heterozygous mutation in TMED2. PLoS One 12: e0182995.

Luo, W., Y. Wang, and G. Reiser. (2011). Proteinase-activated receptors, nucleotide P2Y receptors, and μ-opioid receptor-1B are under the control of the type I transmembrane proteins p23 and p24A in post-Golgi trafficking. J Neurochem 117: 71-81.

Examples:

TC#NameOrganismal TypeExample
9.B.188.1.1

The transmembrane (2 TMSs, N- and C-termini) Emp24 domain-containing protein 1, TMED1 of 227 aas.

Animals

TMED1 of Homo sapiens

 
9.B.188.1.2

The transmembrane (2 TMSs, N- and C-termini) Emp24 domain-containing protein 2, TMED2 or RNP24 of 201 aas. A role for TMED2 in liver health has been suggested (Hou et al. 2017).

Animals

TMED2 of Homo sapiens

 
9.B.188.1.3

The transmembrane (2 TMSs, N- and C-termini) Emp24 domain-containing protein 3, TMED3 of 217 aas.

Animals

TMED3 of Homo sapiens

 
9.B.188.1.4

Transmembrane emp24 domain-containing protein 10 precursor, Tmed10 or TMP21, of 219 aas and 2 TMSs, N- and C-terminal. It is involved in vesicular protein trafficking in the early secretory pathway, probably as a cargo receptor at the lumenal side for incorporation of secretory cargo molecules into transport vesicles (Luo et al. 2011).

Tmed10 of Homo sapiens