TMED2_HUMAN » Transmembrane emp24 domain-containing protein 2

TMED2_HUMAN » Transmembrane emp24 domain-containing protein 2
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Topology in Vesicle membrane
Topologyvesicle lumenal side
cytoplasmic side
TMED2_HUMAN » Transmembrane emp24 domain-containing protein 2 » Membrane protein p24A;p24;p24 family protein beta-1;p24beta1;
Hydrophobic Thickness 32.0 ± 2.0 Å
Tilt Angle 1 ± 2°
ΔGtransfer -35.9 kcal/mol
ΔGfold -12.4 kcal/mol
Links UniProtKB, Pfam, Interpro, iHOP, STRING, HGNC
Topology Out
TM Segments 169-191 (163-198)
Pathways none
PDB none
OPM none
Complexes none
Interactions

1B07, Complex: 1B07:TMED2, PubMed

ESR1, Complex: TMED2:ESR1, PubMed

LMAN1, Complex: LMAN1:TMED2, PubMed

NICA, Complex: TMED2:NICA, PubMed

TMED4, Complex: TMED2:TMED4, PubMed

TMED7, Complex: TMED7:TMED2, PubMed

TMED9, Complex: TMED2:TMED9, PubMed

TMEDA, Complex: TMEDA:TMED2, PubMed

Domains

AA: 20-196, PDBID: 1M23, Subunit A, Seq Identity:16%, emp24/gp25L/p24 family/GOLD

UniProt annotation for TMED2_HUMAN » Transmembrane emp24 domain-containing protein 2
FUNCTION: Involved in vesicular protein trafficking. Mainly functions 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. In 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 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.

SUBUNIT: Monomer and homodimer in the endoplasmic reticulum, endoplasmic reticulum-Golgi intermediate compartment and Golgi. Probably oligomerizes with other members of the EMP24/GP25L family such as TMED7, TMED9 and TMED10. Interacts with TMED10. Associates with the COPI vesicle coat (coatomer); TMED10:TMED2 heterotetramers are proposed to be involved in coatomer association. Interacts (via C-terminus) with COPG1; the interaction involves dimeric TMED2. Interacts with SEC23A; indicative for an association of TMED2 with the COPII vesicle coat. Interacts with ARF1 and ARFGAP1 (By similarity). Interacts with CD59, SEC24A, SEC24B, SEC24C, SEC24D and ATLA1. Interacts with KDELR1; the interaction is decreased by KDEL ligand (By similarity). Interacts with F2RL1; the interaction occurs at the Golgi apparatus. Interacts with CASR (immaturely glycosylated form); the interaction occurs in the endoplasmic reticulum-Golgi intermediate compartment or cis-Golgi. Interacts with F2RL1; the interaction occurs at the Golgi apparatus. Interacts with GORASP1 and GORASP2 (By similarity). Found in a complex composed at least of SURF4, TMED2 and TMED10.

MISCELLANEOUS: Ectopic expression of TMED2 alone does not result in its proper cis-Golgi network localization. Coexpression of TMED10 is necessary, and coexpression of TMED3 and/or TMED9 is facilitating localization. Down-regulation of TMED10 expression reduces TMED2 protein level.

UniProt features for TMED2_HUMAN » Transmembrane emp24 domain-containing protein 2
SIGNAL 1 20 Potential.
CHAIN 21 201 Transmembrane emp24 domain-containing protein 2.
DOMAIN 30 112 GOLD.
REGION 1 181 Interaction with F2RL1.
REGION 118 157 Required for TMED10 and TMED2 cis-Golgi network localization.
COILED 117 167 Potential.
MOTIF 194 201 COPI vesicle coat-binding (Potential).
MOTIF 194 195 COPII vesicle coat-binding (Potential).
Amino Acid Sequence for TMED2_HUMAN » Transmembrane emp24 domain-containing protein 2
MVTLAELLVL LAALLATVSG YFVSIDAHAE ECFFERVTSG TKMGLIFEVA EGGFLDIDVE ITGPDNKGIY KGDRESSGKY TFAAHMDGTY KFCFSNRMST MTPKIVMFTI DIGEAPKGQD METEAHQNKL EEMINELAVA MTAVKHEQEY MEVRERIHRA INDNTNSRVV LWSFFEALVL VAMTLGQIYY LKRFFEVRRV V