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Transmembrane emp24 domain-containing protein 2 (COPI-coated vesicle membrane protein p24) (Membrane protein p24A) (Sid 394) (p24 family protein beta-1) (p24beta1)

 TMED2_MOUSE             Reviewed;         201 AA.
24-JAN-2001, integrated into UniProtKB/Swiss-Prot.
01-MAY-2000, sequence version 1.
18-JUL-2018, entry version 148.
RecName: Full=Transmembrane emp24 domain-containing protein 2;
AltName: Full=COPI-coated vesicle membrane protein p24;
AltName: Full=Membrane protein p24A;
AltName: Full=Sid 394;
AltName: Full=p24 family protein beta-1;
Flags: Precursor;
Name=Tmed2; Synonyms=Rnp24, Sid394;
Mus musculus (Mouse).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
Muroidea; Muridae; Murinae; Mus; Mus.
Seki N., Hattori A., Hayashi A., Kozuma S., Muramatsu M., Saito T.;
"Mouse mRNA for transmembrane protein.";
Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases.
STRAIN=FVB/N-3; TISSUE=Mammary gland;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung,
Pancreas, Spleen, and Testis;
PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
"A tissue-specific atlas of mouse protein phosphorylation and
Cell 143:1174-1189(2010).
PubMed=20178780; DOI=10.1016/j.ydbio.2010.02.019;
Jerome-Majewska L.A., Achkar T., Luo L., Lupu F., Lacy E.;
"The trafficking protein Tmed2/p24beta(1) is required for
morphogenesis of the mouse embryo and placenta.";
Dev. Biol. 341:154-166(2010).
-!- 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 (By similarity). Required for
morphogenesis of embryo and placenta. {ECO:0000250,
-!- 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 (via GOLD domain) with
TMED10 (via GOLD domain). 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. Interacts with
CD59, SEC24A, SEC24B, SEC24C, SEC24D and ATLA1. Interacts with
KDELR1; the interaction is decreased by KDEL ligand. 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.
Found in a complex composed at least of SURF4, TMED2 and TMED10
(By similarity). {ECO:0000250|UniProtKB:Q15363,
-!- SUBCELLULAR LOCATION: Cytoplasmic vesicle membrane
{ECO:0000250|UniProtKB:Q15363}; Single-pass type I membrane
protein {ECO:0000255}. Cytoplasmic vesicle, COPI-coated vesicle
membrane {ECO:0000250|UniProtKB:Q15363}; Single-pass type I
membrane protein {ECO:0000255}. Golgi apparatus, cis-Golgi network
membrane {ECO:0000250|UniProtKB:Q15363}; Single-pass type I
membrane protein {ECO:0000255}. Golgi apparatus, Golgi stack
membrane {ECO:0000250|UniProtKB:Q15363}; Single-pass type I
membrane protein {ECO:0000255}. Endoplasmic reticulum membrane
{ECO:0000250|UniProtKB:Q15363}; Single-pass type I membrane
protein {ECO:0000255}. Endoplasmic reticulum-Golgi intermediate
compartment membrane {ECO:0000250|UniProtKB:Q15363}; Single-pass
type I membrane protein {ECO:0000255}. Note=Cycles between
compartments of the early secretatory pathway.
-!- DEVELOPMENTAL STAGE: Expressed during embryonal and placental
development. {ECO:0000269|PubMed:20178780}.
-!- MISCELLANEOUS: Embryonic lethal for homozygotes with Glu-15 in the
signal peptide. Animals do not show Tmed2 protein expression and
also have reduced protein levels of Tmed7 and Tmed10. Prior to
death at mid-gestation, embryos exhibit developmental delay,
abnormal rostral-caudal elongation, randomized heart looping, and
absence of the labyrinth layer of the placenta.
-!- SIMILARITY: Belongs to the EMP24/GP25L family. {ECO:0000305}.
Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
Distributed under the Creative Commons Attribution (CC BY 4.0) License
EMBL; AB025218; BAA84689.1; -; mRNA.
EMBL; BC083140; AAH83140.1; -; mRNA.
CCDS; CCDS19679.1; -.
RefSeq; NP_062744.1; NM_019770.2.
RefSeq; XP_003945495.1; XM_003945446.4.
UniGene; Mm.325307; -.
UniGene; Mm.425279; -.
ProteinModelPortal; Q9R0Q3; -.
SMR; Q9R0Q3; -.
BioGrid; 207909; 116.
IntAct; Q9R0Q3; 120.
STRING; 10090.ENSMUSP00000054834; -.
iPTMnet; Q9R0Q3; -.
PhosphoSitePlus; Q9R0Q3; -.
EPD; Q9R0Q3; -.
MaxQB; Q9R0Q3; -.
PaxDb; Q9R0Q3; -.
PeptideAtlas; Q9R0Q3; -.
PRIDE; Q9R0Q3; -.
Ensembl; ENSMUST00000060226; ENSMUSP00000054834; ENSMUSG00000029390.
GeneID; 100862175; -.
GeneID; 56334; -.
KEGG; mmu:100862175; -.
KEGG; mmu:56334; -.
UCSC; uc008zqa.1; mouse.
CTD; 10959; -.
MGI; MGI:1929269; Tmed2.
eggNOG; KOG1692; Eukaryota.
GeneTree; ENSGT00670000097656; -.
HOGENOM; HOG000160229; -.
HOVERGEN; HBG105106; -.
InParanoid; Q9R0Q3; -.
KO; K20347; -.
OrthoDB; EOG091G0L5D; -.
PhylomeDB; Q9R0Q3; -.
TreeFam; TF313000; -.
Reactome; R-MMU-1912420; Pre-NOTCH Processing in Golgi.
Reactome; R-MMU-204005; COPII-mediated vesicle transport.
Reactome; R-MMU-5694530; Cargo concentration in the ER.
Reactome; R-MMU-6807878; COPI-mediated anterograde transport.
Reactome; R-MMU-6811434; COPI-dependent Golgi-to-ER retrograde traffic.
PRO; PR:Q9R0Q3; -.
Proteomes; UP000000589; Chromosome 5.
Bgee; ENSMUSG00000029390; -.
CleanEx; MM_TMED2; -.
ExpressionAtlas; Q9R0Q3; baseline and differential.
Genevisible; Q9R0Q3; MM.
GO; GO:0030137; C:COPI-coated vesicle; ISS:UniProtKB.
GO; GO:0030663; C:COPI-coated vesicle membrane; IEA:UniProtKB-SubCell.
GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
GO; GO:0005793; C:endoplasmic reticulum-Golgi intermediate compartment; ISS:UniProtKB.
GO; GO:0033116; C:endoplasmic reticulum-Golgi intermediate compartment membrane; IEA:UniProtKB-SubCell.
GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
GO; GO:0032580; C:Golgi cisterna membrane; IEA:UniProtKB-SubCell.
GO; GO:0016021; C:integral component of membrane; ISS:HGNC.
GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
GO; GO:0042589; C:zymogen granule membrane; ISS:HGNC.
GO; GO:0048598; P:embryonic morphogenesis; IMP:UniProtKB.
GO; GO:0001892; P:embryonic placenta development; IMP:MGI.
GO; GO:0007030; P:Golgi organization; ISS:UniProtKB.
GO; GO:0001947; P:heart looping; IMP:MGI.
GO; GO:0001701; P:in utero embryonic development; IMP:MGI.
GO; GO:0006886; P:intracellular protein transport; IEA:Ensembl.
GO; GO:0060716; P:labyrinthine layer blood vessel development; IMP:CACAO.
GO; GO:0001893; P:maternal placenta development; IMP:UniProtKB.
GO; GO:0035264; P:multicellular organism growth; IMP:MGI.
GO; GO:0034260; P:negative regulation of GTPase activity; ISS:UniProtKB.
GO; GO:0001843; P:neural tube closure; IMP:MGI.
GO; GO:0010628; P:positive regulation of gene expression; IMP:MGI.
GO; GO:0036342; P:post-anal tail morphogenesis; IMP:MGI.
GO; GO:0072659; P:protein localization to plasma membrane; ISS:UniProtKB.
GO; GO:0032525; P:somite rostral/caudal axis specification; IMP:MGI.
GO; GO:0001756; P:somitogenesis; IMP:MGI.
GO; GO:0016192; P:vesicle-mediated transport; IEA:UniProtKB-KW.
InterPro; IPR009038; GOLD_dom.
InterPro; IPR036598; GOLD_dom_sf.
InterPro; IPR015720; TMP21-related.
PANTHER; PTHR22811; PTHR22811; 1.
Pfam; PF01105; EMP24_GP25L; 1.
SMART; SM01190; EMP24_GP25L; 1.
SUPFAM; SSF101576; SSF101576; 1.
PROSITE; PS50866; GOLD; 1.
1: Evidence at protein level;
Coiled coil; Complete proteome; Cytoplasmic vesicle;
Endoplasmic reticulum; ER-Golgi transport; Golgi apparatus; Membrane;
Protein transport; Reference proteome; Signal; Transmembrane;
Transmembrane helix; Transport.
SIGNAL 1 20 {ECO:0000255}.
CHAIN 21 201 Transmembrane emp24 domain-containing
protein 2.
TOPO_DOM 21 168 Lumenal. {ECO:0000255}.
TRANSMEM 169 189 Helical. {ECO:0000255}.
TOPO_DOM 190 201 Cytoplasmic. {ECO:0000255}.
DOMAIN 30 112 GOLD. {ECO:0000255|PROSITE-
REGION 1 181 Interaction with F2RL1. {ECO:0000250}.
REGION 118 157 Required for TMED10 and TMED2 cis-Golgi
network localization. {ECO:0000250}.
COILED 117 167 {ECO:0000255}.
MOTIF 194 201 COPI vesicle coat-binding. {ECO:0000255}.
MOTIF 194 195 COPII vesicle coat-binding.
MUTAGEN 15 15 L->E: Embryonic lethal.
SEQUENCE 201 AA; 22705 MW; F5DE259FC419CF85 CRC64;

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