TMED2_MOUSE
ID TMED2_MOUSE Reviewed; 201 AA.
AC Q9R0Q3;
DT 24-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 170.
DE RecName: Full=Transmembrane emp24 domain-containing protein 2;
DE AltName: Full=COPI-coated vesicle membrane protein p24;
DE AltName: Full=Membrane protein p24A;
DE AltName: Full=Sid 394;
DE AltName: Full=p24 family protein beta-1;
DE Short=p24beta1;
DE Flags: Precursor;
GN Name=Tmed2; Synonyms=Rnp24, Sid394;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Seki N., Hattori A., Hayashi A., Kozuma S., Muramatsu M., Saito T.;
RT "Mouse mRNA for transmembrane protein.";
RL Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N-3; TISSUE=Mammary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [4]
RP FUNCTION, DEVELOPMENTAL STAGE, AND MUTAGENESIS OF LEU-15.
RX PubMed=20178780; DOI=10.1016/j.ydbio.2010.02.019;
RA Jerome-Majewska L.A., Achkar T., Luo L., Lupu F., Lacy E.;
RT "The trafficking protein Tmed2/p24beta(1) is required for morphogenesis of
RT the mouse embryo and placenta.";
RL Dev. Biol. 341:154-166(2010).
CC -!- FUNCTION: Involved in vesicular protein trafficking. Mainly functions
CC in the early secretory pathway but also in post-Golgi membranes.
CC Thought to act as cargo receptor at the lumenal side for incorporation
CC of secretory cargo molecules into transport vesicles and to be involved
CC in vesicle coat formation at the cytoplasmic side. In COPII vesicle-
CC mediated anterograde transport involved in the transport of GPI-
CC anchored proteins and proposed to act together with TMED10 as their
CC cargo receptor; the function specifically implies SEC24C and SEC24D of
CC the COPII vesicle coat and lipid raft-like microdomains of the ER.
CC Recognizes GPI anchors structural remodeled in the ER by PGAP1 and
CC MPPE1. In COPI vesicle-mediated retrograde transport inhibits the
CC GTPase-activating activity of ARFGAP1 towards ARF1 thus preventing
CC immature uncoating and allowing cargo selection to take place. Involved
CC in trafficking of G protein-coupled receptors (GPCRs). Regulates F2RL1,
CC OPRM1 and P2RY4 exocytic trafficking from the Golgi to the plasma
CC membrane thus contributing to receptor resensitization. Facilitates
CC CASR maturation and stabilization in the early secretory pathway and
CC increases CASR plasma membrane targeting. Proposed to be involved in
CC organization of intracellular membranes such as the maintenance of the
CC Golgi apparatus. May also play a role in the biosynthesis of secreted
CC cargo such as eventual processing (By similarity). Required for
CC morphogenesis of embryo and placenta. {ECO:0000250,
CC ECO:0000269|PubMed:20178780}.
CC -!- SUBUNIT: Monomer and homodimer in the endoplasmic reticulum,
CC endoplasmic reticulum-Golgi intermediate compartment and Golgi.
CC Probably oligomerizes with other members of the EMP24/GP25L family such
CC as TMED7, TMED9 and TMED10. Interacts (via GOLD domain) with TMED10
CC (via GOLD domain). Associates with the COPI vesicle coat (coatomer);
CC TMED10:TMED2 heterotetramers are proposed to be involved in coatomer
CC association. Interacts (via C-terminus) with COPG1; the interaction
CC involves dimeric TMED2. Interacts with SEC23A; indicative for an
CC association of TMED2 with the COPII vesicle coat. Interacts with ARF1
CC and ARFGAP1. Interacts with CD59, SEC24A, SEC24B, SEC24C, SEC24D and
CC ATL1. Interacts with KDELR1; the interaction is decreased by KDEL
CC ligand. Interacts with F2RL1; the interaction occurs at the Golgi
CC apparatus. Interacts with CASR (immaturely glycosylated form); the
CC interaction occurs in the endoplasmic reticulum-Golgi intermediate
CC compartment or cis-Golgi. Interacts with F2RL1; the interaction occurs
CC at the Golgi apparatus. Interacts with GORASP1 and GORASP2. Found in a
CC complex composed at least of SURF4, TMED2 and TMED10 (By similarity).
CC {ECO:0000250|UniProtKB:Q15363, ECO:0000250|UniProtKB:Q63524}.
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle membrane
CC {ECO:0000250|UniProtKB:Q15363}; Single-pass type I membrane protein
CC {ECO:0000255}. Cytoplasmic vesicle, COPI-coated vesicle membrane
CC {ECO:0000250|UniProtKB:Q15363}; Single-pass type I membrane protein
CC {ECO:0000255}. Golgi apparatus, cis-Golgi network membrane
CC {ECO:0000250|UniProtKB:Q15363}; Single-pass type I membrane protein
CC {ECO:0000255}. Golgi apparatus, Golgi stack membrane
CC {ECO:0000250|UniProtKB:Q15363}; Single-pass type I membrane protein
CC {ECO:0000255}. Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q15363}; Single-pass type I membrane protein
CC {ECO:0000255}. Endoplasmic reticulum-Golgi intermediate compartment
CC membrane {ECO:0000250|UniProtKB:Q15363}; Single-pass type I membrane
CC protein {ECO:0000255}. Note=Cycles between compartments of the early
CC secretatory pathway. {ECO:0000250|UniProtKB:Q15363}.
CC -!- DEVELOPMENTAL STAGE: Expressed during embryonal and placental
CC development. {ECO:0000269|PubMed:20178780}.
CC -!- MISCELLANEOUS: Embryonic lethal for homozygotes with Glu-15 in the
CC signal peptide. Animals do not show Tmed2 protein expression and also
CC have reduced protein levels of Tmed7 and Tmed10. Prior to death at mid-
CC gestation, embryos exhibit developmental delay, abnormal rostral-caudal
CC elongation, randomized heart looping, and absence of the labyrinth
CC layer of the placenta.
CC -!- SIMILARITY: Belongs to the EMP24/GP25L family. {ECO:0000305}.
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DR EMBL; AB025218; BAA84689.1; -; mRNA.
DR EMBL; BC083140; AAH83140.1; -; mRNA.
DR CCDS; CCDS19679.1; -.
DR RefSeq; NP_062744.1; NM_019770.2.
DR RefSeq; XP_003945495.1; XM_003945446.4.
DR AlphaFoldDB; Q9R0Q3; -.
DR SMR; Q9R0Q3; -.
DR BioGRID; 207909; 118.
DR IntAct; Q9R0Q3; 120.
DR STRING; 10090.ENSMUSP00000054834; -.
DR iPTMnet; Q9R0Q3; -.
DR PhosphoSitePlus; Q9R0Q3; -.
DR EPD; Q9R0Q3; -.
DR jPOST; Q9R0Q3; -.
DR MaxQB; Q9R0Q3; -.
DR PaxDb; Q9R0Q3; -.
DR PeptideAtlas; Q9R0Q3; -.
DR PRIDE; Q9R0Q3; -.
DR ProteomicsDB; 259574; -.
DR Antibodypedia; 2983; 156 antibodies from 24 providers.
DR DNASU; 56334; -.
DR Ensembl; ENSMUST00000060226; ENSMUSP00000054834; ENSMUSG00000029390.
DR GeneID; 56334; -.
DR KEGG; mmu:56334; -.
DR UCSC; uc008zqa.1; mouse.
DR CTD; 10959; -.
DR MGI; MGI:1929269; Tmed2.
DR VEuPathDB; HostDB:ENSMUSG00000029390; -.
DR eggNOG; KOG1692; Eukaryota.
DR GeneTree; ENSGT00940000155143; -.
DR InParanoid; Q9R0Q3; -.
DR OMA; ADSSWHY; -.
DR OrthoDB; 1328081at2759; -.
DR PhylomeDB; Q9R0Q3; -.
DR TreeFam; TF313000; -.
DR Reactome; R-MMU-1912420; Pre-NOTCH Processing in Golgi.
DR Reactome; R-MMU-204005; COPII-mediated vesicle transport.
DR Reactome; R-MMU-5694530; Cargo concentration in the ER.
DR Reactome; R-MMU-6807878; COPI-mediated anterograde transport.
DR Reactome; R-MMU-6811434; COPI-dependent Golgi-to-ER retrograde traffic.
DR BioGRID-ORCS; 100862175; 0 hits in 1 CRISPR screen.
DR BioGRID-ORCS; 56334; 17 hits in 71 CRISPR screens.
DR ChiTaRS; Tmed2; mouse.
DR PRO; PR:Q9R0Q3; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q9R0Q3; protein.
DR Bgee; ENSMUSG00000029390; Expressed in ectoplacental cone and 101 other tissues.
DR ExpressionAtlas; Q9R0Q3; baseline and differential.
DR Genevisible; Q9R0Q3; MM.
DR GO; GO:0030137; C:COPI-coated vesicle; ISS:UniProtKB.
DR GO; GO:0030663; C:COPI-coated vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0030134; C:COPII-coated ER to Golgi transport vesicle; IBA:GO_Central.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:MGI.
DR GO; GO:0005793; C:endoplasmic reticulum-Golgi intermediate compartment; IDA:MGI.
DR GO; GO:0033116; C:endoplasmic reticulum-Golgi intermediate compartment membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
DR GO; GO:0032580; C:Golgi cisterna membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; ISS:HGNC-UCL.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0042589; C:zymogen granule membrane; ISS:HGNC-UCL.
DR GO; GO:1905069; P:allantois development; IMP:MGI.
DR GO; GO:0060670; P:branching involved in labyrinthine layer morphogenesis; IMP:MGI.
DR GO; GO:0060717; P:chorion development; IMP:MGI.
DR GO; GO:0048598; P:embryonic morphogenesis; IMP:UniProtKB.
DR GO; GO:0001892; P:embryonic placenta development; IMP:MGI.
DR GO; GO:0090158; P:endoplasmic reticulum membrane organization; IMP:MGI.
DR GO; GO:0007029; P:endoplasmic reticulum organization; IMP:MGI.
DR GO; GO:0006888; P:endoplasmic reticulum to Golgi vesicle-mediated transport; IBA:GO_Central.
DR GO; GO:0007030; P:Golgi organization; ISS:UniProtKB.
DR GO; GO:0001947; P:heart looping; IMP:MGI.
DR GO; GO:0001701; P:in utero embryonic development; IMP:MGI.
DR GO; GO:0006886; P:intracellular protein transport; ISO:MGI.
DR GO; GO:0060716; P:labyrinthine layer blood vessel development; IMP:CACAO.
DR GO; GO:0001893; P:maternal placenta development; IMP:UniProtKB.
DR GO; GO:0035264; P:multicellular organism growth; IMP:MGI.
DR GO; GO:1903912; P:negative regulation of endoplasmic reticulum stress-induced eIF2 alpha phosphorylation; IMP:MGI.
DR GO; GO:0034260; P:negative regulation of GTPase activity; ISS:UniProtKB.
DR GO; GO:0001843; P:neural tube closure; IMP:MGI.
DR GO; GO:0036499; P:PERK-mediated unfolded protein response; IMP:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:MGI.
DR GO; GO:0036342; P:post-anal tail morphogenesis; IMP:MGI.
DR GO; GO:0008104; P:protein localization; IMP:MGI.
DR GO; GO:0072659; P:protein localization to plasma membrane; ISS:UniProtKB.
DR GO; GO:2000638; P:regulation of SREBP signaling pathway; IMP:MGI.
DR GO; GO:0032525; P:somite rostral/caudal axis specification; IMP:MGI.
DR GO; GO:0001756; P:somitogenesis; IMP:MGI.
DR InterPro; IPR015720; Emp24-like.
DR InterPro; IPR009038; GOLD_dom.
DR InterPro; IPR036598; GOLD_dom_sf.
DR PANTHER; PTHR22811; PTHR22811; 1.
DR Pfam; PF01105; EMP24_GP25L; 1.
DR SMART; SM01190; EMP24_GP25L; 1.
DR SUPFAM; SSF101576; SSF101576; 1.
DR PROSITE; PS50866; GOLD; 1.
PE 1: Evidence at protein level;
KW Coiled coil; Cytoplasmic vesicle; Endoplasmic reticulum;
KW ER-Golgi transport; Golgi apparatus; Membrane; Protein transport;
KW Reference proteome; Signal; Transmembrane; Transmembrane helix; Transport.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..201
FT /note="Transmembrane emp24 domain-containing protein 2"
FT /id="PRO_0000010382"
FT TOPO_DOM 21..168
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 169..189
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 190..201
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 30..112
FT /note="GOLD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00096"
FT REGION 1..181
FT /note="Interaction with F2RL1"
FT /evidence="ECO:0000250"
FT REGION 118..157
FT /note="Required for TMED10 and TMED2 cis-Golgi network
FT localization"
FT /evidence="ECO:0000250"
FT COILED 117..167
FT /evidence="ECO:0000255"
FT MOTIF 194..201
FT /note="COPI vesicle coat-binding"
FT /evidence="ECO:0000255"
FT MOTIF 194..195
FT /note="COPII vesicle coat-binding"
FT /evidence="ECO:0000255"
FT MUTAGEN 15
FT /note="L->E: Embryonic lethal."
FT /evidence="ECO:0000269|PubMed:20178780"
SQ SEQUENCE 201 AA; 22705 MW; F5DE259FC419CF85 CRC64;
MVTLAELLAL LAALLATASG YFVSIDAHAE ECFFERVTSG TKMGLIFEVA EGGFLDIDVE
ITGPDNKGIY KGDRESSGKY TFAAHMDGTY KFCFSNRMST MTPKIVMFTI DIGEAPKGQD
METEAHQNKL EEMINELAVA MTAVKHEQEY MEVRERIHRA INDNTNSRVV LWSFFEALVL
VAMTLGQIYY LKRFFEVRRV V
