TMED2_RAT
ID TMED2_RAT Reviewed; 201 AA.
AC Q63524;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 148.
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=RNP21.4;
DE AltName: Full=p24 family protein beta-1;
DE Short=p24beta1;
DE Flags: Precursor;
GN Name=Tmed2; Synonyms=Rnp24;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Wistar; TISSUE=Pancreas;
RX PubMed=8663407; DOI=10.1074/jbc.271.29.17183;
RA Blum R., Feick P., Puype M., Vandekerckhove J., Klengel R., Nastainczyk W.,
RA Schulz I.;
RT "Tmp21 and p24A, two type I proteins enriched in pancreatic microsomal
RT membranes, are members of a protein family involved in vesicular
RT trafficking.";
RL J. Biol. Chem. 271:17183-17189(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Prostate;
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 PROTEIN SEQUENCE OF 21-31, SUBUNIT, AND SUBCELLULAR LOCATION.
RX PubMed=9472029; DOI=10.1083/jcb.140.4.751;
RA Dominguez M., Dejgaard K., Fullekrug J., Dahan S., Fazel A., Paccaud J.P.,
RA Thomas D.Y., Bergeron J.J., Nilsson T.;
RT "gp25L/emp24/p24 protein family members of the cis-Golgi network bind both
RT COP I and II coatomer.";
RL J. Cell Biol. 140:751-765(1998).
RN [4]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH TMED10.
RX PubMed=10214941; DOI=10.1016/s0014-5793(99)00246-x;
RA Gommel D., Orci L., Emig E.M., Hannah M.J., Ravazzola M., Nickel W.,
RA Helms J.B., Wieland F.T., Sohn K.;
RT "p24 and p23, the major transmembrane proteins of COPI-coated transport
RT vesicles, form hetero-oligomeric complexes and cycle between the organelles
RT of the early secretory pathway.";
RL FEBS Lett. 447:179-185(1999).
RN [5]
RP INTERACTION WITH TMED10; ARF1; ARFGAP1 AND KDELR1.
RX PubMed=11703931; DOI=10.1016/s1534-5807(01)00004-1;
RA Majoul I., Straub M., Hell S.W., Duden R., Soling H.D.;
RT "KDEL-cargo regulates interactions between proteins involved in COPI
RT vesicle traffic: measurements in living cells using FRET.";
RL Dev. Cell 1:139-153(2001).
RN [6]
RP INTERACTION WITH GORASP1 AND GORASP2, AND MUTAGENESIS OF 200-VAL-VAL-201.
RX PubMed=11739402; DOI=10.1083/jcb.200108102;
RA Barr F.A., Preisinger C., Kopajtich R., Koerner R.;
RT "Golgi matrix proteins interact with p24 cargo receptors and aid their
RT efficient retention in the Golgi apparatus.";
RL J. Cell Biol. 155:885-891(2001).
RN [7]
RP INTERACTION WITH ARFGAP1.
RX PubMed=11748249; DOI=10.1083/jcb.200108017;
RA Lanoix J., Ouwendijk J., Stark A., Szafer E., Cassel D., Dejgaard K.,
RA Weiss M., Nilsson T.;
RT "Sorting of Golgi resident proteins into different subpopulations of COPI
RT vesicles: a role for ArfGAP1.";
RL J. Cell Biol. 155:1199-1212(2001).
RN [8]
RP SUBCELLULAR LOCATION.
RX PubMed=15718469; DOI=10.1126/science.1108061;
RA Malsam J., Satoh A., Pelletier L., Warren G.;
RT "Golgin tethers define subpopulations of COPI vesicles.";
RL Science 307:1095-1098(2005).
RN [9]
RP INTERACTION WITH F2RL1.
RX PubMed=17693410; DOI=10.1074/jbc.m703205200;
RA Luo W., Wang Y., Reiser G.;
RT "p24A, a type I transmembrane protein, controls ARF1-dependent
RT resensitization of protease-activated receptor-2 by influence on receptor
RT trafficking.";
RL J. Biol. Chem. 282:30246-30255(2007).
RN [10]
RP FUNCTION.
RX PubMed=21219331; DOI=10.1111/j.1471-4159.2011.07173.x;
RA Luo W., Wang Y., Reiser G.;
RT "Proteinase-activated receptors, nucleotide P2Y receptors, and mu-opioid
RT receptor-1B are under the control of the type I transmembrane proteins p23
RT and p24A in post-Golgi trafficking.";
RL J. Neurochem. 117:71-81(2011).
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). {ECO:0000250,
CC ECO:0000269|PubMed:21219331}.
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, ECO:0000250|UniProtKB:Q15363}.
CC -!- INTERACTION:
CC Q63524; Q63645: F2rl1; NbExp=2; IntAct=EBI-918600, EBI-4303358;
CC Q63524; O35254: Gorasp1; NbExp=3; IntAct=EBI-918600, EBI-4422879;
CC Q63524; Q9R064: Gorasp2; NbExp=4; IntAct=EBI-918600, EBI-4422912;
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle membrane {ECO:0000305};
CC Single-pass type I membrane protein {ECO:0000255}. Cytoplasmic vesicle,
CC COPI-coated vesicle membrane {ECO:0000269|PubMed:10214941,
CC ECO:0000269|PubMed:15718469, ECO:0000269|PubMed:9472029}; Single-pass
CC type I membrane protein {ECO:0000255}. Golgi apparatus, cis-Golgi
CC network membrane {ECO:0000269|PubMed:10214941}; Single-pass type I
CC membrane protein {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:0000269|PubMed:10214941}; Single-pass type I membrane protein
CC {ECO:0000255}. Endoplasmic reticulum-Golgi intermediate compartment
CC membrane {ECO:0000269|PubMed:10214941}; Single-pass type I membrane
CC protein {ECO:0000255}. Note=Cycles between compartments of the early
CC secretatory pathway. {ECO:0000269|PubMed:10214941}.
CC -!- SIMILARITY: Belongs to the EMP24/GP25L family. {ECO:0000305}.
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DR EMBL; X92097; CAA63068.1; -; mRNA.
DR EMBL; BC062036; AAH62036.1; -; mRNA.
DR RefSeq; NP_113910.1; NM_031722.2.
DR AlphaFoldDB; Q63524; -.
DR SMR; Q63524; -.
DR BioGRID; 249279; 2.
DR ELM; Q63524; -.
DR IntAct; Q63524; 9.
DR STRING; 10116.ENSRNOP00000001397; -.
DR SwissPalm; Q63524; -.
DR jPOST; Q63524; -.
DR PaxDb; Q63524; -.
DR PRIDE; Q63524; -.
DR Ensembl; ENSRNOT00000001397; ENSRNOP00000001397; ENSRNOG00000001053.
DR GeneID; 65165; -.
DR KEGG; rno:65165; -.
DR UCSC; RGD:69243; rat.
DR CTD; 10959; -.
DR RGD; 69243; Tmed2.
DR eggNOG; KOG1692; Eukaryota.
DR GeneTree; ENSGT00940000155143; -.
DR HOGENOM; CLU_066963_4_1_1; -.
DR InParanoid; Q63524; -.
DR OMA; ADSSWHY; -.
DR OrthoDB; 1328081at2759; -.
DR PhylomeDB; Q63524; -.
DR TreeFam; TF313000; -.
DR Reactome; R-RNO-1912420; Pre-NOTCH Processing in Golgi.
DR Reactome; R-RNO-204005; COPII-mediated vesicle transport.
DR Reactome; R-RNO-5694530; Cargo concentration in the ER.
DR Reactome; R-RNO-6807878; COPI-mediated anterograde transport.
DR Reactome; R-RNO-6811434; COPI-dependent Golgi-to-ER retrograde traffic.
DR PRO; PR:Q63524; -.
DR Proteomes; UP000002494; Chromosome 12.
DR Bgee; ENSRNOG00000001053; Expressed in pancreas and 20 other tissues.
DR Genevisible; Q63524; RN.
DR GO; GO:0030137; C:COPI-coated vesicle; IDA: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; ISO:RGD.
DR GO; GO:0005793; C:endoplasmic reticulum-Golgi intermediate compartment; ISS:UniProtKB.
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; IDA:HGNC-UCL.
DR GO; GO:0042589; C:zymogen granule membrane; IDA:HGNC-UCL.
DR GO; GO:1905069; P:allantois development; ISO:RGD.
DR GO; GO:0060670; P:branching involved in labyrinthine layer morphogenesis; ISO:RGD.
DR GO; GO:0060717; P:chorion development; ISO:RGD.
DR GO; GO:0048598; P:embryonic morphogenesis; ISO:RGD.
DR GO; GO:0001892; P:embryonic placenta development; ISO:RGD.
DR GO; GO:0090158; P:endoplasmic reticulum membrane organization; ISO:RGD.
DR GO; GO:0007029; P:endoplasmic reticulum organization; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0001701; P:in utero embryonic development; ISO:RGD.
DR GO; GO:0006886; P:intracellular protein transport; ISO:RGD.
DR GO; GO:0060716; P:labyrinthine layer blood vessel development; ISO:RGD.
DR GO; GO:0001893; P:maternal placenta development; ISO:RGD.
DR GO; GO:0035264; P:multicellular organism growth; ISO:RGD.
DR GO; GO:1903912; P:negative regulation of endoplasmic reticulum stress-induced eIF2 alpha phosphorylation; ISO:RGD.
DR GO; GO:0034260; P:negative regulation of GTPase activity; ISS:UniProtKB.
DR GO; GO:0001843; P:neural tube closure; ISO:RGD.
DR GO; GO:0036499; P:PERK-mediated unfolded protein response; ISO:RGD.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:RGD.
DR GO; GO:0036342; P:post-anal tail morphogenesis; ISO:RGD.
DR GO; GO:0008104; P:protein localization; ISO:RGD.
DR GO; GO:0072659; P:protein localization to plasma membrane; ISS:UniProtKB.
DR GO; GO:2000638; P:regulation of SREBP signaling pathway; ISO:RGD.
DR GO; GO:0032525; P:somite rostral/caudal axis specification; ISO:RGD.
DR GO; GO:0001756; P:somitogenesis; ISO:RGD.
DR GO; GO:0006903; P:vesicle targeting; NAS:HGNC-UCL.
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; Direct protein sequencing;
KW Endoplasmic reticulum; ER-Golgi transport; Golgi apparatus; Membrane;
KW Protein transport; Reference proteome; Signal; Transmembrane;
KW 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_0000010383"
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 200..201
FT /note="VV->AA: Localization at cell surface."
FT /evidence="ECO:0000269|PubMed:11739402"
FT CONFLICT 29
FT /note="A -> P (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 201 AA; 22733 MW; E35A3816429DDF9A CRC64;
MVTLAELLVL LAALLATASG YFVSIDAHAE ECFFERVTSG TKMGLIFEVA EGGFLDIDVE
ITGPDNKGIY KGDRESSGKY TFAAHMDGTY KFCFSNRMST MTPKIVMFTI DIGEAPKGQD
METEAHQNKL EEMINELAVA MTAVKHEQEY MEVRERIHRA INDNTNSRVV LWSFFEALVL
VAMTLGQIYY LKRFFEVRRV V
