Full text data of TMED2
TMED2
(RNP24)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Transmembrane emp24 domain-containing protein 2 (Membrane protein p24A; p24; p24 family protein beta-1; p24beta1; Flags: Precursor)
Transmembrane emp24 domain-containing protein 2 (Membrane protein p24A; p24; p24 family protein beta-1; p24beta1; Flags: Precursor)
UniProt
Q15363
ID TMED2_HUMAN Reviewed; 201 AA.
AC Q15363;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-NOV-1996, sequence version 1.
DT 22-JAN-2014, entry version 117.
DE RecName: Full=Transmembrane emp24 domain-containing protein 2;
DE AltName: Full=Membrane protein p24A;
DE AltName: Full=p24;
DE AltName: Full=p24 family protein beta-1;
DE Short=p24beta1;
DE Flags: Precursor;
GN Name=TMED2; Synonyms=RNP24;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RX PubMed=8663407; DOI=10.1074/jbc.271.29.17183;
RA Blum R., Feick P., Puype M., Vandekerckhove J., Klengel R.,
RA Nastainczyk W., 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=Muscle;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP SUBCELLULAR LOCATION, AND ASSOCIATION WITH COPI AND COPII VESICLE
RP COAT.
RX PubMed=9472029; DOI=10.1083/jcb.140.4.751;
RA Dominguez M., Dejgaard K., Fullekrug J., Dahan S., Fazel A.,
RA Paccaud J.P., Thomas D.Y., Bergeron J.J., Nilsson T.;
RT "gp25L/emp24/p24 protein family members of the cis-Golgi network bind
RT both COP I and II coatomer.";
RL J. Cell Biol. 140:751-765(1998).
RN [4]
RP SUBUNIT.
RX PubMed=10359607; DOI=10.1091/mbc.10.6.1939;
RA Fullekrug J., Suganuma T., Tang B.L., Hong W., Storrie B., Nilsson T.;
RT "Localization and recycling of gp27 (hp24gamma3): complex formation
RT with other p24 family members.";
RL Mol. Biol. Cell 10:1939-1955(1999).
RN [5]
RP FUNCTION, AND MUTAGENESIS OF 194-PHE-PHE-195 AND 198-ARG-ARG-199.
RX PubMed=10761932; DOI=10.1016/S0092-8674(00)80703-5;
RA Goldberg J.;
RT "Decoding of sorting signals by coatomer through a GTPase switch in
RT the COPI coat complex.";
RL Cell 100:671-679(2000).
RN [6]
RP SUBCELLULAR LOCATION.
RX PubMed=10852829;
RA Emery G., Rojo M., Gruenberg J.;
RT "Coupled transport of p24 family members.";
RL J. Cell Sci. 113:2507-2516(2000).
RN [7]
RP SUBCELLULAR LOCATION, AND SUBUNIT.
RX PubMed=12237308; DOI=10.1074/jbc.M206989200;
RA Jenne N., Frey K., Brugger B., Wieland F.T.;
RT "Oligomeric state and stoichiometry of p24 proteins in the early
RT secretory pathway.";
RL J. Biol. Chem. 277:46504-46511(2002).
RN [8]
RP INTERACTION WITH COPG1.
RX PubMed=16940185; DOI=10.1128/MCB.01055-06;
RA Bethune J., Kol M., Hoffmann J., Reckmann I., Brugger B., Wieland F.;
RT "Coatomer, the coat protein of COPI transport vesicles, discriminates
RT endoplasmic reticulum residents from p24 proteins.";
RL Mol. Cell. Biol. 26:8011-8021(2006).
RN [9]
RP FUNCTION, AND 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
RT receptor trafficking.";
RL J. Biol. Chem. 282:30246-30255(2007).
RN [10]
RP INTERACTION WITH ATLA1.
RX PubMed=17321752; DOI=10.1016/j.mcn.2007.01.012;
RA Namekawa M., Muriel M.-P., Janer A., Latouche M., Dauphin A.,
RA Debeir T., Martin E., Duyckaerts C., Prigent A., Depienne C.,
RA Sittler A., Brice A., Ruberg M.;
RT "Mutations in the SPG3A gene encoding the GTPase atlastin interfere
RT with vesicle trafficking in the ER/Golgi interface and Golgi
RT morphogenesis.";
RL Mol. Cell. Neurosci. 35:1-13(2007).
RN [11]
RP IDENTIFICATION IN A COMPLEX WITH SURF4 AND TMED10.
RX PubMed=18287528; DOI=10.1091/mbc.E07-10-0989;
RA Mitrovic S., Ben-Tekaya H., Koegler E., Gruenberg J., Hauri H.-P.;
RT "The cargo receptors Surf4, endoplasmic reticulum-Golgi intermediate
RT compartment (ERGIC)-53, and p25 are required to maintain the
RT architecture of ERGIC and Golgi.";
RL Mol. Biol. Cell 19:1976-1990(2008).
RN [12]
RP FUNCTION, INTERACTION WITH CASR, AND MUTAGENESIS OF 194-PHE-PHE-195.
RX PubMed=20361938; DOI=10.1016/j.bbrc.2010.03.156;
RA Stepanchick A., Breitwieser G.E.;
RT "The cargo receptor p24A facilitates calcium sensing receptor
RT maturation and stabilization in the early secretory pathway.";
RL Biochem. Biophys. Res. Commun. 395:136-140(2010).
RN [13]
RP FUNCTION, AND INTERACTION WITH CD59; SEC24A; SEC24B; SEC24C AND
RP SEC24D.
RX PubMed=20427317; DOI=10.1242/jcs.062950;
RA Bonnon C., Wendeler M.W., Paccaud J.P., Hauri H.P.;
RT "Selective export of human GPI-anchored proteins from the endoplasmic
RT reticulum.";
RL J. Cell Sci. 123:1705-1715(2010).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [15]
RP FUNCTION, AND INTERACTION WITH F2R; P2RY4; P2RY11 AND OPRM1.
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-
RT opioid receptor-1B are under the control of the type I transmembrane
RT proteins p23 and p24A in post-Golgi trafficking.";
RL J. Neurochem. 117:71-81(2011).
CC -!- FUNCTION: Involved in vesicular protein trafficking. Mainly
CC functions in the early secretory pathway but also in post-Golgi
CC membranes. Thought to act as cargo receptor at the lumenal side
CC for incorporation of secretory cargo molecules into transport
CC vesicles and to be involved in vesicle coat formation at the
CC cytoplasmic side. In COPII vesicle-mediated anterograde transport
CC involved in the transport of GPI-anchored proteins and proposed to
CC act together with TMED10 as their cargo receptor; the function
CC specifically implies SEC24C and SEC24D of the COPII vesicle coat
CC and lipid raft-like microdomains of the ER. Recognizes GPI anchors
CC structural remodeled in the ER by PGAP1 and MPPE1. In COPI
CC vesicle-mediated retrograde transport inhibits the GTPase-
CC activating activity of ARFGAP1 towards ARF1 thus preventing
CC immature uncoating and allowing cargo selection to take place.
CC Involved in trafficking of G protein-coupled receptors (GPCRs).
CC Regulates F2RL1, OPRM1 and P2RY4 exocytic trafficking from the
CC Golgi to the plasma membrane thus contributing to receptor
CC resensitization. Facilitates CASR maturation and stabilization in
CC the early secretory pathway and increases CASR plasma membrane
CC targeting. Proposed to be involved in organization of
CC intracellular membranes such as the maintenance of the Golgi
CC apparatus. May also play a role in the biosynthesis of secreted
CC cargo such as eventual processing.
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
CC such as TMED7, TMED9 and TMED10. Interacts with TMED10. Associates
CC with the COPI vesicle coat (coatomer); TMED10:TMED2
CC heterotetramers are proposed to be involved in coatomer
CC association. Interacts (via C-terminus) with COPG1; the
CC interaction involves dimeric TMED2. Interacts with SEC23A;
CC indicative for an association of TMED2 with the COPII vesicle
CC coat. Interacts with ARF1 and ARFGAP1 (By similarity). Interacts
CC with CD59, SEC24A, SEC24B, SEC24C, SEC24D and ATLA1. Interacts
CC with KDELR1; the interaction is decreased by KDEL ligand (By
CC similarity). Interacts with F2RL1; the interaction occurs at the
CC Golgi apparatus. Interacts with CASR (immaturely glycosylated
CC form); the interaction occurs in the endoplasmic reticulum-Golgi
CC intermediate compartment or cis-Golgi. Interacts with F2RL1; the
CC interaction occurs at the Golgi apparatus. Interacts with GORASP1
CC and GORASP2 (By similarity). Found in a complex composed at least
CC of SURF4, TMED2 and TMED10.
CC -!- INTERACTION:
CC P41180:CASR; NbExp=3; IntAct=EBI-998485, EBI-4400127;
CC P13987:CD59; NbExp=4; IntAct=EBI-998485, EBI-297972;
CC P55085:F2RL1; NbExp=6; IntAct=EBI-998485, EBI-4303189;
CC O35587:TMED10 (xeno); NbExp=2; IntAct=EBI-998485, EBI-4405327;
CC P49755:TMED10; NbExp=7; IntAct=EBI-998485, EBI-998422;
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle membrane; Single-pass
CC type I membrane protein. Cytoplasmic vesicle, COPI-coated vesicle
CC membrane; Single-pass type I membrane protein. Golgi apparatus,
CC cis-Golgi network membrane; Single-pass type I membrane protein.
CC Golgi apparatus, Golgi stack membrane; Single-pass type I membrane
CC protein. Endoplasmic reticulum membrane; Single-pass type I
CC membrane protein. Endoplasmic reticulum-Golgi intermediate
CC compartment membrane; Single-pass type I membrane protein.
CC Note=Cycles between compartments of the early secretatory pathway.
CC -!- MISCELLANEOUS: Ectopic expression of TMED2 alone does not result
CC in its proper cis-Golgi network localization. Coexpression of
CC TMED10 is necessary, and coexpression of TMED3 and/or TMED9 is
CC facilitating localization. Down-regulation of TMED10 expression
CC reduces TMED2 protein level.
CC -!- SIMILARITY: Belongs to the EMP24/GP25L family.
CC -!- SIMILARITY: Contains 1 GOLD domain.
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DR EMBL; X92098; CAA63069.1; -; mRNA.
DR EMBL; BC025957; AAH25957.1; -; mRNA.
DR RefSeq; NP_006806.1; NM_006815.3.
DR UniGene; Hs.733403; -.
DR ProteinModelPortal; Q15363; -.
DR IntAct; Q15363; 31.
DR MINT; MINT-5000229; -.
DR STRING; 9606.ENSP00000262225; -.
DR PhosphoSite; Q15363; -.
DR DMDM; 3914237; -.
DR PaxDb; Q15363; -.
DR PeptideAtlas; Q15363; -.
DR PRIDE; Q15363; -.
DR DNASU; 10959; -.
DR Ensembl; ENST00000262225; ENSP00000262225; ENSG00000086598.
DR GeneID; 10959; -.
DR KEGG; hsa:10959; -.
DR UCSC; uc001ufg.3; human.
DR CTD; 10959; -.
DR GeneCards; GC12P124069; -.
DR HGNC; HGNC:16996; TMED2.
DR HPA; HPA014060; -.
DR neXtProt; NX_Q15363; -.
DR PharmGKB; PA142670796; -.
DR eggNOG; NOG271196; -.
DR HOGENOM; HOG000160229; -.
DR HOVERGEN; HBG105106; -.
DR InParanoid; Q15363; -.
DR OMA; DGRHEYC; -.
DR OrthoDB; EOG7RFTJP; -.
DR PhylomeDB; Q15363; -.
DR ChiTaRS; TMED2; human.
DR GeneWiki; TMED2; -.
DR GenomeRNAi; 10959; -.
DR NextBio; 41644; -.
DR PRO; PR:Q15363; -.
DR ArrayExpress; Q15363; -.
DR Bgee; Q15363; -.
DR CleanEx; HS_TMED2; -.
DR Genevestigator; Q15363; -.
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:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005793; C:endoplasmic reticulum-Golgi intermediate compartment; IDA:UniProtKB.
DR GO; GO:0033116; C:endoplasmic reticulum-Golgi intermediate compartment membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0032580; C:Golgi cisterna membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral to membrane; ISS:HGNC.
DR GO; GO:0042589; C:zymogen granule membrane; ISS:HGNC.
DR GO; GO:0035459; P:cargo loading into vesicle; TAS:UniProtKB.
DR GO; GO:0048205; P:COPI coating of Golgi vesicle; TAS:UniProtKB.
DR GO; GO:0048208; P:COPII vesicle coating; TAS:UniProtKB.
DR GO; GO:0048598; P:embryonic morphogenesis; IEA:Ensembl.
DR GO; GO:0007030; P:Golgi organization; IMP:UniProtKB.
DR GO; GO:0001893; P:maternal placenta development; IEA:Ensembl.
DR GO; GO:0034260; P:negative regulation of GTPase activity; IDA:UniProtKB.
DR GO; GO:0072661; P:protein targeting to plasma membrane; IDA:UniProtKB.
DR InterPro; IPR009038; GOLD.
DR Pfam; PF01105; EMP24_GP25L; 1.
DR SUPFAM; SSF101576; SSF101576; 1.
DR PROSITE; PS50866; GOLD; 1.
PE 1: Evidence at protein level;
KW Coiled coil; Complete proteome; Cytoplasmic vesicle;
KW Endoplasmic reticulum; ER-Golgi transport; Golgi apparatus; Membrane;
KW Protein transport; Reference proteome; Signal; Transmembrane;
KW Transmembrane helix; Transport.
FT SIGNAL 1 20 Potential.
FT CHAIN 21 201 Transmembrane emp24 domain-containing
FT protein 2.
FT /FTId=PRO_0000010381.
FT TOPO_DOM 21 168 Lumenal (Potential).
FT TRANSMEM 169 189 Helical; (Potential).
FT TOPO_DOM 190 201 Cytoplasmic (Potential).
FT DOMAIN 30 112 GOLD.
FT REGION 1 181 Interaction with F2RL1.
FT REGION 118 157 Required for TMED10 and TMED2 cis-Golgi
FT network localization.
FT COILED 117 167 Potential.
FT MOTIF 194 201 COPI vesicle coat-binding (Potential).
FT MOTIF 194 195 COPII vesicle coat-binding (Potential).
FT MUTAGEN 194 195 FF->AA: Disrupts association with
FT coatomer; when associated with S-198-199-
FT S.
FT MUTAGEN 194 195 FF->AA: Reduced surface and total
FT expression of CASR.
FT MUTAGEN 198 199 RR->SS: Disrupts association woth
FT coatomer; when associated with A-194-195-
FT A.
FT MUTAGEN 198 199 RR->SS: No inhibition of coatomer-
FT dependent GTP hydrolysis.
SQ SEQUENCE 201 AA; 22761 MW; C452370E459DC894 CRC64;
MVTLAELLVL LAALLATVSG YFVSIDAHAE ECFFERVTSG TKMGLIFEVA EGGFLDIDVE
ITGPDNKGIY KGDRESSGKY TFAAHMDGTY KFCFSNRMST MTPKIVMFTI DIGEAPKGQD
METEAHQNKL EEMINELAVA MTAVKHEQEY MEVRERIHRA INDNTNSRVV LWSFFEALVL
VAMTLGQIYY LKRFFEVRRV V
//
ID TMED2_HUMAN Reviewed; 201 AA.
AC Q15363;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-NOV-1996, sequence version 1.
DT 22-JAN-2014, entry version 117.
DE RecName: Full=Transmembrane emp24 domain-containing protein 2;
DE AltName: Full=Membrane protein p24A;
DE AltName: Full=p24;
DE AltName: Full=p24 family protein beta-1;
DE Short=p24beta1;
DE Flags: Precursor;
GN Name=TMED2; Synonyms=RNP24;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RX PubMed=8663407; DOI=10.1074/jbc.271.29.17183;
RA Blum R., Feick P., Puype M., Vandekerckhove J., Klengel R.,
RA Nastainczyk W., 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=Muscle;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP SUBCELLULAR LOCATION, AND ASSOCIATION WITH COPI AND COPII VESICLE
RP COAT.
RX PubMed=9472029; DOI=10.1083/jcb.140.4.751;
RA Dominguez M., Dejgaard K., Fullekrug J., Dahan S., Fazel A.,
RA Paccaud J.P., Thomas D.Y., Bergeron J.J., Nilsson T.;
RT "gp25L/emp24/p24 protein family members of the cis-Golgi network bind
RT both COP I and II coatomer.";
RL J. Cell Biol. 140:751-765(1998).
RN [4]
RP SUBUNIT.
RX PubMed=10359607; DOI=10.1091/mbc.10.6.1939;
RA Fullekrug J., Suganuma T., Tang B.L., Hong W., Storrie B., Nilsson T.;
RT "Localization and recycling of gp27 (hp24gamma3): complex formation
RT with other p24 family members.";
RL Mol. Biol. Cell 10:1939-1955(1999).
RN [5]
RP FUNCTION, AND MUTAGENESIS OF 194-PHE-PHE-195 AND 198-ARG-ARG-199.
RX PubMed=10761932; DOI=10.1016/S0092-8674(00)80703-5;
RA Goldberg J.;
RT "Decoding of sorting signals by coatomer through a GTPase switch in
RT the COPI coat complex.";
RL Cell 100:671-679(2000).
RN [6]
RP SUBCELLULAR LOCATION.
RX PubMed=10852829;
RA Emery G., Rojo M., Gruenberg J.;
RT "Coupled transport of p24 family members.";
RL J. Cell Sci. 113:2507-2516(2000).
RN [7]
RP SUBCELLULAR LOCATION, AND SUBUNIT.
RX PubMed=12237308; DOI=10.1074/jbc.M206989200;
RA Jenne N., Frey K., Brugger B., Wieland F.T.;
RT "Oligomeric state and stoichiometry of p24 proteins in the early
RT secretory pathway.";
RL J. Biol. Chem. 277:46504-46511(2002).
RN [8]
RP INTERACTION WITH COPG1.
RX PubMed=16940185; DOI=10.1128/MCB.01055-06;
RA Bethune J., Kol M., Hoffmann J., Reckmann I., Brugger B., Wieland F.;
RT "Coatomer, the coat protein of COPI transport vesicles, discriminates
RT endoplasmic reticulum residents from p24 proteins.";
RL Mol. Cell. Biol. 26:8011-8021(2006).
RN [9]
RP FUNCTION, AND 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
RT receptor trafficking.";
RL J. Biol. Chem. 282:30246-30255(2007).
RN [10]
RP INTERACTION WITH ATLA1.
RX PubMed=17321752; DOI=10.1016/j.mcn.2007.01.012;
RA Namekawa M., Muriel M.-P., Janer A., Latouche M., Dauphin A.,
RA Debeir T., Martin E., Duyckaerts C., Prigent A., Depienne C.,
RA Sittler A., Brice A., Ruberg M.;
RT "Mutations in the SPG3A gene encoding the GTPase atlastin interfere
RT with vesicle trafficking in the ER/Golgi interface and Golgi
RT morphogenesis.";
RL Mol. Cell. Neurosci. 35:1-13(2007).
RN [11]
RP IDENTIFICATION IN A COMPLEX WITH SURF4 AND TMED10.
RX PubMed=18287528; DOI=10.1091/mbc.E07-10-0989;
RA Mitrovic S., Ben-Tekaya H., Koegler E., Gruenberg J., Hauri H.-P.;
RT "The cargo receptors Surf4, endoplasmic reticulum-Golgi intermediate
RT compartment (ERGIC)-53, and p25 are required to maintain the
RT architecture of ERGIC and Golgi.";
RL Mol. Biol. Cell 19:1976-1990(2008).
RN [12]
RP FUNCTION, INTERACTION WITH CASR, AND MUTAGENESIS OF 194-PHE-PHE-195.
RX PubMed=20361938; DOI=10.1016/j.bbrc.2010.03.156;
RA Stepanchick A., Breitwieser G.E.;
RT "The cargo receptor p24A facilitates calcium sensing receptor
RT maturation and stabilization in the early secretory pathway.";
RL Biochem. Biophys. Res. Commun. 395:136-140(2010).
RN [13]
RP FUNCTION, AND INTERACTION WITH CD59; SEC24A; SEC24B; SEC24C AND
RP SEC24D.
RX PubMed=20427317; DOI=10.1242/jcs.062950;
RA Bonnon C., Wendeler M.W., Paccaud J.P., Hauri H.P.;
RT "Selective export of human GPI-anchored proteins from the endoplasmic
RT reticulum.";
RL J. Cell Sci. 123:1705-1715(2010).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [15]
RP FUNCTION, AND INTERACTION WITH F2R; P2RY4; P2RY11 AND OPRM1.
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-
RT opioid receptor-1B are under the control of the type I transmembrane
RT proteins p23 and p24A in post-Golgi trafficking.";
RL J. Neurochem. 117:71-81(2011).
CC -!- FUNCTION: Involved in vesicular protein trafficking. Mainly
CC functions in the early secretory pathway but also in post-Golgi
CC membranes. Thought to act as cargo receptor at the lumenal side
CC for incorporation of secretory cargo molecules into transport
CC vesicles and to be involved in vesicle coat formation at the
CC cytoplasmic side. In COPII vesicle-mediated anterograde transport
CC involved in the transport of GPI-anchored proteins and proposed to
CC act together with TMED10 as their cargo receptor; the function
CC specifically implies SEC24C and SEC24D of the COPII vesicle coat
CC and lipid raft-like microdomains of the ER. Recognizes GPI anchors
CC structural remodeled in the ER by PGAP1 and MPPE1. In COPI
CC vesicle-mediated retrograde transport inhibits the GTPase-
CC activating activity of ARFGAP1 towards ARF1 thus preventing
CC immature uncoating and allowing cargo selection to take place.
CC Involved in trafficking of G protein-coupled receptors (GPCRs).
CC Regulates F2RL1, OPRM1 and P2RY4 exocytic trafficking from the
CC Golgi to the plasma membrane thus contributing to receptor
CC resensitization. Facilitates CASR maturation and stabilization in
CC the early secretory pathway and increases CASR plasma membrane
CC targeting. Proposed to be involved in organization of
CC intracellular membranes such as the maintenance of the Golgi
CC apparatus. May also play a role in the biosynthesis of secreted
CC cargo such as eventual processing.
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
CC such as TMED7, TMED9 and TMED10. Interacts with TMED10. Associates
CC with the COPI vesicle coat (coatomer); TMED10:TMED2
CC heterotetramers are proposed to be involved in coatomer
CC association. Interacts (via C-terminus) with COPG1; the
CC interaction involves dimeric TMED2. Interacts with SEC23A;
CC indicative for an association of TMED2 with the COPII vesicle
CC coat. Interacts with ARF1 and ARFGAP1 (By similarity). Interacts
CC with CD59, SEC24A, SEC24B, SEC24C, SEC24D and ATLA1. Interacts
CC with KDELR1; the interaction is decreased by KDEL ligand (By
CC similarity). Interacts with F2RL1; the interaction occurs at the
CC Golgi apparatus. Interacts with CASR (immaturely glycosylated
CC form); the interaction occurs in the endoplasmic reticulum-Golgi
CC intermediate compartment or cis-Golgi. Interacts with F2RL1; the
CC interaction occurs at the Golgi apparatus. Interacts with GORASP1
CC and GORASP2 (By similarity). Found in a complex composed at least
CC of SURF4, TMED2 and TMED10.
CC -!- INTERACTION:
CC P41180:CASR; NbExp=3; IntAct=EBI-998485, EBI-4400127;
CC P13987:CD59; NbExp=4; IntAct=EBI-998485, EBI-297972;
CC P55085:F2RL1; NbExp=6; IntAct=EBI-998485, EBI-4303189;
CC O35587:TMED10 (xeno); NbExp=2; IntAct=EBI-998485, EBI-4405327;
CC P49755:TMED10; NbExp=7; IntAct=EBI-998485, EBI-998422;
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle membrane; Single-pass
CC type I membrane protein. Cytoplasmic vesicle, COPI-coated vesicle
CC membrane; Single-pass type I membrane protein. Golgi apparatus,
CC cis-Golgi network membrane; Single-pass type I membrane protein.
CC Golgi apparatus, Golgi stack membrane; Single-pass type I membrane
CC protein. Endoplasmic reticulum membrane; Single-pass type I
CC membrane protein. Endoplasmic reticulum-Golgi intermediate
CC compartment membrane; Single-pass type I membrane protein.
CC Note=Cycles between compartments of the early secretatory pathway.
CC -!- MISCELLANEOUS: Ectopic expression of TMED2 alone does not result
CC in its proper cis-Golgi network localization. Coexpression of
CC TMED10 is necessary, and coexpression of TMED3 and/or TMED9 is
CC facilitating localization. Down-regulation of TMED10 expression
CC reduces TMED2 protein level.
CC -!- SIMILARITY: Belongs to the EMP24/GP25L family.
CC -!- SIMILARITY: Contains 1 GOLD domain.
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DR EMBL; X92098; CAA63069.1; -; mRNA.
DR EMBL; BC025957; AAH25957.1; -; mRNA.
DR RefSeq; NP_006806.1; NM_006815.3.
DR UniGene; Hs.733403; -.
DR ProteinModelPortal; Q15363; -.
DR IntAct; Q15363; 31.
DR MINT; MINT-5000229; -.
DR STRING; 9606.ENSP00000262225; -.
DR PhosphoSite; Q15363; -.
DR DMDM; 3914237; -.
DR PaxDb; Q15363; -.
DR PeptideAtlas; Q15363; -.
DR PRIDE; Q15363; -.
DR DNASU; 10959; -.
DR Ensembl; ENST00000262225; ENSP00000262225; ENSG00000086598.
DR GeneID; 10959; -.
DR KEGG; hsa:10959; -.
DR UCSC; uc001ufg.3; human.
DR CTD; 10959; -.
DR GeneCards; GC12P124069; -.
DR HGNC; HGNC:16996; TMED2.
DR HPA; HPA014060; -.
DR neXtProt; NX_Q15363; -.
DR PharmGKB; PA142670796; -.
DR eggNOG; NOG271196; -.
DR HOGENOM; HOG000160229; -.
DR HOVERGEN; HBG105106; -.
DR InParanoid; Q15363; -.
DR OMA; DGRHEYC; -.
DR OrthoDB; EOG7RFTJP; -.
DR PhylomeDB; Q15363; -.
DR ChiTaRS; TMED2; human.
DR GeneWiki; TMED2; -.
DR GenomeRNAi; 10959; -.
DR NextBio; 41644; -.
DR PRO; PR:Q15363; -.
DR ArrayExpress; Q15363; -.
DR Bgee; Q15363; -.
DR CleanEx; HS_TMED2; -.
DR Genevestigator; Q15363; -.
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:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005793; C:endoplasmic reticulum-Golgi intermediate compartment; IDA:UniProtKB.
DR GO; GO:0033116; C:endoplasmic reticulum-Golgi intermediate compartment membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0032580; C:Golgi cisterna membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral to membrane; ISS:HGNC.
DR GO; GO:0042589; C:zymogen granule membrane; ISS:HGNC.
DR GO; GO:0035459; P:cargo loading into vesicle; TAS:UniProtKB.
DR GO; GO:0048205; P:COPI coating of Golgi vesicle; TAS:UniProtKB.
DR GO; GO:0048208; P:COPII vesicle coating; TAS:UniProtKB.
DR GO; GO:0048598; P:embryonic morphogenesis; IEA:Ensembl.
DR GO; GO:0007030; P:Golgi organization; IMP:UniProtKB.
DR GO; GO:0001893; P:maternal placenta development; IEA:Ensembl.
DR GO; GO:0034260; P:negative regulation of GTPase activity; IDA:UniProtKB.
DR GO; GO:0072661; P:protein targeting to plasma membrane; IDA:UniProtKB.
DR InterPro; IPR009038; GOLD.
DR Pfam; PF01105; EMP24_GP25L; 1.
DR SUPFAM; SSF101576; SSF101576; 1.
DR PROSITE; PS50866; GOLD; 1.
PE 1: Evidence at protein level;
KW Coiled coil; Complete proteome; Cytoplasmic vesicle;
KW Endoplasmic reticulum; ER-Golgi transport; Golgi apparatus; Membrane;
KW Protein transport; Reference proteome; Signal; Transmembrane;
KW Transmembrane helix; Transport.
FT SIGNAL 1 20 Potential.
FT CHAIN 21 201 Transmembrane emp24 domain-containing
FT protein 2.
FT /FTId=PRO_0000010381.
FT TOPO_DOM 21 168 Lumenal (Potential).
FT TRANSMEM 169 189 Helical; (Potential).
FT TOPO_DOM 190 201 Cytoplasmic (Potential).
FT DOMAIN 30 112 GOLD.
FT REGION 1 181 Interaction with F2RL1.
FT REGION 118 157 Required for TMED10 and TMED2 cis-Golgi
FT network localization.
FT COILED 117 167 Potential.
FT MOTIF 194 201 COPI vesicle coat-binding (Potential).
FT MOTIF 194 195 COPII vesicle coat-binding (Potential).
FT MUTAGEN 194 195 FF->AA: Disrupts association with
FT coatomer; when associated with S-198-199-
FT S.
FT MUTAGEN 194 195 FF->AA: Reduced surface and total
FT expression of CASR.
FT MUTAGEN 198 199 RR->SS: Disrupts association woth
FT coatomer; when associated with A-194-195-
FT A.
FT MUTAGEN 198 199 RR->SS: No inhibition of coatomer-
FT dependent GTP hydrolysis.
SQ SEQUENCE 201 AA; 22761 MW; C452370E459DC894 CRC64;
MVTLAELLVL LAALLATVSG YFVSIDAHAE ECFFERVTSG TKMGLIFEVA EGGFLDIDVE
ITGPDNKGIY KGDRESSGKY TFAAHMDGTY KFCFSNRMST MTPKIVMFTI DIGEAPKGQD
METEAHQNKL EEMINELAVA MTAVKHEQEY MEVRERIHRA INDNTNSRVV LWSFFEALVL
VAMTLGQIYY LKRFFEVRRV V
//