TMEDA_MESAU
ID TMEDA_MESAU Reviewed; 219 AA.
AC O35587;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 25-MAY-2022, entry version 110.
DE RecName: Full=Transmembrane emp24 domain-containing protein 10;
DE Short=Protein TMED10;
DE AltName: Full=21 kDa transmembrane-trafficking protein;
DE AltName: Full=Integral membrane protein p23;
DE AltName: Full=Transmembrane protein Tmp21;
DE AltName: Full=p24 family protein delta-1;
DE Short=p24delta1;
DE Flags: Precursor;
GN Name=TMED10; Synonyms=TMP21;
OS Mesocricetus auratus (Golden hamster).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC Cricetidae; Cricetinae; Mesocricetus.
OX NCBI_TaxID=10036;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=9382861; DOI=10.1083/jcb.139.5.1119;
RA Rojo M., Pepperkok R., Emery G., Kellner R., Stang E., Parton R.G.,
RA Gruenberg J.;
RT "Involvement of the transmembrane protein p23 in biosynthetic protein
RT transport.";
RL J. Cell Biol. 139:1119-1135(1997).
RN [2]
RP SUBCELLULAR LOCATION.
RX PubMed=9527489; DOI=10.1002/elps.1150181415;
RA Shevchenko A., Keller P., Scheiffele P., Mann M., Simons K.;
RT "Identification of components of trans-Golgi network-derived transport
RT vesicles and detergent-insoluble complexes by nanoelectrospray tandem mass
RT spectrometry.";
RL Electrophoresis 18:2591-2600(1997).
RN [3]
RP INTERACTION WITH CD59; SEC24B; SEC24C AND 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).
CC -!- FUNCTION: Cargo receptor involved in protein vesicular trafficking and
CC quality control in the endoplasmic reticulum (ER) and Golgi
CC (PubMed:9382861). The p24 protein family is a group of transmembrane
CC proteins that bind coat protein complex I/COPI and coat protein complex
CC II/COPII involved in vesicular trafficking between the membranes. Acts
CC at the lumenal side for incorporation of secretory cargo molecules into
CC transport vesicles and involved in vesicle coat formation at the
CC cytoplasmic side (By similarity). Mainly functions in the early
CC secretory pathway and cycles between the ER, ER-Golgi intermediate
CC compartment (ERGIC) and Golgi, mediating cargo transport through COPI
CC and COPII-coated vesicles (PubMed:9382861). In COPII vesicle-mediated
CC anterograde transport, involved in the transport of GPI-anchored
CC proteins by acting together with TMED2 as their cargo receptor; the
CC function specifically implies SEC24C and SEC24D of the COPII vesicle
CC coat and lipid raft-like microdomains of the ER (By similarity).
CC Recognizes GPI anchors structural remodeled in the ER by the GPI
CC inositol-deacylase/PGAP1 and the metallophosphoesterase MPPE1/PGAP5 (By
CC similarity). In COPI vesicle-mediated retrograde transport, involved in
CC the biogenesis of COPI vesicles and vesicle coat recruitment. Involved
CC in trafficking of amyloid beta A4 protein and soluble APP-beta release
CC (independent from the modulation of gamma-secretase activity) (By
CC similarity). Involved in the KDELR2-mediated retrograde transport of
CC the toxin A subunit (CTX-A-K63)together with COPI and the COOH terminus
CC of KDELR2 (By similarity). On Golgi membranes, acts as primary receptor
CC for ARF1-GDP, a GTP-binding protein involved in COPI-vesicle formation.
CC Increases coatomer-dependent GTPase-activating activity of ARFGAP2
CC which mediates the hydrolysis of ARF1-bound GTP and therefore modulates
CC protein trafficking from the Golgi apparatus. Involved in the exocytic
CC trafficking of G protein-coupled receptors F2LR1/PAR2 (trypsin and
CC tryspin-like enzyme receptor), OPRM1 (opioid receptor) and P2RY4 (UTD
CC and UDP receptor) from the Golgi to the plasma membrane, thus
CC contributing to receptor resensitization. In addition to its cargo
CC receptor activity, may also act as a protein channel after
CC oligomerization, facilitating the post-translational entry of
CC leaderless cytoplasmic cargo into the ERGIC. Involved in the
CC translocation into ERGIC, the vesicle entry and the secretion of
CC leaderless cargos (lacking the secretion signal sequence), including
CC the mature form of interleukin 1/IL-1 family members, the alpha-
CC crystallin B chain HSPB5, the carbohydrate-binding proteins galectin-
CC 1/LGALS1 and galectin-3/LGALS3, the microtubule-associated protein
CC Tau/MAPT, and the annexin A1/ANXA1; the translocation process is
CC dependent on cargo protein unfolding and enhanced by chaperones
CC HSP90AB1 and HSP90B1/GRP9. Could also associates with the presenilin-
CC dependent gamma-secretase complex in order to regulate gamma-cleavages
CC of the amyloid beta A4 protein to yield amyloid-beta 40/Abeta40 (By
CC similarity). {ECO:0000250|UniProtKB:P49755,
CC ECO:0000250|UniProtKB:Q28735, ECO:0000250|UniProtKB:Q63584,
CC ECO:0000269|PubMed:9382861}.
CC -!- SUBUNIT: Predominantly dimeric and to a lesser extent monomeric in the
CC ER. Monomer and dimer in ERGIC and cis-Golgi network. Forms
CC homooligomer (via GOLD domain); the assembly is promoted by direct
CC binding with leaderless cargos and may form a protein channel that
CC facilitates cargo entry into the ERGIC. Forms heterooligomeric
CC complexes with other members of the p24 family such as TMED2, TMED7 and
CC TMED9. Interacts (via GOLD domain) with TMED2 (via GOLD domain); the
CC complex is required for export of TMED10 from the ER to the cis-Golgi
CC network; the complex is proposed to be involved in cis-Golgi network
CC dynamics and / or biogenesis. Associates with the COPI vesicle coat
CC subunits (coatomer) (By similarity). Tetramerization of the cytoplasmic
CC domain at the Golgi membrane in vitro; the complex is proposed to
CC interact with COPI coatomer and induce budding of the vesicles (By
CC similarity). Interacts with COPG1; the interaction involves TMED10
CC homodimer. Interacts with ARF1 (GDP-bound); the interaction probably
CC involves a TMED10 oligomer (By similarity). Interacts with SEC23A,
CC SEC24B, SEC24C and SEC24D components of the coat protein complex
CC II/COPII, indicative of an association of TMED10 with the COPII vesicle
CC coat (PubMed:20427317). Interacts with CD59 (PubMed:20427317).
CC Interacts with MPPE1/PGAP5; the complex might recruit and sort GPI-
CC anchored proteins to the ER-exit site, or the interaction might lead to
CC recycling of PGAP5 between the ER and the Golgi. Interacts with
CC F2LR1/PAR2 (By similarity). Interacts with KDELR2/ERD2; the interaction
CC is disrupted by KDELR2 ligand (By similarity). Found in a complex
CC composed at least of SURF4, TMED2 and TMED10. Associates with the
CC presenilin-dependent gamma-secretase complex. Interacts with STX17; the
CC interaction is direct. Interacts with IL-1; the interaction is direct.
CC Interacts with RAB21 (active GTP-bound form); the interaction is
CC indirect and regulates TMED10 abundance and localization at the Golgi
CC (By similarity). {ECO:0000250|UniProtKB:P49755,
CC ECO:0000250|UniProtKB:Q28735, ECO:0000250|UniProtKB:Q63584,
CC ECO:0000269|PubMed:20427317}.
CC -!- INTERACTION:
CC O35587; P13987: CD59; Xeno; NbExp=5; IntAct=EBI-4405327, EBI-297972;
CC O35587; Q15363: TMED2; Xeno; NbExp=2; IntAct=EBI-4405327, EBI-998485;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:P49755}; Single-pass type I membrane protein
CC {ECO:0000255}. Endoplasmic reticulum-Golgi intermediate compartment
CC membrane {ECO:0000250|UniProtKB:P49755}; Single-pass type I membrane
CC protein {ECO:0000255}. Golgi apparatus membrane
CC {ECO:0000269|PubMed:9382861, ECO:0000269|PubMed:9527489}; Single-pass
CC type I membrane protein {ECO:0000255}. Golgi apparatus, cis-Golgi
CC network membrane {ECO:0000269|PubMed:9382861}; Single-pass type I
CC membrane protein {ECO:0000255}. Golgi apparatus, trans-Golgi network
CC membrane {ECO:0000269|PubMed:9527489}; Single-pass type I membrane
CC protein {ECO:0000255}. Cytoplasmic vesicle, secretory vesicle membrane
CC {ECO:0000250|UniProtKB:P49755}; Single-pass type I membrane protein
CC {ECO:0000255}. Cell membrane {ECO:0000250|UniProtKB:Q63584}; Single-
CC pass type I membrane protein {ECO:0000255}. Melanosome
CC {ECO:0000250|UniProtKB:P49755}.
CC -!- DOMAIN: The GOLD domain is required for proper p24 heterooligomeric
CC complex formation and efficient transport of GPI-anchored proteins.
CC {ECO:0000250|UniProtKB:P49755}.
CC -!- DOMAIN: The lumenal domain mediates localization to the plasma membrane
CC by partially overriding the ER retention by the cytoplasmic domain.
CC {ECO:0000250|UniProtKB:Q63584}.
CC -!- MISCELLANEOUS: Ectopic expression of TMED10 alone does not result in
CC its proper cis-Golgi network localization. Interaction of TMED10 with
CC TMED2 is both necessary and sufficient for transport of the couple to
CC the cis-Golgi network, and TMED3 and/or TMED9 contribute to
CC facilitating the process. {ECO:0000250|UniProtKB:P49755}.
CC -!- SIMILARITY: Belongs to the EMP24/GP25L family. {ECO:0000305}.
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DR EMBL; AJ001513; CAA04796.1; -; mRNA.
DR RefSeq; NP_001268617.1; NM_001281688.1.
DR AlphaFoldDB; O35587; -.
DR SMR; O35587; -.
DR IntAct; O35587; 6.
DR STRING; 10036.XP_005086428.1; -.
DR GeneID; 101832157; -.
DR CTD; 10972; -.
DR eggNOG; KOG1691; Eukaryota.
DR OrthoDB; 1370889at2759; -.
DR Proteomes; UP000189706; Unplaced.
DR GO; GO:0030137; C:COPI-coated vesicle; ISS:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
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:0070765; C:gamma-secretase complex; ISS:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0030140; C:trans-Golgi network transport vesicle; IDA:UniProtKB.
DR GO; GO:0030658; C:transport vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0042589; C:zymogen granule membrane; IEA:Ensembl.
DR GO; GO:0008320; F:protein transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0019905; F:syntaxin binding; IEA:Ensembl.
DR GO; GO:0035964; P:COPI-coated vesicle budding; ISS:UniProtKB.
DR GO; GO:0106273; P:cytosol to ERGIC protein transport; ISS:UniProtKB.
DR GO; GO:0007030; P:Golgi organization; IEA:Ensembl.
DR GO; GO:0006886; P:intracellular protein transport; IEA:Ensembl.
DR GO; GO:1902960; P:negative regulation of aspartic-type endopeptidase activity involved in amyloid precursor protein catabolic process; IEA:Ensembl.
DR GO; GO:0032732; P:positive regulation of interleukin-1 production; ISS:UniProtKB.
DR GO; GO:0050714; P:positive regulation of protein secretion; ISS:UniProtKB.
DR GO; GO:0106272; P:protein localization to ERGIC; ISS:UniProtKB.
DR GO; GO:0045055; P:regulated exocytosis; IEA:Ensembl.
DR GO; GO:1902003; P:regulation of amyloid-beta formation; ISS:UniProtKB.
DR GO; GO:0006890; P:retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum; ISS:UniProtKB.
DR InterPro; IPR015720; Emp24-like.
DR InterPro; IPR009038; GOLD_dom.
DR PANTHER; PTHR22811; PTHR22811; 1.
DR Pfam; PF01105; EMP24_GP25L; 1.
DR SMART; SM01190; EMP24_GP25L; 1.
DR PROSITE; PS50866; GOLD; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Cytoplasmic vesicle; Endoplasmic reticulum;
KW ER-Golgi transport; Glycoprotein; Golgi apparatus; Membrane; Methylation;
KW Protein transport; Reference proteome; Signal; Transmembrane;
KW Transmembrane helix; Transport.
FT SIGNAL 1..31
FT /evidence="ECO:0000250"
FT CHAIN 32..219
FT /note="Transmembrane emp24 domain-containing protein 10"
FT /id="PRO_0000010400"
FT TOPO_DOM 32..185
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 186..206
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 207..219
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT DOMAIN 41..193
FT /note="GOLD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00096"
FT REGION 1..142
FT /note="Required for interaction with STX17"
FT /evidence="ECO:0000250"
FT REGION 147..178
FT /note="Required for TMED10 and TMED2 cis-Golgi network
FT localization"
FT /evidence="ECO:0000250"
FT REGION 204..219
FT /note="Interaction with COPG1"
FT /evidence="ECO:0000250"
FT REGION 207..219
FT /note="Interaction with ARF1 and IL1B"
FT /evidence="ECO:0000250|UniProtKB:P49755"
FT MOTIF 211..219
FT /note="COPI vesicle coat-binding"
FT /evidence="ECO:0000255"
FT MOTIF 211..212
FT /note="COPII vesicle coat-binding"
FT /evidence="ECO:0000255"
FT MOD_RES 171
FT /note="Dimethylated arginine"
FT /evidence="ECO:0000250|UniProtKB:Q63584"
FT MOD_RES 176
FT /note="Dimethylated arginine"
FT /evidence="ECO:0000250|UniProtKB:Q63584"
FT CARBOHYD 179
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 219 AA; 24821 MW; 1FCF2E49ABB565EB CRC64;
MSGSSGPLSW PGPRPCALLF LLLLGPSSVL AISFHLPVNS RKCLREEIHK DLLVTGAYEI
TDQSGGAGGL RTHLKITDSA GHILYAKEDA TKGKFAFTTE DYDMFEVCFE SKGTGRIPDQ
LVILDMKHGV EAKNYEEIAK VEKLKPLEVE LRRLEDLSES IVNDFAYMKK REEEMRDTNE
STNTRVLYFS IFSMLCLIGL ATWQVFYLRR FFKAKKLIE
