TMEDA_RABIT
ID TMEDA_RABIT Reviewed; 219 AA.
AC Q28735;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 134.
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 Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=New Zealand white; TISSUE=Liver;
RX PubMed=8947548; DOI=10.1083/jcb.135.5.1239;
RA Sohn K., Orci L., Ravazzola M., Amherdt M., Bremser M., Lottspeich F.,
RA Fiedler K., Helms J.B., Wieland F.T.;
RT "A major transmembrane protein of Golgi-derived COPI-coated vesicles
RT involved in coatomer binding.";
RL J. Cell Biol. 135:1239-1248(1996).
RN [2]
RP FUNCTION, ASSOCIATION WITH COATOMER, AND MUTAGENESIS OF 211-PHE-PHE-212 AND
RP 215-LYS-LYS-216.
RX PubMed=9990005; DOI=10.1073/pnas.96.4.1224;
RA Reinhard C., Harter C., Bremser M., Brugger B., Sohn K., Helms J.B.,
RA Wieland F.T.;
RT "Receptor-induced polymerization of coatomer.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:1224-1228(1999).
RN [3]
RP FUNCTION, AND SUBUNIT.
RX PubMed=9813083; DOI=10.1083/jcb.143.3.601;
RA Majoul I., Sohn K., Wieland F.T., Pepperkok R., Pizza M., Hillemann J.,
RA Soling H.D.;
RT "KDEL receptor (Erd2p)-mediated retrograde transport of the cholera toxin A
RT subunit from the Golgi involves COPI, p23, and the COOH terminus of
RT Erd2p.";
RL J. Cell Biol. 143:601-612(1998).
RN [4]
RP FUNCTION, AND ASSOCIATION WITH COPI VESICLE COAT.
RX PubMed=18182008; DOI=10.1111/j.1600-0854.2007.00697.x;
RA Langer J.D., Roth C.M., Bethune J., Stoops E.H., Brugger B., Herten D.P.,
RA Wieland F.T.;
RT "A conformational change in the alpha-subunit of coatomer induced by ligand
RT binding to gamma-COP revealed by single-pair FRET.";
RL Traffic 9:597-607(2008).
RN [5]
RP STRUCTURE BY NMR OF 207-219.
RX PubMed=10799309; DOI=10.1006/bbrc.2000.2511;
RA Weidler M., Reinhard C., Friedrich G., Wieland F.T., Rosch P.;
RT "Structure of the cytoplasmic domain of p23 in solution: implications for
RT the formation of COPI vesicles.";
RL Biochem. Biophys. Res. Commun. 271:401-408(2000).
CC -!- FUNCTION: Cargo receptor involved in protein vesicular trafficking and
CC quality control in the endoplasmic reticulum (ER) and Golgi. The p24
CC protein family is a group of transmembrane proteins that bind coat
CC protein complex I/COPI and coat protein complex II/COPII involved in
CC vesicular trafficking between the membranes (By similarity). Acts at
CC the lumenal side for incorporation of secretory cargo molecules into
CC transport vesicles and involved in vesicle coat formation at the
CC cytoplasmic side. Mainly functions in the early secretory pathway and
CC cycles between the ER, ER-Golgi intermediate compartment (ERGIC) and
CC Golgi, mediating cargo transport through COPI and COPII-coated vesicles
CC (PubMed:9990005, PubMed:9813083). In COPII vesicle-mediated anterograde
CC transport, involved in the transport of GPI-anchored proteins by acting
CC together with TMED2 as their cargo receptor; the function specifically
CC implies SEC24C and SEC24D of the COPII vesicle coat and lipid raft-like
CC microdomains of the ER (By similarity). Recognizes GPI anchors
CC structural remodeled in the ER by the GPI inositol-deacylase/PGAP1 and
CC the metallophosphoesterase MPPE1/PGAP5 (By similarity). In COPI
CC vesicle-mediated retrograde transport, involved in the biogenesis of
CC COPI vesicles and vesicle coat recruitment (PubMed:9990005,
CC PubMed:9813083, PubMed:18182008). Involved in trafficking of amyloid
CC beta A4 protein and soluble APP-beta release (independent from the
CC modulation of gamma-secretase activity) (By similarity). Involved in
CC the KDELR2-mediated retrograde transport of the toxin A subunit (CTX-A-
CC K63)together with COPI and the COOH terminus of KDELR2
CC (PubMed:9813083). On Golgi membranes, acts as primary receptor for
CC 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:Q63584, ECO:0000269|PubMed:18182008,
CC ECO:0000269|PubMed:9813083, ECO:0000269|PubMed:9990005}.
CC -!- SUBUNIT: Predominantly dimeric and to a lesser extent monomeric in the
CC ER (PubMed:18182008). Monomer and dimer in ERGIC and cis-Golgi network.
CC Forms homooligomer (via GOLD domain); the assembly is promoted by
CC direct binding with leaderless cargos and may form a protein channel
CC that facilitates cargo entry into the ERGIC. Forms heterooligomeric
CC complexes with other members of the p24 family such as TMED2, TMED7 and
CC TMED9 (By similarity). Interacts (via GOLD domain) with TMED2 (via GOLD
CC domain); the complex is required for export of TMED10 from the ER to
CC the cis-Golgi network; the complex is proposed to be involved in cis-
CC Golgi network dynamics and / or biogenesis. Associates with the COPI
CC vesicle coat subunits (coatomer) (PubMed:9990005, PubMed:9813083,
CC PubMed:18182008). Tetramerization of the cytoplasmic domain at the
CC Golgi membrane in vitro; the complex is proposed to interact with COPI
CC coatomer and induce budding of the vesicles (PubMed:18182008).
CC Interacts with COPG1; the interaction involves TMED10 homodimer.
CC Interacts with ARF1 (GDP-bound); the interaction probably involves a
CC TMED10 oligomer. Interacts with SEC23A, SEC24B, SEC24C and SEC24D
CC components of the coat protein complex II/COPII, indicative of an
CC association of TMED10 with the COPII vesicle coat. Interacts with CD59.
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 (PubMed:9813083) (By similarity). Found
CC in a complex composed at least of SURF4, TMED2 and TMED10. Associates
CC with the presenilin-dependent gamma-secretase complex. Interacts with
CC STX17; the interaction is direct. Interacts with IL-1; the interaction
CC is direct. Interacts with RAB21 (active GTP-bound form); the
CC interaction is indirect and regulates TMED10 abundance and localization
CC at the Golgi (By similarity). {ECO:0000250|UniProtKB:P49755,
CC ECO:0000250|UniProtKB:Q63584, ECO:0000269|PubMed:18182008,
CC ECO:0000269|PubMed:9813083, ECO:0000269|PubMed:9990005}.
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:0000250|UniProtKB:P49755}; Single-pass type I membrane protein
CC {ECO:0000255}. Golgi apparatus, cis-Golgi network membrane
CC {ECO:0000250|UniProtKB:P49755}; Single-pass type I membrane protein
CC {ECO:0000255}. Golgi apparatus, trans-Golgi network membrane
CC {ECO:0000250|UniProtKB:Q63584}; Single-pass type I membrane protein
CC {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; X98303; CAA66947.1; -; mRNA.
DR RefSeq; NP_001075877.1; NM_001082408.1.
DR RefSeq; XP_008270117.1; XM_008271895.2.
DR PDB; 1M23; NMR; -; A=207-219.
DR PDB; 1P23; NMR; -; A/B/C/D=207-219.
DR PDBsum; 1M23; -.
DR PDBsum; 1P23; -.
DR AlphaFoldDB; Q28735; -.
DR SMR; Q28735; -.
DR BioGRID; 1172317; 1.
DR ELM; Q28735; -.
DR IntAct; Q28735; 1.
DR STRING; 9986.ENSOCUP00000004033; -.
DR Ensembl; ENSOCUT00000004668; ENSOCUP00000004033; ENSOCUG00000004669.
DR GeneID; 100009296; -.
DR KEGG; ocu:100009296; -.
DR CTD; 10972; -.
DR eggNOG; KOG1691; Eukaryota.
DR GeneTree; ENSGT00550000074954; -.
DR InParanoid; Q28735; -.
DR OrthoDB; 1370889at2759; -.
DR EvolutionaryTrace; Q28735; -.
DR Proteomes; UP000001811; Chromosome 20.
DR Bgee; ENSOCUG00000004669; Expressed in upper lobe of left lung and 15 other tissues.
DR ExpressionAtlas; Q28735; baseline.
DR GO; GO:0030137; C:COPI-coated vesicle; IDA: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:0030667; C:secretory granule membrane; ISS:UniProtKB.
DR GO; GO:0030140; C:trans-Golgi network transport vesicle; ISS:UniProtKB.
DR GO; GO:0030658; C:transport vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0008320; F:protein transmembrane transporter activity; ISS:UniProtKB.
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: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:1902003; P:regulation of amyloid-beta formation; ISS:UniProtKB.
DR GO; GO:0006890; P:retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum; IMP: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 3D-structure; 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_0000010403"
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"
FT MUTAGEN 211..212
FT /note="FF->AA: Impairs association with coatomer; when
FT associated with 215-S-S-216."
FT /evidence="ECO:0000269|PubMed:9990005"
FT MUTAGEN 215..216
FT /note="KK->SS: Impairs association with coatomer; when
FT associated with 211-A-A-212."
FT /evidence="ECO:0000269|PubMed:9990005"
FT HELIX 208..218
FT /evidence="ECO:0007829|PDB:1M23"
SQ SEQUENCE 219 AA; 24914 MW; 5AFA700D0A4DAB4C CRC64;
MSGWSGPLAR RGPGPLALLF LFLLGPSSVL AISFHLPVNS RKCLREEIHK DLLVTGAYEI
TDQSGGAGGL RTHLKITDSA GHILYSKEDA SKGKFAFTTE DYDMFEVCFE SKGTGRIPDQ
LVILDMKHGV EAKNYEEIAK VEKLKPLEVE LRRLEDLSES IVNDFAYMKK REEEMRDTNE
STNTRVLYFS IFSMFCLIGL ATWQVFYLRR FFKAKKLIE
