TMEDA_BOVIN
ID TMEDA_BOVIN Reviewed; 219 AA.
AC Q5E971; A4FV04;
DT 26-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 15-MAR-2005, sequence version 1.
DT 03-AUG-2022, entry version 107.
DE RecName: Full=Transmembrane emp24 domain-containing protein 10;
DE Short=Protein TMED10;
DE AltName: Full=21 kDa transmembrane-trafficking protein;
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 Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=16305752; DOI=10.1186/1471-2164-6-166;
RA Harhay G.P., Sonstegard T.S., Keele J.W., Heaton M.P., Clawson M.L.,
RA Snelling W.M., Wiedmann R.T., Van Tassell C.P., Smith T.P.L.;
RT "Characterization of 954 bovine full-CDS cDNA sequences.";
RL BMC Genomics 6:166-166(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Fetal cerebellum;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (SEP-2006) to the EMBL/GenBank/DDBJ databases.
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. Acts at the lumenal side
CC for incorporation of secretory cargo molecules into transport vesicles
CC and involved in vesicle coat formation at the cytoplasmic side. Mainly
CC functions in the early secretory pathway and cycles between the ER, ER-
CC Golgi intermediate compartment (ERGIC) and Golgi, mediating cargo
CC transport through COPI and COPII-coated vesicles. In COPII vesicle-
CC mediated anterograde transport, involved in the transport of GPI-
CC anchored proteins by acting together with TMED2 as their cargo
CC receptor; the function specifically implies SEC24C and SEC24D of the
CC COPII vesicle coat and lipid raft-like microdomains of the ER (By
CC similarity). Recognizes GPI anchors structural remodeled in the ER by
CC the GPI inositol-deacylase/PGAP1 and the metallophosphoesterase
CC MPPE1/PGAP5 (By similarity). In COPI vesicle-mediated retrograde
CC transport, involved in the biogenesis of COPI vesicles and vesicle coat
CC recruitment. Involved in trafficking of amyloid beta A4 protein and
CC soluble APP-beta release (independent from the modulation of gamma-
CC secretase activity) (By similarity). Involved in the KDELR2-mediated
CC retrograde transport of the toxin A subunit (CTX-A-K63)together with
CC COPI and the COOH terminus of KDELR2 (By similarity). On Golgi
CC membranes, acts as primary receptor for ARF1-GDP, a GTP-binding protein
CC involved in COPI-vesicle formation. Increases coatomer-dependent
CC GTPase-activating activity of ARFGAP2 which mediates the hydrolysis of
CC ARF1-bound GTP and therefore modulates protein trafficking from the
CC Golgi apparatus. Involved in the exocytic trafficking of G protein-
CC coupled receptors F2LR1/PAR2 (trypsin and tryspin-like enzyme
CC receptor), OPRM1 (opioid receptor) and P2RY4 (UTD and UDP receptor)
CC from the Golgi to the plasma membrane, thus contributing to receptor
CC resensitization. In addition to its cargo receptor activity, may also
CC act as a protein channel after oligomerization, facilitating the post-
CC translational entry of leaderless cytoplasmic cargo into the ERGIC.
CC Involved in the translocation into ERGIC, the vesicle entry and the
CC secretion of leaderless cargos (lacking the secretion signal sequence),
CC including the mature form of interleukin 1/IL-1 family members, the
CC alpha-crystallin B chain HSPB5, the carbohydrate-binding proteins
CC galectin-1/LGALS1 and galectin-3/LGALS3, the microtubule-associated
CC protein Tau/MAPT, and the annexin A1/ANXA1; the translocation process
CC is 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 -!- 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. Interacts with SEC23A, SEC24B, SEC24C and
CC SEC24D components of the coat protein complex II/COPII, indicative of
CC an association of TMED10 with the COPII vesicle coat. Interacts with
CC CD59. Interacts with MPPE1/PGAP5; the complex might recruit and sort
CC GPI-anchored proteins to the ER-exit site, or the interaction might
CC lead to 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 -!- 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; BT021049; AAX09066.1; -; mRNA.
DR EMBL; BC123529; AAI23530.1; -; mRNA.
DR RefSeq; NP_001035639.1; NM_001040549.2.
DR AlphaFoldDB; Q5E971; -.
DR SMR; Q5E971; -.
DR IntAct; Q5E971; 1.
DR MINT; Q5E971; -.
DR STRING; 9913.ENSBTAP00000007481; -.
DR PaxDb; Q5E971; -.
DR PeptideAtlas; Q5E971; -.
DR PRIDE; Q5E971; -.
DR Ensembl; ENSBTAT00000007481; ENSBTAP00000007481; ENSBTAG00000005694.
DR GeneID; 529761; -.
DR KEGG; bta:529761; -.
DR CTD; 10972; -.
DR VEuPathDB; HostDB:ENSBTAG00000005694; -.
DR VGNC; VGNC:35935; TMED10.
DR eggNOG; KOG1691; Eukaryota.
DR GeneTree; ENSGT00550000074954; -.
DR InParanoid; Q5E971; -.
DR OMA; AMGNDYH; -.
DR OrthoDB; 1370889at2759; -.
DR Proteomes; UP000009136; Chromosome 10.
DR Bgee; ENSBTAG00000005694; Expressed in spermatocyte and 109 other tissues.
DR GO; GO:0030137; C:COPI-coated vesicle; ISS:UniProtKB.
DR GO; GO:0030134; C:COPII-coated ER to Golgi transport vesicle; IBA:GO_Central.
DR GO; GO:0005783; C:endoplasmic reticulum; IBA:GO_Central.
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:0005794; C:Golgi apparatus; IBA:GO_Central.
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: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:0006888; P:endoplasmic reticulum to Golgi vesicle-mediated transport; IBA:GO_Central.
DR GO; GO:0007030; P:Golgi organization; IBA:GO_Central.
DR GO; GO:0006886; P:intracellular protein transport; IBA:GO_Central.
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 2: Evidence at transcript 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_0000010398"
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; 24828 MW; C1E131C19A915E68 CRC64;
MSGSSGPQAQ RGPCPFALLL LLLLGPSSVL AISFHLPVNS RKCLREEIHK DLLVTGAYEI
TDQSGGAGGL RTHLKITDSA GHILYSKEDA TKGKFAFTTE DYDMFEVCFE SKGTGRIPDQ
LVILDMKHGV EAKNYEEIAK VEKLKPLEVE LRRLEDLSES IVNDFAYMKK REEEMRDTNE
STNTRVLYFS IFSMFCLIGL ATWQVFYLRR FFKAKKLIE
