TMEDA_HUMAN
ID TMEDA_HUMAN Reviewed; 219 AA.
AC P49755; B2R605; Q15602; Q16536; Q86TC2; Q86TS5;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 15-DEC-1998, sequence version 2.
DT 03-AUG-2022, entry version 199.
DE RecName: Full=Transmembrane emp24 domain-containing protein 10;
DE Short=Protein TMED10;
DE AltName: Full=21 kDa transmembrane-trafficking protein;
DE AltName: Full=S31I125;
DE AltName: Full=S31III125;
DE AltName: Full=Tmp-21-I;
DE AltName: Full=Transmembrane protein Tmp21;
DE AltName: Full=p23;
DE AltName: Full=p24 family protein delta-1;
DE Short=p24delta1;
DE AltName: Full=p24delta;
DE Flags: Precursor;
GN Name=TMED10 {ECO:0000312|HGNC:HGNC:16998}; Synonyms=TMP21;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC 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., 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 [GENOMIC DNA].
RA Sanseau P., Sherington R., Trower M.K., St George-Hyslop P.H., Dykes C.W.;
RT "New human gene, member of a large family implicated in protein
RT trafficking.";
RL Submitted (JUL-1996) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RX PubMed=7596406; DOI=10.1038/375754a0;
RA Sherrington R., Rogaev E.I., Liang Y., Rogaeva E.A., Levesque G., Ikeda M.,
RA Chi H., Lin C., Li G., Holman K., Tsuda T., Mar L., Foncin J.-F.,
RA Bruni A.C., Montesi M.P., Sorbi S., Rainero I., Pinessi L., Nee L.,
RA Chumakov I., Pollen D., Brookes A., Sanseau P., Polinsky R.J., Wasco W.,
RA da Silva H.A.R., Haines J.L., Pericak-Vance M.A., Tanzi R.E., Roses A.D.,
RA Fraser P.E., Rommens J.M., St George-Hyslop P.H.;
RT "Cloning of a gene bearing missense mutations in early-onset familial
RT Alzheimer's disease.";
RL Nature 375:754-760(1995).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Pancreas;
RX PubMed=10376215; DOI=10.3109/10425179909008429;
RA Hoerer J., Blum R., Feick P., Nastainczyk W., Schulz I.;
RT "A comparative study of rat and human Tmp21 (p23) reveals the pseudogene-
RT like features of human Tmp21-II.";
RL DNA Seq. 10:121-126(1999).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Fetal brain;
RA Li W.B., Gruber C., Jessee J., Polayes D.;
RT "Full-length cDNA libraries and normalization.";
RL Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Amygdala;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skeletal muscle;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Colon;
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 [11]
RP PROTEIN SEQUENCE [LARGE SCALE ANALYSIS] OF 32-42.
RC TISSUE=Leukemic T-cell;
RX PubMed=19892738; DOI=10.1073/pnas.0908958106;
RA Xu G., Shin S.B., Jaffrey S.R.;
RT "Global profiling of protease cleavage sites by chemoselective labeling of
RT protein N-termini.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:19310-19315(2009).
RN [12]
RP 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 [13]
RP SUBCELLULAR LOCATION, ASSOCIATION WITH COPI AND COPII VESICLE COAT, AND
RP MUTAGENESIS OF 211-PHE-PHE-212 AND 215-LYS-LYS-216.
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 [14]
RP FUNCTION.
RX PubMed=10052452; DOI=10.1016/s0092-8674(00)80654-6;
RA Bremser M., Nickel W., Schweikert M., Ravazzola M., Amherdt M.,
RA Hughes C.A., Sollner T.H., Rothman J.E., Wieland F.T.;
RT "Coupling of coat assembly and vesicle budding to packaging of putative
RT cargo receptors.";
RL Cell 96:495-506(1999).
RN [15]
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 with
RT other p24 family members.";
RL Mol. Biol. Cell 10:1939-1955(1999).
RN [16]
RP MUTAGENESIS OF 211-PHE-PHE-212 AND 215-LYS-LYS-216.
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 the
RT COPI coat complex.";
RL Cell 100:671-679(2000).
RN [17]
RP INTERACTION WITH COPG1, AND MUTAGENESIS OF 211-PHE-PHE-212 AND
RP 215-LYS-LYS-216.
RX PubMed=11056392; DOI=10.1093/oxfordjournals.jbchem.a022817;
RA Futatsumori M., Kasai K., Takatsu H., Shin H.-W., Nakayama K.;
RT "Identification and characterization of novel isoforms of COP I subunits.";
RL J. Biochem. 128:793-801(2000).
RN [18]
RP FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, AND MISCELLANEOUS.
RX PubMed=10852829; DOI=10.1242/jcs.113.13.2507;
RA Emery G., Rojo M., Gruenberg J.;
RT "Coupled transport of p24 family members.";
RL J. Cell Sci. 113:2507-2516(2000).
RN [19]
RP FUNCTION, AND INTERACTION WITH ARF1.
RX PubMed=11726511; DOI=10.1093/emboj/20.23.6751;
RA Gommel D.U., Memon A.R., Heiss A., Lottspeich F., Pfannstiel J.,
RA Lechner J., Reinhard C., Helms J.B., Nickel W., Wieland F.T.;
RT "Recruitment to Golgi membranes of ADP-ribosylation factor 1 is mediated by
RT the cytoplasmic domain of p23.";
RL EMBO J. 20:6751-6760(2001).
RN [20]
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 secretory
RT pathway.";
RL J. Biol. Chem. 277:46504-46511(2002).
RN [21]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RC TISSUE=Melanoma;
RX PubMed=17081065; DOI=10.1021/pr060363j;
RA Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H., Mangini N.J.,
RA Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R., Yamagishi S.,
RA Shabanowitz J., Hearing V.J., Wu C., Appella E., Hunt D.F.;
RT "Proteomic and bioinformatic characterization of the biogenesis and
RT function of melanosomes.";
RL J. Proteome Res. 5:3135-3144(2006).
RN [22]
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 [23]
RP FUNCTION, AND SUBUNIT.
RX PubMed=16641999; DOI=10.1038/nature04667;
RA Chen F., Hasegawa H., Schmitt-Ulms G., Kawarai T., Bohm C., Katayama T.,
RA Gu Y., Sanjo N., Glista M., Rogaeva E., Wakutani Y., Pardossi-Piquard R.,
RA Ruan X., Tandon A., Checler F., Marambaud P., Hansen K., Westaway D.,
RA St George-Hyslop P., Fraser P.;
RT "TMP21 is a presenilin complex component that modulates gamma-secretase but
RT not epsilon-secretase activity.";
RL Nature 440:1208-1212(2006).
RN [24]
RP FUNCTION.
RX PubMed=17288597; DOI=10.1186/1750-1326-2-4;
RA Vetrivel K.S., Gong P., Bowen J.W., Cheng H., Chen Y., Carter M.,
RA Nguyen P.D., Placanica L., Wieland F.T., Li Y.M., Kounnas M.Z.,
RA Thinakaran G.;
RT "Dual roles of the transmembrane protein p23/TMP21 in the modulation of
RT amyloid precursor protein metabolism.";
RL Mol. Neurodegener. 2:4-4(2007).
RN [25]
RP IDENTIFICATION IN A COMPLEX WITH SURF4 AND TMED2.
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 architecture
RT of ERGIC and Golgi.";
RL Mol. Biol. Cell 19:1976-1990(2008).
RN [26]
RP INTERACTION WITH MPPE1.
RX PubMed=19837036; DOI=10.1016/j.cell.2009.08.040;
RA Fujita M., Maeda Y., Ra M., Yamaguchi Y., Taguchi R., Kinoshita T.;
RT "GPI glycan remodeling by PGAP5 regulates transport of GPI-anchored
RT proteins from the ER to the Golgi.";
RL Cell 139:352-365(2009).
RN [27]
RP FUNCTION.
RX PubMed=19296914; DOI=10.1016/j.cellsig.2009.03.006;
RA Luo R., Ha V.L., Hayashi R., Randazzo P.A.;
RT "Arf GAP2 is positively regulated by coatomer and cargo.";
RL Cell. Signal. 21:1169-1179(2009).
RN [28]
RP FUNCTION.
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 [29]
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., Buerckstuemmer T.,
RA 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 [30]
RP INTERACTION WITH STX17.
RX PubMed=21545355; DOI=10.1042/bc20110006;
RA Muppirala M., Gupta V., Swarup G.;
RT "Syntaxin 17 cycles between the ER and ERGIC and is required to maintain
RT the architecture of ERGIC and Golgi.";
RL Biol. Cell 103:333-350(2011).
RN [31]
RP FUNCTION, INTERACTION WITH F2RL1, AND SUBCELLULAR LOCATION.
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).
RN [32]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [33]
RP CLEAVAGE OF SIGNAL PEPTIDE [LARGE SCALE ANALYSIS] AFTER ALA-31, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [34]
RP FUNCTION, SUBUNIT, AND DOMAIN.
RX PubMed=27569046; DOI=10.1016/j.jmb.2016.08.023;
RA Nagae M., Hirata T., Morita-Matsumoto K., Theiler R., Fujita M.,
RA Kinoshita T., Yamaguchi Y.;
RT "3D structure and interaction of p24beta and p24delta golgi dynamics
RT domains: implication for p24 complex formation and cargo transport.";
RL J. Mol. Biol. 428:4087-4099(2016).
RN [35]
RP INTERACTION WITH RAB21.
RX PubMed=31455601; DOI=10.1242/bio.045336;
RA Del Olmo T., Lacarriere-Keita C., Normandin C., Jean D., Boisvert F.M.,
RA Jean S.;
RT "RAB21 interacts with TMED10 and modulates its localization and
RT abundance.";
RL Biol. Open 8:0-0(2019).
RN [36]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH IL1B, AND REGION.
RX PubMed=32272059; DOI=10.1016/j.cell.2020.03.031;
RA Zhang M., Liu L., Lin X., Wang Y., Li Y., Guo Q., Li S., Sun Y., Tao X.,
RA Zhang D., Lv X., Zheng L., Ge L.;
RT "A Translocation Pathway for Vesicle-Mediated Unconventional Protein
RT Secretion.";
RL Cell 181:637-652(2020).
CC -!- FUNCTION: Cargo receptor involved in protein vesicular trafficking and
CC quality control in the endoplasmic reticulum (ER) and Golgi
CC (PubMed:10052452, PubMed:11726511, PubMed:16641999, PubMed:17288597,
CC PubMed:19296914, PubMed:20427317, PubMed:21219331, PubMed:27569046).
CC The p24 protein family is a group of transmembrane proteins that bind
CC coat protein complex I/COPI and coat protein complex II/COPII involved
CC in vesicular trafficking between the membranes (PubMed:10052452). 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 (PubMed:20427317, PubMed:27569046). Mainly functions
CC in the early secretory pathway and cycles between the ER, ER-Golgi
CC intermediate compartment (ERGIC) and Golgi, mediating cargo transport
CC through COPI and COPII-coated vesicles (PubMed:10052452,
CC PubMed:10852829, PubMed:12237308). 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 (PubMed:20427317,
CC PubMed:27569046). Recognizes GPI anchors structural remodeled in the ER
CC by 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 (PubMed:11726511). Involved in trafficking of amyloid beta
CC A4 protein and soluble APP-beta release (independent from the
CC modulation of gamma-secretase activity) (PubMed:17288597). 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 (By similarity).
CC On Golgi membranes, acts as primary receptor for ARF1-GDP, a GTP-
CC binding protein involved in COPI-vesicle formation (PubMed:11726511).
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 (PubMed:19296914).
CC Involved in the exocytic trafficking of G protein-coupled receptors
CC F2LR1/PAR2 (trypsin and tryspin-like enzyme receptor), OPRM1 (opioid
CC receptor) and P2RY4 (UTD and UDP receptor) from the Golgi to the plasma
CC membrane, thus contributing to receptor resensitization
CC (PubMed:21219331). 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 (PubMed:32272059). Involved in the translocation into ERGIC, the
CC vesicle entry and the secretion of leaderless cargos (lacking the
CC secretion signal sequence), including the mature form of interleukin
CC 1/IL-1 family members, the alpha-crystallin B chain HSPB5, the
CC carbohydrate-binding proteins galectin-1/LGALS1 and galectin-3/LGALS3,
CC the microtubule-associated protein Tau/MAPT, and the annexin A1/ANXA1;
CC the translocation process is dependent on cargo protein unfolding and
CC enhanced by chaperones HSP90AB1 and HSP90B1/GRP9 (PubMed:32272059).
CC Could also associates with the presenilin-dependent gamma-secretase
CC complex in order to regulate gamma-cleavages of the amyloid beta A4
CC protein to yield amyloid-beta 40/Abeta40 (PubMed:16641999).
CC {ECO:0000250|UniProtKB:Q28735, ECO:0000250|UniProtKB:Q63584,
CC ECO:0000269|PubMed:10052452, ECO:0000269|PubMed:10852829,
CC ECO:0000269|PubMed:11726511, ECO:0000269|PubMed:12237308,
CC ECO:0000269|PubMed:16641999, ECO:0000269|PubMed:17288597,
CC ECO:0000269|PubMed:19296914, ECO:0000269|PubMed:20427317,
CC ECO:0000269|PubMed:21219331, ECO:0000269|PubMed:27569046,
CC ECO:0000269|PubMed:32272059, ECO:0000303|PubMed:10052452}.
CC -!- SUBUNIT: Predominantly dimeric and to a lesser extent monomeric in the
CC ER (PubMed:12237308). Monomer and dimer in ERGIC and cis-Golgi network
CC (PubMed:12237308). Forms homooligomer (via GOLD domain); the assembly
CC is promoted by direct binding with leaderless cargos and may form a
CC protein channel that facilitates cargo entry into the ERGIC
CC (PubMed:32272059). Forms heterooligomeric complexes with other members
CC of the p24 family such as TMED2, TMED7 and TMED9 (PubMed:9472029,
CC PubMed:10359607, PubMed:20427317, PubMed:32272059). Interacts (via GOLD
CC domain) with TMED2 (via GOLD domain); the complex is required for
CC export of TMED10 from the ER to the cis-Golgi network; the complex is
CC proposed to be involved in cis-Golgi network dynamics and / or
CC biogenesis (PubMed:10852829, PubMed:27569046). Associates with the COPI
CC vesicle coat subunits (coatomer) (PubMed:9472029, PubMed:11056392,
CC PubMed:16940185). 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 (By similarity). Interacts
CC with COPG1; the interaction involves TMED10 homodimer
CC (PubMed:16940185). Interacts with ARF1 (GDP-bound); the interaction
CC probably involves a TMED10 oligomer (PubMed:11726511). Interacts with
CC SEC23A, SEC24B, SEC24C and SEC24D components of the coat protein
CC complex II/COPII, indicative of an association of TMED10 with the COPII
CC vesicle coat (PubMed:9472029). 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 (PubMed:19837036).
CC Interacts with F2LR1/PAR2 (PubMed:21219331). Interacts with
CC KDELR2/ERD2; the interaction is disrupted by KDELR2 ligand (By
CC similarity). Found in a complex composed at least of SURF4, TMED2 and
CC TMED10 (PubMed:18287528). Associates with the presenilin-dependent
CC gamma-secretase complex (PubMed:16641999). Interacts with STX17; the
CC interaction is direct (PubMed:21545355). Interacts with IL-1; the
CC interaction is direct (PubMed:32272059). Interacts with RAB21 (active
CC GTP-bound form); the interaction is indirect and regulates TMED10
CC abundance and localization at the Golgi (PubMed:31455601).
CC {ECO:0000250|UniProtKB:Q28735, ECO:0000250|UniProtKB:Q63584,
CC ECO:0000269|PubMed:10359607, ECO:0000269|PubMed:10852829,
CC ECO:0000269|PubMed:11056392, ECO:0000269|PubMed:11726511,
CC ECO:0000269|PubMed:12237308, ECO:0000269|PubMed:16641999,
CC ECO:0000269|PubMed:16940185, ECO:0000269|PubMed:18287528,
CC ECO:0000269|PubMed:19837036, ECO:0000269|PubMed:20427317,
CC ECO:0000269|PubMed:21219331, ECO:0000269|PubMed:21545355,
CC ECO:0000269|PubMed:27569046, ECO:0000269|PubMed:31455601,
CC ECO:0000269|PubMed:32272059, ECO:0000269|PubMed:9472029}.
CC -!- INTERACTION:
CC P49755; P05067: APP; NbExp=3; IntAct=EBI-998422, EBI-77613;
CC P49755; Q8WXH2: JPH3; NbExp=3; IntAct=EBI-998422, EBI-1055254;
CC P49755; Q92542: NCSTN; NbExp=5; IntAct=EBI-998422, EBI-998440;
CC P49755; P49768: PSEN1; NbExp=4; IntAct=EBI-998422, EBI-297277;
CC P49755; Q9NZ42: PSENEN; NbExp=3; IntAct=EBI-998422, EBI-998468;
CC P49755; P17706-1: PTPN2; NbExp=5; IntAct=EBI-998422, EBI-4409481;
CC P49755; Q15363: TMED2; NbExp=7; IntAct=EBI-998422, EBI-998485;
CC P49755; Q8XAL7: nleF; Xeno; NbExp=6; IntAct=EBI-998422, EBI-10039292;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:10852829, ECO:0000269|PubMed:12237308,
CC ECO:0000269|PubMed:9472029}; Single-pass type I membrane protein
CC {ECO:0000255}. Endoplasmic reticulum-Golgi intermediate compartment
CC membrane {ECO:0000269|PubMed:12237308, ECO:0000269|PubMed:32272059,
CC ECO:0000269|PubMed:9382861}; Single-pass type I membrane protein
CC {ECO:0000255}. Golgi apparatus membrane {ECO:0000269|PubMed:10852829,
CC ECO:0000269|PubMed:12237308, ECO:0000269|PubMed:21219331,
CC ECO:0000269|PubMed:9382861, ECO:0000269|PubMed:9472029}; 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:0000250|UniProtKB:Q63584}; Single-pass type I membrane
CC protein {ECO:0000255}. Cytoplasmic vesicle, secretory vesicle membrane
CC {ECO:0000305}; Single-pass type I membrane protein {ECO:0000255}. Cell
CC membrane {ECO:0000250|UniProtKB:Q63584}; Single-pass type I membrane
CC protein {ECO:0000255}. Melanosome {ECO:0000269|PubMed:17081065}.
CC Note=Identified by mass spectrometry in melanosome fractions from stage
CC I to stage IV. {ECO:0000269|PubMed:17081065}.
CC -!- DOMAIN: The GOLD domain is required for proper p24 heterooligomeric
CC complex formation and efficient transport of GPI-anchored proteins.
CC {ECO:0000269|PubMed:27569046}.
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 (PubMed:10852829).
CC Interaction of TMED10 with TMED2 is both necessary and sufficient for
CC transport of the couple to the cis-Golgi network, and TMED3 and/or
CC TMED9 contribute to facilitating the process (PubMed:10852829).
CC {ECO:0000269|PubMed:10852829}.
CC -!- SIMILARITY: Belongs to the EMP24/GP25L family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC42003.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=CAD66561.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; X97442; CAA66071.1; -; mRNA.
DR EMBL; X97444; CAA66073.1; -; mRNA.
DR EMBL; U61734; AAB03625.1; -; Genomic_DNA.
DR EMBL; L40397; AAC42003.1; ALT_FRAME; mRNA.
DR EMBL; AJ004913; CAA06213.1; -; mRNA.
DR EMBL; BX248754; CAD66561.1; ALT_INIT; mRNA.
DR EMBL; AK312384; BAG35302.1; -; mRNA.
DR EMBL; AL832012; CAD89913.1; -; mRNA.
DR EMBL; AC007055; AAD31941.1; -; Genomic_DNA.
DR EMBL; CH471061; EAW81223.1; -; Genomic_DNA.
DR EMBL; BC001496; AAH01496.1; -; mRNA.
DR EMBL; BC001825; AAH01825.1; -; mRNA.
DR CCDS; CCDS9840.1; -.
DR PIR; G01159; G01159.
DR RefSeq; NP_006818.3; NM_006827.5.
DR AlphaFoldDB; P49755; -.
DR SMR; P49755; -.
DR BioGRID; 116169; 147.
DR CORUM; P49755; -.
DR ELM; P49755; -.
DR IntAct; P49755; 74.
DR MINT; P49755; -.
DR STRING; 9606.ENSP00000303145; -.
DR ChEMBL; CHEMBL4295772; -.
DR TCDB; 9.B.188.1.4; the transmembrane emp24 domain-containing protein (tmed) family.
DR GlyGen; P49755; 3 sites, 2 O-linked glycans (2 sites).
DR iPTMnet; P49755; -.
DR MetOSite; P49755; -.
DR PhosphoSitePlus; P49755; -.
DR SwissPalm; P49755; -.
DR BioMuta; TMED10; -.
DR DMDM; 3915893; -.
DR EPD; P49755; -.
DR jPOST; P49755; -.
DR MassIVE; P49755; -.
DR MaxQB; P49755; -.
DR PaxDb; P49755; -.
DR PeptideAtlas; P49755; -.
DR PRIDE; P49755; -.
DR ProteomicsDB; 56070; -.
DR TopDownProteomics; P49755; -.
DR Antibodypedia; 25817; 445 antibodies from 34 providers.
DR DNASU; 10972; -.
DR Ensembl; ENST00000303575.9; ENSP00000303145.4; ENSG00000170348.9.
DR GeneID; 10972; -.
DR KEGG; hsa:10972; -.
DR MANE-Select; ENST00000303575.9; ENSP00000303145.4; NM_006827.6; NP_006818.3.
DR UCSC; uc001xrm.2; human.
DR CTD; 10972; -.
DR DisGeNET; 10972; -.
DR GeneCards; TMED10; -.
DR HGNC; HGNC:16998; TMED10.
DR HPA; ENSG00000170348; Low tissue specificity.
DR MIM; 605406; gene.
DR neXtProt; NX_P49755; -.
DR OpenTargets; ENSG00000170348; -.
DR PharmGKB; PA128394579; -.
DR VEuPathDB; HostDB:ENSG00000170348; -.
DR eggNOG; KOG1691; Eukaryota.
DR GeneTree; ENSGT00550000074954; -.
DR HOGENOM; CLU_066963_3_1_1; -.
DR InParanoid; P49755; -.
DR OMA; AMGNDYH; -.
DR OrthoDB; 1370889at2759; -.
DR PhylomeDB; P49755; -.
DR TreeFam; TF313729; -.
DR PathwayCommons; P49755; -.
DR Reactome; R-HSA-204005; COPII-mediated vesicle transport.
DR Reactome; R-HSA-5694530; Cargo concentration in the ER.
DR Reactome; R-HSA-6807878; COPI-mediated anterograde transport.
DR Reactome; R-HSA-6811434; COPI-dependent Golgi-to-ER retrograde traffic.
DR SignaLink; P49755; -.
DR SIGNOR; P49755; -.
DR BioGRID-ORCS; 10972; 347 hits in 1092 CRISPR screens.
DR ChiTaRS; TMED10; human.
DR GeneWiki; TMED10; -.
DR GenomeRNAi; 10972; -.
DR Pharos; P49755; Tbio.
DR PRO; PR:P49755; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; P49755; protein.
DR Bgee; ENSG00000170348; Expressed in parotid gland and 206 other tissues.
DR ExpressionAtlas; P49755; baseline and differential.
DR Genevisible; P49755; HS.
DR GO; GO:0005801; C:cis-Golgi network; ISS:HGNC-UCL.
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; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0005793; C:endoplasmic reticulum-Golgi intermediate compartment; IDA:UniProtKB.
DR GO; GO:0033116; C:endoplasmic reticulum-Golgi intermediate compartment membrane; TAS:Reactome.
DR GO; GO:0012507; C:ER to Golgi transport vesicle membrane; TAS:Reactome.
DR GO; GO:0070765; C:gamma-secretase complex; IDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
DR GO; GO:0016021; C:integral component of membrane; ISS:HGNC-UCL.
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:0030133; C:transport vesicle; TAS:Reactome.
DR GO; GO:0042589; C:zymogen granule membrane; ISS:HGNC-UCL.
DR GO; GO:0008320; F:protein transmembrane transporter activity; IMP:UniProtKB.
DR GO; GO:0019905; F:syntaxin binding; IPI:UniProtKB.
DR GO; GO:0048205; P:COPI coating of Golgi vesicle; TAS:UniProtKB.
DR GO; GO:0035964; P:COPI-coated vesicle budding; IDA:UniProtKB.
DR GO; GO:0048208; P:COPII vesicle coating; TAS:UniProtKB.
DR GO; GO:0106273; P:cytosol to ERGIC protein transport; IMP: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; IDA:UniProtKB.
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; IMP:UniProtKB.
DR GO; GO:0050714; P:positive regulation of protein secretion; IMP:UniProtKB.
DR GO; GO:0106272; P:protein localization to ERGIC; IMP:UniProtKB.
DR GO; GO:0045055; P:regulated exocytosis; ISS:HGNC-UCL.
DR GO; GO:1902003; P:regulation of amyloid-beta formation; IMP:UniProtKB.
DR GO; GO:0006890; P:retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0035459; P:vesicle cargo loading; TAS:UniProtKB.
DR GO; GO:0048199; P:vesicle targeting, to, from or within Golgi; ISS:HGNC-UCL.
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; Direct protein sequencing;
KW Endoplasmic reticulum; ER-Golgi transport; Glycoprotein; Golgi apparatus;
KW Membrane; Methylation; Protein transport; Reference proteome; Signal;
KW Transmembrane; Transmembrane helix; Transport.
FT SIGNAL 1..31
FT /evidence="ECO:0000269|PubMed:19892738,
FT ECO:0007744|PubMed:25944712"
FT CHAIN 32..219
FT /note="Transmembrane emp24 domain-containing protein 10"
FT /id="PRO_0000010399"
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:0000269|PubMed:21545355"
FT REGION 147..178
FT /note="Required for TMED10 and TMED2 cis-Golgi network
FT localization"
FT REGION 204..219
FT /note="Interaction with COPG1"
FT REGION 207..219
FT /note="Interaction with ARF1 and IL1B"
FT /evidence="ECO:0000269|PubMed:11726511,
FT ECO:0000269|PubMed:32272059"
FT MOTIF 211..219
FT /note="COPI vesicle coat-binding"
FT MOTIF 211..212
FT /note="COPII vesicle coat-binding"
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 VARIANT 64
FT /note="S -> Y (in dbSNP:rs4929)"
FT /id="VAR_012051"
FT VARIANT 152
FT /note="R -> G (in dbSNP:rs17103066)"
FT /id="VAR_049111"
FT MUTAGEN 211..212
FT /note="FF->AA: Disrupts interaction with COPG1 and
FT association with coatomer; when associated with 215-A-A-
FT 216."
FT /evidence="ECO:0000269|PubMed:10761932,
FT ECO:0000269|PubMed:11056392, ECO:0000269|PubMed:9472029"
FT MUTAGEN 211..212
FT /note="FF->AA: No decrease in binding to COPG1. Disrupts
FT interaction with SEC23A."
FT /evidence="ECO:0000269|PubMed:10761932,
FT ECO:0000269|PubMed:11056392, ECO:0000269|PubMed:9472029"
FT MUTAGEN 215..216
FT /note="KK->AA: Disrupts interaction with COPG1 and
FT association with coatomer; when associated with 211-A-A-
FT 212."
FT /evidence="ECO:0000269|PubMed:10761932,
FT ECO:0000269|PubMed:11056392, ECO:0000269|PubMed:9472029"
FT MUTAGEN 215..216
FT /note="KK->AA: Significant reduction in binding to COPG1."
FT /evidence="ECO:0000269|PubMed:10761932,
FT ECO:0000269|PubMed:11056392, ECO:0000269|PubMed:9472029"
FT CONFLICT 75
FT /note="K -> R (in Ref. 7; CAD89913)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 219 AA; 24976 MW; 0A0486BE65C4DBBB CRC64;
MSGLSGPPAR RGPFPLALLL LFLLGPRLVL AISFHLPINS RKCLREEIHK DLLVTGAYEI
SDQSGGAGGL RSHLKITDSA GHILYSKEDA TKGKFAFTTE DYDMFEVCFE SKGTGRIPDQ
LVILDMKHGV EAKNYEEIAK VEKLKPLEVE LRRLEDLSES IVNDFAYMKK REEEMRDTNE
STNTRVLYFS IFSMFCLIGL ATWQVFYLRR FFKAKKLIE
