TMED3_HUMAN
ID TMED3_HUMAN Reviewed; 217 AA.
AC Q9Y3Q3; A8K069; B4DN05; Q2T9F8;
DT 28-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 172.
DE RecName: Full=Transmembrane emp24 domain-containing protein 3;
DE AltName: Full=Membrane protein p24B;
DE AltName: Full=p24 family protein gamma-4;
DE Short=p24gamma4;
DE AltName: Full=p26;
DE Flags: Precursor;
GN Name=TMED3; Synonyms=C15orf22; ORFNames=UNQ5357/PRO1078;
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] (ISOFORM 1).
RC TISSUE=Placenta;
RA Blum R., Nastainczyk W., Kohler B., Schulz I.;
RT "Cloning, localization and in vivo trafficking of p24B, a novel p24-
RT member.";
RL Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RG The European IMAGE consortium;
RL Submitted (JUL-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human chromosome
RT 15.";
RL Nature 440:671-675(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Kidney, Lung, and Skin;
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 [8]
RP FUNCTION, AND SUBCELLULAR LOCATION.
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 [9]
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 [10]
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 [11]
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).
CC -!- FUNCTION: Potential role in vesicular protein trafficking, mainly in
CC the early secretory pathway. Contributes to the coupled localization of
CC TMED2 and TMED10 in the cis-Golgi network.
CC {ECO:0000269|PubMed:10852829}.
CC -!- SUBUNIT: Monomer in endoplasmic reticulum, endoplasmic reticulum-Golgi
CC intermediate compartment and cis-Golgi network. Interacts (via C-
CC terminus) with COPG1; the interaction involves dimeric TMED3; however,
CC there are conflicting reports on the interaction. Interacts with
CC GORASP1 and GORASP2 (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum-Golgi intermediate
CC compartment membrane {ECO:0000269|PubMed:12237308}; Single-pass type I
CC membrane protein {ECO:0000255}. Golgi apparatus, cis-Golgi network
CC membrane {ECO:0000269|PubMed:10852829, ECO:0000269|PubMed:12237308};
CC Single-pass type I membrane protein {ECO:0000255}. Golgi apparatus,
CC Golgi stack membrane {ECO:0000250|UniProtKB:Q6AY25}; Single-pass type I
CC membrane protein {ECO:0000255}. Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:10852829}; Single-pass type I membrane protein
CC {ECO:0000255}. Cytoplasmic vesicle, COPI-coated vesicle membrane
CC {ECO:0000305|PubMed:16940185}; Single-pass type I membrane protein
CC {ECO:0000255}. Note=Probably cycles between compartments of the early
CC secretatory pathway. {ECO:0000269|PubMed:10852829}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9Y3Q3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9Y3Q3-2; Sequence=VSP_044371;
CC -!- SIMILARITY: Belongs to the EMP24/GP25L family. {ECO:0000305}.
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DR EMBL; AJ132270; CAB40416.1; -; mRNA.
DR EMBL; AL109672; CAB52017.1; -; mRNA.
DR EMBL; AY358974; AAQ89333.1; -; mRNA.
DR EMBL; CR457384; CAG33665.1; -; mRNA.
DR EMBL; AK289434; BAF82123.1; -; mRNA.
DR EMBL; AK297710; BAG60067.1; -; mRNA.
DR EMBL; AC011797; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC027811; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC000027; AAH00027.1; -; mRNA.
DR EMBL; BC010853; AAH10853.1; -; mRNA.
DR EMBL; BC017495; AAH17495.1; -; mRNA.
DR EMBL; BC022232; AAH22232.1; -; mRNA.
DR EMBL; BC111547; AAI11548.1; -; mRNA.
DR CCDS; CCDS10310.1; -. [Q9Y3Q3-1]
DR CCDS; CCDS81914.1; -. [Q9Y3Q3-2]
DR RefSeq; NP_001317305.1; NM_001330376.1. [Q9Y3Q3-2]
DR RefSeq; NP_031390.1; NM_007364.3. [Q9Y3Q3-1]
DR AlphaFoldDB; Q9Y3Q3; -.
DR SMR; Q9Y3Q3; -.
DR BioGRID; 116993; 36.
DR IntAct; Q9Y3Q3; 11.
DR STRING; 9606.ENSP00000299705; -.
DR TCDB; 9.B.188.1.3; the transmembrane emp24 domain-containing protein (tmed) family.
DR iPTMnet; Q9Y3Q3; -.
DR PhosphoSitePlus; Q9Y3Q3; -.
DR BioMuta; TMED3; -.
DR EPD; Q9Y3Q3; -.
DR jPOST; Q9Y3Q3; -.
DR MassIVE; Q9Y3Q3; -.
DR MaxQB; Q9Y3Q3; -.
DR PaxDb; Q9Y3Q3; -.
DR PeptideAtlas; Q9Y3Q3; -.
DR PRIDE; Q9Y3Q3; -.
DR ProteomicsDB; 4661; -.
DR ProteomicsDB; 86059; -. [Q9Y3Q3-1]
DR Antibodypedia; 27806; 158 antibodies from 20 providers.
DR DNASU; 23423; -.
DR Ensembl; ENST00000299705.10; ENSP00000299705.5; ENSG00000166557.14. [Q9Y3Q3-1]
DR Ensembl; ENST00000424155.6; ENSP00000414983.2; ENSG00000166557.14. [Q9Y3Q3-2]
DR GeneID; 23423; -.
DR KEGG; hsa:23423; -.
DR MANE-Select; ENST00000299705.10; ENSP00000299705.5; NM_007364.4; NP_031390.1.
DR UCSC; uc002beu.4; human. [Q9Y3Q3-1]
DR CTD; 23423; -.
DR DisGeNET; 23423; -.
DR GeneCards; TMED3; -.
DR HGNC; HGNC:28889; TMED3.
DR HPA; ENSG00000166557; Tissue enhanced (salivary).
DR neXtProt; NX_Q9Y3Q3; -.
DR OpenTargets; ENSG00000166557; -.
DR PharmGKB; PA134958958; -.
DR VEuPathDB; HostDB:ENSG00000166557; -.
DR eggNOG; KOG1693; Eukaryota.
DR GeneTree; ENSGT00940000159833; -.
DR HOGENOM; CLU_066963_6_0_1; -.
DR InParanoid; Q9Y3Q3; -.
DR OMA; GIGQVMM; -.
DR PhylomeDB; Q9Y3Q3; -.
DR TreeFam; TF313000; -.
DR PathwayCommons; Q9Y3Q3; -.
DR Reactome; R-HSA-6807878; COPI-mediated anterograde transport.
DR Reactome; R-HSA-6811434; COPI-dependent Golgi-to-ER retrograde traffic.
DR SignaLink; Q9Y3Q3; -.
DR BioGRID-ORCS; 23423; 14 hits in 1073 CRISPR screens.
DR ChiTaRS; TMED3; human.
DR GenomeRNAi; 23423; -.
DR Pharos; Q9Y3Q3; Tbio.
DR PRO; PR:Q9Y3Q3; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q9Y3Q3; protein.
DR Bgee; ENSG00000166557; Expressed in parotid gland and 193 other tissues.
DR ExpressionAtlas; Q9Y3Q3; baseline and differential.
DR Genevisible; Q9Y3Q3; HS.
DR GO; GO:0030126; C:COPI vesicle coat; 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:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0032580; C:Golgi cisterna membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0030133; C:transport vesicle; TAS:Reactome.
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 InterPro; IPR015720; Emp24-like.
DR InterPro; IPR009038; GOLD_dom.
DR InterPro; IPR036598; GOLD_dom_sf.
DR PANTHER; PTHR22811; PTHR22811; 1.
DR Pfam; PF01105; EMP24_GP25L; 1.
DR SMART; SM01190; EMP24_GP25L; 1.
DR SUPFAM; SSF101576; SSF101576; 1.
DR PROSITE; PS50866; GOLD; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasmic vesicle; Endoplasmic reticulum;
KW Golgi apparatus; Membrane; Protein transport; Reference proteome; Signal;
KW Transmembrane; Transmembrane helix; Transport.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..217
FT /note="Transmembrane emp24 domain-containing protein 3"
FT /id="PRO_0000010384"
FT TOPO_DOM 24..180
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 181..201
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 202..217
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 38..120
FT /note="GOLD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00096"
FT MOTIF 204..217
FT /note="COPI vesicle coat-binding"
FT /evidence="ECO:0000255"
FT MOTIF 204..205
FT /note="COPII vesicle coat-binding"
FT /evidence="ECO:0000255"
FT VAR_SEQ 140..216
FT /note="MESACVTIHEALKTVIDSQTHYRLREAQDRARAEDLNSRVSYWSVGETIALF
FT VVSFSQVLLLKSFFTEKRPISRAVH -> RFRGAYWKEVDKMVDYMQPGGTPATEGLGR
FT LAP (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_044371"
FT VARIANT 86
FT /note="D -> N (in dbSNP:rs3784543)"
FT /id="VAR_049110"
SQ SEQUENCE 217 AA; 24777 MW; 515C3F0B6C17EBDD CRC64;
MGSTVPRSAS VLLLLLLLRR AEQPCGAELT FELPDNAKQC FHEEVEQGVK FSLDYQVITG
GHYDVDCYVE DPQGNTIYRE TKKQYDSFTY RAEVKGVYQF CFSNEFSTFS HKTVYFDFQV
GDEPPILPDM GNRVTALTQM ESACVTIHEA LKTVIDSQTH YRLREAQDRA RAEDLNSRVS
YWSVGETIAL FVVSFSQVLL LKSFFTEKRP ISRAVHS
