TMED4_HUMAN
ID TMED4_HUMAN Reviewed; 227 AA.
AC Q7Z7H5; A4D2K8; B4DFJ4; Q56VW3; Q7Z432; Q8N2P6;
DT 29-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2003, sequence version 1.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=Transmembrane emp24 domain-containing protein 4;
DE AltName: Full=Endoplasmic reticulum stress-response protein 25;
DE Short=ERS25;
DE AltName: Full=GMP25iso;
DE AltName: Full=Putative NF-kappa-B-activating protein 156;
DE AltName: Full=p24 family protein alpha-3;
DE Short=p24alpha3;
DE Flags: Precursor;
GN Name=TMED4; Synonyms=ERS25;
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 [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3).
RC TISSUE=Brain cortex, Embryo, and Thalamus;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Endometrium;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12690205; DOI=10.1126/science.1083423;
RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D.,
RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S.,
RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R.,
RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N.,
RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E.,
RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R.,
RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T.,
RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W.,
RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A.,
RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X.,
RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E.,
RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J.,
RA Adams M.D., Tsui L.-C.;
RT "Human chromosome 7: DNA sequence and biology.";
RL Science 300:767-772(2003).
RN [4]
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain, and Pancreas;
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 [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 6-227 (ISOFORM 3).
RA Kim J.W.;
RT "Identification of human transforming gene.";
RL Submitted (DEC-2002) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 119-227 (ISOFORMS 1/2).
RC TISSUE=Lung fibroblast;
RX PubMed=12761501; DOI=10.1038/sj.onc.1206406;
RA Matsuda A., Suzuki Y., Honda G., Muramatsu S., Matsuzaki O., Nagano Y.,
RA Doi T., Shimotohno K., Harada T., Nishida E., Hayashi H., Sugano S.;
RT "Large-scale identification and characterization of human genes that
RT activate NF-kappaB and MAPK signaling pathways.";
RL Oncogene 22:3307-3318(2003).
RN [8]
RP IDENTIFICATION.
RX PubMed=18326488; DOI=10.1074/jbc.m709656200;
RA Hwang S.O., Boswell S.A., Seo J.-S., Lee S.W.;
RT "Novel oxidative stress-responsive gene ERS25 functions as a regulator of
RT the heat-shock and cell death response.";
RL J. Biol. Chem. 283:13063-13069(2008).
RN [9]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-117.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [10]
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 [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: Involved in vesicular protein trafficking, mainly in the
CC early secretory pathway. targeting. Involved in the maintenance of the
CC Golgi apparatus. Appears to play a role in the biosynthesis of secreted
CC cargo including processing. Involved in endoplasmic reticulum stress
CC response. May play a role in the regulation of heat-shock response and
CC apoptosis (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000250};
CC Single-pass type I membrane protein {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q7Z7H5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q7Z7H5-2; Sequence=VSP_035698;
CC Name=3;
CC IsoId=Q7Z7H5-3; Sequence=VSP_035699, VSP_035700;
CC -!- SIMILARITY: Belongs to the EMP24/GP25L family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAP20105.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAC77362.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK074557; BAC11058.1; -; mRNA.
DR EMBL; AK290125; BAF82814.1; -; mRNA.
DR EMBL; AK294122; BAG57455.1; -; mRNA.
DR EMBL; BX647965; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; CH236960; EAL23751.1; -; Genomic_DNA.
DR EMBL; CH471128; EAW61090.1; -; Genomic_DNA.
DR EMBL; CH471128; EAW61091.1; -; Genomic_DNA.
DR EMBL; BC052641; AAH52641.1; -; mRNA.
DR EMBL; BC057851; AAH57851.1; -; mRNA.
DR EMBL; AY191223; AAP20105.1; ALT_INIT; mRNA.
DR EMBL; AB097009; BAC77362.1; ALT_INIT; mRNA.
DR CCDS; CCDS5493.1; -. [Q7Z7H5-1]
DR CCDS; CCDS78227.1; -. [Q7Z7H5-3]
DR RefSeq; NP_001289987.1; NM_001303058.1. [Q7Z7H5-3]
DR RefSeq; NP_001289989.1; NM_001303060.1.
DR RefSeq; NP_872353.2; NM_182547.3. [Q7Z7H5-1]
DR AlphaFoldDB; Q7Z7H5; -.
DR SMR; Q7Z7H5; -.
DR BioGRID; 128780; 82.
DR IntAct; Q7Z7H5; 24.
DR STRING; 9606.ENSP00000404042; -.
DR GlyConnect; 1844; 1 N-Linked glycan (1 site).
DR GlyGen; Q7Z7H5; 1 site, 1 N-linked glycan (1 site).
DR iPTMnet; Q7Z7H5; -.
DR PhosphoSitePlus; Q7Z7H5; -.
DR SwissPalm; Q7Z7H5; -.
DR BioMuta; TMED4; -.
DR DMDM; 62287892; -.
DR EPD; Q7Z7H5; -.
DR jPOST; Q7Z7H5; -.
DR MassIVE; Q7Z7H5; -.
DR MaxQB; Q7Z7H5; -.
DR PaxDb; Q7Z7H5; -.
DR PeptideAtlas; Q7Z7H5; -.
DR PRIDE; Q7Z7H5; -.
DR ProteomicsDB; 69548; -. [Q7Z7H5-1]
DR ProteomicsDB; 69549; -. [Q7Z7H5-2]
DR ProteomicsDB; 69550; -. [Q7Z7H5-3]
DR Antibodypedia; 13441; 146 antibodies from 26 providers.
DR DNASU; 222068; -.
DR Ensembl; ENST00000457408.7; ENSP00000404042.2; ENSG00000158604.15. [Q7Z7H5-1]
DR Ensembl; ENST00000481238.1; ENSP00000417443.1; ENSG00000158604.15. [Q7Z7H5-3]
DR GeneID; 222068; -.
DR KEGG; hsa:222068; -.
DR MANE-Select; ENST00000457408.7; ENSP00000404042.2; NM_182547.4; NP_872353.2.
DR UCSC; uc003tli.4; human. [Q7Z7H5-1]
DR CTD; 222068; -.
DR DisGeNET; 222068; -.
DR GeneCards; TMED4; -.
DR HGNC; HGNC:22301; TMED4.
DR HPA; ENSG00000158604; Low tissue specificity.
DR MIM; 612038; gene.
DR neXtProt; NX_Q7Z7H5; -.
DR OpenTargets; ENSG00000158604; -.
DR PharmGKB; PA134983854; -.
DR VEuPathDB; HostDB:ENSG00000158604; -.
DR eggNOG; KOG1690; Eukaryota.
DR GeneTree; ENSGT00940000159012; -.
DR HOGENOM; CLU_066963_2_2_1; -.
DR InParanoid; Q7Z7H5; -.
DR OMA; GVTCAWQ; -.
DR OrthoDB; 1294924at2759; -.
DR PhylomeDB; Q7Z7H5; -.
DR TreeFam; TF314123; -.
DR PathwayCommons; Q7Z7H5; -.
DR SignaLink; Q7Z7H5; -.
DR BioGRID-ORCS; 222068; 10 hits in 1075 CRISPR screens.
DR ChiTaRS; TMED4; human.
DR GeneWiki; TMED4; -.
DR GenomeRNAi; 222068; -.
DR Pharos; Q7Z7H5; Tdark.
DR PRO; PR:Q7Z7H5; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; Q7Z7H5; protein.
DR Bgee; ENSG00000158604; Expressed in oviduct epithelium and 188 other tissues.
DR ExpressionAtlas; Q7Z7H5; baseline and differential.
DR Genevisible; Q7Z7H5; HS.
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; IBA:GO_Central.
DR GO; GO:0005794; C:Golgi apparatus; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; HMP: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 Alternative splicing; Coiled coil; Endoplasmic reticulum; Glycoprotein;
KW Membrane; Protein transport; Reference proteome; Signal; Transmembrane;
KW Transmembrane helix; Transport.
FT SIGNAL 1..29
FT /evidence="ECO:0000255"
FT CHAIN 30..227
FT /note="Transmembrane emp24 domain-containing protein 4"
FT /id="PRO_0000010387"
FT TOPO_DOM 30..194
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 195..212
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 213..227
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 39..137
FT /note="GOLD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00096"
FT COILED 147..176
FT /evidence="ECO:0000255"
FT MOTIF 220..227
FT /note="COPI vesicle coat-binding"
FT /evidence="ECO:0000255"
FT MOTIF 220..221
FT /note="COPII vesicle coat-binding"
FT /evidence="ECO:0000255"
FT CARBOHYD 117
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT VAR_SEQ 59..74
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_035698"
FT VAR_SEQ 179..186
FT /note="YREERFRL -> ASAYLLVI (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039, ECO:0000303|Ref.6"
FT /id="VSP_035699"
FT VAR_SEQ 187..227
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039, ECO:0000303|Ref.6"
FT /id="VSP_035700"
SQ SEQUENCE 227 AA; 25943 MW; 3C650402F472A051 CRC64;
MAGVGAGPLR AMGRQALLLL ALCATGAQGL YFHIGETEKR CFIEEIPDET MVIGNYRTQM
WDKQKEVFLP STPGLGMHVE VKDPDGKVVL SRQYGSEGRF TFTSHTPGDH QICLHSNSTR
MALFAGGKLR VHLDIQVGEH ANNYPEIAAK DKLTELQLRA RQLLDQVEQI QKEQDYQRYR
EERFRLTSES TNQRVLWWSI AQTVILILTG IWQMRHLKSF FEAKKLV
