ID EMC4_HUMAN Reviewed; 183 AA. AC Q5J8M3; A8K3A9; B4DJQ4; Q96KX9; Q9BUI5; Q9P0T9; DT 03-OCT-2006, integrated into UniProtKB/Swiss-Prot. DT 03-OCT-2006, sequence version 2. DT 27-MAR-2024, entry version 140. DE RecName: Full=ER membrane protein complex subunit 4; DE AltName: Full=Cell proliferation-inducing gene 17 protein; DE AltName: Full=Transmembrane protein 85; GN Name=EMC4; Synonyms=TMEM85; ORFNames=HSPC184, PIG17; 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] (ISOFORM 1). RA Kim J.W.; RT "Identification of a proliferation-inducing gene."; RL Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Umbilical cord blood; RX PubMed=11042152; DOI=10.1101/gr.140200; RA Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G., RA Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W., RA Tao J., Huang Q.-H., Zhou J., Hu G.-X., Gu J., Chen S.-J., Chen Z.; RT "Cloning and functional analysis of cDNAs with open reading frames for 300 RT previously undefined genes expressed in CD34+ hematopoietic stem/progenitor RT cells."; RL Genome Res. 10:1546-1560(2000). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3). RC TISSUE=Brain, Placenta, 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 [4] 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 [5] 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 [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Brain; 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 [7] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling RT networks."; RL Cell 127:635-648(2006). RN [8] RP FUNCTION, TISSUE SPECIFICITY, AND ALTERNATIVE SPLICING. RX PubMed=18586032; DOI=10.1016/j.febslet.2008.06.042; RA Ring G., Khoury C.M., Solar A.J., Yang Z., Mandato C.A., Greenwood M.T.; RT "Transmembrane protein 85 from both human (TMEM85) and yeast (YGL231c) RT inhibit hydrogen peroxide mediated cell death in yeast."; RL FEBS Lett. 582:2637-2642(2008). RN [9] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). 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 ACETYLATION [LARGE SCALE ANALYSIS] AT THR-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=22223895; DOI=10.1074/mcp.m111.015131; RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., RA Giglione C.; RT "Comparative large-scale characterisation of plant vs. mammal proteins RT reveals similar and idiosyncratic N-alpha acetylation features."; RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012). RN [12] RP IDENTIFICATION IN THE EMC COMPLEX, AND SUBCELLULAR LOCATION. RX PubMed=22119785; DOI=10.1038/ncb2383; RA Christianson J.C., Olzmann J.A., Shaler T.A., Sowa M.E., Bennett E.J., RA Richter C.M., Tyler R.E., Greenblatt E.J., Harper J.W., Kopito R.R.; RT "Defining human ERAD networks through an integrative mapping strategy."; RL Nat. Cell Biol. 14:93-105(2012). RN [13] RP ACETYLATION [LARGE SCALE ANALYSIS] AT THR-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-36, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-36, AND IDENTIFICATION BY RP 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 [16] RP ACETYLATION AT THR-2, AND CLEAVAGE OF INITIATOR METHIONINE. RX PubMed=25489052; DOI=10.1093/hmg/ddu611; RA Myklebust L.M., Van Damme P., Stoeve S.I., Doerfel M.J., Abboud A., RA Kalvik T.V., Grauffel C., Jonckheere V., Wu Y., Swensen J., Kaasa H., RA Liszczak G., Marmorstein R., Reuter N., Lyon G.J., Gevaert K., Arnesen T.; RT "Biochemical and cellular analysis of Ogden syndrome reveals downstream Nt- RT acetylation defects."; RL Hum. Mol. Genet. 24:1956-1976(2015). RN [17] RP ACETYLATION [LARGE SCALE ANALYSIS] AT THR-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [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 [18] RP FUNCTION. RX PubMed=30415835; DOI=10.1016/j.cell.2018.10.009; RA Chitwood P.J., Juszkiewicz S., Guna A., Shao S., Hegde R.S.; RT "EMC Is Required to Initiate Accurate Membrane Protein Topogenesis."; RL Cell 175:1507-1519(2018). RN [19] RP FUNCTION. RX PubMed=29809151; DOI=10.7554/elife.37018; RA Shurtleff M.J., Itzhak D.N., Hussmann J.A., Schirle Oakdale N.T., RA Costa E.A., Jonikas M., Weibezahn J., Popova K.D., Jan C.H., Sinitcyn P., RA Vembar S.S., Hernandez H., Cox J., Burlingame A.L., Brodsky J.L., Frost A., RA Borner G.H., Weissman J.S.; RT "The ER membrane protein complex interacts cotranslationally to enable RT biogenesis of multipass membrane proteins."; RL Elife 7:0-0(2018). RN [20] RP FUNCTION, AND SUBUNIT. RX PubMed=29242231; DOI=10.1126/science.aao3099; RA Guna A., Volkmar N., Christianson J.C., Hegde R.S.; RT "The ER membrane protein complex is a transmembrane domain insertase."; RL Science 359:470-473(2018). RN [21] {ECO:0007744|PDB:6Z3W} RP STRUCTURE BY ELECTRON MICROSCOPY (6.40 ANGSTROMS) OF THE EMC COMPLEX, RP FUNCTION, AND TOPOLOGY. RX PubMed=32459176; DOI=10.7554/elife.57887; RA O'Donnell J.P., Phillips B.P., Yagita Y., Juszkiewicz S., Wagner A., RA Malinverni D., Keenan R.J., Miller E.A., Hegde R.S.; RT "The architecture of EMC reveals a path for membrane protein insertion."; RL Elife 9:0-0(2020). RN [22] RP FUNCTION, AND TOPOLOGY. RX PubMed=32439656; DOI=10.1126/science.abb5008; RA Pleiner T., Tomaleri G.P., Januszyk K., Inglis A.J., Hazu M., RA Voorhees R.M.; RT "Structural basis for membrane insertion by the human ER membrane protein RT complex."; RL Science 369:433-436(2020). CC -!- FUNCTION: Part of the endoplasmic reticulum membrane protein complex CC (EMC) that enables the energy-independent insertion into endoplasmic CC reticulum membranes of newly synthesized membrane proteins CC (PubMed:30415835, PubMed:29809151, PubMed:29242231, PubMed:32459176, CC PubMed:32439656). Preferentially accommodates proteins with CC transmembrane domains that are weakly hydrophobic or contain CC destabilizing features such as charged and aromatic residues CC (PubMed:30415835, PubMed:29809151, PubMed:29242231). Involved in the CC cotranslational insertion of multi-pass membrane proteins in which CC stop-transfer membrane-anchor sequences become ER membrane spanning CC helices (PubMed:30415835, PubMed:29809151). It is also required for the CC post-translational insertion of tail-anchored/TA proteins in CC endoplasmic reticulum membranes (PubMed:29809151, PubMed:29242231). By CC mediating the proper cotranslational insertion of N-terminal CC transmembrane domains in an N-exo topology, with translocated N- CC terminus in the lumen of the ER, controls the topology of multi-pass CC membrane proteins like the G protein-coupled receptors CC (PubMed:30415835). By regulating the insertion of various proteins in CC membranes, it is indirectly involved in many cellular processes CC (Probable). {ECO:0000269|PubMed:29242231, ECO:0000269|PubMed:29809151, CC ECO:0000269|PubMed:30415835, ECO:0000269|PubMed:32439656, CC ECO:0000269|PubMed:32459176, ECO:0000305|PubMed:18586032}. CC -!- SUBUNIT: Component of the ER membrane protein complex (EMC). CC {ECO:0000269|PubMed:22119785, ECO:0000269|PubMed:29242231, CC ECO:0000269|PubMed:32459176}. CC -!- INTERACTION: CC Q5J8M3; Q9NRM0-1: SLC2A9; NbExp=3; IntAct=EBI-2814031, EBI-25396304; CC Q5J8M3; Q9NRM0-2: SLC2A9; NbExp=2; IntAct=EBI-2814031, EBI-25396386; CC Q5J8M3; PRO_0000449624 [P0DTD1]: rep; Xeno; NbExp=3; IntAct=EBI-2814031, EBI-25475868; CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane CC {ECO:0000269|PubMed:22119785}; Multi-pass membrane protein CC {ECO:0000305|PubMed:32439656, ECO:0000305|PubMed:32459176}. Note=Could CC also be a single-pass transmembrane protein with cytosolic N-terminus CC and lumenal C-terminus. {ECO:0000305|PubMed:32439656, CC ECO:0000305|PubMed:32459176}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; Synonyms=TMEM85v1; CC IsoId=Q5J8M3-1; Sequence=Displayed; CC Name=2; Synonyms=TMEM85v2; CC IsoId=Q5J8M3-2; Sequence=VSP_020798, VSP_020799; CC Name=3; CC IsoId=Q5J8M3-3; Sequence=VSP_037374, VSP_037375; CC -!- TISSUE SPECIFICITY: Isoform 1 is expressed in brain and heart. Isoform CC 2 is expressed in heart. {ECO:0000269|PubMed:18586032}. CC -!- SIMILARITY: Belongs to the EMC4 family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AY336092; AAR24622.1; -; mRNA. DR EMBL; AF151018; AAF36104.1; -; mRNA. DR EMBL; AK075227; BAC11486.1; -; mRNA. DR EMBL; AK290524; BAF83213.1; -; mRNA. DR EMBL; AK296184; BAG58916.1; -; mRNA. DR EMBL; AC079203; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471125; EAW92292.1; -; Genomic_DNA. DR EMBL; BC002583; AAH02583.1; -; mRNA. DR CCDS; CCDS10035.1; -. [Q5J8M3-1] DR CCDS; CCDS66732.1; -. [Q5J8M3-2] DR RefSeq; NP_001273349.1; NM_001286420.1. [Q5J8M3-2] DR RefSeq; NP_057538.1; NM_016454.3. [Q5J8M3-1] DR PDB; 6Z3W; EM; 6.40 A; D=1-183. DR PDB; 7ADO; EM; 3.39 A; D=1-183. DR PDB; 7ADP; EM; 3.60 A; D=1-183. DR PDB; 8EOI; EM; 3.40 A; D=14-183. DR PDB; 8S9S; EM; 3.60 A; 4=1-183. DR PDBsum; 6Z3W; -. DR PDBsum; 7ADO; -. DR PDBsum; 7ADP; -. DR PDBsum; 8EOI; -. DR PDBsum; 8S9S; -. DR AlphaFoldDB; Q5J8M3; -. DR EMDB; EMD-11732; -. DR EMDB; EMD-11733; -. DR EMDB; EMD-28376; -. DR EMDB; EMD-40245; -. DR EMDB; EMD-40246; -. DR SMR; Q5J8M3; -. DR BioGRID; 119397; 297. DR ComplexPortal; CPX-5848; Endoplasmic reticulum membrane complex, EMC8 variant. DR ComplexPortal; CPX-5881; Endoplasmic reticulum membrane complex, EMC9 variant. DR IntAct; Q5J8M3; 31. DR MINT; Q5J8M3; -. DR STRING; 9606.ENSP00000267750; -. DR TCDB; 3.A.27.1.1; the endoplasmic reticulum membrane protein insertion complex (emc) family. DR iPTMnet; Q5J8M3; -. DR PhosphoSitePlus; Q5J8M3; -. DR SwissPalm; Q5J8M3; -. DR BioMuta; EMC4; -. DR DMDM; 115502869; -. DR EPD; Q5J8M3; -. DR jPOST; Q5J8M3; -. DR MassIVE; Q5J8M3; -. DR MaxQB; Q5J8M3; -. DR PaxDb; 9606-ENSP00000267750; -. DR PeptideAtlas; Q5J8M3; -. DR ProteomicsDB; 62980; -. [Q5J8M3-1] DR ProteomicsDB; 62981; -. [Q5J8M3-2] DR ProteomicsDB; 62982; -. [Q5J8M3-3] DR Pumba; Q5J8M3; -. DR TopDownProteomics; Q5J8M3-1; -. [Q5J8M3-1] DR TopDownProteomics; Q5J8M3-2; -. [Q5J8M3-2] DR Antibodypedia; 65253; 99 antibodies from 21 providers. DR DNASU; 51234; -. DR Ensembl; ENST00000249209.8; ENSP00000249209.4; ENSG00000128463.13. [Q5J8M3-2] DR Ensembl; ENST00000267750.9; ENSP00000267750.4; ENSG00000128463.13. [Q5J8M3-1] DR GeneID; 51234; -. DR KEGG; hsa:51234; -. DR MANE-Select; ENST00000267750.9; ENSP00000267750.4; NM_016454.4; NP_057538.1. DR UCSC; uc001zhq.5; human. [Q5J8M3-1] DR AGR; HGNC:28032; -. DR CTD; 51234; -. DR GeneCards; EMC4; -. DR HGNC; HGNC:28032; EMC4. DR HPA; ENSG00000128463; Low tissue specificity. DR MIM; 616245; gene. DR neXtProt; NX_Q5J8M3; -. DR OpenTargets; ENSG00000128463; -. DR PharmGKB; PA143485634; -. DR VEuPathDB; HostDB:ENSG00000128463; -. DR eggNOG; KOG3318; Eukaryota. DR GeneTree; ENSGT00390000006970; -. DR HOGENOM; CLU_098404_0_1_1; -. DR InParanoid; Q5J8M3; -. DR OMA; VYVLMQF; -. DR OrthoDB; 5472678at2759; -. DR PhylomeDB; Q5J8M3; -. DR TreeFam; TF313750; -. DR PathwayCommons; Q5J8M3; -. DR SignaLink; Q5J8M3; -. DR BioGRID-ORCS; 51234; 310 hits in 1162 CRISPR screens. DR ChiTaRS; EMC4; human. DR GenomeRNAi; 51234; -. DR Pharos; Q5J8M3; Tbio. DR PRO; PR:Q5J8M3; -. DR Proteomes; UP000005640; Chromosome 15. DR RNAct; Q5J8M3; Protein. DR Bgee; ENSG00000128463; Expressed in left ventricle myocardium and 186 other cell types or tissues. DR ExpressionAtlas; Q5J8M3; baseline and differential. DR GO; GO:0072546; C:EMC complex; IDA:UniProtKB. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB. DR GO; GO:0016020; C:membrane; IDA:UniProtKB. DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW. DR GO; GO:0045050; P:protein insertion into ER membrane by stop-transfer membrane-anchor sequence; IDA:ComplexPortal. DR GO; GO:0071816; P:tail-anchored membrane protein insertion into ER membrane; IDA:UniProtKB. DR InterPro; IPR009445; TMEM85/Emc4. DR PANTHER; PTHR19315; ER MEMBRANE PROTEIN COMPLEX SUBUNIT 4; 1. DR PANTHER; PTHR19315:SF9; ER MEMBRANE PROTEIN COMPLEX SUBUNIT 4; 1. DR Pfam; PF06417; DUF1077; 1. DR PIRSF; PIRSF017207; UCP017207_TM-p85; 1. DR Genevisible; Q5J8M3; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Apoptosis; KW Endoplasmic reticulum; Membrane; Phosphoprotein; Reference proteome; KW Transmembrane; Transmembrane helix. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000269|PubMed:25489052, FT ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:22814378, FT ECO:0007744|PubMed:25944712" FT CHAIN 2..183 FT /note="ER membrane protein complex subunit 4" FT /id="PRO_0000251914" FT TOPO_DOM 2..66 FT /note="Cytoplasmic" FT /evidence="ECO:0000305|PubMed:32459176" FT TRANSMEM 67..87 FT /note="Helical" FT /evidence="ECO:0000305|PubMed:32459176" FT TOPO_DOM 88..98 FT /note="Lumenal" FT /evidence="ECO:0000305|PubMed:32459176" FT TRANSMEM 99..120 FT /note="Helical" FT /evidence="ECO:0000305|PubMed:32459176" FT TOPO_DOM 121..127 FT /note="Cytoplasmic" FT /evidence="ECO:0000305|PubMed:32459176" FT TRANSMEM 128..148 FT /note="Helical" FT /evidence="ECO:0000305|PubMed:32459176" FT TOPO_DOM 149..183 FT /note="Lumenal" FT /evidence="ECO:0000305|PubMed:32459176" FT REGION 20..39 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 2 FT /note="N-acetylthreonine" FT /evidence="ECO:0000269|PubMed:25489052, FT ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:22814378, FT ECO:0007744|PubMed:25944712" FT MOD_RES 36 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163, FT ECO:0007744|PubMed:24275569" FT VAR_SEQ 68..136 FT /note="RCWDIALGPLKQIPMNLFIMYMAGNTISIFPTMMVCMMAWRPIQALMAISAT FT FKMLESSSQKFLQGLVY -> VQRYRCYRSPWASPELHTHPLLLGGVNVDSSYPEDLET FT KLLEAGISVFYISATKVLNNLKNRRCLEHKV (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_037374" FT VAR_SEQ 119..149 FT /note="TFKMLESSSQKFLQGLVYLIGNLMGLALAVY -> KNGVQWWRTAFVNMRKQ FT RLVPMYLGLIYILL (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334" FT /id="VSP_020798" FT VAR_SEQ 137..183 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_037375" FT VAR_SEQ 150..183 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334" FT /id="VSP_020799" FT VARIANT 98 FT /note="P -> T (in dbSNP:rs11544437)" FT /id="VAR_053775" FT CONFLICT 47 FT /note="Y -> H (in Ref. 1; AAR24622)" FT /evidence="ECO:0000305" FT CONFLICT 129 FT /note="K -> R (in Ref. 1; AAR24622)" FT /evidence="ECO:0000305" FT HELIX 141..155 FT /evidence="ECO:0007829|PDB:7ADO" FT HELIX 161..164 FT /evidence="ECO:0007829|PDB:7ADO" FT HELIX 165..167 FT /evidence="ECO:0007829|PDB:8EOI" FT STRAND 176..181 FT /evidence="ECO:0007829|PDB:7ADO" SQ SEQUENCE 183 AA; 20087 MW; 96888D46FF22DEDE CRC64; MTAQGGLVAN RGRRFKWAIE LSGPGGGSRG RSDRGSGQGD SLYPVGYLDK QVPDTSVQET DRILVEKRCW DIALGPLKQI PMNLFIMYMA GNTISIFPTM MVCMMAWRPI QALMAISATF KMLESSSQKF LQGLVYLIGN LMGLALAVYK CQSMGLLPTH ASDWLAFIEP PERMEFSGGG LLL //