ID EMC8_HUMAN Reviewed; 210 AA. AC O43402; C9JB21; DT 26-SEP-2001, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-1998, sequence version 1. DT 10-JUN-2026, entry version 181. DE RecName: Full=ER membrane protein complex subunit 8; DE AltName: Full=Neighbor of COX4; DE AltName: Full=Protein FAM158B; GN Name=EMC8; Synonyms=C16orf2, C16orf4, COX4AL, COX4NB, FAM158B, NOC4; 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 [GENOMIC DNA / MRNA] (ISOFORM 1). RC TISSUE=Placenta, and Retina; RX PubMed=10337626; DOI=10.1007/s003359901031; RA Bachman N.J., Wu W., Schmidt T.R., Grossman L.I., Lomax M.I.; RT "The 5-prime region of the COX4 gene contains a novel overlapping gene, RT NOC4."; RL Mamm. Genome 10:506-512(1999). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15616553; DOI=10.1038/nature03187; RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M., RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., RA Myers R.M., Rubin E.M., Pennacchio L.A.; RT "The sequence and analysis of duplication-rich human chromosome 16."; RL Nature 432:988-994(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Epidermal carcinoma, Muscle, and Placenta; 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 [4] 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 [5] 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 [6] 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 [7] 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 [8] 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 [9] 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 [10] RP FUNCTION, AND SUBUNIT. 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 [11] {ECO:0007744|PDB:6WW7} RP STRUCTURE BY ELECTRON MICROSCOPY (3.40 ANGSTROMS) OF THE EMC COMPLEX, 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:29242231, PubMed:29809151, PubMed:30415835, PubMed:32439656, CC PubMed:32459176). Preferentially accommodates proteins with CC transmembrane domains that are weakly hydrophobic or contain CC destabilizing features such as charged and aromatic residues CC (PubMed:29242231, PubMed:29809151, PubMed:30415835). 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:29809151, PubMed:30415835). It is also required for the CC post-translational insertion of tail-anchored/TA proteins in CC endoplasmic reticulum membranes (PubMed:29242231, PubMed:29809151). 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}. CC -!- SUBUNIT: Component of the ER membrane protein complex (EMC) CC (PubMed:22119785, PubMed:29242231). EMC8 and EMC9 are mutually CC exclusive subunits of the EMC complex (PubMed:32439656, CC PubMed:32459176). {ECO:0000269|PubMed:22119785, CC ECO:0000269|PubMed:29242231, ECO:0000269|PubMed:32439656, CC ECO:0000269|PubMed:32459176}. CC -!- INTERACTION: CC O43402; Q15006: EMC2; NbExp=17; IntAct=EBI-741841, EBI-359031; CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane CC {ECO:0000269|PubMed:22119785}; Peripheral membrane protein CC {ECO:0000305|PubMed:32439656}; Cytoplasmic side CC {ECO:0000269|PubMed:32439656}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=O43402-1; Sequence=Displayed; CC Name=2; CC IsoId=O43402-2; Sequence=VSP_045089; CC -!- TISSUE SPECIFICITY: Expressed in liver, pancreas, heart, lung, kidney, CC brain, skeletal muscle, and placenta. Expression levels are highest in CC pancreas and moderate in heart, skeletal muscle, and placenta. CC -!- SIMILARITY: Belongs to the EMC8/EMC9 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; AF005888; AAB94489.1; -; mRNA. DR EMBL; AF005889; AAB94820.1; -; Genomic_DNA. DR EMBL; AC018695; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC005886; AAH05886.1; -; mRNA. DR EMBL; BC001472; AAH01472.1; -; mRNA. DR EMBL; BC007445; AAH07445.1; -; mRNA. DR EMBL; BC020250; AAH20250.1; -; mRNA. DR EMBL; BQ674834; -; NOT_ANNOTATED_CDS; mRNA. DR CCDS; CCDS10954.1; -. [O43402-1] DR CCDS; CCDS45541.1; -. [O43402-2] DR RefSeq; NP_001135760.1; NM_001142288.2. [O43402-2] DR RefSeq; NP_006058.1; NM_006067.5. [O43402-1] DR PDB; 6WW7; EM; 3.40 A; H=1-210. DR PDB; 7ADO; EM; 3.39 A; H=1-210. DR PDB; 7ADP; EM; 3.60 A; H=1-210. DR PDB; 8EOI; EM; 3.40 A; H=3-210. DR PDB; 8J0N; EM; 3.47 A; H=1-210. DR PDB; 8J0O; EM; 3.32 A; H=1-210. DR PDB; 8S9S; EM; 3.60 A; 8=1-210. DR PDB; 9C7V; EM; 6.60 A; 8=1-210. DR PDBsum; 6WW7; -. DR PDBsum; 7ADO; -. DR PDBsum; 7ADP; -. DR PDBsum; 8EOI; -. DR PDBsum; 8J0N; -. DR PDBsum; 8J0O; -. DR PDBsum; 8S9S; -. DR PDBsum; 9C7V; -. DR AlphaFoldDB; O43402; -. DR EMDB; EMD-11732; -. DR EMDB; EMD-11733; -. DR EMDB; EMD-21929; -. DR EMDB; EMD-28376; -. DR EMDB; EMD-35906; -. DR EMDB; EMD-35907; -. DR EMDB; EMD-40245; -. DR EMDB; EMD-40246; -. DR EMDB; EMD-45295; -. DR SMR; O43402; -. DR BioGRID; 115611; 229. DR ComplexPortal; CPX-5848; Endoplasmic reticulum membrane complex, EMC8 variant. DR CORUM; O43402; -. DR FunCoup; O43402; 4253. DR IntAct; O43402; 119. DR MINT; O43402; -. DR STRING; 9606.ENSP00000253457; -. DR TCDB; 3.A.27.1.1; the endoplasmic reticulum membrane protein insertion complex (emc) family. DR GlyCosmos; O43402; 2 sites, 1 glycan. DR GlyGen; O43402; 2 sites, 1 O-linked glycan (2 sites). DR iPTMnet; O43402; -. DR PhosphoSitePlus; O43402; -. DR SwissPalm; O43402; -. DR BioMuta; EMC8; -. DR jPOST; O43402; -. DR MassIVE; O43402; -. DR PaxDb; 9606-ENSP00000253457; -. DR PeptideAtlas; O43402; -. DR ProteomicsDB; 48928; -. [O43402-1] DR Pumba; O43402; -. DR Antibodypedia; 30647; 276 antibodies from 22 providers. DR DNASU; 10328; -. DR Ensembl; ENST00000253457.8; ENSP00000253457.3; ENSG00000131148.10. [O43402-1] DR Ensembl; ENST00000435200.2; ENSP00000391730.1; ENSG00000131148.10. [O43402-2] DR GeneID; 10328; -. DR KEGG; hsa:10328; -. DR MANE-Select; ENST00000253457.8; ENSP00000253457.3; NM_006067.5; NP_006058.1. DR UCSC; uc010vol.3; human. [O43402-1] DR AGR; HGNC:7864; -. DR ClinPGx; PA31668; -. DR CTD; 10328; -. DR DisGeNET; 10328; -. DR GeneCards; EMC8; -. DR HGNC; HGNC:7864; EMC8. DR HPA; ENSG00000131148; Low tissue specificity. DR MIM; 604886; gene. DR OpenTargets; ENSG00000131148; -. DR VEuPathDB; HostDB:ENSG00000131148; -. DR eggNOG; KOG3289; Eukaryota. DR GeneTree; ENSGT00390000006738; -. DR HOGENOM; CLU_087337_0_1_1; -. DR InParanoid; O43402; -. DR OMA; PHCAING; -. DR OrthoDB; 194468at2759; -. DR PAN-GO; O43402; 4 GO annotations based on evolutionary models. DR PhylomeDB; O43402; -. DR PathwayCommons; O43402; -. DR SignaLink; O43402; -. DR Agora; ENSG00000131148; -. DR BioGRID-ORCS; 10328; 22 hits in 1170 CRISPR screens. DR ChiTaRS; EMC8; human. DR GenomeRNAi; 10328; -. DR Pharos; O43402; Tbio. DR PRO; PR:O43402; -. DR Proteomes; UP000005640; Chromosome 16. DR RNAct; O43402; protein. DR Bgee; ENSG00000131148; Expressed in oocyte and 196 other cell types or tissues. DR ExpressionAtlas; O43402; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0072546; C:EMC complex; IDA:UniProtKB. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HPA. DR GO; GO:0005789; C:endoplasmic reticulum membrane; NAS:ComplexPortal. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. 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 CDD; cd08060; MPN_UPF0172; 1. DR InterPro; IPR005366; EMC8/9. DR InterPro; IPR037518; MPN. DR PANTHER; PTHR12941; ER MEMBRANE PROTEIN COMPLEX; 1. DR PANTHER; PTHR12941:SF13; ER MEMBRANE PROTEIN COMPLEX SUBUNIT 8; 1. DR Pfam; PF03665; UPF0172; 1. DR PROSITE; PS50249; MPN; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Endoplasmic reticulum; Membrane; KW Proteomics identification; Reference proteome. FT CHAIN 1..210 FT /note="ER membrane protein complex subunit 8" FT /id="PRO_0000221187" FT DOMAIN 4..150 FT /note="MPN" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01182" FT VAR_SEQ 127..210 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_045089" FT STRAND 3..6 FT /evidence="ECO:0007829|PDB:8J0O" FT HELIX 8..20 FT /evidence="ECO:0007829|PDB:8J0O" FT STRAND 22..32 FT /evidence="ECO:0007829|PDB:8J0O" FT STRAND 51..64 FT /evidence="ECO:0007829|PDB:8J0O" FT HELIX 68..82 FT /evidence="ECO:0007829|PDB:8J0O" FT TURN 83..86 FT /evidence="ECO:0007829|PDB:8J0O" FT STRAND 88..95 FT /evidence="ECO:0007829|PDB:8J0O" FT STRAND 97..100 FT /evidence="ECO:0007829|PDB:7ADO" FT HELIX 106..118 FT /evidence="ECO:0007829|PDB:8J0O" FT STRAND 119..121 FT /evidence="ECO:0007829|PDB:6WW7" FT STRAND 123..127 FT /evidence="ECO:0007829|PDB:8J0O" FT STRAND 133..135 FT /evidence="ECO:0007829|PDB:8J0O" FT STRAND 141..146 FT /evidence="ECO:0007829|PDB:8J0O" FT STRAND 148..150 FT /evidence="ECO:0007829|PDB:8J0O" FT STRAND 152..154 FT /evidence="ECO:0007829|PDB:8J0O" FT TURN 155..157 FT /evidence="ECO:0007829|PDB:6WW7" FT HELIX 164..176 FT /evidence="ECO:0007829|PDB:8J0O" FT HELIX 180..182 FT /evidence="ECO:0007829|PDB:7ADO" FT HELIX 186..191 FT /evidence="ECO:0007829|PDB:8J0O" FT STRAND 193..195 FT /evidence="ECO:0007829|PDB:8J0O" FT HELIX 200..209 FT /evidence="ECO:0007829|PDB:8J0O" SQ SEQUENCE 210 AA; 23773 MW; 41367FDD98769250 CRC64; MPGVKLTTQA YCKMVLHGAK YPHCAVNGLL VAEKQKPRKE HLPLGGPGAH HTLFVDCIPL FHGTLALAPM LEVALTLIDS WCKDHSYVIA GYYQANERVK DASPNQVAEK VASRIAEGFS DTALIMVDNT KFTMDCVAPT IHVYEHHENR WRCRDPHHDY CEDWPEAQRI SASLLDSRSY ETLVDFDNHL DDIRNDWTNP EINKAVLHLC //