EMC8_HUMAN
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 03-AUG-2022, entry version 163.
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: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}.
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:32459176,
CC PubMed:32439656). {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=13; 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}.
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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_001142288.1. [O43402-2]
DR RefSeq; NP_006058.1; NM_006067.4. [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 PDBsum; 6WW7; -.
DR PDBsum; 7ADO; -.
DR PDBsum; 7ADP; -.
DR AlphaFoldDB; O43402; -.
DR SMR; O43402; -.
DR BioGRID; 115611; 161.
DR ComplexPortal; CPX-5848; Endoplasmic reticulum membrane complex, EMC8 variant.
DR IntAct; O43402; 39.
DR MINT; O43402; -.
DR STRING; 9606.ENSP00000253457; -.
DR TCDB; 3.A.27.1.1; the endoplasmic reticulum membrane protein insertion complex (emc) family.
DR GlyGen; O43402; 2 sites, 1 O-linked glycan (2 sites).
DR iPTMnet; O43402; -.
DR PhosphoSitePlus; O43402; -.
DR SwissPalm; O43402; -.
DR BioMuta; EMC8; -.
DR EPD; O43402; -.
DR jPOST; O43402; -.
DR MassIVE; O43402; -.
DR MaxQB; O43402; -.
DR PaxDb; O43402; -.
DR PeptideAtlas; O43402; -.
DR PRIDE; O43402; -.
DR ProteomicsDB; 48928; -. [O43402-1]
DR Antibodypedia; 30647; 276 antibodies from 22 providers.
DR DNASU; 10328; -.
DR Ensembl; ENST00000253457.8; ENSP00000253457.3; ENSG00000131148.9. [O43402-1]
DR Ensembl; ENST00000435200.2; ENSP00000391730.1; ENSG00000131148.9. [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 CTD; 10328; -.
DR DisGeNET; 10328; -.
DR GeneCards; EMC8; -.
DR HGNC; HGNC:7864; EMC8.
DR HPA; ENSG00000131148; Low tissue specificity.
DR MIM; 604886; gene.
DR neXtProt; NX_O43402; -.
DR OpenTargets; ENSG00000131148; -.
DR PharmGKB; PA31668; -.
DR VEuPathDB; HostDB:ENSG00000131148; -.
DR eggNOG; KOG3289; Eukaryota.
DR GeneTree; ENSGT00390000006738; -.
DR HOGENOM; CLU_087337_0_1_1; -.
DR InParanoid; O43402; -.
DR OMA; HVTPMAE; -.
DR PhylomeDB; O43402; -.
DR TreeFam; TF313860; -.
DR PathwayCommons; O43402; -.
DR SignaLink; O43402; -.
DR BioGRID-ORCS; 10328; 22 hits in 1090 CRISPR screens.
DR ChiTaRS; EMC8; human.
DR GenomeRNAi; 10328; -.
DR Pharos; O43402; Tdark.
DR PRO; PR:O43402; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; O43402; protein.
DR Bgee; ENSG00000131148; Expressed in oocyte and 194 other tissues.
DR ExpressionAtlas; O43402; baseline and differential.
DR Genevisible; O43402; HS.
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; IC:ComplexPortal.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
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; PTHR12941; 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 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 HELIX 8..20
FT /evidence="ECO:0007829|PDB:7ADO"
FT STRAND 24..32
FT /evidence="ECO:0007829|PDB:7ADO"
FT STRAND 56..63
FT /evidence="ECO:0007829|PDB:7ADO"
FT HELIX 68..82
FT /evidence="ECO:0007829|PDB:7ADO"
FT HELIX 83..85
FT /evidence="ECO:0007829|PDB:7ADO"
FT STRAND 88..95
FT /evidence="ECO:0007829|PDB:7ADO"
FT STRAND 97..100
FT /evidence="ECO:0007829|PDB:7ADO"
FT HELIX 106..115
FT /evidence="ECO:0007829|PDB:7ADO"
FT TURN 116..118
FT /evidence="ECO:0007829|PDB:7ADO"
FT STRAND 119..121
FT /evidence="ECO:0007829|PDB:6WW7"
FT STRAND 123..127
FT /evidence="ECO:0007829|PDB:7ADO"
FT STRAND 141..146
FT /evidence="ECO:0007829|PDB:6WW7"
FT STRAND 149..153
FT /evidence="ECO:0007829|PDB:7ADO"
FT TURN 155..157
FT /evidence="ECO:0007829|PDB:6WW7"
FT HELIX 166..176
FT /evidence="ECO:0007829|PDB:7ADO"
FT HELIX 180..182
FT /evidence="ECO:0007829|PDB:7ADO"
FT HELIX 186..189
FT /evidence="ECO:0007829|PDB:7ADO"
FT HELIX 200..208
FT /evidence="ECO:0007829|PDB:7ADO"
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
