EMC7_HUMAN
ID EMC7_HUMAN Reviewed; 242 AA.
AC Q9NPA0; B2RC00; Q96ED5;
DT 27-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=ER membrane protein complex subunit 7;
DE Flags: Precursor;
GN Name=EMC7; Synonyms=C11orf3, C15orf24; ORFNames=HT022, UNQ905/PRO1926;
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].
RX PubMed=10873569; DOI=10.1006/bbrc.2000.2910;
RA O'Brien K.P., Tapia-Paez I., Staahle-Baeckdahl M., Kedra D., Dumanski J.P.;
RT "Characterization of five novel human genes in the 11q13-q22 region.";
RL Biochem. Biophys. Res. Commun. 273:90-94(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Muscle;
RA Ievolella C., Lanfranchi G.;
RT "Full-length of some new muscular transcript.";
RL Submitted (AUG-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Hypothalamus;
RA Xu X., Yang Y., Gao G., Xiao H., Chen Z., Han Z.;
RL Submitted (MAR-2000) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 MRNA].
RC TISSUE=Brain cortex, and Lung;
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].
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 [8]
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 [9]
RP CLEAVAGE OF SIGNAL PEPTIDE [LARGE SCALE ANALYSIS] AFTER SER-23, AND
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 [10]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 4-12.
RX PubMed=17825839; DOI=10.1016/j.jmb.2007.07.028;
RA Miller P.J., Pazy Y., Conti B., Riddle D., Appella E., Collins E.J.;
RT "Single MHC mutation eliminates enthalpy associated with T cell receptor
RT binding.";
RL J. Mol. Biol. 373:315-327(2007).
RN [11]
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 [12]
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 [13]
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 [14] {ECO:0007744|PDB:6Z3W}
RP STRUCTURE BY ELECTRON MICROSCOPY (6.40 ANGSTROMS) OF THE EMC COMPLEX, AND
RP FUNCTION.
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 [15] {ECO:0007744|PDB:6WW7}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.40 ANGSTROMS) OF THE EMC COMPLEX,
RP TOPOLOGY, AND SIGNAL PEPTIDE.
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 {ECO:0000269|PubMed:22119785, ECO:0000269|PubMed:29242231,
CC ECO:0000269|PubMed:32439656, ECO:0000269|PubMed:32459176}.
CC -!- INTERACTION:
CC Q9NPA0; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-6309137, EBI-3867333;
CC Q9NPA0; Q07627: KRTAP1-1; NbExp=3; IntAct=EBI-6309137, EBI-11959885;
CC Q9NPA0; Q701N4: KRTAP5-2; NbExp=3; IntAct=EBI-6309137, EBI-11958178;
CC Q9NPA0; P26371: KRTAP5-9; NbExp=3; IntAct=EBI-6309137, EBI-3958099;
CC Q9NPA0; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-6309137, EBI-16439278;
CC Q9NPA0; P0DPK4: NOTCH2NLC; NbExp=3; IntAct=EBI-6309137, EBI-22310682;
CC Q9NPA0; Q5T9L3-1: WLS; NbExp=3; IntAct=EBI-6309137, EBI-22114623;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:22119785}; Single-pass type I membrane protein
CC {ECO:0000269|PubMed:32439656}.
CC -!- SIMILARITY: Belongs to the EMC7 family. {ECO:0000305}.
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DR EMBL; AJ250344; CAB96539.1; -; mRNA.
DR EMBL; AJ245874; CAC01611.1; -; mRNA.
DR EMBL; AF242729; AAG44477.1; -; mRNA.
DR EMBL; AY358445; AAQ88810.1; -; mRNA.
DR EMBL; AK314883; BAG37397.1; -; mRNA.
DR EMBL; BC012456; AAH12456.1; -; mRNA.
DR EMBL; BC104934; AAI04935.1; -; mRNA.
DR EMBL; BC104936; AAI04937.1; -; mRNA.
DR CCDS; CCDS10032.1; -.
DR RefSeq; NP_064539.1; NM_020154.2.
DR PDB; 1B0G; X-ray; 2.50 A; C/F=4-12.
DR PDB; 1LP9; X-ray; 2.00 A; C/J=4-12.
DR PDB; 2J8U; X-ray; 2.88 A; C/J=4-12.
DR PDB; 2JCC; X-ray; 2.50 A; C/J=4-12.
DR PDB; 2UWE; X-ray; 2.40 A; C/J=4-12.
DR PDB; 6WW7; EM; 3.40 A; G=1-242.
DR PDB; 6Z3W; EM; 6.40 A; G=1-242.
DR PDB; 7ADO; EM; 3.39 A; G=1-242.
DR PDBsum; 1B0G; -.
DR PDBsum; 1LP9; -.
DR PDBsum; 2J8U; -.
DR PDBsum; 2JCC; -.
DR PDBsum; 2UWE; -.
DR PDBsum; 6WW7; -.
DR PDBsum; 6Z3W; -.
DR PDBsum; 7ADO; -.
DR AlphaFoldDB; Q9NPA0; -.
DR SMR; Q9NPA0; -.
DR BioGRID; 121211; 187.
DR ComplexPortal; CPX-5848; Endoplasmic reticulum membrane complex, EMC8 variant.
DR ComplexPortal; CPX-5881; Endoplasmic reticulum membrane complex, EMC9 variant.
DR IntAct; Q9NPA0; 47.
DR MINT; Q9NPA0; -.
DR STRING; 9606.ENSP00000256545; -.
DR TCDB; 3.A.27.1.1; the endoplasmic reticulum membrane protein insertion complex (emc) family.
DR iPTMnet; Q9NPA0; -.
DR PhosphoSitePlus; Q9NPA0; -.
DR BioMuta; EMC7; -.
DR DMDM; 74752878; -.
DR EPD; Q9NPA0; -.
DR jPOST; Q9NPA0; -.
DR MassIVE; Q9NPA0; -.
DR MaxQB; Q9NPA0; -.
DR PaxDb; Q9NPA0; -.
DR PeptideAtlas; Q9NPA0; -.
DR PRIDE; Q9NPA0; -.
DR ProteomicsDB; 81944; -.
DR Antibodypedia; 2446; 49 antibodies from 18 providers.
DR DNASU; 56851; -.
DR Ensembl; ENST00000256545.9; ENSP00000256545.4; ENSG00000134153.10.
DR GeneID; 56851; -.
DR KEGG; hsa:56851; -.
DR MANE-Select; ENST00000256545.9; ENSP00000256545.4; NM_020154.3; NP_064539.1.
DR UCSC; uc001zhm.4; human.
DR CTD; 56851; -.
DR DisGeNET; 56851; -.
DR GeneCards; EMC7; -.
DR HGNC; HGNC:24301; EMC7.
DR HPA; ENSG00000134153; Low tissue specificity.
DR neXtProt; NX_Q9NPA0; -.
DR OpenTargets; ENSG00000134153; -.
DR PharmGKB; PA134900493; -.
DR VEuPathDB; HostDB:ENSG00000134153; -.
DR eggNOG; KOG3306; Eukaryota.
DR GeneTree; ENSGT00390000017490; -.
DR InParanoid; Q9NPA0; -.
DR OMA; EMENMQM; -.
DR OrthoDB; 1348328at2759; -.
DR PhylomeDB; Q9NPA0; -.
DR TreeFam; TF106158; -.
DR PathwayCommons; Q9NPA0; -.
DR SignaLink; Q9NPA0; -.
DR BioGRID-ORCS; 56851; 512 hits in 1086 CRISPR screens.
DR ChiTaRS; EMC7; human.
DR EvolutionaryTrace; Q9NPA0; -.
DR GenomeRNAi; 56851; -.
DR Pharos; Q9NPA0; Tdark.
DR PRO; PR:Q9NPA0; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q9NPA0; protein.
DR Bgee; ENSG00000134153; Expressed in decidua and 205 other tissues.
DR ExpressionAtlas; Q9NPA0; baseline and differential.
DR Genevisible; Q9NPA0; HS.
DR GO; GO:0072546; C:EMC complex; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IC:ComplexPortal.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IDA:UniProtKB.
DR GO; GO:0030246; F:carbohydrate binding; IEA:InterPro.
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; IPR013784; Carb-bd-like_fold.
DR InterPro; IPR039163; EMC7.
DR InterPro; IPR019008; EMC7_beta_sandwich.
DR PANTHER; PTHR13605; PTHR13605; 1.
DR Pfam; PF09430; DUF2012; 1.
DR SUPFAM; SSF49452; SSF49452; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Endoplasmic reticulum; Membrane; Reference proteome; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..23
FT /evidence="ECO:0000269|PubMed:32439656,
FT ECO:0007744|PubMed:25944712"
FT CHAIN 24..242
FT /note="ER membrane protein complex subunit 7"
FT /id="PRO_0000240860"
FT TOPO_DOM 24..159
FT /note="Lumenal"
FT /evidence="ECO:0000269|PubMed:32439656"
FT TRANSMEM 160..180
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 181..242
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:32439656"
FT REGION 217..242
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 217..235
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT STRAND 47..49
FT /evidence="ECO:0007829|PDB:7ADO"
FT STRAND 54..56
FT /evidence="ECO:0007829|PDB:7ADO"
FT HELIX 58..64
FT /evidence="ECO:0007829|PDB:7ADO"
FT STRAND 66..69
FT /evidence="ECO:0007829|PDB:6WW7"
FT TURN 70..73
FT /evidence="ECO:0007829|PDB:6WW7"
FT STRAND 74..76
FT /evidence="ECO:0007829|PDB:6WW7"
FT STRAND 84..86
FT /evidence="ECO:0007829|PDB:7ADO"
FT STRAND 91..97
FT /evidence="ECO:0007829|PDB:7ADO"
FT STRAND 108..111
FT /evidence="ECO:0007829|PDB:7ADO"
FT STRAND 118..121
FT /evidence="ECO:0007829|PDB:6WW7"
FT STRAND 125..127
FT /evidence="ECO:0007829|PDB:6WW7"
FT STRAND 136..138
FT /evidence="ECO:0007829|PDB:6WW7"
SQ SEQUENCE 242 AA; 26471 MW; A71930B89A4C2458 CRC64;
MAAALWGFFP VLLLLLLSGD VQSSEVPGAA AEGSGGSGVG IGDRFKIEGR AVVPGVKPQD
WISAARVLVD GEEHVGFLKT DGSFVVHDIP SGSYVVEVVS PAYRFDPVRV DITSKGKMRA
RYVNYIKTSE VVRLPYPLQM KSSGPPSYFI KRESWGWTDF LMNPMVMMMV LPLLIFVLLP
KVVNTSDPDM RREMEQSMNM LNSNHELPDV SEFMTRLFSS KSSGKSSSGS SKTGKSGAGK
RR
