EMC6_HUMAN
ID EMC6_HUMAN Reviewed; 110 AA.
AC Q9BV81;
DT 31-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 131.
DE RecName: Full=ER membrane protein complex subunit 6;
DE AltName: Full=Transmembrane protein 93;
GN Name=EMC6; Synonyms=TMEM93;
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].
RC TISSUE=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 [2]
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 [3]
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 [4]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-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 [5]
RP FUNCTION, AND SUBCELLULAR LOCATION.
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 [6]
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 [7]
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 [8] {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 [9] {ECO:0007744|PDB:6WW7}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.40 ANGSTROMS) OF THE EMC COMPLEX,
RP FUNCTION, TOPOLOGY, AND MUTAGENESIS OF ASP-27 AND THR-31.
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:32439656,
CC ECO:0000269|PubMed:32459176}.
CC -!- INTERACTION:
CC Q9BV81; Q13520: AQP6; NbExp=3; IntAct=EBI-2820492, EBI-13059134;
CC Q9BV81; O43315: AQP9; NbExp=3; IntAct=EBI-2820492, EBI-17444777;
CC Q9BV81; P11912: CD79A; NbExp=3; IntAct=EBI-2820492, EBI-7797864;
CC Q9BV81; Q15125: EBP; NbExp=3; IntAct=EBI-2820492, EBI-3915253;
CC Q9BV81; Q9Y282: ERGIC3; NbExp=3; IntAct=EBI-2820492, EBI-781551;
CC Q9BV81; Q5JX71: FAM209A; NbExp=3; IntAct=EBI-2820492, EBI-18304435;
CC Q9BV81; Q5SR56: MFSD14B; NbExp=3; IntAct=EBI-2820492, EBI-373355;
CC Q9BV81; Q15546: MMD; NbExp=3; IntAct=EBI-2820492, EBI-17873222;
CC Q9BV81; Q8N4V1: MMGT1; NbExp=6; IntAct=EBI-2820492, EBI-6163737;
CC Q9BV81; P15941-11: MUC1; NbExp=3; IntAct=EBI-2820492, EBI-17263240;
CC Q9BV81; Q13113: PDZK1IP1; NbExp=3; IntAct=EBI-2820492, EBI-716063;
CC Q9BV81; Q3KNW5: SLC10A6; NbExp=3; IntAct=EBI-2820492, EBI-18159983;
CC Q9BV81; Q9NP94: SLC39A2; NbExp=3; IntAct=EBI-2820492, EBI-12898013;
CC Q9BV81; P30825: SLC7A1; NbExp=3; IntAct=EBI-2820492, EBI-4289564;
CC Q9BV81; Q96MV1: TLCD4; NbExp=3; IntAct=EBI-2820492, EBI-12947623;
CC Q9BV81; Q9NUH8: TMEM14B; NbExp=3; IntAct=EBI-2820492, EBI-8638294;
CC Q9BV81; Q96Q45-2: TMEM237; NbExp=3; IntAct=EBI-2820492, EBI-10982110;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:22119785, ECO:0000269|PubMed:30415835}; Multi-pass
CC membrane protein {ECO:0000269|PubMed:32439656,
CC ECO:0000269|PubMed:32459176}.
CC -!- SIMILARITY: Belongs to the EMC6 family. {ECO:0000305}.
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DR EMBL; BC001409; AAH01409.1; -; mRNA.
DR CCDS; CCDS11033.1; -.
DR RefSeq; NP_001014764.1; NM_001014764.2.
DR RefSeq; NP_112588.1; NM_031298.3.
DR PDB; 6WW7; EM; 3.40 A; F=1-110.
DR PDB; 6Z3W; EM; 6.40 A; F=1-110.
DR PDB; 7ADO; EM; 3.39 A; F=1-110.
DR PDB; 7ADP; EM; 3.60 A; F=1-110.
DR PDBsum; 6WW7; -.
DR PDBsum; 6Z3W; -.
DR PDBsum; 7ADO; -.
DR PDBsum; 7ADP; -.
DR AlphaFoldDB; Q9BV81; -.
DR SMR; Q9BV81; -.
DR BioGRID; 123656; 61.
DR ComplexPortal; CPX-5848; Endoplasmic reticulum membrane complex, EMC8 variant.
DR ComplexPortal; CPX-5881; Endoplasmic reticulum membrane complex, EMC9 variant.
DR IntAct; Q9BV81; 27.
DR STRING; 9606.ENSP00000380322; -.
DR TCDB; 3.A.27.1.1; the endoplasmic reticulum membrane protein insertion complex (emc) family.
DR iPTMnet; Q9BV81; -.
DR PhosphoSitePlus; Q9BV81; -.
DR BioMuta; EMC6; -.
DR DMDM; 74733294; -.
DR EPD; Q9BV81; -.
DR jPOST; Q9BV81; -.
DR MassIVE; Q9BV81; -.
DR MaxQB; Q9BV81; -.
DR PaxDb; Q9BV81; -.
DR PeptideAtlas; Q9BV81; -.
DR PRIDE; Q9BV81; -.
DR ProteomicsDB; 79179; -.
DR TopDownProteomics; Q9BV81; -.
DR Antibodypedia; 23098; 62 antibodies from 16 providers.
DR DNASU; 83460; -.
DR Ensembl; ENST00000248378.6; ENSP00000248378.4; ENSG00000127774.7.
DR Ensembl; ENST00000397133.2; ENSP00000380322.1; ENSG00000127774.7.
DR GeneID; 83460; -.
DR KEGG; hsa:83460; -.
DR MANE-Select; ENST00000248378.6; ENSP00000248378.4; NM_031298.4; NP_112588.1.
DR UCSC; uc002fwf.3; human.
DR CTD; 83460; -.
DR DisGeNET; 83460; -.
DR GeneCards; EMC6; -.
DR HGNC; HGNC:28430; EMC6.
DR HPA; ENSG00000127774; Tissue enhanced (skeletal).
DR neXtProt; NX_Q9BV81; -.
DR OpenTargets; ENSG00000127774; -.
DR PharmGKB; PA142670745; -.
DR VEuPathDB; HostDB:ENSG00000127774; -.
DR eggNOG; KOG4455; Eukaryota.
DR GeneTree; ENSGT00390000003917; -.
DR HOGENOM; CLU_110781_3_0_1; -.
DR InParanoid; Q9BV81; -.
DR OMA; FIYGMVH; -.
DR OrthoDB; 1547548at2759; -.
DR PhylomeDB; Q9BV81; -.
DR TreeFam; TF332611; -.
DR PathwayCommons; Q9BV81; -.
DR SignaLink; Q9BV81; -.
DR BioGRID-ORCS; 83460; 191 hits in 1097 CRISPR screens.
DR ChiTaRS; EMC6; human.
DR GenomeRNAi; 83460; -.
DR Pharos; Q9BV81; Tbio.
DR PRO; PR:Q9BV81; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q9BV81; protein.
DR Bgee; ENSG00000127774; Expressed in hindlimb stylopod muscle and 186 other tissues.
DR Genevisible; Q9BV81; 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:0097631; C:integral component of omegasome membrane; IDA:UniProtKB.
DR GO; GO:0000045; P:autophagosome assembly; IMP: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:ComplexPortal.
DR InterPro; IPR008504; Emc6.
DR InterPro; IPR029008; EMC6-like.
DR PANTHER; PTHR20994; PTHR20994; 1.
DR Pfam; PF07019; EMC6; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Endoplasmic reticulum; Membrane;
KW Reference proteome; Transmembrane; Transmembrane helix.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:22814378"
FT CHAIN 2..110
FT /note="ER membrane protein complex subunit 6"
FT /id="PRO_0000254156"
FT TOPO_DOM 2..28
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:32439656"
FT TRANSMEM 29..44
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:32439656"
FT TOPO_DOM 45..50
FT /note="Lumenal"
FT /evidence="ECO:0000269|PubMed:32439656"
FT TRANSMEM 51..71
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:32439656"
FT TOPO_DOM 72..89
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:32439656"
FT TRANSMEM 90..106
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:32439656"
FT TOPO_DOM 107..110
FT /note="Lumenal"
FT /evidence="ECO:0000269|PubMed:32439656"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT MUTAGEN 27
FT /note="D->A: No effect on EMC assembly but decreased
FT membrane insertion of hydrophobic transmembrane helices-
FT containing proteins by the EMC."
FT /evidence="ECO:0000269|PubMed:32439656"
FT MUTAGEN 31
FT /note="T->A: No effect on EMC assembly but decreased
FT membrane insertion of hydrophobic transmembrane helices-
FT containing proteins by the EMC."
FT /evidence="ECO:0000269|PubMed:32439656"
FT HELIX 18..43
FT /evidence="ECO:0007829|PDB:7ADO"
FT HELIX 49..69
FT /evidence="ECO:0007829|PDB:7ADO"
FT HELIX 71..73
FT /evidence="ECO:0007829|PDB:7ADO"
FT TURN 75..77
FT /evidence="ECO:0007829|PDB:7ADO"
FT HELIX 82..85
FT /evidence="ECO:0007829|PDB:7ADO"
FT STRAND 86..88
FT /evidence="ECO:0007829|PDB:7ADO"
FT HELIX 91..107
FT /evidence="ECO:0007829|PDB:7ADO"
SQ SEQUENCE 110 AA; 12017 MW; 5120B6E4CC12FD48 CRC64;
MAAVVAKREG PPFISEAAVR GNAAVLDYCR TSVSALSGAT AGILGLTGLY GFIFYLLASV
LLSLLLILKA GRRWNKYFKS RRPLFTGGLI GGLFTYVLFW TFLYGMVHVY
