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   10-JUN-2026, entry version 149.
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: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       {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=8; 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_001014764.3.
DR   RefSeq; NP_112588.1; NM_031298.4.
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   PDB; 8EOI; EM; 3.40 A; F=11-110.
DR   PDB; 8J0N; EM; 3.47 A; F=1-110.
DR   PDB; 8J0O; EM; 3.32 A; F=1-110.
DR   PDB; 8S9S; EM; 3.60 A; 6=1-110.
DR   PDB; 9C7V; EM; 6.60 A; 6=1-110.
DR   PDBsum; 6WW7; -.
DR   PDBsum; 6Z3W; -.
DR   PDBsum; 7ADO; -.
DR   PDBsum; 7ADP; -.
DR   PDBsum; 8EOI; -.
DR   PDBsum; 8J0N; -.
DR   PDBsum; 8J0O; -.
DR   PDBsum; 8S9S; -.
DR   PDBsum; 9C7V; -.
DR   AlphaFoldDB; Q9BV81; -.
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; Q9BV81; -.
DR   BioGRID; 123656; 79.
DR   ComplexPortal; CPX-5848; Endoplasmic reticulum membrane complex, EMC8 variant.
DR   ComplexPortal; CPX-5881; Endoplasmic reticulum membrane complex, EMC9 variant.
DR   CORUM; Q9BV81; -.
DR   FunCoup; Q9BV81; 1516.
DR   IntAct; Q9BV81; 46.
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   jPOST; Q9BV81; -.
DR   MassIVE; Q9BV81; -.
DR   PaxDb; 9606-ENSP00000380322; -.
DR   PeptideAtlas; Q9BV81; -.
DR   ProteomicsDB; 79179; -.
DR   Pumba; Q9BV81; -.
DR   TopDownProteomics; Q9BV81; -.
DR   Antibodypedia; 23098; 53 antibodies from 15 providers.
DR   DNASU; 83460; -.
DR   Ensembl; ENST00000248378.6; ENSP00000248378.4; ENSG00000127774.8.
DR   Ensembl; ENST00000397133.2; ENSP00000380322.1; ENSG00000127774.8.
DR   Ensembl; ENST00000890763.1; ENSP00000560822.1; ENSG00000127774.8.
DR   Ensembl; ENST00000890764.1; ENSP00000560823.1; ENSG00000127774.8.
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   AGR; HGNC:28430; -.
DR   ClinPGx; PA142670745; -.
DR   CTD; 83460; -.
DR   DisGeNET; 83460; -.
DR   GeneCards; EMC6; -.
DR   HGNC; HGNC:28430; EMC6.
DR   HPA; ENSG00000127774; Tissue enhanced (skeletal).
DR   MIM; 620261; gene.
DR   OpenTargets; ENSG00000127774; -.
DR   VEuPathDB; HostDB:ENSG00000127774; -.
DR   eggNOG; KOG4455; Eukaryota.
DR   GeneTree; ENSGT00390000003917; -.
DR   HOGENOM; CLU_110781_3_0_1; -.
DR   InParanoid; Q9BV81; -.
DR   OMA; MKANFEW; -.
DR   OrthoDB; 16510at2759; -.
DR   PAN-GO; Q9BV81; 2 GO annotations based on evolutionary models.
DR   PhylomeDB; Q9BV81; -.
DR   PathwayCommons; Q9BV81; -.
DR   SignaLink; Q9BV81; -.
DR   Agora; ENSG00000127774; -.
DR   BioGRID-ORCS; 83460; 204 hits in 1187 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 188 other cell types or tissues.
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:1903349; C: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; ER MEMBRANE PROTEIN COMPLEX SUBUNIT 6; 1.
DR   PANTHER; PTHR20994:SF0; ER MEMBRANE PROTEIN COMPLEX SUBUNIT 6; 1.
DR   Pfam; PF07019; EMC6; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Acetylation; Endoplasmic reticulum; Membrane;
KW   Proteomics identification; Reference proteome; Transmembrane;
KW   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
FT                   helices-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
FT                   helices-containing proteins by the EMC."
FT                   /evidence="ECO:0000269|PubMed:32439656"
FT   HELIX           16..44
FT                   /evidence="ECO:0007829|PDB:8J0O"
FT   HELIX           48..70
FT                   /evidence="ECO:0007829|PDB:8J0O"
FT   HELIX           71..73
FT                   /evidence="ECO:0007829|PDB:7ADO"
FT   HELIX           74..77
FT                   /evidence="ECO:0007829|PDB:8J0O"
FT   HELIX           82..85
FT                   /evidence="ECO:0007829|PDB:8J0O"
FT   STRAND          86..90
FT                   /evidence="ECO:0007829|PDB:8J0O"
FT   HELIX           91..107
FT                   /evidence="ECO:0007829|PDB:8J0O"
SQ   SEQUENCE   110 AA;  12017 MW;  5120B6E4CC12FD48 CRC64;
     MAAVVAKREG PPFISEAAVR GNAAVLDYCR TSVSALSGAT AGILGLTGLY GFIFYLLASV
     LLSLLLILKA GRRWNKYFKS RRPLFTGGLI GGLFTYVLFW TFLYGMVHVY
//