ID   EMC9_HUMAN              Reviewed;         208 AA.
AC   Q9Y3B6; D3DS60; Q9BUM3;
DT   26-SEP-2001, integrated into UniProtKB/Swiss-Prot.
DT   17-OCT-2006, sequence version 3.
DT   10-JUN-2026, entry version 163.
DE   RecName: Full=ER membrane protein complex subunit 9;
DE   AltName: Full=Protein FAM158A;
GN   Name=EMC9; Synonyms=C14orf122, FAM158A; ORFNames=CGI-112;
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].
RX   PubMed=10810093; DOI=10.1101/gr.10.5.703;
RA   Lai C.-H., Chou C.-Y., Ch'ang L.-Y., Liu C.-S., Lin W.-C.;
RT   "Identification of novel human genes evolutionarily conserved in
RT   Caenorhabditis elegans by comparative proteomics.";
RL   Genome Res. 10:703-713(2000).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Skin;
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 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   [5]
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   [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:6Y4L, ECO:0007744|PDB:6Z3W}
RP   X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 1-200 IN COMPLEX WITH EMC2,
RP   STRUCTURE BY ELECTRON MICROSCOPY (6.40 ANGSTROMS) OF THE EMC COMPLEX,
RP   FUNCTION, SUBCELLULAR LOCATION, TOPOLOGY, AND INTERACTION WITH EMC2.
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).
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:32459176).
CC       Preferentially accommodates proteins with transmembrane domains that
CC       are weakly hydrophobic or contain destabilizing features such as
CC       charged and aromatic residues (PubMed:29242231, PubMed:29809151,
CC       PubMed:30415835). Involved in the cotranslational insertion of multi-
CC       pass membrane proteins in which stop-transfer membrane-anchor sequences
CC       become ER membrane spanning helices (PubMed:29809151, PubMed:30415835).
CC       It is also required for the post-translational insertion of tail-
CC       anchored/TA proteins in endoplasmic reticulum membranes
CC       (PubMed:29242231, PubMed:29809151). By mediating the proper
CC       cotranslational insertion of N-terminal transmembrane domains in an N-
CC       exo topology, with translocated N-terminus in the lumen of the ER,
CC       controls the topology of multi-pass membrane proteins like the G
CC       protein-coupled receptors (PubMed:30415835). By regulating the
CC       insertion of various proteins in membranes, it is indirectly involved
CC       in many cellular processes (Probable). {ECO:0000269|PubMed:29242231,
CC       ECO:0000269|PubMed:29809151, ECO:0000269|PubMed:30415835,
CC       ECO:0000269|PubMed:32459176, ECO:0000305}.
CC   -!- SUBUNIT: Component of the ER membrane protein complex (EMC)
CC       (PubMed:22119785, PubMed:29242231, PubMed:32459176). EMC8 and EMC9 are
CC       mutually exclusive subunits of the EMC complex (PubMed:32459176).
CC       {ECO:0000269|PubMed:22119785, ECO:0000269|PubMed:29242231,
CC       ECO:0000269|PubMed:32459176}.
CC   -!- INTERACTION:
CC       Q9Y3B6; Q15006: EMC2; NbExp=14; IntAct=EBI-748366, EBI-359031;
CC       Q9Y3B6; Q14524-3: SCN5A; NbExp=3; IntAct=EBI-748366, EBI-14276801;
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC       {ECO:0000305|PubMed:32459176}; Peripheral membrane protein
CC       {ECO:0000305|PubMed:32459176}; Cytoplasmic side
CC       {ECO:0000269|PubMed:22119785}.
CC   -!- SIMILARITY: Belongs to the EMC8/EMC9 family. {ECO:0000305}.
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DR   EMBL; AF151870; AAD34107.1; -; mRNA.
DR   EMBL; CH471078; EAW66103.1; -; Genomic_DNA.
DR   EMBL; CH471078; EAW66104.1; -; Genomic_DNA.
DR   EMBL; BC002491; AAH02491.1; -; mRNA.
DR   CCDS; CCDS9613.1; -.
DR   RefSeq; NP_057133.2; NM_016049.3.
DR   RefSeq; XP_005267778.1; XM_005267721.6.
DR   RefSeq; XP_054188321.1; XM_054332346.1.
DR   RefSeq; XP_054232134.1; XM_054376159.1.
DR   PDB; 6Y4L; X-ray; 2.20 A; B=1-200.
DR   PDB; 6Z3W; EM; 6.40 A; H=1-208.
DR   PDBsum; 6Y4L; -.
DR   PDBsum; 6Z3W; -.
DR   AlphaFoldDB; Q9Y3B6; -.
DR   SMR; Q9Y3B6; -.
DR   BioGRID; 119223; 169.
DR   ComplexPortal; CPX-5881; Endoplasmic reticulum membrane complex, EMC9 variant.
DR   CORUM; Q9Y3B6; -.
DR   FunCoup; Q9Y3B6; 848.
DR   IntAct; Q9Y3B6; 157.
DR   MINT; Q9Y3B6; -.
DR   STRING; 9606.ENSP00000403210; -.
DR   TCDB; 3.A.27.1.1; the endoplasmic reticulum membrane protein insertion complex (emc) family.
DR   GlyGen; Q9Y3B6; 1 site.
DR   iPTMnet; Q9Y3B6; -.
DR   PhosphoSitePlus; Q9Y3B6; -.
DR   BioMuta; EMC9; -.
DR   DMDM; 116241305; -.
DR   jPOST; Q9Y3B6; -.
DR   MassIVE; Q9Y3B6; -.
DR   PaxDb; 9606-ENSP00000403210; -.
DR   PeptideAtlas; Q9Y3B6; -.
DR   ProteomicsDB; 86003; -.
DR   Pumba; Q9Y3B6; -.
DR   Antibodypedia; 55830; 41 antibodies from 12 providers.
DR   DNASU; 51016; -.
DR   Ensembl; ENST00000216799.9; ENSP00000216799.4; ENSG00000100908.15.
DR   Ensembl; ENST00000419198.6; ENSP00000403210.2; ENSG00000100908.15.
DR   Ensembl; ENST00000642147.1; ENSP00000494976.1; ENSG00000285377.2.
DR   Ensembl; ENST00000646772.2; ENSP00000495623.1; ENSG00000285377.2.
DR   Ensembl; ENST00000872607.1; ENSP00000542666.1; ENSG00000100908.15.
DR   Ensembl; ENST00000967220.1; ENSP00000637279.1; ENSG00000100908.15.
DR   GeneID; 51016; -.
DR   KEGG; hsa:51016; -.
DR   MANE-Select; ENST00000216799.9; ENSP00000216799.4; NM_016049.4; NP_057133.2.
DR   UCSC; uc001wmi.3; human.
DR   AGR; HGNC:20273; -.
DR   ClinPGx; PA162386700; -.
DR   CTD; 51016; -.
DR   GeneCards; EMC9; -.
DR   HGNC; HGNC:20273; EMC9.
DR   HPA; ENSG00000100908; Low tissue specificity.
DR   MIM; 621496; gene.
DR   OpenTargets; ENSG00000100908; -.
DR   VEuPathDB; HostDB:ENSG00000100908; -.
DR   eggNOG; KOG3289; Eukaryota.
DR   GeneTree; ENSGT00390000006738; -.
DR   HOGENOM; CLU_087337_0_1_1; -.
DR   InParanoid; Q9Y3B6; -.
DR   OMA; CLSDCVP; -.
DR   OrthoDB; 194468at2759; -.
DR   PAN-GO; Q9Y3B6; 4 GO annotations based on evolutionary models.
DR   PhylomeDB; Q9Y3B6; -.
DR   PathwayCommons; Q9Y3B6; -.
DR   SignaLink; Q9Y3B6; -.
DR   Agora; ENSG00000100908; -.
DR   BioGRID-ORCS; 51016; 15 hits in 1158 CRISPR screens.
DR   ChiTaRS; EMC9; human.
DR   GeneWiki; Fam158a; -.
DR   GenomeRNAi; 51016; -.
DR   Pharos; Q9Y3B6; Tdark.
DR   PRO; PR:Q9Y3B6; -.
DR   Proteomes; UP000005640; Chromosome 14.
DR   RNAct; Q9Y3B6; protein.
DR   Bgee; ENSG00000100908; Expressed in pituitary gland and 99 other cell types or tissues.
DR   ExpressionAtlas; Q9Y3B6; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR   GO; GO:0072546; C:EMC complex; IDA:UniProtKB.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; NAS:ComplexPortal.
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:SF12; ER MEMBRANE PROTEIN COMPLEX SUBUNIT 9; 1.
DR   Pfam; PF03665; UPF0172; 1.
DR   PROSITE; PS50249; MPN; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Endoplasmic reticulum; Membrane; Proteomics identification;
KW   Reference proteome.
FT   CHAIN           1..208
FT                   /note="ER membrane protein complex subunit 9"
FT                   /id="PRO_0000221189"
FT   DOMAIN          4..139
FT                   /note="MPN"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01182"
FT   VARIANT         97
FT                   /note="A -> V (in dbSNP:rs11574512)"
FT                   /id="VAR_052532"
FT   CONFLICT        8..10
FT                   /note="ALA -> GPG (in Ref. 1; AAD34107)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        35..36
FT                   /note="PR -> TG (in Ref. 1; AAD34107)"
FT                   /evidence="ECO:0000305"
FT   STRAND          4..6
FT                   /evidence="ECO:0007829|PDB:6Y4L"
FT   HELIX           8..20
FT                   /evidence="ECO:0007829|PDB:6Y4L"
FT   STRAND          26..32
FT                   /evidence="ECO:0007829|PDB:6Y4L"
FT   STRAND          45..48
FT                   /evidence="ECO:0007829|PDB:6Y4L"
FT   HELIX           58..73
FT                   /evidence="ECO:0007829|PDB:6Y4L"
FT   STRAND          77..84
FT                   /evidence="ECO:0007829|PDB:6Y4L"
FT   HELIX           95..107
FT                   /evidence="ECO:0007829|PDB:6Y4L"
FT   STRAND          112..116
FT                   /evidence="ECO:0007829|PDB:6Y4L"
FT   STRAND          120..123
FT                   /evidence="ECO:0007829|PDB:6Y4L"
FT   STRAND          129..136
FT                   /evidence="ECO:0007829|PDB:6Y4L"
FT   STRAND          139..142
FT                   /evidence="ECO:0007829|PDB:6Y4L"
FT   HELIX           145..147
FT                   /evidence="ECO:0007829|PDB:6Y4L"
FT   STRAND          148..150
FT                   /evidence="ECO:0007829|PDB:6Y4L"
FT   HELIX           153..165
FT                   /evidence="ECO:0007829|PDB:6Y4L"
FT   HELIX           168..171
FT                   /evidence="ECO:0007829|PDB:6Y4L"
FT   HELIX           175..180
FT                   /evidence="ECO:0007829|PDB:6Y4L"
SQ   SEQUENCE   208 AA;  23061 MW;  173647F7DFF63510 CRC64;
     MGEVEISALA YVKMCLHAAR YPHAAVNGLF LAPAPRSGEC LCLTDCVPLF HSHLALSVML
     EVALNQVDVW GAQAGLVVAG YYHANAAVND QSPGPLALKI AGRIAEFFPD AVLIMLDNQK
     LVPQPRVPPV IVLENQGLRW VPKDKNLVMW RDWEESRQMV GALLEDRAHQ HLVDFDCHLD
     DIRQDWTNQR LNTQITQWVG PTNGNGNA
//