EMC9_HUMAN
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 03-AUG-2022, entry version 146.
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:30415835, PubMed:29809151, PubMed:29242231, 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:30415835, PubMed:29809151,
CC PubMed:29242231). 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:30415835, PubMed:29809151).
CC It is also required for the post-translational insertion of tail-
CC anchored/TA proteins in endoplasmic reticulum membranes
CC (PubMed:29809151, PubMed:29242231). 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=10; 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_005267721.4.
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; 22.
DR ComplexPortal; CPX-5881; Endoplasmic reticulum membrane complex, EMC9 variant.
DR IntAct; Q9Y3B6; 11.
DR MINT; Q9Y3B6; -.
DR STRING; 9606.ENSP00000403210; -.
DR TCDB; 3.A.27.1.1; the endoplasmic reticulum membrane protein insertion complex (emc) family.
DR iPTMnet; Q9Y3B6; -.
DR PhosphoSitePlus; Q9Y3B6; -.
DR BioMuta; EMC9; -.
DR DMDM; 116241305; -.
DR EPD; Q9Y3B6; -.
DR jPOST; Q9Y3B6; -.
DR MassIVE; Q9Y3B6; -.
DR MaxQB; Q9Y3B6; -.
DR PaxDb; Q9Y3B6; -.
DR PeptideAtlas; Q9Y3B6; -.
DR PRIDE; Q9Y3B6; -.
DR ProteomicsDB; 86003; -.
DR Antibodypedia; 55830; 50 antibodies from 13 providers.
DR DNASU; 51016; -.
DR Ensembl; ENST00000216799.9; ENSP00000216799.4; ENSG00000100908.14.
DR Ensembl; ENST00000419198.6; ENSP00000403210.2; ENSG00000100908.14.
DR Ensembl; ENST00000642147.1; ENSP00000494976.1; ENSG00000285377.2.
DR Ensembl; ENST00000646772.2; ENSP00000495623.1; ENSG00000285377.2.
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 CTD; 51016; -.
DR GeneCards; EMC9; -.
DR HGNC; HGNC:20273; EMC9.
DR HPA; ENSG00000100908; Low tissue specificity.
DR neXtProt; NX_Q9Y3B6; -.
DR OpenTargets; ENSG00000100908; -.
DR PharmGKB; PA162386700; -.
DR VEuPathDB; HostDB:ENSG00000100908; -.
DR eggNOG; KOG3289; Eukaryota.
DR GeneTree; ENSGT00390000006738; -.
DR HOGENOM; CLU_087337_0_1_1; -.
DR InParanoid; Q9Y3B6; -.
DR OMA; QANACAS; -.
DR OrthoDB; 1284861at2759; -.
DR PhylomeDB; Q9Y3B6; -.
DR TreeFam; TF313860; -.
DR PathwayCommons; Q9Y3B6; -.
DR SignaLink; Q9Y3B6; -.
DR BioGRID-ORCS; 51016; 15 hits in 1079 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 97 other tissues.
DR ExpressionAtlas; Q9Y3B6; baseline and differential.
DR Genevisible; Q9Y3B6; HS.
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; IC: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; PTHR12941; 1.
DR Pfam; PF03665; UPF0172; 1.
DR PROSITE; PS50249; MPN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Endoplasmic reticulum; Membrane; 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
