EDEM1_HUMAN
ID EDEM1_HUMAN Reviewed; 657 AA.
AC Q92611; A8K9C8; B4DXP3;
DT 16-NOV-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1997, sequence version 1.
DT 03-AUG-2022, entry version 187.
DE RecName: Full=ER degradation-enhancing alpha-mannosidase-like protein 1;
GN Name=EDEM1; Synonyms=EDEM, KIAA0212;
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] (ISOFORM 1).
RC TISSUE=Bone marrow;
RX PubMed=9039502; DOI=10.1093/dnares/3.5.321;
RA Nagase T., Seki N., Ishikawa K., Ohira M., Kawarabayasi Y., Ohara O.,
RA Tanaka A., Kotani H., Miyajima N., Nomura N.;
RT "Prediction of the coding sequences of unidentified human genes. VI. The
RT coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of
RT cDNA clones from cell line KG-1 and brain.";
RL DNA Res. 3:321-329(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Testis, and Thymus;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [4]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [6]
RP FUNCTION.
RX PubMed=12610306; DOI=10.1126/science.1079474;
RA Molinari M., Calanca V., Galli C., Lucca P., Paganetti P.;
RT "Role of EDEM in the release of misfolded glycoproteins from the calnexin
RT cycle.";
RL Science 299:1397-1400(2003).
RN [7]
RP INTERACTION WITH DERL2 AND DERL3.
RX PubMed=16449189; DOI=10.1083/jcb.200507057;
RA Oda Y., Okada T., Yoshida H., Kaufman R.J., Nagata K., Mori K.;
RT "Derlin-2 and Derlin-3 are regulated by the mammalian unfolded protein
RT response and are required for ER-associated degradation.";
RL J. Cell Biol. 172:383-393(2006).
RN [8]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=19934218; DOI=10.1242/jcs.055228;
RA Kosmaoglou M., Kanuga N., Aguila M., Garriga P., Cheetham M.E.;
RT "A dual role for EDEM1 in the processing of rod opsin.";
RL J. Cell Sci. 122:4465-4472(2009).
RN [9]
RP FUNCTION, MUTAGENESIS OF GLU-225; ASP-370 AND GLU-493, AND INTERACTION WITH
RP SEL1L.
RX PubMed=19524542; DOI=10.1016/j.molcel.2009.05.018;
RA Cormier J.H., Tamura T., Sunryd J.C., Hebert D.N.;
RT "EDEM1 recognition and delivery of misfolded proteins to the SEL1L-
RT containing ERAD complex.";
RL Mol. Cell 34:627-633(2009).
RN [10]
RP FUNCTION.
RX PubMed=25092655; DOI=10.1083/jcb.201404075;
RA Ninagawa S., Okada T., Sumitomo Y., Kamiya Y., Kato K., Horimoto S.,
RA Ishikawa T., Takeda S., Sakuma T., Yamamoto T., Mori K.;
RT "EDEM2 initiates mammalian glycoprotein ERAD by catalyzing the first
RT mannose trimming step.";
RL J. Cell Biol. 206:347-356(2014).
CC -!- FUNCTION: Extracts misfolded glycoproteins, but not glycoproteins
CC undergoing productive folding, from the calnexin cycle. It is directly
CC involved in endoplasmic reticulum-associated degradation (ERAD) and
CC targets misfolded glycoproteins for degradation in an N-glycan-
CC independent manner, probably by forming a complex with SEL1L. It has
CC low mannosidase activity, catalyzing mannose trimming from Man8GlcNAc2
CC to Man7GlcNAc2. {ECO:0000269|PubMed:12610306,
CC ECO:0000269|PubMed:19524542, ECO:0000269|PubMed:19934218,
CC ECO:0000269|PubMed:25092655}.
CC -!- SUBUNIT: Interacts with DNAJC10 (By similarity). Interacts with DERL2
CC and DERL3. Binds to SEL1L. {ECO:0000250, ECO:0000269|PubMed:16449189,
CC ECO:0000269|PubMed:19524542}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:19934218}; Single-pass type II membrane protein
CC {ECO:0000269|PubMed:19934218}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q92611-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q92611-2; Sequence=VSP_056703, VSP_056704;
CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 47 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA13203.2; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; D86967; BAA13203.2; ALT_INIT; mRNA.
DR EMBL; AK292643; BAF85332.1; -; mRNA.
DR EMBL; AK302065; BAG63455.1; -; mRNA.
DR EMBL; AC026202; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471055; EAW63925.1; -; Genomic_DNA.
DR EMBL; BC019088; AAH19088.1; -; mRNA.
DR CCDS; CCDS33686.1; -. [Q92611-1]
DR RefSeq; NP_055489.1; NM_014674.2. [Q92611-1]
DR AlphaFoldDB; Q92611; -.
DR SMR; Q92611; -.
DR BioGRID; 115047; 210.
DR IntAct; Q92611; 20.
DR MINT; Q92611; -.
DR STRING; 9606.ENSP00000256497; -.
DR CAZy; GH47; Glycoside Hydrolase Family 47.
DR GlyGen; Q92611; 7 sites.
DR iPTMnet; Q92611; -.
DR PhosphoSitePlus; Q92611; -.
DR BioMuta; EDEM1; -.
DR DMDM; 17368550; -.
DR EPD; Q92611; -.
DR jPOST; Q92611; -.
DR MassIVE; Q92611; -.
DR MaxQB; Q92611; -.
DR PaxDb; Q92611; -.
DR PeptideAtlas; Q92611; -.
DR PRIDE; Q92611; -.
DR ProteomicsDB; 5457; -.
DR ProteomicsDB; 75356; -. [Q92611-1]
DR Antibodypedia; 25261; 102 antibodies from 27 providers.
DR DNASU; 9695; -.
DR Ensembl; ENST00000256497.9; ENSP00000256497.4; ENSG00000134109.11. [Q92611-1]
DR Ensembl; ENST00000445686.1; ENSP00000394099.1; ENSG00000134109.11. [Q92611-2]
DR GeneID; 9695; -.
DR KEGG; hsa:9695; -.
DR MANE-Select; ENST00000256497.9; ENSP00000256497.4; NM_014674.3; NP_055489.1.
DR UCSC; uc003bqi.4; human. [Q92611-1]
DR CTD; 9695; -.
DR DisGeNET; 9695; -.
DR GeneCards; EDEM1; -.
DR HGNC; HGNC:18967; EDEM1.
DR HPA; ENSG00000134109; Tissue enhanced (lymphoid).
DR MIM; 607673; gene.
DR neXtProt; NX_Q92611; -.
DR OpenTargets; ENSG00000134109; -.
DR PharmGKB; PA128394554; -.
DR VEuPathDB; HostDB:ENSG00000134109; -.
DR eggNOG; KOG2429; Eukaryota.
DR GeneTree; ENSGT00940000157717; -.
DR HOGENOM; CLU_003818_5_6_1; -.
DR InParanoid; Q92611; -.
DR OMA; NWTFVKD; -.
DR PhylomeDB; Q92611; -.
DR TreeFam; TF300807; -.
DR PathwayCommons; Q92611; -.
DR Reactome; R-HSA-381038; XBP1(S) activates chaperone genes.
DR Reactome; R-HSA-901032; ER Quality Control Compartment (ERQC).
DR SignaLink; Q92611; -.
DR BioGRID-ORCS; 9695; 13 hits in 1079 CRISPR screens.
DR ChiTaRS; EDEM1; human.
DR GeneWiki; EDEM1; -.
DR GenomeRNAi; 9695; -.
DR Pharos; Q92611; Tbio.
DR PRO; PR:Q92611; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q92611; protein.
DR Bgee; ENSG00000134109; Expressed in bone marrow cell and 177 other tissues.
DR ExpressionAtlas; Q92611; baseline and differential.
DR Genevisible; Q92611; HS.
DR GO; GO:0016235; C:aggresome; IDA:HPA.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:MGI.
DR GO; GO:0044322; C:endoplasmic reticulum quality control compartment; IDA:UniProtKB.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0004571; F:mannosyl-oligosaccharide 1,2-alpha-mannosidase activity; IMP:ParkinsonsUK-UCL.
DR GO; GO:0051787; F:misfolded protein binding; IDA:UniProtKB.
DR GO; GO:0005975; P:carbohydrate metabolic process; IEA:InterPro.
DR GO; GO:1904380; P:endoplasmic reticulum mannose trimming; IBA:GO_Central.
DR GO; GO:1904382; P:mannose trimming involved in glycoprotein ERAD pathway; IMP:ParkinsonsUK-UCL.
DR GO; GO:1904154; P:positive regulation of retrograde protein transport, ER to cytosol; IMP:ParkinsonsUK-UCL.
DR GO; GO:0045047; P:protein targeting to ER; IMP:UniProtKB.
DR GO; GO:0006986; P:response to unfolded protein; IEA:UniProtKB-KW.
DR GO; GO:0036510; P:trimming of terminal mannose on C branch; IEA:Ensembl.
DR GO; GO:0030433; P:ubiquitin-dependent ERAD pathway; ISS:UniProtKB.
DR GO; GO:0097466; P:ubiquitin-dependent glycoprotein ERAD pathway; IMP:ParkinsonsUK-UCL.
DR Gene3D; 1.50.10.10; -; 1.
DR InterPro; IPR012341; 6hp_glycosidase-like_sf.
DR InterPro; IPR044674; EDEM1/2/3.
DR InterPro; IPR001382; Glyco_hydro_47.
DR InterPro; IPR036026; Seven-hairpin_glycosidases.
DR PANTHER; PTHR45679; PTHR45679; 1.
DR Pfam; PF01532; Glyco_hydro_47; 1.
DR PRINTS; PR00747; GLYHDRLASE47.
DR SUPFAM; SSF48225; SSF48225; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Endoplasmic reticulum; Glycoprotein; Membrane;
KW Reference proteome; Signal-anchor; Transmembrane; Transmembrane helix;
KW Unfolded protein response.
FT CHAIN 1..657
FT /note="ER degradation-enhancing alpha-mannosidase-like
FT protein 1"
FT /id="PRO_0000210321"
FT TOPO_DOM 1..4
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 5..25
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 26..657
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT REGION 48..94
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 181
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 198
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 299
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 342
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 624
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..195
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056703"
FT VAR_SEQ 561..657
FT /note="LFDEDNPVHKSGTRYMFTTEGHIVSVDEHLRELPWKEFFSEEGGQDQGGKSV
FT HRPKPHELKVINSSSNCNRVPDERRYSLPLKSIYMRQIDQMVGLI -> VCVLQDEPRN
FT I (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056704"
FT MUTAGEN 225
FT /note="E->Q: Normal affinity for misfolded glycoproteins,
FT but impaired SEL1L binding."
FT /evidence="ECO:0000269|PubMed:19524542"
FT MUTAGEN 370
FT /note="D->N: Normal affinity for misfolded glycoproteins,
FT but impaired SEL1L binding."
FT /evidence="ECO:0000269|PubMed:19524542"
FT MUTAGEN 493
FT /note="E->Q: Normal affinity for misfolded glycoproteins,
FT but impaired SEL1L binding."
FT /evidence="ECO:0000269|PubMed:19524542"
SQ SEQUENCE 657 AA; 73768 MW; E0097901B3BF02FB CRC64;
MQWRALVLGL VLLRLGLHGV LWLVFGLGPS MGFYQRFPLS FGFQRLRSPD GPASPTSGPV
GRPGGVSGPS WLQPPGTGAA QSPRKAPRRP GPGMCGPANW GYVLGGRGRG PDEYEKRYSG
AFPPQLRAQM RDLARGMFVF GYDNYMAHAF PQDELNPIHC RGRGPDRGDP SNLNINDVLG
NYSLTLVDAL DTLAIMGNSS EFQKAVKLVI NTVSFDKDST VQVFEATIRV LGSLLSAHRI
ITDSKQPFGD MTIKDYDNEL LYMAHDLAVR LLPAFENTKT GIPYPRVNLK TGVPPDTNNE
TCTAGAGSLL VEFGILSRLL GDSTFEWVAR RAVKALWNLR SNDTGLLGNV VNIQTGHWVG
KQSGLGAGLD SFYEYLLKSY ILFGEKEDLE MFNAAYQSIQ NYLRRGREAC NEGEGDPPLY
VNVNMFSGQL MNTWIDSLQA FFPGLQVLIG DVEDAICLHA FYYAIWKRYG ALPERYNWQL
QAPDVLFYPL RPELVESTYL LYQATKNPFY LHVGMDILQS LEKYTKVKCG YATLHHVIDK
STEDRMESFF LSETCKYLYL LFDEDNPVHK SGTRYMFTTE GHIVSVDEHL RELPWKEFFS
EEGGQDQGGK SVHRPKPHEL KVINSSSNCN RVPDERRYSL PLKSIYMRQI DQMVGLI
