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 10-JUN-2026, entry version 205. 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}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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_014674.3. [Q92611-1] DR AlphaFoldDB; Q92611; -. DR SMR; Q92611; -. DR BioGRID; 115047; 217. DR FunCoup; Q92611; 888. DR IntAct; Q92611; 47. DR MINT; Q92611; -. DR NDEx; IQUERY-CP-EDEM1; 1 NDEx IQuery Curated Pathway. DR STRING; 9606.ENSP00000256497; -. DR GlyCosmos; Q92611; 5 sites, No reported glycans. DR GlyGen; Q92611; 8 sites, 7 N-linked glycans (2 sites). DR iPTMnet; Q92611; -. DR PhosphoSitePlus; Q92611; -. DR BioMuta; EDEM1; -. DR DMDM; 17368550; -. DR jPOST; Q92611; -. DR MassIVE; Q92611; -. DR PaxDb; 9606-ENSP00000256497; -. DR PeptideAtlas; Q92611; -. DR ProteomicsDB; 5457; -. DR ProteomicsDB; 75356; -. [Q92611-1] DR Pumba; Q92611; -. DR Antibodypedia; 25261; 96 antibodies from 26 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 AGR; HGNC:18967; -. DR ClinPGx; PA128394554; -. 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 OpenTargets; ENSG00000134109; -. DR VEuPathDB; HostDB:ENSG00000134109; -. DR eggNOG; KOG2429; Eukaryota. DR GeneTree; ENSGT00940000157717; -. DR HOGENOM; CLU_003818_5_6_1; -. DR InParanoid; Q92611; -. DR OMA; EEFWRMF; -. DR OrthoDB; 8118055at2759; -. DR PAN-GO; Q92611; 0 GO annotations based on evolutionary models. DR PhylomeDB; Q92611; -. 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 Agora; ENSG00000134109; -. DR BioGRID-ORCS; 9695; 15 hits in 1159 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 179 other cell types or tissues. DR ExpressionAtlas; Q92611; baseline and differential. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:MGI. DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB. DR GO; GO:0044322; C:endoplasmic reticulum quality control compartment; IDA: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; IMP:ParkinsonsUK-UCL. DR GO; GO:0036503; P:ERAD pathway; IMP:ParkinsonsUK-UCL. DR GO; GO:1904382; P:mannose trimming involved in glycoprotein ERAD pathway; TAS:Reactome. 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:0006511; P:ubiquitin-dependent protein catabolic process; IMP:ParkinsonsUK-UCL. DR FunFam; 1.50.10.10:FF:000016; alpha-1,2-Mannosidase; 1. 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:SF5; ER DEGRADATION-ENHANCING ALPHA-MANNOSIDASE-LIKE PROTEIN 1; 1. DR PANTHER; PTHR45679; ER DEGRADATION-ENHANCING ALPHA-MANNOSIDASE-LIKE PROTEIN 2; 1. DR Pfam; PF01532; Glyco_hydro_47; 1. DR PRINTS; PR00747; GLYHDRLASE47. DR SUPFAM; SSF48225; Seven-hairpin glycosidases; 1. PE 1: Evidence at protein level; KW Alternative splicing; Endoplasmic reticulum; Glycoprotein; Membrane; KW Proteomics identification; Reference proteome; Signal-anchor; KW Transmembrane; Transmembrane helix; 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 //