ID EDEM2_HUMAN Reviewed; 578 AA. AC Q9BV94; B4DTG9; Q6GU33; Q6IA89; Q6UWZ4; Q9H4U0; Q9H886; Q9NTL9; Q9NVE6; DT 16-NOV-2001, integrated into UniProtKB/Swiss-Prot. DT 16-NOV-2001, sequence version 2. DT 10-JUN-2026, entry version 200. DE RecName: Full=ER degradation-enhancing alpha-mannosidase-like protein 2; DE Flags: Precursor; GN Name=EDEM2; Synonyms=C20orf31, C20orf49; ORFNames=UNQ573/PRO1135; 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] (ISOFORMS 1 AND 2). RC TISSUE=Placenta, and Thyroid; 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 [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RX PubMed=12975309; DOI=10.1101/gr.1293003; RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A., RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.; RT "The secreted protein discovery initiative (SPDI), a large-scale effort to RT identify novel human secreted and transmembrane proteins: a bioinformatics RT assessment."; RL Genome Res. 13:2265-2270(2003). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=11780052; DOI=10.1038/414865a; RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.; RT "The DNA sequence and comparative analysis of human chromosome 20."; RL Nature 414:865-871(2001). RN [5] 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 [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT THR-456. RC TISSUE=Colon, and 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 [7] RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND GLYCOSYLATION. RX PubMed=15537790; DOI=10.1093/glycob/cwi014; RA Mast S.W., Diekman K., Karaveg K., Davis A., Sifers R.N., Moremen K.W.; RT "Human EDEM2, a novel homolog of family 47 glycosidases, is involved in ER- RT associated degradation of glycoproteins."; RL Glycobiology 15:421-436(2005). RN [8] RP FUNCTION, AND MUTAGENESIS OF GLU-117. 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: Involved in the endoplasmic reticulum-associated degradation CC (ERAD) pathway that targets misfolded glycoproteins for degradation in CC an N-glycan-dependent manner (PubMed:15537790, PubMed:25092655). May CC initiate ERAD by promoting the first mannose trimming step of ERAD CC substrates, from Man9GlcNAc2 to Man8GlcNAc2 (PubMed:25092655). Seems to CC recognize and bind to exposed hydrophobic regions in target proteins CC (By similarity). {ECO:0000250|UniProtKB:Q8BJT9, CC ECO:0000269|PubMed:15537790, ECO:0000269|PubMed:25092655}. CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum lumen CC {ECO:0000269|PubMed:15537790}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q9BV94-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9BV94-2; Sequence=VSP_013183; CC -!- TISSUE SPECIFICITY: Expressed ubiquitously in all tissues tested with CC slightly higher levels detected in small intestine and peripheral blood CC leukocytes and weakest levels in brain and skeletal muscle. CC {ECO:0000269|PubMed:15537790}. CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:15537790}. CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 47 family. {ECO:0000305}. CC -!- CAUTION: Has similarity to alpha 1,2-mannosidases, but the catalytic CC activity of this protein is controversial (PubMed:15537790, CC PubMed:25092655). One study shows that it is important for a specific CC oligosaccharide trimming step from Man9GlcNAc2 to Man8GlcNAc2, CC suggesting activity as a mannosidase (PubMed:25092655). However, CC another study reports that this protein has no mannosidase activity CC (PubMed:15537790). {ECO:0000269|PubMed:15537790, CC ECO:0000269|PubMed:25092655}. 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; AK001645; BAA91806.1; -; mRNA. DR EMBL; AK023931; BAB14731.1; -; mRNA. DR EMBL; AK300212; BAG61981.1; -; mRNA. DR EMBL; AY358580; AAQ88943.1; -; mRNA. DR EMBL; CR457266; CAG33547.1; -; mRNA. DR EMBL; AL135844; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL356652; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471077; EAW76228.1; -; Genomic_DNA. DR EMBL; BC001371; AAH01371.1; -; mRNA. DR EMBL; BC016184; AAH16184.1; -; mRNA. DR CCDS; CCDS13247.1; -. [Q9BV94-1] DR CCDS; CCDS46592.1; -. [Q9BV94-2] DR RefSeq; NP_001138497.1; NM_001145025.2. [Q9BV94-2] DR RefSeq; NP_060687.2; NM_018217.3. [Q9BV94-1] DR AlphaFoldDB; Q9BV94; -. DR SMR; Q9BV94; -. DR BioGRID; 120859; 174. DR FunCoup; Q9BV94; 1577. DR IntAct; Q9BV94; 116. DR STRING; 9606.ENSP00000363616; -. DR GlyCosmos; Q9BV94; 4 sites, No reported glycans. DR GlyGen; Q9BV94; 4 sites. DR iPTMnet; Q9BV94; -. DR PhosphoSitePlus; Q9BV94; -. DR BioMuta; EDEM2; -. DR DMDM; 17368685; -. DR jPOST; Q9BV94; -. DR MassIVE; Q9BV94; -. DR PaxDb; 9606-ENSP00000363616; -. DR PeptideAtlas; Q9BV94; -. DR ProteomicsDB; 79184; -. [Q9BV94-1] DR ProteomicsDB; 79185; -. [Q9BV94-2] DR Pumba; Q9BV94; -. DR Antibodypedia; 25993; 143 antibodies from 29 providers. DR DNASU; 55741; -. DR Ensembl; ENST00000374491.3; ENSP00000363615.2; ENSG00000088298.14. [Q9BV94-2] DR Ensembl; ENST00000374492.8; ENSP00000363616.3; ENSG00000088298.14. [Q9BV94-1] DR GeneID; 55741; -. DR KEGG; hsa:55741; -. DR MANE-Select; ENST00000374492.8; ENSP00000363616.3; NM_018217.3; NP_060687.2. DR UCSC; uc002xbo.3; human. [Q9BV94-1] DR AGR; HGNC:15877; -. DR ClinPGx; PA25747; -. DR CTD; 55741; -. DR DisGeNET; 55741; -. DR GeneCards; EDEM2; -. DR HGNC; HGNC:15877; EDEM2. DR HPA; ENSG00000088298; Low tissue specificity. DR MIM; 610302; gene. DR OpenTargets; ENSG00000088298; -. DR VEuPathDB; HostDB:ENSG00000088298; -. DR eggNOG; KOG2429; Eukaryota. DR GeneTree; ENSGT00940000159233; -. DR HOGENOM; CLU_003818_5_4_1; -. DR InParanoid; Q9BV94; -. DR OMA; HNYHRVW; -. DR OrthoDB; 8118055at2759; -. DR PAN-GO; Q9BV94; 3 GO annotations based on evolutionary models. DR PhylomeDB; Q9BV94; -. DR PathwayCommons; Q9BV94; -. DR Reactome; R-HSA-901032; ER Quality Control Compartment (ERQC). DR Reactome; R-HSA-9694548; Maturation of spike protein. DR SignaLink; Q9BV94; -. DR Agora; ENSG00000088298; -. DR BioGRID-ORCS; 55741; 18 hits in 1158 CRISPR screens. DR ChiTaRS; EDEM2; human. DR GeneWiki; EDEM2; -. DR GenomeRNAi; 55741; -. DR Pharos; Q9BV94; Tbio. DR PRO; PR:Q9BV94; -. DR Proteomes; UP000005640; Chromosome 20. DR RNAct; Q9BV94; protein. DR Bgee; ENSG00000088298; Expressed in granulocyte and 164 other cell types or tissues. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:ParkinsonsUK-UCL. DR GO; GO:0005788; C:endoplasmic reticulum lumen; IEA:UniProtKB-SubCell. DR GO; GO:0044322; C:endoplasmic reticulum quality control compartment; TAS:Reactome. DR GO; GO:0016020; C:membrane; IEA:InterPro. 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:0005975; P:carbohydrate metabolic process; IEA:InterPro. DR GO; GO:1904380; P:endoplasmic reticulum mannose trimming; IMP:ParkinsonsUK-UCL. DR GO; GO:0030968; P:endoplasmic reticulum unfolded protein response; IBA:GO_Central. DR GO; GO:0036503; P: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:0036510; P:trimming of terminal mannose on C branch; TAS:Reactome. DR GO; GO:0097466; P:ubiquitin-dependent glycoprotein ERAD pathway; IBA:GO_Central. DR GO; GO:0019082; P:viral protein processing; TAS:Reactome. DR FunFam; 1.50.10.10:FF:000015; 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; ER DEGRADATION-ENHANCING ALPHA-MANNOSIDASE-LIKE PROTEIN 2; 1. DR PANTHER; PTHR45679:SF6; 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; KW Proteomics identification; Reference proteome; Signal; KW Unfolded protein response. FT SIGNAL 1..21 FT /evidence="ECO:0000255" FT CHAIN 22..578 FT /note="ER degradation-enhancing alpha-mannosidase-like FT protein 2" FT /id="PRO_0000012086" FT REGION 517..557 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 538..548 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT CARBOHYD 90 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 112 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 289 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 450 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT VAR_SEQ 36..72 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:12975309, FT ECO:0000303|PubMed:14702039" FT /id="VSP_013183" FT VARIANT 456 FT /note="A -> T (in dbSNP:rs3746429)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_012165" FT VARIANT 510 FT /note="R -> Q (in dbSNP:rs6060248)" FT /id="VAR_055842" FT VARIANT 556 FT /note="L -> F (in dbSNP:rs1052056)" FT /id="VAR_055843" FT MUTAGEN 117 FT /note="E->Q: Loss of ERAD activity." FT /evidence="ECO:0000269|PubMed:25092655" FT CONFLICT 482 FT /note="P -> L (in Ref. 2; AAQ88943)" FT /evidence="ECO:0000305" FT CONFLICT 511 FT /note="S -> C (in Ref. 1; BAA91806)" FT /evidence="ECO:0000305" SQ SEQUENCE 578 AA; 64753 MW; EEEADA069C159759 CRC64; MPFRLLIPLG LLCALLPQHH GAPGPDGSAP DPAHYRERVK AMFYHAYDSY LENAFPFDEL RPLTCDGHDT WGSFSLTLID ALDTLLILGN VSEFQRVVEV LQDSVDFDID VNASVFETNI RVVGGLLSAH LLSKKAGVEV EAGWPCSGPL LRMAEEAARK LLPAFQTPTG MPYGTVNLLH GVNPGETPVT CTAGIGTFIV EFATLSSLTG DPVFEDVARV ALMRLWESRS DIGLVGNHID VLTGKWVAQD AGIGAGVDSY FEYLVKGAIL LQDKKLMAMF LEYNKAIRNY TRFDDWYLWV QMYKGTVSMP VFQSLEAYWP GLQSLIGDID NAMRTFLNYY TVWKQFGGLP EFYNIPQGYT VEKREGYPLR PELIESAMYL YRATGDPTLL ELGRDAVESI EKISKVECGF ATIKDLRDHK LDNRMESFFL AETVKYLYLL FDPTNFIHNN GSTFDAVITP YGECILGAGG YIFNTEAHPI DPAALHCCQR LKEEQWEVED LMREFYSLKR SRSKFQKNTV SSGPWEPPAR PGTLFSPENH DQARERKPAK QKVPLLSCPS QPFTSKLALL GQVFLDSS //