EDEM2_HUMAN
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 03-AUG-2022, entry version 182.
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}.
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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_001145025.1. [Q9BV94-2]
DR RefSeq; NP_060687.2; NM_018217.2. [Q9BV94-1]
DR AlphaFoldDB; Q9BV94; -.
DR SMR; Q9BV94; -.
DR BioGRID; 120859; 173.
DR IntAct; Q9BV94; 41.
DR STRING; 9606.ENSP00000363616; -.
DR CAZy; GH47; Glycoside Hydrolase Family 47.
DR GlyGen; Q9BV94; 4 sites.
DR iPTMnet; Q9BV94; -.
DR PhosphoSitePlus; Q9BV94; -.
DR BioMuta; EDEM2; -.
DR DMDM; 17368685; -.
DR EPD; Q9BV94; -.
DR jPOST; Q9BV94; -.
DR MassIVE; Q9BV94; -.
DR MaxQB; Q9BV94; -.
DR PaxDb; Q9BV94; -.
DR PeptideAtlas; Q9BV94; -.
DR PRIDE; Q9BV94; -.
DR ProteomicsDB; 79184; -. [Q9BV94-1]
DR ProteomicsDB; 79185; -. [Q9BV94-2]
DR Antibodypedia; 25993; 147 antibodies from 29 providers.
DR DNASU; 55741; -.
DR Ensembl; ENST00000374491.3; ENSP00000363615.2; ENSG00000088298.13. [Q9BV94-2]
DR Ensembl; ENST00000374492.8; ENSP00000363616.3; ENSG00000088298.13. [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 CTD; 55741; -.
DR DisGeNET; 55741; -.
DR GeneCards; EDEM2; -.
DR HGNC; HGNC:15877; EDEM2.
DR HPA; ENSG00000088298; Low tissue specificity.
DR MIM; 610302; gene.
DR neXtProt; NX_Q9BV94; -.
DR OpenTargets; ENSG00000088298; -.
DR PharmGKB; PA25747; -.
DR VEuPathDB; HostDB:ENSG00000088298; -.
DR eggNOG; KOG2429; Eukaryota.
DR GeneTree; ENSGT00940000159233; -.
DR HOGENOM; CLU_003818_5_4_1; -.
DR InParanoid; Q9BV94; -.
DR OMA; DWHLWVS; -.
DR OrthoDB; 434316at2759; -.
DR PhylomeDB; Q9BV94; -.
DR TreeFam; TF300807; -.
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 BioGRID-ORCS; 55741; 16 hits in 1080 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 162 other tissues.
DR Genevisible; Q9BV94; HS.
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; 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:0006986; P:response to unfolded protein; IEA:UniProtKB-KW.
DR GO; GO:0036511; P:trimming of first mannose on A branch; TAS:Reactome.
DR GO; GO:0036512; P:trimming of second mannose on A branch; TAS:Reactome.
DR GO; GO:0036509; P:trimming of terminal mannose on B branch; 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; IMP:ParkinsonsUK-UCL.
DR GO; GO:0019082; P:viral protein processing; TAS:Reactome.
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;
KW Reference proteome; Signal; 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 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
