EDEM3_HUMAN
ID EDEM3_HUMAN Reviewed; 932 AA.
AC Q9BZQ6; B2RCH6; B7ZLZ2; Q0VGM5; Q5TEZ0; Q7L2Y5; Q9HCW1; Q9UFV7;
DT 16-NOV-2001, integrated into UniProtKB/Swiss-Prot.
DT 05-FEB-2008, sequence version 2.
DT 03-AUG-2022, entry version 173.
DE RecName: Full=ER degradation-enhancing alpha-mannosidase-like protein 3;
DE EC=3.2.1.113 {ECO:0000250|UniProtKB:P32906};
DE AltName: Full=Alpha-1,2-mannosidase EDEM3;
DE Flags: Precursor;
GN Name=EDEM3; Synonyms=C1orf22;
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=Placenta;
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 GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 78-319 AND 853-932 (ISOFORM 1).
RC TISSUE=Brain, and Lung;
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 NUCLEOTIDE SEQUENCE [MRNA] OF 27-932 (ISOFORM 1).
RX PubMed=11318611; DOI=10.1006/geno.2001.6500;
RA Sood R., Bonner T.I., Malakowska I., Stephan D.A., Robbins C.M.,
RA Connors T.D., Morgenbesser S.D., Su K., Faruque M.U., Pinkett H.,
RA Graham C., Baxevanis A.D., Klinger K.W., Landes G.M., Trent J.M.,
RA Carpten J.D.;
RT "Cloning and characterization of 13 novel transcripts and the human RGS8
RT gene from the 1q25 region encompassing the hereditary prostate cancer
RT (HPC1) locus.";
RL Genomics 73:211-222(2001).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 553-932 (ISOFORM 1), AND VARIANT
RP SER-820.
RC TISSUE=Testis;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [6]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-195.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [7]
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).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [10]
RP INVOLVEMENT IN CDG2V, FUNCTION, AND VARIANTS CDG2V GLY-61; 314-ARG--LEU-932
RP DEL; ASN-456 AND 469-TYR--LEU-932 DEL.
RX PubMed=34143952; DOI=10.1016/j.ajhg.2021.05.010;
RA Polla D.L., Edmondson A.C., Duvet S., March M.E., Sousa A.B., Lehman A.,
RA Niyazov D., van Dijk F., Demirdas S., van Slegtenhorst M.A., Kievit A.J.A.,
RA Schulz C., Armstrong L., Bi X., Rader D.J., Izumi K., Zackai E.H.,
RA de Franco E., Jorge P., Huffels S.C., Hommersom M., Ellard S.,
RA Lefeber D.J., Santani A., Hand N.J., van Bokhoven H., He M.,
RA de Brouwer A.P.M.;
RT "Bi-allelic variants in the ER quality-control mannosidase gene EDEM3 cause
RT a congenital disorder of glycosylation.";
RL Am. J. Hum. Genet. 108:1342-1349(2021).
CC -!- FUNCTION: Involved in endoplasmic reticulum-associated degradation
CC (ERAD). Accelerates the glycoprotein ERAD by proteasomes, by catalyzing
CC mannose trimming from Man8GlcNAc2 to Man7GlcNAc2 in the N-glycans
CC (PubMed:25092655). May also participate in mannose trimming from all
CC glycoproteins and not just misfolded ones targeted to ERAD
CC (PubMed:34143952). May have alpha 1,2-mannosidase activity (By
CC similarity). {ECO:0000250, ECO:0000269|PubMed:25092655,
CC ECO:0000269|PubMed:34143952}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4 H2O + N(4)-(alpha-D-Man-(1->2)-alpha-D-Man-(1->2)-alpha-D-
CC Man-(1->3)-[alpha-D-Man-(1->2)-alpha-D-Man-(1->3)-[alpha-D-Man-
CC (1->2)-alpha-D-Man-(1->6)]-alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-
CC beta-D-GlcNAc-(1->4)-alpha-D-GlcNAc)-L-asparaginyl-[protein] (N-
CC glucan mannose isomer 9A1,2,3B1,2,3) = 4 beta-D-mannose + N(4)-
CC (alpha-D-Man-(1->3)-[alpha-D-Man-(1->3)-[alpha-D-Man-(1->6)]-alpha-D-
CC Man-(1->6)]-beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-beta-D-GlcNAc)-L-
CC asparaginyl-[protein] (N-glucan mannose isomer 5A1,2);
CC Xref=Rhea:RHEA:56008, Rhea:RHEA-COMP:14356, Rhea:RHEA-COMP:14367,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:28563, ChEBI:CHEBI:59087,
CC ChEBI:CHEBI:139493; EC=3.2.1.113;
CC Evidence={ECO:0000250|UniProtKB:P32906};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3 H2O + N(4)-(alpha-D-Man-(1->2)-alpha-D-Man-(1->2)-alpha-D-
CC Man-(1->3)-[alpha-D-Man-(1->3)-[alpha-D-Man-(1->2)-alpha-D-Man-
CC (1->6)]-alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-
CC alpha-D-GlcNAc)-L-asparaginyl-[protein] (N-glucan mannose isomer
CC 8A1,2,3B1,3) = 3 beta-D-mannose + N(4)-(alpha-D-Man-(1->3)-[alpha-D-
CC Man-(1->3)-[alpha-D-Man-(1->6)]-alpha-D-Man-(1->6)]-beta-D-Man-
CC (1->4)-beta-D-GlcNAc-(1->4)-beta-D-GlcNAc)-L-asparaginyl-[protein]
CC (N-glucan mannose isomer 5A1,2); Xref=Rhea:RHEA:56028, Rhea:RHEA-
CC COMP:14358, Rhea:RHEA-COMP:14367, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:28563, ChEBI:CHEBI:59087, ChEBI:CHEBI:60628;
CC EC=3.2.1.113; Evidence={ECO:0000250|UniProtKB:P32906};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000250|UniProtKB:P45700};
CC -!- PATHWAY: Protein modification; protein glycosylation.
CC {ECO:0000250|UniProtKB:P32906}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum lumen {ECO:0000255|PROSITE-
CC ProRule:PRU10138}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9BZQ6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9BZQ6-2; Sequence=VSP_056375, VSP_056376;
CC -!- DOMAIN: Contains a protease-associated domain (PA) of unknown function.
CC -!- DISEASE: Congenital disorder of glycosylation 2V (CDG2V) [MIM:619493]:
CC A form of congenital disorder of glycosylation, a genetically
CC heterogeneous group of multisystem disorders caused by a defect in
CC glycoprotein biosynthesis and characterized by under-glycosylated serum
CC glycoproteins. Congenital disorders of glycosylation result in a wide
CC variety of clinical features, such as defects in the nervous system
CC development, psychomotor retardation, dysmorphic features, hypotonia,
CC coagulation disorders, and immunodeficiency. The broad spectrum of
CC features reflects the critical role of N-glycoproteins during embryonic
CC development, differentiation, and maintenance of cell functions. CDG2V
CC is an autosomal recessive form characterized by neurodevelopmental
CC delay and variable facial dysmorphic features.
CC {ECO:0000269|PubMed:34143952}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 47 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAG60613.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAG37573.1; Type=Erroneous initiation; Note=Truncated N-terminus.; 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; AK315118; BAG37573.1; ALT_INIT; mRNA.
DR EMBL; AL096819; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC016464; AAH16464.2; -; mRNA.
DR EMBL; BC105586; AAI05587.1; -; mRNA.
DR EMBL; BC144149; AAI44150.1; -; mRNA.
DR EMBL; AF288393; AAG60613.1; ALT_INIT; mRNA.
DR EMBL; AL117441; CAB55926.1; -; mRNA.
DR CCDS; CCDS1363.2; -. [Q9BZQ6-1]
DR PIR; T17236; T17236.
DR RefSeq; NP_001306889.1; NM_001319960.1.
DR RefSeq; NP_079467.3; NM_025191.3. [Q9BZQ6-1]
DR AlphaFoldDB; Q9BZQ6; -.
DR SMR; Q9BZQ6; -.
DR BioGRID; 123207; 170.
DR IntAct; Q9BZQ6; 17.
DR MINT; Q9BZQ6; -.
DR STRING; 9606.ENSP00000318147; -.
DR CAZy; GH47; Glycoside Hydrolase Family 47.
DR GlyConnect; 1220; 4 N-Linked glycans (1 site).
DR GlyGen; Q9BZQ6; 8 sites, 4 N-linked glycans (1 site).
DR iPTMnet; Q9BZQ6; -.
DR PhosphoSitePlus; Q9BZQ6; -.
DR BioMuta; EDEM3; -.
DR DMDM; 166897965; -.
DR EPD; Q9BZQ6; -.
DR jPOST; Q9BZQ6; -.
DR MassIVE; Q9BZQ6; -.
DR MaxQB; Q9BZQ6; -.
DR PaxDb; Q9BZQ6; -.
DR PeptideAtlas; Q9BZQ6; -.
DR PRIDE; Q9BZQ6; -.
DR ProteomicsDB; 7240; -.
DR ProteomicsDB; 79892; -. [Q9BZQ6-1]
DR Antibodypedia; 20607; 131 antibodies from 25 providers.
DR DNASU; 80267; -.
DR Ensembl; ENST00000318130.13; ENSP00000318147.7; ENSG00000116406.20. [Q9BZQ6-1]
DR GeneID; 80267; -.
DR KEGG; hsa:80267; -.
DR MANE-Select; ENST00000318130.13; ENSP00000318147.7; NM_025191.4; NP_079467.3.
DR UCSC; uc010pok.3; human. [Q9BZQ6-1]
DR CTD; 80267; -.
DR DisGeNET; 80267; -.
DR GeneCards; EDEM3; -.
DR HGNC; HGNC:16787; EDEM3.
DR HPA; ENSG00000116406; Low tissue specificity.
DR MIM; 610214; gene.
DR MIM; 619493; phenotype.
DR neXtProt; NX_Q9BZQ6; -.
DR OpenTargets; ENSG00000116406; -.
DR PharmGKB; PA38186; -.
DR VEuPathDB; HostDB:ENSG00000116406; -.
DR eggNOG; KOG2430; Eukaryota.
DR GeneTree; ENSGT00940000159391; -.
DR HOGENOM; CLU_003818_4_1_1; -.
DR InParanoid; Q9BZQ6; -.
DR OMA; RRWDRRE; -.
DR OrthoDB; 434316at2759; -.
DR PhylomeDB; Q9BZQ6; -.
DR TreeFam; TF300807; -.
DR PathwayCommons; Q9BZQ6; -.
DR Reactome; R-HSA-901032; ER Quality Control Compartment (ERQC).
DR SignaLink; Q9BZQ6; -.
DR UniPathway; UPA00378; -.
DR BioGRID-ORCS; 80267; 15 hits in 1088 CRISPR screens.
DR ChiTaRS; EDEM3; human.
DR GeneWiki; EDEM3; -.
DR GenomeRNAi; 80267; -.
DR Pharos; Q9BZQ6; Tbio.
DR PRO; PR:Q9BZQ6; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q9BZQ6; protein.
DR Bgee; ENSG00000116406; Expressed in pylorus and 194 other tissues.
DR ExpressionAtlas; Q9BZQ6; baseline and differential.
DR Genevisible; Q9BZQ6; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; IBA:GO_Central.
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:0004559; F:alpha-mannosidase activity; IBA:GO_Central.
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:0006486; P:protein glycosylation; IEA:UniProtKB-UniPathway.
DR GO; GO:0006986; P:response to unfolded protein; IEA:UniProtKB-KW.
DR CDD; cd02126; PA_EDEM3_like; 1.
DR Gene3D; 1.50.10.10; -; 1.
DR InterPro; IPR012341; 6hp_glycosidase-like_sf.
DR InterPro; IPR044674; EDEM1/2/3.
DR InterPro; IPR037322; EDEM3_PA.
DR InterPro; IPR001382; Glyco_hydro_47.
DR InterPro; IPR003137; PA_domain.
DR InterPro; IPR036026; Seven-hairpin_glycosidases.
DR PANTHER; PTHR45679; PTHR45679; 1.
DR Pfam; PF01532; Glyco_hydro_47; 1.
DR Pfam; PF02225; PA; 1.
DR PRINTS; PR00747; GLYHDRLASE47.
DR SUPFAM; SSF48225; SSF48225; 1.
DR PROSITE; PS00014; ER_TARGET; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Congenital disorder of glycosylation;
KW Endoplasmic reticulum; Glycoprotein; Hydrolase; Metal-binding;
KW Reference proteome; Signal; Unfolded protein response.
FT SIGNAL 1..41
FT /evidence="ECO:0000255"
FT CHAIN 42..932
FT /note="ER degradation-enhancing alpha-mannosidase-like
FT protein 3"
FT /id="PRO_0000210323"
FT DOMAIN 674..779
FT /note="PA"
FT REGION 790..908
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 929..932
FT /note="Prevents secretion from ER"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10138"
FT COMPBIAS 807..905
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 146
FT /note="Proton donor"
FT /evidence="ECO:0000250"
FT ACT_SITE 293
FT /evidence="ECO:0000250"
FT ACT_SITE 387
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:P31723"
FT ACT_SITE 405
FT /evidence="ECO:0000250"
FT BINDING 491
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P32906"
FT CARBOHYD 118
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 195
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT CARBOHYD 504
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 511
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 810
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 814
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 900
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..43
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_056375"
FT VAR_SEQ 796..797
FT /note="RD -> RAAILKGKMIPSYIINSN (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_056376"
FT VARIANT 61
FT /note="D -> G (in CDG2V; unknown pathological significance;
FT dbSNP:rs777353823)"
FT /evidence="ECO:0000269|PubMed:34143952"
FT /id="VAR_086113"
FT VARIANT 314..932
FT /note="Missing (in CDG2V; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:34143952"
FT /id="VAR_086114"
FT VARIANT 456
FT /note="D -> N (in CDG2V; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:34143952"
FT /id="VAR_086115"
FT VARIANT 469..932
FT /note="Missing (in CDG2V; unknown pathological
FT significance; dbSNP:rs902837579)"
FT /evidence="ECO:0000269|PubMed:34143952"
FT /id="VAR_086116"
FT VARIANT 820
FT /note="I -> S (in dbSNP:rs9425343)"
FT /evidence="ECO:0000269|PubMed:17974005"
FT /id="VAR_059306"
FT CONFLICT 276
FT /note="I -> T (in Ref. 1; BAG37573)"
FT /evidence="ECO:0000305"
FT CONFLICT 318..319
FT /note="HY -> VS (in Ref. 4; AAI05587)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 932 AA; 104664 MW; 3C040FDF48284D36 CRC64;
MSEAGGRGCG SPVPQRARWR LVAATAAFCL VSATSVWTAG AEPMSREEKQ KLGNQVLEMF
DHAYGNYMEH AYPADELMPL TCRGRVRGQE PSRGDVDDAL GKFSLTLIDS LDTLVVLNKT
KEFEDAVRKV LRDVNLDNDV VVSVFETNIR VLGGLLGGHS LAIMLKEKGE YMQWYNDELL
QMAKQLGYKL LPAFNTTSGL PYPRINLKFG IRKPEARTGT ETDTCTACAG TLILEFAALS
RFTGATIFEE YARKALDFLW EKRQRSSNLV GVTINIHTGD WVRKDSGVGA GIDSYYEYLL
KAYVLLGDDS FLERFNTHYD AIMRYISQPP LLLDVHIHKP MLNARTWMDA LLAFFPGLQV
LKGDIRPAIE THEMLYQVIK KHNFLPEAFT TDFRVHWAQH PLRPEFAEST YFLYKATGDP
YYLEVGKTLI ENLNKYARVP CGFAAMKDVR TGSHEDRMDS FFLAEMFKYL YLLFADKEDI
IFDIEDYIFT TEAHLLPLWL STTNQSISKK NTTSEYTELD DSNFDWTCPN TQILFPNDPL
YAQSIREPLK NVVDKSCPRG IIRVEESFRS GAKPPLRARD FMATNPEHLE ILKKMGVSLI
HLKDGRVQLV QHAIQAASSI DAEDGLRFMQ EMIELSSQQQ KEQQLPPRAV QIVSHPFFGR
VVLTAGPAQF GLDLSKHKET RGFVASSKPS NGCSELTNPE AVMGKIALIQ RGQCMFAEKA
RNIQNAGAIG GIVIDDNEGS SSDTAPLFQM AGDGKDTDDI KIPMLFLFSK EGSIILDAIR
EYEEVEVLLS DKAKDRDPEM ENEEQPSSEN DSQNQSGEQI SSSSQEVDLV DQESSEENSL
NSHPESLSLA DMDNAASISP SEQTSNPTEN HETTNLNGEC TDLDNQLQEQ SETEEDSNPN
VSWGKKVQPI DSILADWNED IEAFEMMEKD EL
