ID GANAB_HUMAN Reviewed; 944 AA. AC Q14697; A6NC20; Q8WTS9; Q9P0X0; DT 05-JUL-2004, integrated into UniProtKB/Swiss-Prot. DT 05-JUL-2004, sequence version 3. DT 27-MAR-2024, entry version 206. DE RecName: Full=Neutral alpha-glucosidase AB; DE EC=3.2.1.207 {ECO:0000269|PubMed:10929008}; DE AltName: Full=Alpha-glucosidase 2; DE AltName: Full=Glucosidase II subunit alpha {ECO:0000303|PubMed:27259053}; DE Flags: Precursor; GN Name=GANAB {ECO:0000303|PubMed:28375157, ECO:0000312|HGNC:HGNC:4138}; GN Synonyms=G2AN, KIAA0088; 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 [MRNA] (ISOFORM 1), AND VARIANT TYR-850. RC TISSUE=Brain; RA Stuerzenhofecker B., Nguyenvan P., Soeling H.D.; RT "Sequence and analysis of the endoplasmic reticulum protein glucosidase RT II."; RL Submitted (JUL-1997) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, CATALYTIC ACTIVITY, RP ACTIVITY REGULATION, PATHWAY, MUTAGENESIS OF ASP-542, ACTIVE SITE, RP INTERACTION WITH PRKCSH, SUBCELLULAR LOCATION, AND ALTERNATIVE SPLICING. RX PubMed=10929008; DOI=10.1093/glycob/10.8.815; RA Pelletier M.F., Marcil A., Sevigny G., Jakob C.A., Tessier D.C., Chevet E., RA Menard R., Bergeron J.J.M., Thomas D.Y.; RT "The heterodimeric structure of glucosidase II is required for its RT activity, solubility, and localization in vivo."; RL Glycobiology 10:815-827(2000). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16554811; DOI=10.1038/nature04632; RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G., RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., RA Hattori M., Rogers J., Lander E.S., Sakaki Y.; RT "Human chromosome 11 DNA sequence and analysis including novel gene RT identification."; RL Nature 440:497-500(2006). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 2-944 (ISOFORM 1), AND VARIANT RP TYR-850. RC TISSUE=Bone marrow; RX PubMed=7788527; DOI=10.1093/dnares/2.1.37; RA Nagase T., Miyajima N., Tanaka A., Sazuka T., Seki N., Sato S., Tabata S., RA Ishikawa K., Kawarabayasi Y., Kotani H., Nomura N.; RT "Prediction of the coding sequences of unidentified human genes. III. The RT coding sequences of 40 new genes (KIAA0081-KIAA0120) deduced by analysis of RT cDNA clones from human cell line KG-1."; RL DNA Res. 2:37-43(1995). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND NUCLEOTIDE SEQUENCE RP [LARGE SCALE MRNA] OF 457-944 (ISOFORMS 1/2). RC TISSUE=Lymph, and Uterus; 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 PROTEIN SEQUENCE OF 915-929, AND IDENTIFICATION BY MASS SPECTROMETRY. RC TISSUE=Brain, and Cajal-Retzius cell; RA Lubec G., Afjehi-Sadat L.; RL Submitted (MAR-2007) to UniProtKB. RN [7] RP GLYCOSYLATION, AND TISSUE SPECIFICITY. RX PubMed=3881423; DOI=10.1016/s0021-9258(20)71234-2; RA Martiniuk F., Ellenbogen A., Hirschhorn R.; RT "Identity of neutral alpha-glucosidase AB and the glycoprotein processing RT enzyme glucosidase II. Biochemical and genetic studies."; RL J. Biol. Chem. 260:1238-1242(1985). RN [8] RP INTERACTION WITH PRKCSH. RX PubMed=8910335; DOI=10.1074/jbc.271.44.27509; RA Trombetta E.S., Simons J.F., Helenius A.; RT "Endoplasmic reticulum glucosidase II is composed of a catalytic subunit, RT conserved from yeast to mammals, and a tightly bound noncatalytic HDEL- RT containing subunit."; RL J. Biol. Chem. 271:27509-27516(1996). RN [9] RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS]. RC TISSUE=Melanoma; RX PubMed=17081065; DOI=10.1021/pr060363j; RA Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H., Mangini N.J., RA Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R., Yamagishi S., RA Shabanowitz J., Hearing V.J., Wu C., Appella E., Hunt D.F.; RT "Proteomic and bioinformatic characterization of the biogenesis and RT function of melanosomes."; RL J. Proteome Res. 5:3135-3144(2006). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-52, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [12] 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 [13] 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 [14] RP INVOLVEMENT IN PKD3, VARIANTS PKD3 ARG-383 AND LEU-400, VARIANT TRP-817, RP ALTERNATIVE SPLICING (ISOFORMS 1 AND 2), TISSUE SPECIFICITY, RP CHARACTERIZATION OF VARIANTS PKD3 ARG-383 AND LEU-400, CHARACTERIZATION OF RP VARIANTS ARG-95; ALA-232; CYS-309 AND TRP-817, AND FUNCTION. RX PubMed=27259053; DOI=10.1016/j.ajhg.2016.05.004; RG Genkyst Study Group, HALT Progression of Polycystic Kidney Disease Group; RG Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease; RA Porath B., Gainullin V.G., Cornec-Le Gall E., Dillinger E.K., Heyer C.M., RA Hopp K., Edwards M.E., Madsen C.D., Mauritz S.R., Banks C.J., Baheti S., RA Reddy B., Herrero J.I., Banales J.M., Hogan M.C., Tasic V., Watnick T.J., RA Chapman A.B., Vigneau C., Lavainne F., Audrezet M.P., Ferec C., Le Meur Y., RA Torres V.E., Harris P.C.; RT "Mutations in GANAB, encoding the glucosidase IIalpha subunit, cause RT autosomal-dominant polycystic kidney and liver disease."; RL Am. J. Hum. Genet. 98:1193-1207(2016). RN [15] RP VARIANTS ASN-785; TYR-850 AND 918-GLN--ARG-944 DEL, AND CHARACTERIZATION OF RP VARIANTS ASN-785 AND TYR-850. RX PubMed=28375157; DOI=10.1172/jci90129; RA Besse W., Dong K., Choi J., Punia S., Fedeles S.V., Choi M., RA Gallagher A.R., Huang E.B., Gulati A., Knight J., Mane S., Tahvanainen E., RA Tahvanainen P., Sanna-Cherchi S., Lifton R.P., Watnick T., Pei Y.P., RA Torres V.E., Somlo S.; RT "Isolated polycystic liver disease genes define effectors of polycystin-1 RT function."; RL J. Clin. Invest. 127:1772-1785(2017). RN [16] RP VARIANT PKD3 4-VAL-ALA-5 DEL, VARIANTS PRO-590; 815-ARG--ARG-944 DEL AND RP 864-ARG--ARG-944 DEL, AND SUBCELLULAR LOCATION. RX PubMed=33097077; DOI=10.1186/s13023-020-01585-4; RA van de Laarschot L.F.M., Te Morsche R.H.M., Hoischen A., Venselaar H., RA Roelofs H.M., Cnossen W.R., Banales J.M., Roepman R., Drenth J.P.H.; RT "Novel GANAB variants associated with polycystic liver disease."; RL Orphanet J. Rare Dis. 15:302-302(2020). CC -!- FUNCTION: Catalytic subunit of glucosidase II that cleaves sequentially CC the 2 innermost alpha-1,3-linked glucose residues from the CC Glc(2)Man(9)GlcNAc(2) oligosaccharide precursor of immature CC glycoproteins (PubMed:10929008). Required for PKD1/Polycystin-1 and CC PKD2/Polycystin-2 maturation and localization to the cell surface and CC cilia (PubMed:27259053). {ECO:0000269|PubMed:10929008, CC ECO:0000269|PubMed:27259053}. CC -!- CATALYTIC ACTIVITY: CC Reaction=H2O + N(4)-(alpha-D-Glc-(1->3)-alpha-D-Man-(1->2)-alpha-D-Man- CC (1->2)-alpha-D-Man-(1->3)-[alpha-D-Man-(1->2)-alpha-D-Man-(1->3)- CC [alpha-D-Man-(1->2)-alpha-D-Man-(1->6)]-alpha-D-Man-(1->6)]-beta-D- CC Man-(1->4)-beta-D-GlcNAc-(1->4)-beta-D-GlcNAc)-L-asparaginyl- CC [protein] = beta-D-glucose + N(4)-(alpha-D-Man-(1->2)-alpha-D-Man- CC (1->2)-alpha-D-Man-(1->3)-[alpha-D-Man-(1->2)-alpha-D-Man-(1->3)- CC [alpha-D-Man-(1->2)-alpha-D-Man-(1->6)]-alpha-D-Man-(1->6)]-beta-D- CC Man-(1->4)-beta-D-GlcNAc-(1->4)-beta-D-GlcNAc)-L-asparaginyl- CC [protein] (N-glucan mannose isomer 9A1,2,3B1,2,3); CC Xref=Rhea:RHEA:56000, Rhea:RHEA-COMP:14356, Rhea:RHEA-COMP:14357, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15903, ChEBI:CHEBI:59080, CC ChEBI:CHEBI:139493; EC=3.2.1.207; CC Evidence={ECO:0000269|PubMed:10929008}; CC -!- CATALYTIC ACTIVITY: CC Reaction=H2O + N(4)-(alpha-D-Glc-(1->3)-alpha-D-Glc-(1->3)-alpha-D-Man- CC (1->2)-alpha-D-Man-(1->2)-alpha-D-Man-(1->3)-[alpha-D-Man-(1->2)- CC alpha-D-Man-(1->3)-[alpha-D-Man-(1->2)-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] = beta-D-glucose + N(4)-(alpha-D-Glc-(1->3)- CC alpha-D-Man-(1->2)-alpha-D-Man-(1->2)-alpha-D-Man-(1->3)-[alpha-D- CC Man-(1->2)-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 beta-D-GlcNAc)-L-asparaginyl-[protein]; Xref=Rhea:RHEA:55996, CC Rhea:RHEA-COMP:14355, Rhea:RHEA-COMP:14357, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15903, ChEBI:CHEBI:59080, ChEBI:CHEBI:59082; CC EC=3.2.1.207; Evidence={ECO:0000269|PubMed:10929008}; CC -!- ACTIVITY REGULATION: Inhibited by deoxynojirimycin. CC {ECO:0000269|PubMed:10929008}. CC -!- PATHWAY: Glycan metabolism; N-glycan metabolism. CC {ECO:0000269|PubMed:10929008}. CC -!- SUBUNIT: Heterodimer of a catalytic alpha subunit (GANAB) and a beta CC subunit (PRKCSH) (PubMed:10929008). Binds glycosylated PTPRC (By CC similarity). {ECO:0000250|UniProtKB:Q8BHN3, CC ECO:0000269|PubMed:10929008}. CC -!- INTERACTION: CC Q14697-1; P14314: PRKCSH; NbExp=3; IntAct=EBI-11614043, EBI-716953; CC Q14697-2; P14314: PRKCSH; NbExp=2; IntAct=EBI-16399534, EBI-716953; CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum CC {ECO:0000269|PubMed:33097077, ECO:0000305|PubMed:10929008}. Golgi CC apparatus {ECO:0000250|UniProtKB:P79403}. Melanosome CC {ECO:0000269|PubMed:17081065}. Note=Identified by mass spectrometry in CC melanosome fractions from stage I to stage IV. CC {ECO:0000269|PubMed:17081065}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q14697-1; Sequence=Displayed; CC Name=2; CC IsoId=Q14697-2; Sequence=VSP_010674; CC Name=3; CC IsoId=Q14697-3; Sequence=VSP_039976, VSP_039977; CC -!- TISSUE SPECIFICITY: Detected in placenta (PubMed:3881423). Isoform 1 CC and isoform 2 are expressed in the kidney and liver (PubMed:27259053). CC {ECO:0000269|PubMed:27259053, ECO:0000269|PubMed:3881423}. CC -!- DISEASE: Polycystic kidney disease 3 with or without polycystic liver CC disease (PKD3) [MIM:600666]: A form of polycystic kidney disease, a CC disorder characterized by progressive formation and enlargement of CC cysts in both kidneys, typically leading to end-stage renal disease in CC adult life. Cysts also occur in other organs, particularly the liver. CC PKD3 inheritance is autosomal dominant. {ECO:0000269|PubMed:27259053, CC ECO:0000269|PubMed:33097077}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Note=GANAB variations may act as a disease modifier in CC autosomal dominant polycystic liver disease in patients who have CC causative mutations in other genes, such as PKHD1 or ALG8. CC {ECO:0000269|PubMed:28375157, ECO:0000269|PubMed:33097077}. CC -!- MISCELLANEOUS: [Isoform 3]: May be produced at very low levels due to a CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA CC decay. {ECO:0000305}. CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 31 family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH65266.1; Type=Erroneous translation; Note=Wrong choice of CDS.; 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; AJ000332; CAA04006.1; -; mRNA. DR EMBL; AF144074; AAF66685.1; -; mRNA. DR EMBL; AP001458; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; D42041; BAA07642.1; -; mRNA. DR EMBL; BC017433; AAH17433.2; -; mRNA. DR EMBL; BC017435; AAH17435.2; -; mRNA. DR EMBL; BC065266; AAH65266.1; ALT_SEQ; mRNA. DR CCDS; CCDS41656.1; -. [Q14697-2] DR CCDS; CCDS8026.1; -. [Q14697-1] DR RefSeq; NP_001265121.1; NM_001278192.1. DR RefSeq; NP_001265122.1; NM_001278193.1. DR RefSeq; NP_001265123.1; NM_001278194.1. DR RefSeq; NP_938148.1; NM_198334.2. [Q14697-1] DR RefSeq; NP_938149.2; NM_198335.3. [Q14697-2] DR PDB; 8D43; EM; 2.88 A; A=1-944. DR PDB; 8EMR; EM; 2.92 A; A=1-944. DR PDBsum; 8D43; -. DR PDBsum; 8EMR; -. DR AlphaFoldDB; Q14697; -. DR EMDB; EMD-27173; -. DR EMDB; EMD-28262; -. DR SMR; Q14697; -. DR BioGRID; 116802; 372. DR ComplexPortal; CPX-6822; Glucosidase II complex. DR IntAct; Q14697; 87. DR MINT; Q14697; -. DR STRING; 9606.ENSP00000340466; -. DR BindingDB; Q14697; -. DR ChEMBL; CHEMBL2519; -. DR DrugBank; DB00491; Miglitol. DR CAZy; GH31; Glycoside Hydrolase Family 31. DR GlyConnect; 1560; 2 N-Linked glycans (1 site). [Q14697-2] DR GlyCosmos; Q14697; 1 site, No reported glycans. DR GlyGen; Q14697; 2 sites, 1 O-linked glycan (1 site). DR iPTMnet; Q14697; -. DR MetOSite; Q14697; -. DR PhosphoSitePlus; Q14697; -. DR SwissPalm; Q14697; -. DR BioMuta; GANAB; -. DR DMDM; 54037162; -. DR REPRODUCTION-2DPAGE; IPI00383581; -. DR EPD; Q14697; -. DR jPOST; Q14697; -. DR MassIVE; Q14697; -. DR MaxQB; Q14697; -. DR PaxDb; 9606-ENSP00000340466; -. DR PeptideAtlas; Q14697; -. DR PRIDE; Q14697; -. DR ProteomicsDB; 60137; -. [Q14697-1] DR ProteomicsDB; 60138; -. [Q14697-2] DR ProteomicsDB; 60139; -. [Q14697-3] DR Pumba; Q14697; -. DR TopDownProteomics; Q14697-1; -. [Q14697-1] DR Antibodypedia; 14863; 229 antibodies from 29 providers. DR DNASU; 23193; -. DR Ensembl; ENST00000346178.8; ENSP00000340466.4; ENSG00000089597.18. [Q14697-2] DR Ensembl; ENST00000356638.8; ENSP00000349053.3; ENSG00000089597.18. [Q14697-1] DR Ensembl; ENST00000526210.1; ENSP00000433799.1; ENSG00000089597.18. [Q14697-3] DR Ensembl; ENST00000532402.5; ENSP00000432181.1; ENSG00000089597.18. [Q14697-3] DR Ensembl; ENST00000534613.5; ENSP00000434921.1; ENSG00000089597.18. [Q14697-3] DR GeneID; 23193; -. DR KEGG; hsa:23193; -. DR MANE-Select; ENST00000356638.8; ENSP00000349053.3; NM_198334.3; NP_938148.1. DR UCSC; uc001nua.5; human. [Q14697-1] DR AGR; HGNC:4138; -. DR CTD; 23193; -. DR DisGeNET; 23193; -. DR GeneCards; GANAB; -. DR GeneReviews; GANAB; -. DR HGNC; HGNC:4138; GANAB. DR HPA; ENSG00000089597; Low tissue specificity. DR MalaCards; GANAB; -. DR MIM; 104160; gene. DR MIM; 600666; phenotype. DR MIM; 617874; phenotype. DR neXtProt; NX_Q14697; -. DR OpenTargets; ENSG00000089597; -. DR Orphanet; 730; Autosomal dominant polycystic kidney disease. DR PharmGKB; PA28551; -. DR VEuPathDB; HostDB:ENSG00000089597; -. DR eggNOG; KOG1066; Eukaryota. DR GeneTree; ENSGT00940000159139; -. DR HOGENOM; CLU_3086528_0_0_1; -. DR InParanoid; Q14697; -. DR OMA; QAGIWYP; -. DR OrthoDB; 5480935at2759; -. DR PhylomeDB; Q14697; -. DR TreeFam; TF300337; -. DR BioCyc; MetaCyc:HS01658-MONOMER; -. DR BRENDA; 3.2.1.207; 2681. DR PathwayCommons; Q14697; -. DR Reactome; R-HSA-532668; N-glycan trimming in the ER and Calnexin/Calreticulin cycle. DR Reactome; R-HSA-901042; Calnexin/calreticulin cycle. DR Reactome; R-HSA-9683686; Maturation of spike protein. DR Reactome; R-HSA-9694548; Maturation of spike protein. DR SignaLink; Q14697; -. DR UniPathway; UPA00957; -. DR BioGRID-ORCS; 23193; 83 hits in 1166 CRISPR screens. DR ChiTaRS; GANAB; human. DR GeneWiki; GANAB; -. DR GenomeRNAi; 23193; -. DR Pharos; Q14697; Tchem. DR PRO; PR:Q14697; -. DR Proteomes; UP000005640; Chromosome 11. DR RNAct; Q14697; Protein. DR Bgee; ENSG00000089597; Expressed in stromal cell of endometrium and 210 other cell types or tissues. DR ExpressionAtlas; Q14697; baseline and differential. DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0017177; C:glucosidase II complex; IDA:UniProtKB. DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IMP:UniProtKB. DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:0090599; F:alpha-glucosidase activity; IDA:UniProtKB. DR GO; GO:0030246; F:carbohydrate binding; IEA:InterPro. DR GO; GO:0033919; F:glucan 1,3-alpha-glucosidase activity; IDA:UniProtKB. DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB. DR GO; GO:0005975; P:carbohydrate metabolic process; IEA:InterPro. DR GO; GO:0006491; P:N-glycan processing; IDA:UniProtKB. DR CDD; cd06603; GH31_GANC_GANAB_alpha; 1. DR CDD; cd14752; GH31_N; 1. DR Gene3D; 3.20.20.80; Glycosidases; 2. DR Gene3D; 2.60.40.1760; glycosyl hydrolase (family 31); 1. DR Gene3D; 2.60.40.1180; Golgi alpha-mannosidase II; 2. DR InterPro; IPR011013; Gal_mutarotase_sf_dom. DR InterPro; IPR030458; Glyco_hydro_31_AS. DR InterPro; IPR048395; Glyco_hydro_31_C. DR InterPro; IPR030459; Glyco_hydro_31_CS. DR InterPro; IPR025887; Glyco_hydro_31_N_dom. DR InterPro; IPR000322; Glyco_hydro_31_TIM. DR InterPro; IPR013780; Glyco_hydro_b. DR InterPro; IPR017853; Glycoside_hydrolase_SF. DR PANTHER; PTHR22762; ALPHA-GLUCOSIDASE; 1. DR PANTHER; PTHR22762:SF162; NEUTRAL ALPHA-GLUCOSIDASE AB; 1. DR Pfam; PF13802; Gal_mutarotas_2; 1. DR Pfam; PF01055; Glyco_hydro_31_2nd; 1. DR Pfam; PF21365; Glyco_hydro_31_3rd; 1. DR SUPFAM; SSF51445; (Trans)glycosidases; 1. DR SUPFAM; SSF74650; Galactose mutarotase-like; 1. DR SUPFAM; SSF51011; Glycosyl hydrolase domain; 1. DR PROSITE; PS00129; GLYCOSYL_HYDROL_F31_1; 1. DR PROSITE; PS00707; GLYCOSYL_HYDROL_F31_2; 1. DR Genevisible; Q14697; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Direct protein sequencing; KW Disease variant; Disulfide bond; Endoplasmic reticulum; Glycoprotein; KW Glycosidase; Golgi apparatus; Hydrolase; Phosphoprotein; KW Reference proteome; Signal. FT SIGNAL 1..28 FT /evidence="ECO:0000255" FT CHAIN 29..944 FT /note="Neutral alpha-glucosidase AB" FT /id="PRO_0000018571" FT REGION 181..238 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 196..234 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 542 FT /note="Nucleophile" FT /evidence="ECO:0000305|PubMed:10929008" FT ACT_SITE 618 FT /note="Proton donor" FT /evidence="ECO:0000250|UniProtKB:Q8BHN3" FT BINDING 283 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:Q8BHN3" FT BINDING 429 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:Q8BHN3" FT BINDING 602 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:Q8BHN3" FT BINDING 676 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:Q8BHN3" FT MOD_RES 52 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT CARBOHYD 97 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:3881423" FT DISULFID 41..47 FT /evidence="ECO:0000250|UniProtKB:Q8BHN3" FT DISULFID 633..644 FT /evidence="ECO:0000250|UniProtKB:Q8BHN3" FT VAR_SEQ 49..52 FT /note="RQRS -> CCWC (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_039976" FT VAR_SEQ 53..944 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_039977" FT VAR_SEQ 187 FT /note="S -> SFSDKVNLTLGSIWDKIKNLFSR (in isoform 2)" FT /evidence="ECO:0000303|PubMed:10929008" FT /id="VSP_010674" FT VARIANT 4..5 FT /note="Missing (in PKD3; uncertain significance; no FT apparent effect on the endoplasmic reticulum localization; FT dbSNP:rs750723025)" FT /evidence="ECO:0000269|PubMed:33097077" FT /id="VAR_085221" FT VARIANT 95 FT /note="Q -> R (no effect on PKD1 and PKD2 localization to FT the cell surface; dbSNP:rs1392032530)" FT /evidence="ECO:0000269|PubMed:27259053" FT /id="VAR_077088" FT VARIANT 154 FT /note="R -> W (in dbSNP:rs2276296)" FT /id="VAR_024529" FT VARIANT 173 FT /note="R -> Q (in dbSNP:rs2276295)" FT /id="VAR_022086" FT VARIANT 232 FT /note="T -> A (no effect on PKD1 and PKD2 localization to FT the cell surface)" FT /evidence="ECO:0000269|PubMed:27259053" FT /id="VAR_077089" FT VARIANT 309 FT /note="R -> C (no effect on PKD1 and PKD2 localization to FT the cell surface; dbSNP:rs1063445)" FT /evidence="ECO:0000269|PubMed:27259053" FT /id="VAR_050272" FT VARIANT 383 FT /note="T -> R (in PKD3; fails to promote PKD1 and PKD2 FT localization to the cell surface; dbSNP:rs879255642)" FT /evidence="ECO:0000269|PubMed:27259053" FT /id="VAR_077090" FT VARIANT 400 FT /note="R -> L (in PKD3; fails to promote PKD1 and PKD2 FT localization to the cell surface; dbSNP:rs770519542)" FT /evidence="ECO:0000269|PubMed:27259053" FT /id="VAR_077091" FT VARIANT 590 FT /note="R -> P (found in a patient with polycystic liver FT disease; uncertain significance; dbSNP:rs1465649718)" FT /evidence="ECO:0000269|PubMed:33097077" FT /id="VAR_085222" FT VARIANT 785 FT /note="H -> N (found in a patient affected by polycystic FT liver disease; uncertain significance; the patient carried FT additional PKHD1 variant; the mutation results in FT significantly reduced alpha-glucosidase activity; FT dbNP:rs753910059; dbSNP:rs753910059)" FT /evidence="ECO:0000269|PubMed:28375157" FT /id="VAR_080920" FT VARIANT 815..944 FT /note="Missing (found in a patient with polycystic liver FT disease; uncertain significance; no apparent effect on the FT endoplasmic reticulum localization)" FT /evidence="ECO:0000269|PubMed:33097077" FT /id="VAR_085223" FT VARIANT 817 FT /note="R -> W (in PKD3; fails to promote PKD1 and PKD2 FT localization to the cell surface; dbSNP:rs879255643)" FT /evidence="ECO:0000269|PubMed:27259053" FT /id="VAR_077092" FT VARIANT 850 FT /note="H -> Y (in dbSNP:rs114915323)" FT /evidence="ECO:0000269|PubMed:28375157, FT ECO:0000269|PubMed:7788527, ECO:0000269|Ref.1" FT /id="VAR_080921" FT VARIANT 864..944 FT /note="Missing (found in a patient with polycystic liver FT disease; uncertain significance; no apparent effect on the FT endoplasmic reticulum localization; dbSNP:rs1210158408)" FT /evidence="ECO:0000269|PubMed:33097077" FT /id="VAR_085224" FT VARIANT 918..944 FT /note="Missing (found in a patient affected by polycystic FT liver disease; uncertain significance)" FT /evidence="ECO:0000269|PubMed:28375157" FT /id="VAR_080922" FT MUTAGEN 542 FT /note="D->N: Loss of activity." FT /evidence="ECO:0000269|PubMed:10929008" FT CONFLICT 400 FT /note="R -> C (in Ref. 5; AAH65266)" FT /evidence="ECO:0000305" FT CONFLICT 461 FT /note="R -> W (in Ref. 5; AAH65266)" FT /evidence="ECO:0000305" FT HELIX 35..37 FT /evidence="ECO:0007829|PDB:8EMR" FT TURN 41..43 FT /evidence="ECO:0007829|PDB:8EMR" FT HELIX 45..51 FT /evidence="ECO:0007829|PDB:8EMR" FT STRAND 59..69 FT /evidence="ECO:0007829|PDB:8EMR" FT STRAND 74..80 FT /evidence="ECO:0007829|PDB:8EMR" FT TURN 81..83 FT /evidence="ECO:0007829|PDB:8EMR" FT STRAND 86..94 FT /evidence="ECO:0007829|PDB:8EMR" FT TURN 95..97 FT /evidence="ECO:0007829|PDB:8EMR" FT STRAND 98..107 FT /evidence="ECO:0007829|PDB:8EMR" FT STRAND 117..121 FT /evidence="ECO:0007829|PDB:8EMR" FT STRAND 129..133 FT /evidence="ECO:0007829|PDB:8EMR" FT STRAND 135..141 FT /evidence="ECO:0007829|PDB:8EMR" FT STRAND 143..152 FT /evidence="ECO:0007829|PDB:8EMR" FT TURN 153..156 FT /evidence="ECO:0007829|PDB:8EMR" FT STRAND 157..162 FT /evidence="ECO:0007829|PDB:8EMR" FT STRAND 165..174 FT /evidence="ECO:0007829|PDB:8EMR" FT STRAND 244..249 FT /evidence="ECO:0007829|PDB:8EMR" FT STRAND 255..258 FT /evidence="ECO:0007829|PDB:8EMR" FT STRAND 272..274 FT /evidence="ECO:0007829|PDB:8EMR" FT STRAND 277..279 FT /evidence="ECO:0007829|PDB:8EMR" FT STRAND 301..305 FT /evidence="ECO:0007829|PDB:8EMR" FT STRAND 310..315 FT /evidence="ECO:0007829|PDB:8EMR" FT STRAND 321..326 FT /evidence="ECO:0007829|PDB:8EMR" FT STRAND 352..360 FT /evidence="ECO:0007829|PDB:8EMR" FT STRAND 362..367 FT /evidence="ECO:0007829|PDB:8EMR" FT HELIX 372..383 FT /evidence="ECO:0007829|PDB:8EMR" FT HELIX 391..394 FT /evidence="ECO:0007829|PDB:8EMR" FT HELIX 406..418 FT /evidence="ECO:0007829|PDB:8EMR" FT STRAND 425..427 FT /evidence="ECO:0007829|PDB:8EMR" FT HELIX 430..432 FT /evidence="ECO:0007829|PDB:8EMR" FT TURN 443..445 FT /evidence="ECO:0007829|PDB:8EMR" FT HELIX 449..458 FT /evidence="ECO:0007829|PDB:8EMR" FT STRAND 462..466 FT /evidence="ECO:0007829|PDB:8EMR" FT STRAND 475..477 FT /evidence="ECO:0007829|PDB:8EMR" FT HELIX 478..486 FT /evidence="ECO:0007829|PDB:8EMR" FT STRAND 495..497 FT /evidence="ECO:0007829|PDB:8EMR" FT STRAND 503..505 FT /evidence="ECO:0007829|PDB:8EMR" FT HELIX 515..523 FT /evidence="ECO:0007829|PDB:8EMR" FT TURN 527..529 FT /evidence="ECO:0007829|PDB:8EMR" FT STRAND 537..540 FT /evidence="ECO:0007829|PDB:8EMR" FT TURN 544..546 FT /evidence="ECO:0007829|PDB:8EMR" FT STRAND 549..552 FT /evidence="ECO:0007829|PDB:8EMR" FT TURN 568..570 FT /evidence="ECO:0007829|PDB:8EMR" FT HELIX 572..574 FT /evidence="ECO:0007829|PDB:8EMR" FT HELIX 575..589 FT /evidence="ECO:0007829|PDB:8EMR" FT TURN 590..592 FT /evidence="ECO:0007829|PDB:8EMR" FT HELIX 608..610 FT /evidence="ECO:0007829|PDB:8EMR" FT HELIX 623..637 FT /evidence="ECO:0007829|PDB:8EMR" FT TURN 638..640 FT /evidence="ECO:0007829|PDB:8EMR" FT STRAND 651..653 FT /evidence="ECO:0007829|PDB:8EMR" FT HELIX 657..667 FT /evidence="ECO:0007829|PDB:8EMR" FT STRAND 679..681 FT /evidence="ECO:0007829|PDB:8EMR" FT TURN 686..688 FT /evidence="ECO:0007829|PDB:8EMR" FT HELIX 691..706 FT /evidence="ECO:0007829|PDB:8EMR" FT HELIX 708..721 FT /evidence="ECO:0007829|PDB:8EMR" FT STRAND 725..727 FT /evidence="ECO:0007829|PDB:8EMR" FT HELIX 729..732 FT /evidence="ECO:0007829|PDB:8EMR" FT HELIX 738..741 FT /evidence="ECO:0007829|PDB:8EMR" FT STRAND 746..748 FT /evidence="ECO:0007829|PDB:8EMR" FT TURN 749..751 FT /evidence="ECO:0007829|PDB:8EMR" FT STRAND 752..754 FT /evidence="ECO:0007829|PDB:8EMR" FT STRAND 763..769 FT /evidence="ECO:0007829|PDB:8EMR" FT STRAND 775..778 FT /evidence="ECO:0007829|PDB:8EMR" FT TURN 779..781 FT /evidence="ECO:0007829|PDB:8EMR" FT STRAND 784..794 FT /evidence="ECO:0007829|PDB:8EMR" FT STRAND 802..812 FT /evidence="ECO:0007829|PDB:8EMR" FT HELIX 822..825 FT /evidence="ECO:0007829|PDB:8EMR" FT STRAND 828..833 FT /evidence="ECO:0007829|PDB:8EMR" FT STRAND 838..846 FT /evidence="ECO:0007829|PDB:8EMR" FT STRAND 849..852 FT /evidence="ECO:0007829|PDB:8EMR" FT HELIX 853..856 FT /evidence="ECO:0007829|PDB:8EMR" FT STRAND 861..868 FT /evidence="ECO:0007829|PDB:8EMR" FT STRAND 871..878 FT /evidence="ECO:0007829|PDB:8EMR" FT STRAND 888..896 FT /evidence="ECO:0007829|PDB:8EMR" FT STRAND 903..906 FT /evidence="ECO:0007829|PDB:8EMR" FT STRAND 908..910 FT /evidence="ECO:0007829|PDB:8EMR" FT STRAND 917..920 FT /evidence="ECO:0007829|PDB:8EMR" FT TURN 921..924 FT /evidence="ECO:0007829|PDB:8EMR" FT STRAND 925..934 FT /evidence="ECO:0007829|PDB:8EMR" FT STRAND 940..943 FT /evidence="ECO:0007829|PDB:8EMR" SQ SEQUENCE 944 AA; 106874 MW; 9E3426FE9A016BF1 CRC64; MAAVAAVAAR RRRSWASLVL AFLGVCLGIT LAVDRSNFKT CEESSFCKRQ RSIRPGLSPY RALLDSLQLG PDSLTVHLIH EVTKVLLVLE LQGLQKNMTR FRIDELEPRR PRYRVPDVLV ADPPIARLSV SGRDENSVEL TMAEGPYKII LTARPFRLDL LEDRSLLLSV NARGLLEFEH QRAPRVSQGS KDPAEGDGAQ PEETPRDGDK PEETQGKAEK DEPGAWEETF KTHSDSKPYG PMSVGLDFSL PGMEHVYGIP EHADNLRLKV TEGGEPYRLY NLDVFQYELY NPMALYGSVP VLLAHNPHRD LGIFWLNAAE TWVDISSNTA GKTLFGKMMD YLQGSGETPQ TDVRWMSETG IIDVFLLLGP SISDVFRQYA SLTGTQALPP LFSLGYHQSR WNYRDEADVL EVDQGFDDHN LPCDVIWLDI EHADGKRYFT WDPSRFPQPR TMLERLASKR RKLVAIVDPH IKVDSGYRVH EELRNLGLYV KTRDGSDYEG WCWPGSAGYP DFTNPTMRAW WANMFSYDNY EGSAPNLFVW NDMNEPSVFN GPEVTMLKDA QHYGGWEHRD VHNIYGLYVH MATADGLRQR SGGMERPFVL ARAFFAGSQR FGAVWTGDNT AEWDHLKISI PMCLSLGLVG LSFCGADVGG FFKNPEPELL VRWYQMGAYQ PFFRAHAHLD TGRREPWLLP SQHNDIIRDA LGQRYSLLPF WYTLLYQAHR EGIPVMRPLW VQYPQDVTTF NIDDQYLLGD ALLVHPVSDS GAHGVQVYLP GQGEVWYDIQ SYQKHHGPQT LYLPVTLSSI PVFQRGGTIV PRWMRVRRSS ECMKDDPITL FVALSPQGTA QGELFLDDGH TFNYQTRQEF LLRRFSFSGN TLVSSSADPE GHFETPIWIE RVVIIGAGKP AAVVLQTKGS PESRLSFQHD PETSVLVLRK PGINVASDWS IHLR //