GANAB_HUMAN
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 03-AUG-2022, entry version 197.
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)-alpha-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)-alpha-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)-alpha-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 alpha-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};
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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 AlphaFoldDB; Q14697; -.
DR SMR; Q14697; -.
DR BioGRID; 116802; 275.
DR ComplexPortal; CPX-6822; Glucosidase II complex.
DR IntAct; Q14697; 81.
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 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; Q14697; -.
DR PeptideAtlas; Q14697; -.
DR PRIDE; Q14697; -.
DR ProteomicsDB; 60137; -. [Q14697-1]
DR ProteomicsDB; 60138; -. [Q14697-2]
DR ProteomicsDB; 60139; -. [Q14697-3]
DR TopDownProteomics; Q14697-1; -. [Q14697-1]
DR Antibodypedia; 14863; 190 antibodies from 28 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 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; 100626at2759; -.
DR PhylomeDB; Q14697; -.
DR TreeFam; TF300337; -.
DR BioCyc; MetaCyc:HS01658-MON; -.
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; 77 hits in 1079 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 208 other tissues.
DR ExpressionAtlas; Q14697; baseline and differential.
DR Genevisible; Q14697; HS.
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:0004553; F:hydrolase activity, hydrolyzing O-glycosyl compounds; IBA:GO_Central.
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 Gene3D; 2.60.40.1180; -; 2.
DR InterPro; IPR011013; Gal_mutarotase_sf_dom.
DR InterPro; IPR000322; Glyco_hydro_31.
DR InterPro; IPR030458; Glyco_hydro_31_AS.
DR InterPro; IPR030459; Glyco_hydro_31_CS.
DR InterPro; IPR025887; Glyco_hydro_31_N_dom.
DR InterPro; IPR013780; Glyco_hydro_b.
DR InterPro; IPR017853; Glycoside_hydrolase_SF.
DR Pfam; PF13802; Gal_mutarotas_2; 1.
DR Pfam; PF01055; Glyco_hydro_31; 1.
DR SUPFAM; SSF51445; SSF51445; 1.
DR SUPFAM; SSF74650; SSF74650; 1.
DR PROSITE; PS00129; GLYCOSYL_HYDROL_F31_1; 1.
DR PROSITE; PS00707; GLYCOSYL_HYDROL_F31_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Direct protein sequencing; Disease variant;
KW Disulfide bond; Endoplasmic reticulum; Glycoprotein; Glycosidase;
KW Golgi apparatus; Hydrolase; Phosphoprotein; 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; unknown pathological significance;
FT no apparent effect on the endoplasmic reticulum
FT localization; 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 (likely benign variant; no effect on PKD1 and
FT PKD2 localization to the cell surface)"
FT /evidence="ECO:0000269|PubMed:27259053"
FT /id="VAR_077089"
FT VARIANT 309
FT /note="R -> C (likely benign variant; no effect on PKD1 and
FT PKD2 localization to 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; unknown pathological significance;
FT 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; unknown pathological significance; the
FT patient carried additional PKHD1 variant; the mutation
FT results in significantly reduced alpha-glucosidase
FT activity; 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; unknown pathological significance; no apparent
FT effect on the 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; unknown pathological significance; no apparent
FT effect on the endoplasmic reticulum localization;
FT 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; unknown pathological 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"
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
