ID LYAG_HUMAN Reviewed; 952 AA. AC P10253; Q09GN4; Q14351; Q16302; Q8IWE7; DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot. DT 11-JAN-2011, sequence version 4. DT 04-NOV-2026, entry version 256. DE RecName: Full=Lysosomal alpha-glucosidase; DE EC=3.2.1.20 {ECO:0000269|PubMed:18429042, ECO:0000269|PubMed:1856189, ECO:0000269|PubMed:29061980, ECO:0000269|PubMed:7717400}; DE AltName: Full=Acid maltase; DE AltName: Full=Aglucosidase alfa; DE Contains: DE RecName: Full=76 kDa lysosomal alpha-glucosidase; DE Contains: DE RecName: Full=70 kDa lysosomal alpha-glucosidase; DE Flags: Precursor; GN Name=GAA; 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], PROTEIN SEQUENCE OF 70-89; 123-145; 204-215; RP 230-249; 332-345; 349-370; 394-409; 480-513; 520-545; 703-719; 726-731 AND RP 795-803, AND VARIANTS ARG-199; HIS-223 AND ILE-780. RC TISSUE=Placenta, Testis, and Urine; RX PubMed=3049072; DOI=10.1002/j.1460-2075.1988.tb02998.x; RA Hoefsloot L.H., Hoogeveen-Westerveld M., Kroos M.A., van Beeumen J., RA Reuser A.J.J., Oostra B.A.; RT "Primary structure and processing of lysosomal alpha-glucosidase; homology RT with the intestinal sucrase-isomaltase complex."; RL EMBO J. 7:1697-1704(1988). RN [2] RP SEQUENCE REVISION. RA Reuser A.J.J.; RL Submitted (JUN-1990) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ILE-780. RX PubMed=2268276; DOI=10.1042/bj2720493; RA Hoefsloot L.H., Hoogeveen-Westerveld M., Reuser A.J.J., Oostra B.A.; RT "Characterization of the human lysosomal alpha-glucosidase gene."; RL Biochem. J. 272:493-497(1990). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT ILE-780. RX PubMed=2111708; DOI=10.1089/dna.1990.9.85; RA Martiniuk F., Mehler M., Tzall S., Meredith G., Hirschhorn R.; RT "Sequence of the cDNA and 5'-flanking region for human acid alpha- RT glucosidase, detection of an intron in the 5' untranslated leader sequence, RT definition of 18-bp polymorphisms, and differences with previous cDNA and RT amino acid sequences."; RL DNA Cell Biol. 9:85-94(1990). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA], VARIANT LOPD LEU-457, AND VARIANTS ARG-199; RP HIS-223 AND ILE-780. RA Ghaffari S.R., Sabokbar T., Tahmasebi S., Dastan J.; RT "Identification of a novel mutation in the acid alpha glucosidase gene RT causing juvenile form of Pompe disease in Iranian population."; RL Submitted (AUG-2006) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16625196; DOI=10.1038/nature04689; RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.; RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the RT human lineage."; RL Nature 440:1045-1049(2006). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Duodenum; 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 [8] RP NUCLEOTIDE SEQUENCE [MRNA] OF 631-680, AND VARIANT IOPD HIS-645. RX PubMed=7695647; DOI=10.1006/bbrc.1995.1418; RA Lin C.-Y., Shieh J.-J.; RT "Identification of a de novo point mutation resulting in infantile form of RT Pompe's disease."; RL Biochem. Biophys. Res. Commun. 208:886-893(1995). RN [9] RP FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF TRP-516 AND ASP-518, AND RP ACTIVE SITE. RX PubMed=1856189; DOI=10.1016/s0021-9258(18)92727-4; RA Hermans M.M.P., Kroos M.A., van Beeumen J., Oostra B.A., Reuser A.J.J.; RT "Human lysosomal alpha-glucosidase. Characterization of the catalytic RT site."; RL J. Biol. Chem. 266:13507-13512(1991). RN [10] RP GLYCOSYLATION AT ASN-140; ASN-233; ASN-390; ASN-470; ASN-652; ASN-882 AND RP ASN-925. RX PubMed=8435067; DOI=10.1042/bj2890681; RA Hermans M.M.P., Wisselaar H.A., Kroos M.A., Oostra B.A., Reuser A.J.J.; RT "Human lysosomal alpha-glucosidase: functional characterization of the RT glycosylation sites."; RL Biochem. J. 289:681-686(1993). RN [11] RP GLYCOSYLATION AT ASN-470. RX PubMed=12754519; DOI=10.1038/nbt827; RA Zhang H., Li X.-J., Martin D.B., Aebersold R.; RT "Identification and quantification of N-linked glycoproteins using RT hydrazide chemistry, stable isotope labeling and mass spectrometry."; RL Nat. Biotechnol. 21:660-666(2003). RN [12] RP REVIEW ON VARIANTS. RX PubMed=7603530; DOI=10.1002/mus.880181414; RA Reuser A.J.J., Kroos M.A., Hermans M.M.P., Bijvoet A.G.A., Verbeet M.P., RA van Diggelen O.P., Kleijer W.J., van der Ploeg A.T.; RT "Glycogenosis type II (acid maltase deficiency)."; RL Muscle Nerve 3:S61-S69(1995). RN [13] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-390. RC TISSUE=Plasma; RX PubMed=16335952; DOI=10.1021/pr0502065; RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., RA Smith R.D.; RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction, RT hydrazide chemistry, and mass spectrometry."; RL J. Proteome Res. 4:2070-2080(2005). RN [14] RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS]. RC TISSUE=Placenta; RX PubMed=17897319; DOI=10.1111/j.1600-0854.2007.00643.x; RA Schroeder B., Wrocklage C., Pan C., Jaeger R., Koesters B., Schaefer H., RA Elsaesser H.-P., Mann M., Hasilik A.; RT "Integral and associated lysosomal membrane proteins."; RL Traffic 8:1676-1686(2007). RN [15] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-140; ASN-470; ASN-882 AND RP ASN-925. 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 [16] 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 [17] 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 [18] 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 [19] {ECO:0007744|PDB:5KZW, ECO:0007744|PDB:5KZX} RP X-RAY CRYSTALLOGRAPHY, GLYCOSYLATION AT ASN-140; ASN-233; ASN-390; ASN-470; RP ASN-652 AND ASN-882, AND DISULFIDE BONDS. RA Deming D.T., Garman S.C.; RT "The structure of human GAA: structural basis of Pompe disease."; RL Submitted (JUL-2016) to the PDB data bank. RN [20] {ECO:0007744|PDB:5NN3, ECO:0007744|PDB:5NN4, ECO:0007744|PDB:5NN5, ECO:0007744|PDB:5NN6, ECO:0007744|PDB:5NN8} RP X-RAY CRYSTALLOGRAPHY IN COMPLEXES WITH SUBSTRATE ANALOGS, FUNCTION, RP CATALYTIC ACTIVITY, GLYCOSYLATION AT ASN-140; ASN-233; ASN-390; ASN-470; RP ASN-652 AND ASN-882, AND DISULFIDE BONDS. RX PubMed=29061980; DOI=10.1038/s41467-017-01263-3; RA Roig-Zamboni V., Cobucci-Ponzano B., Iacono R., Ferrara M.C., Germany S., RA Bourne Y., Parenti G., Moracci M., Sulzenbacher G.; RT "Structure of human lysosomal acid alpha-glucosidase-a guide for the RT treatment of Pompe disease."; RL Nat. Commun. 8:1111-1111(2017). RN [21] RP VARIANT ASN-91. RX PubMed=2203258; RA Martiniuk F., Bodkin M., Tzall S., Hirschhorn R.; RT "Identification of the base-pair substitution responsible for a human acid RT alpha glucosidase allele with lower 'affinity' for glycogen (GAA 2) and RT transient gene expression in deficient cells."; RL Am. J. Hum. Genet. 47:440-445(1990). RN [22] RP VARIANT IOPD THR-318. RX PubMed=1652892; RA Zhong N., Martiniuk F., Tzall S., Hirschhorn R.; RT "Identification of a missense mutation in one allele of a patient with RT Pompe disease, and use of endonuclease digestion of PCR-amplified RNA to RT demonstrate lack of mRNA expression from the second allele."; RL Am. J. Hum. Genet. 49:635-645(1991). RN [23] RP VARIANT IOPD LYS-521. RX PubMed=1898413; DOI=10.1016/0006-291x(91)91906-s; RA Hermans M.M.P., de Graaff E., Kroos M.A., Wisselaar H.A., Oostra B.A., RA Reuser A.J.J.; RT "Identification of a point mutation in the human lysosomal alpha- RT glucosidase gene causing infantile glycogenosis type II."; RL Biochem. Biophys. Res. Commun. 179:919-926(1991). RN [24] RP VARIANTS LOPD ARG-643 AND TRP-725. RX PubMed=8401535; DOI=10.1002/humu.1380020406; RA Hermans M.M.P., Kroos M.A., de Graaff E., Oostra B.A., Reuser A.J.J.; RT "Two mutations affecting the transport and maturation of lysosomal alpha- RT glucosidase in an adult case of glycogen storage disease type II."; RL Hum. Mutat. 2:268-273(1993). RN [25] RP VARIANT LOPD GLU-645, AND VARIANTS ILE-816 AND ILE-927. RX PubMed=8094613; DOI=10.1042/bj2890687; RA Hermans M.M.P., de Graaff E., Kroos M.A., Wisselaar H.A., Willemsen R., RA Oostra B.A., Reuser A.J.J.; RT "The conservative substitution Asp-645-->Glu in lysosomal alpha-glucosidase RT affects transport and phosphorylation of the enzyme in an adult patient RT with glycogen-storage disease type II."; RL Biochem. J. 289:687-693(1993). RN [26] RP VARIANT LOPD GLU-645, AND VARIANTS ILE-816 AND ILE-927. RX PubMed=1684505; DOI=10.1089/dna.1991.10.681; RA Martiniuk F., Mehler M., Bodkin M., Tzall S., Hirschhorn K., Zhong N., RA Hirschhorn R.; RT "Identification of a missense mutation in an adult-onset patient with RT glycogenosis type II expressing only one allele."; RL DNA Cell Biol. 10:681-687(1991). RN [27] RP VARIANTS ILE-816 AND ILE-927. RX PubMed=8486380; DOI=10.1006/geno.1993.1185; RA Hermans M.M.P., Svetkey L.P., Oostra B.A., Chen Y.T., Reuser A.J.J.; RT "The loss of a polymorphic glycosylation site caused by Thr-927-->Ile is RT linked to a second polymorphic Val-816-->Ile substitution in lysosomal RT alpha-glucosidase of American blacks."; RL Genomics 16:300-301(1993). RN [28] RP VARIANT IOPD VAL-519. RX PubMed=7866409; DOI=10.1002/humu.1380040410; RA Huie M.L., Hirschhorn R., Chen A.S., Martiniuk F., Zhong N.; RT "Mutation at the catalytic site (M519V) in glycogen storage disease type II RT (Pompe disease)."; RL Hum. Mutat. 4:291-293(1994). RN [29] RP VARIANT IOPD TRP-647. RX PubMed=7981676; DOI=10.1093/hmg/3.7.1081; RA Huie M.L., Chen A.S., Brooks S.S., Grix A., Hirschhorn R.; RT "A de novo 13 nt deletion, a newly identified C647W missense mutation and a RT deletion of exon 18 in infantile onset glycogen storage disease type II RT (GSDII)."; RL Hum. Mol. Genet. 3:1081-1087(1994). RN [30] RP VARIANT LOPD LEU-545. RX PubMed=7881422; DOI=10.1093/hmg/3.12.2213; RA Hermans M.M.P., de Graaff E., Kroos M.A., Mohkamsing S., Eussen B.J., RA Joosse M., Willemsen R., Kleijer W.J., Oostra B.A., Reuser A.J.J.; RT "The effect of a single base pair deletion (delta T525) and a C1634T RT missense mutation (Pro545Leu) on the expression of lysosomal alpha- RT glucosidase in patients with glycogen storage disease type II."; RL Hum. Mol. Genet. 3:2213-2218(1994). RN [31] RP VARIANTS IOPD ARG-299 AND LYS-903 DEL, VARIANTS ARG-199; HIS-223 AND RP ILE-780, FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=7717400; RA Boerkoel C.F., Exelbert R., Nicastri C., Nichols R.C., Miller F.W., RA Plotz P.H., Raben N.; RT "Leaky splicing mutation in the acid maltase gene is associated with RT delayed onset of glycogenosis type II."; RL Am. J. Hum. Genet. 56:887-897(1995). RN [32] RP VARIANT LYS-689. RX PubMed=8912788; DOI=10.1111/j.1469-1809.1996.tb00433.x; RA Huie M.L., Menaker M., McAlpine P.J., Hirschhorn R.; RT "Identification of an E689K substitution as the molecular basis of the RT human acid alpha-glucosidase type 4 allozyme (GAA*4)."; RL Ann. Hum. Genet. 60:365-368(1996). RN [33] RP VARIANT LOPD VAL-529. RX PubMed=8834250; DOI=10.1007/bf02267074; RA Tsunoda H., Ohshima T., Tohyama J., Sasaki M., Sakuragawa N., Martiniuk F.; RT "Acid alpha-glucosidase deficiency: identification and expression of a RT missense mutation (S529V) in a Japanese adult phenotype."; RL Hum. Genet. 97:496-499(1996). RN [34] RP VARIANT IOPD ASP-949. RX PubMed=9529346; DOI=10.1086/301788; RA Becker J.A., Vlach J., Raben N., Nagaraju K., Adams E.M., Hermans M.M., RA Reuser A.J., Brooks S.S., Tifft C.J., Hirschhorn R., Huie M.L., RA Nicolino M., Plotz P.H.; RT "The African origin of the common mutation in African American patients RT with glycogen-storage disease type II."; RL Am. J. Hum. Genet. 62:991-994(1998). RN [35] RP VARIANTS IOPD ASN-645 AND TRP-647, AND VARIANTS LOPD SER-648; GLN-672 AND RP TRP-672. RX PubMed=9535769; DOI=10.1006/bbrc.1998.8255; RA Huie M.L., Tsujino S., Brooks S.S., Engel A., Elias E., Bonthron D.T., RA Bessley C., Shanske S., Dimauro S., Goto Y., Hirschhorn R.; RT "Glycogen storage disease type II: identification of four novel missense RT mutations (D645N, G648S, R672W, R672Q) and two insertions/deletions in the RT acid alpha-glucosidase locus of patients of differing phenotype."; RL Biochem. Biophys. Res. Commun. 244:921-927(1998). RN [36] RP VARIANT IOPD ARG-309. RX PubMed=9660056; DOI=10.1111/j.1399-0004.1998.tb02749.x; RA Kroos M.A., van Leenen D., Verbiest J., Reuser A.J.J., Hermans M.M.P.; RT "Glycogen storage disease type II: identification of a dinucleotide RT deletion and a common missense mutation in the lysosomal alpha-glucosidase RT gene."; RL Clin. Genet. 53:379-382(1998). RN [37] RP VARIANTS IOPD PRO-566; ARG-643 AND ARG-768, AND VARIANTS ASN-91; ARG-199 RP AND HIS-223. RX PubMed=9521422; RX DOI=10.1002/(sici)1098-1004(1998)11:3<209::aid-humu5>3.0.co;2-c; RA Hermans M.M.P., Kroos M.A., Smeitink J.A.M., van der Ploeg A.T., RA Kleijer W.J., Reuser A.J.J.; RT "Glycogen storage disease type II: genetic and biochemical analysis of RT novel mutations in infantile patients from Turkish ancestry."; RL Hum. Mutat. 11:209-215(1998). RN [38] RP VARIANT IOPD GLY-VAL-PRO-VAL-SER-ASN-925 INS. RX PubMed=10206684; RX DOI=10.1002/(sici)1098-1004(1998)11:5<413::aid-humu16>3.0.co;2-i; RA Beesley C.E., Child A.H., Yacoub M.Y.; RT "The identification of five novel mutations in the lysosomal acid alpha- RT (1,4) glucosidase gene from patients with glycogen storage disease type RT II."; RL Hum. Mutat. 11:413-413(1998). RN [39] RP VARIANTS LOPD LEU-545 AND TRP-638. RX PubMed=10737124; DOI=10.1007/s100480050030; RA Vorgerd M., Burwinkel B., Reichmann H., Malin J.-P., Kilimann M.W.; RT "Adult-onset glycogen storage disease type II: phenotypic and allelic RT heterogeneity in German patients."; RL Neurogenetics 1:205-211(1998). RN [40] RP VARIANT IOPD ARG-481. RX PubMed=10189220; RX DOI=10.1002/(sici)1098-1004(1999)13:1<83::aid-humu13>3.0.co;2-2; RA Raben N., Lee E., Lee L., Hirschhorn R., Plotz P.H.; RT "Novel mutations in African American patients with glycogen storage disease RT Type II."; RL Hum. Mutat. 13:83-84(1999). RN [41] RP VARIANTS IOPD HIS-600 AND ASN-675 DEL, AND VARIANT LOPD ARG-615. RX PubMed=10338092; RX DOI=10.1002/(sici)1098-1004(1999)13:5<380::aid-humu6>3.0.co;2-a; RA Ko T.-M., Hwu W.-L., Lin Y.-W., Tseng L.-H., Hwa H.-L., Wang T.-R., RA Chuang S.-M.; RT "Molecular genetic study of Pompe disease in Chinese patients in Taiwan."; RL Hum. Mutat. 13:380-384(1999). RN [42] RP VARIANTS LOPD PRO-208; LEU-308; LEU-324; MET-585; 607-GLY--HIS-612 DEL; RP ARG-643 AND THR-672. RX PubMed=11071489; DOI=10.1212/wnl.55.8.1122; RA Laforet P., Nicolino M., Eymard P.B., Puech J.P., Caillaud C., Poenaru L., RA Fardeau M.; RT "Juvenile and adult-onset acid maltase deficiency in France: genotype- RT phenotype correlation."; RL Neurology 55:1122-1128(2000). RN [43] RP VARIANTS IOPD ARG-219; LYS-262 AND VAL-408. RX PubMed=11738358; DOI=10.1016/s0960-8966(01)00247-4; RA Fernandez-Hojas R., Huie M.L., Navarro C., Dominguez C., Roig M., RA Lopez-Coronas D., Teijeira S., Anyane-Yeboa K., Hirschhorn R.; RT "Identification of six novel mutations in the acid alpha-glucosidase gene RT in three Spanish patients with infantile onset glycogen storage disease RT type II (Pompe disease)."; RL Neuromuscul. Disord. 12:159-166(2002). RN [44] RP VARIANT IOPD TRP-224, AND CHARACTERIZATION OF VARIANT IOPD TRP-224. RX PubMed=12923862; DOI=10.1002/ajmg.a.20164; RA Pittis M.G., Montalvo A.L., Miocic S., Martini C., Deganuto M., RA Candusso M., Ciana G., Bembi B.; RT "Identification of four novel mutations in the alpha glucosidase gene in RT five Italian patients with infantile onset glycogen storage disease type RT II."; RL Am. J. Med. Genet. A 121:225-230(2003). RN [45] RP VARIANTS LOPD LEU-361 AND CYS-437. RX PubMed=12601120; DOI=10.1212/01.wnl.0000048661.95327.bf; RA Lam C.W., Yuen Y.P., Chan K.Y., Tong S.F., Lai C.K., Chow T.C., Lee K.C., RA Chan Y.W., Martiniuk F.; RT "Juvenile-onset glycogen storage disease type II with novel mutations in RT acid alpha-glucosidase gene."; RL Neurology 60:715-717(2003). RN [46] RP VARIANTS LOPD TRP-224; CYS-600; ARG-619 AND HIS-660, CHARACTERIZATION OF RP VARIANTS LOPD TRP-224; ARG-619 AND HIS-660, AND CHARACTERIZATION OF VARIANT RP SER-576. RX PubMed=14643388; DOI=10.1016/s0887-8994(03)00267-4; RA Pipo J.R., Feng J.-H., Yamamoto T., Ohsaki Y., Nanba E., Tsujino S., RA Sakuragawa N., Martiniuk F., Ninomiya H., Oka A., Ohno K.; RT "New GAA mutations in Japanese patients with GSDII (Pompe disease)."; RL Pediatr. Neurol. 29:284-287(2003). RN [47] RP VARIANTS IOPD GLY-103; ARG-219; ARG-293; PRO-308; ARG-312; PRO-355; RP ARG-374; PRO-405; ASP-459 DEL; ARG-478; THR-519; LYS-579; ASP-607 AND RP ASP-880, VARIANTS LOPD ARG-285; CYS-292; PHE-455; ARG-481; LEU-545; RP ARG-549; PRO-552; SER-575 AND CYS-600, CHARACTERIZATION OF VARIANTS, AND RP FUNCTION. RX PubMed=14695532; DOI=10.1002/humu.10286; RA Hermans M.M.P., van Leenen D., Kroos M.A., Beesley C.E., RA Van der Ploeg A.T., Sakuraba H., Wevers R., Kleijer W.J., Michelakakis H., RA Kirk E.P., Fletcher J., Bosshard N., Basel-Vanagaite L., Besley G., RA Reuser A.J.J.; RT "Twenty-two novel mutations in the lysosomal alpha-glucosidase gene (GAA) RT underscore the genotype-phenotype correlation in glycogen storage disease RT type II."; RL Hum. Mutat. 23:47-56(2004). RN [48] RP VARIANTS IOPD PRO-355 AND CYS-702, AND CHARACTERIZATION OF VARIANTS IOPD RP PRO-355 AND CYS-702. RX PubMed=14972326; DOI=10.1016/j.ymgme.2003.11.011; RA Montalvo A.L.E., Cariati R., Deganuto M., Guerci V., Garcia R., Ciana G., RA Bembi B., Pittis M.G.; RT "Glycogenosis type II: identification and expression of three novel RT mutations in the acid alpha-glucosidase gene causing the infantile form of RT the disease."; RL Mol. Genet. Metab. 81:203-208(2004). RN [49] RP VARIANTS IOPD ASN-645 AND GLN-901. RX PubMed=15145338; DOI=10.1016/j.nmd.2004.02.012; RA Kroos M.A., Kirschner J., Gellerich F.N., Hermans M.M., Van der Ploeg A.T., RA Reuser A.J., Korinthenberg R.; RT "A case of childhood Pompe disease demonstrating phenotypic variability of RT p.Asp645Asn."; RL Neuromuscul. Disord. 14:371-374(2004). RN [50] RP VARIANTS LOPD VAL-237 AND ARG-293. RX PubMed=15668445; DOI=10.1212/01.wnl.0000149528.95362.20; RA Anneser J.M., Pongratz D.E., Podskarbi T., Shin Y.S., Schoser B.G.; RT "Mutations in the acid alpha-glucosidase gene (M. Pompe) in a patient with RT an unusual phenotype."; RL Neurology 64:368-370(2005). RN [51] RP VARIANT IOPD GLY-330. RX PubMed=16782080; DOI=10.1016/j.cca.2006.04.007; RA Dou W., Gu X., Fu L., Peng C., Zheng J., Martiniuk F., Sheng H.Z.; RT "A novel missense mutation in the acid alpha-glucosidase gene causing the RT classic infantile form of Pompe disease."; RL Clin. Chim. Acta 374:145-146(2006). RN [52] RP VARIANT IOPD ASN-404. RX PubMed=16433701; DOI=10.1111/j.1399-0004.2005.00557.x; RA Amartino H., Painceira D., Pomponio R.J., Niizawa G., Sabio Paz V., RA Blanco M., Chamoles N.; RT "Two clinical forms of glycogen-storage disease type II in two generations RT of the same family."; RL Clin. Genet. 69:187-188(2006). RN [53] RP VARIANTS LOPD ARG-309; PRO-355; LEU-361; PRO-445; ASN-489; ARG-549; RP GLN-612; ARG-643; TRP-672 AND CYS-746. RX PubMed=16917947; DOI=10.1002/humu.20374; RA Montalvo A.L., Bembi B., Donnarumma M., Filocamo M., Parenti G., Rossi M., RA Merlini L., Buratti E., De Filippi P., Dardis A., Stroppiano M., Ciana G., RA Pittis M.G.; RT "Mutation profile of the GAA gene in 40 Italian patients with late onset RT glycogen storage disease type II."; RL Hum. Mutat. 27:999-1006(2006). RN [54] RP VARIANT IOPD ARG-377. RX PubMed=16860134; DOI=10.1016/j.jpeds.2006.02.035; RA Kishnani P.S., Nicolino M., Voit T., Rogers R.C., Tsai A.C., Waterson J., RA Herman G.E., Amalfitano A., Thurberg B.L., Richards S., Davison M., RA Corzo D., Chen Y.T.; RT "Chinese hamster ovary cell-derived recombinant human acid alpha- RT glucosidase in infantile-onset Pompe disease."; RL J. Pediatr. 149:89-97(2006). RN [55] RP VARIANTS LOPD PRO-355; ALA-522 AND VAL-610, AND VARIANT ARG-359. RX PubMed=17643989; DOI=10.1016/j.nmd.2007.06.002; RA Muller-Felber W., Horvath R., Gempel K., Podskarbi T., Shin Y., RA Pongratz D., Walter M.C., Baethmann M., Schlotter-Weigel B., Lochmuller H., RA Schoser B.; RT "Late onset Pompe disease: clinical and neurophysiological spectrum of 38 RT patients including long-term follow-up in 18 patients."; RL Neuromuscul. Disord. 17:698-706(2007). RN [56] RP VARIANTS IOPD HIS-190; SER-285; PHE-291; PRO-291; LYS-318; ARG-335; RP ARG-347; ARG-482; VAL-483; GLN-521; SER-522; LYS-570; GLN-572; LYS-585; RP PRO-594; LYS-614; ASN-737; SER-746 AND PRO-935. RX PubMed=18425781; DOI=10.1002/humu.20745; RA Kroos M., Pomponio R.J., van Vliet L., Palmer R.E., Phipps M., RA Van der Helm R., Halley D., Reuser A.; RT "Update of the Pompe disease mutation database with 107 sequence variants RT and a format for severity rating."; RL Hum. Mutat. 29:E13-E26(2008). RN [57] RP VARIANTS IOPD GLY-103; CYS-191; ARG-219; TRP-224; LYS-262; ARG-293; RP PRO-355; LEU-375; ARG-401; ASN-489; ALA-522; PRO-552; TYR-599; TRP-638; RP ARG-643 AND ASN-645, CHARACTERIZATION OF VARIANTS IOPD CYS-191; LEU-375; RP ARG-401; ALA-522 AND TYR-599, FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=18429042; DOI=10.1002/humu.20753; RA Pittis M.G., Donnarumma M., Montalvo A.L.E., Dominissini S., Kroos M., RA Rosano C., Stroppiano M., Bianco M.G., Donati M.A., Parenti G., D'Amico A., RA Ciana G., Di Rocco M., Reuser A., Bembi B., Filocamo M.; RT "Molecular and functional characterization of eight novel GAA mutations in RT Italian infants with Pompe disease."; RL Hum. Mutat. 29:E27-E36(2008). RN [58] RP VARIANTS IOPD PRO-46; LEU-217; LYS-262; GLN-521; PRO-552; TYR-612; LYS-635; RP VAL-638; ARG-643 AND TRP-647, AND VARIANTS LOPD PRO-486; PRO-552; PRO-594; RP LYS-635; ARG-643 AND TRP-647. RX PubMed=19588081; DOI=10.1007/s00415-009-5219-y; RA Oba-Shinjo S.M., da Silva R., Andrade F.G., Palmer R.E., Pomponio R.J., RA Ciociola K.M., Carvalho S.M., Gutierrez P.S., Porta G., Marrone C.D., RA Munoz V., Grzesiuk A.K., Llerena J.C. Jr., Berditchevsky C.R., Sobreira C., RA Horovitz D., Hatem T.P., Frota E.R., Pecchini R., Kouyoumdjian J.A., RA Werneck L., Amado V.M., Camelo J.S. Jr., Mattaliano R.J., Marie S.K.; RT "Pompe disease in a Brazilian series: clinical and molecular analyses with RT identification of nine new mutations."; RL J. Neurol. 256:1881-1890(2009). RN [59] RP VARIANT LOPD SER-558. RX PubMed=20350966; DOI=10.1177/0883073809356035; RA Alcantara-Ortigoza M.A., Gonzalez-del Angel A., Barrientos-Rios R., RA Cupples C., Garrido-Garcia L.M., de Leon-Bojorge B., Alva-Chaire Adel C.; RT "Screening of late-onset Pompe disease in a sample of Mexican patients with RT myopathies of unknown etiology: identification of a novel mutation in the RT acid alpha-glucosidase gene."; RL J. Child Neurol. 25:1034-1037(2010). RN [60] RP VARIANTS IOPD PRO-224; LEU-251; LEU-254; LYS-262; SER-266; PRO-291; RP VAL-408; ARG-478; TYR-525; PHE-557; ARG-615; GLU-645; ARG-711; GLY-746 AND RP CYS-746, AND VARIANT ALA-271. RX PubMed=20080426; DOI=10.1016/j.ymgme.2009.12.014; RA Labrousse P., Chien Y.H., Pomponio R.J., Keutzer J., Lee N.C., Akmaev V.R., RA Scholl T., Hwu W.L.; RT "Genetic heterozygosity and pseudodeficiency in the Pompe disease newborn RT screening pilot program."; RL Mol. Genet. Metab. 99:379-383(2010). RN [61] RP VARIANT LOPD GLY-103, AND VARIANT ASN-91. RX PubMed=21109266; DOI=10.1016/j.jns.2010.10.031; RA Fidzianska A., Lugowska A., Tylki-Szymanska A.; RT "Late form of Pompe disease with glycogen storage in peripheral nerves RT axons."; RL J. Neurol. Sci. 301:59-62(2011). RN [62] RP VARIANTS HIS-74; LEU-220; MET-222; CYS-458; LEU-629 AND ILE-718, AND RP VARIANTS IOPD HIS-89; ARG-103; GLY-108; PHE-127; GLN-224; ARG-234; LYS-234; RP ASP-290; GLY-310; ILE-316; GLU-335; VAL-391; LEU-397; VAL-419; HIS-457; RP TYR-523; SER-558; CYS-575; ARG-576; HIS-594; LEU-601; ALA-602; ASP-611; RP PRO-627; ASP-648; 700-THR-LEU-701 DEL; LEU-702; LYS-743; PRO-819 AND RP PHE-916. RX PubMed=22644586; DOI=10.1002/humu.22108; RA Kroos M., Hoogeveen-Westerveld M., Michelakakis H., Pomponio R., RA Van der Ploeg A., Halley D., Reuser A., Augoustides-Savvopoulou P., RA Ausems M., Llona J.B., Bautista Lorite J., van der Beek N., Bonafe L., RA Cuk M., D'Hooghe M., Engelen B., Farouk A., Fumic K., Garcia-Delgado E., RA Herzog A., Hurst J., Jones S., Kariminejad M.H., Kucukcongar A., RA Lissens W., Lund A., Majoor-Krakauer D., Kumamoto S., Maravi E., Marie S., RA Mengel E., Mavridou I., Munteis Olivas E., Najmabadi H., Okumiya T., RA Peric S., Paschke E., Plecko B., Robberecht W., Serdaroglu P., Shboul M., RA Tansek M.Z., Tarnutzer A., Stojanovic V.R., Tylki-Szymanska A., RA Venancio M., Verhoeven K.; RT "Update of the pompe disease mutation database with 60 novel GAA sequence RT variants and additional studies on the functional effect of 34 previously RT reported variants."; RL Hum. Mutat. 33:1161-1165(2012). RN [63] RP VARIANTS IOPD LYS-234; 431-LEU--GLN-433 DEL; LEU-568; LEU-601; CYS-766 AND RP ARG-913. RX PubMed=22676651; DOI=10.1186/1750-1172-7-35; RA Herzog A., Hartung R., Reuser A.J., Hermanns P., Runz H., Karabul N., RA Goekce S., Pohlenz J., Kampmann C., Lampe C., Beck M., Mengel E.; RT "A cross-sectional single-centre study on the spectrum of Pompe disease, RT German patients: molecular analysis of the GAA gene, manifestation and RT genotype-phenotype correlations."; RL Orphanet J. Rare Dis. 7:35-35(2012). RN [64] RP VARIANTS IOPD VAL-391; HIS-437; PRO-552; ASP-611; VAL-641; TRP-647 AND RP PRO-705, AND VARIANTS ASN-91; ARG-199; HIS-223; SER-576; LYS-689; ILE-780 RP AND ILE-816. RX PubMed=25681614; DOI=10.1016/j.gene.2015.02.023; RA Turaca L.T., de Faria D.O., Kyosen S.O., Teixeira V.D., Motta F.L., RA Pessoa J.G., Rodrigues E Silva M., de Almeida S.S., D'Almeida V., RA Munoz Rojas M.V., Martins A.M., Pesquero J.B.; RT "Novel GAA mutations in patients with Pompe disease."; RL Gene 561:124-131(2015). CC -!- FUNCTION: Essential for the degradation of glycogen in lysosomes CC (PubMed:14695532, PubMed:18429042, PubMed:1856189, PubMed:7717400). Has CC highest activity on alpha-1,4-linked glycosidic linkages, but can also CC hydrolyze alpha-1,6-linked glucans (PubMed:29061980). CC {ECO:0000269|PubMed:14695532, ECO:0000269|PubMed:18429042, CC ECO:0000269|PubMed:1856189, ECO:0000269|PubMed:29061980, CC ECO:0000269|PubMed:7717400}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Hydrolysis of terminal, non-reducing (1->4)-linked alpha-D- CC glucose residues with release of alpha-D-glucose.; EC=3.2.1.20; CC Evidence={ECO:0000269|PubMed:18429042, ECO:0000269|PubMed:1856189, CC ECO:0000269|PubMed:29061980, ECO:0000269|PubMed:7717400}; CC -!- SUBCELLULAR LOCATION: Lysosome {ECO:0000269|PubMed:17897319}. Lysosome CC membrane {ECO:0000269|PubMed:17897319}. CC -!- PTM: The different forms of acid glucosidase are obtained by CC proteolytic processing. {ECO:0000269|PubMed:3049072}. CC -!- PTM: Phosphorylation of mannose residues ensures efficient transport of CC the enzyme to the lysosomes via the mannose 6-phosphate receptor. CC -!- POLYMORPHISM: There are three common alleles of GAA: GAA*1, GAA*2 and CC GAA*4. The sequence shown is that of allele GAA*1, which is the most CC common. Alleles GAA*2 and GAA*4 are much rarer. CC {ECO:0000269|PubMed:21109266, ECO:0000269|PubMed:2203258, CC ECO:0000269|PubMed:25681614, ECO:0000269|PubMed:8912788, CC ECO:0000269|PubMed:9521422}. CC -!- DISEASE: Pompe disease, infantile-onset (IOPD) [MIM:232300]: An early- CC onset form of Pompe disease, an autosomal recessive lysosomal storage CC disease characterized by lysosomal alpha-glucosidase deficiency, a CC broad clinical spectrum and age at onset ranging from infancy to CC adulthood. The classic early-onset form of IOPD presents at birth with CC massive accumulation of glycogen in muscle, heart and liver. CC Cardiomyopathy and muscular hypotonia are the cardinal features of this CC form whose life expectancy is less than two years. A milder infantile CC form manifests as progressive muscular disorder of childhood and CC patients have better prognosis. {ECO:0000269|PubMed:10189220, CC ECO:0000269|PubMed:10206684, ECO:0000269|PubMed:10338092, CC ECO:0000269|PubMed:11738358, ECO:0000269|PubMed:12923862, CC ECO:0000269|PubMed:14695532, ECO:0000269|PubMed:14972326, CC ECO:0000269|PubMed:15145338, ECO:0000269|PubMed:16433701, CC ECO:0000269|PubMed:1652892, ECO:0000269|PubMed:16782080, CC ECO:0000269|PubMed:16860134, ECO:0000269|PubMed:18425781, CC ECO:0000269|PubMed:18429042, ECO:0000269|PubMed:1898413, CC ECO:0000269|PubMed:19588081, ECO:0000269|PubMed:20080426, CC ECO:0000269|PubMed:22644586, ECO:0000269|PubMed:22676651, CC ECO:0000269|PubMed:25681614, ECO:0000269|PubMed:7695647, CC ECO:0000269|PubMed:7717400, ECO:0000269|PubMed:7866409, CC ECO:0000269|PubMed:7981676, ECO:0000269|PubMed:8834250, CC ECO:0000269|PubMed:9521422, ECO:0000269|PubMed:9529346, CC ECO:0000269|PubMed:9535769, ECO:0000269|PubMed:9660056}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Pompe disease, late-onset (LOPD) [MIM:621314]: A late-onset CC form of Pompe disease, an autosomal recessive lysosomal storage disease CC characterized by lysosomal alpha-glucosidase deficiency, a broad CC clinical spectrum and age at onset ranging from infancy to adulthood. CC LOPD includes juvenile and adult forms and manifests as limb-girdle CC muscular dystrophy beginning in the lower limbs. Final outcome depends CC on respiratory muscle failure. Patients with the adult form can be free CC of clinical symptoms for most of their life but finally develop a CC slowly progressive myopathy. {ECO:0000269|PubMed:10338092, CC ECO:0000269|PubMed:10737124, ECO:0000269|PubMed:11071489, CC ECO:0000269|PubMed:12601120, ECO:0000269|PubMed:14643388, CC ECO:0000269|PubMed:14695532, ECO:0000269|PubMed:15668445, CC ECO:0000269|PubMed:1684505, ECO:0000269|PubMed:16917947, CC ECO:0000269|PubMed:17643989, ECO:0000269|PubMed:19588081, CC ECO:0000269|PubMed:20350966, ECO:0000269|PubMed:21109266, CC ECO:0000269|PubMed:7881422, ECO:0000269|PubMed:8094613, CC ECO:0000269|PubMed:8401535, ECO:0000269|PubMed:8834250, CC ECO:0000269|PubMed:9535769, ECO:0000269|Ref.5}. Note=The disease is CC caused by variants affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 31 family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=GAA; Note=Mutations in alpha-glucosidase; CC URL="https://medlineplus.gov/genetics/gene/gaa/"; CC -!- WEB RESOURCE: Name=Wikipedia; Note=Alpha-glucosidase entry; CC URL="https://en.wikipedia.org/wiki/Alpha-glucosidase"; CC -!- WEB RESOURCE: Name=Glucosidase, alpha, acid (Pompe disease) (GAA); CC Note=Leiden Open Variation Database (LOVD); CC URL="https://databases.lovd.nl/shared/genes/GAA"; 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; Y00839; CAA68763.1; -; mRNA. DR EMBL; Y00839; CAA68764.1; -; mRNA. DR EMBL; X55080; CAC12967.1; -; Genomic_DNA. DR EMBL; X55081; CAC12967.1; JOINED; Genomic_DNA. DR EMBL; X55095; CAC12967.1; JOINED; Genomic_DNA. DR EMBL; X55082; CAC12967.1; JOINED; Genomic_DNA. DR EMBL; X55084; CAC12967.1; JOINED; Genomic_DNA. DR EMBL; X55083; CAC12967.1; JOINED; Genomic_DNA. DR EMBL; X55098; CAC12967.1; JOINED; Genomic_DNA. DR EMBL; X55085; CAC12967.1; JOINED; Genomic_DNA. DR EMBL; X55086; CAC12967.1; JOINED; Genomic_DNA. DR EMBL; X55087; CAC12967.1; JOINED; Genomic_DNA. DR EMBL; X55088; CAC12967.1; JOINED; Genomic_DNA. DR EMBL; X55089; CAC12967.1; JOINED; Genomic_DNA. DR EMBL; X55090; CAC12967.1; JOINED; Genomic_DNA. DR EMBL; X55096; CAC12967.1; JOINED; Genomic_DNA. DR EMBL; X55091; CAC12967.1; JOINED; Genomic_DNA. DR EMBL; X55092; CAC12967.1; JOINED; Genomic_DNA. DR EMBL; X55093; CAC12967.1; JOINED; Genomic_DNA. DR EMBL; X55094; CAC12967.1; JOINED; Genomic_DNA. DR EMBL; X55097; CAC12967.1; JOINED; Genomic_DNA. DR EMBL; M34424; AAA52506.1; -; mRNA. DR EMBL; DQ907243; ABI53718.1; -; mRNA. DR EMBL; AC087741; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC040431; AAH40431.1; -; mRNA. DR EMBL; S76893; AAB33842.1; -; mRNA. DR CCDS; CCDS32760.1; -. DR PIR; A40577; A32609. DR RefSeq; NP_000143.2; NM_000152.5. DR RefSeq; NP_001073271.1; NM_001079803.3. DR RefSeq; NP_001073272.1; NM_001079804.3. DR RefSeq; NP_001393670.1; NM_001406741.1. DR RefSeq; NP_001393671.1; NM_001406742.1. DR RefSeq; XP_047291675.1; XM_047435719.1. DR RefSeq; XP_054189174.1; XM_054333199.1. DR PDB; 5KZW; X-ray; 2.00 A; A=79-952. DR PDB; 5KZX; X-ray; 2.00 A; A=79-952. DR PDB; 5NN3; X-ray; 1.90 A; A=81-952. DR PDB; 5NN4; X-ray; 1.83 A; A=81-952. DR PDB; 5NN5; X-ray; 2.00 A; A=81-952. DR PDB; 5NN6; X-ray; 2.00 A; A=81-952. DR PDB; 5NN8; X-ray; 2.45 A; A=81-952. DR PDB; 7P2Z; X-ray; 1.85 A; AAA/AaA=81-952. DR PDB; 7P32; X-ray; 1.82 A; AAA=81-952. DR PDB; 8CB1; X-ray; 1.75 A; A=204-952, G=81-203. DR PDB; 8CB6; X-ray; 1.90 A; A=204-952, F=81-203. DR PDB; 9GSV; X-ray; 1.80 A; A=1-952. DR PDB; 9GSW; X-ray; 1.95 A; A=1-952. DR PDB; 9GTC; X-ray; 2.58 A; A=1-952. DR PDB; 9GTD; X-ray; 2.25 A; A=1-952. DR PDB; 9GTL; X-ray; 2.00 A; A=1-952. DR PDB; 9GTN; X-ray; 1.80 A; A=1-952. DR PDB; 9GTT; X-ray; 2.35 A; A=1-952. DR PDB; 9GTW; X-ray; 1.75 A; A=1-952. DR AlphaFoldDB; P10253; -. DR MDRepo; P10253; -. DR SMR; P10253; -. DR BioGRID; 108823; 138. DR FunCoup; P10253; 652. DR IntAct; P10253; 101. DR NDEx; IQUERY-CP-GAA; 1 NDEx IQuery Curated Pathway. DR STRING; 9606.ENSP00000305692; -. DR BindingDB; P10253; -. DR ChEMBL; CHEMBL2608; -. DR DrugBank; DB01841; 4,6-Dideoxyglucose. DR DrugBank; DB00284; Acarbose. DR DrugBank; DB01272; Alglucosidase alfa. DR DrugBank; DB14109; alpha-Arbutin. DR DrugBank; DB06645; Anamorelin. DR DrugBank; DB05200; AT2220. DR DrugBank; DB02379; Beta-D-Glucose. DR DrugBank; DB03206; Duvoglustat. DR DrugBank; DB09526; Hydroquinone. DR DrugBank; DB03323; Maltose. DR DrugBank; DB00491; Miglitol. DR DrugBank; DB14128; Nadide. DR DrugBank; DB14962; Trastuzumab deruxtecan. DR DrugCentral; P10253; -. DR GuidetoPHARMACOLOGY; 2611; -. DR Allergome; 9614; Hom s Glucosidase. DR CAZy; GH31; Glycoside Hydrolase Family 31. DR GlyConnect; P10253; 19 N-Linked glycans (7 sites). DR GlyCosmos; P10253; 21 sites, 83 glycans. DR GlyGen; P10253; 21 sites, 82 N-linked glycans (7 sites), 4 N-linked;o-linked glycans (3 sites), 2 O-linked glycans (12 sites). DR iPTMnet; P10253; -. DR MetOSite; P10253; -. DR PhosphoSitePlus; P10253; -. DR SwissPalm; P10253; -. DR BioMuta; GAA; -. DR DMDM; 317373572; -. DR CPTAC; CPTAC-2224; -. DR jPOST; P10253; -. DR MassIVE; P10253; -. DR PaxDb; 9606-ENSP00000305692; -. DR PeptideAtlas; P10253; -. DR ProteomicsDB; 52587; -. DR Pumba; P10253; -. DR Antibodypedia; 32676; 404 antibodies from 39 providers. DR DNASU; 2548; -. DR Ensembl; ENST00000302262.8; ENSP00000305692.3; ENSG00000171298.16. DR Ensembl; ENST00000390015.7; ENSP00000374665.3; ENSG00000171298.16. DR Ensembl; ENST00000570803.6; ENSP00000460543.2; ENSG00000171298.16. DR Ensembl; ENST00000577106.6; ENSP00000458306.2; ENSG00000171298.16. DR Ensembl; ENST00000707779.1; ENSP00000516980.1; ENSG00000291507.1. DR Ensembl; ENST00000707781.1; ENSP00000516982.1; ENSG00000291507.1. DR Ensembl; ENST00000714057.1; ENSP00000519347.1; ENSG00000171298.16. DR Ensembl; ENST00000714058.1; ENSP00000519348.1; ENSG00000171298.16. DR Ensembl; ENST00000945487.1; ENSP00000615546.1; ENSG00000171298.16. DR Ensembl; ENST00000945488.1; ENSP00000615547.1; ENSG00000171298.16. DR GeneID; 2548; -. DR KEGG; hsa:2548; -. DR MANE-Select; ENST00000302262.8; ENSP00000305692.3; NM_000152.5; NP_000143.2. DR UCSC; uc002jxo.4; human. DR AGR; HGNC:4065; -. DR ClinPGx; PA28476; -. DR CTD; 2548; -. DR DisGeNET; 2548; -. DR GeneCards; GAA; -. DR GeneReviews; GAA; -. DR HGNC; HGNC:4065; GAA. DR HPA; ENSG00000171298; Low tissue specificity. DR MalaCards; GAA; -. DR MIM; 232300; phenotype. DR MIM; 606800; gene. DR MIM; 621314; phenotype. DR OpenTargets; ENSG00000171298; -. DR Orphanet; 308552; Glycogen storage disease due to acid maltase deficiency, infantile onset. DR Orphanet; 420429; Glycogen storage disease due to acid maltase deficiency, late-onset. DR VEuPathDB; HostDB:ENSG00000171298; -. DR eggNOG; KOG1065; Eukaryota. DR GeneTree; ENSGT00940000159355; -. DR HOGENOM; CLU_000631_11_2_1; -. DR InParanoid; P10253; -. DR OMA; AADCLHI; -. DR OrthoDB; 5839090at2759; -. DR PAN-GO; P10253; 3 GO annotations based on evolutionary models. DR PhylomeDB; P10253; -. DR BRENDA; 3.2.1.20; 2681. DR PathwayCommons; P10253; -. DR Reactome; R-HSA-5357609; Glycogen storage disease type II (GAA). DR Reactome; R-HSA-6798695; Neutrophil degranulation. DR Reactome; R-HSA-70221; Glycogen breakdown (glycogenolysis). DR SignaLink; P10253; -. DR SIGNOR; P10253; -. DR Agora; ENSG00000171298; -. DR BioGRID-ORCS; 2548; 12 hits in 1155 CRISPR screens. DR ChiTaRS; GAA; human. DR GeneWiki; Acid_alpha-glucosidase; -. DR GenomeRNAi; 2548; -. DR Pharos; P10253; Tclin. DR PRO; PR:P10253; -. DR Proteomes; UP000005640; Chromosome 17. DR RNAct; P10253; protein. DR Bgee; ENSG00000171298; Expressed in granulocyte and 177 other cell types or tissues. DR ExpressionAtlas; P10253; baseline and differential. DR GO; GO:0035577; C:azurophil granule membrane; TAS:Reactome. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0101003; C:ficolin-1-rich granule membrane; TAS:Reactome. DR GO; GO:0043202; C:lysosomal lumen; TAS:Reactome. DR GO; GO:0005765; C:lysosomal membrane; HDA:UniProtKB. DR GO; GO:0005764; C:lysosome; IDA:BHF-UCL. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0070821; C:tertiary granule membrane; TAS:Reactome. DR GO; GO:0004558; F:alpha-1,4-glucosidase activity; IDA:UniProtKB. DR GO; GO:0090599; F:alpha-glucosidase activity; EXP:Reactome. DR GO; GO:0030246; F:carbohydrate binding; IEA:InterPro. DR GO; GO:0043896; F:glucan 1,6-alpha-glucosidase activity; IDA:MGI. DR GO; GO:0002086; P:diaphragm contraction; IMP:BHF-UCL. DR GO; GO:0006006; P:glucose metabolic process; IC:BHF-UCL. DR GO; GO:0005980; P:glycogen catabolic process; IDA:UniProtKB. DR GO; GO:0061723; P:glycophagy; IMP:MGI. DR GO; GO:0007040; P:lysosome organization; IMP:BHF-UCL. DR GO; GO:0000023; P:maltose metabolic process; IC:BHF-UCL. DR GO; GO:0005985; P:sucrose metabolic process; IC:BHF-UCL. DR CDD; cd06602; GH31_MGAM_SI_GAA; 1. DR CDD; cd14752; GH31_N; 1. DR CDD; cd00111; Trefoil; 1. DR FunFam; 4.10.110.10:FF:000007; Lysosomal alpha-glucosidase; 1. DR FunFam; 3.20.20.80:FF:000072; lysosomal alpha-glucosidase isoform X2; 1. DR FunFam; 2.60.40.1180:FF:000001; Maltase-glucoamylase, intestinal; 1. DR FunFam; 2.60.40.1180:FF:000005; Maltase-glucoamylase, intestinal; 1. DR FunFam; 2.60.40.1760:FF:000001; Maltase-glucoamylase, intestinal; 1. DR Gene3D; 3.20.20.80; Glycosidases; 1. DR Gene3D; 2.60.40.1760; glycosyl hydrolase (family 31); 1. DR Gene3D; 2.60.40.1180; Golgi alpha-mannosidase II; 2. DR Gene3D; 4.10.110.10; Spasmolytic Protein, domain 1; 1. DR InterPro; IPR011013; Gal_mutarotase_sf_dom. DR InterPro; IPR017853; GH_hydrolase_sf. 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; IPR017957; P_trefoil_CS. DR InterPro; IPR000519; P_trefoil_dom. DR InterPro; IPR044913; P_trefoil_dom_sf. DR PANTHER; PTHR22762; ALPHA-GLUCOSIDASE; 1. DR PANTHER; PTHR22762:SF92; LYSOSOMAL ALPHA-GLUCOSIDASE; 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 Pfam; PF00088; Trefoil; 1. DR SMART; SM00018; PD; 1. DR SUPFAM; SSF51445; (Trans)glycosidases; 1. DR SUPFAM; SSF74650; Galactose mutarotase-like; 1. DR SUPFAM; SSF51011; Glycosyl hydrolase domain; 1. DR SUPFAM; SSF57492; Trefoil; 1. DR PROSITE; PS00129; GLYCOSYL_HYDROL_F31_1; 1. DR PROSITE; PS00707; GLYCOSYL_HYDROL_F31_2; 1. DR PROSITE; PS00025; P_TREFOIL_1; 1. DR PROSITE; PS51448; P_TREFOIL_2; 1. PE 1: Evidence at protein level; KW 3D-structure; Direct protein sequencing; Disease variant; Disulfide bond; KW Glycogen storage disease; Glycoprotein; Glycosidase; Hydrolase; Lysosome; KW Membrane; Phosphoprotein; Proteomics identification; Reference proteome; KW Signal. FT SIGNAL 1..27 FT /evidence="ECO:0000255" FT PROPEP 28..69 FT /evidence="ECO:0000269|PubMed:3049072" FT /id="PRO_0000018565" FT CHAIN 70..952 FT /note="Lysosomal alpha-glucosidase" FT /id="PRO_0000018566" FT CHAIN 123..952 FT /note="76 kDa lysosomal alpha-glucosidase" FT /id="PRO_0000018567" FT CHAIN 204..952 FT /note="70 kDa lysosomal alpha-glucosidase" FT /id="PRO_0000018568" FT DOMAIN 80..131 FT /note="P-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00779" FT REGION 47..82 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 518 FT /note="Nucleophile" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10066, FT ECO:0000269|PubMed:1856189, ECO:0000305|PubMed:29061980" FT ACT_SITE 521 FT /evidence="ECO:0000250" FT BINDING 404 FT /ligand="substrate" FT /evidence="ECO:0000305|PubMed:29061980" FT BINDING 600 FT /ligand="substrate" FT /evidence="ECO:0000305|PubMed:29061980" FT BINDING 616 FT /ligand="substrate" FT /evidence="ECO:0000305|PubMed:29061980" FT BINDING 674 FT /ligand="substrate" FT /evidence="ECO:0000305|PubMed:29061980" FT CARBOHYD 140 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:19159218, FT ECO:0000269|PubMed:29061980, ECO:0000269|PubMed:8435067, FT ECO:0000269|Ref.19, ECO:0007744|PDB:5KZW, FT ECO:0007744|PDB:5NN3" FT CARBOHYD 233 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:29061980, FT ECO:0000269|PubMed:8435067, ECO:0000269|Ref.19, FT ECO:0007744|PDB:5KZW, ECO:0007744|PDB:5NN3" FT CARBOHYD 390 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:16335952, FT ECO:0000269|PubMed:29061980, ECO:0000269|PubMed:8435067, FT ECO:0000269|Ref.19, ECO:0007744|PDB:5KZW, FT ECO:0007744|PDB:5NN3" FT CARBOHYD 470 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:12754519, FT ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:29061980, FT ECO:0000269|PubMed:8435067, ECO:0000269|Ref.19, FT ECO:0007744|PDB:5KZW, ECO:0007744|PDB:5NN3" FT CARBOHYD 652 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:29061980, FT ECO:0000269|PubMed:8435067, ECO:0000269|Ref.19, FT ECO:0007744|PDB:5KZW, ECO:0007744|PDB:5NN3" FT CARBOHYD 882 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:19159218, FT ECO:0000269|PubMed:29061980, ECO:0000269|PubMed:8435067, FT ECO:0000269|Ref.19, ECO:0007744|PDB:5KZW, FT ECO:0007744|PDB:5NN3" FT CARBOHYD 925 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:19159218, FT ECO:0000269|PubMed:8435067" FT DISULFID 82..109 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00779, FT ECO:0000269|PubMed:29061980, ECO:0000269|Ref.19, FT ECO:0007744|PDB:5KZW, ECO:0007744|PDB:5KZX, FT ECO:0007744|PDB:5NN3, ECO:0007744|PDB:5NN4, FT ECO:0007744|PDB:5NN5, ECO:0007744|PDB:5NN6, FT ECO:0007744|PDB:5NN8" FT DISULFID 92..108 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00779, FT ECO:0000269|PubMed:29061980, ECO:0000269|Ref.19, FT ECO:0007744|PDB:5KZW, ECO:0007744|PDB:5KZX, FT ECO:0007744|PDB:5NN3, ECO:0007744|PDB:5NN4, FT ECO:0007744|PDB:5NN5, ECO:0007744|PDB:5NN6, FT ECO:0007744|PDB:5NN8" FT DISULFID 103..127 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00779, FT ECO:0000269|PubMed:29061980, ECO:0000269|Ref.19, FT ECO:0007744|PDB:5KZW, ECO:0007744|PDB:5KZX, FT ECO:0007744|PDB:5NN3, ECO:0007744|PDB:5NN4, FT ECO:0007744|PDB:5NN5, ECO:0007744|PDB:5NN6, FT ECO:0007744|PDB:5NN8" FT DISULFID 533..558 FT /evidence="ECO:0000269|PubMed:29061980, ECO:0000269|Ref.19, FT ECO:0007744|PDB:5KZW, ECO:0007744|PDB:5KZX, FT ECO:0007744|PDB:5NN3, ECO:0007744|PDB:5NN4, FT ECO:0007744|PDB:5NN5, ECO:0007744|PDB:5NN6, FT ECO:0007744|PDB:5NN8" FT DISULFID 647..658 FT /evidence="ECO:0000269|PubMed:29061980, ECO:0000269|Ref.19, FT ECO:0007744|PDB:5KZW, ECO:0007744|PDB:5KZX, FT ECO:0007744|PDB:5NN3, ECO:0007744|PDB:5NN4, FT ECO:0007744|PDB:5NN5, ECO:0007744|PDB:5NN6, FT ECO:0007744|PDB:5NN8" FT VARIANT 46 FT /note="S -> P (in IOPD; dbSNP:rs777215354)" FT /evidence="ECO:0000269|PubMed:19588081" FT /id="VAR_068564" FT VARIANT 74 FT /note="R -> H (in dbSNP:rs764797280)" FT /evidence="ECO:0000269|PubMed:22644586" FT /id="VAR_068565" FT VARIANT 89 FT /note="R -> H (in IOPD; uncertain significance; FT dbSNP:rs200586324)" FT /evidence="ECO:0000269|PubMed:22644586" FT /id="VAR_068566" FT VARIANT 91 FT /note="D -> N (in allele GAA*2; lower affinity for glycogen FT and starch but not for lower-molecular weight substrates; FT dbSNP:rs1800299)" FT /evidence="ECO:0000269|PubMed:21109266, FT ECO:0000269|PubMed:2203258, ECO:0000269|PubMed:25681614, FT ECO:0000269|PubMed:9521422" FT /id="VAR_004285" FT VARIANT 103 FT /note="C -> G (in IOPD and LOPD; loss of activity; shows FT enzyme localization primarily in the ER-Golgi compartment FT suggesting that mutation could affect the normal processing FT and stability of the enzyme; dbSNP:rs398123174)" FT /evidence="ECO:0000269|PubMed:14695532, FT ECO:0000269|PubMed:18429042, ECO:0000269|PubMed:21109266" FT /id="VAR_018078" FT VARIANT 103 FT /note="C -> R (in IOPD)" FT /evidence="ECO:0000269|PubMed:22644586" FT /id="VAR_068567" FT VARIANT 108 FT /note="C -> G (in IOPD)" FT /evidence="ECO:0000269|PubMed:22644586" FT /id="VAR_068568" FT VARIANT 127 FT /note="C -> F (in IOPD)" FT /evidence="ECO:0000269|PubMed:22644586" FT /id="VAR_068569" FT VARIANT 190 FT /note="R -> H (in IOPD; dbSNP:rs528367092)" FT /evidence="ECO:0000269|PubMed:18425781" FT /id="VAR_068570" FT VARIANT 191 FT /note="Y -> C (in IOPD; extremely low residual enzymatic FT activity)" FT /evidence="ECO:0000269|PubMed:18429042" FT /id="VAR_046467" FT VARIANT 199 FT /note="H -> R (in dbSNP:rs1042393)" FT /evidence="ECO:0000269|PubMed:25681614, FT ECO:0000269|PubMed:3049072, ECO:0000269|PubMed:7717400, FT ECO:0000269|PubMed:9521422, ECO:0000269|Ref.5" FT /id="VAR_004286" FT VARIANT 208 FT /note="L -> P (in LOPD)" FT /evidence="ECO:0000269|PubMed:11071489" FT /id="VAR_029025" FT VARIANT 217 FT /note="P -> L (in IOPD)" FT /evidence="ECO:0000269|PubMed:19588081" FT /id="VAR_068571" FT VARIANT 219 FT /note="G -> R (in IOPD; loss of activity; FT dbSNP:rs370950728)" FT /evidence="ECO:0000269|PubMed:11738358, FT ECO:0000269|PubMed:14695532, ECO:0000269|PubMed:18429042" FT /id="VAR_018079" FT VARIANT 220 FT /note="V -> L (in dbSNP:rs530478036)" FT /evidence="ECO:0000269|PubMed:22644586" FT /id="VAR_068572" FT VARIANT 222 FT /note="V -> M (in dbSNP:rs374569672)" FT /evidence="ECO:0000269|PubMed:22644586" FT /id="VAR_068573" FT VARIANT 223 FT /note="R -> H (in dbSNP:rs1042395)" FT /evidence="ECO:0000269|PubMed:25681614, FT ECO:0000269|PubMed:3049072, ECO:0000269|PubMed:7717400, FT ECO:0000269|PubMed:9521422, ECO:0000269|Ref.5" FT /id="VAR_004287" FT VARIANT 224 FT /note="R -> P (in IOPD; dbSNP:rs200210219)" FT /evidence="ECO:0000269|PubMed:20080426" FT /id="VAR_068574" FT VARIANT 224 FT /note="R -> Q (in IOPD; dbSNP:rs200210219)" FT /evidence="ECO:0000269|PubMed:22644586" FT /id="VAR_068575" FT VARIANT 224 FT /note="R -> W (in IOPD and LOPD; partial loss of activity; FT dbSNP:rs757700700)" FT /evidence="ECO:0000269|PubMed:12923862, FT ECO:0000269|PubMed:14643388, ECO:0000269|PubMed:18429042" FT /id="VAR_029026" FT VARIANT 234 FT /note="T -> K (in IOPD)" FT /evidence="ECO:0000269|PubMed:22644586, FT ECO:0000269|PubMed:22676651" FT /id="VAR_068576" FT VARIANT 234 FT /note="T -> R (in IOPD)" FT /evidence="ECO:0000269|PubMed:22644586" FT /id="VAR_068577" FT VARIANT 237 FT /note="A -> V (in LOPD; uncertain significance; FT dbSNP:rs121907944)" FT /evidence="ECO:0000269|PubMed:15668445" FT /id="VAR_029027" FT VARIANT 251 FT /note="S -> L (in IOPD; dbSNP:rs200856561)" FT /evidence="ECO:0000269|PubMed:20080426" FT /id="VAR_068578" FT VARIANT 254 FT /note="S -> L (in IOPD; dbSNP:rs577915581)" FT /evidence="ECO:0000269|PubMed:20080426" FT /id="VAR_068579" FT VARIANT 262 FT /note="E -> K (in IOPD; dbSNP:rs201896815)" FT /evidence="ECO:0000269|PubMed:11738358, FT ECO:0000269|PubMed:18429042, ECO:0000269|PubMed:19588081, FT ECO:0000269|PubMed:20080426" FT /id="VAR_029028" FT VARIANT 266 FT /note="P -> S (in IOPD; dbSNP:rs1555599667)" FT /evidence="ECO:0000269|PubMed:20080426" FT /id="VAR_068580" FT VARIANT 271 FT /note="T -> A" FT /evidence="ECO:0000269|PubMed:20080426" FT /id="VAR_068581" FT VARIANT 285 FT /note="P -> R (in LOPD; partial loss of activity; FT dbSNP:rs764622267)" FT /evidence="ECO:0000269|PubMed:14695532" FT /id="VAR_018080" FT VARIANT 285 FT /note="P -> S (in IOPD; dbSNP:rs886042086)" FT /evidence="ECO:0000269|PubMed:18425781" FT /id="VAR_068582" FT VARIANT 290 FT /note="N -> D (in IOPD; uncertain significance; FT dbSNP:rs552929702)" FT /evidence="ECO:0000269|PubMed:22644586" FT /id="VAR_068583" FT VARIANT 291 FT /note="L -> F (in IOPD; dbSNP:rs773417785)" FT /evidence="ECO:0000269|PubMed:18425781" FT /id="VAR_068584" FT VARIANT 291 FT /note="L -> P (in IOPD)" FT /evidence="ECO:0000269|PubMed:18425781, FT ECO:0000269|PubMed:20080426" FT /id="VAR_068585" FT VARIANT 292 FT /note="Y -> C (in LOPD; partial loss of activity; FT dbSNP:rs1057516600)" FT /evidence="ECO:0000269|PubMed:14695532" FT /id="VAR_018081" FT VARIANT 293 FT /note="G -> R (in IOPD and LOPD; almost complete loss of FT activity; dbSNP:rs121907945)" FT /evidence="ECO:0000269|PubMed:14695532, FT ECO:0000269|PubMed:15668445, ECO:0000269|PubMed:18429042" FT /id="VAR_018082" FT VARIANT 299 FT /note="L -> R (in IOPD; dbSNP:rs121907940)" FT /evidence="ECO:0000269|PubMed:7717400" FT /id="VAR_004288" FT VARIANT 308 FT /note="H -> L (in LOPD)" FT /evidence="ECO:0000269|PubMed:11071489" FT /id="VAR_046468" FT VARIANT 308 FT /note="H -> P (in IOPD; complete loss of activity)" FT /evidence="ECO:0000269|PubMed:14695532" FT /id="VAR_018083" FT VARIANT 309 FT /note="G -> R (in IOPD and LOPD; dbSNP:rs543300039)" FT /evidence="ECO:0000269|PubMed:16917947, FT ECO:0000269|PubMed:9660056" FT /id="VAR_018084" FT VARIANT 310 FT /note="V -> G (in IOPD; uncertain significance; FT dbSNP:rs763091901)" FT /evidence="ECO:0000269|PubMed:22644586" FT /id="VAR_068586" FT VARIANT 312 FT /note="L -> R (in IOPD; loss of activity)" FT /evidence="ECO:0000269|PubMed:14695532" FT /id="VAR_018085" FT VARIANT 316 FT /note="N -> I (in IOPD)" FT /evidence="ECO:0000269|PubMed:22644586" FT /id="VAR_068587" FT VARIANT 318 FT /note="M -> K (in IOPD)" FT /evidence="ECO:0000269|PubMed:18425781" FT /id="VAR_068588" FT VARIANT 318 FT /note="M -> T (in IOPD; dbSNP:rs121907936)" FT /evidence="ECO:0000269|PubMed:1652892" FT /id="VAR_004289" FT VARIANT 324 FT /note="P -> L (in LOPD; uncertain significance; FT dbSNP:rs750030887)" FT /evidence="ECO:0000269|PubMed:11071489" FT /id="VAR_029029" FT VARIANT 330 FT /note="W -> G (in IOPD)" FT /evidence="ECO:0000269|PubMed:16782080" FT /id="VAR_029030" FT VARIANT 335 FT /note="G -> E (in IOPD; dbSNP:rs730880022)" FT /evidence="ECO:0000269|PubMed:22644586" FT /id="VAR_068589" FT VARIANT 335 FT /note="G -> R (in IOPD; dbSNP:rs202095215)" FT /evidence="ECO:0000269|PubMed:18425781" FT /id="VAR_068590" FT VARIANT 347 FT /note="P -> R (in IOPD)" FT /evidence="ECO:0000269|PubMed:18425781" FT /id="VAR_068591" FT VARIANT 355 FT /note="L -> P (in IOPD and LOPD; loss of activity; FT dbSNP:rs766074609)" FT /evidence="ECO:0000269|PubMed:14695532, FT ECO:0000269|PubMed:14972326, ECO:0000269|PubMed:16917947, FT ECO:0000269|PubMed:17643989, ECO:0000269|PubMed:18429042" FT /id="VAR_018086" FT VARIANT 359 FT /note="G -> R" FT /evidence="ECO:0000269|PubMed:17643989" FT /id="VAR_068592" FT VARIANT 361 FT /note="P -> L (in LOPD; dbSNP:rs755253527)" FT /evidence="ECO:0000269|PubMed:12601120, FT ECO:0000269|PubMed:16917947" FT /id="VAR_029031" FT VARIANT 374 FT /note="C -> R (in IOPD; loss of activity)" FT /evidence="ECO:0000269|PubMed:14695532" FT /id="VAR_018087" FT VARIANT 375 FT /note="R -> L (in IOPD; extremely low residual enzymatic FT activity; dbSNP:rs142752477)" FT /evidence="ECO:0000269|PubMed:18429042" FT /id="VAR_046469" FT VARIANT 377 FT /note="G -> R (in IOPD; dbSNP:rs752002666)" FT /evidence="ECO:0000269|PubMed:16860134" FT /id="VAR_029032" FT VARIANT 391 FT /note="M -> V (in IOPD; uncertain significance; FT dbSNP:rs778634337)" FT /evidence="ECO:0000269|PubMed:22644586, FT ECO:0000269|PubMed:25681614" FT /id="VAR_068593" FT VARIANT 397 FT /note="P -> L (in IOPD; uncertain significance; FT dbSNP:rs776008078)" FT /evidence="ECO:0000269|PubMed:22644586" FT /id="VAR_068594" FT VARIANT 401 FT /note="Q -> R (in IOPD; extremely low residual enzymatic FT activity)" FT /evidence="ECO:0000269|PubMed:18429042" FT /id="VAR_046470" FT VARIANT 402 FT /note="W -> R (in IOPD)" FT /id="VAR_004290" FT VARIANT 404 FT /note="D -> N (in IOPD; dbSNP:rs141533320)" FT /evidence="ECO:0000269|PubMed:16433701" FT /id="VAR_029033" FT VARIANT 405 FT /note="L -> P (in IOPD; loss of activity)" FT /evidence="ECO:0000269|PubMed:14695532" FT /id="VAR_018088" FT VARIANT 408 FT /note="M -> V (in IOPD; dbSNP:rs560575383)" FT /evidence="ECO:0000269|PubMed:11738358, FT ECO:0000269|PubMed:20080426" FT /id="VAR_029034" FT VARIANT 419 FT /note="D -> V (in IOPD)" FT /evidence="ECO:0000269|PubMed:22644586" FT /id="VAR_068595" FT VARIANT 431..433 FT /note="Missing (in IOPD)" FT /evidence="ECO:0000269|PubMed:22676651" FT /id="VAR_070017" FT VARIANT 437 FT /note="R -> C (in LOPD; dbSNP:rs770610356)" FT /evidence="ECO:0000269|PubMed:12601120" FT /id="VAR_029035" FT VARIANT 437 FT /note="R -> H (in IOPD; uncertain significance; FT dbSNP:rs150868652)" FT /evidence="ECO:0000269|PubMed:25681614" FT /id="VAR_074277" FT VARIANT 445 FT /note="A -> P (in LOPD)" FT /evidence="ECO:0000269|PubMed:16917947" FT /id="VAR_029036" FT VARIANT 455 FT /note="Y -> F (in LOPD; almost complete loss of activity)" FT /evidence="ECO:0000269|PubMed:14695532" FT /id="VAR_018089" FT VARIANT 457 FT /note="P -> H (in IOPD)" FT /evidence="ECO:0000269|PubMed:22644586" FT /id="VAR_068596" FT VARIANT 457 FT /note="P -> L (in LOPD)" FT /evidence="ECO:0000269|Ref.5" FT /id="VAR_029040" FT VARIANT 458 FT /note="Y -> C (in dbSNP:rs1358826817)" FT /evidence="ECO:0000269|PubMed:22644586" FT /id="VAR_068597" FT VARIANT 459 FT /note="Missing (in IOPD)" FT /evidence="ECO:0000269|PubMed:14695532" FT /id="VAR_018090" FT VARIANT 478 FT /note="G -> R (in IOPD; loss of activity; FT dbSNP:rs778068209)" FT /evidence="ECO:0000269|PubMed:14695532, FT ECO:0000269|PubMed:20080426" FT /id="VAR_004291" FT VARIANT 481 FT /note="W -> R (in LOPD; loss of activity; FT dbSNP:rs772883420)" FT /evidence="ECO:0000269|PubMed:10189220, FT ECO:0000269|PubMed:14695532" FT /id="VAR_004292" FT VARIANT 482 FT /note="P -> R (in IOPD)" FT /evidence="ECO:0000269|PubMed:18425781" FT /id="VAR_068598" FT VARIANT 483 FT /note="G -> V (in IOPD)" FT /evidence="ECO:0000269|PubMed:18425781" FT /id="VAR_068599" FT VARIANT 486 FT /note="A -> P (in LOPD)" FT /evidence="ECO:0000269|PubMed:19588081" FT /id="VAR_068600" FT VARIANT 489 FT /note="D -> N (in IOPD and LOPD; dbSNP:rs398123169)" FT /evidence="ECO:0000269|PubMed:16917947, FT ECO:0000269|PubMed:18429042" FT /id="VAR_029037" FT VARIANT 519 FT /note="M -> T (in IOPD; loss of activity; FT dbSNP:rs786204720)" FT /evidence="ECO:0000269|PubMed:14695532" FT /id="VAR_004293" FT VARIANT 519 FT /note="M -> V (in IOPD)" FT /evidence="ECO:0000269|PubMed:7866409" FT /id="VAR_004294" FT VARIANT 521 FT /note="E -> K (in IOPD; dbSNP:rs121907937)" FT /evidence="ECO:0000269|PubMed:1898413" FT /id="VAR_004295" FT VARIANT 521 FT /note="E -> Q (in IOPD)" FT /evidence="ECO:0000269|PubMed:18425781, FT ECO:0000269|PubMed:19588081" FT /id="VAR_068601" FT VARIANT 522 FT /note="P -> A (in IOPD and LOPD; no residual enzymatic FT activity; dbSNP:rs1057517146)" FT /evidence="ECO:0000269|PubMed:17643989, FT ECO:0000269|PubMed:18429042" FT /id="VAR_046471" FT VARIANT 522 FT /note="P -> S (in IOPD; dbSNP:rs892129065)" FT /evidence="ECO:0000269|PubMed:18425781" FT /id="VAR_068602" FT VARIANT 523 FT /note="S -> Y (in IOPD)" FT /evidence="ECO:0000269|PubMed:22644586" FT /id="VAR_068603" FT VARIANT 525 FT /note="F -> Y (in IOPD)" FT /evidence="ECO:0000269|PubMed:20080426" FT /id="VAR_068604" FT VARIANT 529 FT /note="S -> V (in LOPD; requires 2 nucleotide FT substitutions; dbSNP:rs121907941)" FT /evidence="ECO:0000269|PubMed:8834250" FT /id="VAR_004296" FT VARIANT 545 FT /note="P -> L (in LOPD; partial loss of activity; FT dbSNP:rs121907942)" FT /evidence="ECO:0000269|PubMed:10737124, FT ECO:0000269|PubMed:14695532, ECO:0000269|PubMed:7881422" FT /id="VAR_004297" FT VARIANT 549 FT /note="G -> R (in LOPD; partial loss of activity)" FT /evidence="ECO:0000269|PubMed:14695532, FT ECO:0000269|PubMed:16917947" FT /id="VAR_018091" FT VARIANT 552 FT /note="L -> P (in IOPD and LOPD; loss of activity; FT dbSNP:rs779556619)" FT /evidence="ECO:0000269|PubMed:14695532, FT ECO:0000269|PubMed:18429042, ECO:0000269|PubMed:19588081, FT ECO:0000269|PubMed:25681614" FT /id="VAR_018092" FT VARIANT 557 FT /note="I -> F (in IOPD; dbSNP:rs747150965)" FT /evidence="ECO:0000269|PubMed:20080426" FT /id="VAR_068605" FT VARIANT 558 FT /note="C -> S (in LOPD)" FT /evidence="ECO:0000269|PubMed:20350966, FT ECO:0000269|PubMed:22644586" FT /id="VAR_068606" FT VARIANT 566 FT /note="S -> P (in IOPD)" FT /evidence="ECO:0000269|PubMed:9521422" FT /id="VAR_004298" FT VARIANT 568 FT /note="H -> L (in IOPD)" FT /evidence="ECO:0000269|PubMed:22676651" FT /id="VAR_070018" FT VARIANT 570 FT /note="N -> K (in IOPD; dbSNP:rs765362308)" FT /evidence="ECO:0000269|PubMed:18425781" FT /id="VAR_068607" FT VARIANT 572 FT /note="H -> Q (in IOPD; dbSNP:rs772962666)" FT /evidence="ECO:0000269|PubMed:18425781" FT /id="VAR_068608" FT VARIANT 575 FT /note="Y -> C (in IOPD)" FT /evidence="ECO:0000269|PubMed:22644586" FT /id="VAR_068609" FT VARIANT 575 FT /note="Y -> S (in LOPD)" FT /evidence="ECO:0000269|PubMed:14695532" FT /id="VAR_018093" FT VARIANT 576 FT /note="G -> A" FT /id="VAR_004299" FT VARIANT 576 FT /note="G -> R (in IOPD)" FT /evidence="ECO:0000269|PubMed:22644586" FT /id="VAR_068610" FT VARIANT 576 FT /note="G -> S (retains about half of the activity compared FT with the wild-type; dbSNP:rs1800307)" FT /evidence="ECO:0000269|PubMed:14643388, FT ECO:0000269|PubMed:25681614" FT /id="VAR_004300" FT VARIANT 579 FT /note="E -> K (in IOPD; loss of activity; FT dbSNP:rs991082382)" FT /evidence="ECO:0000269|PubMed:14695532" FT /id="VAR_018094" FT VARIANT 585 FT /note="R -> K (in IOPD; dbSNP:rs747373179)" FT /evidence="ECO:0000269|PubMed:18425781" FT /id="VAR_068611" FT VARIANT 585 FT /note="R -> M (in LOPD)" FT /evidence="ECO:0000269|PubMed:11071489" FT /id="VAR_046472" FT VARIANT 594 FT /note="R -> H (in IOPD; dbSNP:rs775450536)" FT /evidence="ECO:0000269|PubMed:22644586" FT /id="VAR_068612" FT VARIANT 594 FT /note="R -> P (in IOPD and LOPD; dbSNP:rs775450536)" FT /evidence="ECO:0000269|PubMed:18425781, FT ECO:0000269|PubMed:19588081" FT /id="VAR_068613" FT VARIANT 599 FT /note="S -> Y (in IOPD; no residual enzymatic activity; FT dbSNP:rs753505203)" FT /evidence="ECO:0000269|PubMed:18429042" FT /id="VAR_046473" FT VARIANT 600 FT /note="R -> C (in LOPD; loss of activity; FT dbSNP:rs764670084)" FT /evidence="ECO:0000269|PubMed:14643388, FT ECO:0000269|PubMed:14695532" FT /id="VAR_018095" FT VARIANT 600 FT /note="R -> H (in IOPD; dbSNP:rs377544304)" FT /evidence="ECO:0000269|PubMed:10338092" FT /id="VAR_008689" FT VARIANT 601 FT /note="S -> L (in IOPD; dbSNP:rs374470794)" FT /evidence="ECO:0000269|PubMed:22644586, FT ECO:0000269|PubMed:22676651" FT /id="VAR_068614" FT VARIANT 602 FT /note="T -> A (in IOPD; dbSNP:rs781484283)" FT /evidence="ECO:0000269|PubMed:22644586" FT /id="VAR_068615" FT VARIANT 607..612 FT /note="Missing (in LOPD)" FT /evidence="ECO:0000269|PubMed:11071489" FT /id="VAR_046474" FT VARIANT 607 FT /note="G -> D (in IOPD; loss of activity; FT dbSNP:rs1393386120)" FT /evidence="ECO:0000269|PubMed:14695532" FT /id="VAR_018096" FT VARIANT 610 FT /note="A -> V (in LOPD)" FT /evidence="ECO:0000269|PubMed:17643989" FT /id="VAR_068616" FT VARIANT 611 FT /note="G -> D (in IOPD; dbSNP:rs1057517105)" FT /evidence="ECO:0000269|PubMed:22644586, FT ECO:0000269|PubMed:25681614" FT /id="VAR_068617" FT VARIANT 612 FT /note="H -> Q (in LOPD; dbSNP:rs768397968)" FT /evidence="ECO:0000269|PubMed:16917947" FT /id="VAR_029038" FT VARIANT 612 FT /note="H -> Y (in IOPD)" FT /evidence="ECO:0000269|PubMed:19588081" FT /id="VAR_068618" FT VARIANT 614 FT /note="T -> K (in IOPD; dbSNP:rs369531647)" FT /evidence="ECO:0000269|PubMed:18425781" FT /id="VAR_068619" FT VARIANT 615 FT /note="G -> R (in IOPD and LOPD; dbSNP:rs549029029)" FT /evidence="ECO:0000269|PubMed:10338092, FT ECO:0000269|PubMed:20080426" FT /id="VAR_008690" FT VARIANT 619 FT /note="S -> R (in LOPD; loss of function of the mutant FT enzyme; dbSNP:rs914396317)" FT /evidence="ECO:0000269|PubMed:14643388" FT /id="VAR_046475" FT VARIANT 627 FT /note="S -> P (in IOPD)" FT /evidence="ECO:0000269|PubMed:22644586" FT /id="VAR_068620" FT VARIANT 629 FT /note="P -> L (in dbSNP:rs746961289)" FT /evidence="ECO:0000269|PubMed:22644586" FT /id="VAR_068621" FT VARIANT 635 FT /note="N -> K (in IOPD and LOPD; dbSNP:rs1414146587)" FT /evidence="ECO:0000269|PubMed:19588081" FT /id="VAR_068622" FT VARIANT 638 FT /note="G -> V (in IOPD)" FT /evidence="ECO:0000269|PubMed:19588081" FT /id="VAR_068623" FT VARIANT 638 FT /note="G -> W (in IOPD and LOPD; dbSNP:rs757617999)" FT /evidence="ECO:0000269|PubMed:10737124, FT ECO:0000269|PubMed:18429042" FT /id="VAR_046476" FT VARIANT 641 FT /note="L -> V (in IOPD; uncertain significance; FT dbSNP:rs1420043899)" FT /evidence="ECO:0000269|PubMed:25681614" FT /id="VAR_074278" FT VARIANT 643 FT /note="G -> R (in IOPD and LOPD; dbSNP:rs28937909)" FT /evidence="ECO:0000269|PubMed:11071489, FT ECO:0000269|PubMed:16917947, ECO:0000269|PubMed:18429042, FT ECO:0000269|PubMed:19588081, ECO:0000269|PubMed:8401535, FT ECO:0000269|PubMed:9521422" FT /id="VAR_004301" FT VARIANT 645 FT /note="D -> E (in IOPD and LOPD; deficient in FT phosphorylation and in proteolytic processing; FT dbSNP:rs28940868)" FT /evidence="ECO:0000269|PubMed:1684505, FT ECO:0000269|PubMed:20080426, ECO:0000269|PubMed:8094613" FT /id="VAR_004302" FT VARIANT 645 FT /note="D -> H (in IOPD; almost complete loss of activity; FT dbSNP:rs368438393)" FT /evidence="ECO:0000269|PubMed:7695647" FT /id="VAR_004303" FT VARIANT 645 FT /note="D -> N (in IOPD; dbSNP:rs368438393)" FT /evidence="ECO:0000269|PubMed:15145338, FT ECO:0000269|PubMed:18429042, ECO:0000269|PubMed:9535769" FT /id="VAR_004304" FT VARIANT 647 FT /note="C -> W (in IOPD and LOPD; dbSNP:rs776948121)" FT /evidence="ECO:0000269|PubMed:19588081, FT ECO:0000269|PubMed:25681614, ECO:0000269|PubMed:7981676, FT ECO:0000269|PubMed:9535769" FT /id="VAR_004305" FT VARIANT 648 FT /note="G -> D (in IOPD; dbSNP:rs1448515860)" FT /evidence="ECO:0000269|PubMed:22644586" FT /id="VAR_068624" FT VARIANT 648 FT /note="G -> S (in LOPD; dbSNP:rs536906561)" FT /evidence="ECO:0000269|PubMed:9535769" FT /id="VAR_004306" FT VARIANT 660 FT /note="R -> H (in LOPD; loss of function of the mutant FT enzyme; dbSNP:rs374143224)" FT /evidence="ECO:0000269|PubMed:14643388" FT /id="VAR_046477" FT VARIANT 672 FT /note="R -> Q (in LOPD; dbSNP:rs778418246)" FT /evidence="ECO:0000269|PubMed:9535769" FT /id="VAR_004307" FT VARIANT 672 FT /note="R -> T (in LOPD)" FT /evidence="ECO:0000269|PubMed:11071489" FT /id="VAR_046478" FT VARIANT 672 FT /note="R -> W (in LOPD; dbSNP:rs757111744)" FT /evidence="ECO:0000269|PubMed:16917947, FT ECO:0000269|PubMed:9535769" FT /id="VAR_004308" FT VARIANT 675 FT /note="Missing (in IOPD)" FT /evidence="ECO:0000269|PubMed:10338092" FT /id="VAR_008692" FT VARIANT 689 FT /note="E -> K (in allele GAA*4; dbSNP:rs1800309)" FT /evidence="ECO:0000269|PubMed:25681614, FT ECO:0000269|PubMed:8912788" FT /id="VAR_004309" FT VARIANT 700..701 FT /note="Missing (in IOPD; uncertain significance)" FT /evidence="ECO:0000269|PubMed:22644586" FT /id="VAR_068625" FT VARIANT 702 FT /note="R -> C (in IOPD; no enzymatic activity; shows enzyme FT localization primarily in the ER-Golgi compartment FT suggesting that mutation could affect the normal processing FT and stability of the enzyme; dbSNP:rs786204645)" FT /evidence="ECO:0000269|PubMed:14972326" FT /id="VAR_046479" FT VARIANT 702 FT /note="R -> L (in IOPD; dbSNP:rs398123172)" FT /evidence="ECO:0000269|PubMed:22644586" FT /id="VAR_068626" FT VARIANT 705 FT /note="L -> P (in IOPD; uncertain significance)" FT /evidence="ECO:0000269|PubMed:25681614" FT /id="VAR_074279" FT VARIANT 711 FT /note="T -> R (in IOPD; uncertain significance; FT dbSNP:rs759292700)" FT /evidence="ECO:0000269|PubMed:20080426" FT /id="VAR_068627" FT VARIANT 718 FT /note="V -> I (in dbSNP:rs141017311)" FT /evidence="ECO:0000269|PubMed:22644586" FT /id="VAR_068628" FT VARIANT 725 FT /note="R -> W (in LOPD; dbSNP:rs121907938)" FT /evidence="ECO:0000269|PubMed:8401535" FT /id="VAR_004310" FT VARIANT 737 FT /note="T -> N (in IOPD; dbSNP:rs1381005435)" FT /evidence="ECO:0000269|PubMed:18425781" FT /id="VAR_068629" FT VARIANT 743 FT /note="Q -> K (in IOPD)" FT /evidence="ECO:0000269|PubMed:22644586" FT /id="VAR_068630" FT VARIANT 746 FT /note="W -> C (in IOPD and LOPD; dbSNP:rs1800312)" FT /evidence="ECO:0000269|PubMed:16917947, FT ECO:0000269|PubMed:20080426" FT /id="VAR_004311" FT VARIANT 746 FT /note="W -> G (in IOPD; dbSNP:rs1479740763)" FT /evidence="ECO:0000269|PubMed:20080426" FT /id="VAR_068631" FT VARIANT 746 FT /note="W -> S (in IOPD; dbSNP:rs752921215)" FT /evidence="ECO:0000269|PubMed:18425781" FT /id="VAR_068632" FT VARIANT 766 FT /note="Y -> C (in IOPD; dbSNP:rs144016984)" FT /evidence="ECO:0000269|PubMed:22676651" FT /id="VAR_070019" FT VARIANT 768 FT /note="P -> R (in IOPD)" FT /evidence="ECO:0000269|PubMed:9521422" FT /id="VAR_004312" FT VARIANT 780 FT /note="V -> I (in dbSNP:rs1126690)" FT /evidence="ECO:0000269|PubMed:2111708, FT ECO:0000269|PubMed:2268276, ECO:0000269|PubMed:25681614, FT ECO:0000269|PubMed:3049072, ECO:0000269|PubMed:7717400, FT ECO:0000269|Ref.5" FT /id="VAR_004313" FT VARIANT 816 FT /note="V -> I (in dbSNP:rs1800314)" FT /evidence="ECO:0000269|PubMed:1684505, FT ECO:0000269|PubMed:25681614, ECO:0000269|PubMed:8094613, FT ECO:0000269|PubMed:8486380" FT /id="VAR_004314" FT VARIANT 819 FT /note="R -> P (in IOPD)" FT /evidence="ECO:0000269|PubMed:22644586" FT /id="VAR_068633" FT VARIANT 880 FT /note="A -> D (in IOPD; loss of activity)" FT /evidence="ECO:0000269|PubMed:14695532" FT /id="VAR_018097" FT VARIANT 901 FT /note="L -> Q (in IOPD)" FT /evidence="ECO:0000269|PubMed:15145338" FT /id="VAR_029039" FT VARIANT 903 FT /note="Missing (in IOPD; loss of activity)" FT /evidence="ECO:0000269|PubMed:7717400" FT /id="VAR_004315" FT VARIANT 913 FT /note="P -> R (in IOPD; dbSNP:rs1480070037)" FT /evidence="ECO:0000269|PubMed:22676651" FT /id="VAR_070020" FT VARIANT 916 FT /note="V -> F (in IOPD; dbSNP:rs1221948995)" FT /evidence="ECO:0000269|PubMed:22644586" FT /id="VAR_068634" FT VARIANT 925 FT /note="N -> NGVPVSN (in IOPD)" FT /evidence="ECO:0000269|PubMed:10206684" FT /id="VAR_004316" FT VARIANT 927 FT /note="T -> I (loss of glycosylation site; FT dbSNP:rs1800315)" FT /evidence="ECO:0000269|PubMed:1684505, FT ECO:0000269|PubMed:8094613, ECO:0000269|PubMed:8486380" FT /id="VAR_004317" FT VARIANT 935 FT /note="L -> P (in IOPD)" FT /evidence="ECO:0000269|PubMed:18425781" FT /id="VAR_068635" FT VARIANT 949 FT /note="V -> D (in IOPD; dbSNP:rs1245412108)" FT /evidence="ECO:0000269|PubMed:9529346" FT /id="VAR_004318" FT MUTAGEN 516 FT /note="W->R: Loss of activity." FT /evidence="ECO:0000269|PubMed:1856189" FT MUTAGEN 518 FT /note="D->G,N,E: Loss of activity." FT /evidence="ECO:0000269|PubMed:1856189" FT HELIX 80..82 FT /evidence="ECO:0007829|PDB:5KZW" FT HELIX 86..88 FT /evidence="ECO:0007829|PDB:8CB1" FT STRAND 94..96 FT /evidence="ECO:0007829|PDB:8CB1" FT HELIX 100..105 FT /evidence="ECO:0007829|PDB:8CB1" FT STRAND 126..128 FT /evidence="ECO:0007829|PDB:8CB1" FT STRAND 137..143 FT /evidence="ECO:0007829|PDB:8CB1" FT STRAND 145..153 FT /evidence="ECO:0007829|PDB:8CB1" FT STRAND 159..163 FT /evidence="ECO:0007829|PDB:8CB1" FT STRAND 166..173 FT /evidence="ECO:0007829|PDB:8CB1" FT STRAND 175..184 FT /evidence="ECO:0007829|PDB:8CB1" FT STRAND 208..215 FT /evidence="ECO:0007829|PDB:8CB1" FT STRAND 218..224 FT /evidence="ECO:0007829|PDB:8CB1" FT TURN 225..227 FT /evidence="ECO:0007829|PDB:8CB1" FT STRAND 230..233 FT /evidence="ECO:0007829|PDB:8CB1" FT HELIX 234..236 FT /evidence="ECO:0007829|PDB:8CB1" FT STRAND 240..242 FT /evidence="ECO:0007829|PDB:8CB1" FT STRAND 245..251 FT /evidence="ECO:0007829|PDB:8CB1" FT STRAND 253..255 FT /evidence="ECO:0007829|PDB:8CB1" FT STRAND 257..259 FT /evidence="ECO:0007829|PDB:8CB1" FT STRAND 262..264 FT /evidence="ECO:0007829|PDB:9GTN" FT STRAND 272..278 FT /evidence="ECO:0007829|PDB:8CB1" FT STRAND 297..301 FT /evidence="ECO:0007829|PDB:8CB1" FT STRAND 307..312 FT /evidence="ECO:0007829|PDB:8CB1" FT STRAND 318..323 FT /evidence="ECO:0007829|PDB:8CB1" FT TURN 324..326 FT /evidence="ECO:0007829|PDB:8CB1" FT STRAND 327..335 FT /evidence="ECO:0007829|PDB:8CB1" FT STRAND 337..342 FT /evidence="ECO:0007829|PDB:8CB1" FT HELIX 347..358 FT /evidence="ECO:0007829|PDB:8CB1" FT HELIX 360..365 FT /evidence="ECO:0007829|PDB:9GTW" FT HELIX 366..369 FT /evidence="ECO:0007829|PDB:8CB1" FT STRAND 370..373 FT /evidence="ECO:0007829|PDB:9GSV" FT HELIX 381..393 FT /evidence="ECO:0007829|PDB:8CB1" FT STRAND 399..403 FT /evidence="ECO:0007829|PDB:8CB1" FT HELIX 405..407 FT /evidence="ECO:0007829|PDB:8CB1" FT TURN 420..423 FT /evidence="ECO:0007829|PDB:8CB1" FT HELIX 424..433 FT /evidence="ECO:0007829|PDB:8CB1" FT STRAND 437..442 FT /evidence="ECO:0007829|PDB:8CB1" FT HELIX 456..464 FT /evidence="ECO:0007829|PDB:8CB1" FT STRAND 473..475 FT /evidence="ECO:0007829|PDB:8CB1" FT STRAND 478..480 FT /evidence="ECO:0007829|PDB:8CB1" FT STRAND 483..486 FT /evidence="ECO:0007829|PDB:8CB1" FT HELIX 493..509 FT /evidence="ECO:0007829|PDB:8CB1" FT STRAND 515..517 FT /evidence="ECO:0007829|PDB:8CB1" FT TURN 520..522 FT /evidence="ECO:0007829|PDB:8CB1" FT STRAND 525..528 FT /evidence="ECO:0007829|PDB:8CB1" FT TURN 537..539 FT /evidence="ECO:0007829|PDB:8CB1" FT TURN 552..555 FT /evidence="ECO:0007829|PDB:8CB1" FT STRAND 564..567 FT /evidence="ECO:0007829|PDB:8CB1" FT HELIX 568..571 FT /evidence="ECO:0007829|PDB:8CB1" FT HELIX 572..574 FT /evidence="ECO:0007829|PDB:8CB1" FT HELIX 575..591 FT /evidence="ECO:0007829|PDB:8CB1" FT STRAND 597..601 FT /evidence="ECO:0007829|PDB:8CB1" FT HELIX 606..608 FT /evidence="ECO:0007829|PDB:8CB1" FT STRAND 611..613 FT /evidence="ECO:0007829|PDB:8CB1" FT STRAND 618..620 FT /evidence="ECO:0007829|PDB:8CB1" FT HELIX 621..636 FT /evidence="ECO:0007829|PDB:8CB1" FT STRAND 641..643 FT /evidence="ECO:0007829|PDB:8CB1" FT STRAND 649..651 FT /evidence="ECO:0007829|PDB:8CB1" FT HELIX 655..665 FT /evidence="ECO:0007829|PDB:8CB1" FT STRAND 668..670 FT /evidence="ECO:0007829|PDB:8CB1" FT STRAND 677..679 FT /evidence="ECO:0007829|PDB:5NN8" FT HELIX 684..686 FT /evidence="ECO:0007829|PDB:8CB1" FT HELIX 689..719 FT /evidence="ECO:0007829|PDB:8CB1" FT STRAND 723..725 FT /evidence="ECO:0007829|PDB:8CB1" FT HELIX 727..730 FT /evidence="ECO:0007829|PDB:8CB1" FT HELIX 735..737 FT /evidence="ECO:0007829|PDB:8CB1" FT STRAND 742..746 FT /evidence="ECO:0007829|PDB:8CB1" FT TURN 747..749 FT /evidence="ECO:0007829|PDB:8CB1" FT STRAND 750..753 FT /evidence="ECO:0007829|PDB:8CB1" FT STRAND 761..767 FT /evidence="ECO:0007829|PDB:8CB1" FT STRAND 769..774 FT /evidence="ECO:0007829|PDB:8CB1" FT HELIX 775..777 FT /evidence="ECO:0007829|PDB:8CB1" FT HELIX 787..790 FT /evidence="ECO:0007829|PDB:9GTN" FT STRAND 796..808 FT /evidence="ECO:0007829|PDB:8CB1" FT STRAND 815..819 FT /evidence="ECO:0007829|PDB:8CB1" FT STRAND 822..827 FT /evidence="ECO:0007829|PDB:8CB1" FT HELIX 833..836 FT /evidence="ECO:0007829|PDB:8CB1" FT STRAND 841..846 FT /evidence="ECO:0007829|PDB:8CB1" FT STRAND 853..859 FT /evidence="ECO:0007829|PDB:8CB1" FT HELIX 867..870 FT /evidence="ECO:0007829|PDB:8CB1" FT STRAND 874..881 FT /evidence="ECO:0007829|PDB:8CB1" FT STRAND 884..891 FT /evidence="ECO:0007829|PDB:8CB1" FT TURN 894..898 FT /evidence="ECO:0007829|PDB:8CB1" FT STRAND 900..907 FT /evidence="ECO:0007829|PDB:8CB1" FT STRAND 916..918 FT /evidence="ECO:0007829|PDB:8CB1" FT STRAND 926..929 FT /evidence="ECO:0007829|PDB:8CB1" FT TURN 930..933 FT /evidence="ECO:0007829|PDB:8CB1" FT STRAND 934..942 FT /evidence="ECO:0007829|PDB:8CB1" FT STRAND 948..951 FT /evidence="ECO:0007829|PDB:8CB1" SQ SEQUENCE 952 AA; 105324 MW; 6E2717BF7201F469 CRC64; MGVRHPPCSH RLLAVCALVS LATAALLGHI LLHDFLLVPR ELSGSSPVLE ETHPAHQQGA SRPGPRDAQA HPGRPRAVPT QCDVPPNSRF DCAPDKAITQ EQCEARGCCY IPAKQGLQGA QMGQPWCFFP PSYPSYKLEN LSSSEMGYTA TLTRTTPTFF PKDILTLRLD VMMETENRLH FTIKDPANRR YEVPLETPHV HSRAPSPLYS VEFSEEPFGV IVRRQLDGRV LLNTTVAPLF FADQFLQLST SLPSQYITGL AEHLSPLMLS TSWTRITLWN RDLAPTPGAN LYGSHPFYLA LEDGGSAHGV FLLNSNAMDV VLQPSPALSW RSTGGILDVY IFLGPEPKSV VQQYLDVVGY PFMPPYWGLG FHLCRWGYSS TAITRQVVEN MTRAHFPLDV QWNDLDYMDS RRDFTFNKDG FRDFPAMVQE LHQGGRRYMM IVDPAISSSG PAGSYRPYDE GLRRGVFITN ETGQPLIGKV WPGSTAFPDF TNPTALAWWE DMVAEFHDQV PFDGMWIDMN EPSNFIRGSE DGCPNNELEN PPYVPGVVGG TLQAATICAS SHQFLSTHYN LHNLYGLTEA IASHRALVKA RGTRPFVISR STFAGHGRYA GHWTGDVWSS WEQLASSVPE ILQFNLLGVP LVGADVCGFL GNTSEELCVR WTQLGAFYPF MRNHNSLLSL PQEPYSFSEP AQQAMRKALT LRYALLPHLY TLFHQAHVAG ETVARPLFLE FPKDSSTWTV DHQLLWGEAL LITPVLQAGK AEVTGYFPLG TWYDLQTVPV EALGSLPPPP AAPREPAIHS EGQWVTLPAP LDTINVHLRA GYIIPLQGPG LTTTESRQQP MALAVALTKG GEARGELFWD DGESLEVLER GAYTQVIFLA RNNTIVNELV RVTSEGAGLQ LQKVTVLGVA TAPQQVLSNG VPVSNFTYSP DTKVLDICVS LLMGEQFLVS WC //