Reviewed, UniProtKB/Swiss-Prot P10253 (LYAG_HUMAN)

Names and origin

Protein names

Recommended name:
    Lysosomal alpha-glucosidase
    EC=3.2.1.20
Alternative name(s):
    Acid maltase
    Aglucosidase alfa
Cleaved into the following 2 chains:
    1- Recommended name:
            76 kDa lysosomal alpha-glucosidase
    2- Recommended name:
            70 kDa lysosomal alpha-glucosidase

Gene names

Name:

GAA

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	952 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Essential for the degradation of glygogen to glucose in lysosomes.
Catalytic activity	Hydrolysis of terminal, non-reducing (1->4)-linked alpha-D-glucose residues with release of alpha-D-glucose.
Subcellular location	Lysosome.
Post-translational modification	The different forms of acid glucosidase are obtained by proteolytic processing. Phosphorylation of mannose residues ensures efficient transport of the enzyme to the lysosomes via the mannose 6-phosphate receptor.
Polymorphism	There are three common alleles of GAA: GAA*1, GAA*2 and GAA*4. The sequence shown is that of allele GAA*1, which is the most common. Alleles GAA*2 and GAA*4 are much rarer.
Involvement in disease	Defects in GAA are the cause of glycogen storage disease type 2 (GSD2) [MIM:232300]; also called acid alpha-glucosidase (GAA) deficiency or acid maltase deficiency (AMD). GSD2 is a metabolic disorder with a broad clinical spectrum. The severe infantile form, or Pompe disease, presents at birth with massive accumulation of glycogen in muscle, heart and liver. Cardiomyopathy and muscular hypotonia are the cardinal features of this form whose life expectancy is less than two years. The juvenile and adult forms present as limb-girdle muscular dystrophy beginning in the lower limbs. Final outcome depends on respiratory muscle failure. Patients with the adult form can be free of clinical symptoms for most of their life but finally develop a slowly progressive myopathy. Ref.5 Ref.8 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 Ref.23 Ref.24 Ref.25 Ref.26 Ref.28 Ref.29 Ref.30 Ref.31 Ref.32 Ref.33 Ref.34 Ref.35 Ref.36 Ref.37 Ref.38 Ref.39 Ref.40 Ref.41 Ref.42 Ref.43 Ref.44 Ref.45 Ref.46 Ref.47 Ref.48
Sequence similarities	Belongs to the glycosyl hydrolase 31 family. Contains 1 P-type (trefoil) domain.

Ontologies

Keywords
Cellular component	Lysosome
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Signal
Molecular function	Glycosidase Hydrolase
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	cardiac muscle contraction Inferred from mutant phenotype. Source: UniProtKB diaphragm contraction Ref.47 Inferred from mutant phenotype. Source: UniProtKB glucose metabolic process Inferred by curator. Source: UniProtKB glycogen catabolic process Inferred from direct assay. Source: UniProtKB lysosome organization Ref.26 Inferred from mutant phenotype. Source: UniProtKB maltose metabolic process Inferred by curator. Source: UniProtKB muscle organ development Ref.26 Inferred from mutant phenotype. Source: UniProtKB sucrose metabolic process Inferred by curator. Source: UniProtKB tongue morphogenesis Inferred from mutant phenotype. Source: UniProtKB vacuolar sequestering Inferred from mutant phenotype. Source: UniProtKB ventricular cardiac muscle tissue morphogenesis Inferred from mutant phenotype. Source: UniProtKB
Cellular component	lysosome Inferred from direct assay. Source: UniProtKB
Molecular function	alpha-glucosidase activity Inferred from direct assay. Source: UniProtKB sugar binding Inferred by curator. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 27	27	Potential
	Propeptide	28 – 69	42			PRO_0000018565
	Chain	70 – 952	883	Lysosomal alpha-glucosidase		PRO_0000018566
	Chain	123 – 952	830	76 kDa lysosomal alpha-glucosidase		PRO_0000018567
	Chain	204 – 952	749	70 kDa lysosomal alpha-glucosidase		PRO_0000018568
Regions
	Domain	80 – 131	52	P-type
Sites
	Active site	518	1	Nucleophile Ref.9
	Active site	521	1	By similarity
Amino acid modifications
	Glycosylation	140	1	N-linked (GlcNAc...) Ref.10 Ref.15
	Glycosylation	233	1	N-linked (GlcNAc...) Ref.10
	Glycosylation	390	1	N-linked (GlcNAc...) Ref.10 Ref.13
	Glycosylation	470	1	N-linked (GlcNAc...) Ref.10 Ref.15 Ref.11
	Glycosylation	652	1	N-linked (GlcNAc...) Ref.10
	Glycosylation	882	1	N-linked (GlcNAc...) Ref.10 Ref.15
	Glycosylation	925	1	N-linked (GlcNAc...) Ref.10 Ref.15
	Disulfide bond	82 ↔ 109		By similarity
	Disulfide bond	92 ↔ 108		By similarity
	Disulfide bond	103 ↔ 127		By similarity
Natural variations
	Natural variant	91	1	D → N in allele GAA*2; lower affinity for glycogen and starch but not for lower-molecular weight substrates. dbSNP rs1800299. Ref.31 Ref.16		VAR_004285
	Natural variant	103	1	C → G in GSD2; infantile form; severe; loss of activity; shows enzyme localization primarily in the ER-Golgi compartment suggesting that mutation could affect the normal processing and stability of the enzyme. Ref.41 Ref.48		VAR_018078
	Natural variant	191	1	Y → C in GSD2; extremely low residual enzymatic activity. Ref.48		VAR_046467
	Natural variant	199	1	H → R: dbSNP rs1042393. Ref.5 Ref.26 Ref.31 Ref.1		VAR_004286
	Natural variant	208	1	L → P in GSD2. Ref.36		VAR_029025
	Natural variant	219	1	G → R in GSD2; infantile form; severe; loss of activity. Ref.37 Ref.41 Ref.48		VAR_018079
	Natural variant	223	1	H → R: dbSNP rs1042395. Ref.26 Ref.31 Ref.3 Ref.4 Ref.6 Ref.7		VAR_004287
	Natural variant	224	1	R → W in GSD2; infantile; mild partial loss of activity. Ref.38 Ref.40 Ref.48		VAR_029026
	Natural variant	237	1	A → V in GSD2. Ref.44		VAR_029027
	Natural variant	262	1	E → K in GSD2; infantile; severe. Ref.37 Ref.48		VAR_029028
	Natural variant	285	1	P → R in GSD2; juvenile form; mild; partial loss of activity. Ref.41		VAR_018080
	Natural variant	292	1	Y → C in GSD2; juvenile form; mild; partial loss of activity. Ref.41		VAR_018081
	Natural variant	293	1	G → R in GSD2; infantile form; severe; almost complete loss of activity. Ref.41 Ref.44 Ref.48		VAR_018082
	Natural variant	299	1	L → R in GSD2; infantile form. Ref.26		VAR_004288
	Natural variant	308	1	H → L in GSD2. Ref.36		VAR_046468
	Natural variant	308	1	H → P in GSD2; infantile form; severe; complete loss of activity. Ref.41		VAR_018083
	Natural variant	309	1	G → R in GSD2; severe. Ref.30 Ref.47		VAR_018084
	Natural variant	312	1	L → R in GSD2; infantile form; severe; loss of activity. Ref.41		VAR_018085
	Natural variant	318	1	M → T in GSD2; severe. Ref.17		VAR_004289
	Natural variant	324	1	P → L in GSD2. Ref.36		VAR_029029
	Natural variant	330	1	W → G in GSD2; infantile form; severe. Ref.45		VAR_029030
	Natural variant	355	1	L → P in GSD2; infantile form; severe; loss of activity. Ref.41 Ref.42 Ref.47 Ref.48		VAR_018086
	Natural variant	361	1	P → L in GSD2; juvenile form; severe. Ref.39 Ref.47		VAR_029031
	Natural variant	374	1	C → R in GSD2; infantile form; severe; loss of activity. Ref.41		VAR_018087
	Natural variant	375	1	R → L in GSD2; extremely low residual enzymatic activity. Ref.48		VAR_046469
	Natural variant	377	1	G → R in GSD2; severe.		VAR_029032
	Natural variant	401	1	Q → R in GSD2; extremely low residual enzymatic activity. Ref.48		VAR_046470
	Natural variant	402	1	W → R in GSD2; severe.		VAR_004290
	Natural variant	404	1	D → N in GSD2; severe. Ref.46		VAR_029033
	Natural variant	405	1	L → P in GSD2; infantile form; severe; loss of activity. Ref.41		VAR_018088
	Natural variant	408	1	M → V in GSD2; juvenile form; severe. Ref.37		VAR_029034
	Natural variant	437	1	R → C in GSD2; juvenile form; severe. Ref.39		VAR_029035
	Natural variant	445	1	A → P in GSD2. Ref.47		VAR_029036
	Natural variant	455	1	Y → F in GSD2; juvenile form; almost complete loss of activity. Ref.41		VAR_018089
	Natural variant	457	1	P → L in GSD2; juvenile form. Ref.5		VAR_029040
	Natural variant	459	1	Missing in GSD2; infantile form; severe.		VAR_018090
	Natural variant	478	1	G → R in GSD2; severe; loss of activity. Ref.41		VAR_004291
	Natural variant	481	1	W → R in GSD2; severe; loss of activity. Ref.34 Ref.41		VAR_004292
	Natural variant	489	1	D → N in GSD2; severe. Ref.47 Ref.48		VAR_029037
	Natural variant	519	1	M → T in GSD2; severe; loss of activity. Ref.41		VAR_004293
	Natural variant	519	1	M → V in GSD2. Ref.23		VAR_004294
	Natural variant	521	1	E → K in GSD2; severe. Ref.18		VAR_004295
	Natural variant	522	1	P → A in GSD2; no residual enzymatic activity. Ref.48		VAR_046471
	Natural variant	529	1	S → V in GSD2; mild; requires 2 nucleotide substitutions. Ref.28		VAR_004296
	Natural variant	545	1	P → L in GSD2; mild; partial loss of activity. Ref.25 Ref.33 Ref.41		VAR_004297
	Natural variant	549	1	G → R in GSD2; juvenile form; mild; partial loss of activity. Ref.41 Ref.47		VAR_018091
	Natural variant	552	1	L → P in GSD2; infantile/juvenile form; severe; loss of activity. Ref.41 Ref.48		VAR_018092
	Natural variant	566	1	S → P in GSD2; infantile form. Ref.31		VAR_004298
	Natural variant	575	1	Y → S in GSD2; juvenile form. Ref.41		VAR_018093
	Natural variant	576	1	G → A		VAR_004299
	Natural variant	576	1	G → S Retains about half of the activity compared with the wild-type. dbSNP rs1800307. Ref.40		VAR_004300
	Natural variant	579	1	E → K in GSD2; infantile form; severe; loss of activity. Ref.41		VAR_018094
	Natural variant	585	1	R → M in GSD2. Ref.36		VAR_046472
	Natural variant	599	1	S → Y in GSD2; no residual enzymatic activity. Ref.48		VAR_046473
	Natural variant	600	1	R → C in GSD2; juvenile form; loss of activity. Ref.40 Ref.41		VAR_018095
	Natural variant	600	1	R → H in GSD2; infantile form.		VAR_008689
	Natural variant	607 – 612	6	Missing in GSD2.		VAR_046474
	Natural variant	607	1	G → D in GSD2; infantile form; severe; loss of activity. Ref.41		VAR_018096
	Natural variant	612	1	H → Q in GSD2. Ref.47		VAR_029038
	Natural variant	615	1	G → R in GSD2; infantile/adult form.		VAR_008690
	Natural variant	619	1	S → R in GSD2; loss of function of the mutant enzyme. Ref.40		VAR_046475
	Natural variant	638	1	G → W in GSD2. Ref.33 Ref.48		VAR_046476
	Natural variant	643	1	G → R in GSD2; infantile form. Ref.19 Ref.31 Ref.36 Ref.47 Ref.48		VAR_004301
	Natural variant	645	1	D → E in GSD2; infantile form; most common mutation; deficient in phosphorylation and in proteolytic processing. Ref.20 Ref.21		VAR_004302
	Natural variant	645	1	D → H in GSD2; almost complete loss of activity. Ref.8		VAR_004303
	Natural variant	645	1	D → N in GSD2. Ref.29 Ref.43 Ref.48		VAR_004304
	Natural variant	647	1	C → W in GSD2. Ref.24 Ref.29		VAR_004305
	Natural variant	648	1	G → S in GSD2. Ref.29		VAR_004306
	Natural variant	660	1	R → H in GSD2; loss of function of the mutant enzyme. Ref.40		VAR_046477
	Natural variant	672	1	R → Q in GSD2. Ref.29		VAR_004307
	Natural variant	672	1	R → T in GSD2. Ref.36		VAR_046478
	Natural variant	672	1	R → W in GSD2. Ref.29 Ref.47		VAR_004308
	Natural variant	675	1	Missing in GSD2; infantile form.		VAR_008692
	Natural variant	689	1	E → K in allele GAA*4. dbSNP rs1800309. Ref.27		VAR_004309
	Natural variant	702	1	R → C in GSD2; no enzymatic activity; shows enzyme localization primarily in the ER-Golgi compartment suggesting that mutation could affect the normal processing and stability of the enzyme. Ref.42		VAR_046479
	Natural variant	725	1	R → W in GSD2; adult form. Ref.19		VAR_004310
	Natural variant	746	1	W → C: dbSNP rs1800312. Ref.47		VAR_004311
	Natural variant	768	1	P → R in GSD2; infantile form. Ref.31		VAR_004312
	Natural variant	780	1	I → V: dbSNP rs1126690. Ref.26 Ref.6 Ref.7		VAR_004313
	Natural variant	816	1	V → I: dbSNP rs1800314. Ref.20 Ref.21 Ref.22		VAR_004314
	Natural variant	880	1	A → D in GSD2; infantile form; severe; loss of activity. Ref.41		VAR_018097
	Natural variant	901	1	L → Q in GSD2; infantile form; severe. Ref.43		VAR_029039
	Natural variant	903	1	Missing in GSD2; infantile form; severe; loss of activity.		VAR_004315
	Natural variant	925	1	N → NGVPVSN in GSD2.		VAR_004316
	Natural variant	927	1	T → I Loss of glycosylation site. dbSNP rs1800315. Ref.20 Ref.21 Ref.22		VAR_004317
	Natural variant	949	1	V → D in GSD2.		VAR_004318
Experimental info
	Mutagenesis	516	1	W → R: Loss of activity. Ref.9
	Mutagenesis	518	1	D → G, N or E: Loss of activity. Ref.9

Sequences

	Sequence		Length	Mass (Da)
	P10253-1 [UniParc]. Last modified July 7, 2009. Version 3. Checksum: E1532FCBD76C317B	FASTA	952	105,319
	10 20 30 40 50 60 MGVRHPPCSH RLLAVCALVS LATAALLGHI LLHDFLLVPR ELSGSSPVLE ETHPAHQQGA 70 80 90 100 110 120 SRPGPRDAQA HPGRPRAVPT QCDVPPNSRF DCAPDKAITQ EQCEARGCCY IPAKQGLQGA 130 140 150 160 170 180 QMGQPWCFFP PSYPSYKLEN LSSSEMGYTA TLTRTTPTFF PKDILTLRLD VMMETENRLH 190 200 210 220 230 240 FTIKDPANRR YEVPLETPHV HSRAPSPLYS VEFSEEPFGV IVHRQLDGRV LLNTTVAPLF 250 260 270 280 290 300 FADQFLQLST SLPSQYITGL AEHLSPLMLS TSWTRITLWN RDLAPTPGAN LYGSHPFYLA 310 320 330 340 350 360 LEDGGSAHGV FLLNSNAMDV VLQPSPALSW RSTGGILDVY IFLGPEPKSV VQQYLDVVGY 370 380 390 400 410 420 PFMPPYWGLG FHLCRWGYSS TAITRQVVEN MTRAHFPLDV QWNDLDYMDS RRDFTFNKDG 430 440 450 460 470 480 FRDFPAMVQE LHQGGRRYMM IVDPAISSSG PAGSYRPYDE GLRRGVFITN ETGQPLIGKV 490 500 510 520 530 540 WPGSTAFPDF TNPTALAWWE DMVAEFHDQV PFDGMWIDMN EPSNFIRGSE DGCPNNELEN 550 560 570 580 590 600 PPYVPGVVGG TLQAATICAS SHQFLSTHYN LHNLYGLTEA IASHRALVKA RGTRPFVISR 610 620 630 640 650 660 STFAGHGRYA GHWTGDVWSS WEQLASSVPE ILQFNLLGVP LVGADVCGFL GNTSEELCVR 670 680 690 700 710 720 WTQLGAFYPF MRNHNSLLSL PQEPYSFSEP AQQAMRKALT LRYALLPHLY TLFHQAHVAG 730 740 750 760 770 780 ETVARPLFLE FPKDSSTWTV DHQLLWGEAL LITPVLQAGK AEVTGYFPLG TWYDLQTVPI 790 800 810 820 830 840 EALGSLPPPP AAPREPAIHS EGQWVTLPAP LDTINVHLRA GYIIPLQGPG LTTTESRQQP 850 860 870 880 890 900 MALAVALTKG GEARGELFWD DGESLEVLER GAYTQVIFLA RNNTIVNELV RVTSEGAGLQ 910 920 930 940 950 LQKVTVLGVA TAPQQVLSNG VPVSNFTYSP DTKVLDICVS LLMGEQFLVS WC

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Primary structure and processing of lysosomal alpha-glucosidase; homology with the intestinal sucrase-isomaltase complex." Hoefsloot L.H., Hoogeveen-Westerveld M., Kroos M.A., van Beeumen J., Reuser A.J.J., Oostra B.A. EMBO J. 7:1697-1704(1988) [PubMed: 3049072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE OF 70-89; 123-145; 204-215; 230-249; 332-345; 349-370; 394-409; 480-513; 520-545; 703-719; 726-731 AND 795-803, VARIANT ARG-199. Tissue: Placenta, Testis and Urine.
[2]	Reuser A.J.J. Submitted (JUN-1990) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION.
[3]	"Characterization of the human lysosomal alpha-glucosidase gene." Hoefsloot L.H., Hoogeveen-Westerveld M., Reuser A.J.J., Oostra B.A. Biochem. J. 272:493-497(1990) [PubMed: 2268276] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ARG-223.
[4]	"Sequence of the cDNA and 5'-flanking region for human acid alpha-glucosidase, detection of an intron in the 5' untranslated leader sequence, definition of 18-bp polymorphisms, and differences with previous cDNA and amino acid sequences." Martiniuk F., Mehler M., Tzall S., Meredith G., Hirschhorn R. DNA Cell Biol. 9:85-94(1990) [PubMed: 2111708] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ARG-223.
[5]	"Identification of a novel mutation in the acid alpha glucosidase gene causing juvenile form of Pompe disease in Iranian population." Ghaffari S.R., Sabokbar T., Tahmasebi S., Dastan J. Submitted (AUG-2006) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS ARG-199 AND GSD2 LEU-457.
[6]	"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage." Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L. , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C. Nature 440:1045-1049(2006) [PubMed: 16625196] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANTS ARG-223 AND VAL-780.
[7]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS ARG-223 AND VAL-780. Tissue: Duodenum.
[8]	"Identification of a de novo point mutation resulting in infantile form of Pompe's disease." Lin C.-Y., Shieh J.-J. Biochem. Biophys. Res. Commun. 208:886-893(1995) [PubMed: 7695647] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 631-680, VARIANT GSD2 HIS-645.
[9]	"Human lysosomal alpha-glucosidase. Characterization of the catalytic site." Hermans M.M.P., Kroos M.A., van Beeumen J., Oostra B.A., Reuser A.J.J. J. Biol. Chem. 266:13507-13512(1991) [PubMed: 1856189] [Abstract] Cited for: MUTAGENESIS OF TRP-516 AND ASP-518, ACTIVE SITE.
[10]	"Human lysosomal alpha-glucosidase: functional characterization of the glycosylation sites." Hermans M.M.P., Wisselaar H.A., Kroos M.A., Oostra B.A., Reuser A.J.J. Biochem. J. 289:681-686(1993) [PubMed: 8435067] [Abstract] Cited for: GLYCOSYLATION AT ASN-140; ASN-233; ASN-390; ASN-470; ASN-652; ASN-882 AND ASN-925.
[11]	"Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry." Zhang H., Li X.-J., Martin D.B., Aebersold R. Nat. Biotechnol. 21:660-666(2003) [PubMed: 12754519] [Abstract] Cited for: GLYCOSYLATION AT ASN-470.
[12]	"Glycogenosis type II (acid maltase deficiency)." Reuser A.J.J., Kroos M.A., Hermans M.M.P., Bijvoet A.G.A., Verbeet M.P., van Diggelen O.P., Kleijer W.J., van der Ploeg A.T. Muscle Nerve 3:S61-S69(1995) [PubMed: 7603530] [Abstract] Cited for: REVIEW ON VARIANTS.
[13]	"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry." Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D. J. Proteome Res. 4:2070-2080(2005) [PubMed: 16335952] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-390, MASS SPECTROMETRY. Tissue: Plasma.
[14]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[15]	"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry." Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H. J. Proteome Res. 8:651-661(2009) [PubMed: 19159218] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-140; ASN-470; ASN-882 AND ASN-925, MASS SPECTROMETRY. Tissue: Liver.
[16]	"Identification of the base-pair substitution responsible for a human acid alpha glucosidase allele with lower 'affinity' for glycogen (GAA 2) and transient gene expression in deficient cells." Martiniuk F., Bodkin M., Tzall S., Hirschhorn R. Am. J. Hum. Genet. 47:440-445(1990) [PubMed: 2203258] [Abstract] Cited for: VARIANT ASN-91.
[17]	"Identification of a missense mutation in one allele of a patient with Pompe disease, and use of endonuclease digestion of PCR-amplified RNA to demonstrate lack of mRNA expression from the second allele." Zhong N., Martiniuk F., Tzall S., Hirschhorn R. Am. J. Hum. Genet. 49:635-645(1991) [PubMed: 1652892] [Abstract] Cited for: VARIANT GSD2 THR-318.
[18]	"Identification of a point mutation in the human lysosomal alpha-glucosidase gene causing infantile glycogenosis type II." Hermans M.M.P., de Graaff E., Kroos M.A., Wisselaar H.A., Oostra B.A., Reuser A.J.J. Biochem. Biophys. Res. Commun. 179:919-926(1991) [PubMed: 1898413] [Abstract] Cited for: VARIANT GSD2 LYS-521.
[19]	"Two mutations affecting the transport and maturation of lysosomal alpha-glucosidase in an adult case of glycogen storage disease type II." Hermans M.M.P., Kroos M.A., de Graaff E., Oostra B.A., Reuser A.J.J. Hum. Mutat. 2:268-273(1993) [PubMed: 8401535] [Abstract] Cited for: VARIANTS GSD2 ARG-643 AND TRP-725.
[20]	"The conservative substitution Asp-645-->Glu in lysosomal alpha-glucosidase affects transport and phosphorylation of the enzyme in an adult patient with glycogen-storage disease type II." Hermans M.M.P., de Graaff E., Kroos M.A., Wisselaar H.A., Willemsen R., Oostra B.A., Reuser A.J.J. Biochem. J. 289:687-693(1993) [PubMed: 8094613] [Abstract] Cited for: VARIANT GSD2 GLU-645, VARIANTS ILE-816 AND ILE-927.
[21]	"Identification of a missense mutation in an adult-onset patient with glycogenosis type II expressing only one allele." Martiniuk F., Mehler M., Bodkin M., Tzall S., Hirschhorn K., Zhong N., Hirschhorn R. DNA Cell Biol. 10:681-687(1991) [PubMed: 1684505] [Abstract] Cited for: VARIANT GSD2 GLU-645, VARIANTS ILE-816 AND ILE-927.
[22]	"The loss of a polymorphic glycosylation site caused by Thr-927-->Ile is linked to a second polymorphic Val-816-->Ile substitution in lysosomal alpha-glucosidase of American blacks." Hermans M.M.P., Svetkey L.P., Oostra B.A., Chen Y.T., Reuser A.J.J. Genomics 16:300-301(1993) [PubMed: 8486380] [Abstract] Cited for: VARIANTS ILE-816 AND ILE-927.
[23]	"Mutation at the catalytic site (M519V) in glycogen storage disease type II (Pompe disease)." Huie M.L., Hirschhorn R., Chen A.S., Martiniuk F., Zhong N. Hum. Mutat. 4:291-293(1994) [PubMed: 7866409] [Abstract] Cited for: VARIANT GSD2 VAL-519.
[24]	"A de novo 13 nt deletion, a newly identified C647W missense mutation and a deletion of exon 18 in infantile onset glycogen storage disease type II (GSDII)." Huie M.L., Chen A.S., Brooks S.S., Grix A., Hirschhorn R. Hum. Mol. Genet. 3:1081-1087(1994) [PubMed: 7981676] [Abstract] Cited for: VARIANT GSD2 TRP-647.
[25]	"The effect of a single base pair deletion (delta T525) and a C1634T missense mutation (Pro545Leu) on the expression of lysosomal alpha-glucosidase in patients with glycogen storage disease type II." Hermans M.M.P., de Graaff E., Kroos M.A., Mohkamsing S., Eussen B.J., Joosse M., Willemsen R., Kleijer W.J., Oostra B.A., Reuser A.J.J. Hum. Mol. Genet. 3:2213-2218(1994) [PubMed: 7881422] [Abstract] Cited for: VARIANT GSD2 LEU-545.
[26]	"Leaky splicing mutation in the acid maltase gene is associated with delayed onset of glycogenosis type II." Boerkoel C.F., Exelbert R., Nicastri C., Nichols R.C., Miller F.W., Plotz P.H., Raben N. Am. J. Hum. Genet. 56:887-897(1995) [PubMed: 7717400] [Abstract] Cited for: VARIANTS GSD2 ARG-299 AND LYS-903 DEL, VARIANTS ARG-199; ARG-223 AND VAL-780.
[27]	"Identification of an E689K substitution as the molecular basis of the human acid alpha-glucosidase type 4 allozyme (GAA*4)." Huie M.L., Menaker M., McAlpine P.J., Hirschhorn R. Ann. Hum. Genet. 60:365-368(1996) [PubMed: 8912788] [Abstract] Cited for: VARIANT LYS-689.
[28]	"Acid alpha-glucosidase deficiency: identification and expression of a missense mutation (S529V) in a Japanese adult phenotype." Tsunoda H., Ohshima T., Tohyama J., Sasaki M., Sakuragawa N., Martiniuk F. Hum. Genet. 97:496-499(1996) [PubMed: 8834250] [Abstract] Cited for: VARIANT GSD2 VAL-529.
[29]	"Glycogen storage disease type II: identification of four novel missense mutations (D645N, G648S, R672W, R672Q) and two insertions/deletions in the acid alpha-glucosidase locus of patients of differing phenotype." Huie M.L., Tsujino S., Brooks S.S., Engel A., Elias E., Bonthron D.T., Bessley C., Shanske S., Dimauro S., Goto Y., Hirschhorn R. Biochem. Biophys. Res. Commun. 244:921-927(1998) [PubMed: 9535769] [Abstract] Cited for: VARIANTS GSD2 ASN-645; TRP-647; SER-648; GLN-672 AND TRP-672.
[30]	"Glycogen storage disease type II: identification of a dinucleotide deletion and a common missense mutation in the lysosomal alpha-glucosidase gene." Kroos M.A., van Leenen D., Verbiest J., Reuser A.J.J., Hermans M.M.P. Clin. Genet. 53:379-382(1998) [PubMed: 9660056] [Abstract] Cited for: VARIANT GSD2 ARG-309.
[31]	"Glycogen storage disease type II: genetic and biochemical analysis of novel mutations in infantile patients from Turkish ancestry." Hermans M.M.P., Kroos M.A., Smeitink J.A.M., van der Ploeg A.T., Kleijer W.J., Reuser A.J.J. Hum. Mutat. 11:209-215(1998) [PubMed: 9521422] [Abstract] Cited for: VARIANTS GSD2 PRO-566; ARG-643 AND ARG-768, VARIANTS ASN-91; ARG-199 AND ARG-223.
[32]	"The identification of five novel mutations in the lysosomal acid alpha-(1,4) glucosidase gene from patients with glycogen storage disease type II." Beesley C.E., Child A.H., Yacoub M.Y. Hum. Mutat. 11:413-413(1998) [PubMed: 10206684] [Abstract] Cited for: VARIANT GSD2 GLY-VAL-PRO-VAL-SER-ASN-925 INS.
[33]	"Adult-onset glycogen storage disease type II: phenotypic and allelic heterogeneity in German patients." Vorgerd M., Burwinkel B., Reichmann H., Malin J.-P., Kilimann M.W. Neurogenetics 1:205-211(1998) [PubMed: 10737124] [Abstract] Cited for: VARIANTS GSD2 LEU-545 AND TRP-638.
[34]	"Novel mutations in African American patients with glycogen storage disease Type II." Raben N., Lee E., Lee L., Hirschhorn R., Plotz P.H. Hum. Mutat. 13:83-84(1999) [PubMed: 10189220] [Abstract] Cited for: VARIANT GSD2 ARG-481.
[35]	"Molecular genetic study of Pompe disease in Chinese patients in Taiwan." Ko T.-M., Hwu W.-L., Lin Y.-W., Tseng L.-H., Hwa H.-L., Wang T.-R., Chuang S.-M. Hum. Mutat. 13:380-384(1999) [PubMed: 10338092] [Abstract] Cited for: VARIANTS GSD2, VARIANTS.
[36]	"Juvenile and adult-onset acid maltase deficiency in France: genotype-phenotype correlation." Laforet P., Nicolino M., Eymard P.B., Puech J.P., Caillaud C., Poenaru L., Fardeau M. Neurology 55:1122-1128(2000) [PubMed: 11071489] [Abstract] Cited for: VARIANTS GSD2 PRO-208; LEU-308; LEU-324; MET-585; 607-GLY--HIS-612 DEL; ARG-643 AND THR-672.
[37]	"Identification of six novel mutations in the acid alpha-glucosidase gene in three Spanish patients with infantile onset glycogen storage disease type II (Pompe disease)." Fernandez-Hojas R., Huie M.L., Navarro C., Dominguez C., Roig M., Lopez-Coronas D., Teijeira S., Anyane-Yeboa K., Hirschhorn R. Neuromuscul. Disord. 12:159-166(2002) [PubMed: 11738358] [Abstract] Cited for: VARIANTS GSD2 ARG-219; LYS-262 AND VAL-408.
[38]	"Identification of four novel mutations in the alpha glucosidase gene in five Italian patients with infantile onset glycogen storage disease type II." Pittis M.G., Montalvo A.L., Miocic S., Martini C., Deganuto M., Candusso M., Ciana G., Bembi B. Am. J. Med. Genet. A 121:225-230(2003) [PubMed: 12923862] [Abstract] Cited for: VARIANT GSD2 TRP-224, CHARACTERIZATION OF VARIANT GSD2 TRP-224.
[39]	"Juvenile-onset glycogen storage disease type II with novel mutations in acid alpha-glucosidase gene." Lam C.W., Yuen Y.P., Chan K.Y., Tong S.F., Lai C.K., Chow T.C., Lee K.C., Chan Y.W., Martiniuk F. Neurology 60:715-717(2003) [PubMed: 12601120] [Abstract] Cited for: VARIANTS GSD2 LEU-361 AND CYS-437.
[40]	"New GAA mutations in Japanese patients with GSDII (Pompe disease)." Pipo J.R., Feng J.-H., Yamamoto T., Ohsaki Y., Nanba E., Tsujino S., Sakuragawa N., Martiniuk F., Ninomiya H., Oka A., Ohno K. Pediatr. Neurol. 29:284-287(2003) [PubMed: 14643388] [Abstract] Cited for: VARIANTS GSD2 TRP-224; CYS-600; ARG-619 AND HIS-660, CHARACTERIZATION OF VARIANTS GSD2 TRP-224; ARG-619 AND HIS-660, CHARACTERIZATION OF VARIANT SER-576.
[41]	"Twenty-two novel mutations in the lysosomal alpha-glucosidase gene (GAA) underscore the genotype-phenotype correlation in glycogen storage disease type II." Hermans M.M.P., van Leenen D., Kroos M.A., Beesley C.E., Van der Ploeg A.T., Sakuraba H., Wevers R., Kleijer W.J., Michelakakis H., Kirk E.P., Fletcher J., Bosshard N., Basel-Vanagaite L., Besley G., Reuser A.J.J. Hum. Mutat. 23:47-56(2004) [PubMed: 14695532] [Abstract] Cited for: VARIANTS GSD2 GLY-103; ARG-219; ARG-285; CYS-292; ARG-293; PRO-308; ARG-312; PRO-355; ARG-374; PRO-405; PHE-455; ASP-459 DEL; ARG-478; ARG-481; THR-519; LEU-545; ARG-549; PRO-552; SER-575; LYS-579; CYS-600; ASP-607 AND ASP-880, CHARACTERIZATION OF VARIANTS.
[42]	"Glycogenosis type II: identification and expression of three novel mutations in the acid alpha-glucosidase gene causing the infantile form of the disease." Montalvo A.L.E., Cariati R., Deganuto M., Guerci V., Garcia R., Ciana G., Bembi B., Pittis M.G. Mol. Genet. Metab. 81:203-208(2004) [PubMed: 14972326] [Abstract] Cited for: VARIANTS GSD2 PRO-355 AND CYS-702, CHARACTERIZATION OF VARIANTS GSD2 PRO-355 AND CYS-702.
[43]	"A case of childhood Pompe disease demonstrating phenotypic variability of p.Asp645Asn." Kroos M.A., Kirschner J., Gellerich F.N., Hermans M.M., Van der Ploeg A.T., Reuser A.J., Korinthenberg R. Neuromuscul. Disord. 14:371-374(2004) [PubMed: 15145338] [Abstract] Cited for: VARIANT GSD2 GLN-901, VARIANT ASN-645.
[44]	"Mutations in the acid alpha-glucosidase gene (M. Pompe) in a patient with an unusual phenotype." Anneser J.M., Pongratz D.E., Podskarbi T., Shin Y.S., Schoser B.G. Neurology 64:368-370(2005) [PubMed: 15668445] [Abstract] Cited for: VARIANTS GSD2 VAL-237 AND ARG-293.
[45]	"A novel missense mutation in the acid alpha-glucosidase gene causing the classic infantile form of Pompe disease." Dou W., Gu X., Fu L., Peng C., Zheng J., Martiniuk F., Sheng H.Z. Clin. Chim. Acta 374:145-146(2006) [PubMed: 16782080] [Abstract] Cited for: VARIANT GSD2 GLY-330.
[46]	"Two clinical forms of glycogen-storage disease type II in two generations of the same family." Amartino H., Painceira D., Pomponio R.J., Niizawa G., Sabio Paz V., Blanco M., Chamoles N. Clin. Genet. 69:187-188(2006) [PubMed: 16433701] [Abstract] Cited for: VARIANT GSD2 GLY-ASN-404.
[47]	"Mutation profile of the GAA gene in 40 Italian patients with late onset glycogen storage disease type II." Montalvo A.L., Bembi B., Donnarumma M., Filocamo M., Parenti G., Rossi M., Merlini L., Buratti E., De Filippi P., Dardis A., Stroppiano M., Ciana G., Pittis M.G. Hum. Mutat. 27:999-1006(2006) [PubMed: 16917947] [Abstract] Cited for: VARIANTS GSD2 ARG-309; PRO-355; LEU-361; PRO-445; ASN-489; ARG-549; GLN-612; ARG-643; TRP-672 AND CYS-746.
[48]	"Molecular and functional characterization of eight novel GAA mutations in Italian infants with Pompe disease." Pittis M.G., Donnarumma M., Montalvo A.L.E., Dominissini S., Kroos M., Rosano C., Stroppiano M., Bianco M.G., Donati M.A., Parenti G., D'Amico A., Ciana G., Di Rocco M., Reuser A., Bembi B., Filocamo M. Hum. Mutat. 29:E27-E36(2008) [PubMed: 18429042] [Abstract] Cited for: VARIANTS GSD2 GLY-103; CYS-191; ARG-219; TRP-224; LYS-262; ARG-293; PRO-355; LEU-375; ARG-401; ASN-489; ALA-522; PRO-552; TYR-599; TRP-638; ARG-643 AND ASN-645, CHARACTERIZATION OF VARIANTS GSD2 CYS-191; LEU-375; ARG-401; ALA-522 AND TYR-599.
+	Additional computationally mapped references.

Web resources

GAA

Information about alpha-glucosidase

GeneReviews

Wikipedia

Alpha-glucosidase entry

Cross-references

Sequence databases
EMBLGenBankDDBJ	Y00839 mRNA. Translation: CAA68763.1. Y00839 mRNA. Translation: CAA68764.1. X55080 , X55081, X55095, X55082, X55084, X55083, X55098, X55085, X55086, X55087, X55088, X55089, X55090, X55096, X55091, X55092, X55093, X55094, X55097 Genomic DNA. Translation: CAC12967.1. M34424 mRNA. Translation: AAA52506.1. DQ907243 mRNA. Translation: ABI53718.1. AC087741 Genomic DNA. No translation available. BC040431 mRNA. Translation: AAH40431.1. S76893 mRNA. Translation: AAB33842.1.
IPI	IPI00293088.
PIR	A32609. A40577.
RefSeq	NP_000143.2. NP_001073271.1. NP_001073272.1.
UniGene	Hs.1437
3D structure databases
ModBase	Search...
Protein-protein interaction databases
STRING	P10253.
Protein family/group databases
CAZy	GH31. Glycoside Hydrolase Family 31.
Proteomic databases
PRIDE	P10253.
Genome annotation databases
Ensembl	ENST00000302262; ENSP00000305692; ENSG00000171298; Homo sapiens. [Genome view] ENST00000390015; ENSP00000374665; ENSG00000171298; Homo sapiens. [Genome view] ENST00000414495; ENSP00000397325; ENSG00000171298; Homo sapiens. [Genome view]
GeneID	2548.
KEGG	hsa:2548.
Organism-specific databases
CTD	2548.
GeneCards	GC17P075689.
H-InvDB	HIX0027175.
HGNC	HGNC:4065. GAA.
MIM	232300. phenotype. 606800. gene.
Orphanet	365. Glycogen storage disease type 2.
PharmGKB	PA28476.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	P10253.
Enzyme and pathway databases
BRENDA	3.2.1.20. 247.
Gene expression databases
ArrayExpress	P10253.
Bgee	P10253.
CleanEx	HS_GAA.
Genevestigator	P10253.
GermOnline	ENSG00000171298. Homo sapiens.
Family and domain databases
InterPro	IPR000322. Glyco_hydro_31. IPR000519. P_trefoil. IPR017957. P_trefoil_CS. [Graphical view]
PANTHER	PTHR22762. Glyco_hydro_31. 1 hit.
Pfam	PF01055. Glyco_hydro_31. 1 hit. PF00088. Trefoil. 1 hit. [Graphical view]
SMART	SM00018. PD. 1 hit. [Graphical view]
PROSITE	PS00129. GLYCOSYL_HYDROL_F31_1. 1 hit. PS00707. GLYCOSYL_HYDROL_F31_2. 1 hit. PS00025. P_TREFOIL_1. 1 hit. PS51448. P_TREFOIL_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
DrugBank	DB00284. Acarbose.
NextBio	10047.
SOURCE	Search...

Entry information

Entry name

LYAG_HUMAN

Accession

Primary (citable) accession number: P10253
Secondary accession number(s): Q09GN4 , Q14351, Q16302, Q8IWE7

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1989
Last sequence update:	July 7, 2009
Last modified:	October 13, 2009
This is version 123 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.