P06280 Q6LER7 AGAL_HUMAN Alpha-galactosidase A 3.2.1.22 Alpha-D-galactosidase A Alpha-D-galactoside galactohydrolase Galactosylgalactosylglucosylceramidase GLA Melibiase Agalsidase GLA Homo sapiens Human Eukaryota Metazoa Chordata Craniata Vertebrata Euteleostomi Mammalia Eutheria Euarchontoglires Primates Haplorrhini Catarrhini Hominidae Homo Signal sequence and DNA-mediated expression of human lysosomal alpha-galactosidase A. NUCLEOTIDE SEQUENCE [MRNA] Fibroblast Nucleotide sequence of the human alpha-galactosidase A gene. NUCLEOTIDE SEQUENCE [GENOMIC DNA] Lymphoblast Sixty-nine kilobases of contiguous human genomic sequence containing the alpha-galactosidase A and Bruton's tyrosine kinase loci. NUCLEOTIDE SEQUENCE [GENOMIC DNA] The DNA sequence of the human X chromosome. NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] Uterus Human alpha-galactosidase A: nucleotide sequence of a cDNA clone encoding the mature enzyme. NUCLEOTIDE SEQUENCE [MRNA] OF 27-429 PARTIAL PROTEIN SEQUENCE Lung A genomic clone containing the promoter for the gene encoding the human lysosomal enzyme, alpha-galactosidase A. NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-64 Structural organization of the human alpha-galactosidase A gene: further evidence for the absence of a 3' untranslated region. NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-64 Editing of human alpha-galactosidase RNA resulting in a pyrimidine to purine conversion. RNA EDITING OF POSITION 396 Only sphingolipid activator protein B (SAP-B or saposin B) stimulates the degradation of globotriaosylceramide by recombinant human lysosomal alpha-galactosidase in a detergent-free liposomal system. FUNCTION CATALYTIC ACTIVITY ACTIVITY REGULATION Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry. GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-215 Liver Initial characterization of the human central proteome. IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS] N-terminome analysis of the human mitochondrial proteome. IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS] The molecular defect leading to Fabry disease: structure of human alpha-galactosidase. X-RAY CRYSTALLOGRAPHY (3.45 ANGSTROMS) OF 32-422 IN COMPLEX WITH PRODUCT HOMODIMERIZATION GLYCOSYLATION AT ASN-139; ASN-192 AND ASN-215 Molecular basis of Fabry disease: mutations and polymorphisms in the human alpha-galactosidase A gene. REVIEW ON FD VARIANTS A case of Fabry's disease in a patient with no alpha-galactosidase A activity caused by a single amino acid substitution of Pro-40 by Ser. INVOLVEMENT IN FD VARIANT FD SER-40 An atypical variant of Fabry's disease with manifestations confined to the myocardium. VARIANT FD VAL-296 Identification of point mutations in the alpha-galactosidase A gene in classical and atypical hemizygotes with Fabry disease. VARIANT FD GLN-301 Fabry disease: six gene rearrangements and an exonic point mutation in the alpha-galactosidase gene. VARIANT FD TRP-356 Point mutations in the upstream region of the alpha-galactosidase A gene exon 6 in an atypical variant of Fabry disease. VARIANTS FD GLN-66; CYS-112; GLU-279; GLN-301 AND ARG-328 Nature and frequency of mutations in the alpha-galactosidase A gene that cause Fabry disease. VARIANTS FD SER-34; GLY-56; ARG-162; GLN-227; VAL-264; VAL-266; PHE-297; TYR-313; ALA-328 AND ARG-404 DEL Mutation analysis in patients with the typical form of Anderson-Fabry disease. VARIANTS FD SER-34; SER-215; ALA-269; LYS-327 AND ARG-361 Detection of 8 new mutations in the alpha-galactosidase A gene in Fabry disease. VARIANTS FD ARG-35; LEU-49; VAL-165 AND GLU-316 Fabry disease: twenty-three mutations including sense and antisense CpG alterations and identification of a deletional hot-spot in the alpha-galactosidase A gene. VARIANTS FD SER-52; PHE-56; LYS-59; ARG-89; LYS-100; HIS-112; PRO-131; PRO-143; VAL-144; SER-146; TYR-172; ASN-219; ASN-244; LYS-272; ASP-288 AND GLN-342 Galactose stabilizes various missense mutants of alpha-galactosidase in Fabry disease. VARIANTS FD GLN-66; CYS-112; VAL-156; VAL-166; ALA-260; GLU-279; ILE-296; GLN-301; LYS-320; ARG-328 AND SER-373 Alpha-galactosidase gene mutations in Fabry disease: heterogeneous expressions of mutant enzyme proteins. VARIANTS FD TYR-142; VAL-156 AND VAL-166 Two novel mutations (L32P) and (G85N) among five different missense mutations in six Danish families with Fabry's disease. VARIANTS FD PRO-32; SER-34; ASP-85; THR-156 AND GLN-301 An atypical variant of Fabry's disease in men with left ventricular hypertrophy. VARIANTS FD PRO-20 AND ILE-296 Point mutation in the alpha-galactosidase A gene of atypical Fabry disease with only nephropathy. VARIANT FD GLN-301 Fabry disease: fourteen alpha-galactosidase A mutations in unrelated families from the United Kingdom and other European countries. VARIANTS FD VAL-42; SER-49; TYR-56; HIS-92; GLY-93; THR-205; CYS-236; GLY-287; HIS-298 AND ARG-340 Novel trinucleotide deletion in Fabry's disease. VARIANT FD PHE-383 DEL Fluorescence-assisted mismatch analysis (FAMA) for exhaustive screening of the alpha-galactosidase A gene and detection of carriers in Fabry disease. VARIANTS FD ARG-52; CYS-162; ARG-265 AND 316-VAL--ASP-322 DEL A sensitive mutation screening strategy for Fabry disease: detection of nine mutations in the alpha-galactosidase A gene. VARIANTS FD ARG-52; GLU-128; THR-205; THR-284; LYS-298 AND GLU-358 DEL Uneven X inactivation in a female monozygotic twin pair with Fabry disease and discordant expression of a novel mutation in the alpha-galactosidase A gene. VARIANT FD ASN-231 Screening and detection of gene mutations in Japanese patients with Fabry disease by non-radioactive single-stranded conformation polymorphism analysis. VARIANTS FD PRO-20; SER-40; GLN-66; VAL-72; CYS-112; TYR-142; VAL-156; VAL-166; ASN-242; ALA-260; ASP-261; GLU-279; ILE-296; GLN-301; LYS-320; ARG-328; GLU-358 DEL AND SER-373 Fabry disease: thirty-five mutations in the alpha-galactosidase A gene in patients with classic and variant phenotypes. VARIANTS FD VAL-31; 45-LEU-HIS-46 DELINS ARG-SER; ARG-46; CYS-86; PRO-89; THR-91; TYR-92; TYR-94; VAL-97; THR-100; LEU-113; SER-134; ARG-138; THR-143; ARG-148; VAL-163; VAL-170; TYR-202; 205-PRO--TYR-207 DEL; ASP-216; SER-263; CYS-287; SER-298 AND ARG-404 DEL Identification of a novel point mutation (S65T) in alpha-galactosidase A gene in Chinese patients with Fabry disease. VARIANT FD THR-65 A novel mutation (E358K) in the alpha-galactosidase A gene detected in a Japanese family with Fabry disease. VARIANT FD LYS-358 Novel missense mutation (M72V) of alpha-galactosidase gene and its expression product in an atypical Fabry hemizygote. VARIANT FD VAL-72 Mutation analysis in 11 French patients with Fabry disease. VARIANTS FD SER-40; SER-215; ASP-224; TYR-313 AND TRP-THR-SER-247 INS Fabry disease: identification of novel alpha-galactosidase A mutations and molecular carrier detection by use of fluorescent chemical cleavage of mismatches. VARIANTS FD TRP-202; GLY-223; ASP-224; GLN-301 AND LYS-327 The multiple cases of Fabry disease in a Russian family caused by an E341K amino acid substitution in the alpha-galactosidase A. VARIANT FD LYS-341 Characterization of two alpha-galactosidase mutants (Q279E and R301Q) found in an atypical variant of Fabry disease. CHARACTERIZATION OF VARIANTS FD GLU-279 AND GLN-301 FUNCTION CATALYTIC ACTIVITY ACTIVITY REGULATION Twenty novel mutations in the alpha-galactosidase A gene causing Fabry disease. VARIANTS FD VAL-42; CYS-112; ARG-142; ARG-148; VAL-165; ASP-183; SER-215; CYS-235; LEU-236; HIS-244; LEU-259; ILE-267; PHE-289; GLU-321; GLU-358 DEL AND TYR-378 Identification of four novel mutations in five unrelated Korean families with Fabry disease. VARIANT FD ASN-266 Fabry disease: twenty-two novel mutations in the alpha-galactosidase A gene and genotype/phenotype correlations in severely and mildly affected hemizygotes and heterozygotes. VARIANTS FD LEU-40; SER-95; CYS-112; HIS-112; ASN-148; ARG-172; VAL-187; SER-224; ARG-226; GLN-227; THR-230; HIS-266; GLN-301 AND TYR-320 Identification of a novel de novo mutation (G373D) in the alpha-galactosidase A gene (GLA) in a patient affected with Fabry disease. VARIANT FD ASP-373 Fabry disease: 20 novel GLA mutations in 35 families. VARIANTS FD TYR-46; GLY-47; PRO-49; SER-94; SER-95; CYS-112; SER-113; THR-143; SER-215; ARG-258; ARG-259; ILE-267; HIS-279; HIS-280; HIS-298; TYR-313; HIS-363; ASP-377; ALA-409 AND THR-409 Natural history of Fabry renal disease: influence of alpha-galactosidase A activity and genetic mutations on clinical course. VARIANT FD PRO-143 Two novel mutations in the alpha-galactosidase A gene in Chinese patients with Fabry disease. VARIANT FD ALA-410 Analysis of splice-site mutations of the alpha-galactosidase A gene in Fabry disease. CHARACTERIZATION OF VARIANT FD THR-65 Remarkable variability in renal disease in a large Slovenian family with Fabry disease. VARIANT FD SER-272 Detection of alpha-galactosidase a mutations causing Fabry disease by denaturing high performance liquid chromatography. VARIANTS FD VAL-31; LEU-42; ARG-43; ASN-93; CYS-112; HIS-112; SER-112; SER-134; VAL-135; ASP-171; PHE-201; SER-215; GLU-234; ASP-261; TYR-264; VAL-264; GLY-276; PRO-285; PHE-300; ALA-328; VAL-328; LYS-338; ALA-358; GLU-358 DEL; ARG-404 DEL AND SER-414 Later-onset Fabry disease: an adult variant presenting with the cramp-fasciculation syndrome. VARIANT FD THR-143 Newborn screening for Fabry disease in Taiwan reveals a high incidence of the later-onset GLA mutation c.936+919G>A (IVS4+919G>A). VARIANTS FD 12-CYS--LEU-14 DEL; PRO-46; GLN-66; ASN-93; VAL-120; THR-219; GLN-356 AND CYS-360 CHARACTERIZATION OF VARIANTS FD 12-CYS--LEU-14 DEL; PRO-46; GLN-66; ASN-93; VAL-120; THR-219; GLN-356 AND CYS-360 Functional and clinical consequences of novel alpha-galactosidase A mutations in Fabry disease. CHARACTERIZATION OF VARIANTS FD ASP-20; PRO-20; PRO-21; GLY-33; GLU-35; TRP-36; SER-40; THR-42; PRO-45; ASP-48; TYR-56; LEU-60; PHE-64; ASP-80; HIS-86; ASN-91; THR-91; SER-94; TYR-94; ILE-113; THR-121; LEU-164; GLY-164; GLN-167; PHE-180; VAL-187; SER-196; THR-198; TYR-202; ARG-204; ARG-213; LEU-214; MET-219; PRO-227; SER-228; VAL-242; PHE-243; PRO-247; LYS-249; THR-253; ALA-254; ARG-259; ARG-262; GLY-269; GLY-276; VAL-309; ASN-315; ALA-316; SER-317; TYR-320; ARG-323; ARG-327; LEU-327; ARG-328; ARG-330; PRO-342; GLY-352; PRO-356; LYS-358; SER-360; ALA-375; SER-392; SER-399 AND ARG-404 DEL CHARACTERIZATION OF VARIANTS PRO-3; VAL-3; GLY-71; THR-154; VAL-289 AND ASN-313 CATALYTIC ACTIVITY FUNCTION A novel mutation of alpha-galactosidase A gene causes Fabry disease mimicking primary erythromelalgia in a Chinese family. VARIANT FD ARG-47 CHARACTERIZATION OF VARIANTS FD ARG-47 AND GLY-47 CATALYTIC ACTIVITY FUNCTION Alpha-Galactosidase A p.A143T, a non-Fabry disease-causing variant. VARIANT FD THR-143 Catalyzes the hydrolysis of glycosphingolipids and participates in their degradation in the lysosome. Hydrolysis of terminal, non-reducing alpha-D-galactose residues in alpha-D-galactosides, including galactose oligosaccharides, galactomannans and galactolipids. a globoside Gb3Cer (d18:1(4E)) + H2O = a beta-D-Gal-(1->4)-beta-D-Glc-(1<->1)-Cer(d18:1(4E)) + D-galactose a globoside Gb3Cer + H2O = a beta-D-galactosyl-(1->4)-beta-D-glucosyl-(1<->1)-ceramide + D-galactose Galactosylgalactosylglucosylceramidase activity is stimulated by saposin B and ammonium chloride. Homodimer. P06280 Q2TAA5 false 2 P06280 Q99523 false 3 Lysosome Partially edited. Fabry disease FD Rare X-linked sphingolipidosis disease where glycolipid accumulates in many tissues. The disease consists of an inborn error of glycosphingolipid catabolism. FD patients show systemic accumulation of globotriaosylceramide (Gb3) and related glycosphingolipids in the plasma and cellular lysosomes throughout the body. Clinical recognition in males results from characteristic skin lesions (angiokeratomas) over the lower trunk. Patients may show ocular deposits, febrile episodes, and burning pain in the extremities. Death results from renal failure, cardiac or cerebral complications of hypertension or other vascular disease. Heterozygous females may exhibit the disorder in an attenuated form, they are more likely to show corneal opacities. The disease is caused by variants affecting the gene represented in this entry. Available under the names Replagal (from Shire) and Fabrazyme (from Genzyme). Used as a long-term enzyme replacement therapy in patients with a confirmed diagnosis of Fabry disease. The differences between Replagal (also known as agalsidase alpha) and Fabrazyme (also known as agalsidase beta) lies in the glycosylation patterns. Agalsidase beta is produced in the hamster CHO cell line while agalsidase alpha is produced in human cell lines. Belongs to the glycosyl hydrolase 27 family. 3D-structure Direct protein sequencing Disease variant Disulfide bond Glycoprotein Glycosidase Hydrolase Lipid metabolism Lysosome Pharmaceutical Proteomics identification Reference proteome RNA editing Signal substrate L P L V A D A P L P A V L P D G N S G E G R L W P L P S M L M T M V G R LH RS L P H P H R H Y W G W R E D R L R P R S C R C S C F C G C Y E K P L I F S T E Q E G M V G D G D Y C Y H L P L R I N I T D H D Y D G D N C S C Y W S A V R K R T R C R H R S F I F L F S LA PT L V A T G E L P Y S A V G R C R C Y A P A T G V P S S N S R I T A T A V W C W R G V V G V L D V L V L Q D V G D C R C Y L F G D M I M V R S I T S F C W C Y W R P T K R P L N S Y D I M I N I T C G N D N S W R R P R Q N S A T D N D E S C W C W L I N I V L F D H D N S P S SWTS N K I T V A G R P L P R G A G D W R N S D V D Y P R D H D N D V M I V A V G N K N S S G Q E Q H Q H M T A P W C W G A D I F I V M I M V S F N H N K N S L F R Q A V D N D Y D N V A V E I S N K N Y Q E P R Q K Q L Q R G A G R G V Q R E K W R E K R P R Q A G R P R Q R W E A E K G C G S G R R H G D G S G A A D C Y R S F Y W S P A P T T A L S MQLRNPELHLGCALALRFLALVSWDIPGARALDNGLARTPTMGWLHWERFMCNLDCQEEPDSCISEKLFMEMAELMVSEGWKDAGYEYLCIDDCWMAPQRDSEGRLQADPQRFPHGIRQLANYVHSKGLKLGIYADVGNKTCAGFPGSFGYYDIDAQTFADWGVDLLKFDGCYCDSLENLADGYKHMSLALNRTGRSIVYSCEWPLYMWPFQKPNYTEIRQYCNHWRNFADIDDSWKSIKSILDWTSFNQERIVDVAGPGGWNDPDMLVIGNFGLSWNQQVTQMALWAIMAAPLFMSNDLRHISPQAKALLQDKDVIAINQDPLGKQGYQLRQGDNFEVWERPLSGLAWAVAMINRQEIGGPRSYTIAVASLGKGVACNPACFITQLLPVKRKLGFYEWTSRLRSHINPTGTVLLQLENTMQMSLKDLL Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms Distributed under the Creative Commons Attribution (CC BY 4.0) License