alkaline phosphatases and sulfatases; This family includes alkaline phosphatases and sulfatases. Alkaline phosphatases are non-specific phosphomonoesterases that catalyze the hydrolysis reaction via a phosphoseryl intermediate to produce inorganic phosphate and the corresponding alcohol, optimally at high pH. Alkaline phosphatase exists as a dimer, each monomer binding 2 zinc atoms and one magnesium atom, which are essential for enzymatic activity. Sulfatases catalyze the hydrolysis of sulfate esters from wide range of substrates, including steroids, carbohydrates and proteins. Sulfate esters may be formed from various alcohols and amines. The biological roles of sulfatase includes the cycling of sulfur in the environment, in the degradation of sulfated glycosaminoglycans and glycolipids in the lysosome, and in remodeling sulfated glycosaminoglycans in the extracellular space. Both alkaline phosphatase and sulfatase are essential for human metabolism. Deficiency of individual enzyme cause genetic diseases.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1372261749   5 GGSPTKQTTWEGGHRVPALAYWPGRVPANVTSTALLRCYST-PTV 48
Cdd:cd16161   243 GGSVAKASTWEGGHREPAIVYWPGRIPANSTSAALVSTLDIfPTV 287

arylsulfatase G; Arylsulfatase G is a subfamily of sulfatases which specifically hydrolyze sulfate esters in a wide variety of substrates such as glycosaminoglycans, steroid sulfates, or sulfolipids. ARSG has arylsulfatase activity toward different pseudosubstrates like p-nitrocatechol sulfate and 4-methylumbelliferyl sulfate. An active site Cys is post-translationally converted to the critical active site C(alpha)-formylglycine. ARSG mRNA expression was found to be tissue-specific with highest expression in liver, kidney, and pancreas, suggesting a metabolic role of ARSG that might be associated with a non-classified lysosomal storage disorder.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1372261749   5 GGSPTKQTTWEGGHRVPALAYWPGRVPANVTSTALLRCYST-PTV 48
Cdd:cd16161   243 GGSVAKASTWEGGHREPAIVYWPGRIPANSTSAALVSTLDIfPTV 287

arylsulfatase G; Arylsulfatase G is a subfamily of sulfatases which specifically hydrolyze sulfate esters in a wide variety of substrates such as glycosaminoglycans, steroid sulfates, or sulfolipids. ARSG has arylsulfatase activity toward different pseudosubstrates like p-nitrocatechol sulfate and 4-methylumbelliferyl sulfate. An active site Cys is post-translationally converted to the critical active site C(alpha)-formylglycine. ARSG mRNA expression was found to be tissue-specific with highest expression in liver, kidney, and pancreas, suggesting a metabolic role of ARSG that might be associated with a non-classified lysosomal storage disorder.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1372261749   5 GGSPTKQTTWEGGHRVPALAYWPGRVPANVTSTALLRCYST-PTV 48
Cdd:cd16161   243 GGSVAKASTWEGGHREPAIVYWPGRIPANSTSAALVSTLDIfPTV 287

uncharacterized arylsulfatase subfamily; Sulfatases catalyze the hydrolysis of sulfate esters from wide range of substrates, including steroids, carbohydrates and proteins. Sulfate esters may be formed from various alcohols and amines. The biological roles of sulfatase includes the cycling of sulfur in the environment, in the degradation of sulfated glycosaminoglycans and glycolipids in the lysosome, and in remodeling sulfated glycosaminoglycans in the extracellular space. The sulfatases are essential for human metabolism. At least eight human monogenic diseases are caused by the deficiency of individual sulfatases.

                          10        20        30
                  ....*....|....*....|....*....|....*
gi 1372261749   5 GGSP---TKQTTWEGGHRVPALAYWPGRVPANVTS 36
Cdd:cd16142   228 GYTPfrgEKGTTWEGGVRVPAIVRWPGKIKPGRVS 262

Arylsulfatase A or related enzyme, AlkP superfamily [Inorganic ion transport and metabolism];

                          10        20        30
                  ....*....|....*....|....*....|
gi 1372261749  10 KQTTWEGGHRVPALAYWPGRVPANVTSTAL 39
Cdd:COG3119   250 KGTLYEGGIRVPLIVRWPGKIKAGSVSDAL 279

galactosamine-6-sulfatase; also known as N-acetylgalactosamine-6-sulfatase (GALNS); Lysosomal galactosamine-6-sulfatase removes sulfate groups from a terminal N-acetylgalactosamine-6-sulfate (or galactose-6-sulfate) in mucopolysaccharides such as keratan sulfate and chondroitin-6-sulfate. Defects in GALNS lead to accumulation of substrates, resulting in the development of the lysosomal storage disease mucopolysaccharidosis IV A.

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 1372261749  10 KQTTWEGGHRVPALAYWPGRVPANVTS---TALLRCYST 45
Cdd:cd16157   282 KQTTFEGGMREPAIAWWPGHIKPGQVShqlGSLMDLFTT 320

uncharacterized arylsulfatase subfamily; Sulfatases catalyze the hydrolysis of sulfate esters from wide range of substrates, including steroids, carbohydrates and proteins. Sulfate esters may be formed from various alcohols and amines. The biological roles of sulfatase includes the cycling of sulfur in the environment, in the degradation of sulfated glycosaminoglycans and glycolipids in the lysosome, and in remodeling sulfated glycosaminoglycans in the extracellular space. The sulfatases are essential for human metabolism. At least eight human monogenic diseases are caused by the deficiency of individual sulfatases.

                          10        20
                  ....*....|....*....|....*..
gi 1372261749  10 KQTTWEGGHRVPALAYWPGRVPANVTS 36
Cdd:cd16145   293 KRSLYEGGIRVPFIARWPGKIPAGSVS 319

uncharacterized arylsulfatase; Sulfatases catalyze the hydrolysis of sulfate esters from wide range of substrates, including steroids, carbohydrates and proteins. Sulfate esters may be formed from various alcohols and amines. The biological roles of sulfatase includes the cycling of sulfur in the environment, in the degradation of sulfated glycosaminoglycans and glycolipids in the lysosome, and in remodeling sulfated glycosaminoglycans in the extracellular space. The sulfatases are essential for human metabolism. At least eight human monogenic diseases are caused by the deficiency of individual sulfatases.

                          10        20        30
                  ....*....|....*....|....*....|.
gi 1372261749   9 TKQTTWEGGHRVPALAYWPGRVPANVTSTAL 39
Cdd:cd16146   262 KKGSVYEGGHRVPFFIRWPGKILAGKDVDTL 292

Estrone sulfatase; Human estrone sulfatase (ES) is responsible for maintaining high levels of the active estrogen in tumor cells. ES catalyzes the hydrolysis of E1 sulfate, which is a component of the three-enzyme system that has been implicated in intracrine biosynthesis of estradiol. It is associated with the membrane of the endoplasmic reticulum (ER). The structure of ES consisting of two antiparallel alpha helices that protrude from the roughly spherical molecule. These highly hydrophobic helices anchor the functional domain on the membrane surface facing the ER lumen.

                          10        20        30
                  ....*....|....*....|....*....|..
gi 1372261749   2 IKIGGsptKQTTWEGGHRVPALAYWPGRVPAN 33
Cdd:cd16159   336 IYGGK---KMGGWEGGIRVPTIVRWPGVIPPG 364

N-sulfoglucosamine sulfohydrolase (SGSH; sulfamidase); N-sulfoglucosamine sulfohydrolase (SGSH) belongs to the sulfatase family and catalyses the cleavage of N-linked sulfate groups from the GAGs heparin sulfate and heparin. The active site is characterized by the amino-acid sequence motif C(X)PSR that is highly conserved among most sulfatases. The cysteine residue is post-translationally converted to a formylglycine (FGly) residue, which is crucial for the catalytic process. Loss of function of SGSH results a disease called mucopolysaccharidosis type IIIA (Sanfilippo A syndrome), a fatal childhood-onset neurodegenerative disease with mild facial, visceral and skeletal abnormalities.

                          10        20        30
                  ....*....|....*....|....*....|
gi 1372261749  10 KQTTWEGGHRVPALAYWPGRVPANVTSTAL 39
Cdd:cd16027   234 KGTLYDSGLRVPLIVRWPGKIKPGSVSDAL 263

unchracterized sulfatase homologous to glucosamine (N-acetyl)-6-sulfatase(G6S, GNS); N-acetylglucosamine-6-sulfatase also known as glucosamine (N-acetyl)-6-sulfatase hydrolyzes of the 6-sulfate groups of the N-acetyl-D-glucosamine 6-sulfate units of heparan sulfate and keratan sulfate. Deficiency of N-acetylglucosamine-6-sulfatase results in the disease of Sanfilippo Syndrome type IIId or Mucopolysaccharidosis III (MPS-III), a rare autosomal recessive lysosomal storage disease.

                          10        20        30
                  ....*....|....*....|....*....|
gi 1372261749  10 KQTTWEGGHRVPALAYWPGRVPANVTSTAL 39
Cdd:cd16031   286 KRLMYEESIRVPLIIRDPRLIKAGTVVDAL 315