acid sphingomyelinase and related proteins, metallophosphatase domain; Acid sphingomyelinase (ASMase) is a ubiquitously expressed phosphodiesterase which hydrolyzes sphingomyelin in acid pH conditions to form ceramide, a bioactive second messenger, as part of the sphingomyelin signaling pathway. ASMase is localized at the noncytosolic leaflet of biomembranes (for example the luminal leaflet of endosomes, lysosomes and phagosomes, and the extracellular leaflet of plasma membranes). ASMase-deficient humans develop Niemann-Pick disease. This disease is characterized by lysosomal storage of sphingomyelin in all tissues. Although ASMase-deficient mice are resistant to stress-induced apoptosis, they have greater susceptibility to bacterial infection. The latter correlates with defective phagolysosomal fusion and antibacterial killing activity in ASMase-deficient macrophages. ASMase belongs to the metallophosphatase (MPP) superfamily. MPPs are functionally diverse, but all share a conserved domain with an active site consisting of two metal ions (usually manganese, iron, or zinc) coordinated with octahedral geometry by a cage of histidine, aspartate, and asparagine residues. The MPP superfamily includes: the phosphoprotein phosphatases (PPPs), Mre11/SbcD-like exonucleases, Dbr1-like RNA lariat debranching enzymes, YfcE-like phosphodiesterases, purple acid phosphatases (PAPs), YbbF-like UDP-2,3-diacylglucosamine hydrolases, and acid sphingomyelinases (ASMases). The conserved domain is a double beta-sheet sandwich with a di-metal active site made up of residues located at the C-terminal side of the sheets. This domain is thought to allow for productive metal coordination.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24651379 221 ICQFSDIHHDPYYTPGS-LATCAEPMCCqRNKETTEGTSDAAGYWGDYRdCDLPWHAFESALDNAVAN-SKCDFIYQTGD 298
Cdd:cd00842   1 FLHISDIHYDPLYKVGSeYANCRSPLCC-RDESGPGDVKPPAGYWGTYG-CDSPWSLVESALEAIKKNhPKPDFILWTGD 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24651379 299 IVDHMVWATSVEKNTMVLTKVSERLNAAFGDVPVYPCIGNHEPHPLNLFSPEGvpdeISTKWLYEHLYNDWSKWLPAETK 378
Cdd:cd00842  79 LVRHDVDEQTPEETVESESNLTNLLKKYFPNVPVYPALGNHDSYPVNQFPPHS----NSPSWLYDALAELWKPWLPTEAK 154

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24651379 379 ETILKGGYYTVVPRKGFRIIALNSNDCYTDNFWLYHSGTDKIPQLQWFHDTLLEAEKNGEYVHVLTHIPSGDGTCWSVWA 458
Cdd:cd00842 155 ETFKKGGYYSVDVKDGLRVISLNTNLYYKKNFWLYSNNTDPCGQLQWLEDELEDAEQKGEKVWIIGHIPPGLNSYDADWS 234

                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 24651379 459 REFNRCVSRFRSTISGIFTGHSHKDELFVYYSE-DEGHPTAVAWNGGAVTTYSNKNPNYR 517
Cdd:cd00842 235 ERFYQIINRYSDTIAGQFFGHTHRDEFRVFYDDkDTGSPINVAYIAPSVTPYTGNNPSFR 294

Saposin (B) Domains; Present in multiple copies in prosaposin and in pulmonary surfactant-associated protein B. In plant aspartic proteinases, a saposin domain is circularly permuted. This causes the prediction algorithm to predict two such domains, where only one is truly present.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24651379     99 CVACRSVTRVLIRTIREEDGELHgenssvlMKEFAMDVCRRLNLQTEEVCEGLIDSNLPSVEYIMRNSEsDSQSFCSlfm 178
Cdd:smart00741   3 CELCEFVVKQLENLLKDNKTEEE-------IKKALEKVCKKLPKSLSDQCKEFVDQYGPEIIDLLEQGL-DPKDVCQ--- 71

                   ....*
gi 24651379    179 EFNFC 183
Cdd:smart00741  72 KLGLC 76

acid sphingomyelinase and related proteins, metallophosphatase domain; Acid sphingomyelinase (ASMase) is a ubiquitously expressed phosphodiesterase which hydrolyzes sphingomyelin in acid pH conditions to form ceramide, a bioactive second messenger, as part of the sphingomyelin signaling pathway. ASMase is localized at the noncytosolic leaflet of biomembranes (for example the luminal leaflet of endosomes, lysosomes and phagosomes, and the extracellular leaflet of plasma membranes). ASMase-deficient humans develop Niemann-Pick disease. This disease is characterized by lysosomal storage of sphingomyelin in all tissues. Although ASMase-deficient mice are resistant to stress-induced apoptosis, they have greater susceptibility to bacterial infection. The latter correlates with defective phagolysosomal fusion and antibacterial killing activity in ASMase-deficient macrophages. ASMase belongs to the metallophosphatase (MPP) superfamily. MPPs are functionally diverse, but all share a conserved domain with an active site consisting of two metal ions (usually manganese, iron, or zinc) coordinated with octahedral geometry by a cage of histidine, aspartate, and asparagine residues. The MPP superfamily includes: the phosphoprotein phosphatases (PPPs), Mre11/SbcD-like exonucleases, Dbr1-like RNA lariat debranching enzymes, YfcE-like phosphodiesterases, purple acid phosphatases (PAPs), YbbF-like UDP-2,3-diacylglucosamine hydrolases, and acid sphingomyelinases (ASMases). The conserved domain is a double beta-sheet sandwich with a di-metal active site made up of residues located at the C-terminal side of the sheets. This domain is thought to allow for productive metal coordination.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24651379 221 ICQFSDIHHDPYYTPGS-LATCAEPMCCqRNKETTEGTSDAAGYWGDYRdCDLPWHAFESALDNAVAN-SKCDFIYQTGD 298
Cdd:cd00842   1 FLHISDIHYDPLYKVGSeYANCRSPLCC-RDESGPGDVKPPAGYWGTYG-CDSPWSLVESALEAIKKNhPKPDFILWTGD 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24651379 299 IVDHMVWATSVEKNTMVLTKVSERLNAAFGDVPVYPCIGNHEPHPLNLFSPEGvpdeISTKWLYEHLYNDWSKWLPAETK 378
Cdd:cd00842  79 LVRHDVDEQTPEETVESESNLTNLLKKYFPNVPVYPALGNHDSYPVNQFPPHS----NSPSWLYDALAELWKPWLPTEAK 154

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24651379 379 ETILKGGYYTVVPRKGFRIIALNSNDCYTDNFWLYHSGTDKIPQLQWFHDTLLEAEKNGEYVHVLTHIPSGDGTCWSVWA 458
Cdd:cd00842 155 ETFKKGGYYSVDVKDGLRVISLNTNLYYKKNFWLYSNNTDPCGQLQWLEDELEDAEQKGEKVWIIGHIPPGLNSYDADWS 234

                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 24651379 459 REFNRCVSRFRSTISGIFTGHSHKDELFVYYSE-DEGHPTAVAWNGGAVTTYSNKNPNYR 517
Cdd:cd00842 235 ERFYQIINRYSDTIAGQFFGHTHRDEFRVFYDDkDTGSPINVAYIAPSVTPYTGNNPSFR 294

Acid sphingomyelin phosphodiesterase C-terminal region; This entry corresponds to the C-terminal region of the phosphodiesterase domain found in acid sphingomyelin phosphodiesterases. It contains two disulphide bridges.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24651379   509 YSNkNPNYREYAVNPETYTVTNHWTWIYNLTAANLKpdEQPEWFLEYEFIKEF-TEDMSPAGISKLLDEFAENP-ELMRK 586
Cdd:pfam19272  22 ESN-NPGVRLYQYDPKDYKLLDMLQYYLNLTEANLK--GESNWKLEYILTKAYgIEDLQPQSLYGLAKQFAVPHsKQFEK 98

                          90       100
                  ....*....|....*....|....*..
gi 24651379   587 YWRYRVTSADPQVNggCDRSCLAGSLC 613
Cdd:pfam19272  99 YYNYFFVSYDSSIV--CEGGCKALQIC 123

Saposin (B) Domains; Present in multiple copies in prosaposin and in pulmonary surfactant-associated protein B. In plant aspartic proteinases, a saposin domain is circularly permuted. This causes the prediction algorithm to predict two such domains, where only one is truly present.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24651379     99 CVACRSVTRVLIRTIREEDGELHgenssvlMKEFAMDVCRRLNLQTEEVCEGLIDSNLPSVEYIMRNSEsDSQSFCSlfm 178
Cdd:smart00741   3 CELCEFVVKQLENLLKDNKTEEE-------IKKALEKVCKKLPKSLSDQCKEFVDQYGPEIIDLLEQGL-DPKDVCQ--- 71

                   ....*
gi 24651379    179 EFNFC 183
Cdd:smart00741  72 KLGLC 76

acid sphingomyelinase and related proteins, metallophosphatase domain; Acid sphingomyelinase (ASMase) is a ubiquitously expressed phosphodiesterase which hydrolyzes sphingomyelin in acid pH conditions to form ceramide, a bioactive second messenger, as part of the sphingomyelin signaling pathway. ASMase is localized at the noncytosolic leaflet of biomembranes (for example the luminal leaflet of endosomes, lysosomes and phagosomes, and the extracellular leaflet of plasma membranes). ASMase-deficient humans develop Niemann-Pick disease. This disease is characterized by lysosomal storage of sphingomyelin in all tissues. Although ASMase-deficient mice are resistant to stress-induced apoptosis, they have greater susceptibility to bacterial infection. The latter correlates with defective phagolysosomal fusion and antibacterial killing activity in ASMase-deficient macrophages. ASMase belongs to the metallophosphatase (MPP) superfamily. MPPs are functionally diverse, but all share a conserved domain with an active site consisting of two metal ions (usually manganese, iron, or zinc) coordinated with octahedral geometry by a cage of histidine, aspartate, and asparagine residues. The MPP superfamily includes: the phosphoprotein phosphatases (PPPs), Mre11/SbcD-like exonucleases, Dbr1-like RNA lariat debranching enzymes, YfcE-like phosphodiesterases, purple acid phosphatases (PAPs), YbbF-like UDP-2,3-diacylglucosamine hydrolases, and acid sphingomyelinases (ASMases). The conserved domain is a double beta-sheet sandwich with a di-metal active site made up of residues located at the C-terminal side of the sheets. This domain is thought to allow for productive metal coordination.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24651379 221 ICQFSDIHHDPYYTPGS-LATCAEPMCCqRNKETTEGTSDAAGYWGDYRdCDLPWHAFESALDNAVAN-SKCDFIYQTGD 298
Cdd:cd00842   1 FLHISDIHYDPLYKVGSeYANCRSPLCC-RDESGPGDVKPPAGYWGTYG-CDSPWSLVESALEAIKKNhPKPDFILWTGD 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24651379 299 IVDHMVWATSVEKNTMVLTKVSERLNAAFGDVPVYPCIGNHEPHPLNLFSPEGvpdeISTKWLYEHLYNDWSKWLPAETK 378
Cdd:cd00842  79 LVRHDVDEQTPEETVESESNLTNLLKKYFPNVPVYPALGNHDSYPVNQFPPHS----NSPSWLYDALAELWKPWLPTEAK 154

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24651379 379 ETILKGGYYTVVPRKGFRIIALNSNDCYTDNFWLYHSGTDKIPQLQWFHDTLLEAEKNGEYVHVLTHIPSGDGTCWSVWA 458
Cdd:cd00842 155 ETFKKGGYYSVDVKDGLRVISLNTNLYYKKNFWLYSNNTDPCGQLQWLEDELEDAEQKGEKVWIIGHIPPGLNSYDADWS 234

                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 24651379 459 REFNRCVSRFRSTISGIFTGHSHKDELFVYYSE-DEGHPTAVAWNGGAVTTYSNKNPNYR 517
Cdd:cd00842 235 ERFYQIINRYSDTIAGQFFGHTHRDEFRVFYDDkDTGSPINVAYIAPSVTPYTGNNPSFR 294

Homo sapiens Nbla03831 and related proteins, metallophosphatase domain; Nbla03831 (also known as LOC56985) is an uncharacterized Homo sapiens protein with a domain that belongs to the metallophosphatase (MPP) superfamily. MPPs are functionally diverse, but all share a conserved domain with an active site consisting of two metal ions (usually manganese, iron, or zinc) coordinated with octahedral geometry by a cage of histidine, aspartate, and asparagine residues. The MPP superfamily includes: Mre11/SbcD-like exonucleases, Dbr1-like RNA lariat debranching enzymes, YfcE-like phosphodiesterases, purple acid phosphatases (PAPs), YbbF-like UDP-2,3-diacylglucosamine hydrolases, and acid sphingomyelinases (ASMases). The conserved domain is a double beta-sheet sandwich with a di-metal active site made up of residues located at the C-terminal side of the sheets. This domain is thought to allow for productive metal coordination.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24651379 286 ANSKCDFIYQTGDIVDHMVWATSVEKNTMVLTKVSERLNaafgdVPVYPCIGNHEphplnlfspegvpdeistkwlyehL 365
Cdd:cd07396  43 RESNLAFVVQLGDIIDGYNAKDRSKEALDAVLSILDRLK-----GPVHHVLGNHE------------------------F 93

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24651379 366 YNdwskwLPAETKETI-----LKGGYYTVVPRKGFRIIALNsndcytdnFWLYHSGTDKiPQLQWFHDTLLEAEKNGEYV 440
Cdd:cd07396  94 YN-----FPREYLNHLktlngEDAYYYSFSPGPGFRFLVLD--------FVKFNGGIGE-EQLAWLRNELTSADANGEKV 159

                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*..
gi 24651379 441 HVLTHIP----SGDGTCwSVW-AREFNRCVSRFrSTISGIFTGHSHK 482
Cdd:cd07396 160 IVLSHLPiypeAADPQC-LLWnYEEVLAILESY-PCVKACFSGHNHE 204

Calcineurin-like phosphoesterase; This family includes a diverse range of phosphoesterases, including protein phosphoserine phosphatases, nucleotidases, sphingomyelin phosphodiesterases and 2'-3' cAMP phosphodiesterases as well as nucleases such as bacterial SbcD or yeast MRE11. The most conserved regions in this superfamily centre around the metal chelating residues.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24651379   274 WHAFESALDNAVANSKCDFIYQTGDIVDHMVWATSVEKNtmvltkvserLNAAFGDVPVYPCIGNHEPHPLNLFSPEGVP 353
Cdd:pfam00149  15 LDDLLELLKKLLEEGKPDLVLHAGDLVDRGPPSEEVLEL----------LERLIKYVPVYLVRGNHDFDYGECLRLYPYL 84

                          90       100
                  ....*....|....*....|.
gi 24651379   354 DEISTKWLYehlYNDWSKWLP 374
Cdd:pfam00149  85 GLLARPWKR---FLEVFNFLP 102

metallophosphatase superfamily, metallophosphatase domain; Metallophosphatases (MPPs), also known as metallophosphoesterases, phosphodiesterases (PDEs), binuclear metallophosphoesterases, and dimetal-containing phosphoesterases (DMPs), represent a diverse superfamily of enzymes with a conserved domain containing an active site consisting of two metal ions (usually manganese, iron, or zinc) coordinated with octahedral geometry by a cage of histidine, aspartate, and asparagine residues. This superfamily includes: the phosphoprotein phosphatases (PPPs), Mre11/SbcD-like exonucleases, Dbr1-like RNA lariat debranching enzymes, YfcE-like phosphodiesterases, purple acid phosphatases (PAPs), YbbF-like UDP-2,3-diacylglucosamine hydrolases, and acid sphingomyelinases (ASMases). The conserved domain is a double beta-sheet sandwich with a di-metal active site made up of residues located at the C-terminal side of the sheets. This domain is thought to allow for productive metal coordination.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24651379 272 LPWHAFESALDNAVANS-KCDFIYQTGDIVDHMvwATSVEKNTMVLTKVSErlnaafgDVPVYPCIGNHE 340
Cdd:cd00838   8 GNLEALEAVLEAALAKAeKPDLVICLGDLVDYG--PDPEEVELKALRLLLA-------GIPVYVVPGNHD 68