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 320091594 201 ILFLTDLHWDHDYLEG-TDPDCADPLCCRRGSGLPPASrPGAGYWGEYsKCDLPLRTLESLLSGLGP-AGPFDMVYWTGD 278
Cdd:cd00842    1 FLHISDIHYDPLYKVGsEYANCRSPLCCRDESGPGDVK-PPAGYWGTY-GCDSPWSLVESALEAIKKnHPKPDFILWTGD 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 320091594 279 IPAHDVWHQTRQDQLRALTTVTALVRKFLGPVPVYPAVGNHESTPVNSFPPPfiegNHSSRWLYEAMAKAWEPWLPAEAL 358
Cdd:cd00842   79 LVRHDVDEQTPEETVESESNLTNLLKKYFPNVPVYPALGNHDSYPVNQFPPH----SNSPSWLYDALAELWKPWLPTEAK 154

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 320091594 359 RTLRIGGFYALSPYPGLRLISLNMNFCSRENFWLLINSTDPAGQLQWLVGELQAAEDRGDKVHIIGHIPPGH--CLKSWS 436
Cdd:cd00842  155 ETFKKGGYYSVDVKDGLRVISLNTNLYYKKNFWLYSNNTDPCGQLQWLEDELEDAEQKGEKVWIIGHIPPGLnsYDADWS 234

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 320091594 437 WNYYRIVARYENTLAAQFFGHTHVDEFEVFYDEETLSRPLAVAFLAPSATTYIGLNP 493
Cdd:cd00842  235 ERFYQIINRYSDTIAGQFFGHTHRDEFRVFYDDKDTGSPINVAYIAPSVTPYTGNNP 291

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 320091594 201 ILFLTDLHWDHDYLEG-TDPDCADPLCCRRGSGLPPASrPGAGYWGEYsKCDLPLRTLESLLSGLGP-AGPFDMVYWTGD 278
Cdd:cd00842    1 FLHISDIHYDPLYKVGsEYANCRSPLCCRDESGPGDVK-PPAGYWGTY-GCDSPWSLVESALEAIKKnHPKPDFILWTGD 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 320091594 279 IPAHDVWHQTRQDQLRALTTVTALVRKFLGPVPVYPAVGNHESTPVNSFPPPfiegNHSSRWLYEAMAKAWEPWLPAEAL 358
Cdd:cd00842   79 LVRHDVDEQTPEETVESESNLTNLLKKYFPNVPVYPALGNHDSYPVNQFPPH----SNSPSWLYDALAELWKPWLPTEAK 154

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 320091594 359 RTLRIGGFYALSPYPGLRLISLNMNFCSRENFWLLINSTDPAGQLQWLVGELQAAEDRGDKVHIIGHIPPGH--CLKSWS 436
Cdd:cd00842  155 ETFKKGGYYSVDVKDGLRVISLNTNLYYKKNFWLYSNNTDPCGQLQWLEDELEDAEQKGEKVWIIGHIPPGLnsYDADWS 234

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 320091594 437 WNYYRIVARYENTLAAQFFGHTHVDEFEVFYDEETLSRPLAVAFLAPSATTYIGLNP 493
Cdd:cd00842  235 ERFYQIINRYSDTIAGQFFGHTHRDEFRVFYDDKDTGSPINVAYIAPSVTPYTGNNP 291

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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 320091594    87 LTCPICKGLFTAINLGLKKEPNVARVGSVAIKLCNLLKIAPPAVCQSIVHLFEDDMVEVWRRsVLSPSEACGLL 160
Cdd:smart00741   1 LLCELCEFVVKQLENLLKDNKTEEEIKKALEKVCKKLPKSLSDQCKEFVDQYGPEIIDLLEQ-GLDPKDVCQKL 73

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 320091594 201 ILFLTDLHWDHDYLEG-TDPDCADPLCCRRGSGLPPASrPGAGYWGEYsKCDLPLRTLESLLSGLGP-AGPFDMVYWTGD 278
Cdd:cd00842    1 FLHISDIHYDPLYKVGsEYANCRSPLCCRDESGPGDVK-PPAGYWGTY-GCDSPWSLVESALEAIKKnHPKPDFILWTGD 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 320091594 279 IPAHDVWHQTRQDQLRALTTVTALVRKFLGPVPVYPAVGNHESTPVNSFPPPfiegNHSSRWLYEAMAKAWEPWLPAEAL 358
Cdd:cd00842   79 LVRHDVDEQTPEETVESESNLTNLLKKYFPNVPVYPALGNHDSYPVNQFPPH----SNSPSWLYDALAELWKPWLPTEAK 154

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 320091594 359 RTLRIGGFYALSPYPGLRLISLNMNFCSRENFWLLINSTDPAGQLQWLVGELQAAEDRGDKVHIIGHIPPGH--CLKSWS 436
Cdd:cd00842  155 ETFKKGGYYSVDVKDGLRVISLNTNLYYKKNFWLYSNNTDPCGQLQWLEDELEDAEQKGEKVWIIGHIPPGLnsYDADWS 234

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 320091594 437 WNYYRIVARYENTLAAQFFGHTHVDEFEVFYDEETLSRPLAVAFLAPSATTYIGLNP 493
Cdd:cd00842  235 ERFYQIINRYSDTIAGQFFGHTHRDEFRVFYDDKDTGSPINVAYIAPSVTPYTGNNP 291

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 320091594 277 GDIpahdVWHQTRQDQ-LRALTTVTALVRKFlgPVPVYPAVGNHEstpvnsfpppfiegnhssrwLYEamakawepwLPA 355
Cdd:cd07396   54 GDI----IDGYNAKDRsKEALDAVLSILDRL--KGPVHHVLGNHE--------------------FYN---------FPR 98

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 320091594 356 EALRTLRI-----GGFYALSPYPGLRLISLNmnfcsrenfWLLINSTDPAGQLQWLVGELQAAEDRGDKVHIIGHIP--- 427
Cdd:cd07396   99 EYLNHLKTlngedAYYYSFSPGPGFRFLVLD---------FVKFNGGIGEEQLAWLRNELTSADANGEKVIVLSHLPiyp 169

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|.
gi 320091594 428 ---PGHCLkswSWNYYRIVA---RYENtLAAQFFGHTH-----VDEFEVFY 467
Cdd:cd07396  170 eaaDPQCL---LWNYEEVLAileSYPC-VKACFSGHNHeggyeQDSHGVHH 216

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 320091594  254 LRTLESLLSGLGPAGPFDMVYWTGDIPAHDVWHQTRQDqlralttvtaLVRKFLGPVPVYPAVGNHESTPVNSFPPPFIE 333
Cdd:pfam00149  15 LDDLLELLKKLLEEGKPDLVLHAGDLVDRGPPSEEVLE----------LLERLIKYVPVYLVRGNHDFDYGECLRLYPYL 84

                          90
                  ....*....|....*...
gi 320091594  334 GNHSSRWLYEAMAKAWEP 351
Cdd:pfam00149  85 GLLARPWKRFLEVFNFLP 102