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 300795589 202 ILFLTDLHWDHDYLEG-TDPDCADPLCCRRGSGLPPASrPGAGYWGEYsKCDLPLRTLESLLSGLGP-AGPFDMVYWTGD 279
Cdd:cd00842    1 FLHISDIHYDPLYKVGsEYANCRSPLCCRDESGPGDVK-PPAGYWGTY-GCDSPWSLVESALEAIKKnHPKPDFILWTGD 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300795589 280 IPAHDVWHQTRQDQLRALTTVTALVRKFLGPVPVYPAVGNHESTPVNSFPPPfiegNHSSRWLYEAMAKAWEPWLPAEAL 359
Cdd:cd00842   79 LVRHDVDEQTPEETVESESNLTNLLKKYFPNVPVYPALGNHDSYPVNQFPPH----SNSPSWLYDALAELWKPWLPTEAK 154

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300795589 360 RTLRIGGFYALSPYPGLRLISLNMNFCSRENFWLLINSTDPAGQLQWLVGELQAAEDRGDKVHIIGHIPPGH--CLKSWS 437
Cdd:cd00842  155 ETFKKGGYYSVDVKDGLRVISLNTNLYYKKNFWLYSNNTDPCGQLQWLEDELEDAEQKGEKVWIIGHIPPGLnsYDADWS 234

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 300795589 438 WNYYRIVARYENTLAAQFFGHTHVDEFEVFYDEETLSRPLAVAFLAPSATTYIGLNPGYR 497
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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 300795589    89 LTCPICKGLFTAI-NLGLKEPNVARVGSVAIKLCNLLKIAPPAVCQSIVHLFEDDMVEVWRRsVLSPSEACGLL 161
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 300795589 202 ILFLTDLHWDHDYLEG-TDPDCADPLCCRRGSGLPPASrPGAGYWGEYsKCDLPLRTLESLLSGLGP-AGPFDMVYWTGD 279
Cdd:cd00842    1 FLHISDIHYDPLYKVGsEYANCRSPLCCRDESGPGDVK-PPAGYWGTY-GCDSPWSLVESALEAIKKnHPKPDFILWTGD 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300795589 280 IPAHDVWHQTRQDQLRALTTVTALVRKFLGPVPVYPAVGNHESTPVNSFPPPfiegNHSSRWLYEAMAKAWEPWLPAEAL 359
Cdd:cd00842   79 LVRHDVDEQTPEETVESESNLTNLLKKYFPNVPVYPALGNHDSYPVNQFPPH----SNSPSWLYDALAELWKPWLPTEAK 154

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300795589 360 RTLRIGGFYALSPYPGLRLISLNMNFCSRENFWLLINSTDPAGQLQWLVGELQAAEDRGDKVHIIGHIPPGH--CLKSWS 437
Cdd:cd00842  155 ETFKKGGYYSVDVKDGLRVISLNTNLYYKKNFWLYSNNTDPCGQLQWLEDELEDAEQKGEKVWIIGHIPPGLnsYDADWS 234

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 300795589 438 WNYYRIVARYENTLAAQFFGHTHVDEFEVFYDEETLSRPLAVAFLAPSATTYIGLNPGYR 497
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 300795589  475 RPLAVAFLAPSATTYIGL------NPGYRVYQID-GNYSgsshvVLDHETYILNLTQANIPGAiPHWQLLYRARETYGLP 547
Cdd:pfam19272   1 NPVNSLFVAPAVTPVKSVlekesnNPGVRLYQYDpKDYK-----LLDMLQYYLNLTEANLKGE-SNWKLEYILTKAYGIE 74

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 300795589  548 NTLPTAWHNLVYR-MRGDMQLFQTFWFLYHKGHPPSEPCGTPCRLATLCA 596
Cdd:pfam19272  75 DLQPQSLYGLAKQfAVPHSKQFEKYYNYFFVSYDSSIVCEGGCKALQICA 124

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 300795589  255 LRTLESLLSGLGPAGPFDMVYWTGDIPAHDVWHQTRQDqlralttvtaLVRKFLGPVPVYPAVGNHESTPVNSFPPPFIE 334
Cdd:pfam00149  15 LDDLLELLKKLLEEGKPDLVLHAGDLVDRGPPSEEVLE----------LLERLIKYVPVYLVRGNHDFDYGECLRLYPYL 84

                          90
                  ....*....|....*...
gi 300795589  335 GNHSSRWLYEAMAKAWEP 352
Cdd:pfam00149  85 GLLARPWKRFLEVFNFLP 102

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 300795589 202 ILFLTDLHWDHDYLEG-TDPDCADPLCCRRGSGLPPASrPGAGYWGEYsKCDLPLRTLESLLSGLGP-AGPFDMVYWTGD 279
Cdd:cd00842    1 FLHISDIHYDPLYKVGsEYANCRSPLCCRDESGPGDVK-PPAGYWGTY-GCDSPWSLVESALEAIKKnHPKPDFILWTGD 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300795589 280 IPAHDVWHQTRQDQLRALTTVTALVRKFLGPVPVYPAVGNHESTPVNSFPPPfiegNHSSRWLYEAMAKAWEPWLPAEAL 359
Cdd:cd00842   79 LVRHDVDEQTPEETVESESNLTNLLKKYFPNVPVYPALGNHDSYPVNQFPPH----SNSPSWLYDALAELWKPWLPTEAK 154

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300795589 360 RTLRIGGFYALSPYPGLRLISLNMNFCSRENFWLLINSTDPAGQLQWLVGELQAAEDRGDKVHIIGHIPPGH--CLKSWS 437
Cdd:cd00842  155 ETFKKGGYYSVDVKDGLRVISLNTNLYYKKNFWLYSNNTDPCGQLQWLEDELEDAEQKGEKVWIIGHIPPGLnsYDADWS 234

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 300795589 438 WNYYRIVARYENTLAAQFFGHTHVDEFEVFYDEETLSRPLAVAFLAPSATTYIGLNPGYR 497
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 300795589 278 GDIpahdVWHQTRQDQ-LRALTTVTALVRKFlgPVPVYPAVGNHEstpvnsfpppfiegnhssrwLYEamakawepwLPA 356
Cdd:cd07396   54 GDI----IDGYNAKDRsKEALDAVLSILDRL--KGPVHHVLGNHE--------------------FYN---------FPR 98

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300795589 357 EALRTLRI-----GGFYALSPYPGLRLISLNmnfcsrenfWLLINSTDPAGQLQWLVGELQAAEDRGDKVHIIGHIP--- 428
Cdd:cd07396   99 EYLNHLKTlngedAYYYSFSPGPGFRFLVLD---------FVKFNGGIGEEQLAWLRNELTSADANGEKVIVLSHLPiyp 169

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|.
gi 300795589 429 ---PGHCLkswSWNYYRIVA---RYENtLAAQFFGHTH-----VDEFEVFY 468
Cdd:cd07396  170 eaaDPQCL---LWNYEEVLAileSYPC-VKACFSGHNHeggyeQDSHGVHH 216

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 300795589    89 LTCPICKGLFTAI-NLGLKEPNVARVGSVAIKLCNLLKIAPPAVCQSIVHLFEDDMVEVWRRsVLSPSEACGLL 161
Cdd:smart00741   1 LLCELCEFVVKQLeNLLKDNKTEEEIKKALEKVCKKLPKSLSDQCKEFVDQYGPEIIDLLEQ-GLDPKDVCQKL 73