Conserved Protein Domain Family
MPP_ASMase

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cd00842: MPP_ASMase 
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.
Statistics
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PSSM-Id: 277321
View PSSM: cd00842
Aligned: 68 rows
Threshold Bit Score: 225.256
Threshold Setting Gi: 72387676
Created: 1-Nov-2000
Updated: 2-Oct-2020
Structure
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Aligned Rows:
 
putative activeputative metal
Feature 1:putative active site [active site]
Evidence:

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1             # #                                                                        
P17405       201 ILFLTDLHWDHDYLEGtd-------pdCadplccrrgsg-----------------------lppasrpgagyWGEYs-k 249 human
XP_002296197   7 FLWFSDIHFDPYYASGqaynapfndvsCknvt-------------------------------------stssIGIHg-- 47  Thalassiosira p...
Q5KH67        58 FLHITDIHPDPHYKTGstf-----dsgChrkpkkdgksegkkatenerg---nedlddkefdtliknedlagkWGTAvsd 129 Cryptococcus ne...
NP_595346     49 FLHITDMHPDIYYEKGstv-----dhyChsydhnsddtp------------------------lgkskvgylsPGPGy-e 98  Schizosaccharom...
Q6CEE7        51 FLHITDIHPDPYFHVGava-----edkChvdpdhkdsdypdedselvwfratgkkkhnhhkgkdhekmpkagyYGHPlss 125 Yarrowia lipoly...
Q04119        97 FLHITDIHPDPYYVEGssi-----davChtgkpsk-------------------------------kkdvapkFGKAmsg 140 Saccharomyces c...
XP_500965     51 FLHITDIHPDPYFHVGava-----edkChvdpdhkdsdypdedselvwfratgkkkhnhhkgkdhekmpkagyYGHPlss 125 Yarrowia lipoly...
EAL20739      58 FLHITDIHPDPHYKTGstf-----dsgChrkpkkdgksegkkatenerg---nedlddkefdtliknedlagkWGTAvsd 129 Cryptococcus ne...
XP_647257     22 FLHISDVHYSSAMNSLlyna----svmCigptvtkefdhkehed--------------liedterlnlptnglYGRYg-- 81  Dictyostelium d...
XP_001748110 158 FLWITDVHYDHFYLDDts--------sCssnvg-----------------------------------dsrpeFGRSd-- 192 Monosiga brevic...
Feature 1                                         #                                              
P17405       250 CDLPLRTLESLLSGLgpa-----gpfDMVYWTGDIPAHdvwhqtrqdqlr----------------------------al 296 human
XP_002296197  48 CDSPEELVRSTFEQAvrvcanapsppSFIIITGDTVRHsvdmlfanvtnegsesrsegevsiasnspyhikameaagkiv 127 Thalassiosira p...
Q5KH67       130 CDCPMSLVNITFDWLkeew---anevDFVVWTGDNARHdidrriprtpkeif------------------------dsnr 182 Cryptococcus ne...
NP_595346     99 CDSSPALIDKTLEWLkehqddvlggiDFILWTGDNSRHdndnhfprtqseil-------------------------asn 153 Schizosaccharom...
Q6CEE7       126 CDGPISLMNATFDWIdqni---rdeiDFIIWTGDNVRHdndnryprleqdifgynqivsskf-----helfrynetrdge 197 Yarrowia lipoly...
Q04119       141 CDSPVILMEETLRWIkenl---rdkiDFVIWTGDNIRHdndrkhprteaqifdmnni---------------vadkmtel 202 Saccharomyces c...
XP_500965    126 CDGPISLMNATFDWIdqni---rdeiDFIIWTGDNVRHdndnryprleqdifgynqivsskf-----helfrynetrdge 197 Yarrowia lipoly...
EAL20739     130 CDCPMSLVNITFDWLkeew---anevDFVVWTGDNARHdidrriprtpkeif------------------------dsnr 182 Cryptococcus ne...
XP_647257     82 CDTNQLLLSEVISEMlnvn----snpDFIIYTGDGAGHglpngpwsesq------------------------------- 126 Dictyostelium d...
XP_001748110 193 CDAPFALLNVSFEAAklal----pdpGFVLVTGDSVRHdmdenfpdstkrlqlvhdtlq----------nvstlldahye 258 Monosiga brevic...
Feature 1                             ##                                                         
P17405       297 ttvtalvrkfLGPVPVYPAVGNHESTPVNsfpppfi-----------egnhssrWLYEAMAKAWEPWLpaeal------- 358 human
XP_002296197 128 qdmttilhesFPNTPVVLSVGNNDVVPDYylelkeentplgnlslavddagmlgVIFQALSNTTTSEGkskkailtedde 207 Thalassiosira p...
Q5KH67       183 mivdrmldafGRDMPIVPSIGNNDIYPHNvlaa------------------gpsRITEEFLLIWKHFIpseaa------- 237 Cryptococcus ne...
NP_595346    154 edlvnkmieaFPDVPIVSAIGNNDIYPHNimea------------------gpsSMTRQLAGAWDALIpyeer------- 208 Schizosaccharom...
Q6CEE7       198 ghngggdpqhPLVIPIIPSLGNNDVFPHNlyla------------------gpsFQSRRMLQIWSEFVpeaqq------- 252 Yarrowia lipoly...
Q04119       203 fsagneedprDFDVSVIPSLGNNDVFPHNmfal------------------gptLQTREYYRIWKNFVpqqqqr------ 258 Saccharomyces c...
XP_500965    198 ghngggdpqhPLVIPIIPSLGNNDVFPHNlyla------------------gpsFQSRRMLQIWSEFVpeaqq------- 252 Yarrowia lipoly...
EAL20739     183 mivdrmldafGRDMPIVPSIGNNDIYPHNvlaa------------------gpsRITEEFLLIWKHFIpseaa------- 237 Cryptococcus ne...
XP_647257    127 stlakslygaYPNTQFIPTIGNNDVFPDYnsq-------------------cndSNLQFLYETWAQWIptnqvs------ 181 Dictyostelium d...
XP_001748110 259 rslrlhspatEAHEAVLNTFGNNDVLVDYqmdl-----------------gtnnTLLRAVADAWRAVLtpaet------- 314 Monosiga brevic...
Feature 1                                                                                #       
P17405       359 rtlriGGFYalsp-ypgLRLISLNMNFCSRENfwll-----instDPAGQLQWLVGELQAAEDRGDKVHIIGHIPPGhcl 432 human
XP_002296197 208 wtflrGGYYsrsfhdgsLVVLSLNTVLYASFFeptp-----mnadDPGKQFEWMRKMMSYSREMRGQVIIIGHIPPSlgs 282 Thalassiosira p...
Q5KH67       238 hvferGAYFsvevipdrLAVISLNTLFWYDANtlvdgc-rdhsndPGALEMDWLEVQLNNFRQRGMQVWLTGHVPPHmnh 316 Cryptococcus ne...
NP_595346    209 htfekGSYYlcdvipdkLAAISINTLYLSNKNaavdgcpddnldePGSLFMRWFKIQLEAYRLKGMKVWLLGHIPPTrgq 288 Schizosaccharom...
Q6CEE7       253 hifsrGSYYfqevitgkLAVISLNTLYFYKSNpmsdgc--dektdPGYKHLVWLGVVLDEMRQRGMKVWLSGHVPPVekn 330 Yarrowia lipoly...
Q04119       259 tfdrsASFLtevi-pgkLAVLSINTLYLFKANplvdnc--nskkePGYQLLLWFGYVLEELRSRGMKVWLSGHVPPIakn 335 Saccharomyces c...
XP_500965    253 hifsrGSYYfqevitgkLAVISLNTLYFYKSNpmsdgc--dektdPGYKHLVWLGVVLDEMRQRGMKVWLSGHVPPVekn 330 Yarrowia lipoly...
EAL20739     238 hvferGAYFsvevipdrLAVISLNTLFWYDANtlvdgc-rdhsndPGALEMDWLEVQLNNFRQRGMQVWLTGHVPPHmnh 316 Cryptococcus ne...
XP_647257    182 sflyrGSFVvsp--vsgLTIISLNTILYSVKNkntf-----stpqDPCGQFAWLEQQLIAAKQAGNSVYIIGHIFPGldp 254 Dictyostelium d...
XP_001748110 315 ldvqtGGYMarnv-tehLTIISINTVLYSFKRlpatg----rllpDPYGQFAWLIKQLELVRQTNRQAYIVGHIPPVlds 389 Monosiga brevic...
Feature 1                                             # #                                        
P17405       433 ks-------------wswnYYRIVARYeNTLAAQFFGHTHVDEFevfydeet---------------------------- 471 human
XP_002296197 283 yrhnqf-----wkttyvktYFNIVAEFdDVIVAQLFGHLHSDEFrvglpssahfntd----------------------- 334 Thalassiosira p...
Q5KH67       317 yyd-----------ncylrYGDLALRYqDTIVGHLFGHMNVDHFffidvde----------------------------- 356 Cryptococcus ne...
NP_595346    289 wye-----------dcytsFTDLLYEFrDIIVGQLYGHMNINHFvflefdklpvdtesygiksaqpkyvksli------- 350 Schizosaccharom...
Q6CEE7       331 yed-----------schlkLAYWLTEYrDIIVGSVFGHMNIDHFvvmdpkkiekaqsqdlgtpglgykshvtdfldvais 399 Yarrowia lipoly...
Q04119       336 fdq-----------scydkFTLWTHEYrDIIIGGLYGHMNIDHFiptdgkkarksllkameqstrvqqgedsneed---- 400 Saccharomyces c...
XP_500965    331 yed-----------schlkLAYWLTEYrDIIVGSVFGHMNIDHFvvmdpkkiekaqsqdlgtpglgykshvtdfldvais 399 Yarrowia lipoly...
EAL20739     317 yyd-----------ncylrYGDLALRYqDTIVGHLFGHMNVDHFffidvdeleatseltstssnttlsdlpllhgprlpr 385 Cryptococcus ne...
XP_647257    255 fylqgt-----wksqyqtaFFNITSDYqTTITAGFFGHIHRDEIrsiqfdnps--------------------------- 302 Dictyostelium d...
XP_001748110 390 yfhtddqvknewaehyvqtFYEILAPFsEQIRAFLFGHLHKTEFrapppgv----------------------------- 440 Monosiga brevic...
Feature 1                                                                         
P17405       472 ------------------------------------lsrplavaFLAPSATTYi----gLNPGYR 496 human
XP_002296197 335 -------------------------------eetslipsmnaplLLGPSITPLh----gNNPSFR 364 Thalassiosira pseudonana CCMP1335
Q5KH67       357 -------------------------------------leatselTSTSSNTTLsdlpllHGPRLP 384 Cryptococcus neoformans var. n...
NP_595346    351 ---------------daqyaelptfpenlteeflngtvgnyslaTVGGSIIPE------MFPTFR 394 Schizosaccharomyces pombe
Q6CEE7       400 ashpvhtfgsiykrnyiesvredyseipgpkkwldeyasnfaiaHVSPSVIPN------YFPSLR 458 Yarrowia lipolytica CLIB122
Q04119       401 -------------eetelnrildhamaakevflmgakpsnkeayMNTVRDTYYrk---vWNKLER 449 Saccharomyces cerevisiae S288c
XP_500965    400 ashpvhtfgsiykrnyiesvredyseipgpkkwldeyasnfaiaHVSPSVIPN------YFPSLR 458 Yarrowia lipolytica CLIB122
EAL20739     386 pgp--gkytamgrsgarkleeelrkdfgqmpgpgilklkdyavmNVAPSVIPT------YYPGIR 442 Cryptococcus neoformans var. n...
XP_647257    303 -----------------------------------ltnnhyfpmFIGSSITPVy----fNNPTFK 328 Dictyostelium discoideum AX4
XP_001748110 441 --------------------------------------nlsapiILSCALTPNf----gNNPNFA 463 Monosiga brevicollis MX1

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