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Conserved domains on  [gi|767966367|ref|XP_011518606|]
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sphingomyelin phosphodiesterase isoform X1 [Homo sapiens]

Protein Classification

sphingomyelin phosphodiesterase( domain architecture ID 12219190)

sphingomyelin phosphodiesterase isoform is a lysosomal acid sphingomyelinase (ASM) that catalyzes the hydrolysis of sphingomyelin to produce ceramide and phosphocholine.

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
MPP_ASMase cd00842
acid sphingomyelinase and related proteins, metallophosphatase domain; Acid sphingomyelinase ...
 203-451 3.31e-97

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.


:

Pssm-ID: 277321 [Multi-domain]  Cd Length: 294  Bit Score: 294.21  E-value: 3.31e-97
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767966367 203 ILFLTDLHWDHDYLEG-TDPDCADPLCCRRGSGLPPASrPGAGYWGEYsKCDLPLRTLESLLSGLGP-AGPFDMVYWTGD 280
Cdd:cd00842    1 FLHISDIHYDPLYKVGsEYANCRSPLCCRDESGPGDVK-PPAGYWGTY-GCDSPWSLVESALEAIKKnHPKPDFILWTGD 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767966367 281 IPAHDVWHQTRQDQLRALTTVTALVRKFLGPVPVYPAVGNHESTPVNSFPPPfiegNHSSRWLYEAMAKAWEPWLPAEAL 360
Cdd:cd00842   79 LVRHDVDEQTPEETVESESNLTNLLKKYFPNVPVYPALGNHDSYPVNQFPPH----SNSPSWLYDALAELWKPWLPTEAK 154

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767966367 361 RTLRY----------------LSSV-------------------------ETQEGK---RKVHIIGHIPPGH--CLKSWS 394
Cdd:cd00842  155 ETFKKggyysvdvkdglrvisLNTNlyykknfwlysnntdpcgqlqwledELEDAEqkgEKVWIIGHIPPGLnsYDADWS 234

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 767966367 395 WNYYRIVARYENTLAAQFFGHTHVDEFEVFYDEETLSRPLAVAFLAPSATTYIGLNP 451
Cdd:cd00842  235 ERFYQIINRYSDTIAGQFFGHTHRDEFRVFYDDKDTGSPINVAYIAPSVTPYTGNNP 291
SapB smart00741
Saposin (B) Domains; Present in multiple copies in prosaposin and in pulmonary ...
 89-162 7.66e-08

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.


:

Pssm-ID: 214797 [Multi-domain]  Cd Length: 76  Bit Score: 49.41  E-value: 7.66e-08
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 767966367    89 LTCPICKGLFTAINLGLKKEPNVARVGSVAIKLCNLLKIAPPAVCQSIVHLFEDDMVEVWRRsVLSPSEACGLL 162
Cdd:smart00741   1 LLCELCEFVVKQLENLLKDNKTEEEIKKALEKVCKKLPKSLSDQCKEFVDQYGPEIIDLLEQ-GLDPKDVCQKL 73
 
Name Accession Description Interval E-value
MPP_ASMase cd00842
acid sphingomyelinase and related proteins, metallophosphatase domain; Acid sphingomyelinase ...
 203-451 3.31e-97

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.


Pssm-ID: 277321 [Multi-domain]  Cd Length: 294  Bit Score: 294.21  E-value: 3.31e-97
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767966367 203 ILFLTDLHWDHDYLEG-TDPDCADPLCCRRGSGLPPASrPGAGYWGEYsKCDLPLRTLESLLSGLGP-AGPFDMVYWTGD 280
Cdd:cd00842    1 FLHISDIHYDPLYKVGsEYANCRSPLCCRDESGPGDVK-PPAGYWGTY-GCDSPWSLVESALEAIKKnHPKPDFILWTGD 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767966367 281 IPAHDVWHQTRQDQLRALTTVTALVRKFLGPVPVYPAVGNHESTPVNSFPPPfiegNHSSRWLYEAMAKAWEPWLPAEAL 360
Cdd:cd00842   79 LVRHDVDEQTPEETVESESNLTNLLKKYFPNVPVYPALGNHDSYPVNQFPPH----SNSPSWLYDALAELWKPWLPTEAK 154

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767966367 361 RTLRY----------------LSSV-------------------------ETQEGK---RKVHIIGHIPPGH--CLKSWS 394
Cdd:cd00842  155 ETFKKggyysvdvkdglrvisLNTNlyykknfwlysnntdpcgqlqwledELEDAEqkgEKVWIIGHIPPGLnsYDADWS 234

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 767966367 395 WNYYRIVARYENTLAAQFFGHTHVDEFEVFYDEETLSRPLAVAFLAPSATTYIGLNP 451
Cdd:cd00842  235 ERFYQIINRYSDTIAGQFFGHTHRDEFRVFYDDKDTGSPINVAYIAPSVTPYTGNNP 291
SapB smart00741
Saposin (B) Domains; Present in multiple copies in prosaposin and in pulmonary ...
 89-162 7.66e-08

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.


Pssm-ID: 214797 [Multi-domain]  Cd Length: 76  Bit Score: 49.41  E-value: 7.66e-08
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 767966367    89 LTCPICKGLFTAINLGLKKEPNVARVGSVAIKLCNLLKIAPPAVCQSIVHLFEDDMVEVWRRsVLSPSEACGLL 162
Cdd:smart00741   1 LLCELCEFVVKQLENLLKDNKTEEEIKKALEKVCKKLPKSLSDQCKEFVDQYGPEIIDLLEQ-GLDPKDVCQKL 73
Metallophos pfam00149
Calcineurin-like phosphoesterase; This family includes a diverse range of phosphoesterases, ...
 256-353 2.83e-06

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.


Pssm-ID: 459691 [Multi-domain]  Cd Length: 114  Bit Score: 46.05  E-value: 2.83e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767966367  256 LRTLESLLSGLGPAGPFDMVYWTGDIPAHDVWHQTRQDqlralttvtaLVRKFLGPVPVYPAVGNHESTPVNSFPPPFIE 335
Cdd:pfam00149  15 LDDLLELLKKLLEEGKPDLVLHAGDLVDRGPPSEEVLE----------LLERLIKYVPVYLVRGNHDFDYGECLRLYPYL 84

                          90
                  ....*....|....*...
gi 767966367  336 GNHSSRWLYEAMAKAWEP 353
Cdd:pfam00149  85 GLLARPWKRFLEVFNFLP 102
 
Name Accession Description Interval E-value
MPP_ASMase cd00842
acid sphingomyelinase and related proteins, metallophosphatase domain; Acid sphingomyelinase ...
 203-451 3.31e-97

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.


Pssm-ID: 277321 [Multi-domain]  Cd Length: 294  Bit Score: 294.21  E-value: 3.31e-97
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767966367 203 ILFLTDLHWDHDYLEG-TDPDCADPLCCRRGSGLPPASrPGAGYWGEYsKCDLPLRTLESLLSGLGP-AGPFDMVYWTGD 280
Cdd:cd00842    1 FLHISDIHYDPLYKVGsEYANCRSPLCCRDESGPGDVK-PPAGYWGTY-GCDSPWSLVESALEAIKKnHPKPDFILWTGD 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767966367 281 IPAHDVWHQTRQDQLRALTTVTALVRKFLGPVPVYPAVGNHESTPVNSFPPPfiegNHSSRWLYEAMAKAWEPWLPAEAL 360
Cdd:cd00842   79 LVRHDVDEQTPEETVESESNLTNLLKKYFPNVPVYPALGNHDSYPVNQFPPH----SNSPSWLYDALAELWKPWLPTEAK 154

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767966367 361 RTLRY----------------LSSV-------------------------ETQEGK---RKVHIIGHIPPGH--CLKSWS 394
Cdd:cd00842  155 ETFKKggyysvdvkdglrvisLNTNlyykknfwlysnntdpcgqlqwledELEDAEqkgEKVWIIGHIPPGLnsYDADWS 234

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 767966367 395 WNYYRIVARYENTLAAQFFGHTHVDEFEVFYDEETLSRPLAVAFLAPSATTYIGLNP 451
Cdd:cd00842  235 ERFYQIINRYSDTIAGQFFGHTHRDEFRVFYDDKDTGSPINVAYIAPSVTPYTGNNP 291
SapB smart00741
Saposin (B) Domains; Present in multiple copies in prosaposin and in pulmonary ...
 89-162 7.66e-08

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.


Pssm-ID: 214797 [Multi-domain]  Cd Length: 76  Bit Score: 49.41  E-value: 7.66e-08
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 767966367    89 LTCPICKGLFTAINLGLKKEPNVARVGSVAIKLCNLLKIAPPAVCQSIVHLFEDDMVEVWRRsVLSPSEACGLL 162
Cdd:smart00741   1 LLCELCEFVVKQLENLLKDNKTEEEIKKALEKVCKKLPKSLSDQCKEFVDQYGPEIIDLLEQ-GLDPKDVCQKL 73
Metallophos pfam00149
Calcineurin-like phosphoesterase; This family includes a diverse range of phosphoesterases, ...
 256-353 2.83e-06

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.


Pssm-ID: 459691 [Multi-domain]  Cd Length: 114  Bit Score: 46.05  E-value: 2.83e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767966367  256 LRTLESLLSGLGPAGPFDMVYWTGDIPAHDVWHQTRQDqlralttvtaLVRKFLGPVPVYPAVGNHESTPVNSFPPPFIE 335
Cdd:pfam00149  15 LDDLLELLKKLLEEGKPDLVLHAGDLVDRGPPSEEVLE----------LLERLIKYVPVYLVRGNHDFDYGECLRLYPYL 84

                          90
                  ....*....|....*...
gi 767966367  336 GNHSSRWLYEAMAKAWEP 353
Cdd:pfam00149  85 GLLARPWKRFLEVFNFLP 102
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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