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Conserved domains on  [gi|1435761090|ref|NP_001352064|]
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sphingomyelin phosphodiesterase isoform 5 [Homo sapiens]

Protein Classification

sphingomyelin phosphodiesterase( domain architecture ID 18382240)

sphingomyelin phosphodiesterase catalyzes the conversion of sphingomyelin to ceramide

CATH:  3.60.21.10
EC:  3.1.4.-
Gene Ontology:  GO:0004767|GO:0046872|GO:0006685|GO:0046513
PubMed:  15052326|19536191|23579450|8003970|25837850

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 ...
 203-454 4.82e-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: 297.67  E-value: 4.82e-97
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1435761090 203 ILFLTDLHWDHDYLEG-TDPDCADPLCCRRGSGLPPASrPGAGYWGEYsKCDLPLRTLESLLSGLGP-AGPFDMVYWTGD 280
Cdd:cd00842     1 FLHISDIHYDPLYKVGsEYANCRSPLCCRDESGPGDVK-PPAGYWGTY-GCDSPWSLVESALEAIKKnHPKPDFILWTGD 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1435761090 281 IPAHDVWHQTRQDQLRALTTVTALVRKFLGPVPVYPAVGNHESTPVNSFPPPfiegNHSSRWLYEAMAKAWEPWLPAEAL 360
Cdd:cd00842    79 LVRHDVDEQTPEETVESESNLTNLLKKYFPNVPVYPALGNHDSYPVNQFPPH----SNSPSWLYDALAELWKPWLPTEAK 154

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1435761090 361 RTLRY----------------LSSV-------------------------ETQEGK---RKVHIIGHIPPGH--CLKSWS 394
Cdd:cd00842   155 ETFKKggyysvdvkdglrvisLNTNlyykknfwlysnntdpcgqlqwledELEDAEqkgEKVWIIGHIPPGLnsYDADWS 234

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1435761090 395 WNYYRIVARYENTLAAQFFGHTHVDEFEVFYDEETLSRPLAVAFLAPSATTYIGLNPGYR 454
Cdd:cd00842   235 ERFYQIINRYSDTIAGQFFGHTHRDEFRVFYDDKDTGSPINVAYIAPSVTPYTGNNPSFR 294
SapB smart00741
Saposin (B) Domains; Present in multiple copies in prosaposin and in pulmonary ...
 89-162 9.81e-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: 9.81e-08
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1435761090   89 LTCPICKGLFTAINLGLKKEPNVARVGSVAIKLCNLLKIAPPAVCQSIVHLFEDDMVEVWRRsVLSPSEACGLL 162
Cdd:smart00741   1 LLCELCEFVVKQLENLLKDNKTEEEIKKALEKVCKKLPKSLSDQCKEFVDQYGPEIIDLLEQ-GLDPKDVCQKL 73
ASMase_C super family cl44707
Acid sphingomyelin phosphodiesterase C-terminal region; This entry corresponds to the ...
 432-553 2.94e-07

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.


The actual alignment was detected with superfamily member pfam19272:

Pssm-ID: 466022  Cd Length: 143  Bit Score: 50.06  E-value: 2.94e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1435761090 432 RPLAVAFLAPSATTYIGL------NPGYRVYQID-GNYSgsshvVLDHETYILNLTQANIPGAiPHWQLLYRARETYGLP 504
Cdd:pfam19272   1 NPVNSLFVAPAVTPVKSVlekesnNPGVRLYQYDpKDYK-----LLDMLQYYLNLTEANLKGE-SNWKLEYILTKAYGIE 74

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1435761090 505 NTLPTAWHNLVYR-MRGDMQLFQTFWFLYHKGHPPSEPCGTPCRLATLCA 553
Cdd:pfam19272  75 DLQPQSLYGLAKQfAVPHSKQFEKYYNYFFVSYDSSIVCEGGCKALQICA 124
 
Name Accession Description Interval E-value
MPP_ASMase cd00842
acid sphingomyelinase and related proteins, metallophosphatase domain; Acid sphingomyelinase ...
 203-454 4.82e-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: 297.67  E-value: 4.82e-97
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1435761090 203 ILFLTDLHWDHDYLEG-TDPDCADPLCCRRGSGLPPASrPGAGYWGEYsKCDLPLRTLESLLSGLGP-AGPFDMVYWTGD 280
Cdd:cd00842     1 FLHISDIHYDPLYKVGsEYANCRSPLCCRDESGPGDVK-PPAGYWGTY-GCDSPWSLVESALEAIKKnHPKPDFILWTGD 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1435761090 281 IPAHDVWHQTRQDQLRALTTVTALVRKFLGPVPVYPAVGNHESTPVNSFPPPfiegNHSSRWLYEAMAKAWEPWLPAEAL 360
Cdd:cd00842    79 LVRHDVDEQTPEETVESESNLTNLLKKYFPNVPVYPALGNHDSYPVNQFPPH----SNSPSWLYDALAELWKPWLPTEAK 154

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1435761090 361 RTLRY----------------LSSV-------------------------ETQEGK---RKVHIIGHIPPGH--CLKSWS 394
Cdd:cd00842   155 ETFKKggyysvdvkdglrvisLNTNlyykknfwlysnntdpcgqlqwledELEDAEqkgEKVWIIGHIPPGLnsYDADWS 234

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1435761090 395 WNYYRIVARYENTLAAQFFGHTHVDEFEVFYDEETLSRPLAVAFLAPSATTYIGLNPGYR 454
Cdd:cd00842   235 ERFYQIINRYSDTIAGQFFGHTHRDEFRVFYDDKDTGSPINVAYIAPSVTPYTGNNPSFR 294
SapB smart00741
Saposin (B) Domains; Present in multiple copies in prosaposin and in pulmonary ...
 89-162 9.81e-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: 9.81e-08
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1435761090   89 LTCPICKGLFTAINLGLKKEPNVARVGSVAIKLCNLLKIAPPAVCQSIVHLFEDDMVEVWRRsVLSPSEACGLL 162
Cdd:smart00741   1 LLCELCEFVVKQLENLLKDNKTEEEIKKALEKVCKKLPKSLSDQCKEFVDQYGPEIIDLLEQ-GLDPKDVCQKL 73
ASMase_C pfam19272
Acid sphingomyelin phosphodiesterase C-terminal region; This entry corresponds to the ...
 432-553 2.94e-07

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.


Pssm-ID: 466022  Cd Length: 143  Bit Score: 50.06  E-value: 2.94e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1435761090 432 RPLAVAFLAPSATTYIGL------NPGYRVYQID-GNYSgsshvVLDHETYILNLTQANIPGAiPHWQLLYRARETYGLP 504
Cdd:pfam19272   1 NPVNSLFVAPAVTPVKSVlekesnNPGVRLYQYDpKDYK-----LLDMLQYYLNLTEANLKGE-SNWKLEYILTKAYGIE 74

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1435761090 505 NTLPTAWHNLVYR-MRGDMQLFQTFWFLYHKGHPPSEPCGTPCRLATLCA 553
Cdd:pfam19272  75 DLQPQSLYGLAKQfAVPHSKQFEKYYNYFFVSYDSSIVCEGGCKALQICA 124
Metallophos pfam00149
Calcineurin-like phosphoesterase; This family includes a diverse range of phosphoesterases, ...
 256-353 6.15e-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: 45.67  E-value: 6.15e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1435761090 256 LRTLESLLSGLGPAGPFDMVYWTGDIPAHDVWHQTRQDqlralttvtaLVRKFLGPVPVYPAVGNHESTPVNSFPPPFIE 335
Cdd:pfam00149  15 LDDLLELLKKLLEEGKPDLVLHAGDLVDRGPPSEEVLE----------LLERLIKYVPVYLVRGNHDFDYGECLRLYPYL 84

                          90
                  ....*....|....*...
gi 1435761090 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 ...
 203-454 4.82e-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: 297.67  E-value: 4.82e-97
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1435761090 203 ILFLTDLHWDHDYLEG-TDPDCADPLCCRRGSGLPPASrPGAGYWGEYsKCDLPLRTLESLLSGLGP-AGPFDMVYWTGD 280
Cdd:cd00842     1 FLHISDIHYDPLYKVGsEYANCRSPLCCRDESGPGDVK-PPAGYWGTY-GCDSPWSLVESALEAIKKnHPKPDFILWTGD 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1435761090 281 IPAHDVWHQTRQDQLRALTTVTALVRKFLGPVPVYPAVGNHESTPVNSFPPPfiegNHSSRWLYEAMAKAWEPWLPAEAL 360
Cdd:cd00842    79 LVRHDVDEQTPEETVESESNLTNLLKKYFPNVPVYPALGNHDSYPVNQFPPH----SNSPSWLYDALAELWKPWLPTEAK 154

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1435761090 361 RTLRY----------------LSSV-------------------------ETQEGK---RKVHIIGHIPPGH--CLKSWS 394
Cdd:cd00842   155 ETFKKggyysvdvkdglrvisLNTNlyykknfwlysnntdpcgqlqwledELEDAEqkgEKVWIIGHIPPGLnsYDADWS 234

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1435761090 395 WNYYRIVARYENTLAAQFFGHTHVDEFEVFYDEETLSRPLAVAFLAPSATTYIGLNPGYR 454
Cdd:cd00842   235 ERFYQIINRYSDTIAGQFFGHTHRDEFRVFYDDKDTGSPINVAYIAPSVTPYTGNNPSFR 294
SapB smart00741
Saposin (B) Domains; Present in multiple copies in prosaposin and in pulmonary ...
 89-162 9.81e-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: 9.81e-08
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1435761090   89 LTCPICKGLFTAINLGLKKEPNVARVGSVAIKLCNLLKIAPPAVCQSIVHLFEDDMVEVWRRsVLSPSEACGLL 162
Cdd:smart00741   1 LLCELCEFVVKQLENLLKDNKTEEEIKKALEKVCKKLPKSLSDQCKEFVDQYGPEIIDLLEQ-GLDPKDVCQKL 73
ASMase_C pfam19272
Acid sphingomyelin phosphodiesterase C-terminal region; This entry corresponds to the ...
 432-553 2.94e-07

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.


Pssm-ID: 466022  Cd Length: 143  Bit Score: 50.06  E-value: 2.94e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1435761090 432 RPLAVAFLAPSATTYIGL------NPGYRVYQID-GNYSgsshvVLDHETYILNLTQANIPGAiPHWQLLYRARETYGLP 504
Cdd:pfam19272   1 NPVNSLFVAPAVTPVKSVlekesnNPGVRLYQYDpKDYK-----LLDMLQYYLNLTEANLKGE-SNWKLEYILTKAYGIE 74

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1435761090 505 NTLPTAWHNLVYR-MRGDMQLFQTFWFLYHKGHPPSEPCGTPCRLATLCA 553
Cdd:pfam19272  75 DLQPQSLYGLAKQfAVPHSKQFEKYYNYFFVSYDSSIVCEGGCKALQICA 124
Metallophos pfam00149
Calcineurin-like phosphoesterase; This family includes a diverse range of phosphoesterases, ...
 256-353 6.15e-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: 45.67  E-value: 6.15e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1435761090 256 LRTLESLLSGLGPAGPFDMVYWTGDIPAHDVWHQTRQDqlralttvtaLVRKFLGPVPVYPAVGNHESTPVNSFPPPFIE 335
Cdd:pfam00149  15 LDDLLELLKKLLEEGKPDLVLHAGDLVDRGPPSEEVLE----------LLERLIKYVPVYLVRGNHDFDYGECLRLYPYL 84

                          90
                  ....*....|....*...
gi 1435761090 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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