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Conserved domains on  [gi|2462527150|ref|XP_054225712|]
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sphingomyelin phosphodiesterase isoform X2 [Homo sapiens]

Protein Classification

acid sphingomyelinase family protein( domain architecture ID 17655516)

acid sphingomyelinase family protein such as human acid sphingomyelinase-like phosphodiesterase 3b, a lipid-modulating phosphodiesterase active on the surface of macrophages and dendritic cells

CATH:  3.60.21.10
EC:  3.1.4.-
Gene Ontology:  GO:0004767|GO:0046872|GO:0006685
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 ...
 47-191 7.49e-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.


:

Pssm-ID: 277321 [Multi-domain]  Cd Length: 294  Bit Score: 226.80  E-value: 7.49e-73
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462527150  47 RPWKPRKGKERI--GGFYALSPYPGLRLISLNMNFCSRENFWLLINSTDPAGQLQWLVGELQAAEDRGDKVHIIGHIPPG 124
Cdd:cd00842   146 KPWLPTEAKETFkkGGYYSVDVKDGLRVISLNTNLYYKKNFWLYSNNTDPCGQLQWLEDELEDAEQKGEKVWIIGHIPPG 225

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2462527150 125 H--CLKSWSWNYYRIVARYENTLAAQFFGHTHVDEFEVFYDEETLSRPLAVAFLAPSATTYIGLNPGYR 191
Cdd:cd00842   226 LnsYDADWSERFYQIINRYSDTIAGQFFGHTHRDEFRVFYDDKDTGSPINVAYIAPSVTPYTGNNPSFR 294
ASMase_C super family cl44707
Acid sphingomyelin phosphodiesterase C-terminal region; This entry corresponds to the ...
 169-290 2.04e-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: 49.68  E-value: 2.04e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462527150 169 RPLAVAFLAPSATTYIGL------NPGYRVYQID-GNYSgsshvVLDHETYILNLTQANIPGAiPHWQLLYRARETYGLP 241
Cdd:pfam19272   1 NPVNSLFVAPAVTPVKSVlekesnNPGVRLYQYDpKDYK-----LLDMLQYYLNLTEANLKGE-SNWKLEYILTKAYGIE 74

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 2462527150 242 NTLPTAWHNLVYR-MRGDMQLFQTFWFLYHKGHPPSEPCGTPCRLATLCA 290
Cdd:pfam19272  75 DLQPQSLYGLAKQfAVPHSKQFEKYYNYFFVSYDSSIVCEGGCKALQICA 124
 
Name Accession Description Interval E-value
MPP_ASMase cd00842
acid sphingomyelinase and related proteins, metallophosphatase domain; Acid sphingomyelinase ...
 47-191 7.49e-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.


Pssm-ID: 277321 [Multi-domain]  Cd Length: 294  Bit Score: 226.80  E-value: 7.49e-73
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462527150  47 RPWKPRKGKERI--GGFYALSPYPGLRLISLNMNFCSRENFWLLINSTDPAGQLQWLVGELQAAEDRGDKVHIIGHIPPG 124
Cdd:cd00842   146 KPWLPTEAKETFkkGGYYSVDVKDGLRVISLNTNLYYKKNFWLYSNNTDPCGQLQWLEDELEDAEQKGEKVWIIGHIPPG 225

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2462527150 125 H--CLKSWSWNYYRIVARYENTLAAQFFGHTHVDEFEVFYDEETLSRPLAVAFLAPSATTYIGLNPGYR 191
Cdd:cd00842   226 LnsYDADWSERFYQIINRYSDTIAGQFFGHTHRDEFRVFYDDKDTGSPINVAYIAPSVTPYTGNNPSFR 294
ASMase_C pfam19272
Acid sphingomyelin phosphodiesterase C-terminal region; This entry corresponds to the ...
 169-290 2.04e-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: 49.68  E-value: 2.04e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462527150 169 RPLAVAFLAPSATTYIGL------NPGYRVYQID-GNYSgsshvVLDHETYILNLTQANIPGAiPHWQLLYRARETYGLP 241
Cdd:pfam19272   1 NPVNSLFVAPAVTPVKSVlekesnNPGVRLYQYDpKDYK-----LLDMLQYYLNLTEANLKGE-SNWKLEYILTKAYGIE 74

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 2462527150 242 NTLPTAWHNLVYR-MRGDMQLFQTFWFLYHKGHPPSEPCGTPCRLATLCA 290
Cdd:pfam19272  75 DLQPQSLYGLAKQfAVPHSKQFEKYYNYFFVSYDSSIVCEGGCKALQICA 124
CpdA COG1409
3',5'-cyclic AMP phosphodiesterase CpdA [Signal transduction mechanisms];
54-198 3.44e-06

3',5'-cyclic AMP phosphodiesterase CpdA [Signal transduction mechanisms];


Pssm-ID: 441019 [Multi-domain]  Cd Length: 234  Bit Score: 47.38  E-value: 3.44e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462527150  54 GKERIGGFYALSPYPGLRLISLNMNFCSRENFWLlinstdPAGQLQWLVGELQAAEDRgdKVHIIGHIPPGHCLkSWSWN 133
Cdd:COG1409    89 GDLPPGGLYYSFDYGGVRFIGLDSNVPGRSSGEL------GPEQLAWLEEELAAAPAK--PVIVFLHHPPYSTG-SGSDR 159

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2462527150 134 YY--------RIVARYENTLAaqFFGHTHVDEFEVFYdeetlSRPLAVaflAPSATTYIGLNPGYRVYQIDGN 198
Cdd:COG1409   160 IGlrnaeellALLARYGVDLV--LSGHVHRYERTRRD-----GVPYIV---AGSTGGQVRLPPGYRVIEVDGD 222
 
Name Accession Description Interval E-value
MPP_ASMase cd00842
acid sphingomyelinase and related proteins, metallophosphatase domain; Acid sphingomyelinase ...
 47-191 7.49e-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.


Pssm-ID: 277321 [Multi-domain]  Cd Length: 294  Bit Score: 226.80  E-value: 7.49e-73
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462527150  47 RPWKPRKGKERI--GGFYALSPYPGLRLISLNMNFCSRENFWLLINSTDPAGQLQWLVGELQAAEDRGDKVHIIGHIPPG 124
Cdd:cd00842   146 KPWLPTEAKETFkkGGYYSVDVKDGLRVISLNTNLYYKKNFWLYSNNTDPCGQLQWLEDELEDAEQKGEKVWIIGHIPPG 225

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2462527150 125 H--CLKSWSWNYYRIVARYENTLAAQFFGHTHVDEFEVFYDEETLSRPLAVAFLAPSATTYIGLNPGYR 191
Cdd:cd00842   226 LnsYDADWSERFYQIINRYSDTIAGQFFGHTHRDEFRVFYDDKDTGSPINVAYIAPSVTPYTGNNPSFR 294
MPP_Nbla03831 cd07396
Homo sapiens Nbla03831 and related proteins, metallophosphatase domain; Nbla03831 (also known ...
 61-162 1.23e-07

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.


Pssm-ID: 277341 [Multi-domain]  Cd Length: 245  Bit Score: 51.95  E-value: 1.23e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462527150  61 FYALSPYPGLRLISLNmnfcsrenfWLLINSTDPAGQLQWLVGELQAAEDRGDKVHIIGHIP------PGHCLkswSWNY 134
Cdd:cd07396   114 YYSFSPGPGFRFLVLD---------FVKFNGGIGEEQLAWLRNELTSADANGEKVIVLSHLPiypeaaDPQCL---LWNY 181

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 2462527150 135 YRIVA---RYENtLAAQFFGHTH-----VDEFEVFY 162
Cdd:cd07396   182 EEVLAileSYPC-VKACFSGHNHeggyeQDSHGVHH 216
ASMase_C pfam19272
Acid sphingomyelin phosphodiesterase C-terminal region; This entry corresponds to the ...
 169-290 2.04e-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: 49.68  E-value: 2.04e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462527150 169 RPLAVAFLAPSATTYIGL------NPGYRVYQID-GNYSgsshvVLDHETYILNLTQANIPGAiPHWQLLYRARETYGLP 241
Cdd:pfam19272   1 NPVNSLFVAPAVTPVKSVlekesnNPGVRLYQYDpKDYK-----LLDMLQYYLNLTEANLKGE-SNWKLEYILTKAYGIE 74

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 2462527150 242 NTLPTAWHNLVYR-MRGDMQLFQTFWFLYHKGHPPSEPCGTPCRLATLCA 290
Cdd:pfam19272  75 DLQPQSLYGLAKQfAVPHSKQFEKYYNYFFVSYDSSIVCEGGCKALQICA 124
CpdA COG1409
3',5'-cyclic AMP phosphodiesterase CpdA [Signal transduction mechanisms];
54-198 3.44e-06

3',5'-cyclic AMP phosphodiesterase CpdA [Signal transduction mechanisms];


Pssm-ID: 441019 [Multi-domain]  Cd Length: 234  Bit Score: 47.38  E-value: 3.44e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462527150  54 GKERIGGFYALSPYPGLRLISLNMNFCSRENFWLlinstdPAGQLQWLVGELQAAEDRgdKVHIIGHIPPGHCLkSWSWN 133
Cdd:COG1409    89 GDLPPGGLYYSFDYGGVRFIGLDSNVPGRSSGEL------GPEQLAWLEEELAAAPAK--PVIVFLHHPPYSTG-SGSDR 159

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2462527150 134 YY--------RIVARYENTLAaqFFGHTHVDEFEVFYdeetlSRPLAVaflAPSATTYIGLNPGYRVYQIDGN 198
Cdd:COG1409   160 IGlrnaeellALLARYGVDLV--LSGHVHRYERTRRD-----GVPYIV---AGSTGGQVRLPPGYRVIEVDGD 222
 
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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