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Conserved domains on  [gi|2500687|sp|Q60648|]
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RecName: Full=Ganglioside GM2 activator; AltName: Full=Cerebroside sulfate activator protein; AltName: Full=GM2-AP; AltName: Full=Sphingolipid activator protein 3; Short=SAP-3; Flags: Precursor

Protein Classification

ML domain-containing protein( domain architecture ID 5313)

ML (MD-2-related lipid-recognition) domain-containing protein; the ML domain is present in MD-1, MD-2, GM2 activator protein, Niemann-Pick type C2 (Npc2) protein, phosphatidylinositol/phosphatidylglycerol transfer protein (PG/PI-TP), mite allergen Der p 2 and several proteins of unknown function in plants, animals and fungi; it is predicted to mediate diverse biological functions through interaction with specific lipids

Gene Ontology:  GO:0008289
PubMed:  12076526

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
ML super family cl00274
The ML (MD-2-related lipid-recognition) domain is present in MD-1, MD-2, GM2 activator protein, ...
 33-192 4.34e-92

The ML (MD-2-related lipid-recognition) domain is present in MD-1, MD-2, GM2 activator protein, Niemann-Pick type C2 (Npc2) protein, phosphatidylinositol/phosphatidylglycerol transfer protein (PG/PI-TP), mite allergen Der p 2 and several proteins of unknown function in plants, animals and fungi. These single-domain proteins form two anti-parallel beta-pleated sheets stabilized by three disulfide bonds and with an accessible central hydrophobic cavity, and are predicted to mediate diverse biological functions through interaction with specific lipids.


The actual alignment was detected with superfamily member cd00258:

Pssm-ID: 469700  Cd Length: 162  Bit Score: 265.98  E-value: 4.34e-92
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2500687   33 GFSWDNCDEGKDPAVIKSLTIQPDPIVVPGDVVVSLEGKTSVPLTAPQKVELTVEKEVAGFWVKIPCVEQLGSCSYENIC 112
Cdd:cd00258   2 GFSWSNCDGESLPAVIKSLTVNPDPINIPGDLTVSTVGSTSVPLSSPLKVILTLEKEVAGLWMKIPCLDNIGSCTYDNAC 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2500687  113 DLIDEYIPPGESCPEPLHTYGLPCHCPFKEGTYSLPTSNFTVPDLELPSWLSTGNYRIQSILSSGGKRLGCIKIAASLKG 192
Cdd:cd00258  82 DLLDTLIPPGQQCPEPLRTYGLPCHCPFKEGVYSLPDSTFTLPNVDLPSWLTNGNYRITGILMADGKELGCGKFTFSLES 161
 
Name Accession Description Interval E-value
GM2-AP cd00258
GM2 activator protein (GM2-AP) is a non-enzymatic lysosomal protein that acts as cofactor in ...
 33-192 4.34e-92

GM2 activator protein (GM2-AP) is a non-enzymatic lysosomal protein that acts as cofactor in the sequential degradation of gangliosides. GM2A is an essential cofactor for beta-hexosaminidase A (Hex A) in the enzymatic hydrolysis of GM2 ganglioside to GM3. Mutation of the gene results in the AB variant of Tay-Sachs disease. GM2-AP and similar proteins belong to the ML domain family.


Pssm-ID: 238161  Cd Length: 162  Bit Score: 265.98  E-value: 4.34e-92
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2500687   33 GFSWDNCDEGKDPAVIKSLTIQPDPIVVPGDVVVSLEGKTSVPLTAPQKVELTVEKEVAGFWVKIPCVEQLGSCSYENIC 112
Cdd:cd00258   2 GFSWSNCDGESLPAVIKSLTVNPDPINIPGDLTVSTVGSTSVPLSSPLKVILTLEKEVAGLWMKIPCLDNIGSCTYDNAC 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2500687  113 DLIDEYIPPGESCPEPLHTYGLPCHCPFKEGTYSLPTSNFTVPDLELPSWLSTGNYRIQSILSSGGKRLGCIKIAASLKG 192
Cdd:cd00258  82 DLLDTLIPPGQQCPEPLRTYGLPCHCPFKEGVYSLPDSTFTLPNVDLPSWLTNGNYRITGILMADGKELGCGKFTFSLES 161
E1_DerP2_DerF2 pfam02221
ML domain; ML domain - MD-2-related lipid recognition domain. This family consists of proteins ...
 33-190 2.11e-27

ML domain; ML domain - MD-2-related lipid recognition domain. This family consists of proteins from plants, animals and fungi, including dust mite allergen Der P 2. It has been implicate in lipid recognition, particularly in the recognition of pathogen related products. A mutation in Npc2 causes a rare form of Niemann-Pick type C2 disease. This domain has a similar topology to immunoglobulin domains.


Pssm-ID: 460498  Cd Length: 133  Bit Score: 100.52  E-value: 2.11e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2500687     33 GFSWDNCDEGKDPAV-IKSLTIQPD-PIVVPGDVVVSLEGKTSVPLTAPQKVelTVEKEVAgfWVKIPCVEQlgscSYEN 110
Cdd:pfam02221   1 SVPFRDCGRNKDDAPtPKSVDISPPcPLVRGQNLTISASGTTSDEISQGLKV--DVEVRLG--GITLPFPLP----ETRD 72

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2500687    111 ICDLIDeyippgescpeplhtYGLPCHCPFKEGTYSlptsnFTVPDLELPSWLSTGNYRIQ-SILSSGGKRLGCIKIAAS 189
Cdd:pfam02221  73 LCDELE---------------VGSGLSCPIKAGEYV-----TYTLTLPLPSEYPPGKYTVEaELYDQDGKPLTCFKIDVS 132


                  .
gi 2500687    190 L 190
Cdd:pfam02221 133 I 133
ML smart00737
Domain involved in innate immunity and lipid metabolism; ML (MD-2-related lipid-recognition) ...
 36-188 1.75e-09

Domain involved in innate immunity and lipid metabolism; ML (MD-2-related lipid-recognition) is a novel domain identified in MD-1, MD-2, GM2A, Npc2 and multiple proteins of unknown function in plants, animals and fungi. These single-domain proteins were predicted to form a beta-rich fold containing multiple strands, and to mediate diverse biological functions through interacting with specific lipids.


Pssm-ID: 214796  Cd Length: 119  Bit Score: 53.14  E-value: 1.75e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2500687      36 WDNCDEGkDPAVIKSLTIQPDPIVVPGDVVVSLEGKTSVPLTapqKVELTVEKEVAGFWVKIPCVEQlgscsyeNICDLI 115
Cdd:smart00737   1 FKDCGSN-DPGQISSVSISPCPPVRGKTLTISISFTLNEDIS---KLKVVVHVKIGGIEVPIPGETY-------DLCKLT 69

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2500687     116 DEYippgescpeplhtyglpchCPFKEGTYSLPTSNFTVpdlelPSWLSTGNYRIQ-SILSSGGKRLGCIKIAA 188
Cdd:smart00737  70 GSK-------------------CPIEKGETVNYTNSLTV-----PGIFPPGKYTVKwELTDEDGEELACINFTV 119
 
Name Accession Description Interval E-value
GM2-AP cd00258
GM2 activator protein (GM2-AP) is a non-enzymatic lysosomal protein that acts as cofactor in ...
 33-192 4.34e-92

GM2 activator protein (GM2-AP) is a non-enzymatic lysosomal protein that acts as cofactor in the sequential degradation of gangliosides. GM2A is an essential cofactor for beta-hexosaminidase A (Hex A) in the enzymatic hydrolysis of GM2 ganglioside to GM3. Mutation of the gene results in the AB variant of Tay-Sachs disease. GM2-AP and similar proteins belong to the ML domain family.


Pssm-ID: 238161  Cd Length: 162  Bit Score: 265.98  E-value: 4.34e-92
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2500687   33 GFSWDNCDEGKDPAVIKSLTIQPDPIVVPGDVVVSLEGKTSVPLTAPQKVELTVEKEVAGFWVKIPCVEQLGSCSYENIC 112
Cdd:cd00258   2 GFSWSNCDGESLPAVIKSLTVNPDPINIPGDLTVSTVGSTSVPLSSPLKVILTLEKEVAGLWMKIPCLDNIGSCTYDNAC 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2500687  113 DLIDEYIPPGESCPEPLHTYGLPCHCPFKEGTYSLPTSNFTVPDLELPSWLSTGNYRIQSILSSGGKRLGCIKIAASLKG 192
Cdd:cd00258  82 DLLDTLIPPGQQCPEPLRTYGLPCHCPFKEGVYSLPDSTFTLPNVDLPSWLTNGNYRITGILMADGKELGCGKFTFSLES 161
E1_DerP2_DerF2 pfam02221
ML domain; ML domain - MD-2-related lipid recognition domain. This family consists of proteins ...
 33-190 2.11e-27

ML domain; ML domain - MD-2-related lipid recognition domain. This family consists of proteins from plants, animals and fungi, including dust mite allergen Der P 2. It has been implicate in lipid recognition, particularly in the recognition of pathogen related products. A mutation in Npc2 causes a rare form of Niemann-Pick type C2 disease. This domain has a similar topology to immunoglobulin domains.


Pssm-ID: 460498  Cd Length: 133  Bit Score: 100.52  E-value: 2.11e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2500687     33 GFSWDNCDEGKDPAV-IKSLTIQPD-PIVVPGDVVVSLEGKTSVPLTAPQKVelTVEKEVAgfWVKIPCVEQlgscSYEN 110
Cdd:pfam02221   1 SVPFRDCGRNKDDAPtPKSVDISPPcPLVRGQNLTISASGTTSDEISQGLKV--DVEVRLG--GITLPFPLP----ETRD 72

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2500687    111 ICDLIDeyippgescpeplhtYGLPCHCPFKEGTYSlptsnFTVPDLELPSWLSTGNYRIQ-SILSSGGKRLGCIKIAAS 189
Cdd:pfam02221  73 LCDELE---------------VGSGLSCPIKAGEYV-----TYTLTLPLPSEYPPGKYTVEaELYDQDGKPLTCFKIDVS 132


                  .
gi 2500687    190 L 190
Cdd:pfam02221 133 I 133
ML cd00912
The ML (MD-2-related lipid-recognition) domain is present in MD-1, MD-2, GM2 activator protein, ...
 36-188 5.73e-15

The ML (MD-2-related lipid-recognition) domain is present in MD-1, MD-2, GM2 activator protein, Niemann-Pick type C2 (Npc2) protein, phosphatidylinositol/phosphatidylglycerol transfer protein (PG/PI-TP), mite allergen Der p 2 and several proteins of unknown function in plants, animals and fungi. These single-domain proteins form two anti-parallel beta-pleated sheets stabilized by three disulfide bonds and with an accessible central hydrophobic cavity, and are predicted to mediate diverse biological functions through interaction with specific lipids.


Pssm-ID: 238454  Cd Length: 127  Bit Score: 67.93  E-value: 5.73e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2500687   36 WDNCDEGkdPAVIKSLTIQPD-----PIVVPGDVVVSLEGKTSVPLTAPqKVELTVEKevagFWVKIPCVEqlgscSYEN 110
Cdd:cd00912   1 LVDCSDN--SANIKEVLLSPCdplpcPDHRGGNYNLSVTGTLREDIKSL-YVDLALMS----QGIKVLNPD-----NSYD 68

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2500687  111 ICDLIDEyippgescpeplhtygLPCHCPFKEG-TYSLPTSNFTVPdlelPSWLSTGNYRIQSILSSGGKRLGCIKIAA 188
Cdd:cd00912  69 FCEAGLP----------------KPSFCPLRKGqQYSYAKTVNVPE----FTIPTIEYQVVLEDVTDKGEVLACAQATI 127
ML smart00737
Domain involved in innate immunity and lipid metabolism; ML (MD-2-related lipid-recognition) ...
 36-188 1.75e-09

Domain involved in innate immunity and lipid metabolism; ML (MD-2-related lipid-recognition) is a novel domain identified in MD-1, MD-2, GM2A, Npc2 and multiple proteins of unknown function in plants, animals and fungi. These single-domain proteins were predicted to form a beta-rich fold containing multiple strands, and to mediate diverse biological functions through interacting with specific lipids.


Pssm-ID: 214796  Cd Length: 119  Bit Score: 53.14  E-value: 1.75e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2500687      36 WDNCDEGkDPAVIKSLTIQPDPIVVPGDVVVSLEGKTSVPLTapqKVELTVEKEVAGFWVKIPCVEQlgscsyeNICDLI 115
Cdd:smart00737   1 FKDCGSN-DPGQISSVSISPCPPVRGKTLTISISFTLNEDIS---KLKVVVHVKIGGIEVPIPGETY-------DLCKLT 69

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2500687     116 DEYippgescpeplhtyglpchCPFKEGTYSLPTSNFTVpdlelPSWLSTGNYRIQ-SILSSGGKRLGCIKIAA 188
Cdd:smart00737  70 GSK-------------------CPIEKGETVNYTNSLTV-----PGIFPPGKYTVKwELTDEDGEELACINFTV 119
DUF1091 pfam06477
Protein of unknown function (DUF1091); This is a family of uncharacterized proteins. Based on ...
 134-170 1.29e-04

Protein of unknown function (DUF1091); This is a family of uncharacterized proteins. Based on its distant similarity to pfam02221 and conserved pattern of cysteine residues it is possible that these domains are also lipid binding.


Pssm-ID: 461928  Cd Length: 83  Bit Score: 39.22  E-value: 1.29e-04
                          10        20        30
                  ....*....|....*....|....*....|....*..
gi 2500687    134 LPCHCPFKEGTYSLptSNFTVPDLELPSWLSTGNYRI 170
Cdd:pfam06477  49 LNHTCPYPKGNYYL--RNFVLDEDLLPSFLPEGDYKI 83
DM8 smart00697
Repeats found in several Drosophila proteins;
110-179 2.98e-04

Repeats found in several Drosophila proteins;


Pssm-ID: 214778  Cd Length: 93  Bit Score: 38.52  E-value: 2.98e-04
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2500687     110 NICDLIDEY--IPPGESCPEPLHTYG-LPCHCPFKEGTYSLptSNFTVPDLELPSWLSTGNYRIQSILSSGGK 179
Cdd:smart00697  11 DVCKLLKSRnqIPLIRIILKSLLKFSnFNDTCPLPKGHYYL--RNFRLDENLLPSFLPDGDYRLNLTFFFGKI 81
 
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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