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Conserved domains on  [gi|263190474|ref|NP_001161079|]
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ganglioside GM2 activator isoform 2 precursor [Homo sapiens]

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, ...
32-140 3.59e-66

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: 200.11  E-value: 3.59e-66
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 263190474  32 SSFSWDNCDEGKDPAVIRSLTLEPDPIIVPGNVTLSVMGSTSVPLSSPLKVDLVLEKEVAGLWIKIPCTDYIGSCTFEHF 111
Cdd:cd00258    1 NGFSWSNCDGESLPAVIKSLTVNPDPINIPGDLTVSTVGSTSVPLSSPLKVILTLEKEVAGLWMKIPCLDNIGSCTYDNA 80
                         90       100
                 ....*....|....*....|....*....
gi 263190474 112 CDVLDMLIPTGEPCPEPLRTYGLPCHCPF 140
Cdd:cd00258   81 CDLLDTLIPPGQQCPEPLRTYGLPCHCPF 109
 
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 ...
32-140 3.59e-66

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: 200.11  E-value: 3.59e-66
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 263190474  32 SSFSWDNCDEGKDPAVIRSLTLEPDPIIVPGNVTLSVMGSTSVPLSSPLKVDLVLEKEVAGLWIKIPCTDYIGSCTFEHF 111
Cdd:cd00258    1 NGFSWSNCDGESLPAVIKSLTVNPDPINIPGDLTVSTVGSTSVPLSSPLKVILTLEKEVAGLWMKIPCLDNIGSCTYDNA 80
                         90       100
                 ....*....|....*....|....*....
gi 263190474 112 CDVLDMLIPTGEPCPEPLRTYGLPCHCPF 140
Cdd:cd00258   81 CDLLDTLIPPGQQCPEPLRTYGLPCHCPF 109
E1_DerP2_DerF2 pfam02221
ML domain; ML domain - MD-2-related lipid recognition domain. This family consists of proteins ...
33-142 2.21e-12

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: 61.23  E-value: 2.21e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 263190474   33 SFSWDNCDEGKDPAV-IRSLTLEPD-PIIVPGNVTLSVMGSTSVPLSSPLKVDLvlekEVAGLWIKIPCTDYigscTFEH 110
Cdd:pfam02221   1 SVPFRDCGRNKDDAPtPKSVDISPPcPLVRGQNLTISASGTTSDEISQGLKVDV----EVRLGGITLPFPLP----ETRD 72
                          90       100       110
                  ....*....|....*....|....*....|..
gi 263190474  111 FCDVLDmliptgepcpeplrtYGLPCHCPFSS 142
Cdd:pfam02221  73 LCDELE---------------VGSGLSCPIKA 89
ML smart00737
Domain involved in innate immunity and lipid metabolism; ML (MD-2-related lipid-recognition) ...
36-126 4.62e-07

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: 46.59  E-value: 4.62e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 263190474    36 WDNCDEGkDPAVIRSLTLEPDPIIVPGNVTLSVMGSTSVPLSSpLKVDLVLEKEvaGLWIKIPCTDYigsctfeHFCDVl 115
Cdd:smart00737   1 FKDCGSN-DPGQISSVSISPCPPVRGKTLTISISFTLNEDISK-LKVVVHVKIG--GIEVPIPGETY-------DLCKL- 68
                           90
                   ....*....|.
gi 263190474   116 dmlipTGEPCP 126
Cdd:smart00737  69 -----TGSKCP 74
 
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 ...
32-140 3.59e-66

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: 200.11  E-value: 3.59e-66
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 263190474  32 SSFSWDNCDEGKDPAVIRSLTLEPDPIIVPGNVTLSVMGSTSVPLSSPLKVDLVLEKEVAGLWIKIPCTDYIGSCTFEHF 111
Cdd:cd00258    1 NGFSWSNCDGESLPAVIKSLTVNPDPINIPGDLTVSTVGSTSVPLSSPLKVILTLEKEVAGLWMKIPCLDNIGSCTYDNA 80
                         90       100
                 ....*....|....*....|....*....
gi 263190474 112 CDVLDMLIPTGEPCPEPLRTYGLPCHCPF 140
Cdd:cd00258   81 CDLLDTLIPPGQQCPEPLRTYGLPCHCPF 109
E1_DerP2_DerF2 pfam02221
ML domain; ML domain - MD-2-related lipid recognition domain. This family consists of proteins ...
33-142 2.21e-12

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: 61.23  E-value: 2.21e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 263190474   33 SFSWDNCDEGKDPAV-IRSLTLEPD-PIIVPGNVTLSVMGSTSVPLSSPLKVDLvlekEVAGLWIKIPCTDYigscTFEH 110
Cdd:pfam02221   1 SVPFRDCGRNKDDAPtPKSVDISPPcPLVRGQNLTISASGTTSDEISQGLKVDV----EVRLGGITLPFPLP----ETRD 72
                          90       100       110
                  ....*....|....*....|....*....|..
gi 263190474  111 FCDVLDmliptgepcpeplrtYGLPCHCPFSS 142
Cdd:pfam02221  73 LCDELE---------------VGSGLSCPIKA 89
ML cd00912
The ML (MD-2-related lipid-recognition) domain is present in MD-1, MD-2, GM2 activator protein, ...
36-140 9.34e-12

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: 59.45  E-value: 9.34e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 263190474  36 WDNCDEGkdPAVIRSLTLEPD-----PIIVPGNVTLSVMGSTSVPLSSPlKVDLVLEKEvaglWIKIPCTDyigscTFEH 110
Cdd:cd00912    1 LVDCSDN--SANIKEVLLSPCdplpcPDHRGGNYNLSVTGTLREDIKSL-YVDLALMSQ----GIKVLNPD-----NSYD 68
                         90       100       110
                 ....*....|....*....|....*....|
gi 263190474 111 FCDVLDmliptgepcpeplrtyGLPCHCPF 140
Cdd:cd00912   69 FCEAGL----------------PKPSFCPL 82
ML smart00737
Domain involved in innate immunity and lipid metabolism; ML (MD-2-related lipid-recognition) ...
36-126 4.62e-07

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: 46.59  E-value: 4.62e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 263190474    36 WDNCDEGkDPAVIRSLTLEPDPIIVPGNVTLSVMGSTSVPLSSpLKVDLVLEKEvaGLWIKIPCTDYigsctfeHFCDVl 115
Cdd:smart00737   1 FKDCGSN-DPGQISSVSISPCPPVRGKTLTISISFTLNEDISK-LKVVVHVKIG--GIEVPIPGETY-------DLCKL- 68
                           90
                   ....*....|.
gi 263190474   116 dmlipTGEPCP 126
Cdd:smart00737  69 -----TGSKCP 74
 
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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