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Conserved domains on  [gi|2462610575|ref|XP_054212400|]
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laforin isoform X2 [Homo sapiens]

Protein Classification

CBM20_laforin and PTP_DSP_cys domain-containing protein( domain architecture ID 12944637)

CBM20_laforin and PTP_DSP_cys domain-containing protein

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
CBM20_laforin cd05806
Laforin protein tyrosine phosphatase, N-terminal CBM20 (carbohydrate-binding module, family 20) ...
 1-129 1.88e-57

Laforin protein tyrosine phosphatase, N-terminal CBM20 (carbohydrate-binding module, family 20) domain. Laforin, encoded by the EPM2A gene, is a dual-specificity phosphatase that dephosphorylates complex carbohydrates. Mutations in the gene encoding laforin result in Lafora disease, a fatal autosomal recessive neurodegenerative disorder characterized by the presence of intracellular deposits of insoluble, abnormally branched, glycogen-like polymers, known as Lafora bodies, in neurons, muscle, liver, and other tissues. The molecular basis for the formation of these Lafora bodies is unknown. Laforin is one of the only phosphatases that contains a carbohydrate-binding module. The CBM20 domain is found in a large number of starch degrading enzymes including alpha-amylase, beta-amylase, glucoamylase, and CGTase (cyclodextrin glucanotransferase). CBM20 is also present in proteins that have a regulatory role in starch metabolism in plants (e.g. alpha-amylase) or glycogen metabolism in mammals (e.g. laforin). CBM20 folds as an antiparallel beta-barrel structure with two starch binding sites. These two sites are thought to differ functionally with site 1 acting as the initial starch recognition site and site 2 involved in the specific recognition of appropriate regions of starch.


:

Pssm-ID: 99881  Cd Length: 112  Bit Score: 179.25  E-value: 1.88e-57
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462610575   1 MRFRFGVVVPPAvaGARPELLVVGSRPELGRWEPRGAVRLRPAGTAagdgaLALQEPGLWLGEVELaaeeaaqdgAEPGR 80
Cdd:cd05806     1 MLFRFGVVLTFA--DRDTELLVLGSRPELGSWDPQRAVPMRPARKA-----LSPQEPSLWLGEVEL---------SEPGS 64

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 2462610575  81 VDTFWYKFLKREPGgELSWEGNGPHHDRCCTYNENNLVDGVYCLPIGHW 129
Cdd:cd05806    65 EDTFWYKFLKREAG-ALIWEGNGPHHDRCCVYDSSNLVDGVYCLPVGHW 112
PTP_DSP_cys super family cl28904
cys-based protein tyrosine phosphatase and dual-specificity phosphatase superfamily; This ...
 155-240 2.36e-33

cys-based protein tyrosine phosphatase and dual-specificity phosphatase superfamily; This superfamily is composed of cys-based phosphatases, which includes classical protein tyrosine phosphatases (PTPs) as well as dual-specificity phosphatases (DUSPs or DSPs). They are characterized by a CxxxxxR conserved catalytic loop (where C is the catalytic cysteine, x is any amino acid, and R is an arginine). PTPs are part of the tyrosine phosphorylation/dephosphorylation regulatory mechanism, and are important in the response of the cells to physiologic and pathologic changes in their environment. DUSPs show more substrate diversity (including RNA and lipids) and include pTyr, pSer, and pThr phosphatases.


The actual alignment was detected with superfamily member cd14526:

Pssm-ID: 475123 [Multi-domain]  Cd Length: 146  Bit Score: 118.45  E-value: 2.36e-33
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462610575 155 MHYSRILPNIWLGSCPRQVEHVTIKLKHelGITAVMNFQTEWDIvqnssgcnrYPEPMTPDTMIKLYREEGLAYIWMPTP 234
Cdd:cd14526     1 LNYSRILPNLIVGSCPQNPEDVDRLKKE--GVTAVLNLQTDSDM---------EYWGVDIDSIRKACKESGIRYVRLPIR 69


                  ....*.
gi 2462610575 235 DMSTED 240
Cdd:cd14526    70 DFDTED 75
 
Name Accession Description Interval E-value
CBM20_laforin cd05806
Laforin protein tyrosine phosphatase, N-terminal CBM20 (carbohydrate-binding module, family 20) ...
 1-129 1.88e-57

Laforin protein tyrosine phosphatase, N-terminal CBM20 (carbohydrate-binding module, family 20) domain. Laforin, encoded by the EPM2A gene, is a dual-specificity phosphatase that dephosphorylates complex carbohydrates. Mutations in the gene encoding laforin result in Lafora disease, a fatal autosomal recessive neurodegenerative disorder characterized by the presence of intracellular deposits of insoluble, abnormally branched, glycogen-like polymers, known as Lafora bodies, in neurons, muscle, liver, and other tissues. The molecular basis for the formation of these Lafora bodies is unknown. Laforin is one of the only phosphatases that contains a carbohydrate-binding module. The CBM20 domain is found in a large number of starch degrading enzymes including alpha-amylase, beta-amylase, glucoamylase, and CGTase (cyclodextrin glucanotransferase). CBM20 is also present in proteins that have a regulatory role in starch metabolism in plants (e.g. alpha-amylase) or glycogen metabolism in mammals (e.g. laforin). CBM20 folds as an antiparallel beta-barrel structure with two starch binding sites. These two sites are thought to differ functionally with site 1 acting as the initial starch recognition site and site 2 involved in the specific recognition of appropriate regions of starch.


Pssm-ID: 99881  Cd Length: 112  Bit Score: 179.25  E-value: 1.88e-57
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462610575   1 MRFRFGVVVPPAvaGARPELLVVGSRPELGRWEPRGAVRLRPAGTAagdgaLALQEPGLWLGEVELaaeeaaqdgAEPGR 80
Cdd:cd05806     1 MLFRFGVVLTFA--DRDTELLVLGSRPELGSWDPQRAVPMRPARKA-----LSPQEPSLWLGEVEL---------SEPGS 64

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 2462610575  81 VDTFWYKFLKREPGgELSWEGNGPHHDRCCTYNENNLVDGVYCLPIGHW 129
Cdd:cd05806    65 EDTFWYKFLKREAG-ALIWEGNGPHHDRCCVYDSSNLVDGVYCLPVGHW 112
DSP_laforin-like cd14526
dual specificity phosphatase domain of laforin and similar domains; This family is composed of ...
 155-240 2.36e-33

dual specificity phosphatase domain of laforin and similar domains; This family is composed of glucan phosphatases including vertebrate dual specificity protein phosphatase laforin, also called lafora PTPase (LAFPTPase), and plant starch excess4 (SEX4). Laforin is a glycogen phosphatase; its gene is mutated in Lafora progressive myoclonus epilepsy or Lafora disease (LD), a fatal autosomal recessive neurodegenerative disorder characterized by the presence of progressive neurological deterioration, myoclonus, and epilepsy. One characteristic of LD is the accumulation of insoluble glucans. Laforin prevents LD by at least two mechanisms: by preventing hyperphosphorylation of glycogen by dephosphorylating it, allowing proper glycogen formation, and by promoting the ubiquitination of proteins involved in glycogen metabolism via its interaction with malin. Laforin contains an N-terminal CBM20 (carbohydrate-binding module, family 20) domain and a C-terminal catalytic dual specificity phosphatase (DSP) domain. Plant SEX4 regulate starch metabolism by selectively dephosphorylating glucose moieties within starch glucan chains. It contains an N-terminal catalytic DSP domain and a C-terminal Early (E) set domain.


Pssm-ID: 350375 [Multi-domain]  Cd Length: 146  Bit Score: 118.45  E-value: 2.36e-33
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462610575 155 MHYSRILPNIWLGSCPRQVEHVTIKLKHelGITAVMNFQTEWDIvqnssgcnrYPEPMTPDTMIKLYREEGLAYIWMPTP 234
Cdd:cd14526     1 LNYSRILPNLIVGSCPQNPEDVDRLKKE--GVTAVLNLQTDSDM---------EYWGVDIDSIRKACKESGIRYVRLPIR 69


                  ....*.
gi 2462610575 235 DMSTED 240
Cdd:cd14526    70 DFDTED 75
CBM_2 smart01065
Starch binding domain;
4-106 9.17e-10

Starch binding domain;


Pssm-ID: 215006 [Multi-domain]  Cd Length: 88  Bit Score: 54.28  E-value: 9.17e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462610575    4 RFGVVVPPAVAGARpeLLVVGSRPELGRWEPRGAVRLRPAGTAAGD--GALALQEPGlwlgevelaaeeaaqdgaepgrv 81
Cdd:smart01065   4 TFKVRNGYTQPGES--VYVVGSVPELGNWNPKKAVPLSPDTDGYPLwkGTVSLPPAG----------------------- 58

                           90       100
                   ....*....|....*....|....*
gi 2462610575   82 DTFWYKFLKREPGGELSWEGNGPHH 106
Cdd:smart01065  59 TTIEYKYVKVDEDGSVTWESGPNRR 83
CBM_20 pfam00686
Starch binding domain;
19-106 6.32e-07

Starch binding domain;


Pssm-ID: 425821 [Multi-domain]  Cd Length: 95  Bit Score: 46.51  E-value: 6.32e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462610575  19 ELLVVGSRPELGRWEPRGAVRLRPAGTAAGDgalalqepgLWLgevelaaeeaaqdgaepGRVD-----TFWYKFLKREP 93
Cdd:pfam00686  16 SVYIVGSIPELGNWNPKKAIALSASEYSSYP---------LWS-----------------GTVSlpagtTIEYKYIKVDS 69

                          90
                  ....*....|...
gi 2462610575  94 GGELSWEgNGPHH 106
Cdd:pfam00686  70 DGSVTWE-SGPNR 81
 
Name Accession Description Interval E-value
CBM20_laforin cd05806
Laforin protein tyrosine phosphatase, N-terminal CBM20 (carbohydrate-binding module, family 20) ...
 1-129 1.88e-57

Laforin protein tyrosine phosphatase, N-terminal CBM20 (carbohydrate-binding module, family 20) domain. Laforin, encoded by the EPM2A gene, is a dual-specificity phosphatase that dephosphorylates complex carbohydrates. Mutations in the gene encoding laforin result in Lafora disease, a fatal autosomal recessive neurodegenerative disorder characterized by the presence of intracellular deposits of insoluble, abnormally branched, glycogen-like polymers, known as Lafora bodies, in neurons, muscle, liver, and other tissues. The molecular basis for the formation of these Lafora bodies is unknown. Laforin is one of the only phosphatases that contains a carbohydrate-binding module. The CBM20 domain is found in a large number of starch degrading enzymes including alpha-amylase, beta-amylase, glucoamylase, and CGTase (cyclodextrin glucanotransferase). CBM20 is also present in proteins that have a regulatory role in starch metabolism in plants (e.g. alpha-amylase) or glycogen metabolism in mammals (e.g. laforin). CBM20 folds as an antiparallel beta-barrel structure with two starch binding sites. These two sites are thought to differ functionally with site 1 acting as the initial starch recognition site and site 2 involved in the specific recognition of appropriate regions of starch.


Pssm-ID: 99881  Cd Length: 112  Bit Score: 179.25  E-value: 1.88e-57
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462610575   1 MRFRFGVVVPPAvaGARPELLVVGSRPELGRWEPRGAVRLRPAGTAagdgaLALQEPGLWLGEVELaaeeaaqdgAEPGR 80
Cdd:cd05806     1 MLFRFGVVLTFA--DRDTELLVLGSRPELGSWDPQRAVPMRPARKA-----LSPQEPSLWLGEVEL---------SEPGS 64

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 2462610575  81 VDTFWYKFLKREPGgELSWEGNGPHHDRCCTYNENNLVDGVYCLPIGHW 129
Cdd:cd05806    65 EDTFWYKFLKREAG-ALIWEGNGPHHDRCCVYDSSNLVDGVYCLPVGHW 112
DSP_laforin-like cd14526
dual specificity phosphatase domain of laforin and similar domains; This family is composed of ...
 155-240 2.36e-33

dual specificity phosphatase domain of laforin and similar domains; This family is composed of glucan phosphatases including vertebrate dual specificity protein phosphatase laforin, also called lafora PTPase (LAFPTPase), and plant starch excess4 (SEX4). Laforin is a glycogen phosphatase; its gene is mutated in Lafora progressive myoclonus epilepsy or Lafora disease (LD), a fatal autosomal recessive neurodegenerative disorder characterized by the presence of progressive neurological deterioration, myoclonus, and epilepsy. One characteristic of LD is the accumulation of insoluble glucans. Laforin prevents LD by at least two mechanisms: by preventing hyperphosphorylation of glycogen by dephosphorylating it, allowing proper glycogen formation, and by promoting the ubiquitination of proteins involved in glycogen metabolism via its interaction with malin. Laforin contains an N-terminal CBM20 (carbohydrate-binding module, family 20) domain and a C-terminal catalytic dual specificity phosphatase (DSP) domain. Plant SEX4 regulate starch metabolism by selectively dephosphorylating glucose moieties within starch glucan chains. It contains an N-terminal catalytic DSP domain and a C-terminal Early (E) set domain.


Pssm-ID: 350375 [Multi-domain]  Cd Length: 146  Bit Score: 118.45  E-value: 2.36e-33
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462610575 155 MHYSRILPNIWLGSCPRQVEHVTIKLKHelGITAVMNFQTEWDIvqnssgcnrYPEPMTPDTMIKLYREEGLAYIWMPTP 234
Cdd:cd14526     1 LNYSRILPNLIVGSCPQNPEDVDRLKKE--GVTAVLNLQTDSDM---------EYWGVDIDSIRKACKESGIRYVRLPIR 69


                  ....*.
gi 2462610575 235 DMSTED 240
Cdd:cd14526    70 DFDTED 75
CBM20 cd05467
The family 20 carbohydrate-binding module (CBM20), also known as the starch-binding domain, is ...
 19-119 2.22e-14

The family 20 carbohydrate-binding module (CBM20), also known as the starch-binding domain, is found in a large number of starch degrading enzymes including alpha-amylase, beta-amylase, glucoamylase, and CGTase (cyclodextrin glucanotransferase). CBM20 is also present in proteins that have a regulatory role in starch metabolism in plants (e.g. alpha-amylase) or glycogen metabolism in mammals (e.g. laforin). CBM20 folds as an antiparallel beta-barrel structure with two starch binding sites. These two sites are thought to differ functionally with site 1 acting as the initial starch recognition site and site 2 involved in the specific recognition of appropriate regions of starch.


Pssm-ID: 119437  Cd Length: 96  Bit Score: 67.32  E-value: 2.22e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462610575  19 ELLVVGSRPELGRWEPRGAVRLRPAGtaagdgalalqEPGLWLGevelaaeeaaQDGAEPGRVDTFWYKFLKREPGGELS 98
Cdd:cd05467    15 SVYVVGSHPELGNWDPAKALRLNTSN-----------SYPLWTG----------EIPLPAPEGQVIEYKYVIVDDDGNVQ 73

                          90       100
                  ....*....|....*....|.
gi 2462610575  99 WEGNGPHHDRCCTYNENNLVD 119
Cdd:cd05467    74 WESGSNRVLTVPSTSSLIVVD 94
CBM_2 smart01065
Starch binding domain;
4-106 9.17e-10

Starch binding domain;


Pssm-ID: 215006 [Multi-domain]  Cd Length: 88  Bit Score: 54.28  E-value: 9.17e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462610575    4 RFGVVVPPAVAGARpeLLVVGSRPELGRWEPRGAVRLRPAGTAAGD--GALALQEPGlwlgevelaaeeaaqdgaepgrv 81
Cdd:smart01065   4 TFKVRNGYTQPGES--VYVVGSVPELGNWNPKKAVPLSPDTDGYPLwkGTVSLPPAG----------------------- 58

                           90       100
                   ....*....|....*....|....*
gi 2462610575   82 DTFWYKFLKREPGGELSWEGNGPHH 106
Cdd:smart01065  59 TTIEYKYVKVDEDGSVTWESGPNRR 83
CBM_20 pfam00686
Starch binding domain;
19-106 6.32e-07

Starch binding domain;


Pssm-ID: 425821 [Multi-domain]  Cd Length: 95  Bit Score: 46.51  E-value: 6.32e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462610575  19 ELLVVGSRPELGRWEPRGAVRLRPAGTAAGDgalalqepgLWLgevelaaeeaaqdgaepGRVD-----TFWYKFLKREP 93
Cdd:pfam00686  16 SVYIVGSIPELGNWNPKKAIALSASEYSSYP---------LWS-----------------GTVSlpagtTIEYKYIKVDS 69

                          90
                  ....*....|...
gi 2462610575  94 GGELSWEgNGPHH 106
Cdd:pfam00686  70 DGSVTWE-SGPNR 81
CBM20_alpha_amylase cd05808
Alpha-amylase, C-terminal CBM20 (carbohydrate-binding module, family 20) domain. This domain ...
 19-101 4.65e-06

Alpha-amylase, C-terminal CBM20 (carbohydrate-binding module, family 20) domain. This domain is found in several bacterial and fungal alpha-amylases including the maltopentaose-forming amylases (G5-amylases). Most alpha-amylases have, in addition to the C-terminal CBM20 domain, an N-terminal catalytic domain belonging to glycosyl hydrolase family 13, which hydrolyzes internal alpha-1,4-glucosidic bonds in starch and related saccharides, yielding maltotriose and maltose. Two types of soluble substrates are used by alpha-amylases including long substrates (e.g. amylose) and short substrates (e.g. maltodextrins or maltooligosaccharides). The CBM20 domain is found in a large number of starch degrading enzymes including alpha-amylase, beta-amylase, glucoamylase, and CGTase (cyclodextrin glucanotransferase). CBM20 is also present in proteins that have a regulatory role in starch metabolism in plants (e.g. alpha-amylase) or glycogen metabolism in mammals (e.g. laforin). CBM20 folds as an antiparallel beta-barrel structure with two starch binding sites. These two sites are thought to differ functionally with site 1 acting as the initial starch recognition site and site 2 involved in the specific recognition of appropriate regions of starch.


Pssm-ID: 99883  Cd Length: 95  Bit Score: 44.28  E-value: 4.65e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462610575  19 ELLVVGSRPELGRWEPRGAVRLRPAGTAAGDGALALqepglwlgevelaaeeaaqdgaePGRVdTFWYKFLKREPGGELS 98
Cdd:cd05808    16 NVYVVGNVPELGNWSPANAVALSAATYPVWSGTVDL-----------------------PAGT-AIEYKYIKKDGSGTVT 71


                  ...
gi 2462610575  99 WEG 101
Cdd:cd05808    72 WES 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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