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Conserved domains on  [gi|13959539|sp|O15198|]
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RecName: Full=Mothers against decapentaplegic homolog 9; Short=MAD homolog 9; Short=Mothers against DPP homolog 9; AltName: Full=Madh6; AltName: Full=SMAD family member 9; Short=SMAD 9; Short=Smad9

Protein Classification

mothers against decapentaplegic homolog 9( domain architecture ID 10180329)

mothers against decapentaplegic homolog 9 is a transcriptional modulator activated by BMP (bone morphogenetic proteins) type 1 receptor kinase

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
MH2 super family cl00056
C-terminal Mad Homology 2 (MH2) domain; The MH2 domain is found in the SMAD (small mothers ...
 267-467 1.09e-151

C-terminal Mad Homology 2 (MH2) domain; The MH2 domain is found in the SMAD (small mothers against decapentaplegic) family of proteins and is responsible for type I receptor interactions, phosphorylation-triggered homo- and hetero-oligomerization, and transactivation. It is negatively regulated by the N-terminal MH1 domain which prevents it from forming a complex with SMAD4. The MH2 domain is multifunctional and provides SMADs with their specificity and selectivity, as well as transcriptional activity. Several transcriptional co-activators and repressors have also been reported to regulate SMAD signaling by interacting with the MH2 domain. Mutations in the MH2 domains of SMAD2 and especially SMAD4 have been detected in colorectal and other human cancers.


The actual alignment was detected with superfamily member cd10497:

Pssm-ID: 469593  Cd Length: 201  Bit Score: 429.30  E-value: 1.09e-151
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13959539 267 YEEPQHWCSVAYYELNNRVGETFQASSRSVLIDGFTDPSNNRNRFCLGLLSNVNRNSTIENTRRHIGKGVHLYYVGGEVY 346
Cdd:cd10497   1 YQEPKYWCSIAYYELNNRVGEAFHASSTSIIVDGFTDPSNNSDRFCLGLLSNVNRNSTIENTRRHIGKGVHLYYVGGEVY 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13959539 347 AECVSDSSIFVQSRNCNYQHGFHPATVCKIPSGCSLKVFNNQLFAQLLAQSVHHGFEVVYELTKMCTIRMSFVKGWGAEY 426
Cdd:cd10497  81 AECLSDSSIFVQSRNCNYHHGFHPTTVCKIPPGCSLKIFNNQEFAQLLSQSVNHGFEAVYELTKMCTIRMSFVKGWGAEY 160

                       170       180       190       200
                ....*....|....*....|....*....|....*....|.
gi 13959539 427 HRQDVTSTPCWIEIHLHGPLQWLDKVLTQMGSPHNPISSVS 467
Cdd:cd10497 161 HRQDVTSTPCWIEIHLHGPLQWLDKVLTQMGSPHNPISSVS 201
MH1_SMAD_1_5_9 cd10490
N-terminal Mad Homology 1 (MH1) domain in SMAD1, SMAD5 and SMAD9 (also known as SMAD8); The ...
 13-136 3.15e-87

N-terminal Mad Homology 1 (MH1) domain in SMAD1, SMAD5 and SMAD9 (also known as SMAD8); The MH1 is a small DNA-binding domain present in SMAD (small mothers against decapentaplegic) family of proteins, which are signal transducers and transcriptional modulators that mediate multiple signaling pathways. MH1 binds to the DNA major groove in an unusual manner via a beta hairpin structure. It negatively regulates the functions of the MH2 domain, the C-terminal domain of SMAD. This MH1 domain is found in SMAD1, SMAD5 and SMAD9, all closely related receptor regulated SMADs (R-SMADs). SMAD1 plays an essential role in bone development and postnatal bone formation through activation by bone morphogenetic protein (BMP) type 1 receptor kinase. SMAD5 is involved in bone morphogenetic proteins (BMP) signal modulation and may also play a role in the pathway involving inhibition of hematopoietic progenitor cells by TGF-beta. SMAD9 mediates the differentiation of mesenchymal stem cells (MSCs) into tendon-like cells by inhibiting the osteogenic pathway.


:

Pssm-ID: 199814  Cd Length: 124  Bit Score: 262.44  E-value: 3.15e-87
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13959539  13 FTSPAVKRLLGWKQGDEEEKWAEKAVDSLVKKLKKKKGAMDELERALSCPGQPSKCVTIPRSLDGRLQVSHRKGLPHVIY 92
Cdd:cd10490   1 FTSPAVKRLLGWKQGDEEEKWAEKAVDSLVKKLKKKKGALEELEKALSCPGQPSKCVTIPRSLDGRLQVSHRKGLPHVIY 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....
gi 13959539  93 CRVWRWPDLQSHHELKPLECCEFPFGSKQKEVCINPYHYRRVET 136
Cdd:cd10490  81 CRVWRWPDLQSHHELKPLECCEFPFGSKQKEVCINPYHYKRVES 124
Atrophin-1 super family cl38111
Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian ...
 140-258 6.00e-03

Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian atrophy (DRPLA) gene. DRPLA OMIM:125370 is a progressive neurodegenerative disorder. It is caused by the expansion of a CAG repeat in the DRPLA gene on chromosome 12p. This results in an extended polyglutamine region in atrophin-1, that is thought to confer toxicity to the protein, possibly through altering its interactions with other proteins. The expansion of a CAG repeat is also the underlying defect in six other neurodegenerative disorders, including Huntington's disease. One interaction of expanded polyglutamine repeats that is thought to be pathogenic is that with the short glutamine repeat in the transcriptional coactivator CREB binding protein, CBP. This interaction draws CBP away from its usual nuclear location to the expanded polyglutamine repeat protein aggregates that are characteriztic of the polyglutamine neurodegenerative disorders. This interferes with CBP-mediated transcription and causes cytotoxicity.


The actual alignment was detected with superfamily member pfam03154:

Pssm-ID: 460830 [Multi-domain]  Cd Length: 991  Bit Score: 39.37  E-value: 6.00e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13959539   140 PPVLVPrhseynpqLSLLAKFRSASLHSEPL--MPHNATYPDSFQQPPCSALPPSPSHAFSQSPCTASYPHSPGSPSEPE 217
Cdd:pfam03154 393 PPALKP--------LSSLSTHHPPSAHPPPLqlMPQSQQLPPPPAQPPVLTQSQSLPPPAASHPPTSGLHQVPSQSPFPQ 464

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 13959539   218 SPYQHSVDTPPLPYHATEASETQSGQPVDATADRHVVLSIP 258
Cdd:pfam03154 465 HPFVPGGPPPITPPSGPPTSTSSAMPGIQPPSSASVSSSGP 505
 
Name Accession Description Interval E-value
MH2_SMAD_1_5_9 cd10497
C-terminal Mad Homology 2 (MH2) domain in SMAD1, SMAD5 and SMAD9; The MH2 domain is located at ...
 267-467 1.09e-151

C-terminal Mad Homology 2 (MH2) domain in SMAD1, SMAD5 and SMAD9; The MH2 domain is located at the C-terminus of the SMAD (small mothers against decapentaplegic) family of proteins, which are signal transducers and transcriptional modulators that mediate multiple signaling pathways. The MH2 domain is responsible for type I receptor interaction, phosphorylation-triggered homo- and hetero-oligomerization, and transactivation. It is negatively regulated by the N-terminal MH1 domain, which prevents it from forming a complex with SMAD4. SMAD1, SMAD5 and SMAD9 (also known as SMAD8), are receptor regulated SMADs (R-SMADs). SMAD1 plays an essential role in bone development and postnatal bone formation through activation by bone morphogenetic protein (BMP) type 1 receptor kinase. SMAD5 is involved in BMP signal modulation and may also play a role in the pathway involving inhibition of hematopoietic progenitor cells by TGF-beta. SMAD9 mediates the differentiation of mesenchymal stem cells (MSCs) into tendon-like cells by inhibiting the osteogenic pathway.


Pssm-ID: 199822  Cd Length: 201  Bit Score: 429.30  E-value: 1.09e-151
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13959539 267 YEEPQHWCSVAYYELNNRVGETFQASSRSVLIDGFTDPSNNRNRFCLGLLSNVNRNSTIENTRRHIGKGVHLYYVGGEVY 346
Cdd:cd10497   1 YQEPKYWCSIAYYELNNRVGEAFHASSTSIIVDGFTDPSNNSDRFCLGLLSNVNRNSTIENTRRHIGKGVHLYYVGGEVY 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13959539 347 AECVSDSSIFVQSRNCNYQHGFHPATVCKIPSGCSLKVFNNQLFAQLLAQSVHHGFEVVYELTKMCTIRMSFVKGWGAEY 426
Cdd:cd10497  81 AECLSDSSIFVQSRNCNYHHGFHPTTVCKIPPGCSLKIFNNQEFAQLLSQSVNHGFEAVYELTKMCTIRMSFVKGWGAEY 160

                       170       180       190       200
                ....*....|....*....|....*....|....*....|.
gi 13959539 427 HRQDVTSTPCWIEIHLHGPLQWLDKVLTQMGSPHNPISSVS 467
Cdd:cd10497 161 HRQDVTSTPCWIEIHLHGPLQWLDKVLTQMGSPHNPISSVS 201
MH2 pfam03166
MH2 domain; This is the MH2 (MAD homology 2) domain found at the carboxy terminus of MAD ...
 271-443 1.72e-99

MH2 domain; This is the MH2 (MAD homology 2) domain found at the carboxy terminus of MAD related proteins such as Smads. This domain is separated from the MH1 domain by a non-conserved linker region. The MH2 domain mediates interaction with a wide variety of proteins and provides specificity and selectivity to Smad function and also is critical for mediating interactions in Smad oligomers. Unlike MH1, MH2 does not bind DNA. The well-studied MH2 domain of Smad4 is composed of five alpha helices and three loops enclosing a beta sandwich. Smads are involved in the propagation of TGF-beta signals by direct association with the TGF-beta receptor kinase which phosphorylates the last two Ser of a conserved 'SSXS' motif located at the C-terminus of MH2.


Pssm-ID: 460834  Cd Length: 172  Bit Score: 295.69  E-value: 1.72e-99
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13959539   271 QHWCSVAYYELNNRVGETFQASSRSVLIDGFTDPSNNrNRFCLGLLSNVNRNSTIENTRRHIGKGVHLYYVGGEVYAECV 350
Cdd:pfam03166   1 EIWCSVAYYELNTRVGEAFKVSSPNVTVDGFTDPSDG-NRFCLGLLSNVNRNEAVEKVRKHIGKGVRLSYDGGEVWIYNL 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13959539   351 SDSSIFVQSRNCNYQHGFHPATVCKIPSGCSLKVFNNQLFAQLLAQSVHHGFEVVYELTKMCTIRMSFVKGWGAEYHRQD 430
Cdd:pfam03166  80 SDHPVFVQSPYLNREAGRAPDTVHKVPPGESLKVFDMRKFQQLLSQELRRARLGPQDANKLCSVRISFVKGWGPDYSRQD 159

                         170
                  ....*....|...
gi 13959539   431 VTSTPCWIEIHLH 443
Cdd:pfam03166 160 ITSTPCWIEIHLH 172
DWB smart00524
Domain B in dwarfin family proteins;
272-443 1.80e-99

Domain B in dwarfin family proteins;


Pssm-ID: 197770  Cd Length: 171  Bit Score: 295.37  E-value: 1.80e-99
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13959539    272 HWCSVAYYELNNRVGETFQASSRSVLIDGFTDPSNnRNRFCLGLLSNVNRNSTIENTRRHIGKGVHLYYVGGEVYAECVS 351
Cdd:smart00524   1 SWCKIAYYELNTRVGETFKVSSPSVTVDGFTDPSD-GNRFCLGQLSNVNRNEATELIRKHIGKGVQLSYENGDVWLYNRS 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13959539    352 DSSIFVQSRNCNYQHGFHPATVCKIPSGCSLKVFNNQLFAQLLAQSVHHGFEVVYELTKMCTIRMSFVKGWGAEYHRQDV 431
Cdd:smart00524  80 DSPIFVQSPYLDEPGGRTLDTVHKLPPGYSIKVFDMEKFAQLLARELAKGFEGVYDLARMCTIRISFVKGWGPDYSRQTI 159

                          170
                   ....*....|..
gi 13959539    432 TSTPCWIEIHLH 443
Cdd:smart00524 160 TSTPCWIEVHLN 171
MH1_SMAD_1_5_9 cd10490
N-terminal Mad Homology 1 (MH1) domain in SMAD1, SMAD5 and SMAD9 (also known as SMAD8); The ...
 13-136 3.15e-87

N-terminal Mad Homology 1 (MH1) domain in SMAD1, SMAD5 and SMAD9 (also known as SMAD8); The MH1 is a small DNA-binding domain present in SMAD (small mothers against decapentaplegic) family of proteins, which are signal transducers and transcriptional modulators that mediate multiple signaling pathways. MH1 binds to the DNA major groove in an unusual manner via a beta hairpin structure. It negatively regulates the functions of the MH2 domain, the C-terminal domain of SMAD. This MH1 domain is found in SMAD1, SMAD5 and SMAD9, all closely related receptor regulated SMADs (R-SMADs). SMAD1 plays an essential role in bone development and postnatal bone formation through activation by bone morphogenetic protein (BMP) type 1 receptor kinase. SMAD5 is involved in bone morphogenetic proteins (BMP) signal modulation and may also play a role in the pathway involving inhibition of hematopoietic progenitor cells by TGF-beta. SMAD9 mediates the differentiation of mesenchymal stem cells (MSCs) into tendon-like cells by inhibiting the osteogenic pathway.


Pssm-ID: 199814  Cd Length: 124  Bit Score: 262.44  E-value: 3.15e-87
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13959539  13 FTSPAVKRLLGWKQGDEEEKWAEKAVDSLVKKLKKKKGAMDELERALSCPGQPSKCVTIPRSLDGRLQVSHRKGLPHVIY 92
Cdd:cd10490   1 FTSPAVKRLLGWKQGDEEEKWAEKAVDSLVKKLKKKKGALEELEKALSCPGQPSKCVTIPRSLDGRLQVSHRKGLPHVIY 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....
gi 13959539  93 CRVWRWPDLQSHHELKPLECCEFPFGSKQKEVCINPYHYRRVET 136
Cdd:cd10490  81 CRVWRWPDLQSHHELKPLECCEFPFGSKQKEVCINPYHYKRVES 124
DWA smart00523
Domain A in dwarfin family proteins;
29-138 3.29e-51

Domain A in dwarfin family proteins;


Pssm-ID: 214708  Cd Length: 109  Bit Score: 169.10  E-value: 3.29e-51
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13959539     29 EEEKWAEKAVDSLVKKLKKkkGAMDELERALSCPG-QPSKCVTIPRSLDGRLQVSHRKGLPHVIYCRVWRWPDLQSHHEL 107
Cdd:smart00523   1 VEEKWAKKATESLLKKLKK--KQLEELLQAVESKGgPPTRCVLIPRSLDGRLQVAHRKGLPHVLYCRLFRWPDLQSPHEL 78

                           90       100       110
                   ....*....|....*....|....*....|.
gi 13959539    108 KPLECCEFPFGSKQKEVCINPYHYRRVETPV 138
Cdd:smart00523  79 KALPTCEHAFESKSDEVCCNPYHYSRVERPE 109
MH1 pfam03165
MH1 domain; The MH1 (MAD homology 1) domain is found at the amino terminus of MAD related ...
 34-135 3.87e-49

MH1 domain; The MH1 (MAD homology 1) domain is found at the amino terminus of MAD related proteins such as Smads. This domain is separated from the MH2 domain by a non-conserved linker region. The crystal structure of the MH1 domain shows that a highly conserved 11 residue beta hairpin is used to bind the DNA consensus sequence GNCN in the major groove, shown to be vital for the transcriptional activation of target genes. Not all examples of MH1 can bind to DNA however. Smad2 cannot bind DNA and has a large insertion within the hairpin that presumably abolishes DNA binding. A basic helix (H2) in MH1 with the nuclear localization signal KKLKK has been shown to be essential for Smad3 nuclear import. Smads also use the MH1 domain to interact with transcription factors such as Jun, TFE3, Sp1, and Runx.


Pssm-ID: 460833  Cd Length: 103  Bit Score: 163.31  E-value: 3.87e-49
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13959539    34 AEKAVDSLVKKLKKKKGAMDELERALSCPG-QPSKCVTIPRSLDGRLQVSHRKGLPHVIYCRVWRWPDLQSHHELKPLEC 112
Cdd:pfam03165   1 LKKAVESLLKKLKKKIQQLEELELAVESRGdPPTGCVTIPRSLDGRLQVAGRKGLPHVIYCRLWRWPDLQSQHELKAIPT 80

                          90       100
                  ....*....|....*....|...
gi 13959539   113 CEFPFGSKQKEVCINPYHYRRVE 135
Cdd:pfam03165  81 CETAFESKKDEVCINPYHYSRVE 103
Atrophin-1 pfam03154
Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian ...
 140-258 6.00e-03

Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian atrophy (DRPLA) gene. DRPLA OMIM:125370 is a progressive neurodegenerative disorder. It is caused by the expansion of a CAG repeat in the DRPLA gene on chromosome 12p. This results in an extended polyglutamine region in atrophin-1, that is thought to confer toxicity to the protein, possibly through altering its interactions with other proteins. The expansion of a CAG repeat is also the underlying defect in six other neurodegenerative disorders, including Huntington's disease. One interaction of expanded polyglutamine repeats that is thought to be pathogenic is that with the short glutamine repeat in the transcriptional coactivator CREB binding protein, CBP. This interaction draws CBP away from its usual nuclear location to the expanded polyglutamine repeat protein aggregates that are characteriztic of the polyglutamine neurodegenerative disorders. This interferes with CBP-mediated transcription and causes cytotoxicity.


Pssm-ID: 460830 [Multi-domain]  Cd Length: 991  Bit Score: 39.37  E-value: 6.00e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13959539   140 PPVLVPrhseynpqLSLLAKFRSASLHSEPL--MPHNATYPDSFQQPPCSALPPSPSHAFSQSPCTASYPHSPGSPSEPE 217
Cdd:pfam03154 393 PPALKP--------LSSLSTHHPPSAHPPPLqlMPQSQQLPPPPAQPPVLTQSQSLPPPAASHPPTSGLHQVPSQSPFPQ 464

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 13959539   218 SPYQHSVDTPPLPYHATEASETQSGQPVDATADRHVVLSIP 258
Cdd:pfam03154 465 HPFVPGGPPPITPPSGPPTSTSSAMPGIQPPSSASVSSSGP 505
 
Name Accession Description Interval E-value
MH2_SMAD_1_5_9 cd10497
C-terminal Mad Homology 2 (MH2) domain in SMAD1, SMAD5 and SMAD9; The MH2 domain is located at ...
 267-467 1.09e-151

C-terminal Mad Homology 2 (MH2) domain in SMAD1, SMAD5 and SMAD9; The MH2 domain is located at the C-terminus of the SMAD (small mothers against decapentaplegic) family of proteins, which are signal transducers and transcriptional modulators that mediate multiple signaling pathways. The MH2 domain is responsible for type I receptor interaction, phosphorylation-triggered homo- and hetero-oligomerization, and transactivation. It is negatively regulated by the N-terminal MH1 domain, which prevents it from forming a complex with SMAD4. SMAD1, SMAD5 and SMAD9 (also known as SMAD8), are receptor regulated SMADs (R-SMADs). SMAD1 plays an essential role in bone development and postnatal bone formation through activation by bone morphogenetic protein (BMP) type 1 receptor kinase. SMAD5 is involved in BMP signal modulation and may also play a role in the pathway involving inhibition of hematopoietic progenitor cells by TGF-beta. SMAD9 mediates the differentiation of mesenchymal stem cells (MSCs) into tendon-like cells by inhibiting the osteogenic pathway.


Pssm-ID: 199822  Cd Length: 201  Bit Score: 429.30  E-value: 1.09e-151
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13959539 267 YEEPQHWCSVAYYELNNRVGETFQASSRSVLIDGFTDPSNNRNRFCLGLLSNVNRNSTIENTRRHIGKGVHLYYVGGEVY 346
Cdd:cd10497   1 YQEPKYWCSIAYYELNNRVGEAFHASSTSIIVDGFTDPSNNSDRFCLGLLSNVNRNSTIENTRRHIGKGVHLYYVGGEVY 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13959539 347 AECVSDSSIFVQSRNCNYQHGFHPATVCKIPSGCSLKVFNNQLFAQLLAQSVHHGFEVVYELTKMCTIRMSFVKGWGAEY 426
Cdd:cd10497  81 AECLSDSSIFVQSRNCNYHHGFHPTTVCKIPPGCSLKIFNNQEFAQLLSQSVNHGFEAVYELTKMCTIRMSFVKGWGAEY 160

                       170       180       190       200
                ....*....|....*....|....*....|....*....|.
gi 13959539 427 HRQDVTSTPCWIEIHLHGPLQWLDKVLTQMGSPHNPISSVS 467
Cdd:cd10497 161 HRQDVTSTPCWIEIHLHGPLQWLDKVLTQMGSPHNPISSVS 201
MH2_R-SMAD cd10495
C-terminal Mad Homology 2 (MH2) domain in receptor regulated SMADs; The MH2 domain is located ...
 273-454 4.61e-138

C-terminal Mad Homology 2 (MH2) domain in receptor regulated SMADs; The MH2 domain is located at the C-terminus of the SMAD (small mothers against decapentaplegic) family of proteins, which are signal transducers and transcriptional modulators that mediate multiple signaling pathways. The MH2 domain is responsible for type I receptor interaction, phosphorylation-triggered homo- and hetero-oligomerization, and transactivation. It is negatively regulated by the N-terminal MH1 domain. Receptor regulated SMADs (R-SMADs) include SMAD1, SMAD2, SMAD3, SMAD5 and SMAD9. SMAD1 plays an essential role in bone development and postnatal bone formation through activation by bone morphogenetic protein (BMP) type 1 receptor kinase. SMAD2 regulates multiple cellular processes, such as cell proliferation, apoptosis and differentiation, while SMAD3 modulates signals of activin and TGF-beta. SMAD5 is involved in BMP signal modulation, possibly playing a role in the pathway involving inhibition of hematopoietic progenitor cells by TGF-beta. SMAD9 (also known as SMAD8) can mediate the differentiation of mesenchymal stem cells into tendon-like cells by inhibiting the osteogenic pathway.


Pssm-ID: 199820  Cd Length: 182  Bit Score: 394.05  E-value: 4.61e-138
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13959539 273 WCSVAYYELNNRVGETFQASSRSVLIDGFTDPSNNRNRFCLGLLSNVNRNSTIENTRRHIGKGVHLYYVGGEVYAECVSD 352
Cdd:cd10495   1 WCSISYYELNSRVGEQFKASNPSIIVDGFTDPSNNSDRFCLGLLSNVNRNATIENTRRHIGRGVHLFYVGGEVYAECLSD 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13959539 353 SSIFVQSRNCNYQHGFHPATVCKIPSGCSLKVFNNQLFAQLLAQSVHHGFEVVYELTKMCTIRMSFVKGWGAEYHRQDVT 432
Cdd:cd10495  81 SAIFVQSRNCNLRHGFHPATVCKIPPGCSLKIFNNQSFAQLLEQSVNRGFEAVYELTKMCTIRISFVKGWGAEYHRQDVT 160

                       170       180
                ....*....|....*....|..
gi 13959539 433 STPCWIEIHLHGPLQWLDKVLT 454
Cdd:cd10495 161 STPCWIEIHLHGPLQWLDKVLT 182
MH2_SMAD_2_3 cd10985
C-terminal Mad Homology 2 (MH2) domain in SMAD2 and SMAD3; The MH2 domain is located at the ...
 265-456 3.28e-124

C-terminal Mad Homology 2 (MH2) domain in SMAD2 and SMAD3; The MH2 domain is located at the C-terminus of the SMAD (small mothers against decapentaplegic) family of proteins, which are signal transducers and transcriptional modulators that mediate multiple signaling pathways. The MH2 domain is responsible for type I receptor interaction, phosphorylation-triggered homo- and hetero-oligomerization, and transactivation. It is negatively regulated by the N-terminal MH1 domain. SMAD2 and SMAD3 are receptor regulated SMADs (R-SMADs). SMAD2 regulates multiple cellular processes, such as cell proliferation, apoptosis and differentiation, while SMAD3 modulates signals of activin and TGF-beta.


Pssm-ID: 199826  Cd Length: 191  Bit Score: 359.24  E-value: 3.28e-124
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13959539 265 VCYEEPQHWCSVAYYELNNRVGETFQASSRSVLIDGFTDPSNNrNRFCLGLLSNVNRNSTIENTRRHIGKGVHLYYVGGE 344
Cdd:cd10985   1 VTYCEPAFWCSISYYEMNTRVGETFHASQPSLTVDGFTDPSNS-ERFCLGLLSNVNRNPQVELTRRHIGKGVRLYYIGGE 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13959539 345 VYAECVSDSSIFVQSRNCNYQHGFHPATVCKIPSGCSLKVFNNQLFAQLLAQSVHHGFEVVYELTKMCTIRMSFVKGWGA 424
Cdd:cd10985  80 VFAECLSDSAIFVQSPNCNQRYGWHPATVCKIPPGCNLKIFNNQEFAALLSQSVNQGFEAVYQLTRMCTIRMSFVKGWGA 159

                       170       180       190
                ....*....|....*....|....*....|..
gi 13959539 425 EYHRQDVTSTPCWIEIHLHGPLQWLDKVLTQM 456
Cdd:cd10985 160 EYRRQTVTSTPCWIELHLNGPLQWLDRVLTQM 191
MH2 cd00050
C-terminal Mad Homology 2 (MH2) domain; The MH2 domain is found in the SMAD (small mothers ...
 273-443 1.07e-108

C-terminal Mad Homology 2 (MH2) domain; The MH2 domain is found in the SMAD (small mothers against decapentaplegic) family of proteins and is responsible for type I receptor interactions, phosphorylation-triggered homo- and hetero-oligomerization, and transactivation. It is negatively regulated by the N-terminal MH1 domain which prevents it from forming a complex with SMAD4. The MH2 domain is multifunctional and provides SMADs with their specificity and selectivity, as well as transcriptional activity. Several transcriptional co-activators and repressors have also been reported to regulate SMAD signaling by interacting with the MH2 domain. Mutations in the MH2 domains of SMAD2 and especially SMAD4 have been detected in colorectal and other human cancers.


Pssm-ID: 199819  Cd Length: 170  Bit Score: 319.17  E-value: 1.07e-108
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13959539 273 WCSVAYYELNNRVGETFQASSRSVLIDGFTDPSNNrNRFCLGLLSNVNRNSTIENTRRHIGKGVHLYYVGGEVYAECVSD 352
Cdd:cd00050   1 WCSIAYYELNTRVGELFHVYSPSVAVDGFTDPSNG-DRFCLGQLSNVNRNETIERTRRHIGKGVHLYYVGGEVWAECLSD 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13959539 353 SSIFVQSRNCNYQHGFHPATVCKIPSGCSLKVFNNQLFAQLLAQSVHHGFEVVYELTKMCTIRMSFVKGWGAEYHRQDVT 432
Cdd:cd00050  80 HAIFVQSRNLDYPHGRHPLTVCKIPPGCSIKVFDNQEFAQLLHQSVNTGFEGVYELTKMCTIRMSFVKGWGPEYHRQDIT 159

                       170
                ....*....|.
gi 13959539 433 STPCWIEIHLH 443
Cdd:cd00050 160 STPCWIEIHLH 170
MH2 pfam03166
MH2 domain; This is the MH2 (MAD homology 2) domain found at the carboxy terminus of MAD ...
 271-443 1.72e-99

MH2 domain; This is the MH2 (MAD homology 2) domain found at the carboxy terminus of MAD related proteins such as Smads. This domain is separated from the MH1 domain by a non-conserved linker region. The MH2 domain mediates interaction with a wide variety of proteins and provides specificity and selectivity to Smad function and also is critical for mediating interactions in Smad oligomers. Unlike MH1, MH2 does not bind DNA. The well-studied MH2 domain of Smad4 is composed of five alpha helices and three loops enclosing a beta sandwich. Smads are involved in the propagation of TGF-beta signals by direct association with the TGF-beta receptor kinase which phosphorylates the last two Ser of a conserved 'SSXS' motif located at the C-terminus of MH2.


Pssm-ID: 460834  Cd Length: 172  Bit Score: 295.69  E-value: 1.72e-99
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13959539   271 QHWCSVAYYELNNRVGETFQASSRSVLIDGFTDPSNNrNRFCLGLLSNVNRNSTIENTRRHIGKGVHLYYVGGEVYAECV 350
Cdd:pfam03166   1 EIWCSVAYYELNTRVGEAFKVSSPNVTVDGFTDPSDG-NRFCLGLLSNVNRNEAVEKVRKHIGKGVRLSYDGGEVWIYNL 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13959539   351 SDSSIFVQSRNCNYQHGFHPATVCKIPSGCSLKVFNNQLFAQLLAQSVHHGFEVVYELTKMCTIRMSFVKGWGAEYHRQD 430
Cdd:pfam03166  80 SDHPVFVQSPYLNREAGRAPDTVHKVPPGESLKVFDMRKFQQLLSQELRRARLGPQDANKLCSVRISFVKGWGPDYSRQD 159

                         170
                  ....*....|...
gi 13959539   431 VTSTPCWIEIHLH 443
Cdd:pfam03166 160 ITSTPCWIEIHLH 172
DWB smart00524
Domain B in dwarfin family proteins;
272-443 1.80e-99

Domain B in dwarfin family proteins;


Pssm-ID: 197770  Cd Length: 171  Bit Score: 295.37  E-value: 1.80e-99
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13959539    272 HWCSVAYYELNNRVGETFQASSRSVLIDGFTDPSNnRNRFCLGLLSNVNRNSTIENTRRHIGKGVHLYYVGGEVYAECVS 351
Cdd:smart00524   1 SWCKIAYYELNTRVGETFKVSSPSVTVDGFTDPSD-GNRFCLGQLSNVNRNEATELIRKHIGKGVQLSYENGDVWLYNRS 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13959539    352 DSSIFVQSRNCNYQHGFHPATVCKIPSGCSLKVFNNQLFAQLLAQSVHHGFEVVYELTKMCTIRMSFVKGWGAEYHRQDV 431
Cdd:smart00524  80 DSPIFVQSPYLDEPGGRTLDTVHKLPPGYSIKVFDMEKFAQLLARELAKGFEGVYDLARMCTIRISFVKGWGPDYSRQTI 159

                          170
                   ....*....|..
gi 13959539    432 TSTPCWIEIHLH 443
Cdd:smart00524 160 TSTPCWIEVHLN 171
MH1_SMAD_1_5_9 cd10490
N-terminal Mad Homology 1 (MH1) domain in SMAD1, SMAD5 and SMAD9 (also known as SMAD8); The ...
 13-136 3.15e-87

N-terminal Mad Homology 1 (MH1) domain in SMAD1, SMAD5 and SMAD9 (also known as SMAD8); The MH1 is a small DNA-binding domain present in SMAD (small mothers against decapentaplegic) family of proteins, which are signal transducers and transcriptional modulators that mediate multiple signaling pathways. MH1 binds to the DNA major groove in an unusual manner via a beta hairpin structure. It negatively regulates the functions of the MH2 domain, the C-terminal domain of SMAD. This MH1 domain is found in SMAD1, SMAD5 and SMAD9, all closely related receptor regulated SMADs (R-SMADs). SMAD1 plays an essential role in bone development and postnatal bone formation through activation by bone morphogenetic protein (BMP) type 1 receptor kinase. SMAD5 is involved in bone morphogenetic proteins (BMP) signal modulation and may also play a role in the pathway involving inhibition of hematopoietic progenitor cells by TGF-beta. SMAD9 mediates the differentiation of mesenchymal stem cells (MSCs) into tendon-like cells by inhibiting the osteogenic pathway.


Pssm-ID: 199814  Cd Length: 124  Bit Score: 262.44  E-value: 3.15e-87
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13959539  13 FTSPAVKRLLGWKQGDEEEKWAEKAVDSLVKKLKKKKGAMDELERALSCPGQPSKCVTIPRSLDGRLQVSHRKGLPHVIY 92
Cdd:cd10490   1 FTSPAVKRLLGWKQGDEEEKWAEKAVDSLVKKLKKKKGALEELEKALSCPGQPSKCVTIPRSLDGRLQVSHRKGLPHVIY 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....
gi 13959539  93 CRVWRWPDLQSHHELKPLECCEFPFGSKQKEVCINPYHYRRVET 136
Cdd:cd10490  81 CRVWRWPDLQSHHELKPLECCEFPFGSKQKEVCINPYHYKRVES 124
MH1_R-SMAD cd10488
N-terminal Mad Homology 1 (MH1) domain of receptor regulated SMADs; The MH1 is a small ...
 16-136 2.18e-70

N-terminal Mad Homology 1 (MH1) domain of receptor regulated SMADs; The MH1 is a small DNA-binding domain present in SMAD (small mothers against decapentaplegic) family of proteins, which are signal transducers and transcriptional modulators that mediate multiple signaling pathways. It binds to the major groove in an unusual manner via a beta hairpin structure. It negatively regulates the functions of the MH2 domain, the C-terminal domain of SMAD. This MH1 domain is found in all receptor regulated SMADs (R-SMADs) including SMAD1, SMAD2, SMAD3, SMAD5 and SMAD9. SMAD1 plays an essential role in bone development and postnatal bone formation through activation by bone morphogenetic protein (BMP) type 1 receptor kinase. SMAD2 regulates multiple cellular processes, such as cell proliferation, apoptosis and differentiation, while SMAD3 modulates signals of activin and TGF-beta. SMAD4, a common mediator SMAD (co-SMAD) binds R-SMADs, forming an oligomeric complex that binds to DNA and serves as a transcription factor. SMAD5 is involved in bone morphogenetic proteins (BMP) signal modulation, possibly playing a role in the pathway involving inhibition of hematopoietic progenitor cells by TGF-beta. SMAD9 (also known as SMAD8) can mediate the differentiation of mesenchymal stem cells (MSCs) into tendon-like cells by inhibiting the osteogenic pathway


Pssm-ID: 199812  Cd Length: 123  Bit Score: 219.37  E-value: 2.18e-70
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13959539  16 PAVKRLLGWKQG---DEEEKWAEKAVDSLVKKLKKKkGAMDELERALSCPGQPSKCVTIPRSLDGRLQVSHRKGLPHVIY 92
Cdd:cd10488   1 PIVKRLLGWKKGeqnGEEEKWAEKAVKSLVKKLKKK-GQLEELEKAISTQNVNTRCVTIPRSLDGRLQVSHRKGLPHVIY 79

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....
gi 13959539  93 CRVWRWPDLQSHHELKPLECCEFPFGSKQKEVCINPYHYRRVET 136
Cdd:cd10488  80 CRLWRWPDLQSHHELKPLELCEFAFNMKKEEVCINPYHYKRVET 123
MH1_SMAD_2_3 cd10491
N-terminal Mad Homology 1 (MH1) domain in SMAD2 and SMAD3; The MH1 is a small DNA-binding ...
 14-136 1.79e-67

N-terminal Mad Homology 1 (MH1) domain in SMAD2 and SMAD3; The MH1 is a small DNA-binding domain present in SMAD (small mothers against decapentaplegic) family of proteins, which are signal transducers and transcriptional modulators that mediate multiple signaling pathways. MH1 binds to the DNA major groove in an unusual manner via a beta hairpin structure. It negatively regulates the functions of the MH2 domain, the C-terminal domain of SMAD. This MH1 is found in SMAD2 as well as SMAD3. SMAD2 mediates the signal of the transforming growth factor (TGF)-beta, and thereby regulates multiple cellular processes, such as cell proliferation, apoptosis, and differentiation. It plays a role in the transmission of extracellular signals from ligands of the TGF-beta superfamily growth factors into the cell nucleus. SMAD3 modulates signals of activin and TGF-beta. It binds SMAD4, enabling its transmigration into the nucleus where it forms complexes with other proteins and acts as a transcription factor. Increased SMAD3 activity has been implicated in the pathogenesis of scleroderma.


Pssm-ID: 199815  Cd Length: 124  Bit Score: 211.62  E-value: 1.79e-67
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13959539  14 TSPAVKRLLGWKQG--DEEEKWAEKAVDSLVKKLKKKkGAMDELERALSCPGQPSKCVTIPRSLDGRLQVSHRKGLPHVI 91
Cdd:cd10491   1 TPPVVKRLLGWKKGenGQEEKWSEKAVKSLVKKLKKT-GGLDELEKAITTQNSNTKCITIPRSLDGRLQVSHRKGLPHVI 79

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*
gi 13959539  92 YCRVWRWPDLQSHHELKPLECCEFPFGSKQKEVCINPYHYRRVET 136
Cdd:cd10491  80 YCRLWRWPDLQSHHELRAIETCEYAFNLKKDEVCVNPYHYQRVET 124
MH1 cd00049
N-terminal Mad Homology 1 (MH1) domain; The MH1 is a small DNA-binding domain present in SMAD ...
 16-136 1.77e-65

N-terminal Mad Homology 1 (MH1) domain; The MH1 is a small DNA-binding domain present in SMAD (small mothers against decapentaplegic) family of proteins, which are signal transducers and transcriptional modulators that mediate multiple signaling pathways. MH1 binds to the DNA major groove in an unusual manner via a beta hairpin structure. It negatively regulates the functions of the MH2 domain, the C-terminal domain of SMAD. Receptor-regulated SMAD proteins (R-SMADs, including SMAD1, SMAD2, SMAD3, SMAD5, and SMAD9) are activated by phosphorylation by transforming growth factor (TGF)-beta type I receptors. The active R-SMAD associates with a common mediator SMAD (Co-SMAD or SMAD4) and other cofactors, which together translocate to the nucleus to regulate gene expression. The inhibitory or antagonistic SMADs (I-SMADs, including SMAD6 and SMAD7) negatively regulate TGF-beta signaling by competing with R-SMADs for type I receptor or Co-SMADs. MH1 domains of R-SMAD and SMAD4 contain a nuclear localization signal as well as DNA-binding activity. The activated R-SMAD/SMAD4 complex then binds with very low affinity to a DNA sequence CAGAC called SMAD-binding element (SBE) via the MH1 domain.


Pssm-ID: 199811  Cd Length: 121  Bit Score: 206.29  E-value: 1.77e-65
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13959539  16 PAVKRLLGWKQGDEEEKWAEKAVDSLVKKLKKKkGAMDELERALSCPG-QPSKCVTIPRSLDGRLQVSHRKGLPHVIYCR 94
Cdd:cd00049   1 PIVKRLLGWKQGGEEEKWAKKAVKSLVKKLKEK-KQLDSLEKAITTQGgVPSKCVTIPRSLDGRLQVAHRKGLPHVIYCR 79

                        90       100       110       120
                ....*....|....*....|....*....|....*....|..
gi 13959539  95 VWRWPDLQSHHELKPLECCEFPFGSKQKEVCINPYHYRRVET 136
Cdd:cd00049  80 LWRWPDLHSHHELKALELCQFAFNMKKDEVCVNPYHYQRVES 121
MH2_SMAD_4 cd10498
C-terminal Mad Homology 2 (MH2) domain in SMAD4; The MH2 domain is located at the C-terminus ...
 270-453 5.54e-58

C-terminal Mad Homology 2 (MH2) domain in SMAD4; The MH2 domain is located at the C-terminus of the SMAD (small mothers against decapentaplegic) family of proteins, which are signal transducers and transcriptional modulators that mediate multiple signaling pathways. The MH2 domain is responsible for type I receptor interaction, phosphorylation-triggered homo- and hetero-oligomerization, and transactivation. It is negatively regulated by the N-terminal MH1 domain. SMAD4, which belongs to the Dwarfin family of proteins, is involved in many cell functions such as differentiation, apoptosis, gastrulation, embryonic development and the cell cycle. SMAD4 binds receptor regulated SMADs (R-SMADs) such as SMAD1 or SMAD2, and forms an oligomeric complex that binds to DNA and serves as a transcription factor. SMAD4 is often mutated in several cancers, such as multiploid colorectal cancer, cervical cancer and pancreatic carcinoma, as well as in juvenile polyposis syndrome.


Pssm-ID: 199823  Cd Length: 222  Bit Score: 190.76  E-value: 5.54e-58
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13959539 270 PQHWCSVAYYELNNRVGETFQASSR--SVLIDGFTDPSNNrNRFCLGLLSNVNRNSTIENTRRHIGKGVHLYYVG-GEVY 346
Cdd:cd10498   1 PEYWCSIAYFELDTQVGETFKVPSScpTVTVDGYVDPSGG-NRFCLGQLSNVHRTEASERARLHIGKGVQLDCKGeGDVW 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13959539 347 AECVSDSSIFVQSRNCNYQHGFHPA-TVCKIPSGCSLKVFN-NQLFAQLLAQSVHHGFEV-------------------- 404
Cdd:cd10498  80 LRCLSDHSVFVQSYYLDREAGRAPGdAVHKIYPSAYIKVFDlRQCHRQMQQQAATAQAAAaaqaaavagnipgpgsvggi 159

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 13959539 405 -------------VYELTKMCTIRMSFVKGWGAEYHRQDVTSTPCWIEIHLHGPLQWLDKVL 453
Cdd:cd10498 160 apaislsaaagigVDDLRRLCILRMSFVKGWGPDYPRQSIKETPCWIEIHLHRALQLLDEVL 221
DWA smart00523
Domain A in dwarfin family proteins;
29-138 3.29e-51

Domain A in dwarfin family proteins;


Pssm-ID: 214708  Cd Length: 109  Bit Score: 169.10  E-value: 3.29e-51
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13959539     29 EEEKWAEKAVDSLVKKLKKkkGAMDELERALSCPG-QPSKCVTIPRSLDGRLQVSHRKGLPHVIYCRVWRWPDLQSHHEL 107
Cdd:smart00523   1 VEEKWAKKATESLLKKLKK--KQLEELLQAVESKGgPPTRCVLIPRSLDGRLQVAHRKGLPHVLYCRLFRWPDLQSPHEL 78

                           90       100       110
                   ....*....|....*....|....*....|.
gi 13959539    108 KPLECCEFPFGSKQKEVCINPYHYRRVETPV 138
Cdd:smart00523  79 KALPTCEHAFESKSDEVCCNPYHYSRVERPE 109
MH1 pfam03165
MH1 domain; The MH1 (MAD homology 1) domain is found at the amino terminus of MAD related ...
 34-135 3.87e-49

MH1 domain; The MH1 (MAD homology 1) domain is found at the amino terminus of MAD related proteins such as Smads. This domain is separated from the MH2 domain by a non-conserved linker region. The crystal structure of the MH1 domain shows that a highly conserved 11 residue beta hairpin is used to bind the DNA consensus sequence GNCN in the major groove, shown to be vital for the transcriptional activation of target genes. Not all examples of MH1 can bind to DNA however. Smad2 cannot bind DNA and has a large insertion within the hairpin that presumably abolishes DNA binding. A basic helix (H2) in MH1 with the nuclear localization signal KKLKK has been shown to be essential for Smad3 nuclear import. Smads also use the MH1 domain to interact with transcription factors such as Jun, TFE3, Sp1, and Runx.


Pssm-ID: 460833  Cd Length: 103  Bit Score: 163.31  E-value: 3.87e-49
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13959539    34 AEKAVDSLVKKLKKKKGAMDELERALSCPG-QPSKCVTIPRSLDGRLQVSHRKGLPHVIYCRVWRWPDLQSHHELKPLEC 112
Cdd:pfam03165   1 LKKAVESLLKKLKKKIQQLEELELAVESRGdPPTGCVTIPRSLDGRLQVAGRKGLPHVIYCRLWRWPDLQSQHELKAIPT 80

                          90       100
                  ....*....|....*....|...
gi 13959539   113 CEFPFGSKQKEVCINPYHYRRVE 135
Cdd:pfam03165  81 CETAFESKKDEVCINPYHYSRVE 103
MH1_SMAD_4 cd10492
N-terminal Mad Homology 1 (MH1) domain in SMAD4; The MH1 is a small DNA-binding domain present ...
 18-134 2.95e-38

N-terminal Mad Homology 1 (MH1) domain in SMAD4; The MH1 is a small DNA-binding domain present in SMAD (small mothers against decapentaplegic) family of proteins, which are signal transducers and transcriptional modulators that mediate multiple signaling pathways. MH1 binds to the DNA major groove in an unusual manner via a beta hairpin structure. It negatively regulates the functions of the MH2 domain, the C-terminal domain of SMAD. This MH1 belongs to SMAD4, a common mediator SMAD (co-SMAD), which belongs to the Dwarfin family of proteins and is involved in many cell functions such as differentiation, apoptosis, gastrulation, embryonic development and cell cycle. SMAD4 binds receptor regulated SMADs (R-SMADs) such as SMAD1 or SMAD2, and forms an oligomeric complex that binds to DNA and serves as a transcription factor. SMAD4 is often mutated in several cancers, such as multiploid colorectal cancer and pancreatic carcinoma, as well as in juvenile polyposis syndrome (JPS).


Pssm-ID: 199816  Cd Length: 125  Bit Score: 135.27  E-value: 2.95e-38
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13959539  18 VKRLLGWKQGDEEEKWAEKAVDSLVKKLKKKKGAMDELERALSCPG-QPSKCVTIPRSLDGRLQVSHRKGLPHVIYCRVW 96
Cdd:cd10492   7 VHSLMCHRQGGESESFAKRAIESLVKKLKDKRDELDSLITAITSNGaHPSKCVTIQRTLDGRLQVAGRKGFPHVIYARIW 86

                        90       100       110
                ....*....|....*....|....*....|....*...
gi 13959539  97 RWPDLQShHELKPLECCEFPFGSKQKEVCINPYHYRRV 134
Cdd:cd10492  87 RWPDLHK-NELKHVKFCQYAFDLKCDSVCVNPYHYERV 123
MH2_I-SMAD cd10496
C-terminal Mad Homology 2 (MH2) domain in Inhibitory SMADs; The MH2 domain is located at the ...
 273-442 2.13e-32

C-terminal Mad Homology 2 (MH2) domain in Inhibitory SMADs; The MH2 domain is located at the C-terminus of the SMAD (small mothers against decapentaplegic) family of proteins, which are signal transducers and transcriptional modulators that mediate multiple signaling pathways. The MH2 domain is responsible for type I receptor interaction, phosphorylation-triggered homo- and hetero-oligomerization, and transactivation. It is negatively regulated by the N-terminal MH1 domain, which prevents it from forming a complex with SMAD4. SMAD6 and SMAD7 are inhibitory SMADs (I-SMADs) that function as negative regulators of signaling mediated by the TGF-beta superfamily. SMAD6 specifically inhibits bone morphogenetic protein (BMP) type I receptor mediated signaling, while SMAD7 enhances muscle differentiation and is often associated with cancer, tissue fibrosis and inflammatory diseases.


Pssm-ID: 199821  Cd Length: 165  Bit Score: 120.92  E-value: 2.13e-32
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13959539 273 WCSVAYYELNNRVGETFQASSRSVLIdgFTDPSNNrNRFCLG-LLSNVNRNSTIENTRRHIGKGVHLYYVGGEVYAECVS 351
Cdd:cd10496   1 WCTIAYWELRERVGRLYPVKQPAVNI--FDDLPKG-DGFCLGaLNRQGNASEAVARVRSKIGLGVTLSREPDGVWIYNRS 77

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13959539 352 DSSIFVQSRNCNYQHGFHPaTVCKIPSGCSLKVFNNQLFAQLlaQSVHHGFE----VVYEltkmcTIRMSFVKGWGAEYH 427
Cdd:cd10496  78 EYPIFVNSPTLDSPPSRNL-LVTKVPPGYSLKVFDYERAALL--QRRDDHFSpqgpVDPN-----SVRISFVKGWGPNYS 149

                       170
                ....*....|....*
gi 13959539 428 RQDVTSTPCWIEIHL 442
Cdd:cd10496 150 RQFITSCPCWLEILL 164
MH2_SMAD_6 cd10499
C-terminal Mad Homology 2 (MH2) domain in SMAD6; The MH2 domain is located at the C-terminus ...
 269-442 6.80e-28

C-terminal Mad Homology 2 (MH2) domain in SMAD6; The MH2 domain is located at the C-terminus of the SMAD (small mothers against decapentaplegic) family of proteins, which are signal transducers and transcriptional modulators that mediate multiple signaling pathways. The MH2 domain is responsible for type I receptor interaction, phosphorylation-triggered homo- and hetero-oligomerization, and transactivation. It is negatively regulated by the N-terminal MH1 domain, which prevents it from forming a complex with SMAD4. SMAD6, an inhibitory or antagonistic SMAD (I-SMAD), acts as a negative regulator of signaling mediated by the TGF-beta superfamily of ligands, by competing with SMAD4 and preventing the transcription of SMAD4's gene products. SMAD6 specifically inhibits bone morphogenetic protein (BMP) type I receptor mediated signaling. SMAD6 and SMAD7 act as critical mediators for effective TGF-beta I-mediated suppression of Interleukin-1/Toll-like receptor (IL-1R/TLR) signaling through simultaneous binding to Pellino-1, an adaptor protein of interleukin-1 receptor associated kinase 1 (IRAK1), via their MH2 domains.


Pssm-ID: 199824  Cd Length: 174  Bit Score: 109.14  E-value: 6.80e-28
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13959539 269 EPQHWCSVAYYELNNRVGETFQASSRSVLIdgFTDPSNNrNRFCLGLLSNVNRNSTIENTRRHIGKGVHLYYVGGEVYAE 348
Cdd:cd10499   6 KRSHWCSVAYWEHRTRVGRLYAVYDQSVSI--FYDLPQG-SGFCLGQLNLEQRSESVRRTRSKIGYGILLSKEPDGVWAY 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13959539 349 CVSDSSIFVQSRNCNYQHGfHPATVCKIPSGCSLKVFNNQLfAQLLAQsvHHGFEVVYELTKMCTIRMSFVKGWGAEYHR 428
Cdd:cd10499  83 NRSEHPIFVNSPTLDIPGS-RTLVVRKVPPGYSIKVFDYER-SCLLQH--TAEPELADGPYDPNSVRISFAKGWGPCYSR 158

                       170
                ....*....|....
gi 13959539 429 QDVTSTPCWIEIHL 442
Cdd:cd10499 159 QFITSCPCWLEILL 172
MH2_SMAD_7 cd10500
C-terminal Mad Homology 2 (MH2) domain in SMAD7; The MH2 domain is located at the C-terminus ...
 269-440 9.36e-18

C-terminal Mad Homology 2 (MH2) domain in SMAD7; The MH2 domain is located at the C-terminus of the SMAD (small mothers against decapentaplegic) family of proteins, which are signal transducers and transcriptional modulators that mediate multiple signaling pathways. The MH2 domain is responsible for type I receptor interaction, phosphorylation-triggered homo- and hetero-oligomerization, and transactivation. It is negatively regulated by the N-terminal MH1 domain, which prevents it from forming a complex with SMAD4. SMAD7, an inhibitory or antagonistic SMAD (I-SMAD), acts as a negative regulator of signaling mediated by the TGF-beta superfamily of ligands, by blocking TGF-beta type 1 and activin association with the receptor as well as access to SMAD2. SMAD7 enhances muscle differentiation, playing pivotal roles in embryonic development and adult homoeostasis. SMAD7 and SMAD6 act as critical mediators for effective TGF-beta I-mediated suppression of Interleukin-1/Toll-like receptor (IL-1R/TLR) signaling through simultaneous binding to Pellino-1, an adaptor protein of interleukin-1 receptor associated kinase 1(IRAK1), via their MH2 domains. Altered expression of SMAD7 is often associated with cancer, tissue fibrosis and inflammatory diseases.


Pssm-ID: 199825  Cd Length: 171  Bit Score: 80.47  E-value: 9.36e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13959539 269 EPQHWCSVAYYELNNRVGETFQASSRSvlIDGFTDPSNNrNRFCLGLLSNVNRNSTIENTRRHIGKGVHLYYVGGEVYAE 348
Cdd:cd10500   4 DQSHWCVVAYWEEKTRVGRLYSVQEPS--LDIFYDLPQG-NGFCLGQLNSDNKSQLVQKVRSKIGYGIQLTREVDGVWVY 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13959539 349 CVSDSSIFVQSRNCNYQHGfHPATVCKIPSGCSLKVFNNQLFAQLLAQSVHhgfEVVYELTKMCTIRMSFVKGWGAEYHR 428
Cdd:cd10500  81 NRSSYPIFIKSATLDNPDS-RTLLVHKVFPGFSIKAFDYEKAYSLQRPNDH---EFMQQPWTGFTVQISFVKGWGQCYTR 156

                       170
                ....*....|..
gi 13959539 429 QDVTSTPCWIEI 440
Cdd:cd10500 157 QFISSCPCWLEV 168
MH1_SMAD_6 cd10493
N-terminal Mad Homology 1 (MH1) domain in SMAD6; The MH1 is a small DNA-binding domain present ...
 55-138 1.96e-15

N-terminal Mad Homology 1 (MH1) domain in SMAD6; The MH1 is a small DNA-binding domain present in SMAD (small mothers against decapentaplegic) family of proteins, which are signal transducers and transcriptional modulators that mediate multiple signaling pathways. MH1 binds to the DNA major groove in an unusual manner via a beta hairpin structure. It negatively regulates the functions of the MH2 domain, the C-terminal domain of SMAD. This MH1 belongs to SMAD6, an inhibitory SMAD (I-SMAD) or antagonistic SMAD, which acts as a negative regulator of signaling mediated by TGF-beta superfamily ligands, by competing with SMAD4 and preventing the transcription of SMAD4's gene products. SMAD6 specifically inhibits bone morphogenetic protein (BMP) type I receptor mediated signaling.


Pssm-ID: 199817  Cd Length: 113  Bit Score: 72.11  E-value: 1.96e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13959539  55 LERALSCPGQPSKCVTIPRSldgRLQVSHRKGLPHVIYCRVWRWPDLQSHHELKPLECCEFPFGSKQKEVCINPYHYRRV 134
Cdd:cd10493  33 LEAVESRGGLPSGCVMVPRT---ELRLGGRRVPPQLLLCRLFRWPDLQHPAQLKALCHCQSFGAQDGPTVCCNPYHYSRL 109


                ....
gi 13959539 135 ETPV 138
Cdd:cd10493 110 CGPE 113
MH1_SMAD_6_7 cd10489
N-terminal Mad Homology 1 (MH1) domain in SMAD6 and SMAD7; The MH1 is a small DNA-binding ...
 60-134 1.21e-13

N-terminal Mad Homology 1 (MH1) domain in SMAD6 and SMAD7; The MH1 is a small DNA-binding domain present in SMAD (small mothers against decapentaplegic) family of proteins, which are signal transducers and transcriptional modulators that mediate multiple signaling pathways. MH1 binds to the DNA major groove in an unusual manner via a beta hairpin structure. It negatively regulates the functions of the MH2 domain, the C-terminal domain of SMAD. This MH1 domain is found in SMAD6 and SMAD7, both inhibitory SMADs (I-SMADs) and negative regulators of signaling mediated by TGF-beta superfamily. SMAD6 specifically inhibits bone morphogenetic protein (BMP) type I receptor mediated signaling while SMAD7 enhances muscle differentiation and is often associated with cancer, tissue fibrosis and inflammatory diseases.


Pssm-ID: 199813  Cd Length: 119  Bit Score: 67.41  E-value: 1.21e-13
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 13959539  60 SCPGQPSKCVTIPRSLdgrlqVSHRKGLPHVIYCRVWRWPDLQSHHELKPLECCefPFGSKQKEVCINPYHYRRV 134
Cdd:cd10489  48 SRGGDYLACVLLPRRD-----PRSMPQDPHVLCCQLFRWPDLRHSSELKRLPTC--ESAKDPVYVCCNPYHWSRL 115
MH1_SMAD_7 cd10494
N-terminal Mad Homology 1 (MH1) domain in SMAD7; The MH1 is a small DNA-binding domain present ...
 55-137 2.88e-09

N-terminal Mad Homology 1 (MH1) domain in SMAD7; The MH1 is a small DNA-binding domain present in SMAD (small mothers against decapentaplegic) family of proteins. It binds to the major groove in an unusual manner via a beta hairpin structure. It negatively regulates the functions of the MH2 domain, the C-terminal domain of SMAD. This MH1 belongs to SMAD7, an inhibitory SMAD (I-SMAD) or antagonistic SMAD, which acts as a negative regulator of signaling mediated by TGF-beta superfamily ligands, by blocking TGF-beta type 1 and activin association with the receptor as well as access to SMAD2. SMAD7 enhances muscle differentiation, playing pivotal roles in embryonic development and adult homoeostasis. Altered expression of SMAD7 is often associated with cancer, tissue fibrosis and inflammatory diseases.


Pssm-ID: 199818  Cd Length: 123  Bit Score: 54.88  E-value: 2.88e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13959539  55 LERALSCPGQP-SKCVTIPRSLDGRLQvSHRKGLPhVIYCRVWRWPDLQSHHELKPLECCEfPFGSKQKE-VCINPYHYR 132
Cdd:cd10494  39 LLQAVESRGGArTPCLLLPARLDARLG-QQSYSLP-LLLCKVFRWPDLRHSSEVKRLSCCE-SYGKINPElVCCNPHHLS 115


                ....*...
gi 13959539 133 R---VETP 137
Cdd:cd10494 116 RlceLESP 123
Atrophin-1 pfam03154
Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian ...
 140-258 6.00e-03

Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian atrophy (DRPLA) gene. DRPLA OMIM:125370 is a progressive neurodegenerative disorder. It is caused by the expansion of a CAG repeat in the DRPLA gene on chromosome 12p. This results in an extended polyglutamine region in atrophin-1, that is thought to confer toxicity to the protein, possibly through altering its interactions with other proteins. The expansion of a CAG repeat is also the underlying defect in six other neurodegenerative disorders, including Huntington's disease. One interaction of expanded polyglutamine repeats that is thought to be pathogenic is that with the short glutamine repeat in the transcriptional coactivator CREB binding protein, CBP. This interaction draws CBP away from its usual nuclear location to the expanded polyglutamine repeat protein aggregates that are characteriztic of the polyglutamine neurodegenerative disorders. This interferes with CBP-mediated transcription and causes cytotoxicity.


Pssm-ID: 460830 [Multi-domain]  Cd Length: 991  Bit Score: 39.37  E-value: 6.00e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13959539   140 PPVLVPrhseynpqLSLLAKFRSASLHSEPL--MPHNATYPDSFQQPPCSALPPSPSHAFSQSPCTASYPHSPGSPSEPE 217
Cdd:pfam03154 393 PPALKP--------LSSLSTHHPPSAHPPPLqlMPQSQQLPPPPAQPPVLTQSQSLPPPAASHPPTSGLHQVPSQSPFPQ 464

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 13959539   218 SPYQHSVDTPPLPYHATEASETQSGQPVDATADRHVVLSIP 258
Cdd:pfam03154 465 HPFVPGGPPPITPPSGPPTSTSSAMPGIQPPSSASVSSSGP 505
 
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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