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Conserved domains on  [gi|847087110|ref|XP_012816314|]
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mothers against decapentaplegic homolog 2 isoform X2 [Xenopus tropicalis]

Protein Classification

MH1_SMAD_2_3 and MH2_SMAD_2_3 domain-containing protein( domain architecture ID 10180352)

MH1_SMAD_2_3 and MH2_SMAD_2_3 domain-containing protein

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
MH2_SMAD_2_3 cd10985
C-terminal Mad Homology 2 (MH2) domain in SMAD2 and SMAD3; The MH2 domain is located at the ...
 236-426 5.12e-156

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: 438.98  E-value: 5.12e-156
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 847087110 236 VTYSEPAFWCSIAYYELNQRVGETFHASQPSLTVDGFTDPSNSERFCLGLLSNVNRNATVEMTRRHIGRGVRLYYIGGEV 315
Cdd:cd10985    1 VTYCEPAFWCSISYYEMNTRVGETFHASQPSLTVDGFTDPSNSERFCLGLLSNVNRNPQVELTRRHIGKGVRLYYIGGEV 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 847087110 316 FAECLSDSAIFVQSPNCNQRYGWHPATVCKIPPGCNLKIFNNQEFAALLAQSVNQGFEAVYQLTRMCTIRMSFVKGWGAE 395
Cdd:cd10985   81 FAECLSDSAIFVQSPNCNQRYGWHPATVCKIPPGCNLKIFNNQEFAALLSQSVNQGFEAVYQLTRMCTIRMSFVKGWGAE 160

                        170       180       190
                 ....*....|....*....|....*....|.
gi 847087110 396 YRRQTVTSTPCWIELHLNGPLQWLDKVLTQM 426
Cdd:cd10985  161 YRRQTVTSTPCWIELHLNGPLQWLDRVLTQM 191
MH1_SMAD_2_3 cd10491
N-terminal Mad Homology 1 (MH1) domain in SMAD2 and SMAD3; The MH1 is a small DNA-binding ...
 8-142 9.63e-83

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: 250.14  E-value: 9.63e-83
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 847087110   8 TPPVVKRLLGWKKSasgttgagggeQNGQEEKWCEKAVKSLVKKLKKTGQLDELEKAITTQNCNTKCVTIPRSLDGRLQV 87
Cdd:cd10491    1 TPPVVKRLLGWKKG-----------ENGQEEKWSEKAVKSLVKKLKKTGGLDELEKAITTQNSNTKCITIPRSLDGRLQV 69

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 847087110  88 SHRKGLPHVIYCRLWRWPDLHSHHELKAIENCEYAFNLKKDEVCVNPYHYQRVET 142
Cdd:cd10491   70 SHRKGLPHVIYCRLWRWPDLQSHHELRAIETCEYAFNLKKDEVCVNPYHYQRVET 124
 
Name Accession Description Interval E-value
MH2_SMAD_2_3 cd10985
C-terminal Mad Homology 2 (MH2) domain in SMAD2 and SMAD3; The MH2 domain is located at the ...
 236-426 5.12e-156

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: 438.98  E-value: 5.12e-156
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 847087110 236 VTYSEPAFWCSIAYYELNQRVGETFHASQPSLTVDGFTDPSNSERFCLGLLSNVNRNATVEMTRRHIGRGVRLYYIGGEV 315
Cdd:cd10985    1 VTYCEPAFWCSISYYEMNTRVGETFHASQPSLTVDGFTDPSNSERFCLGLLSNVNRNPQVELTRRHIGKGVRLYYIGGEV 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 847087110 316 FAECLSDSAIFVQSPNCNQRYGWHPATVCKIPPGCNLKIFNNQEFAALLAQSVNQGFEAVYQLTRMCTIRMSFVKGWGAE 395
Cdd:cd10985   81 FAECLSDSAIFVQSPNCNQRYGWHPATVCKIPPGCNLKIFNNQEFAALLSQSVNQGFEAVYQLTRMCTIRMSFVKGWGAE 160

                        170       180       190
                 ....*....|....*....|....*....|.
gi 847087110 396 YRRQTVTSTPCWIELHLNGPLQWLDKVLTQM 426
Cdd:cd10985  161 YRRQTVTSTPCWIELHLNGPLQWLDRVLTQM 191
DWB smart00524
Domain B in dwarfin family proteins;
243-413 1.58e-103

Domain B in dwarfin family proteins;


Pssm-ID: 197770  Cd Length: 171  Bit Score: 304.62  E-value: 1.58e-103
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 847087110   243 FWCSIAYYELNQRVGETFHASQPSLTVDGFTDPSNSERFCLGLLSNVNRNATVEMTRRHIGRGVRLYYIGGEVFAECLSD 322
Cdd:smart00524   1 SWCKIAYYELNTRVGETFKVSSPSVTVDGFTDPSDGNRFCLGQLSNVNRNEATELIRKHIGKGVQLSYENGDVWLYNRSD 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 847087110   323 SAIFVQSPNCNQRYGWHPATVCKIPPGCNLKIFNNQEFAALLAQSVNQGFEAVYQLTRMCTIRMSFVKGWGAEYRRQTVT 402
Cdd:smart00524  81 SPIFVQSPYLDEPGGRTLDTVHKLPPGYSIKVFDMEKFAQLLARELAKGFEGVYDLARMCTIRISFVKGWGPDYSRQTIT 160

                          170
                   ....*....|.
gi 847087110   403 STPCWIELHLN 413
Cdd:smart00524 161 STPCWIEVHLN 171
MH2 pfam03166
MH2 domain; This is the MH2 (MAD homology 2) domain found at the carboxy terminus of MAD ...
 243-413 8.91e-103

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: 303.01  E-value: 8.91e-103
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 847087110  243 FWCSIAYYELNQRVGETFHASQPSLTVDGFTDPSNSERFCLGLLSNVNRNATVEMTRRHIGRGVRLYYIGGEVFAECLSD 322
Cdd:pfam03166   2 IWCSVAYYELNTRVGEAFKVSSPNVTVDGFTDPSDGNRFCLGLLSNVNRNEAVEKVRKHIGKGVRLSYDGGEVWIYNLSD 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 847087110  323 SAIFVQSPNCNQRYGWHPATVCKIPPGCNLKIFNNQEFAALLAQSVNQGFEAVYQLTRMCTIRMSFVKGWGAEYRRQTVT 402
Cdd:pfam03166  82 HPVFVQSPYLNREAGRAPDTVHKVPPGESLKVFDMRKFQQLLSQELRRARLGPQDANKLCSVRISFVKGWGPDYSRQDIT 161

                         170
                  ....*....|.
gi 847087110  403 STPCWIELHLN 413
Cdd:pfam03166 162 STPCWIEIHLH 172
MH1_SMAD_2_3 cd10491
N-terminal Mad Homology 1 (MH1) domain in SMAD2 and SMAD3; The MH1 is a small DNA-binding ...
 8-142 9.63e-83

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: 250.14  E-value: 9.63e-83
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 847087110   8 TPPVVKRLLGWKKSasgttgagggeQNGQEEKWCEKAVKSLVKKLKKTGQLDELEKAITTQNCNTKCVTIPRSLDGRLQV 87
Cdd:cd10491    1 TPPVVKRLLGWKKG-----------ENGQEEKWSEKAVKSLVKKLKKTGGLDELEKAITTQNSNTKCITIPRSLDGRLQV 69

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 847087110  88 SHRKGLPHVIYCRLWRWPDLHSHHELKAIENCEYAFNLKKDEVCVNPYHYQRVET 142
Cdd:cd10491   70 SHRKGLPHVIYCRLWRWPDLQSHHELRAIETCEYAFNLKKDEVCVNPYHYQRVET 124
DWA smart00523
Domain A in dwarfin family proteins;
36-144 2.72e-49

Domain A in dwarfin family proteins;


Pssm-ID: 214708  Cd Length: 109  Bit Score: 163.32  E-value: 2.72e-49
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 847087110    36 QEEKWCEKAVKSLVKKLKKTgQLDELEKAITTQNCN-TKCVTIPRSLDGRLQVSHRKGLPHVIYCRLWRWPDLHSHHELK 114
Cdd:smart00523   1 VEEKWAKKATESLLKKLKKK-QLEELLQAVESKGGPpTRCVLIPRSLDGRLQVAHRKGLPHVLYCRLFRWPDLQSPHELK 79

                           90       100       110
                   ....*....|....*....|....*....|
gi 847087110   115 AIENCEYAFNLKKDEVCVNPYHYQRVETPV 144
Cdd:smart00523  80 ALPTCEHAFESKSDEVCCNPYHYSRVERPE 109
MH1 pfam03165
MH1 domain; The MH1 (MAD homology 1) domain is found at the amino terminus of MAD related ...
 55-141 8.20e-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: 161.77  E-value: 8.20e-49
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 847087110   55 TGQLDELEKAITTQ-NCNTKCVTIPRSLDGRLQVSHRKGLPHVIYCRLWRWPDLHSHHELKAIENCEYAFNLKKDEVCVN 133
Cdd:pfam03165  16 IQQLEELELAVESRgDPPTGCVTIPRSLDGRLQVAGRKGLPHVIYCRLWRWPDLQSQHELKAIPTCETAFESKKDEVCIN 95


                  ....*...
gi 847087110  134 PYHYQRVE 141
Cdd:pfam03165  96 PYHYSRVE 103
 
Name Accession Description Interval E-value
MH2_SMAD_2_3 cd10985
C-terminal Mad Homology 2 (MH2) domain in SMAD2 and SMAD3; The MH2 domain is located at the ...
 236-426 5.12e-156

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: 438.98  E-value: 5.12e-156
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 847087110 236 VTYSEPAFWCSIAYYELNQRVGETFHASQPSLTVDGFTDPSNSERFCLGLLSNVNRNATVEMTRRHIGRGVRLYYIGGEV 315
Cdd:cd10985    1 VTYCEPAFWCSISYYEMNTRVGETFHASQPSLTVDGFTDPSNSERFCLGLLSNVNRNPQVELTRRHIGKGVRLYYIGGEV 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 847087110 316 FAECLSDSAIFVQSPNCNQRYGWHPATVCKIPPGCNLKIFNNQEFAALLAQSVNQGFEAVYQLTRMCTIRMSFVKGWGAE 395
Cdd:cd10985   81 FAECLSDSAIFVQSPNCNQRYGWHPATVCKIPPGCNLKIFNNQEFAALLSQSVNQGFEAVYQLTRMCTIRMSFVKGWGAE 160

                        170       180       190
                 ....*....|....*....|....*....|.
gi 847087110 396 YRRQTVTSTPCWIELHLNGPLQWLDKVLTQM 426
Cdd:cd10985  161 YRRQTVTSTPCWIELHLNGPLQWLDRVLTQM 191
MH2_R-SMAD cd10495
C-terminal Mad Homology 2 (MH2) domain in receptor regulated SMADs; The MH2 domain is located ...
 244-424 2.80e-137

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: 390.97  E-value: 2.80e-137
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 847087110 244 WCSIAYYELNQRVGETFHASQPSLTVDGFTDPSN-SERFCLGLLSNVNRNATVEMTRRHIGRGVRLYYIGGEVFAECLSD 322
Cdd:cd10495    1 WCSISYYELNSRVGEQFKASNPSIIVDGFTDPSNnSDRFCLGLLSNVNRNATIENTRRHIGRGVHLFYVGGEVYAECLSD 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 847087110 323 SAIFVQSPNCNQRYGWHPATVCKIPPGCNLKIFNNQEFAALLAQSVNQGFEAVYQLTRMCTIRMSFVKGWGAEYRRQTVT 402
Cdd:cd10495   81 SAIFVQSRNCNLRHGFHPATVCKIPPGCSLKIFNNQSFAQLLEQSVNRGFEAVYELTKMCTIRISFVKGWGAEYHRQDVT 160

                        170       180
                 ....*....|....*....|..
gi 847087110 403 STPCWIELHLNGPLQWLDKVLT 424
Cdd:cd10495  161 STPCWIEIHLHGPLQWLDKVLT 182
MH2_SMAD_1_5_9 cd10497
C-terminal Mad Homology 2 (MH2) domain in SMAD1, SMAD5 and SMAD9; The MH2 domain is located at ...
 238-437 1.25e-134

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: 385.00  E-value: 1.25e-134
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 847087110 238 YSEPAFWCSIAYYELNQRVGETFHASQPSLTVDGFTDPSN-SERFCLGLLSNVNRNATVEMTRRHIGRGVRLYYIGGEVF 316
Cdd:cd10497    1 YQEPKYWCSIAYYELNNRVGEAFHASSTSIIVDGFTDPSNnSDRFCLGLLSNVNRNSTIENTRRHIGKGVHLYYVGGEVY 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 847087110 317 AECLSDSAIFVQSPNCNQRYGWHPATVCKIPPGCNLKIFNNQEFAALLAQSVNQGFEAVYQLTRMCTIRMSFVKGWGAEY 396
Cdd:cd10497   81 AECLSDSSIFVQSRNCNYHHGFHPTTVCKIPPGCSLKIFNNQEFAQLLSQSVNHGFEAVYELTKMCTIRMSFVKGWGAEY 160

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|.
gi 847087110 397 RRQTVTSTPCWIELHLNGPLQWLDKVLTQMGSPSVRCSSMS 437
Cdd:cd10497  161 HRQDVTSTPCWIEIHLHGPLQWLDKVLTQMGSPHNPISSVS 201
MH2 cd00050
C-terminal Mad Homology 2 (MH2) domain; The MH2 domain is found in the SMAD (small mothers ...
 244-413 5.51e-104

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: 306.07  E-value: 5.51e-104
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 847087110 244 WCSIAYYELNQRVGETFHASQPSLTVDGFTDPSNSERFCLGLLSNVNRNATVEMTRRHIGRGVRLYYIGGEVFAECLSDS 323
Cdd:cd00050    1 WCSIAYYELNTRVGELFHVYSPSVAVDGFTDPSNGDRFCLGQLSNVNRNETIERTRRHIGKGVHLYYVGGEVWAECLSDH 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 847087110 324 AIFVQSPNCNQRYGWHPATVCKIPPGCNLKIFNNQEFAALLAQSVNQGFEAVYQLTRMCTIRMSFVKGWGAEYRRQTVTS 403
Cdd:cd00050   81 AIFVQSRNLDYPHGRHPLTVCKIPPGCSIKVFDNQEFAQLLHQSVNTGFEGVYELTKMCTIRMSFVKGWGPEYHRQDITS 160

                        170
                 ....*....|
gi 847087110 404 TPCWIELHLN 413
Cdd:cd00050  161 TPCWIEIHLH 170
DWB smart00524
Domain B in dwarfin family proteins;
243-413 1.58e-103

Domain B in dwarfin family proteins;


Pssm-ID: 197770  Cd Length: 171  Bit Score: 304.62  E-value: 1.58e-103
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 847087110   243 FWCSIAYYELNQRVGETFHASQPSLTVDGFTDPSNSERFCLGLLSNVNRNATVEMTRRHIGRGVRLYYIGGEVFAECLSD 322
Cdd:smart00524   1 SWCKIAYYELNTRVGETFKVSSPSVTVDGFTDPSDGNRFCLGQLSNVNRNEATELIRKHIGKGVQLSYENGDVWLYNRSD 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 847087110   323 SAIFVQSPNCNQRYGWHPATVCKIPPGCNLKIFNNQEFAALLAQSVNQGFEAVYQLTRMCTIRMSFVKGWGAEYRRQTVT 402
Cdd:smart00524  81 SPIFVQSPYLDEPGGRTLDTVHKLPPGYSIKVFDMEKFAQLLARELAKGFEGVYDLARMCTIRISFVKGWGPDYSRQTIT 160

                          170
                   ....*....|.
gi 847087110   403 STPCWIELHLN 413
Cdd:smart00524 161 STPCWIEVHLN 171
MH2 pfam03166
MH2 domain; This is the MH2 (MAD homology 2) domain found at the carboxy terminus of MAD ...
 243-413 8.91e-103

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: 303.01  E-value: 8.91e-103
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 847087110  243 FWCSIAYYELNQRVGETFHASQPSLTVDGFTDPSNSERFCLGLLSNVNRNATVEMTRRHIGRGVRLYYIGGEVFAECLSD 322
Cdd:pfam03166   2 IWCSVAYYELNTRVGEAFKVSSPNVTVDGFTDPSDGNRFCLGLLSNVNRNEAVEKVRKHIGKGVRLSYDGGEVWIYNLSD 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 847087110  323 SAIFVQSPNCNQRYGWHPATVCKIPPGCNLKIFNNQEFAALLAQSVNQGFEAVYQLTRMCTIRMSFVKGWGAEYRRQTVT 402
Cdd:pfam03166  82 HPVFVQSPYLNREAGRAPDTVHKVPPGESLKVFDMRKFQQLLSQELRRARLGPQDANKLCSVRISFVKGWGPDYSRQDIT 161

                         170
                  ....*....|.
gi 847087110  403 STPCWIELHLN 413
Cdd:pfam03166 162 STPCWIEIHLH 172
MH1_SMAD_2_3 cd10491
N-terminal Mad Homology 1 (MH1) domain in SMAD2 and SMAD3; The MH1 is a small DNA-binding ...
 8-142 9.63e-83

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: 250.14  E-value: 9.63e-83
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 847087110   8 TPPVVKRLLGWKKSasgttgagggeQNGQEEKWCEKAVKSLVKKLKKTGQLDELEKAITTQNCNTKCVTIPRSLDGRLQV 87
Cdd:cd10491    1 TPPVVKRLLGWKKG-----------ENGQEEKWSEKAVKSLVKKLKKTGGLDELEKAITTQNSNTKCITIPRSLDGRLQV 69

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 847087110  88 SHRKGLPHVIYCRLWRWPDLHSHHELKAIENCEYAFNLKKDEVCVNPYHYQRVET 142
Cdd:cd10491   70 SHRKGLPHVIYCRLWRWPDLQSHHELRAIETCEYAFNLKKDEVCVNPYHYQRVET 124
MH1_R-SMAD cd10488
N-terminal Mad Homology 1 (MH1) domain of receptor regulated SMADs; The MH1 is a small ...
 10-142 7.81e-69

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: 214.36  E-value: 7.81e-69
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 847087110  10 PVVKRLLGWKKSasgttgagggEQNGQEEKWCEKAVKSLVKKLKKTGQLDELEKAITTQNCNTKCVTIPRSLDGRLQVSH 89
Cdd:cd10488    1 PIVKRLLGWKKG----------EQNGEEEKWAEKAVKSLVKKLKKKGQLEELEKAISTQNVNTRCVTIPRSLDGRLQVSH 70

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 847087110  90 RKGLPHVIYCRLWRWPDLHSHHELKAIENCEYAFNLKKDEVCVNPYHYQRVET 142
Cdd:cd10488   71 RKGLPHVIYCRLWRWPDLQSHHELKPLELCEFAFNMKKEEVCINPYHYKRVET 123
MH1 cd00049
N-terminal Mad Homology 1 (MH1) domain; The MH1 is a small DNA-binding domain present in SMAD ...
 10-142 3.42e-61

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: 194.34  E-value: 3.42e-61
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 847087110  10 PVVKRLLGWKksasgttgagggeQNGQEEKWCEKAVKSLVKKLKKTGQLDELEKAITTQNC-NTKCVTIPRSLDGRLQVS 88
Cdd:cd00049    1 PIVKRLLGWK-------------QGGEEEKWAKKAVKSLVKKLKEKKQLDSLEKAITTQGGvPSKCVTIPRSLDGRLQVA 67

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 847087110  89 HRKGLPHVIYCRLWRWPDLHSHHELKAIENCEYAFNLKKDEVCVNPYHYQRVET 142
Cdd:cd00049   68 HRKGLPHVIYCRLWRWPDLHSHHELKALELCQFAFNMKKDEVCVNPYHYQRVES 121
MH2_SMAD_4 cd10498
C-terminal Mad Homology 2 (MH2) domain in SMAD4; The MH2 domain is located at the C-terminus ...
 241-423 1.09e-60

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: 196.92  E-value: 1.09e-60
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 847087110 241 PAFWCSIAYYELNQRVGETFH--ASQPSLTVDGFTDPSNSERFCLGLLSNVNRNATVEMTRRHIGRGVRLYYIG-GEVFA 317
Cdd:cd10498    1 PEYWCSIAYFELDTQVGETFKvpSSCPTVTVDGYVDPSGGNRFCLGQLSNVHRTEASERARLHIGKGVQLDCKGeGDVWL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 847087110 318 ECLSDSAIFVQSPNCNQRYGWHPA-TVCKIPPGCNLKIFN-NQEFAALLAQSVNQGFEAVYQ------------------ 377
Cdd:cd10498   81 RCLSDHSVFVQSYYLDREAGRAPGdAVHKIYPSAYIKVFDlRQCHRQMQQQAATAQAAAAAQaaavagnipgpgsvggia 160

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 847087110 378 ---------------LTRMCTIRMSFVKGWGAEYRRQTVTSTPCWIELHLNGPLQWLDKVL 423
Cdd:cd10498  161 paislsaaagigvddLRRLCILRMSFVKGWGPDYPRQSIKETPCWIEIHLHRALQLLDEVL 221
MH1_SMAD_1_5_9 cd10490
N-terminal Mad Homology 1 (MH1) domain in SMAD1, SMAD5 and SMAD9 (also known as SMAD8); The ...
 7-142 1.53e-60

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: 193.10  E-value: 1.53e-60
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 847087110   7 FTPPVVKRLLGWKksasgttgagggeQNGQEEKWCEKAVKSLVKK-LKKTGQLDELEKAITTQNCNTKCVTIPRSLDGRL 85
Cdd:cd10490    1 FTSPAVKRLLGWK-------------QGDEEEKWAEKAVDSLVKKlKKKKGALEELEKALSCPGQPSKCVTIPRSLDGRL 67

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 847087110  86 QVSHRKGLPHVIYCRLWRWPDLHSHHELKAIENCEYAFNLKKDEVCVNPYHYQRVET 142
Cdd:cd10490   68 QVSHRKGLPHVIYCRVWRWPDLQSHHELKPLECCEFPFGSKQKEVCINPYHYKRVES 124
DWA smart00523
Domain A in dwarfin family proteins;
36-144 2.72e-49

Domain A in dwarfin family proteins;


Pssm-ID: 214708  Cd Length: 109  Bit Score: 163.32  E-value: 2.72e-49
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 847087110    36 QEEKWCEKAVKSLVKKLKKTgQLDELEKAITTQNCN-TKCVTIPRSLDGRLQVSHRKGLPHVIYCRLWRWPDLHSHHELK 114
Cdd:smart00523   1 VEEKWAKKATESLLKKLKKK-QLEELLQAVESKGGPpTRCVLIPRSLDGRLQVAHRKGLPHVLYCRLFRWPDLQSPHELK 79

                           90       100       110
                   ....*....|....*....|....*....|
gi 847087110   115 AIENCEYAFNLKKDEVCVNPYHYQRVETPV 144
Cdd:smart00523  80 ALPTCEHAFESKSDEVCCNPYHYSRVERPE 109
MH1 pfam03165
MH1 domain; The MH1 (MAD homology 1) domain is found at the amino terminus of MAD related ...
 55-141 8.20e-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: 161.77  E-value: 8.20e-49
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 847087110   55 TGQLDELEKAITTQ-NCNTKCVTIPRSLDGRLQVSHRKGLPHVIYCRLWRWPDLHSHHELKAIENCEYAFNLKKDEVCVN 133
Cdd:pfam03165  16 IQQLEELELAVESRgDPPTGCVTIPRSLDGRLQVAGRKGLPHVIYCRLWRWPDLQSQHELKAIPTCETAFESKKDEVCIN 95


                  ....*...
gi 847087110  134 PYHYQRVE 141
Cdd:pfam03165  96 PYHYSRVE 103
MH2_I-SMAD cd10496
C-terminal Mad Homology 2 (MH2) domain in Inhibitory SMADs; The MH2 domain is located at the ...
 244-413 2.96e-39

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: 138.64  E-value: 2.96e-39
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 847087110 244 WCSIAYYELNQRVGETFHASQPSLTVdgFTDPSNSERFCLG-LLSNVNRNATVEMTRRHIGRGVRLYYIGGEVFAECLSD 322
Cdd:cd10496    1 WCTIAYWELRERVGRLYPVKQPAVNI--FDDLPKGDGFCLGaLNRQGNASEAVARVRSKIGLGVTLSREPDGVWIYNRSE 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 847087110 323 SAIFVQSPNCNQRYGWHPaTVCKIPPGCNLKIFNNQEFAALlaQSVNQGFEAVYQLTRMcTIRMSFVKGWGAEYRRQTVT 402
Cdd:cd10496   79 YPIFVNSPTLDSPPSRNL-LVTKVPPGYSLKVFDYERAALL--QRRDDHFSPQGPVDPN-SVRISFVKGWGPNYSRQFIT 154

                        170
                 ....*....|.
gi 847087110 403 STPCWIELHLN 413
Cdd:cd10496  155 SCPCWLEILLN 165
MH1_SMAD_4 cd10492
N-terminal Mad Homology 1 (MH1) domain in SMAD4; The MH1 is a small DNA-binding domain present ...
 59-140 5.67e-39

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: 136.81  E-value: 5.67e-39
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 847087110  59 DELEKAITTQNCN----TKCVTIPRSLDGRLQVSHRKGLPHVIYCRLWRWPDLHShHELKAIENCEYAFNLKKDEVCVNP 134
Cdd:cd10492   39 DELDSLITAITSNgahpSKCVTIQRTLDGRLQVAGRKGFPHVIYARIWRWPDLHK-NELKHVKFCQYAFDLKCDSVCVNP 117


                 ....*.
gi 847087110 135 YHYQRV 140
Cdd:cd10492  118 YHYERV 123
MH2_SMAD_6 cd10499
C-terminal Mad Homology 2 (MH2) domain in SMAD6; The MH2 domain is located at the C-terminus ...
 235-413 5.88e-32

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: 119.54  E-value: 5.88e-32
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 847087110 235 PVTYSEPAFWCSIAYYELNQRVGETFHASQPSLTVdgFTDPSNSERFCLGLLSNVNRNATVEMTRRHIGRGVRLYYIGGE 314
Cdd:cd10499    1 SPDATKRSHWCSVAYWEHRTRVGRLYAVYDQSVSI--FYDLPQGSGFCLGQLNLEQRSESVRRTRSKIGYGILLSKEPDG 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 847087110 315 VFAECLSDSAIFVQSPNCNQRYGwHPATVCKIPPGCNLKIFNNQEFAALLAQSVNQGFEAVYQLTrmcTIRMSFVKGWGA 394
Cdd:cd10499   79 VWAYNRSEHPIFVNSPTLDIPGS-RTLVVRKVPPGYSIKVFDYERSCLLQHTAEPELADGPYDPN---SVRISFAKGWGP 154

                        170
                 ....*....|....*....
gi 847087110 395 EYRRQTVTSTPCWIELHLN 413
Cdd:cd10499  155 CYSRQFITSCPCWLEILLN 173
MH2_SMAD_7 cd10500
C-terminal Mad Homology 2 (MH2) domain in SMAD7; The MH2 domain is located at the C-terminus ...
 240-413 2.40e-21

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: 90.48  E-value: 2.40e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 847087110 240 EPAFWCSIAYYELNQRVGETFHASQPSLtvDGFTDPSNSERFCLGLLSNVNRNATVEMTRRHIGRGVRLYYIGGEVFAEC 319
Cdd:cd10500    4 DQSHWCVVAYWEEKTRVGRLYSVQEPSL--DIFYDLPQGNGFCLGQLNSDNKSQLVQKVRSKIGYGIQLTREVDGVWVYN 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 847087110 320 LSDSAIFVQSPNCNQRYGwHPATVCKIPPGCNLKIFNNQEFAALlaQSVNQgFEAVYQLTRMCTIRMSFVKGWGAEYRRQ 399
Cdd:cd10500   82 RSSYPIFIKSATLDNPDS-RTLLVHKVFPGFSIKAFDYEKAYSL--QRPND-HEFMQQPWTGFTVQISFVKGWGQCYTRQ 157

                        170
                 ....*....|....
gi 847087110 400 TVTSTPCWIELHLN 413
Cdd:cd10500  158 FISSCPCWLEVIFN 171
MH1_SMAD_6 cd10493
N-terminal Mad Homology 1 (MH1) domain in SMAD6; The MH1 is a small DNA-binding domain present ...
 56-144 6.98e-13

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: 64.79  E-value: 6.98e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 847087110  56 GQLDELEKAITTQN-CNTKCVTIPRSldgRLQVSHRKGLPHVIYCRLWRWPDLHSHHELKAIENCEYAFNLKKDEVCVNP 134
Cdd:cd10493   27 RSLDVLLEAVESRGgLPSGCVMVPRT---ELRLGGRRVPPQLLLCRLFRWPDLQHPAQLKALCHCQSFGAQDGPTVCCNP 103

                         90
                 ....*....|
gi 847087110 135 YHYQRVETPV 144
Cdd:cd10493  104 YHYSRLCGPE 113
MH1_SMAD_6_7 cd10489
N-terminal Mad Homology 1 (MH1) domain in SMAD6 and SMAD7; The MH1 is a small DNA-binding ...
 57-140 7.48e-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: 65.10  E-value: 7.48e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 847087110  57 QLDELEKAITTQNCN-TKCVTIPRSLdgrlqVSHRKGLPHVIYCRLWRWPDLHSHHELKAIENCEYAfnLKKDEVCVNPY 135
Cdd:cd10489   38 QLELLLQAVESRGGDyLACVLLPRRD-----PRSMPQDPHVLCCQLFRWPDLRHSSELKRLPTCESA--KDPVYVCCNPY 110


                 ....*
gi 847087110 136 HYQRV 140
Cdd:cd10489  111 HWSRL 115
MH1_SMAD_7 cd10494
N-terminal Mad Homology 1 (MH1) domain in SMAD7; The MH1 is a small DNA-binding domain present ...
 57-143 8.47e-08

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: 50.65  E-value: 8.47e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 847087110  57 QLDELEKAITTQN-CNTKCVTIPRSLDGRLQvSHRKGLPhVIYCRLWRWPDLHSHHELKAIENCEYAFNLKKDEVCVNPY 135
Cdd:cd10494   35 QLEGLLQAVESRGgARTPCLLLPARLDARLG-QQSYSLP-LLLCKVFRWPDLRHSSEVKRLSCCESYGKINPELVCCNPH 112

                         90
                 ....*....|.
gi 847087110 136 HYQR---VETP 143
Cdd:cd10494  113 HLSRlceLESP 123
 
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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