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Conserved domains on  [gi|17508539|ref|NP_492321|]
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Smad protein daf-8 [Caenorhabditis elegans]

Protein Classification

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
DWB smart00524
Domain B in dwarfin family proteins;
348-522 8.79e-81

Domain B in dwarfin family proteins;


:

Pssm-ID: 197770  Cd Length: 171  Bit Score: 249.92  E-value: 8.79e-81
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17508539    348 SWLKLIYYEEGTMIGEKADVEGHHCLIDGFTasrtDSETRSRFSLGWYNNPNRSPQTAEVRGLIGKGVRFYLLAGEVYVE 427
Cdd:smart00524   1 SWCKIAYYELNTRVGETFKVSSPSVTVDGFT----DPSDGNRFCLGQLSNVNRNEATELIRKHIGKGVQLSYENGDVWLY 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17508539    428 NLCNIPVFVQSIGANMKNGFQLNTVSKLPPTGTMKVFDMRLFSKQLRTAAEKTYQDVYCLSRMCTVRVSFCKGWGEHYRR 507
Cdd:smart00524  77 NRSDSPIFVQSPYLDEPGGRTLDTVHKLPPGYSIKVFDMEKFAQLLARELAKGFEGVYDLARMCTIRISFVKGWGPDYSR 156

                          170
                   ....*....|....*
gi 17508539    508 STVLRSPVWFQAHLN 522
Cdd:smart00524 157 QTITSTPCWIEVHLN 171
DWA smart00523
Domain A in dwarfin family proteins;
32-135 1.31e-33

Domain A in dwarfin family proteins;


:

Pssm-ID: 214708  Cd Length: 109  Bit Score: 123.26  E-value: 1.31e-33
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17508539     32 GTIYWALKVT-RLLSRVAKKhqCFEAFYDAVI-KGDPKTRCCPAHnEKLIGNFGRA----IMCVL--RAFRFPVIRYESQ 103
Cdd:smart00523   1 VEEKWAKKATeSLLKKLKKK--QLEELLQAVEsKGGPPTRCVLIP-RSLDGRLQVAhrkgLPHVLycRLFRWPDLQSPHE 77

                           90       100       110
                   ....*....|....*....|....*....|..
gi 17508539    104 VKSILTCRHAFNSHSRNVCLNPYHYRWVELPT 135
Cdd:smart00523  78 LKALPTCEHAFESKSDEVCCNPYHYSRVERPE 109
 
Name Accession Description Interval E-value
DWB smart00524
Domain B in dwarfin family proteins;
348-522 8.79e-81

Domain B in dwarfin family proteins;


Pssm-ID: 197770  Cd Length: 171  Bit Score: 249.92  E-value: 8.79e-81
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17508539    348 SWLKLIYYEEGTMIGEKADVEGHHCLIDGFTasrtDSETRSRFSLGWYNNPNRSPQTAEVRGLIGKGVRFYLLAGEVYVE 427
Cdd:smart00524   1 SWCKIAYYELNTRVGETFKVSSPSVTVDGFT----DPSDGNRFCLGQLSNVNRNEATELIRKHIGKGVQLSYENGDVWLY 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17508539    428 NLCNIPVFVQSIGANMKNGFQLNTVSKLPPTGTMKVFDMRLFSKQLRTAAEKTYQDVYCLSRMCTVRVSFCKGWGEHYRR 507
Cdd:smart00524  77 NRSDSPIFVQSPYLDEPGGRTLDTVHKLPPGYSIKVFDMEKFAQLLARELAKGFEGVYDLARMCTIRISFVKGWGPDYSR 156

                          170
                   ....*....|....*
gi 17508539    508 STVLRSPVWFQAHLN 522
Cdd:smart00524 157 QTITSTPCWIEVHLN 171
MH2 pfam03166
MH2 domain; This is the MH2 (MAD homology 2) domain found at the carboxy terminus of MAD ...
 347-522 4.08e-71

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: 225.19  E-value: 4.08e-71
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17508539   347 PSWLKLIYYEEGTMIGEKADVEGHHCLIDGFTasrtDSETRSRFSLGWYNNPNRSPQTAEVRGLIGKGVRFYLLAGEVYV 426
Cdd:pfam03166   1 EIWCSVAYYELNTRVGEAFKVSSPNVTVDGFT----DPSDGNRFCLGLLSNVNRNEAVEKVRKHIGKGVRLSYDGGEVWI 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17508539   427 ENLCNIPVFVQSIGANMKNGFQLNTVSKLPPTGTMKVFDMRLFSKQLRTAAEKTYQDVYCLSRMCTVRVSFCKGWGEHYR 506
Cdd:pfam03166  77 YNLSDHPVFVQSPYLNREAGRAPDTVHKVPPGESLKVFDMRKFQQLLSQELRRARLGPQDANKLCSVRISFVKGWGPDYS 156

                         170
                  ....*....|....*.
gi 17508539   507 RSTVLRSPVWFQAHLN 522
Cdd:pfam03166 157 RQDITSTPCWIEIHLH 172
MH2_R-SMAD cd10495
C-terminal Mad Homology 2 (MH2) domain in receptor regulated SMADs; The MH2 domain is located ...
 349-533 5.56e-58

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: 191.05  E-value: 5.56e-58
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17508539 349 WLKLIYYEEGTMIGEKADVEGHHCLIDGFTASrtdSETRSRFSLGWYNNPNRSPQTAEVRGLIGKGVRFYLLAGEVYVEN 428
Cdd:cd10495   1 WCSISYYELNSRVGEQFKASNPSIIVDGFTDP---SNNSDRFCLGLLSNVNRNATIENTRRHIGRGVHLFYVGGEVYAEC 77

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17508539 429 LCNIPVFVQSIGANMKNGFQLNTVSKLPPTGTMKVFDMRLFSKQLRTAAEKTYQDVYCLSRMCTVRVSFCKGWGEHYRRS 508
Cdd:cd10495  78 LSDSAIFVQSRNCNLRHGFHPATVCKIPPGCSLKIFNNQSFAQLLEQSVNRGFEAVYELTKMCTIRISFVKGWGAEYHRQ 157

                       170       180
                ....*....|....*....|....*
gi 17508539 509 TVLRSPVWFQAHLNNPMHWVDSVLT 533
Cdd:cd10495 158 DVTSTPCWIEIHLHGPLQWLDKVLT 182
DWA smart00523
Domain A in dwarfin family proteins;
32-135 1.31e-33

Domain A in dwarfin family proteins;


Pssm-ID: 214708  Cd Length: 109  Bit Score: 123.26  E-value: 1.31e-33
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17508539     32 GTIYWALKVT-RLLSRVAKKhqCFEAFYDAVI-KGDPKTRCCPAHnEKLIGNFGRA----IMCVL--RAFRFPVIRYESQ 103
Cdd:smart00523   1 VEEKWAKKATeSLLKKLKKK--QLEELLQAVEsKGGPPTRCVLIP-RSLDGRLQVAhrkgLPHVLycRLFRWPDLQSPHE 77

                           90       100       110
                   ....*....|....*....|....*....|..
gi 17508539    104 VKSILTCRHAFNSHSRNVCLNPYHYRWVELPT 135
Cdd:smart00523  78 LKALPTCEHAFESKSDEVCCNPYHYSRVERPE 109
MH1 pfam03165
MH1 domain; The MH1 (MAD homology 1) domain is found at the amino terminus of MAD related ...
 36-132 3.80e-33

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: 121.71  E-value: 3.80e-33
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17508539    36 WALKVTRLLSRVAKKHQCFEAFYDAVI-KGDPKTRCCPAHNeKLIGNFG--------RAIMCvlRAFRFPVIRYESQVKS 106
Cdd:pfam03165   1 LKKAVESLLKKLKKKIQQLEELELAVEsRGDPPTGCVTIPR-SLDGRLQvagrkglpHVIYC--RLWRWPDLQSQHELKA 77

                          90       100
                  ....*....|....*....|....*.
gi 17508539   107 ILTCRHAFNSHSRNVCLNPYHYRWVE 132
Cdd:pfam03165  78 IPTCETAFESKKDEVCINPYHYSRVE 103
MH1_SMAD_2_3 cd10491
N-terminal Mad Homology 1 (MH1) domain in SMAD2 and SMAD3; The MH1 is a small DNA-binding ...
 29-132 7.02e-08

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: 51.38  E-value: 7.02e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17508539  29 EGDGTIYWALKVTRLLSRVAKKHQCFEAFYDAVIKGDPKTRCCP-----------AHNEKLignfGRAIMCvlRAFRFPV 97
Cdd:cd10491  15 ENGQEEKWSEKAVKSLVKKLKKTGGLDELEKAITTQNSNTKCITiprsldgrlqvSHRKGL----PHVIYC--RLWRWPD 88

                        90       100       110
                ....*....|....*....|....*....|....*
gi 17508539  98 IRYESQVKSILTCRHAFNSHSRNVCLNPYHYRWVE 132
Cdd:cd10491  89 LQSHHELRAIETCEYAFNLKKDEVCVNPYHYQRVE 123
 
Name Accession Description Interval E-value
DWB smart00524
Domain B in dwarfin family proteins;
348-522 8.79e-81

Domain B in dwarfin family proteins;


Pssm-ID: 197770  Cd Length: 171  Bit Score: 249.92  E-value: 8.79e-81
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17508539    348 SWLKLIYYEEGTMIGEKADVEGHHCLIDGFTasrtDSETRSRFSLGWYNNPNRSPQTAEVRGLIGKGVRFYLLAGEVYVE 427
Cdd:smart00524   1 SWCKIAYYELNTRVGETFKVSSPSVTVDGFT----DPSDGNRFCLGQLSNVNRNEATELIRKHIGKGVQLSYENGDVWLY 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17508539    428 NLCNIPVFVQSIGANMKNGFQLNTVSKLPPTGTMKVFDMRLFSKQLRTAAEKTYQDVYCLSRMCTVRVSFCKGWGEHYRR 507
Cdd:smart00524  77 NRSDSPIFVQSPYLDEPGGRTLDTVHKLPPGYSIKVFDMEKFAQLLARELAKGFEGVYDLARMCTIRISFVKGWGPDYSR 156

                          170
                   ....*....|....*
gi 17508539    508 STVLRSPVWFQAHLN 522
Cdd:smart00524 157 QTITSTPCWIEVHLN 171
MH2 pfam03166
MH2 domain; This is the MH2 (MAD homology 2) domain found at the carboxy terminus of MAD ...
 347-522 4.08e-71

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: 225.19  E-value: 4.08e-71
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17508539   347 PSWLKLIYYEEGTMIGEKADVEGHHCLIDGFTasrtDSETRSRFSLGWYNNPNRSPQTAEVRGLIGKGVRFYLLAGEVYV 426
Cdd:pfam03166   1 EIWCSVAYYELNTRVGEAFKVSSPNVTVDGFT----DPSDGNRFCLGLLSNVNRNEAVEKVRKHIGKGVRLSYDGGEVWI 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17508539   427 ENLCNIPVFVQSIGANMKNGFQLNTVSKLPPTGTMKVFDMRLFSKQLRTAAEKTYQDVYCLSRMCTVRVSFCKGWGEHYR 506
Cdd:pfam03166  77 YNLSDHPVFVQSPYLNREAGRAPDTVHKVPPGESLKVFDMRKFQQLLSQELRRARLGPQDANKLCSVRISFVKGWGPDYS 156

                         170
                  ....*....|....*.
gi 17508539   507 RSTVLRSPVWFQAHLN 522
Cdd:pfam03166 157 RQDITSTPCWIEIHLH 172
MH2_R-SMAD cd10495
C-terminal Mad Homology 2 (MH2) domain in receptor regulated SMADs; The MH2 domain is located ...
 349-533 5.56e-58

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: 191.05  E-value: 5.56e-58
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17508539 349 WLKLIYYEEGTMIGEKADVEGHHCLIDGFTASrtdSETRSRFSLGWYNNPNRSPQTAEVRGLIGKGVRFYLLAGEVYVEN 428
Cdd:cd10495   1 WCSISYYELNSRVGEQFKASNPSIIVDGFTDP---SNNSDRFCLGLLSNVNRNATIENTRRHIGRGVHLFYVGGEVYAEC 77

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17508539 429 LCNIPVFVQSIGANMKNGFQLNTVSKLPPTGTMKVFDMRLFSKQLRTAAEKTYQDVYCLSRMCTVRVSFCKGWGEHYRRS 508
Cdd:cd10495  78 LSDSAIFVQSRNCNLRHGFHPATVCKIPPGCSLKIFNNQSFAQLLEQSVNRGFEAVYELTKMCTIRISFVKGWGAEYHRQ 157

                       170       180
                ....*....|....*....|....*
gi 17508539 509 TVLRSPVWFQAHLNNPMHWVDSVLT 533
Cdd:cd10495 158 DVTSTPCWIEIHLHGPLQWLDKVLT 182
MH2_SMAD_2_3 cd10985
C-terminal Mad Homology 2 (MH2) domain in SMAD2 and SMAD3; The MH2 domain is located at the ...
 341-535 8.81e-55

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: 183.21  E-value: 8.81e-55
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17508539 341 VEYEESPSWLKLIYYEEGTMIGEKADVEGHHCLIDGFTasrtDSETRSRFSLGWYNNPNRSPQTAEVRGLIGKGVRFYLL 420
Cdd:cd10985   1 VTYCEPAFWCSISYYEMNTRVGETFHASQPSLTVDGFT----DPSNSERFCLGLLSNVNRNPQVELTRRHIGKGVRLYYI 76

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17508539 421 AGEVYVENLCNIPVFVQSIGANMKNGFQLNTVSKLPPTGTMKVFDMRLFSKQLRTAAEKTYQDVYCLSRMCTVRVSFCKG 500
Cdd:cd10985  77 GGEVFAECLSDSAIFVQSPNCNQRYGWHPATVCKIPPGCNLKIFNNQEFAALLSQSVNQGFEAVYQLTRMCTIRMSFVKG 156

                       170       180       190
                ....*....|....*....|....*....|....*
gi 17508539 501 WGEHYRRSTVLRSPVWFQAHLNNPMHWVDSVLTCM 535
Cdd:cd10985 157 WGAEYRRQTVTSTPCWIELHLNGPLQWLDRVLTQM 191
MH2_SMAD_1_5_9 cd10497
C-terminal Mad Homology 2 (MH2) domain in SMAD1, SMAD5 and SMAD9; The MH2 domain is located at ...
 343-544 5.95e-52

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: 175.84  E-value: 5.95e-52
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17508539 343 YEESPSWLKLIYYEEGTMIGEKADVEGHHCLIDGFTASRTDSEtrsRFSLGWYNNPNRSPQTAEVRGLIGKGVRFYLLAG 422
Cdd:cd10497   1 YQEPKYWCSIAYYELNNRVGEAFHASSTSIIVDGFTDPSNNSD---RFCLGLLSNVNRNSTIENTRRHIGKGVHLYYVGG 77

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17508539 423 EVYVENLCNIPVFVQSIGANMKNGFQLNTVSKLPPTGTMKVFDMRLFSKQLRTAAEKTYQDVYCLSRMCTVRVSFCKGWG 502
Cdd:cd10497  78 EVYAECLSDSSIFVQSRNCNYHHGFHPTTVCKIPPGCSLKIFNNQEFAQLLSQSVNHGFEAVYELTKMCTIRMSFVKGWG 157

                       170       180       190       200
                ....*....|....*....|....*....|....*....|..
gi 17508539 503 EHYRRSTVLRSPVWFQAHLNNPMHWVDSVLTCMGAPPRICSS 544
Cdd:cd10497 158 AEYHRQDVTSTPCWIEIHLHGPLQWLDKVLTQMGSPHNPISS 199
MH2 cd00050
C-terminal Mad Homology 2 (MH2) domain; The MH2 domain is found in the SMAD (small mothers ...
 349-522 1.15e-40

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: 144.67  E-value: 1.15e-40
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17508539 349 WLKLIYYEEGTMIGEKADVEGHHCLIDGFTasrtDSETRSRFSLGWYNNPNRSPQTAEVRGLIGKGVRFYLLAGEVYVEN 428
Cdd:cd00050   1 WCSIAYYELNTRVGELFHVYSPSVAVDGFT----DPSNGDRFCLGQLSNVNRNETIERTRRHIGKGVHLYYVGGEVWAEC 76

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17508539 429 LCNIPVFVQSIGANMKNGFQLNTVSKLPPTGTMKVFDMRLFSKQLRTAAEKTYQDVYCLSRMCTVRVSFCKGWGEHYRRS 508
Cdd:cd00050  77 LSDHAIFVQSRNLDYPHGRHPLTVCKIPPGCSIKVFDNQEFAQLLHQSVNTGFEGVYELTKMCTIRMSFVKGWGPEYHRQ 156

                       170
                ....*....|....
gi 17508539 509 TVLRSPVWFQAHLN 522
Cdd:cd00050 157 DITSTPCWIEIHLH 170
DWA smart00523
Domain A in dwarfin family proteins;
32-135 1.31e-33

Domain A in dwarfin family proteins;


Pssm-ID: 214708  Cd Length: 109  Bit Score: 123.26  E-value: 1.31e-33
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17508539     32 GTIYWALKVT-RLLSRVAKKhqCFEAFYDAVI-KGDPKTRCCPAHnEKLIGNFGRA----IMCVL--RAFRFPVIRYESQ 103
Cdd:smart00523   1 VEEKWAKKATeSLLKKLKKK--QLEELLQAVEsKGGPPTRCVLIP-RSLDGRLQVAhrkgLPHVLycRLFRWPDLQSPHE 77

                           90       100       110
                   ....*....|....*....|....*....|..
gi 17508539    104 VKSILTCRHAFNSHSRNVCLNPYHYRWVELPT 135
Cdd:smart00523  78 LKALPTCEHAFESKSDEVCCNPYHYSRVERPE 109
MH1 pfam03165
MH1 domain; The MH1 (MAD homology 1) domain is found at the amino terminus of MAD related ...
 36-132 3.80e-33

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: 121.71  E-value: 3.80e-33
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17508539    36 WALKVTRLLSRVAKKHQCFEAFYDAVI-KGDPKTRCCPAHNeKLIGNFG--------RAIMCvlRAFRFPVIRYESQVKS 106
Cdd:pfam03165   1 LKKAVESLLKKLKKKIQQLEELELAVEsRGDPPTGCVTIPR-SLDGRLQvagrkglpHVIYC--RLWRWPDLQSQHELKA 77

                          90       100
                  ....*....|....*....|....*.
gi 17508539   107 ILTCRHAFNSHSRNVCLNPYHYRWVE 132
Cdd:pfam03165  78 IPTCETAFESKKDEVCINPYHYSRVE 103
MH2_SMAD_4 cd10498
C-terminal Mad Homology 2 (MH2) domain in SMAD4; The MH2 domain is located at the C-terminus ...
 349-532 7.97e-23

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: 96.77  E-value: 7.97e-23
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17508539 349 WLKLIYYEEGTMIGE--KADVEGHHCLIDGFTasrtDSETRSRFSLGWYNNPNRSPQTAEVRGLIGKGVRFYLLA-GEVY 425
Cdd:cd10498   4 WCSIAYFELDTQVGEtfKVPSSCPTVTVDGYV----DPSGGNRFCLGQLSNVHRTEASERARLHIGKGVQLDCKGeGDVW 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17508539 426 VENLCNIPVFVQSIGANMKNGFQL-NTVSKLPPTGTMKVFDMRLFSKQLRTAAEKTYQ---------------------- 482
Cdd:cd10498  80 LRCLSDHSVFVQSYYLDREAGRAPgDAVHKIYPSAYIKVFDLRQCHRQMQQQAATAQAaaaaqaaavagnipgpgsvggi 159

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 17508539 483 ------------DVYCLSRMCTVRVSFCKGWGEHYRRSTVLRSPVWFQAHLNNPMHWVDSVL 532
Cdd:cd10498 160 apaislsaaagiGVDDLRRLCILRMSFVKGWGPDYPRQSIKETPCWIEIHLHRALQLLDEVL 221
MH2_SMAD_6 cd10499
C-terminal Mad Homology 2 (MH2) domain in SMAD6; The MH2 domain is located at the C-terminus ...
 349-523 2.80e-15

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: 73.70  E-value: 2.80e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17508539 349 WLKLIYYEEGTMIGEKADVeghhclidgFTASRT---DSETRSRFSLGWYNNPNRSPQTAEVRGLIGKGVrfyLLAGE-- 423
Cdd:cd10499  10 WCSVAYWEHRTRVGRLYAV---------YDQSVSifyDLPQGSGFCLGQLNLEQRSESVRRTRSKIGYGI---LLSKEpd 77

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17508539 424 -VYVENLCNIPVFVQSIGANMKNGFQLnTVSKLPPTGTMKVFDMRLfSKQLRTAAEKTYQD-VYCLSrmcTVRVSFCKGW 501
Cdd:cd10499  78 gVWAYNRSEHPIFVNSPTLDIPGSRTL-VVRKVPPGYSIKVFDYER-SCLLQHTAEPELADgPYDPN---SVRISFAKGW 152

                       170       180
                ....*....|....*....|..
gi 17508539 502 GEHYRRSTVLRSPVWFQAHLNN 523
Cdd:cd10499 153 GPCYSRQFITSCPCWLEILLNN 174
MH2_I-SMAD cd10496
C-terminal Mad Homology 2 (MH2) domain in Inhibitory SMADs; The MH2 domain is located at the ...
 349-522 5.15e-15

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: 72.77  E-value: 5.15e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17508539 349 WLKLIYYEEGTMIGEKADVegHHCLIDGFTasrtDSETRSRFSLGWYN-NPNRSPQTAEVRGLIGKGVRFYLLAGEVYVE 427
Cdd:cd10496   1 WCTIAYWELRERVGRLYPV--KQPAVNIFD----DLPKGDGFCLGALNrQGNASEAVARVRSKIGLGVTLSREPDGVWIY 74

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17508539 428 NLCNIPVFVQSIGANMKNGFQLnTVSKLPPTGTMKVFDMRLFSKQLRTAAEKTYQ---DVYclsrmcTVRVSFCKGWGEH 504
Cdd:cd10496  75 NRSEYPIFVNSPTLDSPPSRNL-LVTKVPPGYSLKVFDYERAALLQRRDDHFSPQgpvDPN------SVRISFVKGWGPN 147

                       170
                ....*....|....*...
gi 17508539 505 YRRSTVLRSPVWFQAHLN 522
Cdd:cd10496 148 YSRQFITSCPCWLEILLN 165
MH2_SMAD_7 cd10500
C-terminal Mad Homology 2 (MH2) domain in SMAD7; The MH2 domain is located at the C-terminus ...
 342-522 2.48e-11

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: 62.36  E-value: 2.48e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17508539 342 EYEESPSWLKLIYYEEGTMIGEKADVEGHHclIDGFTasrtDSETRSRFSLGWYNNPNRSPQTAEVRGLIGKGVRFYLLA 421
Cdd:cd10500   1 ERGDQSHWCVVAYWEEKTRVGRLYSVQEPS--LDIFY----DLPQGNGFCLGQLNSDNKSQLVQKVRSKIGYGIQLTREV 74

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17508539 422 GEVYVENLCNIPVFVQSIGANMKNGFQLnTVSKLPPTGTMKVFDM-RLFSKQLRTAAEKTYQDVYCLsrmcTVRVSFCKG 500
Cdd:cd10500  75 DGVWVYNRSSYPIFIKSATLDNPDSRTL-LVHKVFPGFSIKAFDYeKAYSLQRPNDHEFMQQPWTGF----TVQISFVKG 149

                       170       180
                ....*....|....*....|..
gi 17508539 501 WGEHYRRSTVLRSPVWFQAHLN 522
Cdd:cd10500 150 WGQCYTRQFISSCPCWLEVIFN 171
MH1_SMAD_2_3 cd10491
N-terminal Mad Homology 1 (MH1) domain in SMAD2 and SMAD3; The MH1 is a small DNA-binding ...
 29-132 7.02e-08

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: 51.38  E-value: 7.02e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17508539  29 EGDGTIYWALKVTRLLSRVAKKHQCFEAFYDAVIKGDPKTRCCP-----------AHNEKLignfGRAIMCvlRAFRFPV 97
Cdd:cd10491  15 ENGQEEKWSEKAVKSLVKKLKKTGGLDELEKAITTQNSNTKCITiprsldgrlqvSHRKGL----PHVIYC--RLWRWPD 88

                        90       100       110
                ....*....|....*....|....*....|....*
gi 17508539  98 IRYESQVKSILTCRHAFNSHSRNVCLNPYHYRWVE 132
Cdd:cd10491  89 LQSHHELRAIETCEYAFNLKKDEVCVNPYHYQRVE 123
MH1_R-SMAD cd10488
N-terminal Mad Homology 1 (MH1) domain of receptor regulated SMADs; The MH1 is a small ...
 36-133 8.99e-07

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: 47.95  E-value: 8.99e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17508539  36 WALKVTRLLSRVAKKHQCFEAFYDAVIKGDPKTRCC--PAHNEKLIGNFGRA-----IMCvlRAFRFPVIRYESQVKSIL 108
Cdd:cd10488  21 WAEKAVKSLVKKLKKKGQLEELEKAISTQNVNTRCVtiPRSLDGRLQVSHRKglphvIYC--RLWRWPDLQSHHELKPLE 98

                        90       100
                ....*....|....*....|....*
gi 17508539 109 TCRHAFNSHSRNVCLNPYHYRWVEL 133
Cdd:cd10488  99 LCEFAFNMKKEEVCINPYHYKRVET 123
MH1_SMAD_1_5_9 cd10490
N-terminal Mad Homology 1 (MH1) domain in SMAD1, SMAD5 and SMAD9 (also known as SMAD8); The ...
 29-132 1.81e-06

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: 47.11  E-value: 1.81e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17508539  29 EGDGTIYWALK-VTRLLSRVAKKHQCFEAFYDAVIKGDPKTRCCP-----------AHNEKLignfGRAIMCvlRAFRFP 96
Cdd:cd10490  14 QGDEEEKWAEKaVDSLVKKLKKKKGALEELEKALSCPGQPSKCVTiprsldgrlqvSHRKGL----PHVIYC--RVWRWP 87

                        90       100       110
                ....*....|....*....|....*....|....*.
gi 17508539  97 VIRYESQVKSILTCRHAFNSHSRNVCLNPYHYRWVE 132
Cdd:cd10490  88 DLQSHHELKPLECCEFPFGSKQKEVCINPYHYKRVE 123
MH1 cd00049
N-terminal Mad Homology 1 (MH1) domain; The MH1 is a small DNA-binding domain present in SMAD ...
 36-132 1.24e-05

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: 44.50  E-value: 1.24e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17508539  36 WALKVTRLLSRVAKKHQCFEAFYDAV-IKGDPKTRCC--PAHNEKLIGNFGR-----AIMCvlRAFRFPVIRYESQVKSI 107
Cdd:cd00049  18 WAKKAVKSLVKKLKEKKQLDSLEKAItTQGGVPSKCVtiPRSLDGRLQVAHRkglphVIYC--RLWRWPDLHSHHELKAL 95

                        90       100
                ....*....|....*....|....*
gi 17508539 108 LTCRHAFNSHSRNVCLNPYHYRWVE 132
Cdd:cd00049  96 ELCQFAFNMKKDEVCVNPYHYQRVE 120
MH1_SMAD_4 cd10492
N-terminal Mad Homology 1 (MH1) domain in SMAD4; The MH1 is a small DNA-binding domain present ...
 91-128 1.48e-05

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: 44.37  E-value: 1.48e-05
                        10        20        30
                ....*....|....*....|....*....|....*...
gi 17508539  91 RAFRFPVIrYESQVKSILTCRHAFNSHSRNVCLNPYHY 128
Cdd:cd10492  84 RIWRWPDL-HKNELKHVKFCQYAFDLKCDSVCVNPYHY 120
 
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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