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Conserved domains on  [gi|160858175|emb|CAP20377|]
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SMAD family member 6 [Homo sapiens]

Protein Classification

mothers against decapentaplegic homolog; mothers against decapentaplegic homolog 4 family protein( domain architecture ID 10180369)

mothers against decapentaplegic homolog such as SMAD1, SMAD5 and SMAD9 (also known as SMAD8); 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| mothers against decapentaplegic homolog 4 family protein such as 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)

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
MH1_SMAD_6 cd10493
N-terminal Mad Homology 1 (MH1) domain in SMAD6; The MH1 is a small DNA-binding domain present ...
 160-273 4.16e-63

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: 196.14  E-value: 4.16e-63
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160858175 160 EARSRLLLLEQELKTVTYSLLKRLKERSLDTLLEAVESRGGVPGGCVLVPRADLRLGGQPAPPQLLLGRLFRWPDLQHAV 239
Cdd:cd10493    1 EGKSRQVALEQELKSVTYALLKRLKERSLDVLLEAVESRGGLPSGCVMVPRTELRLGGRRVPPQLLLCRLFRWPDLQHPA 80

                         90       100       110
                 ....*....|....*....|....*....|....
gi 160858175 240 ELKPLCGCHSFaAAADGPTVCCNPYHFSRLCGPE 273
Cdd:cd10493   81 QLKALCHCQSF-GAQDGPTVCCNPYHYSRLCGPE 113
 
Name Accession Description Interval E-value
MH1_SMAD_6 cd10493
N-terminal Mad Homology 1 (MH1) domain in SMAD6; The MH1 is a small DNA-binding domain present ...
 160-273 4.16e-63

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: 196.14  E-value: 4.16e-63
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160858175 160 EARSRLLLLEQELKTVTYSLLKRLKERSLDTLLEAVESRGGVPGGCVLVPRADLRLGGQPAPPQLLLGRLFRWPDLQHAV 239
Cdd:cd10493    1 EGKSRQVALEQELKSVTYALLKRLKERSLDVLLEAVESRGGLPSGCVMVPRTELRLGGRRVPPQLLLCRLFRWPDLQHPA 80

                         90       100       110
                 ....*....|....*....|....*....|....
gi 160858175 240 ELKPLCGCHSFaAAADGPTVCCNPYHFSRLCGPE 273
Cdd:cd10493   81 QLKALCHCQSF-GAQDGPTVCCNPYHYSRLCGPE 113
DWA smart00523
Domain A in dwarfin family proteins;
169-273 2.28e-44

Domain A in dwarfin family proteins;


Pssm-ID: 214708  Cd Length: 109  Bit Score: 147.91  E-value: 2.28e-44
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160858175   169 EQELKTVTYSLLKRLKERSLDTLLEAVESRGGVPGGCVLVPR-ADLRLG--GQPAPPQLLLGRLFRWPDLQHAVELKPLC 245
Cdd:smart00523   3 EKWAKKATESLLKKLKKKQLEELLQAVESKGGPPTRCVLIPRsLDGRLQvaHRKGLPHVLYCRLFRWPDLQSPHELKALP 82

                           90       100
                   ....*....|....*....|....*...
gi 160858175   246 GCHSfAAAADGPTVCCNPYHFSRLCGPE 273
Cdd:smart00523  83 TCEH-AFESKSDEVCCNPYHYSRVERPE 109
MH1 pfam03165
MH1 domain; The MH1 (MAD homology 1) domain is found at the amino terminus of MAD related ...
 172-270 1.51e-38

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: 132.50  E-value: 1.51e-38
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160858175  172 LKTVTYSLLKRLKERS--LDTLLEAVESRGGVPGGCVLVPRA-DLRLG--GQPAPPQLLLGRLFRWPDLQHAVELKPLCG 246
Cdd:pfam03165   1 LKKAVESLLKKLKKKIqqLEELELAVESRGDPPTGCVTIPRSlDGRLQvaGRKGLPHVIYCRLWRWPDLQSQHELKAIPT 80

                          90       100
                  ....*....|....*....|....
gi 160858175  247 ChSFAAAADGPTVCCNPYHFSRLC 270
Cdd:pfam03165  81 C-ETAFESKKDEVCINPYHYSRVE 103
 
Name Accession Description Interval E-value
MH1_SMAD_6 cd10493
N-terminal Mad Homology 1 (MH1) domain in SMAD6; The MH1 is a small DNA-binding domain present ...
 160-273 4.16e-63

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: 196.14  E-value: 4.16e-63
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160858175 160 EARSRLLLLEQELKTVTYSLLKRLKERSLDTLLEAVESRGGVPGGCVLVPRADLRLGGQPAPPQLLLGRLFRWPDLQHAV 239
Cdd:cd10493    1 EGKSRQVALEQELKSVTYALLKRLKERSLDVLLEAVESRGGLPSGCVMVPRTELRLGGRRVPPQLLLCRLFRWPDLQHPA 80

                         90       100       110
                 ....*....|....*....|....*....|....
gi 160858175 240 ELKPLCGCHSFaAAADGPTVCCNPYHFSRLCGPE 273
Cdd:cd10493   81 QLKALCHCQSF-GAQDGPTVCCNPYHYSRLCGPE 113
DWA smart00523
Domain A in dwarfin family proteins;
169-273 2.28e-44

Domain A in dwarfin family proteins;


Pssm-ID: 214708  Cd Length: 109  Bit Score: 147.91  E-value: 2.28e-44
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160858175   169 EQELKTVTYSLLKRLKERSLDTLLEAVESRGGVPGGCVLVPR-ADLRLG--GQPAPPQLLLGRLFRWPDLQHAVELKPLC 245
Cdd:smart00523   3 EKWAKKATESLLKKLKKKQLEELLQAVESKGGPPTRCVLIPRsLDGRLQvaHRKGLPHVLYCRLFRWPDLQSPHELKALP 82

                           90       100
                   ....*....|....*....|....*...
gi 160858175   246 GCHSfAAAADGPTVCCNPYHFSRLCGPE 273
Cdd:smart00523  83 TCEH-AFESKSDEVCCNPYHYSRVERPE 109
MH1_SMAD_6_7 cd10489
N-terminal Mad Homology 1 (MH1) domain in SMAD6 and SMAD7; The MH1 is a small DNA-binding ...
 157-273 3.72e-42

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: 142.52  E-value: 3.72e-42
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160858175 157 RSREARSRLLLLEQELKTVTYSLLKRLKERSLDTLLEAVESRGGVPGGCVLVPRADLRlgGQPAPPQLLLGRLFRWPDLQ 236
Cdd:cd10489    8 AHRTRHSQNPLEERDLRAAFHALLKRLKEKQLELLLQAVESRGGDYLACVLLPRRDPR--SMPQDPHVLCCQLFRWPDLR 85

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 160858175 237 HAVELKPLCGCHSfaaAADGPTVCCNPYHFSRLCGPE 273
Cdd:cd10489   86 HSSELKRLPTCES---AKDPVYVCCNPYHWSRLCRPE 119
MH1 cd00049
N-terminal Mad Homology 1 (MH1) domain; The MH1 is a small DNA-binding domain present in SMAD ...
 160-271 6.60e-42

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: 141.96  E-value: 6.60e-42
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160858175 160 EARSRLLL------LEQELKTVTYSLLKRLKER-SLDTLLEAVESRGGVPGGCVLVPRA-DLRLG--GQPAPPQLLLGRL 229
Cdd:cd00049    1 PIVKRLLGwkqggeEEKWAKKAVKSLVKKLKEKkQLDSLEKAITTQGGVPSKCVTIPRSlDGRLQvaHRKGLPHVIYCRL 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 160858175 230 FRWPDLQHAVELKPLCGCHsFAAAADGPTVCCNPYHFSRLCG 271
Cdd:cd00049   81 WRWPDLHSHHELKALELCQ-FAFNMKKDEVCVNPYHYQRVES 121
MH1 pfam03165
MH1 domain; The MH1 (MAD homology 1) domain is found at the amino terminus of MAD related ...
 172-270 1.51e-38

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: 132.50  E-value: 1.51e-38
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160858175  172 LKTVTYSLLKRLKERS--LDTLLEAVESRGGVPGGCVLVPRA-DLRLG--GQPAPPQLLLGRLFRWPDLQHAVELKPLCG 246
Cdd:pfam03165   1 LKKAVESLLKKLKKKIqqLEELELAVESRGDPPTGCVTIPRSlDGRLQvaGRKGLPHVIYCRLWRWPDLQSQHELKAIPT 80

                          90       100
                  ....*....|....*....|....
gi 160858175  247 ChSFAAAADGPTVCCNPYHFSRLC 270
Cdd:pfam03165  81 C-ETAFESKKDEVCINPYHYSRVE 103
MH1_SMAD_7 cd10494
N-terminal Mad Homology 1 (MH1) domain in SMAD7; The MH1 is a small DNA-binding domain present ...
 169-275 4.89e-29

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: 108.43  E-value: 4.89e-29
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160858175 169 EQELKTVTYSLLKRLKERSLDTLLEAVESRGGVPGGCVLVP-RADLRLGGQPAPPQLLLGRLFRWPDLQHAVELKPLCGC 247
Cdd:cd10494   17 EAELKALTHSVLKKLKERQLEGLLQAVESRGGARTPCLLLPaRLDARLGQQSYSLPLLLCKVFRWPDLRHSSEVKRLSCC 96

                         90       100
                 ....*....|....*....|....*...
gi 160858175 248 HSFaAAADGPTVCCNPYHFSRLCGPESP 275
Cdd:cd10494   97 ESY-GKINPELVCCNPHHLSRLCELESP 123
MH1_SMAD_4 cd10492
N-terminal Mad Homology 1 (MH1) domain in SMAD4; The MH1 is a small DNA-binding domain present ...
 178-268 1.01e-17

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: 77.88  E-value: 1.01e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160858175 178 SLLKRLKER--SLDTLLEAVESRGGVPGGCVLVPRA-DLRL--GGQPAPPQLLLGRLFRWPDLqHAVELKPLCGC-HSFA 251
Cdd:cd10492   29 SLVKKLKDKrdELDSLITAITSNGAHPSKCVTIQRTlDGRLqvAGRKGFPHVIYARIWRWPDL-HKNELKHVKFCqYAFD 107

                         90
                 ....*....|....*..
gi 160858175 252 AAADgpTVCCNPYHFSR 268
Cdd:cd10492  108 LKCD--SVCVNPYHYER 122
MH1_R-SMAD cd10488
N-terminal Mad Homology 1 (MH1) domain of receptor regulated SMADs; The MH1 is a small ...
 169-269 2.96e-14

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: 68.37  E-value: 2.96e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160858175 169 EQELKtvtySLLKRLKERSLDTLLEAVESRGGVPGGCVLVPRA-DLRLG--GQPAPPQLLLGRLFRWPDLQHAVELKPLC 245
Cdd:cd10488   23 EKAVK----SLVKKLKKKGQLEELEKAISTQNVNTRCVTIPRSlDGRLQvsHRKGLPHVIYCRLWRWPDLQSHHELKPLE 98

                         90       100
                 ....*....|....*....|....
gi 160858175 246 GCHsFAAAADGPTVCCNPYHFSRL 269
Cdd:cd10488   99 LCE-FAFNMKKEEVCINPYHYKRV 121
MH1_SMAD_1_5_9 cd10490
N-terminal Mad Homology 1 (MH1) domain in SMAD1, SMAD5 and SMAD9 (also known as SMAD8); The ...
 178-269 4.89e-13

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: 65.22  E-value: 4.89e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160858175 178 SLLKRLKER--SLDTLLEAVeSRGGVPGGCVLVPRA---DLRLGGQPAPPQLLLGRLFRWPDLQHAVELKPLCGChSFAA 252
Cdd:cd10490   28 SLVKKLKKKkgALEELEKAL-SCPGQPSKCVTIPRSldgRLQVSHRKGLPHVIYCRVWRWPDLQSHHELKPLECC-EFPF 105

                         90
                 ....*....|....*..
gi 160858175 253 AADGPTVCCNPYHFSRL 269
Cdd:cd10490  106 GSKQKEVCINPYHYKRV 122
MH1_SMAD_2_3 cd10491
N-terminal Mad Homology 1 (MH1) domain in SMAD2 and SMAD3; The MH1 is a small DNA-binding ...
 178-269 9.65e-12

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: 61.39  E-value: 9.65e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160858175 178 SLLKRLKER-SLDTLLEAVESRGgVPGGCVLVPRA---DLRLGGQPAPPQLLLGRLFRWPDLQHAVELKPLCGCHsFAAA 253
Cdd:cd10491   29 SLVKKLKKTgGLDELEKAITTQN-SNTKCITIPRSldgRLQVSHRKGLPHVIYCRLWRWPDLQSHHELRAIETCE-YAFN 106

                         90
                 ....*....|....*.
gi 160858175 254 ADGPTVCCNPYHFSRL 269
Cdd:cd10491  107 LKKDEVCVNPYHYQRV 122
 
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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