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Conserved domains on  [gi|17137382|ref|NP_477260|]
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daughters against dpp, isoform A [Drosophila melanogaster]

Protein Classification

mothers against decapentaplegic homolog; mothers against decapentaplegic homolog 4 family protein( domain architecture ID 10180322)

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
MH2_I-SMAD cd10496
C-terminal Mad Homology 2 (MH2) domain in Inhibitory SMADs; The MH2 domain is located at the ...
 400-565 1.09e-89

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: 273.46  E-value: 1.09e-89
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17137382 400 WCQIAYWEMAHRVGEFFHAKTNAVNIYTDGIvasEVDSMCLRDLTPAGNqIHSVVPKARHTVGLGVTLSLENGDVWIYNR 479
Cdd:cd10496   1 WCTIAYWELRERVGRLYPVKQPAVNIFDDLP---KGDGFCLGALNRQGN-ASEAVARVRSKIGLGVTLSREPDGVWIYNR 76

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17137382 480 GNTTIFVDSPTLSENLDR---VCKVMPGYCLKAFETNRAELLSMRDHGHHPMGPVDYFSIKISFGKGWGRDYKRQDIMGC 556
Cdd:cd10496  77 SEYPIFVNSPTLDSPPSRnllVTKVPPGYSLKVFDYERAALLQRRDDHFSPQGPVDPNSVRISFVKGWGPNYSRQFITSC 156


                ....*....
gi 17137382 557 PCWLEVHFS 565
Cdd:cd10496 157 PCWLEILLN 165
MH1_SMAD_6_7 cd10489
N-terminal Mad Homology 1 (MH1) domain in SMAD6 and SMAD7; The MH1 is a small DNA-binding ...
 197-329 3.45e-40

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: 141.75  E-value: 3.45e-40
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17137382 197 VSTSRATAHPPQ--TQAQNGKRFREDFEALMKQLKRKQRNELLLAVKSRLDPptktqrdvvepttttaptYLQCILIPCK 274
Cdd:cd10489   1 GAVRRLWAHRTRhsQNPLEERDLRAAFHALLKRLKEKQLELLLQAVESRGGD------------------YLACVLLPRR 62

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 17137382 275 TQT--VWEPHVTASRLFFWRELWNAKELKRLPTCPAARDCIYMCCNPLHWFRILHQP 329
Cdd:cd10489  63 DPRsmPQDPHVLCCQLFRWPDLRHSSELKRLPTCESAKDPVYVCCNPYHWSRLCRPE 119
 
Name Accession Description Interval E-value
MH2_I-SMAD cd10496
C-terminal Mad Homology 2 (MH2) domain in Inhibitory SMADs; The MH2 domain is located at the ...
 400-565 1.09e-89

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: 273.46  E-value: 1.09e-89
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17137382 400 WCQIAYWEMAHRVGEFFHAKTNAVNIYTDGIvasEVDSMCLRDLTPAGNqIHSVVPKARHTVGLGVTLSLENGDVWIYNR 479
Cdd:cd10496   1 WCTIAYWELRERVGRLYPVKQPAVNIFDDLP---KGDGFCLGALNRQGN-ASEAVARVRSKIGLGVTLSREPDGVWIYNR 76

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17137382 480 GNTTIFVDSPTLSENLDR---VCKVMPGYCLKAFETNRAELLSMRDHGHHPMGPVDYFSIKISFGKGWGRDYKRQDIMGC 556
Cdd:cd10496  77 SEYPIFVNSPTLDSPPSRnllVTKVPPGYSLKVFDYERAALLQRRDDHFSPQGPVDPNSVRISFVKGWGPNYSRQFITSC 156


                ....*....
gi 17137382 557 PCWLEVHFS 565
Cdd:cd10496 157 PCWLEILLN 165
DWB smart00524
Domain B in dwarfin family proteins;
400-565 8.34e-70

Domain B in dwarfin family proteins;


Pssm-ID: 197770  Cd Length: 171  Bit Score: 222.18  E-value: 8.34e-70
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17137382    400 WCQIAYWEMAHRVGEFFHAKTN--AVNIYTDGivaSEVDSMCLRDLTPAgnQIHSVVPKARHTVGLGVTLSLENGDVWIY 477
Cdd:smart00524   2 WCKIAYYELNTRVGETFKVSSPsvTVDGFTDP---SDGNRFCLGQLSNV--NRNEATELIRKHIGKGVQLSYENGDVWLY 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17137382    478 NRGNTTIFVDSPTLSE----NLDRVCKVMPGYCLKAFETNRAELLSMRDHGHHPMGPVDYF---SIKISFGKGWGRDYKR 550
Cdd:smart00524  77 NRSDSPIFVQSPYLDEpggrTLDTVHKLPPGYSIKVFDMEKFAQLLARELAKGFEGVYDLArmcTIRISFVKGWGPDYSR 156

                          170
                   ....*....|....*
gi 17137382    551 QDIMGCPCWLEVHFS 565
Cdd:smart00524 157 QTITSTPCWIEVHLN 171
MH2 pfam03166
MH2 domain; This is the MH2 (MAD homology 2) domain found at the carboxy terminus of MAD ...
 398-564 1.25e-64

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: 208.63  E-value: 1.25e-64
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17137382   398 QVWCQIAYWEMAHRVGEFFHAKTNavNIYTDGIVA-SEVDSMCLRDLT-PAGNQIhsvVPKARHTVGLGVTLSLENGDVW 475
Cdd:pfam03166   1 EIWCSVAYYELNTRVGEAFKVSSP--NVTVDGFTDpSDGNRFCLGLLSnVNRNEA---VEKVRKHIGKGVRLSYDGGEVW 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17137382   476 IYNRGNTTIFVDSPTL----SENLDRVCKVMPGYCLKAFETNRAELLSMRDHGHHPMGPVD---YFSIKISFGKGWGRDY 548
Cdd:pfam03166  76 IYNLSDHPVFVQSPYLnreaGRAPDTVHKVPPGESLKVFDMRKFQQLLSQELRRARLGPQDankLCSVRISFVKGWGPDY 155

                         170
                  ....*....|....*.
gi 17137382   549 KRQDIMGCPCWLEVHF 564
Cdd:pfam03166 156 SRQDITSTPCWIEIHL 171
MH1_SMAD_6_7 cd10489
N-terminal Mad Homology 1 (MH1) domain in SMAD6 and SMAD7; The MH1 is a small DNA-binding ...
 197-329 3.45e-40

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: 141.75  E-value: 3.45e-40
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17137382 197 VSTSRATAHPPQ--TQAQNGKRFREDFEALMKQLKRKQRNELLLAVKSRLDPptktqrdvvepttttaptYLQCILIPCK 274
Cdd:cd10489   1 GAVRRLWAHRTRhsQNPLEERDLRAAFHALLKRLKEKQLELLLQAVESRGGD------------------YLACVLLPRR 62

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 17137382 275 TQT--VWEPHVTASRLFFWRELWNAKELKRLPTCPAARDCIYMCCNPLHWFRILHQP 329
Cdd:cd10489  63 DPRsmPQDPHVLCCQLFRWPDLRHSSELKRLPTCESAKDPVYVCCNPYHWSRLCRPE 119
DWA smart00523
Domain A in dwarfin family proteins;
212-329 3.32e-33

Domain A in dwarfin family proteins;


Pssm-ID: 214708  Cd Length: 109  Bit Score: 122.49  E-value: 3.32e-33
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17137382    212 QNGKRFREDFEALMKQLKRKQRNELLLAVKSRLDPPTKtqrdvvepttttaptylqCILIP----CKTQT---VWEPHVT 284
Cdd:smart00523   1 VEEKWAKKATESLLKKLKKKQLEELLQAVESKGGPPTR------------------CVLIPrsldGRLQVahrKGLPHVL 62

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 17137382    285 ASRLFFWRELWNAKELKRLPTCPAAR--DCIYMCCNPLHWFRILHQP 329
Cdd:smart00523  63 YCRLFRWPDLQSPHELKALPTCEHAFesKSDEVCCNPYHYSRVERPE 109
MH1 pfam03165
MH1 domain; The MH1 (MAD homology 1) domain is found at the amino terminus of MAD related ...
 217-325 9.30e-27

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: 104.38  E-value: 9.30e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17137382   217 FREDFEALMKQLKRK--QRNELLLAVKSRLDPPTKtqrdvvepttttaptylqCILIPCK-------TQTVWEPHVTASR 287
Cdd:pfam03165   1 LKKAVESLLKKLKKKiqQLEELELAVESRGDPPTG------------------CVTIPRSldgrlqvAGRKGLPHVIYCR 62

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 17137382   288 LFFWRELWNAKELKRLPTCPAArDCIY---MCCNPLHWFRI 325
Cdd:pfam03165  63 LWRWPDLQSQHELKAIPTCETA-FESKkdeVCINPYHYSRV 102
 
Name Accession Description Interval E-value
MH2_I-SMAD cd10496
C-terminal Mad Homology 2 (MH2) domain in Inhibitory SMADs; The MH2 domain is located at the ...
 400-565 1.09e-89

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: 273.46  E-value: 1.09e-89
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17137382 400 WCQIAYWEMAHRVGEFFHAKTNAVNIYTDGIvasEVDSMCLRDLTPAGNqIHSVVPKARHTVGLGVTLSLENGDVWIYNR 479
Cdd:cd10496   1 WCTIAYWELRERVGRLYPVKQPAVNIFDDLP---KGDGFCLGALNRQGN-ASEAVARVRSKIGLGVTLSREPDGVWIYNR 76

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17137382 480 GNTTIFVDSPTLSENLDR---VCKVMPGYCLKAFETNRAELLSMRDHGHHPMGPVDYFSIKISFGKGWGRDYKRQDIMGC 556
Cdd:cd10496  77 SEYPIFVNSPTLDSPPSRnllVTKVPPGYSLKVFDYERAALLQRRDDHFSPQGPVDPNSVRISFVKGWGPNYSRQFITSC 156


                ....*....
gi 17137382 557 PCWLEVHFS 565
Cdd:cd10496 157 PCWLEILLN 165
DWB smart00524
Domain B in dwarfin family proteins;
400-565 8.34e-70

Domain B in dwarfin family proteins;


Pssm-ID: 197770  Cd Length: 171  Bit Score: 222.18  E-value: 8.34e-70
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17137382    400 WCQIAYWEMAHRVGEFFHAKTN--AVNIYTDGivaSEVDSMCLRDLTPAgnQIHSVVPKARHTVGLGVTLSLENGDVWIY 477
Cdd:smart00524   2 WCKIAYYELNTRVGETFKVSSPsvTVDGFTDP---SDGNRFCLGQLSNV--NRNEATELIRKHIGKGVQLSYENGDVWLY 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17137382    478 NRGNTTIFVDSPTLSE----NLDRVCKVMPGYCLKAFETNRAELLSMRDHGHHPMGPVDYF---SIKISFGKGWGRDYKR 550
Cdd:smart00524  77 NRSDSPIFVQSPYLDEpggrTLDTVHKLPPGYSIKVFDMEKFAQLLARELAKGFEGVYDLArmcTIRISFVKGWGPDYSR 156

                          170
                   ....*....|....*
gi 17137382    551 QDIMGCPCWLEVHFS 565
Cdd:smart00524 157 QTITSTPCWIEVHLN 171
MH2 pfam03166
MH2 domain; This is the MH2 (MAD homology 2) domain found at the carboxy terminus of MAD ...
 398-564 1.25e-64

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: 208.63  E-value: 1.25e-64
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17137382   398 QVWCQIAYWEMAHRVGEFFHAKTNavNIYTDGIVA-SEVDSMCLRDLT-PAGNQIhsvVPKARHTVGLGVTLSLENGDVW 475
Cdd:pfam03166   1 EIWCSVAYYELNTRVGEAFKVSSP--NVTVDGFTDpSDGNRFCLGLLSnVNRNEA---VEKVRKHIGKGVRLSYDGGEVW 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17137382   476 IYNRGNTTIFVDSPTL----SENLDRVCKVMPGYCLKAFETNRAELLSMRDHGHHPMGPVD---YFSIKISFGKGWGRDY 548
Cdd:pfam03166  76 IYNLSDHPVFVQSPYLnreaGRAPDTVHKVPPGESLKVFDMRKFQQLLSQELRRARLGPQDankLCSVRISFVKGWGPDY 155

                         170
                  ....*....|....*.
gi 17137382   549 KRQDIMGCPCWLEVHF 564
Cdd:pfam03166 156 SRQDITSTPCWIEIHL 171
MH2_SMAD_6 cd10499
C-terminal Mad Homology 2 (MH2) domain in SMAD6; The MH2 domain is located at the C-terminus ...
 400-562 3.28e-43

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: 152.28  E-value: 3.28e-43
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17137382 400 WCQIAYWEMAHRVGEFFHAKTNAVNIYTDgivASEVDSMCLRDLTPAGNQihSVVPKARHTVGLGVTLSLENGDVWIYNR 479
Cdd:cd10499  10 WCSVAYWEHRTRVGRLYAVYDQSVSIFYD---LPQGSGFCLGQLNLEQRS--ESVRRTRSKIGYGILLSKEPDGVWAYNR 84

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17137382 480 GNTTIFVDSPTLSENLDR---VCKVMPGYCLKAFETNRAELLSMRDHGHHPMGPVDYFSIKISFGKGWGRDYKRQDIMGC 556
Cdd:cd10499  85 SEHPIFVNSPTLDIPGSRtlvVRKVPPGYSIKVFDYERSCLLQHTAEPELADGPYDPNSVRISFAKGWGPCYSRQFITSC 164


                ....*.
gi 17137382 557 PCWLEV 562
Cdd:cd10499 165 PCWLEI 170
MH1_SMAD_6_7 cd10489
N-terminal Mad Homology 1 (MH1) domain in SMAD6 and SMAD7; The MH1 is a small DNA-binding ...
 197-329 3.45e-40

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: 141.75  E-value: 3.45e-40
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17137382 197 VSTSRATAHPPQ--TQAQNGKRFREDFEALMKQLKRKQRNELLLAVKSRLDPptktqrdvvepttttaptYLQCILIPCK 274
Cdd:cd10489   1 GAVRRLWAHRTRhsQNPLEERDLRAAFHALLKRLKEKQLELLLQAVESRGGD------------------YLACVLLPRR 62

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 17137382 275 TQT--VWEPHVTASRLFFWRELWNAKELKRLPTCPAARDCIYMCCNPLHWFRILHQP 329
Cdd:cd10489  63 DPRsmPQDPHVLCCQLFRWPDLRHSSELKRLPTCESAKDPVYVCCNPYHWSRLCRPE 119
MH2 cd00050
C-terminal Mad Homology 2 (MH2) domain; The MH2 domain is found in the SMAD (small mothers ...
 400-563 3.16e-39

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: 141.20  E-value: 3.16e-39
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17137382 400 WCQIAYWEMAHRVGEFFHAKTN--AVNIYTDgivASEVDSMCLRDLTPAgnQIHSVVPKARHTVGLGVTLSLENGDVWIY 477
Cdd:cd00050   1 WCSIAYYELNTRVGELFHVYSPsvAVDGFTD---PSNGDRFCLGQLSNV--NRNETIERTRRHIGKGVHLYYVGGEVWAE 75

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17137382 478 NRGNTTIFVDSPTLSENLDR----VCKVMPGYCLKAFETNRAELLSMRDHGHHPMGPVDYF---SIKISFGKGWGRDYKR 550
Cdd:cd00050  76 CLSDHAIFVQSRNLDYPHGRhpltVCKIPPGCSIKVFDNQEFAQLLHQSVNTGFEGVYELTkmcTIRMSFVKGWGPEYHR 155

                       170
                ....*....|...
gi 17137382 551 QDIMGCPCWLEVH 563
Cdd:cd00050 156 QDITSTPCWIEIH 168
DWA smart00523
Domain A in dwarfin family proteins;
212-329 3.32e-33

Domain A in dwarfin family proteins;


Pssm-ID: 214708  Cd Length: 109  Bit Score: 122.49  E-value: 3.32e-33
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17137382    212 QNGKRFREDFEALMKQLKRKQRNELLLAVKSRLDPPTKtqrdvvepttttaptylqCILIP----CKTQT---VWEPHVT 284
Cdd:smart00523   1 VEEKWAKKATESLLKKLKKKQLEELLQAVESKGGPPTR------------------CVLIPrsldGRLQVahrKGLPHVL 62

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 17137382    285 ASRLFFWRELWNAKELKRLPTCPAAR--DCIYMCCNPLHWFRILHQP 329
Cdd:smart00523  63 YCRLFRWPDLQSPHELKALPTCEHAFesKSDEVCCNPYHYSRVERPE 109
MH2_SMAD_7 cd10500
C-terminal Mad Homology 2 (MH2) domain in SMAD7; The MH2 domain is located at the C-terminus ...
 400-565 4.15e-29

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: 113.21  E-value: 4.15e-29
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17137382 400 WCQIAYWEMAHRVGEFFHAKTNAVNIYTDgivASEVDSMCLRDLtpAGNQIHSVVPKARHTVGLGVTLSLENGDVWIYNR 479
Cdd:cd10500   8 WCVVAYWEEKTRVGRLYSVQEPSLDIFYD---LPQGNGFCLGQL--NSDNKSQLVQKVRSKIGYGIQLTREVDGVWVYNR 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17137382 480 GNTTIFVDSPTLSENLDR---VCKVMPGYCLKAFETNRAELLSMRDHGHHPMGPVDYFSIKISFGKGWGRDYKRQDIMGC 556
Cdd:cd10500  83 SSYPIFIKSATLDNPDSRtllVHKVFPGFSIKAFDYEKAYSLQRPNDHEFMQQPWTGFTVQISFVKGWGQCYTRQFISSC 162


                ....*....
gi 17137382 557 PCWLEVHFS 565
Cdd:cd10500 163 PCWLEVIFN 171
MH1 pfam03165
MH1 domain; The MH1 (MAD homology 1) domain is found at the amino terminus of MAD related ...
 217-325 9.30e-27

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: 104.38  E-value: 9.30e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17137382   217 FREDFEALMKQLKRK--QRNELLLAVKSRLDPPTKtqrdvvepttttaptylqCILIPCK-------TQTVWEPHVTASR 287
Cdd:pfam03165   1 LKKAVESLLKKLKKKiqQLEELELAVESRGDPPTG------------------CVTIPRSldgrlqvAGRKGLPHVIYCR 62

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 17137382   288 LFFWRELWNAKELKRLPTCPAArDCIY---MCCNPLHWFRI 325
Cdd:pfam03165  63 LWRWPDLQSQHELKAIPTCETA-FESKkdeVCINPYHYSRV 102
MH2_R-SMAD cd10495
C-terminal Mad Homology 2 (MH2) domain in receptor regulated SMADs; The MH2 domain is located ...
 400-563 1.44e-26

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: 106.31  E-value: 1.44e-26
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17137382 400 WCQIAYWEMAHRVGEFFHAKTNAVNI--YTDGIVASevDSMCLRDLTPAGNqiHSVVPKARHTVGLGVTLSLENGDVWIY 477
Cdd:cd10495   1 WCSISYYELNSRVGEQFKASNPSIIVdgFTDPSNNS--DRFCLGLLSNVNR--NATIENTRRHIGRGVHLFYVGGEVYAE 76

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17137382 478 NRGNTTIFVDSPTLSE----NLDRVCKVMPGYCLKAFETNR-AELLSmrDHGHHPMGPVDYFS----IKISFGKGWGRDY 548
Cdd:cd10495  77 CLSDSAIFVQSRNCNLrhgfHPATVCKIPPGCSLKIFNNQSfAQLLE--QSVNRGFEAVYELTkmctIRISFVKGWGAEY 154

                       170
                ....*....|....*
gi 17137382 549 KRQDIMGCPCWLEVH 563
Cdd:cd10495 155 HRQDVTSTPCWIEIH 169
MH2_SMAD_2_3 cd10985
C-terminal Mad Homology 2 (MH2) domain in SMAD2 and SMAD3; The MH2 domain is located at the ...
 400-565 4.00e-24

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: 100.00  E-value: 4.00e-24
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17137382 400 WCQIAYWEMAHRVGEFFHAKTNAVNI--YTDgivASEVDSMCLRDLTPAgNQIHSVVPKARHtVGLGVTLSLENGDVWIY 477
Cdd:cd10985   9 WCSISYYEMNTRVGETFHASQPSLTVdgFTD---PSNSERFCLGLLSNV-NRNPQVELTRRH-IGKGVRLYYIGGEVFAE 83

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17137382 478 NRGNTTIFVDSPTLSENLD----RVCKVMPGYCLKAFETNR-AELLSMR-DHGHHPMGPVDYF-SIKISFGKGWGRDYKR 550
Cdd:cd10985  84 CLSDSAIFVQSPNCNQRYGwhpaTVCKIPPGCNLKIFNNQEfAALLSQSvNQGFEAVYQLTRMcTIRMSFVKGWGAEYRR 163

                       170
                ....*....|....*
gi 17137382 551 QDIMGCPCWLEVHFS 565
Cdd:cd10985 164 QTVTSTPCWIELHLN 178
MH2_SMAD_1_5_9 cd10497
C-terminal Mad Homology 2 (MH2) domain in SMAD1, SMAD5 and SMAD9; The MH2 domain is located at ...
 398-565 3.87e-23

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: 97.26  E-value: 3.87e-23
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17137382 398 QVWCQIAYWEMAHRVGEFFHAKTNAvnIYTDGIV--ASEVDSMCLRDLTPAGNqiHSVVPKARHTVGLGVTLSLENGDVW 475
Cdd:cd10497   5 KYWCSIAYYELNNRVGEAFHASSTS--IIVDGFTdpSNNSDRFCLGLLSNVNR--NSTIENTRRHIGKGVHLYYVGGEVY 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17137382 476 IYNRGNTTIFVDS----------PTlsenldRVCKVMPGYCLKAFETNR-AELLSMR-DHGHHPMGPVDYF-SIKISFGK 542
Cdd:cd10497  81 AECLSDSSIFVQSrncnyhhgfhPT------TVCKIPPGCSLKIFNNQEfAQLLSQSvNHGFEAVYELTKMcTIRMSFVK 154

                       170       180
                ....*....|....*....|...
gi 17137382 543 GWGRDYKRQDIMGCPCWLEVHFS 565
Cdd:cd10497 155 GWGAEYHRQDVTSTPCWIEIHLH 177
MH2_SMAD_4 cd10498
C-terminal Mad Homology 2 (MH2) domain in SMAD4; The MH2 domain is located at the C-terminus ...
 400-565 1.31e-17

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: 82.13  E-value: 1.31e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17137382 400 WCQIAYWEMAHRVGEFFHAKTNAVNIYTDGIV-ASEVDSMCLRDLTpagnQIH--SVVPKARHTVGLGVTLSLE-NGDVW 475
Cdd:cd10498   4 WCSIAYFELDTQVGETFKVPSSCPTVTVDGYVdPSGGNRFCLGQLS----NVHrtEASERARLHIGKGVQLDCKgEGDVW 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17137382 476 IYNRGNTTIFVDSPTLSENLDR-----VCKVMPGYCLKAFETNRA----ELLSMRDH-----------GHHP-------M 528
Cdd:cd10498  80 LRCLSDHSVFVQSYYLDREAGRapgdaVHKIYPSAYIKVFDLRQChrqmQQQAATAQaaaaaqaaavaGNIPgpgsvggI 159

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|..
gi 17137382 529 GP-----------VDYF----SIKISFGKGWGRDYKRQDIMGCPCWLEVHFS 565
Cdd:cd10498 160 APaislsaaagigVDDLrrlcILRMSFVKGWGPDYPRQSIKETPCWIEIHLH 211
MH1_SMAD_6 cd10493
N-terminal Mad Homology 1 (MH1) domain in SMAD6; The MH1 is a small DNA-binding domain present ...
 223-325 2.39e-06

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: 46.69  E-value: 2.39e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17137382 223 ALMKQLKRKQRNELLLAVKSRLDPPTK----TQRDVVEPTTTTAPTYLQCilipcktqtvwephvtasRLFFWRELWNAK 298
Cdd:cd10493  19 ALLKRLKERSLDVLLEAVESRGGLPSGcvmvPRTELRLGGRRVPPQLLLC------------------RLFRWPDLQHPA 80

                        90       100
                ....*....|....*....|....*....
gi 17137382 299 ELKRLPTCP--AARDCIYMCCNPLHWFRI 325
Cdd:cd10493  81 QLKALCHCQsfGAQDGPTVCCNPYHYSRL 109
 
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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