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Conserved domains on  [gi|767984140|ref|XP_011519863|]
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mothers against decapentaplegic homolog 6 isoform X1 [Homo sapiens]

Protein Classification

MH2_SMAD_6 domain-containing protein( domain architecture ID 10180379)

MH2_SMAD_6 domain-containing protein

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
MH2_SMAD_6 cd10499
C-terminal Mad Homology 2 (MH2) domain in SMAD6; The MH2 domain is located at the C-terminus ...
 61-233 9.29e-135

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: 376.08  E-value: 9.29e-135
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984140  61 SPDATKPSHWCSVAYWEHRTRVGRLYAVYDQAVSIFYDLPQGSGFCLGQLNLEQRSESVRRTRSKIGFGILLSKEPDGVW 140
Cdd:cd10499    1 SPDATKRSHWCSVAYWEHRTRVGRLYAVYDQSVSIFYDLPQGSGFCLGQLNLEQRSESVRRTRSKIGYGILLSKEPDGVW 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984140 141 AYNRGEHPIFVNSPTLDAPGGRALVVRKVPPGYSIKVFDFERSG-LQHAPEPDAADGPYDPNSVRISFAKGWGPCYSRQF 219
Cdd:cd10499   81 AYNRSEHPIFVNSPTLDIPGSRTLVVRKVPPGYSIKVFDYERSClLQHTAEPELADGPYDPNSVRISFAKGWGPCYSRQF 160

                        170
                 ....*....|....
gi 767984140 220 ITSCPCWLEILLNN 233
Cdd:cd10499  161 ITSCPCWLEILLNN 174
 
Name Accession Description Interval E-value
MH2_SMAD_6 cd10499
C-terminal Mad Homology 2 (MH2) domain in SMAD6; The MH2 domain is located at the C-terminus ...
 61-233 9.29e-135

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: 376.08  E-value: 9.29e-135
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984140  61 SPDATKPSHWCSVAYWEHRTRVGRLYAVYDQAVSIFYDLPQGSGFCLGQLNLEQRSESVRRTRSKIGFGILLSKEPDGVW 140
Cdd:cd10499    1 SPDATKRSHWCSVAYWEHRTRVGRLYAVYDQSVSIFYDLPQGSGFCLGQLNLEQRSESVRRTRSKIGYGILLSKEPDGVW 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984140 141 AYNRGEHPIFVNSPTLDAPGGRALVVRKVPPGYSIKVFDFERSG-LQHAPEPDAADGPYDPNSVRISFAKGWGPCYSRQF 219
Cdd:cd10499   81 AYNRSEHPIFVNSPTLDIPGSRTLVVRKVPPGYSIKVFDYERSClLQHTAEPELADGPYDPNSVRISFAKGWGPCYSRQF 160

                        170
                 ....*....|....
gi 767984140 220 ITSCPCWLEILLNN 233
Cdd:cd10499  161 ITSCPCWLEILLNN 174
MH2 pfam03166
MH2 domain; This is the MH2 (MAD homology 2) domain found at the carboxy terminus of MAD ...
 68-232 3.29e-85

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: 250.62  E-value: 3.29e-85
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984140   68 SHWCSVAYWEHRTRVGRLYAVYDQavSIFYDLP----QGSGFCLGQLNLEQRSESVRRTRSKIGFGILLSKEPDGVWAYN 143
Cdd:pfam03166   1 EIWCSVAYYELNTRVGEAFKVSSP--NVTVDGFtdpsDGNRFCLGLLSNVNRNEAVEKVRKHIGKGVRLSYDGGEVWIYN 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984140  144 RGEHPIFVNSPTLDAPGGRALV-VRKVPPGYSIKVFDFERS-GLQHAPEPDAADGPYDPN---SVRISFAKGWGPCYSRQ 218
Cdd:pfam03166  79 LSDHPVFVQSPYLNREAGRAPDtVHKVPPGESLKVFDMRKFqQLLSQELRRARLGPQDANklcSVRISFVKGWGPDYSRQ 158

                         170
                  ....*....|....
gi 767984140  219 FITSCPCWLEILLN 232
Cdd:pfam03166 159 DITSTPCWIEIHLH 172
DWB smart00524
Domain B in dwarfin family proteins;
69-232 5.40e-85

Domain B in dwarfin family proteins;


Pssm-ID: 197770  Cd Length: 171  Bit Score: 249.92  E-value: 5.40e-85
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984140    69 HWCSVAYWEHRTRVGRLYAVYD--QAVSIFYDLPQGSGFCLGQLNLEQRSESVRRTRSKIGFGILLSKEPDGVWAYNRGE 146
Cdd:smart00524   1 SWCKIAYYELNTRVGETFKVSSpsVTVDGFTDPSDGNRFCLGQLSNVNRNEATELIRKHIGKGVQLSYENGDVWLYNRSD 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984140   147 HPIFVNSPTLDAPGGRAL-VVRKVPPGYSIKVFDFERSGLQHAPEP-DAADGPYDPN---SVRISFAKGWGPCYSRQFIT 221
Cdd:smart00524  81 SPIFVQSPYLDEPGGRTLdTVHKLPPGYSIKVFDMEKFAQLLARELaKGFEGVYDLArmcTIRISFVKGWGPDYSRQTIT 160

                          170
                   ....*....|.
gi 767984140   222 SCPCWLEILLN 232
Cdd:smart00524 161 STPCWIEVHLN 171
 
Name Accession Description Interval E-value
MH2_SMAD_6 cd10499
C-terminal Mad Homology 2 (MH2) domain in SMAD6; The MH2 domain is located at the C-terminus ...
 61-233 9.29e-135

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: 376.08  E-value: 9.29e-135
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984140  61 SPDATKPSHWCSVAYWEHRTRVGRLYAVYDQAVSIFYDLPQGSGFCLGQLNLEQRSESVRRTRSKIGFGILLSKEPDGVW 140
Cdd:cd10499    1 SPDATKRSHWCSVAYWEHRTRVGRLYAVYDQSVSIFYDLPQGSGFCLGQLNLEQRSESVRRTRSKIGYGILLSKEPDGVW 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984140 141 AYNRGEHPIFVNSPTLDAPGGRALVVRKVPPGYSIKVFDFERSG-LQHAPEPDAADGPYDPNSVRISFAKGWGPCYSRQF 219
Cdd:cd10499   81 AYNRSEHPIFVNSPTLDIPGSRTLVVRKVPPGYSIKVFDYERSClLQHTAEPELADGPYDPNSVRISFAKGWGPCYSRQF 160

                        170
                 ....*....|....
gi 767984140 220 ITSCPCWLEILLNN 233
Cdd:cd10499  161 ITSCPCWLEILLNN 174
MH2_I-SMAD cd10496
C-terminal Mad Homology 2 (MH2) domain in Inhibitory SMADs; The MH2 domain is located at the ...
 70-232 2.49e-103

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: 296.19  E-value: 2.49e-103
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984140  70 WCSVAYWEHRTRVGRLYAVYDQAVSIFYDLPQGSGFCLGQLNLEQ-RSESVRRTRSKIGFGILLSKEPDGVWAYNRGEHP 148
Cdd:cd10496    1 WCTIAYWELRERVGRLYPVKQPAVNIFDDLPKGDGFCLGALNRQGnASEAVARVRSKIGLGVTLSREPDGVWIYNRSEYP 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984140 149 IFVNSPTLDAPGGRALVVRKVPPGYSIKVFDFERSG-LQHAPEPDAADGPYDPNSVRISFAKGWGPCYSRQFITSCPCWL 227
Cdd:cd10496   81 IFVNSPTLDSPPSRNLLVTKVPPGYSLKVFDYERAAlLQRRDDHFSPQGPVDPNSVRISFVKGWGPNYSRQFITSCPCWL 160


                 ....*
gi 767984140 228 EILLN 232
Cdd:cd10496  161 EILLN 165
MH2 cd00050
C-terminal Mad Homology 2 (MH2) domain; The MH2 domain is found in the SMAD (small mothers ...
 70-232 2.28e-95

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: 276.41  E-value: 2.28e-95
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984140  70 WCSVAYWEHRTRVGRLYAVY--DQAVSIFYDLPQGSGFCLGQLNLEQRSESVRRTRSKIGFGILLSKEPDGVWAYNRGEH 147
Cdd:cd00050    1 WCSIAYYELNTRVGELFHVYspSVAVDGFTDPSNGDRFCLGQLSNVNRNETIERTRRHIGKGVHLYYVGGEVWAECLSDH 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984140 148 PIFVNSPTLDAPGGR-ALVVRKVPPGYSIKVFDFERSGLQHAPEPD-----AADGPYDPnSVRISFAKGWGPCYSRQFIT 221
Cdd:cd00050   81 AIFVQSRNLDYPHGRhPLTVCKIPPGCSIKVFDNQEFAQLLHQSVNtgfegVYELTKMC-TIRMSFVKGWGPEYHRQDIT 159

                        170
                 ....*....|.
gi 767984140 222 SCPCWLEILLN 232
Cdd:cd00050  160 STPCWIEIHLH 170
MH2 pfam03166
MH2 domain; This is the MH2 (MAD homology 2) domain found at the carboxy terminus of MAD ...
 68-232 3.29e-85

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: 250.62  E-value: 3.29e-85
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984140   68 SHWCSVAYWEHRTRVGRLYAVYDQavSIFYDLP----QGSGFCLGQLNLEQRSESVRRTRSKIGFGILLSKEPDGVWAYN 143
Cdd:pfam03166   1 EIWCSVAYYELNTRVGEAFKVSSP--NVTVDGFtdpsDGNRFCLGLLSNVNRNEAVEKVRKHIGKGVRLSYDGGEVWIYN 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984140  144 RGEHPIFVNSPTLDAPGGRALV-VRKVPPGYSIKVFDFERS-GLQHAPEPDAADGPYDPN---SVRISFAKGWGPCYSRQ 218
Cdd:pfam03166  79 LSDHPVFVQSPYLNREAGRAPDtVHKVPPGESLKVFDMRKFqQLLSQELRRARLGPQDANklcSVRISFVKGWGPDYSRQ 158

                         170
                  ....*....|....
gi 767984140  219 FITSCPCWLEILLN 232
Cdd:pfam03166 159 DITSTPCWIEIHLH 172
DWB smart00524
Domain B in dwarfin family proteins;
69-232 5.40e-85

Domain B in dwarfin family proteins;


Pssm-ID: 197770  Cd Length: 171  Bit Score: 249.92  E-value: 5.40e-85
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984140    69 HWCSVAYWEHRTRVGRLYAVYD--QAVSIFYDLPQGSGFCLGQLNLEQRSESVRRTRSKIGFGILLSKEPDGVWAYNRGE 146
Cdd:smart00524   1 SWCKIAYYELNTRVGETFKVSSpsVTVDGFTDPSDGNRFCLGQLSNVNRNEATELIRKHIGKGVQLSYENGDVWLYNRSD 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984140   147 HPIFVNSPTLDAPGGRAL-VVRKVPPGYSIKVFDFERSGLQHAPEP-DAADGPYDPN---SVRISFAKGWGPCYSRQFIT 221
Cdd:smart00524  81 SPIFVQSPYLDEPGGRTLdTVHKLPPGYSIKVFDMEKFAQLLARELaKGFEGVYDLArmcTIRISFVKGWGPDYSRQTIT 160

                          170
                   ....*....|.
gi 767984140   222 SCPCWLEILLN 232
Cdd:smart00524 161 STPCWIEVHLN 171
MH2_SMAD_7 cd10500
C-terminal Mad Homology 2 (MH2) domain in SMAD7; The MH2 domain is located at the C-terminus ...
 68-232 1.36e-73

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: 221.07  E-value: 1.36e-73
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984140  68 SHWCSVAYWEHRTRVGRLYAVYDQAVSIFYDLPQGSGFCLGQLNLEQRSESVRRTRSKIGFGILLSKEPDGVWAYNRGEH 147
Cdd:cd10500    6 SHWCVVAYWEEKTRVGRLYSVQEPSLDIFYDLPQGNGFCLGQLNSDNKSQLVQKVRSKIGYGIQLTREVDGVWVYNRSSY 85

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984140 148 PIFVNSPTLDAPGGRALVVRKVPPGYSIKVFDFERSG-LQHAPEPDAADGPYDPNSVRISFAKGWGPCYSRQFITSCPCW 226
Cdd:cd10500   86 PIFIKSATLDNPDSRTLLVHKVFPGFSIKAFDYEKAYsLQRPNDHEFMQQPWTGFTVQISFVKGWGQCYTRQFISSCPCW 165


                 ....*.
gi 767984140 227 LEILLN 232
Cdd:cd10500  166 LEVIFN 171
MH2_R-SMAD cd10495
C-terminal Mad Homology 2 (MH2) domain in receptor regulated SMADs; The MH2 domain is located ...
 70-234 7.51e-33

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: 117.48  E-value: 7.51e-33
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984140  70 WCSVAYWEHRTRVGRLYAVYDQAVSI--FYDLPQGSG-FCLGQLNLEQRSESVRRTRSKIGFGILLSKEPDGVWAYNRGE 146
Cdd:cd10495    1 WCSISYYELNSRVGEQFKASNPSIIVdgFTDPSNNSDrFCLGLLSNVNRNATIENTRRHIGRGVHLFYVGGEVYAECLSD 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984140 147 HPIFVNSPTLDAPGGRALV-VRKVPPGYSIKVFDFER-SGLQHAPEPDAADGPYDPN---SVRISFAKGWGPCYSRQFIT 221
Cdd:cd10495   81 SAIFVQSRNCNLRHGFHPAtVCKIPPGCSLKIFNNQSfAQLLEQSVNRGFEAVYELTkmcTIRISFVKGWGAEYHRQDVT 160

                        170
                 ....*....|...
gi 767984140 222 SCPCWLEILLNNP 234
Cdd:cd10495  161 STPCWIEIHLHGP 173
MH2_SMAD_4 cd10498
C-terminal Mad Homology 2 (MH2) domain in SMAD4; The MH2 domain is located at the C-terminus ...
 67-234 7.47e-32

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: 116.03  E-value: 7.47e-32
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984140  67 PSHWCSVAYWEHRTRVGRLYAVYDQAVSIFYD---LPQGSG-FCLGQLNLEQRSESVRRTRSKIGFGILLSKEPDG-VWA 141
Cdd:cd10498    1 PEYWCSIAYFELDTQVGETFKVPSSCPTVTVDgyvDPSGGNrFCLGQLSNVHRTEASERARLHIGKGVQLDCKGEGdVWL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984140 142 YNRGEHPIFVNSPTLDAPGGRA--LVVRKVPPGYSIKVFDFERSGLQ---------------------HAPEPDAADGPY 198
Cdd:cd10498   81 RCLSDHSVFVQSYYLDREAGRApgDAVHKIYPSAYIKVFDLRQCHRQmqqqaataqaaaaaqaaavagNIPGPGSVGGIA 160

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|...
gi 767984140 199 DPNS-----------------VRISFAKGWGPCYSRQFITSCPCWLEILLNNP 234
Cdd:cd10498  161 PAISlsaaagigvddlrrlciLRMSFVKGWGPDYPRQSIKETPCWIEIHLHRA 213
MH2_SMAD_2_3 cd10985
C-terminal Mad Homology 2 (MH2) domain in SMAD2 and SMAD3; The MH2 domain is located at the ...
 65-234 1.19e-29

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: 109.25  E-value: 1.19e-29
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984140  65 TKPSHWCSVAYWEHRTRVGRLYAVYDQAVSI--FYDLPQGSGFCLGQLNLEQRSESVRRTRSKIGFGILLSKEPDGVWAY 142
Cdd:cd10985    4 CEPAFWCSISYYEMNTRVGETFHASQPSLTVdgFTDPSNSERFCLGLLSNVNRNPQVELTRRHIGKGVRLYYIGGEVFAE 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984140 143 NRGEHPIFVNSPTLDAP-GGRALVVRKVPPGYSIKVFDF-ERSGLQHAPEPDAADGPYDPN---SVRISFAKGWGPCYSR 217
Cdd:cd10985   84 CLSDSAIFVQSPNCNQRyGWHPATVCKIPPGCNLKIFNNqEFAALLSQSVNQGFEAVYQLTrmcTIRMSFVKGWGAEYRR 163

                        170
                 ....*....|....*..
gi 767984140 218 QFITSCPCWLEILLNNP 234
Cdd:cd10985  164 QTVTSTPCWIELHLNGP 180
MH2_SMAD_1_5_9 cd10497
C-terminal Mad Homology 2 (MH2) domain in SMAD1, SMAD5 and SMAD9; The MH2 domain is located at ...
 66-234 1.01e-25

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: 99.57  E-value: 1.01e-25
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984140  66 KPSHWCSVAYWEHRTRVGRLYAVYDQAVSI--FYDlPQGSG--FCLGQLNLEQRSESVRRTRSKIGFGILLSKEPDGVWA 141
Cdd:cd10497    3 EPKYWCSIAYYELNNRVGEAFHASSTSIIVdgFTD-PSNNSdrFCLGLLSNVNRNSTIENTRRHIGKGVHLYYVGGEVYA 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984140 142 YNRGEHPIFVNSPTLDAPGG-RALVVRKVPPGYSIKVFDF-ERSGLQHAPEPDAADGPYDPN---SVRISFAKGWGPCYS 216
Cdd:cd10497   82 ECLSDSSIFVQSRNCNYHHGfHPTTVCKIPPGCSLKIFNNqEFAQLLSQSVNHGFEAVYELTkmcTIRMSFVKGWGAEYH 161

                        170
                 ....*....|....*...
gi 767984140 217 RQFITSCPCWLEILLNNP 234
Cdd:cd10497  162 RQDVTSTPCWIEIHLHGP 179
 
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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