3GMJ,1KHU


Conserved Protein Domain Family
MH2_SMAD_1_5_9
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cd10497: MH2_SMAD_1_5_9 
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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.
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Statistics
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PSSM-Id: 199822
Aligned: 14 rows
Threshold Bit Score: 432.766
Created: 29-Jun-2011
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
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trimer
Conserved site includes 53 residues -Click on image for an interactive view with Cn3D
Feature 1:trimer interface [polypeptide binding site]
Evidence:
  • Comment:Upon phosphorylation of the last two Ser residues of the flexible C-terminal SSXS motif, R-SMADs form extremely stable homotrimers as well as heteromeric SMAD complexes with SMAD4.
  • Structure:3GMJ: Drosophila melanogaster Mad MH2 domain homotrimer; contacts at 4.0A
    - View structure with Cn3D
  • Structure:1KHU; Human SMAD1 MH2 domain homotrimer; contacts at 4A.
    - View structure with Cn3D
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Sequence Alignment
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Format: Row Display: Color Bits: Type Selection: 
Feature 1         #          #    ## #          #####    #   ## # ##     ## ###   #           
3GMJ_A     45 YSEPAFWASIAYYELNcRVGEVFHCNnnSVIVDGFTNPSnNSDRCCLGQLSNVNRNSTIENTRRHIG-KGVHLYYVtgEV 123 fruit fly
AAL87851  222 YQDPLNWCSIAYYELNlRVGEPFHASgtSLIIDGFTDPNtSSDRFCLGGMSNVNRNSTIENTRRHIS-KGVHLYYVggEV 300 Hydra vulgaris
EDV24960  230 YQEPNCWCTVAYYELNnRVGEPFHASqaSLIIDGFTDPStNADRFCLGLLSNVNRNSTIENTRRHIG-KGVHLYYVggEV 308 Trichoplax adhaerens
BAE06690  277 YSEPNHWCTIVYYELNnRVGEAFPATstSIIVDGFTNPSsTSNRFCLGQLSNVNRNSTIENTRRHIS-KGVHLYYVggEV 355 Ciona intestinalis
ACU12852  260 YQEPQSWCSIAYYELNnRVGEPFHATttSVIVDGFTDPSnNHDRFCLGLLSNVNRNSTIENTRRHIG-KGVHLYYVggEV 338 common urchin
EEC15162  285 YQEPQYWCTIAYYELNsRVGEIFHAQnhAIVIDGFTDPSnNNNRFCLGLLSNVNRNSTIENTRRHIG-KGVHLYYIggEV 363 black-legged tick
ADI48174  265 YQEPQYWCSIVYYELNnRVGEAFHAShnSIVTDGFCDPSnNADRFCLGLLSNVNRNSTIXNTRRHIA-KGVRLYYVggEV 343 Crepidula fornicata
ABQ23403  264 YQEPVYWASIAYYELNnRVGEPFHAKshSIIVDGFTDPSnSGDRFCLGLISNVNRNSTIENTRRHIG-KGVHLYYVggEV 342 Branchiostoma belc...
EFX70037  238 YQEPIYWCSIAYYELNsRVGEVFHAQshSIIVDGFTNPDnKSDRFCLGQLSNVNRNSTIENTRRHIGkGCVHLYYVggEV 317 common water flea
Q9I962    265 YEEPKHWCSIVYYELNnRVGEAFHASstSILVDGFTDPSnNKNRFCLGLLSNVNRNSTIENTRRHIG-KGVHLYYVggEV 343 Japanese quail

Feature 1            #                                                 #  #  #   # #   ###    
3GMJ_A    124 YAECLSDSAIFVQSRNCNYQHGFHPsTVCKIPPgCSLKIFNNQEFAQLLSQSVNNgFEAVYELTKMCTIRMSFVKGWGAE 203 fruit fly
AAL87851  301 FAECLSDSAVFVQSKNCNYHHGFHPsTVCKIPPqCTLKIFNNQEFAQLLSQSVNHgYEAVYELSKHCTIRMSFVKGWGAE 380 Hydra vulgaris
EDV24960  309 YAECLSESSIFVQSRNCNYHHNFHPtTVCKIPSsCSLKIFDNQDFAALLSESVSKgFEAVYQLTKMCTIRISFVKGWGAE 388 Trichoplax adhaerens
BAE06690  356 YAECLSDSSIFVQSRNCNYHHGFHPtTVCKIPPsCSLKIFNNQEFAALLSQSVNHgYEAVFELTKMCTIRMSFVKGWGAE 435 Ciona intestinalis
ACU12852  339 YAECLSDSSIFVQSRNCNHRHGFHPtTVCKIPPgCSLKIFNNQEFAALLSQYVNHgFEMVYELTKMCTIRMSFVKGWGAE 418 common urchin
EEC15162  364 YAECLSDSAIFVQSRNCNHSHQFHPtTVCKIPSgCSLKIFNNQEFAELLTQAVNHgFEAVYELTKMCTIRMSFVKGWGAE 443 black-legged tick
ADI48174  344 FAECLSDSSIFVQSRNCNYHHGFHPtTVCKIPPgCSLKIFNNQEFAALLSQSVNHgFEAVYDLTKMCTIRMSFVKGWGAE 423 Crepidula fornicata
ABQ23403  343 YAECLSDSAIFVQSRNCNHHHGFHPtTVCKIPPgCSLKIFNNQEFAQLLSQSVNHgFEAVYELTKMCTIRMSFVKGWGAE 422 Branchiostoma belc...
EFX70037  318 YAECLSDSAIFVQSRNCNHHHGFHPtTVCKIPPgCSLKIFNNQEFAQLLSQSVNHgFEAVYELTKMCTIRMSFVKGWGAE 397 common water flea
Q9I962    344 YAECLSDSSIFVQSRNCNYHHGFHPtTVCKIPSgCSLKIFNNQEFAQLLAQSVNHgFETVYELTKMCTLRMSFVKGWGAE 423 Japanese quail

Feature 1     # #   #    # # # #  ## ##  ##   #### #####
3GMJ_A    204 YHRQDVTSTPCWIEIHLHgPLQWLDKVLTQMGSPHNAISSVS 245 fruit fly
AAL87851  381 YHRQGVTSTPCWIEIHLHgPLQWLDKVLTQMGSPQNAITSVS 422 Hydra vulgaris
EDV24960  389 YHRQDVTSTPCWIEIHLHgPLQWLDRVLIQMGSPRDPAGSVS 430 Trichoplax adhaerens
BAE06690  436 YHRQDVTSTPCWIEIHLNgPLQWLDKVLTQMGSPNNAISSVS 477 Ciona intestinalis
ACU12852  419 YHRQDVTSTPCWIEIHLNgPLQWLDKVLTQMGSPHNPISSVS 460 common urchin
EEC15162  444 YHRQDVTSTPCWIEVHLSgPLQWLDKVLTQMGSPHNPISSVS 485 black-legged tick
ADI48174  424 YHRQDVTSTPCWIEIHLNgPLQWLDKVLTQMGSPHNAISSVS 465 Crepidula fornicata
ABQ23403  423 YHRQDVTSTPCWIEIHLHgPLQWLDRVLTQMGSPHNPISSVS 464 Branchiostoma belcheri tsingtauense
EFX70037  398 YHRQDVTSTPCWIEIHLHgPLQWLDKVLTQMGSPHNPISSVS 439 common water flea
Q9I962    424 YHRQDVTSTPCWIEIHLHgPLQWLDKVLTQMGSPHNPISSVS 465 Japanese quail

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