Conserved Protein Domain Family
MH2_I-SMAD

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cd10496: MH2_I-SMAD 
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.
Statistics
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PSSM-Id: 199821
Aligned: 9 rows
Threshold Bit Score: 262.675
Created: 29-Jun-2011
Updated: 10-Sep-2024
Structure
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Aligned Rows:
 
putative trimer
Feature 1:putative trimer interface [polypeptide binding site]
Evidence:
  • Comment:Based on similarity to other members of the family
  • 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 the heteromeric SMAD complexes with SMAD4.

cd10496 is part of a hierarchy of related CD models.
Use the graphical representation to navigate this hierarchy.
cd10496 is a member of the superfamily cl00056
cd10496 Sequence Cluster
Sub-family Hierarchy
Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1              #       ## #        #####            #   # ## #               #   ## #    
O35182       332 WCSVAYWEhrtRVGRLYAVydQAVSIFYDLP---------QGSGFCLGQLNLEq---------rSESVRRTRSKIGf--- 390 house mouse
O15105       261 WCVVAYWEektRVGRLYCVqePSLDIFYDLP---------QGNGFCLGQLNSDn---------kSQLVQKVRSKIGc--- 319 human
NP_001071965 191 WCTLAYWEerdRVGRLYPVkhNFVNVFDQSP---------KGEGFCLSAVSSQ-----------TSRSAKVRRLIGh--- 247 Ciona intestinalis
NP_001139378 162 WCRLAYWElaqRVGPLFPVeaPAVNVFGDVP---------YCDGLSLETLAQQnc-------naPESVRHGRCKIGl--- 222 red flour beetle
EGI61529       7 WCTLAYWElggRVGRLYPVepSTVNVFDSLH---------DGDGLCLATLVENhn--------aPPAVQRTRSKIGlgks 69  Panamanian leaf...
AAF55383     400 WCQIAYWEmahRVGEFFHAktNAVNIYTDGIva------sEVDSMCLRDLTPAgn-------qiHSVVPKARHTVGl--- 463 fruit fly
EDV28965     124 WCAIAYWEfreRVGRIFDVksSTVNIFQQLP---------EGEGFWLGALNRDgvsgnisntdsNQCDSRVFHRIGy--- 191 Trichoplax adha...
EEC10457      28 WCTIAYWElneRVGPLFPVrqPWLHVTFEESaapprggvaAQDALSLLSLARSktt------pcKEAVARTRAKIGm--- 98  black-legged tick
EDO39628     150 WCVVAYWElneCIGPFYHGhqDVINIYETLP---------KPKGFCLAGLDRNqn--------vSDGTKRARNHVGf--- 209 starlet sea ane...
Feature 1                                                                                        
O35182       391 ---------GILLSKEp--DGVWAYNRGEHPIFVNS----PTLDAPGgr--aLVVRKVPPgYSIKVFDF-ERSGLLQHad 452 house mouse
O15105       320 ---------GIQLTREv--DGVWVYNRSSYPIFIKS----ATLDNPDsr--tLLVHKVFPgFSIKAFDY-EKAYSLQRpn 381 human
NP_001071965 248 ---------GVTIGIDptlQEASLYNRSDYPVFVNS----PVLEPIPsr--sQLVHKVLPgECCRIFSH-EVAADLKRlh 311 Ciona intestinalis
NP_001139378 223 ---------GVTLSHEg--GSVWVYNRSENPIFVNS----VTLDSADs----PLPTRVPAeQCLCVYDP-QKAAAHRTcw 282 red flour beetle
EGI61529      70 dlrnffsrfGLTLSQEa--DGVWAYNRSESPIFVNS----PTLDDPEsr--tLLVYRVPPgFCLNIFDR-AKIMQLPYgg 140 Panamanian leaf...
AAF55383     464 ---------GVTLSLEn--GDVWIYNRGNTTIFVDS----PTLSENL-----DRVCKVMPgYCLKAFET-NRAELLSMrd 522 fruit fly
EDV28965     192 ---------GLQLSREd--DSVWIYNRSEHPLYVNSplynKNIQSTHn----TEVKKVQPgYSLKVFNYaRVDMPQQIr- 255 Trichoplax adha...
EEC10457      99 ---------GVTLLHEr--DGVWVYNRSEHGVFVTS----PTLDGPQvr--nLTVFKVPPgYSLRVFDW-ERARRYCRcp 160 black-legged tick
EDO39628     210 ---------GLQLSREe--DGIWIYNRSEYAVFANGtt-fPYVTTTPsasqnITVTKVPPgFSLKIYDYnHSPATCRTfe 277 starlet sea ane...
Feature 1                    #                           #      # # #
O35182       453 --------aAHGPYDphSVRISFAKGWGPCY----SRQFITSCPCWLEILLN 492 house mouse
O15105       382 d-----hefMQQPWTgfTVQISFVKGWGQCY----TRQFISSCPCWLEVIFN 424 human
NP_001071965 312 sh----hvtRTGPYNpyTVRISFVKGWGGNTy---RRQVITSCPCWLEILFN 356 Ciona intestinalis
NP_001139378 283 d------fsTHGPIDpnSIRISFAKGWGPLY----KRQEITSCPCWLEILLA 324 red flour beetle
EGI61529     141 gggqaagftTSGPVDinSVRISFAKGWGPKY----SRQEVTSCPCWLEVLLA 188 Panamanian leafcutter ant
AAF55383     523 h-----ghhPMGPVDyfSIKISFGKGWGRDY----KRQDIMGCPCWLEVHFS 565 fruit fly
EDV28965     256 --------pYVGPRYpySIRISFVKGWGRNY----TRQFITSCPCWLEILLN 295 Trichoplax adhaerens
EEC10457     161 r-----vasLDGPFDpnAVRISFVKGWGPRY----SRQAVTALPCSLELLLR 203 black-legged tick
EDO39628     278 --------gPQSWKVpeSVRISFAKGWGNTSsasyRRPVVTSCPCWLEIHFT 321 starlet sea anemone

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