Conserved Protein Domain Family
MH1_SMAD_6_7
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cd10489: MH1_SMAD_6_7 
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.
Links
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Statistics
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PSSM-Id: 199813
Aligned: 19 rows
Threshold Bit Score: 96.6831
Created: 29-Jun-2011
Updated: 10-Sep-2024
Structure
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Aligned Rows:
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putative DNAZn binding site
Feature 1:putative DNA binding site [nucleic acid binding site]
Evidence:
  • Comment:based on similarity to other SMAD-MH1 domains with structure bound to a palindromic SMAD binding element, GTCTAGAC
  • Comment: MH1 binds to the major groove via a beta hairpin structure
  • Citation:PMID 9741623
Scroll to Sequence Alignment Display
Sequence Alignment
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Format: Row Display: Color Bits: Type Selection: 
Feature 1                                                  #   #  #                              
Q9W734        94 EARSRLVl----------------------------lERELKAVTYALLKRLKER---SLHSLLQAVESRGGt------- 135 chicken
XP_001942613  50 AATSPPSahps-----------------------ppvESDERKFRNALFKRLDDR---QLETLLRAVDTGGVd------- 96  pea aphid
NP_001139378  17 KARRRRGa-----------------------------PDDDGDGVMVLLKQLQEN---QLGMLWTAVESRGRdg------ 58  red flour beetle
XP_002435717  75 KLVKRLWeerarlvgcd-----------eyeavcaleECAHRKAVEATLKRMREP---QLELMLLAVRSRGRs------- 133 black-legged tick
EFZ19204     192 GCCNRPHrhhtrhf----------------psrryrhYRHHRSSRHHRSSSVEDD---QESCCSASEDSSSAaspmrsa- 251 red fire ant
NP_001071965   9 QLRRKLKrrilk--------------------qnpkeEDSVQAHVHALIASFEEN---QLENLFLALDSRGCd------- 58  Ciona intestinalis
XP_002073012 219 AANPRHSipl-------------------------tsATRKRKDFDAFIKQLKHK---QPADLLRAVKSRVDlpaktnss 270 Drosophila will...
XP_001998235 226 SQSRQRTasstptcpmhtqsptlspagagsmsatalrLETVHQNFDALLKKLKSK---QIADLLQAVRSRVDpphkrdp- 301 Drosophila moja...
NP_492746     14 RHVERLWrrr------------------------llvTSDERRARRRFLRLMRGFdaeDVEVIRKAVESDGVd------- 62  nematode
BAA22841     197 VSTSRATahppq--------------------tqaqnGKRFREDFEALMKQLKRK---QRNELLLAVKSRLDpptktqrd 253 fruit fly

Feature 1                                         ##                                #            
Q9W734       136 ---------------pGGCVLVar------geLRLgaa-------rrPPP--HLLLGKLFRWpDLQHPa---ELKALCEC 182 chicken
XP_001942613  97 ---------------aAECVAVr---------PFLf-----------ADP--AVICCRLWRWpDLRTVe---QLKSTPSC 136 pea aphid
NP_001139378  59 ---------------gSNCVLM----------PRD------------RQP--HVLCCQTWRWpDLLQSt---DLKRLPAC 96  red flour beetle
XP_002435717 134 ---------------gRACVPLa---------VADa----------sEAP--HVLCCRLWRWpQLRHHw---ELRRMPWC 174 black-legged tick
EFZ19204     252 ----------arngsgGGVVVPt---------RGSt----------aFDP--HLLCCQIWRWpDLEHSs---ELKRLPMC 297 red fire ant
NP_001071965  59 ---------------sAPCVQLsp------ehQLDpsf-------mkQSH--EIMVCKAFRWpDLENMs---QLCLMPYC 105 Ciona intestinalis
XP_002073012 271 itgggnvvvpsaspsyLKCILIk---------CTTiat-------eeDLH--HVTACRLFFWpDLRNGa---ELKRLPLC 329 Drosophila will...
XP_001998235 302 ----------pdtssyLQCILIk---------CSLp-----------IDKgqHVTTCQLFLWsDLMDAg---ELRRLPTC 348 Drosophila moja...
NP_492746     63 ---------------sKACAPGppmderveedPPDedsglipqidrpMSM--PYLCCKLWRWkDLQVDaalhRLEALPWC 125 nematode
BAA22841     254 vv----epttttaptyLQCILIp---------CKTqt---------vWEP--HVTASRLFFWrELWNAk---ELKRLPTC 306 fruit fly

Feature 1                                   
Q9W734       183 QSfgaa--dgptVCCNPYHFSRLCGPE 207 chicken
XP_001942613 137 QTakq----pdmLCCNPYHWSRRCEIE 159 pea aphid
NP_001139378  97 RFagd----pvyVCCNPYHWSRVYQPD 119 red flour beetle
XP_002435717 175 GAsp------lsVCCNPYHWSIVQRPG 195 black-legged tick
EFZ19204     298 HSakd----pvyICCNPYHWSRLCRSG 320 red fire ant
NP_001071965 106 ESpqs-----nhICLNPYHYSKYIDLP 127 Ciona intestinalis
XP_002073012 330 PTagd----svyACCNPLHWFRILHLI 352 Drosophila willistoni
XP_001998235 349 PSard----svyICCNPLHWYRINYPI 371 Drosophila mojavensis
NP_492746    126 RFgrvtinnatvSCCNPYHYALWIRPE 152 nematode
BAA22841     307 PAard----ciyMCCNPLHWFRILHQP 329 fruit fly

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