3QSV


Conserved Protein Domain Family
MH1_SMAD_4

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cd10492: MH1_SMAD_4 
Click on image for an interactive view with Cn3D
N-terminal Mad Homology 1 (MH1) domain in SMAD4
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 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).
Statistics
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PSSM-Id: 199816
Aligned: 17 rows
Threshold Bit Score: 199.216
Created: 29-Jun-2011
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
 
DNA bindingZn binding site
Conserved site includes 13 residues -Click on image for an interactive view with Cn3D
Feature 1:DNA binding site [nucleic acid binding site]
Evidence:
  • Comment:based on mouse SMAD4-MH1 and other SMAD-MH1 domains with structure
  • Structure:3QSV: Mus musculus SMAD4-MH1 domain binds DNA (a palindromic SMAD binding element, GTCTAGAC), contacts at 4A.
    View structure with Cn3D
  • Comment: MH1 binds to the major groove via a beta hairpin structure
  • Comment:SMAD4 may constitutively homo- and heterodimerizes on DNA independent of direct protein contacts
  • Citation:PMID 9741623

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                                    #   #  #                               ##  #####  # 
3QSV_A         6 DACLSIVHSLMCHrq----ggESETFAKRAIESLVKKLKEKKDELDSLITAITTNGAHPSKCVTIQRTLDGRLQVAGRKG 81  house mouse
P45897       146 DSCQQISHVLQCYqq----ggEDSDFVRKAIESLVKKLKDKRIELDALITAVTSNGKQPTGCVTIQRSLDGRLQVAGRKG 221 Caenorhabditis ...
XP_003227329  14 DACLSIVHSLMCHrq----ggESETFAKRAIESLVKKLKEKKDELDSLITAITTNGAHPSKCVTIQRTLDGRLQVAGRKG 89  green anole
NP_001090536  11 DACLSIVHSLMCHrq----ggESETFAKRAIESLVKKLKEKKDELDSLITAITTNGAHPSKCVTIQRTLDGRLQVAGRKG 86  African clawed ...
NP_001116172  11 DACLSIVHSLMCHrq----ggESETFAKRAIESLVKKLKEKKDELDSLITAITTNGAHPSKCVTIQRTLDGRLQVAGRKG 86  zebrafish
XP_003388571  49 ETCTSIVHSLMCHrq----ggESEQFAKRAVESLVKKLKDKRDELESLVTAITTNGARPSKCVTIPRTLDGRLQVAGRKG 124 Amphimedon quee...
XP_002116214   8 DATLGIVHTLMCHrq----ggESENFAKRAVESLVKKLKDKRDELDALITAVTSNGIQQSKCVTIARTLDGRLQVAGKKG 83  Trichoplax adha...
ABQ23404      14 DACLSIVHSLMCHrq----ggETETFAKRAIESLVKKLKEKKDELDSLITAITTNGAHPSKCVTIQRTLDGRLQVAGRKG 89  Branchiostoma b...
ABC88375      19 DANLSIVLSLMCHttchrqggETEKFAKRAIESLVKKLRKKTDELESLISTITTNGAQPSKCVTIQRTLDGRLQVCERKG 98  starlet sea ane...
CAK32532      50 DACMNIVHSLMCHrk----ggESEEFSKFAIESLIKKLKDRRDELDALIVAVTSNGATQTSCVTIQRTLDSRMQIAGRKC 125 Echinococcus mu...
Feature 1                        ##                               
3QSV_A        82 FPHVIYARLWRWPDLHKNELKHVKYCQYAFDlKCDSVCVNPYHYERVVS 130 house mouse
P45897       222 VPHVVYARIWRWPKVSKNELVKLVQCQTSSD-HPDNICINPYHYERVVS 269 Caenorhabditis elegans
XP_003227329  90 FPHVIYARLWRWPDLHKNELKHVKYCQYAFDlKCDSVCVNPYHYERVVS 138 green anole
NP_001090536  87 FPHVIYARLWRWPDLHKNELKHVKYCQYAFDlKCDSVCVNPYHYERVVS 135 African clawed frog
NP_001116172  87 FPHVIYARLWRWPDLHKNELKHVKYCQFAFDlKCDSVCVNPYHYERVVS 135 zebrafish
XP_003388571 125 FPHVIYAKIWRWPDLHKNELRHAQFCQYAFDlKCESVCVNPYHYERVVS 173 Amphimedon queenslandica
XP_002116214  84 FPHVIYSRIWRWPDLHKNELKHIKLCKFAFDlKLDHVCVNPYHYERVIS 132 Trichoplax adhaerens
ABQ23404      90 FPHVIYARIWRWPDLHKNELKQVKYCQYAFDlKADSVCVNPYHYERVVS 138 Branchiostoma belcheri tsingtauense
ABC88375      99 FPHVIYARLWRWPDIQKMEMKHLDFCRFGYDlKYESVCVNPYHYERIRS 147 starlet sea anemone
CAK32532     126 FPHLIYARLWRWSDAHKTELRHLPFCHFGFDkKLDWVCVNPYHYERTVS 174 Echinococcus multilocularis

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