1OZJ,1MHD


Conserved Protein Domain Family
MH1_SMAD_2_3

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cd10491: MH1_SMAD_2_3 
Click on image for an interactive view with Cn3D
N-terminal Mad Homology 1 (MH1) domain in SMAD2 and SMAD3
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 is found in SMAD2 as well as SMAD3. SMAD2 mediates the signal of the transforming growth factor (TGF)-beta, and thereby regulates multiple cellular processes, such as cell proliferation, apoptosis, and differentiation. It plays a role in the transmission of extracellular signals from ligands of the TGF-beta superfamily growth factors into the cell nucleus. SMAD3 modulates signals of activin and TGF-beta. It binds SMAD4, enabling its transmigration into the nucleus where it forms complexes with other proteins and acts as a transcription factor. Increased SMAD3 activity has been implicated in the pathogenesis of scleroderma.
Statistics
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PSSM-Id: 199815
View PSSM: cd10491
Aligned: 14 rows
Threshold Bit Score: 227.413
Threshold Setting Gi: 21264050
Created: 29-Jun-2011
Updated: 17-Jan-2013
Structure
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Program:
Drawing:
Aligned Rows:
 
DNA bindingZn binding site
Conserved site includes 11 residues -Click on image for an interactive view with Cn3D
Feature 1:DNA binding site [nucleic acid binding site]
Evidence:
  • Comment:based on human SMAD3-MH1 and other SMAD-MH1 domains with structure
  • Comment: MH1 binds to the major groove via a beta hairpin structure
  • Structure:1MHD: human SMAD3-MH1 binds DNA (a palindromic SMAD binding element, GTCTAGAC), contacts at 4.0A
    View structure with Cn3D
  • Citation:PMID 9741623

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                            #   #                                #      
1OZJ_A         8 TPPIVKRLLGWKKgeq-----------ngQEEKWCEKAVKSLVKKLKKTGQLDELEKAITTQNVNTKCITIPRS------ 70
gi 118343994   5 TPPVVKELLGWKRgem-----------saQDEKFAEKAIKSLVKKLKKSGGLEDLKKAVTKQSIDTKCVKIPRS------ 67
gi 21264050    8 TPPVVKRLLGWKKsasgssgaggggeqngQEEKWCEKAVKSLVKKLKKTGQLDELEKAITTQNRNTKCVTIPSNcseiwg 87
gi 148235305   8 TPPIVKRLLGWKKgeq-----------ngQEEKWCEKAVKSLVKKLKKSGQLDELEKALTTQSISTKCITIPRS------ 70
gi 321473505   7 LSSPVKRLLGWKRg--------------eGEEKWSEKAVKSLVKKLKKSGGLDELEKAVTSQSSSTKCITIPRS------ 66
1MHD_A         8 TPPIVKRLLGWKKgeq-----------ngQEEKWCEKAVKSLVKKLKKTGQLDELEKAITTQNVNTKCITIPRS------ 70
gi 260826197   8 TPPIVKRLLGWKKg--------------eGEDKWSEKAVKSLVKKLKKTCGLEELEKSITQQDPNTKCVTIPRS------ 67
gi 241119204   8 TPPVVKRLLGWKKg--------------eGEDKWSEKAVKSLVKKLKKSGGIDELEKSISTQDVHTKCITIPRS------ 67
gi 126506312   9 TPPIVKRLLGWKKd--------------nSEDKWSEKAVKSLVKKLKKTGCLEELERAVTTQNSQTKCITIPRS------ 68
gi 161110488   8 TPPIVKKLLGWKKge------------ssEVDKWSEKAVKSLVKKLKKTGGLDELEKAIRLQDSTTKCITIPRS------ 69
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                   #####  #                  ##                         
1OZJ_A        71 ------------------------LDGRLQVSHRKGLPHVIYCRLWRWPDLHSHHELRAMELCEFAFnmKKDEVCVNPYH 126
gi 118343994  68 ------------------------LDGRLQVSHKKSLPHVLYCRLWRWPDLRNHHELRPVEKCEYAFqlKRDEVCVNPYH 123
gi 21264050   88 lstpntieqwdtsglysypdqtrsLDGRLQVSHRKGLPHVIYCRLWRWPDLHSHHELRAIETCEYAFnlKKDEVCVNPYH 167
gi 148235305  71 ------------------------LDGRLQVSHRKGLPHVIYCRLWRWPDLHSHHELRAMEVCEYAFsmKKDEVCVNPYH 126
gi 321473505  67 ------------------------LDGRLQVSQRKGLPHVIYCRLWRWPDLQTHHELHALENCEYAFqlKRDEVCVNPYH 122
1MHD_A        71 ------------------------LDGRLQVSHRKGLPHVIYCRLWRWPDLHSHHELRAMELCEFAFnmKKDEVCVNPYH 126
gi 260826197  68 ------------------------LDGRLQVSHRKGLPHVIYCRLWRWPDLQSHHELRALETCEYAFslKREEVCVNPYH 123
gi 241119204  68 ------------------------LDGRLQVSHRKGLPHVIYCRLWRWPDLQSHHELRATDNCQYAFnlKKDEVCINPYH 123
gi 126506312  69 ------------------------LDGRLQVSHRKGLPHVIYCRLWRWPDLQSHHELKAVERCEYAFhlKKDEVCVNPYH 124
gi 161110488  70 ------------------------LDGRLQVSHRKGLPHVIYCRLWRWPDLQNHQELRAIDSCEWAFhlKRDEVCVNPYH 125

                 ....*.
Feature 1              
1OZJ_A       127 YQRVET 132
gi 118343994 124 YTRVET 129
gi 21264050  168 YQRVET 173
gi 148235305 127 YQRVET 132
gi 321473505 123 YQRVET 128
1MHD_A       127 YQRVET 132
gi 260826197 124 YQRVET 129
gi 241119204 124 YQRVET 129
gi 126506312 125 YARVET 130
gi 161110488 126 YNRIEA 131

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