1DD1,3GMJ,1KHU


Conserved Protein Domain Family
MH2
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cd00050: MH2 
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C-terminal Mad Homology 2 (MH2) domain
The MH2 domain is found in the SMAD (small mothers against decapentaplegic) family of proteins and is responsible for type I receptor interactions, 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. The MH2 domain is multifunctional and provides SMADs with their specificity and selectivity, as well as transcriptional activity. Several transcriptional co-activators and repressors have also been reported to regulate SMAD signaling by interacting with the MH2 domain. Mutations in the MH2 domains of SMAD2 and especially SMAD4 have been detected in colorectal and other human cancers.
Links
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Statistics
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PSSM-Id: 199819
Aligned: 4 rows
Threshold Bit Score: 281.802
Created: 1-Nov-2000
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
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trimer
Conserved site includes 25 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
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  • Structure:1DD1: Human SMAD4 MH2 domain homotrimer; contacts at 4.0A
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  • Structure:1KHU; Human SMAD1 MH2 domain homotrimer; contacts at 4A.
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Sequence Alignment
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Format: Row Display: Color Bits: Type Selection: 

Feature 1           #         ## #           #####       #   #### #         #   ## #          
1DD1_B     39 WCSIAYFE.[3].QVGETFKV.[6].VTVDGYVDPS.[1].GDRFCLGQLSNV.[2].TEAIERARLHIG.[1].GVQLE 106 human
3GMJ_A     51 WASIAYYE.[3].RVGEVFHC.[4].VIVDGFTNPS.[2].SDRCCLGQLSNV.[2].NSTIENTRRHIG.[1].GVHLY 117 fruit fly
O35182    332 WCSVAYWE.[3].RVGRLYAV.[2].QAVSIFYDLP.[1].GSGFCLGQLNLE.[2].SESVRRTRSKIG.[1].GILLS 395 house mouse
1KHU_A     24 WCSIVYYE.[3].RVGEAFHA.[4].VLVDGFTDPS.[2].KNRFCLGLLSNV.[2].NSTIENTRRHIG.[1].GVHLY 90  human


Feature 1                                                                               #  #  
1DD1_B    107 C.[4].DVWVRCLS.[2].AVFVQSYYLDREA.[6].AVHKIYP.[1].AYIKVFD.[2].QCHRQMQ.[44].DDLRRL 214 human
3GMJ_A    118 Y.[3].EVYAECLS.[2].AIFVQSRNCNYQH.[5].TVCKIPP.[1].CSLKIFN.[2].EFAQLLS.[10].YELTKM 189 fruit fly
O35182    396 K.[3].GVWAYNRG.[2].PIFVNSPTLDAPG.[4].VVRKVPP.[1].YSIKVFD.[2].RSGLLQH.[ 3].AHGPYD 459 house mouse
1KHU_A     91 Y.[3].EVYAECLS.[2].SIFVQSRNCNYHH.[5].TVCKIPS.[1].CSLKIFN.[2].EFAQLLA.[10].YELTKM 162 human


Feature 1                                     #      # # #
1DD1_B    215 .[1].ILRMSF.[1].KGWGPDY.[1].RQSIKETPCWIEIHLH 246 human
3GMJ_A    190 .[1].TIRMSF.[1].KGWGAEY.[1].RQDVTSTPCWIEIHLH 221 fruit fly
O35182    460 .[2].SVRISF.[1].KGWGPCY.[1].RQFITSCPCWLEILLN 492 house mouse
1KHU_A    163 .[1].TIRMSF.[1].KGWGAEY.[1].RQDVTSTPCWIEIHLH 194 human

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