Summary: MH2 domain
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MH2 domain Provide feedback
This is the MH2 (MAD homology 2) domain found at the carboxy terminus of MAD related proteins such as Smads. This domain is separated from the MH1 domain by a non-conserved linker region. The MH2 domain mediates interaction with a wide variety of proteins and provides specificity and selectivity to Smad function and also is critical for mediating interactions in Smad oligomers. Unlike MH1, MH2 does not bind DNA. The well-studied MH2 domain of Smad4 is composed of five alpha helices and three loops enclosing a beta sandwich. Smads are involved in the propagation of TGF-beta signals by direct association with the TGF-beta receptor kinase which phosphorylates the last two Ser of a conserved 'SSXS' motif located at the C-terminus of MH2 [1-3].
Literature references
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Yingling JM, Das P, Savage C, Zhang M, Padgett RW, Wang XF; , Proc Natl Acad Sci U S A 1996;93:8940-8944.: Mammalian dwarfins are phosphorylated in response to transforming growth factor beta and are implicated in control of cell growth. PUBMED:8799132 EPMC:8799132
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Kim J, Johnson K, Chen HJ, Carroll S, Laughon A; , Nature 1997;388:304-308.: Drosophila Mad binds to DNA and directly mediates activation of vestigial by Decapentaplegic. PUBMED:9230443 EPMC:9230443
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Attisano L, Tuen Lee-Hoeflich S; , Genome Biol 2001;2:REVIEWS3010.: The Smads. PUBMED:11532220 EPMC:11532220
Internal database links
SCOOP: | IRF-3 |
Similarity to PfamA using HHSearch: | IRF-3 |
External database links
SCOP: | 1ygs |
This tab holds annotation information from the InterPro database.
InterPro entry IPR001132
Mammalian dwarfins are phosphorylated in response to transforming growth factor beta and are implicated in control of cell growth [ PUBMED:8799132 ]. The dwarfin family also includes the Drosophila protein MAD that is required for the function of decapentaplegic (DPP) and may play a role in DPP signalling. Drosophila Mad binds to DNA and directly mediates activation of vestigial by Dpp [ PUBMED:9230443 ]. This domain is also found in nuclear factor I (NF-I) or CCAAT box-binding transcription factor (CTF).
This entry represents the SMAD (Mothers against decapentaplegic (MAD) homologue) (also called MH2 for MAD homology 2) domain found at the carboxy terminus of MAD related proteins such as Smads. This domain is separated from the MH1 domain by a non-conserved linker region. The MH2 domain mediates interaction with a wide variety of proteins and provides specificity and selectivity to Smad function and also is critical for mediating interactions in Smad oligomers. Unlike MH1, MH2 does not bind DNA. The well-studied MH2 domain of Smad4 is composed of five alpha helices and three loops enclosing a beta sandwich. Smads are involved in the propagation of TGF-beta signals by direct association with the TGF-beta receptor kinase which phosphorylates the last two Ser of a conserved 'SSXS' motif located at the C terminus of MH2 [ PUBMED:11532220 , PUBMED:9230443 , PUBMED:8799132 ].
Gene Ontology
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
Biological process | regulation of transcription, DNA-templated (GO:0006355) |
Domain organisation
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
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Pfam Clan
This family is a member of clan SMAD-FHA (CL0357), which has the following description:
Superfamily members carry a few short helices inserted in loops within the 11 strands in 2 sheets (greek-key) of the parent fold.
The clan contains the following 9 members:
FHA FHA_2 FtsK_SpoIIIE_N IRF-3 MH2 MU2_FHA Pellino PrgH Yop-YscD_cplAlignments
We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB sequence database. More...
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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.
Seed (82) |
Full (4578) |
Representative proteomes | UniProt (8008) |
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RP15 (863) |
RP35 (1879) |
RP55 (4063) |
RP75 (5123) |
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PP/heatmap | 1 |
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key:
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Seed (82) |
Full (4578) |
Representative proteomes | UniProt (8008) |
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RP15 (863) |
RP35 (1879) |
RP55 (4063) |
RP75 (5123) |
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Raw Stockholm | |||||||
Gzipped |
You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.
HMM logo
HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...
Trees
This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.
Note: You can also download the data file for the tree.
Curation and family details
This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.
Curation
Seed source: | Pfam-B_519 (release 3.0) |
Previous IDs: | none |
Type: | Family |
Sequence Ontology: | SO:0100021 |
Author: |
Bateman A |
Number in seed: | 82 |
Number in full: | 4578 |
Average length of the domain: | 169.80 aa |
Average identity of full alignment: | 48 % |
Average coverage of the sequence by the domain: | 38.78 % |
HMM information
HMM build commands: |
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 57096847 -E 1000 --cpu 4 HMM pfamseq
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Model details: |
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Model length: | 174 | ||||||||||||
Family (HMM) version: | 16 | ||||||||||||
Download: | download the raw HMM for this family |
Species distribution
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Structures
For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the MH2 domain has been found. There are 48 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.
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