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31  structures 139  species 2  interactions 1087  sequences 17  architectures

Family: MH2 (PF03166)

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

  1. 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

  2. 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

  3. Attisano L, Tuen Lee-Hoeflich S; , Genome Biol 2001;2:REVIEWS3010.: The Smads. PUBMED:11532220 EPMC:11532220


Internal database links

External database links

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.

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 3 members:

FHA IRF-3 MH2

Alignments

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 using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics sequence database. More...

View options

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
(11)
Full
(1087)
Representative proteomes NCBI
(937)
Meta
(0)
RP15
(143)
RP35
(186)
RP55
(378)
RP75
(549)
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(11)
Full
(1087)
Representative proteomes NCBI
(937)
Meta
(0)
RP15
(143)
RP35
(186)
RP55
(378)
RP75
(549)
Alignment:
Format:
Order:
Sequence:
Gaps:
Download/view:

Download options

We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(11)
Full
(1087)
Representative proteomes NCBI
(937)
Meta
(0)
RP15
(143)
RP35
(186)
RP55
(378)
RP75
(549)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download    
Gzipped Download   Download   Download   Download   Download   Download   Download    

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

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 View help on the curation process

Seed source: Pfam-B_519 (release 3.0)
Previous IDs: none
Type: Family
Author: Bateman A
Number in seed: 11
Number in full: 1087
Average length of the domain: 167.40 aa
Average identity of full alignment: 50 %
Average coverage of the sequence by the domain: 39.60 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 25.0 25.0
Trusted cut-off 25.1 25.0
Noise cut-off 22.2 24.6
Model length: 182
Family (HMM) version: 9
Download: download the raw HMM for this family

Species distribution

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This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

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Interactions

There are 2 interactions for this family. More...

MH2 SARA

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 31 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 seqence.

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