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10  structures 119  species 1  interaction 1320  sequences 19  architectures

Family: MH1 (PF03165)

Summary: MH1 domain

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MH1 domain Provide feedback

The MH1 (MAD homology 1) domain is found at the amino terminus of MAD related proteins such as Smads. This domain is separated from the MH2 domain by a non-conserved linker region. The crystal structure of the MH1 domain shows that a highly conserved 11 residue beta hairpin is used to bind the DNA consensus sequence GNCN in the major groove, shown to be vital for the transcriptional activation of target genes. Not all examples of MH1 can bind to DNA however. Smad2 cannot bind DNA and has a large insertion within the hairpin that presumably abolishes DNA binding. A basic helix (H2) in MH1 with the nuclear localisation signal KKLKK has been shown to be essential for Smad3 nuclear import. Smads also use the MH1 domain to interact with transcription factors such as Jun, TFE3, Sp1, and Runx [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


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR003619

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 MH1 (MAD homology 1) domain is found at the amino terminus of MAD related proteins such as Smads. This domain is separated from the MH2 domain by a non-conserved linker region. The crystal structure of the MH1 domain shows that a highly conserved 11 residue beta hairpin is used to bind the DNA consensus sequence GNCN in the major groove, shown to be vital for the transcriptional activation of target genes. Not all examples of MH1 can bind to DNA however. Smad2 cannot bind DNA and has a large insertion within the hairpin that presumably abolishes DNA binding. A basic helix (H2) in MH1 with the nuclear localisation signal KKLKK has been shown to be essential for Smad3 nuclear import. Smads also use the MH1 domain to interact with transcription factors such as Jun, TFE3, Sp1, and Runx [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 His-Me_finger (CL0263), which has the following description:

This superfamily defined originally by SCOP contains a diverse range of endonucleases. Later Grishin identified the MH1 domain as belonging to the superfamily [1].

The clan contains the following 19 members:

AHH Colicin-DNase DUF1524 Endonuclea_NS_2 Endonuclease_1 Endonuclease_7 Endonuclease_NS GH-E HNH HNH_2 HNH_3 HNH_4 HNH_5 ICEA LHH MH1 NinG WHH zf-His_Me_endon

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
(19)
Full
(1320)
Representative proteomes NCBI
(1055)
Meta
(0)
RP15
(141)
RP35
(193)
RP55
(390)
RP75
(608)
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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
(19)
Full
(1320)
Representative proteomes NCBI
(1055)
Meta
(0)
RP15
(141)
RP35
(193)
RP55
(390)
RP75
(608)
Alignment:
Format:
Order:
Sequence:
Gaps:
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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
(19)
Full
(1320)
Representative proteomes NCBI
(1055)
Meta
(0)
RP15
(141)
RP35
(193)
RP55
(390)
RP75
(608)
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: Domain
Author: Bateman A
Number in seed: 19
Number in full: 1320
Average length of the domain: 101.20 aa
Average identity of full alignment: 42 %
Average coverage of the sequence by the domain: 22.56 %

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 25.2 27.8
Noise cut-off 24.2 24.4
Model length: 103
Family (HMM) version: 11
Download: download the raw HMM for this family

Species distribution

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Interactions

There is 1 interaction for this family. More...

MH1

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 MH1 domain has been found. There are 10 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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