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25  structures 236  species 0  interactions 1177  sequences 30  architectures

Family: WH1 (PF00568)

Summary: WH1 domain

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This is the Wikipedia entry entitled "WH1 domain". More...

WH1 domain Edit Wikipedia article

WH1 domain
Identifiers
Symbol WH1
Pfam PF00568
InterPro IPR000697
SMART WH1
SCOP 1evh
SUPERFAMILY 1evh

Function[edit]

WH1 domain is an evolutionary conserved protein domain.[1] Therefore, it has an important function. WH1 domains are found on WASP proteins, which are often involved in actin polymerization. Hence, WH1 is important for all cellular processes involving actin, this includes cell motility, cell trafficking, cell division and cytokinesis, cell signalling, and the establishment and maintenance of cell junctions and cell shape.[2]

Interactions[edit]

The WASP protein family control actin polymerization by activating the Arp2/3 complex. WASP is defective in Wiskott-Aldrich syndrome (WAS) whereby in most patient cases, the majority of point mutations occur within the N-terminal WH1 domain. The metabotropic glutamate receptors mGluR1alpha and mGluR5 bind a protein called homer, which is a WH1 domain homologue.[3][4]

A subset of WH1 domains has been termed the EVH1 domain and appear to bind a polyproline motif. The EVH1 (WH1, RanBP1-WASP) domain is found in multi-domain proteins implicated in a diverse range of signalling, nuclear transport and cytoskeletal events. This domain of around 115 amino acids is present in species ranging from yeast to mammals. Many EVH1-containing proteins associate with actin-based structures and play a role in cytoskeletal organisation. EVH1 domains recognise and bind the proline-rich motif FPPPP with low-affinity, further interactions then form between flanking residues.[4][5]

WASP family proteins contain an EVH1 (WH1) in their N-terminals which bind proline-rich sequences in the WASP interacting protein. Proteins of the RanBP1 family contain a WH1 domain in their N-terminal region, which seems to bind a different sequence motif present in the C-terminal part of RanGTP protein.[6][7]

Tertiary structure of the WH1 domain of the Mena protein revealed structure similarities with the pleckstrin homology (PH) domain. The overall fold consists of a compact parallel beta-sandwich, closed along one edge by a long alpha-helix. A highly conserved cluster of three surface-exposed aromatic side-chains forms the recognition site for the molecules target ligands.[8]

Examples[edit]

Human genes encoding proteins containing the WH1 domain include:

References[edit]

  1. ^ Symons M, Derry JM, Karlak B, Jiang S, Lemahieu V, Mccormick F, Francke U, Abo A (March 1996). "Wiskott-Aldrich syndrome protein, a novel effector for the GTPase CDC42Hs, is implicated in actin polymerization". Cell 84 (5): 723–34. doi:10.1016/S0092-8674(00)81050-8. PMID 8625410. 
  2. ^ Veltman DM, Insall RH (2010). "WASP family proteins: their evolution and its physiological implications.". Mol Biol Cell 21 (16): 2880–93. doi:10.1091/mbc.E10-04-0372. PMC 2921111. PMID 20573979. 
  3. ^ Ponting CP, Phillips C (1997). "Identification of homer as a homologue of the Wiskott-Aldrich syndrome protein suggests a receptor-binding function for WH1 domains". J. Mol. Med. 75 (11-12): 769–71. doi:10.1007/s001090050166. PMID 9428607. 
  4. ^ a b Niebuhr K, Ebel F, Frank R, Reinhard M, Domann E, Carl UD, Walter U, Gertler FB, Wehland J, Chakraborty T (September 1997). "A novel proline-rich motif present in ActA of Listeria monocytogenes and cytoskeletal proteins is the ligand for the EVH1 domain, a protein module present in the Ena/VASP family". EMBO J. 16 (17): 5433–44. doi:10.1093/emboj/16.17.5433. PMC 1170174. PMID 9312002. 
  5. ^ Ball LJ, Jarchau T, Oschkinat H, Walter U (February 2002). "EVH1 domains: structure, function and interactions". FEBS Lett. 513 (1): 45–52. doi:10.1016/S0014-5793(01)03291-4. PMID 11911879. 
  6. ^ Callebaut I, Cossart P, Dehoux P (December 1998). "EVH1/WH1 domains of VASP and WASP proteins belong to a large family including Ran-binding domains of the RanBP1 family". FEBS Lett. 441 (2): 181–5. doi:10.1016/S0014-5793(98)01541-5. PMID 9883880. 
  7. ^ Beddow AL, Richards SA, Orem NR, Macara IG (April 1995). "The Ran/TC4 GTPase-binding domain: identification by expression cloning and characterization of a conserved sequence motif". Proc. Natl. Acad. Sci. U.S.A. 92 (8): 3328–32. doi:10.1073/pnas.92.8.3328. PMC 42159. PMID 7724562. 
  8. ^ Prehoda KE, Lee DJ, Lim WA (May 1999). "Structure of the enabled/VASP homology 1 domain-peptide complex: a key component in the spatial control of actin assembly". Cell 97 (4): 471–80. doi:10.1016/S0092-8674(00)80757-6. PMID 10338211. 

External links[edit]

This article incorporates text from the public domain Pfam and InterPro IPR007875


This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

WH1 domain Provide feedback

WASp Homology domain 1 (WH1) domain. WASP is the protein that is defective in Wiskott-Aldrich syndrome (WAS). The majority of point mutations occur within the amino- terminal WH1 domain. The metabotropic glutamate receptors mGluR1alpha and mGluR5 bind a protein called homer, which is a WH1 domain homologue [2]. A subset of WH1 domains has been termed a "EVH1" domain [3] and appear to bind a polyproline motif.

Literature references

  1. Symons M, Derry JM, Karlak B, Jiang S, Lemahieu V, Mccormick F, Francke U, Abo A; , Cell 1996;84:723-734.: Wiskott-Aldrich syndrome protein, a novel effector for the GTPase CDC42Hs, is implicated in actin polymerization. PUBMED:8625410 EPMC:8625410

  2. Ponting CP, Phillips C; , J Mol Med. 1997;75:769-771.: Identification of homer as a homologue of the Wiskott-Aldrich syndrome protein suggests a receptor-binding function for WH1 domains PUBMED:9428607 EPMC:9428607

  3. Niebuhr K, Ebel F, Frank R, Reinhard M, Domann E, Carl UD, Walter U, Gertler FB, Wehland J, Chakraborty T; , EMBO J 1997;16:5433-5444.: A novel proline-rich motif present in ActA of Listeria monocytogenes and cytoskeletal proteins is the ligand for the EVH1 domain, a protein module present in the Enas/VASP family. PUBMED:9312002 EPMC:9312002


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR000697

The EVH1 (WH1, RanBP1-WASP) domain is found in multi-domain proteins implicated in a diverse range of signalling, nuclear transport and cytoskeletal events. This domain of around 115 amino acids is present in species ranging from yeast to mammals. Many EVH1-containing proteins associate with actin-based structures and play a role in cytoskeletal organisation. EVH1 domains recognise and bind the proline-rich motif FPPPP with low-affinity, further interactions then form between flanking residues [PUBMED:11911879][PUBMED:9312002].

WASP family proteins contain a EVH1 (WH1) in their N-terminals which bind proline-rich sequences in the WASP interacting protein. Proteins of the RanBP1 family contain a WH1 domain in their N-terminal region, which seems to bind a different sequence motif present in the C-terminal part of RanGTP protein [PUBMED:9883880,PUBMED:7724562].

Tertiary structure of the WH1 domain of the Mena protein revealed structure similarities with the pleckstrin homology (PH) domain. The overall fold consists of a compact parallel beta-sandwich, closed along one edge by a long alpha-helix. A highly conserved cluster of three surface-exposed aromatic side-chains forms the recognition site for the molecules target ligands. [PUBMED:10338211].

Gene Ontology

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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 PH (CL0266), which has the following description:

Members of this clan share a PH-like fold. Many families in this clan bind to short peptide motifs in proteins and are involved in signalling.

The clan contains the following 33 members:

bPH_1 bPH_2 bPH_3 bPH_4 bPH_5 bPH_6 DCP1 DUF1448 FERM_C GRAM ICAP-1_inte_bdg Mcp5_PH PH PH_10 PH_11 PH_2 PH_3 PH_4 PH_5 PH_6 PH_7 PH_8 PH_9 PH_BEACH PID PID_2 PTB Ran_BP1 Rtt106 SSrecog Voldacs Vps36_ESCRT-II WH1

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...

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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
(8)
Full
(1177)
Representative proteomes NCBI
(1088)
Meta
(23)
RP15
(159)
RP35
(234)
RP55
(397)
RP75
(600)
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Format an alignment

  Seed
(8)
Full
(1177)
Representative proteomes NCBI
(1088)
Meta
(23)
RP15
(159)
RP35
(234)
RP55
(397)
RP75
(600)
Alignment:
Format:
Order:
Sequence:
Gaps:
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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
(8)
Full
(1177)
Representative proteomes NCBI
(1088)
Meta
(23)
RP15
(159)
RP35
(234)
RP55
(397)
RP75
(600)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   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.

Pfam alignments:

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: Alignment kindly provided by SMART
Previous IDs: none
Type: Domain
Author: SMART
Number in seed: 8
Number in full: 1177
Average length of the domain: 104.80 aa
Average identity of full alignment: 28 %
Average coverage of the sequence by the domain: 24.22 %

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 21.1 21.1
Trusted cut-off 21.1 21.1
Noise cut-off 21.0 21.0
Model length: 111
Family (HMM) version: 18
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 WH1 domain has been found. There are 25 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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