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28  structures 1235  species 0  interactions 8824  sequences 237  architectures

Family: WH2 (PF02205)

Summary: WH2 motif

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This is the Wikipedia entry entitled "WH2 motif". More...

WH2 motif Edit Wikipedia article

WH2 motif
PDB 2d1k EBI.jpg
Ternary complex of the WH2 domain of mim with actin-dnase I[1]
Identifiers
Symbol WH2
Pfam PF02205
InterPro IPR003124
SMART WH2
SCOP 1ej5
SUPERFAMILY 1ej5

Function

The WH2 motif or WH2 domain is an evolutionarily conserved sequence motif contained in proteins.[2] It is found in WASP proteins which control actin polymerisation, therefore, WH2 is important in cellular processes such as cell contractility, cell motility, cell trafficking and cell signalling.[3]

Motif

The WH2 motif (for Wiskott-Aldrich syndrome homology region 2) has been shown in WAS and Scar1/WASF1 (mammalian homologue) to interact via their WH2 motifs with actin.

The WH2 (WASP-Homology 2, or Wiskott-Aldrich homology 2) domain is an ~18 amino acids actin-binding motif. This domain was first recognized as an essential element for the regulation of the cytoskeleton by the mammalian Wiskott-Aldrich syndrome protein (WASP) family. WH2 proteins occur in eukaryotes from yeast to mammals, in insect viruses, and in some bacteria. The WH2 domain is found as a modular part of larger proteins; it can be associated with the WH1 or EVH1 domain and with the CRIB domain, and the WH2 domain can occur as a tandem repeat. The WH2 domain binds to actin monomers and can facilitate the assembly of actin monomers into actin filaments.[4][5]

Examples

Human genes encoding proteins containing the WH2 motif include:

References

  1. ^ PDB: 2d1k​; Lee SH, Kerff F, Chereau D, Ferron F, Klug A, Dominguez R (February 2007). "Structural basis for the actin-binding function of missing-in-metastasis". Structure. 15 (2): 145–55. doi:10.1016/j.str.2006.12.005. PMC 1853380Freely accessible. PMID 17292833. 
  2. ^ Machesky LM, Insall RH (1998). "Scar1 and the related Wiskott-Aldrich syndrome protein, WASP, regulate the actin cytoskeleton through the Arp2/3 complex". Curr. Biol. 8 (25): 1347–56. doi:10.1016/S0960-9822(98)00015-3. PMID 9889097. 
  3. ^ 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 2921111Freely accessible. PMID 20573979. 
  4. ^ Machesky LM, Insall RH, Volkman LE (2001). "WASP homology sequences in baculoviruses". Trends Cell Biol. 11 (7): 286–287. doi:10.1016/S0962-8924(01)02009-8. PMID 11434350. 
  5. ^ Lappalainen P, Paunola E, Mattila PK (2002). "WH2 domain: a small, versatile adapter for actin monomers". FEBS Lett. 513 (1): 92–97. doi:10.1016/S0014-5793(01)03242-2. PMID 11911886. 

This article incorporates text from the public domain Pfam and InterPro IPR003124


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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.

WH2 motif Provide feedback

The WH2 motif (for Wiskott Aldrich syndrome homology region 2) has been shown in WASP P42768 and Scar1 (mammalian homologue) to be the region that interacts with actin.

Literature references

  1. Machesky LM, Insall RH; , Curr Biol 1998;8:1347-1356.: Scar1 and the related Wiskott-Aldrich syndrome protein, WASP, regulate the actin cytoskeleton through the Arp2/3 complex. PUBMED:9889097 EPMC:9889097


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR003124

The WH2 (WASP-Homology 2, or Wiskott-Aldrich homology 2) domain is an ~18 amino acids actin-binding motif. This domain was first recognised as an essential element for the regulation of the cytoskeleton by the mammalian Wiskott-Aldrich syndrome protein (WASP) family. WH2 proteins occur in eukaryotes from yeast to mammals, in insect viruses, and in some bacteria. The WH2 domain is found as a modular part of larger proteins; it can be associated with the WH1 or EVH1 domain INTERPRO and with the CRIB domain INTERPRO , and the WH2 domain can occur as a tandem repeat. The WH2 domain binds actin monomers and can facilitate the assembly of actin monomers into newly forming actin filaments [ PUBMED:11434350 , PUBMED:11911886 ].

Some proteins known to contain a WH2 domain:

  • Mammalian Wiskott-Aldrich syndrome protein (WASP), a possible regulator of lymphocyte and platelet function. Defects in WASP are the cause of Wiskott- Aldrich syndrome (WAS), an X-linked recessive disease characterised by immune dysregulation and microthrombocytopenia. WASP proteins bind the actin nucleating protein complex Arp2/3.
  • Mammalian N-WASP/WASL and WASF/SCAR/WAVE1-3, and yeast LAS17, which are also proteins from the WASP family that participate in the transduction of signals from the cell surface to the actin cytoskeleton.
  • WAS protein family homologue 1 (WASH1), acts as a nucleation-promoting factor at the surface of endosomes, where it recruits and activates the Arp2/3 complex to induce actin polymerisation.
  • Baker's yeast Verprolin, a protein involved in cytoskeletal organisation and cellular growth.
  • Human WASP interacting protein (WASPIP/WIP), a WASP-, profilin- and actin-binding protein which induces actin polymerisation and redistribution.
  • Nuclear polyhedrosis virus (NPV) P61/78/83 capsid protein, which may be important for the persistence and survival of the virus.
  • Fruit fly Spir(e) protein, an actin nucleation factor involved in the development of oocytes and embryos. Spir is conserved among metazoans.
  • Mammalian metastasis suppressor 1 or Missing in Metastasis (MIM) protein, an actin-binding protein that may be related to cancer progression or tumor metastasis.

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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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 (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
(43)
Full
(8824)
Representative proteomes UniProt
(14524)
RP15
(1079)
RP35
(2722)
RP55
(6256)
RP75
(8931)
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PP/heatmap 1            

1Cannot generate PP/Heatmap alignments for seeds; no PP data available

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

Format an alignment

  Seed
(43)
Full
(8824)
Representative proteomes UniProt
(14524)
RP15
(1079)
RP35
(2722)
RP55
(6256)
RP75
(8931)
Alignment:
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Sequence:
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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
(43)
Full
(8824)
Representative proteomes UniProt
(14524)
RP15
(1079)
RP35
(2722)
RP55
(6256)
RP75
(8931)
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.

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: Family
Sequence Ontology: SO:0100021
Author: SMART
Number in seed: 43
Number in full: 8824
Average length of the domain: 26.70 aa
Average identity of full alignment: 38 %
Average coverage of the sequence by the domain: 4.76 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 23.1 13.0
Trusted cut-off 23.1 13.0
Noise cut-off 23.0 12.9
Model length: 30
Family (HMM) version: 23
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 WH2 domain has been found. There are 28 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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AlphaFold Structure Predictions

The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.

Protein Predicted structure External Information
A0A0G2K0D3 View 3D Structure Click here
A0A1D8PI26 View 3D Structure Click here
A0A1D8PU03 View 3D Structure Click here
A0A2R8Q261 View 3D Structure Click here
A0A2R8Q3C6 View 3D Structure Click here
A0A2R8QFS5 View 3D Structure Click here
A0A2R9YJH1 View 3D Structure Click here
A1L1Q2 View 3D Structure Click here
A1Z782 View 3D Structure Click here
A2BEV5 View 3D Structure Click here
A6NGB9 View 3D Structure Click here
A8DYL3 View 3D Structure Click here
B1AK53 View 3D Structure Click here
D3ZUD3 View 3D Structure Click here
D3ZUI5 View 3D Structure Click here
D3ZYM5 View 3D Structure Click here
E7F568 View 3D Structure Click here
E9PT22 View 3D Structure Click here
F1Q6U7 View 3D Structure Click here
F1QNX8 View 3D Structure Click here
F1QNY1 View 3D Structure Click here
F1QZL9 View 3D Structure Click here
F1R8X0 View 3D Structure Click here
I3ITM8 View 3D Structure Click here
M0R7F3 View 3D Structure Click here
O00401 View 3D Structure Click here
O08816 View 3D Structure Click here
O43312 View 3D Structure Click here
O43516 View 3D Structure Click here
O75128 View 3D Structure Click here
P0C7L0 View 3D Structure Click here
P29536 View 3D Structure Click here
P37370 View 3D Structure Click here
P42768 View 3D Structure Click here
P70315 View 3D Structure Click here
Q0GNC1 View 3D Structure Click here
Q0KI93 View 3D Structure Click here
Q10172 View 3D Structure Click here
Q12446 View 3D Structure Click here
Q1LVS2 View 3D Structure Click here