Summary: WH1 domain
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WH1 domain Edit Wikipedia article
| WH1 domain | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| Symbol | WH1 | ||||||||
| Pfam | PF00568 | ||||||||
| InterPro | IPR000697 | ||||||||
| SMART | WH1 | ||||||||
| SCOPe | 1evh / SUPFAM | ||||||||
| CDD | cd01205 | ||||||||
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Function
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
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
Human genes encoding proteins containing the WH1 domain include:
References
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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
- Eukaryotic Linear Motif resource motif class LIG_EVH1_1
- Eukaryotic Linear Motif resource motif class LIG_EVH1_2
- Eukaryotic Linear Motif resource motif class LIG_WH1
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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.
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
-
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
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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
-
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
Internal database links
| SCOOP: | DUF812 FapA FPP Macoilin Ran_BP1 Spc7 Tmemb_cc2 VID27_PH |
| Similarity to PfamA using HHSearch: | Ran_BP1 |
External database links
| HOMSTRAD: | WH1 |
| SCOP: | 1evh |
| SMART: | WH1 |
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 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 [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].
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 73 members:
ASK_PH BBL5 bPH_1 bPH_2 bPH_3 bPH_4 bPH_5 bPH_6 CARM1 Carm_PH DCP1 DUF1126 DUF1681 DUF3203 EbsA FERM_C Glycoprot_B_PH1 Glycoprot_B_PH2 GRAM hSac2 ICAP-1_inte_bdg INPP5B_PH IQ_SEC7_PH IRS ISP1_C ISP3_C Jak1_Phl Mcp5_PH Myosin_TH1 OCRL_clath_bd PH PH_10 PH_11 PH_12 PH_13 PH_14 PH_15 PH_16 PH_17 PH_18 PH_19 PH_2 PH_3 PH_4 PH_5 PH_6 PH_8 PH_9 PH_BEACH PH_RBD PH_TFIIH PID PID_2 POB3_N Proteasom_Rpn13 PTB Ran_BP1 Rtt106 SCAB-PH Sec3-PIP2_bind Sharpin_PH SIN1_PH SNX17_FERM_C SPT16 SSrecog SYCP2_SLD UCH_N VID27_PH Voldacs Vps36_ESCRT-II WH1 YcxB ZFYVE21_CAlignments
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, the UniProtKB sequence database, 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 (4667) |
Representative proteomes | UniProt (7418) |
NCBI (12643) |
Meta (10) |
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|---|---|---|---|---|---|---|---|---|---|
| RP15 (617) |
RP35 (1442) |
RP55 (3025) |
RP75 (4666) |
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| Jalview | |||||||||
| HTML | |||||||||
| PP/heatmap | 1 | ||||||||
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key:
available,
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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 (4667) |
Representative proteomes | UniProt (7418) |
NCBI (12643) |
Meta (10) |
||||
|---|---|---|---|---|---|---|---|---|---|
| RP15 (617) |
RP35 (1442) |
RP55 (3025) |
RP75 (4666) |
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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: | Alignment kindly provided by SMART |
| Previous IDs: | none |
| Type: | Domain |
| Sequence Ontology: | SO:0000417 |
| Author: | SMART |
| Number in seed: | 8 |
| Number in full: | 4667 |
| Average length of the domain: | 105.10 aa |
| Average identity of full alignment: | 28 % |
| Average coverage of the sequence by the domain: | 23.54 % |
HMM information
| HMM build commands: |
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 47079205 -E 1000 --cpu 4 HMM pfamseq
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| Model details: |
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| Model length: | 111 | ||||||||||||
| Family (HMM) version: | 24 | ||||||||||||
| Download: | download the raw HMM for this family |
Species distribution
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Interactions
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 60 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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