Schultz et al. (1998) Proc. Natl. Acad. Sci. USA 95, 5857-5864
Letunic et al. (2012) Nucleic Acids Res , doi:10.1093/nar/gkr931

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PWWP domain with conserved PWWP motif

SMART accession number:	SM00293
Description:	conservation of Pro-Trp-Trp-Pro residues
Interpro abstract (IPR000313):	Upon characterisation of WHSC1, a gene mapping to the Wolf-Hirschhornsyndrome critical region and at its C terminus similar to the Drosophila melanogaster ASH1/trithorax group proteins, a novel protein domain designated PWWP domain was identified [(PUBMED:9618163)]. The PWWP domain is named after a conserved Pro-Trp-Trp-Pro motif. It is present in proteins of nuclear origin and plays a role in cell growth and differentiation. Due to its position, the composition of amino acids close to the PWWP motif and the pattern of other domains present it has been suggested that the domain is involved in protein-protein interactions [(PUBMED:10802047)].
Family alignment:	View or CHROMA formatCLUSTALW formatMSF formatFASTA formatPIR format

There are 686 PWWP domains in 597 proteins in SMART's nrdb database.

Click on the following links for more information.

• Evolution (species in which this domain is found)

• Click on to expand nodes. To display all proteins with a PWWP domain in a specific node, click on it.

  This tree shows only several representative species. The complete taxonomic breakdown of all proteins with PWWP domain is also avaliable.

  Useful shortcuts: Expand all nodes or Collapse tree
  Go to specific node: Anopheles gambiae, Caenorhabditis elegans, Drosophila melanogaster, Homo sapiens, Mus musculus, Rattus norvegicus, Saccharomyces cerevisiae, Takifugu rubripes

• Literature (relevant references for this domain)

• Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.

  • Stec I et al.
  • WHSC1, a 90 kb SET domain-containing gene, expressed in early development and homologous to a Drosophila dysmorphy gene maps in the Wolf-Hirschhorn syndrome critical region and is fused to IgH in t(4;14) multiple myeloma.
  • Hum Mol Genet. 1998; 7: 1071-82
  • Display abstract

  • Wolf-Hirschhorn syndrome (WHS) is a malformation syndrome associated with a hemizygous deletion of the distal short arm of chromosome 4 (4p16.3). The smallest region of overlap between WHS patients, the WHS critical region, has been confined to 165 kb, of which the complete sequence is known. We have identified and studied a 90 kb gene, designated as WHSC1 , mapping to the 165 kb WHS critical region. This 25 exon gene is expressed ubiquitously in early development and undergoes complex alternative splicing and differential polyadenylation. It encodes a 136 kDa protein containing four domains present in other developmental proteins: a PWWP domain, an HMG box, a SET domain also found in the Drosophila dysmorphy gene ash -encoded protein, and a PHD-type zinc finger. It is expressed preferentially in rapidly growing embryonic tissues, in a pattern corresponding to affected organs in WHS patients. The nature of the protein motifs, the expression pattern and its mapping to the critical region led us to propose WHSC1 as a good candidate gene to be responsible for many of the phenotypic features of WHS. Finally, as a serendipitous finding, of the t(4;14) (p16.3;q32.3) translocations recently described in multiple myelomas, at least three breakpoints merge the IgH and WHSC1 genes, potentially causing fusion proteins replacing WHSC1 exons 1-4 by the IgH 5'-VDJ moiety.

• Metabolism (metabolic pathways involving proteins which contain this domain)

• Click the image to view the interactive version of the map in iPath

  % proteins involved KEGG pathway ID Description 54.55 map00271 Methionine metabolism 27.27 map05210 Colorectal cancer 13.64 map00310 Lysine degradation 4.55 map00280 Valine, leucine and isoleucine degradation This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with PWWP domain which could be assigned to a KEGG orthologous group, and not all proteins containing PWWP domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.

• Structure (3D structures containing this domain)

• 3D Structures of PWWP domains in PDB

  PDB code	Main view	Title
  1h3z		Solution structure of a pwwp domain from schizosaccharomyces pombe
  1khc		Crystal structure of the pwwp domain of mammalian dna methyltransferase dnmt3b
  1n27		Solution structure of the pwwp domain of mouse hepatoma- derived growth factor, related protein 3
  1ri0		Nmr structure of the n-terminal hath domain of human hdgf
  2b8a		High resolution structure of the hdgf pwwp domain
  2daq		Solution structure of second pwwp domain of whsc1l1 protein
  2gfu		Nmr solution structure of the pwwp domain of mismatch repair protein hmsh6
  2nlu		Domain-swapped dimer of the pwwp module of human hepatoma- derived growth factor
  3eae		Pwwp domain of human hepatoma-derived growth factor 2 (hdgf2)
  3flg		The pwwp domain of human dna (cytosine-5-)-methyltransferase beta

• Links (links to other resources describing this domain)

• PFAM	PWWP
  INTERPRO	IPR000313

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