ELM Details - LIG_WW

LIG_WW_1

Functional site class:	WW ligand
Functional site description:	the motif is implicated in protein-protein interactions mediated WW domains
ELM(s):	LIG_WW_4, LIG_WW_1, LIG_WW_2, LIG_WW_3
LIG_WW_1 description:	PPXY is the motif recognized by WW domains of Group I
Pattern:	PP.Y
Present in taxon(s):	Homo sapiens Eukaryota Mus musculus Rattus norvegicus
Not represented in taxon(s):

See instances for LIG_WW_1

Abstract

WW are small modular domains of 38-40 residues long that mediate protein-protein interaction through binding of short proline rich regions within proteins. WW domain-containing proteins are involved in many cellular processes such as ubiquitin mediated protein degradation and mitotic regulation and they are also implicated directly or indirectly in several human diseases such as muscular distrophy and Alzheimer’s and Huntington’s diseases. Based on their ligand specificity, the WW domains can be devided in five class. Group I WW domains bind proteins containing the PPXY motif, while the group II recognizes the PPLP motif. Group IV recognition is serine-phosphorylation dependent.

Selected references

Bonni S, Wang HR, Causing CG, Kavsak P, Stroschein SL, Luo K, Wrana JL

TGF-beta induces assembly of a Smad2-Smurf2 ubiquitin ligase complex that targets SnoN for degradation.

Nat Cell Biol 2001 Jun;3(6) : 587-95.

PMID: 11389444

Chen HI, Sudol M

The WW domain of Yes-associated protein binds a proline-rich ligand that differs from the consensus established for Src homology 3-binding modules.

Proc Natl Acad Sci U S A 1995 Aug 15;92(17) : 7819-23.

PMID: 7644498

Gavva NR, Gavva R, Ermekova K, Sudol M, Shen CJ

Interaction of WW domains with hematopoietic transcription factor p45/NF-E2 and RNA polymerase II.

J Biol Chem 1997 Sep 26;272(39) : 24105-8.

PMID: 9305852

Hamilton MH, Tcherepanova I, Huibregtse JM, McDonnell DP

Nuclear import/export of hRPF1/Nedd4 regulates the ubiquitin-dependent degradation of its nuclear substrates.

J Biol Chem 2001 Jul 13;276(28) : 26324-31.

PMID: 11342538

Harvey KF, Dinudom A, Komwatana P, Jolliffe CN, Day ML, Parasivam G, Cook DI, Kumar S

All three WW domains of murine Nedd4 are involved in the regulation of epithelial sodium channels by intracellular Na+.

J Biol Chem 1999 Apr 30;274(18) : 12525-30.

PMID: 10212229

Jolliffe CN, Harvey KF, Haines BP, Parasivam G, Kumar S

Identification of multiple proteins expressed in murine embryos as binding partners for the WW domains of the ubiquitin-protein ligase Nedd4.

Biochem J 2000 Nov 1;351() : 557-65.

PMID: 11042109

Kay BK, Williamson MP, Sudol M

The importance of being proline: the interaction of proline-rich motifs in signaling proteins with their cognate domains.

FASEB J 2000 Feb;14(2) : 231-41.

PMID: 10657980

Mosser EA, Kasanov JD, Forsberg EC, Kay BK, Ney PA, Bresnick EH

Physical and functional interactions between the transactivation domain of the hematopoietic transcription factor NF-E2 and WW domains.

Biochemistry 1998 Sep 29;37(39) : 13686-95.

PMID: 9753456

Pirozzi G, McConnell SJ, Uveges AJ, Carter JM, Sparks AB, Kay BK, Fowlkes DM

Identification of novel human WW domain-containing proteins by cloning of ligand targets.

J Biol Chem 1997 Jun 6;272(23) : 14611-6.

PMID: 9169421

Traweger A, Fang D, Liu YC, Stelzhammer W, Krizbai IA, Fresser F, Bauer HC, Bauer H

The tight junction-specific protein occludin is a functional target of the E3 ubiquitin-protein ligase itch.

J Biol Chem 2002 Mar 22;277(12) : 10201-8.

PMID: 11782481

Yagi R, Chen LF, Shigesada K, Murakami Y, Ito Y

A WW domain-containing yes-associated protein (YAP) is a novel transcriptional co-activator.

EMBO J 1999 May 4;18(9) : 2551-62.

PMID: 10228168

Zarrinpar A, Lim WA

Converging on proline: the mechanism of WW domain peptide recognition.

Nat Struct Biol 2000 Aug;7(8) : 611-3.

PMID: 10932238

This ELM has been assigned the following Gene Ontology (GO) terms for biological process, cellular component and molecular function.

Biological Process

  cell growth and/or maintenance

GO:0008150

  cell communication

GO:0007154

  signal transduction

GO:0007165

  cell-adhesion

GO:0007155

Cellular Component

  cytosol

GO:0005829

  integral plasma membrane protein

GO:0005887

  integral membrane protein

GO:0016021

Molecular Function

  Binding

GO:0005488

  protein binding

GO:0005515

Instances for LIG_WW_1

Sequence	Position	Subsequence (Click for evidence information)	PDB	Gene Name	Protein Description	Organism
WBP1_MOUSE	173-176	HPGTPPPPYTVGPGY	-	Name=Wbp1;	WW domain-binding protein 1 (WBP-1).	Mus musculus (Mouse).
DAG1_HUMAN	889-892	TPYRSPPPYVPP	1JUQ	Name=DAG1;	Dystroglycan precursor (Dystrophin-associated glycoprotein 1) [Contains: Alpha-dystroglycan (Alpha-DG); Beta-dystroglycan (Beta- DG)].	Homo sapiens (Human).