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FLASH GENE

Symbol

WWP1

contributors: mct/npt/pgu - updated : 10-04-2017

HGNC name	WW domain containing E3 ubiquitin protein ligase 1
HGNC id	17004

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_007013 25 - 4120 NP_008944 - 922 - 2002 11779188

EXPRESSION

Type	ubiquitous

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive liver         Hearing/Equilibrium ear inner cochlea   highly Reproductive female system breast mammary gland   highly Urinary kidney

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective adipose     highly

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

pregnancy

Text

placenta

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	at the N terminus, a proline-rich domain and a polyserine motif with an adjacent C2 domain
	four tandem WW domains for substrate binding
	two highly conserved tryptophans
	a partial HECT (homologous to the E6-associated protein carboxyl terminus) domain
	PPXY motif, not required for spartin ubiquitination
	a C-terminal catalytic HECT domain for ubiquitin transferring

HOMOLOGY

interspecies

homolog to murine Wwp1

Homologene

FAMILY

NEDD4-like protein family

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION	extracellular
	plasma membrane
	intracellular
	intracellular,cytoplasm,cytosolic
	intracellular,nucleus

basic FUNCTION	ubiquitin protein ligase, regulating key trafficking decisions, including targeting of proteins to proteasomes or lysosomes
	upregulates and maintains erythroblastic leukemia viral oncogene homolog 2 (ERBB2) and epithelial growth factor receptor (EGFR) in multiple cell lines
	may promote cell proliferation and survival partially through suppressing RNF11-mediated ERBB2 and EGFR downregulation
	suppressing ERBB4 expression and function in breast cancer
	may play an important role in ER positive breast cancer
	may have a context-dependent role in regulating cell survival through targeting different TP63 proteins for degradation
	markedly inhibited the replicative senescence induced by CDKN1B by promoting CDKN1B degradation
	may promote human fibroblast proliferation by stimulating cell cycle progression
	promotes CDKN1B degradation through the ubiquitin-proteasome pathway, and plays an important role in the regulation of cellular senescence
	function as the E3 ligase for several PY motif-containing proteins
	appears to be involved in insulin resistance through suppressing PRKAA2 expression
	acting as an E3 ubiquitin ligase in TLR-mediated inflammation
	important negative regulator of TLR4-mediated TNF and Il6 production
	participates in a wide variety of biological processes and is tightly related to the initiation and progression of many tumors
	acts as an oncogenic factor and should be considered as a novel interfering molecular target for gastric carcinoma

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

WWP1 forms a protein complex with RNF11

INTERACTION

DNA

RNA

small molecule

protein	ZCCHC14
	interacting with KLF5 (WWP1 mediated the ubiquitination and degradation of KLF5, through the catalytic cysteine residue)
	interaction with RNF11 through the first and third WW domains of WWP1 and the PY motif of RNF11
	interacting partner for RTN4 (interaction which may regulate the RTN4 level by controlling its ubiquitination)
	targets KLF5 for ubiquitin-mediated degradation
	regulates deltaNp63 (TP63) transcriptional activity, acting thus as a potential regulator of the proliferation and survival of epithelial-derived cells
	decreases CDKN1B protein levels and CDKN1B may play a key regulatory role in WWP1-mediated cellular senescence
	EZR ubiquitylation by WWP1 in epithelial cells leads to the upregulation of MET level in absence of HGF stimulation and increases the response of MET to HGF stimulation as measured by the ability of the cells to heal a wound
	down-regulated PRKAA2 under high glucose culture conditions via the ubiquitin-proteasome pathway
	is essential for LATS1 stability and negatively regulate LATS1 by promoting LATS1 degradation through polyubiquitination and the 26S proteasome pathway
	WWP1 could degrade TRAF6, but not IRAK1, in the proteasome pathway
	functions as an E3 ligase when cells are stimulated with LPS by binding to TRAF6 and promoting K48-linked polyubiquitination
	phosphatase PPM1G is a functional switch that controls the balance between monomeric WWP2 and a WWP2/WWP1 heterodimeric state in the cell
	BAP1 antagonized WWP1-mediated ubiquitination of KLF5 to inhibit autophagy and promote melanoma development

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in some cancer cell lines from the prostate and breast tumoral     --over   associated with the estrogen receptor and insulin-like growth factor receptor 1 in breast carcinoma

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cancer reproductive breast promising therapeutic strategy in which developed drugs targeting WWP1 cause activation of LATS1 in suppressing breast cancer cell growth

ANIMAL & CELL MODELS