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FLASH GENE

Symbol

WWP2

contributors: mct - updated : 22-08-2013

HGNC name	WW domain containing E3 ubiquitin protein ligase 2
HGNC id	16804

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	16q22.1      Physical location : 69.796.273 - 69.975.643
Synonym name	Nedd-4-like ubiquitin-protein ligase
	WW domain-containing protein 2
	atrophin 1,interacting protein 2
	NEDD4-like E3 ubiquitin-protein ligase WWP2
	Nedd-4-like ubiquitin-protein ligase
Synonym symbol(s)	AIP2, DRPLAIP2
EC.number	6.3.2.-

DNA

TYPE	functioning gene
STRUCTURE	179.46 kb     25 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_007014 25 splicing 4527 NP_008945 99 870 - 2011 21750408 NM_199424 14 splicing 3690 NP_955456 - 431 - 2011 21750408 NM_199423 10 splicing 2659 - 335 - 2011 21750408 NM_001270454 24 - 4555 NP_001257383 - 870 - 2011 21750408 NM_001270455 9 - 2682 NP_008945 - 870 - 2011 21750408 NM_001270453 21 - 4245 NP_001257382 - 754 - 2011 21750408

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 Cardiovascular heart         Digestive liver         Endocrine pancreas         Nervous brain         Respiratory lung         Urinary kidney

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective cartilage     highly Homo sapiens Muscular striatum cardiac     Nervous central

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

pregnancy

Text

placenta

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	C2 domain
	four WW (phosphoserine- or phosphothreonine binding) domains
	a C terminal HECT domains (conserved cysteine characteristic of E3 ubiquitin ligase)

HOMOLOGY

Homologene

FAMILY

NEDD4-like protein family

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm
	intracellular,nucleus

basic FUNCTION	ubiquitin-protein ligase activity
	important regulator of the POU5F1 protein level in human embryonic stem cells
	crucial role in controlling endogenous POU5F1 protein levels during differentiation processes of embryonal carcinoma cells
	involved in regulating transcription, embryonic stem-cell fate, cellular transport and T-cell activation processes
	functional E3 ubiquitin ligase for PTEN that plays a vital role in tumour-cell survival
	developmental role for WWP2 in chondrogenesis via mechanisms involving cartilage-specific transcription factors

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

ubiquitin ligase complex

INTERACTION

DNA

RNA

small molecule

protein	atrophin 1 binding
	ZCCHC14
	influences craniofacial patterning through its interactions with Goosecoid (GSC), a paired-like homeobox transcription factor that has an important role in craniofacial development
	interacts exclusively with SMAD2, SMAD3 and SMAD7 in the TGFB pathway
	direct target of SOX9 (interacts physically with SOX9 and is associated with SOX9 transcriptional activity via its nuclear translocation)
	regulatory interaction between SOX9, WWP2 and MED25 defines the SOX9 transcriptional mechanisms of chondrogenesis in the forming palate
	physically interacts with PTEN and mediates its degradation through a ubiquitylation-dependent pathway
	plays a negative role by binding to ADARB1 and catalysing its ubiquitination and subsequent degradation
	WWP2 mediated K48-linked ubiquitination and degradation of TICAM1 upon TLR3 activation
	WWP2, an E3 ligase, is a novel TP73-associated protein that ubiquitinates and degrades TP73
	phosphatase PPM1G is a functional switch that controls the balance between monomeric WWP2 and a WWP2/WWP1 heterodimeric state in the cell
	WWP2, a homolog of the HECT-type ubiquitin ligase WWP1, interacts with and targets PAIP1 for ubiquitination and proteasomal degradation

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

Mice deficient in Wwp2 develop malformations of the craniofacial region