Wwp2 WW domain containing E3 ubiquitin protein ligase 2 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Wwp2provided by MGI
Official Full Name: WW domain containing E3 ubiquitin protein ligase 2provided by MGI
Primary source: MGI:MGI:1914144
See related: Ensembl:ENSMUSG00000031930 AllianceGenome:MGI:1914144
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: AIP2; 1300010O06Rik
Summary: Enables RNA polymerase II-specific DNA-binding transcription factor binding activity and ubiquitin protein ligase activity. Involved in cellular protein metabolic process and regulation of transcription, DNA-templated. Acts upstream of or within positive regulation of transcription by RNA polymerase II. Located in cytoplasm and nucleus. Is expressed in several structures, including heart valve; respiratory system; sensory organ; skeleton; and tarsus. Orthologous to human WWP2 (WW domain containing E3 ubiquitin protein ligase 2). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Ubiquitous expression in limb E14.5 (RPKM 69.1), testis adult (RPKM 34.2) and 28 other tissues See more
Orthologs: human all
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Genomic context

Location:: 8 D3; 8 54.15 cM

Exon count:: 26

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	8	NC_000074.7 (108162966..108285922)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	8	NC_000074.6 (107436334..107559290)

Chromosome 8 - NC_000074.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Proliferation, migration and phenotypic transformation of VSMC induced via Hcy related to up-expression of WWP2 and p-STAT3.
Title: Proliferation, migration and phenotypic transformation of VSMC induced via Hcy related to up-expression of WWP2 and p-STAT3.
A WWP2-PTEN-KLF5 signaling axis regulates odontoblast differentiation and dentinogenesis in mice.
Title: A WWP2-PTEN-KLF5 signaling axis regulates odontoblast differentiation and dentinogenesis in mice.
LINC01588 regulates WWP2-mediated cardiomyocyte injury by interacting with HNRNPL.
Title: LINC01588 regulates WWP2-mediated cardiomyocyte injury by interacting with HNRNPL.
Selective targeting of ubiquitination and degradation of PARP1 by E3 ubiquitin ligase WWP2 regulates isoproterenol-induced cardiac remodeling.
Title: Selective targeting of ubiquitination and degradation of PARP1 by E3 ubiquitin ligase WWP2 regulates isoproterenol-induced cardiac remodeling.
WWP2 regulates SIRT1-STAT3 acetylation and phosphorylation involved in hypertensive angiopathy.
Title: WWP2 regulates SIRT1-STAT3 acetylation and phosphorylation involved in hypertensive angiopathy.
WWP2 Promotes Odontoblastic Differentiation by Monoubiquitinating KLF5.
Title: WWP2 Promotes Odontoblastic Differentiation by Monoubiquitinating KLF5.
Knockdown of WWP2 suppresses gastric cancer tumor growth in vivo. WWP2 promotes proliferation of gastric cancer cells by downregulating PTEN, which may provide new therapeutic targets for gastric cancer.
Title: WWP2 regulates proliferation of gastric cancer cells in a PTEN-dependent manner.
Study delineatea a novel regulatory pathway that involves Sox9-[Wwp1/Wwp2/miR-140]-Fyn required for axon specification, acquisition of pyramidal morphology, and proper laminar distribution of cortical neurons.
Title: Polarity Acquisition in Cortical Neurons Is Driven by Synergistic Action of Sox9-Regulated Wwp1 and Wwp2 E3 Ubiquitin Ligases and Intronic miR-140.
Wwp2 has a role in protecting cartilage from osteoarthritis by suppressing Runx2-induced Adamts5 via Runx2 poly-ubiquitination and degradation.
Title: Wwp2 maintains cartilage homeostasis through regulation of Adamts5.
Itch and WWP2 cooperate to regulate TH2 differentiation by enhancing the strength of the TCR signal via inducing atypical ubiquitination of the phosphatase SHP-1.
Title: The E3 ligases Itch and WWP2 cooperate to limit T(H)2 differentiation by enhancing signaling through the TCR.

Submit: New GeneRIF Correction See all GeneRIFs (24)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Gene trapped (1)
Targeted (4) 1 citation
Endonuclease-mediated (3) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

MARC_17527-17528:1016478546:1 (e-PCR)
- UniSTS:268331

AW554328 (e-PCR)
- UniSTS:179809

AA690238 (e-PCR)
- UniSTS:165598

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables RNA polymerase II-specific DNA-binding transcription factor binding	IBA Inferred from Biological aspect of Ancestor more info
enables RNA polymerase II-specific DNA-binding transcription factor binding	IGI Inferred from Genetic Interaction more info	PubMed
enables RNA polymerase II-specific DNA-binding transcription factor binding	IPI Inferred from Physical Interaction more info	PubMed
enables RNA polymerase II-specific DNA-binding transcription factor binding	ISO Inferred from Sequence Orthology more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables transcription factor binding	ISO Inferred from Sequence Orthology more info
enables transferase activity	IEA Inferred from Electronic Annotation more info
enables ubiquitin protein ligase activity	IBA Inferred from Biological aspect of Ancestor more info
enables ubiquitin protein ligase activity	IDA Inferred from Direct Assay more info	PubMed
enables ubiquitin-protein transferase activity	IDA Inferred from Direct Assay more info	PubMed
enables ubiquitin-protein transferase activity	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
involved_in extracellular transport	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of DNA-binding transcription factor activity	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of DNA-templated transcription	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of gene expression	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of protein transport	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of transcription by RNA polymerase II	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of transporter activity	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within positive regulation of transcription by RNA polymerase II	IGI Inferred from Genetic Interaction more info	PubMed
involved_in proteasome-mediated ubiquitin-dependent protein catabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in proteasome-mediated ubiquitin-dependent protein catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in proteasome-mediated ubiquitin-dependent protein catabolic process	ISO Inferred from Sequence Orthology more info
involved_in protein K63-linked ubiquitination	IBA Inferred from Biological aspect of Ancestor more info
involved_in protein K63-linked ubiquitination	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein autoubiquitination	ISO Inferred from Sequence Orthology more info
involved_in protein ubiquitination	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within protein ubiquitination	ISO Inferred from Sequence Orthology more info	PubMed
involved_in protein ubiquitination	ISO Inferred from Sequence Orthology more info
involved_in regulation of membrane potential	ISO Inferred from Sequence Orthology more info
involved_in regulation of monoatomic ion transmembrane transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of monoatomic ion transmembrane transport	ISO Inferred from Sequence Orthology more info
involved_in regulation of potassium ion transmembrane transporter activity	ISO Inferred from Sequence Orthology more info
acts_upstream_of transcription by RNA polymerase II	IGI Inferred from Genetic Interaction more info	PubMed
involved_in ubiquitin-dependent protein catabolic process	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in nucleus	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: NEDD4-like E3 ubiquitin-protein ligase WWP2

Names: HECT-type E3 ubiquitin transferase WWP2; WW domain-containing protein 2; WW domain-containing protein 4

NP_080106.1

EC 2.3.2.26

XP_006531362.1

EC 2.3.2.26

XP_006531364.1

EC 2.3.2.26

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_025830.4 → NP_080106.1 NEDD4-like E3 ubiquitin-protein ligase WWP2

See identical proteins and their annotated locations for NP_080106.1

Status: VALIDATED

Source sequence(s)

AC132126

Consensus CDS

CCDS40467.1

UniProtKB/Swiss-Prot

Q8BTG4, Q923F6, Q9DBH0

UniProtKB/TrEMBL

A0A1D5RM92, I3RSH5

Related

ENSMUSP00000132224.2, ENSMUST00000166615.3

Conserved Domains (5) summary

cd04021
Location:17 → 142

C2_E3_ubiquitin_ligase; C2 domain present in E3 ubiquitin ligase

PRK07003
Location:149 → 299

PRK07003; DNA polymerase III subunit gamma/tau

cd00078
Location:516 → 868

HECTc; HECT domain; C-terminal catalytic domain of a subclass of Ubiquitin-protein ligase (E3). It binds specific ubiquitin-conjugating enzymes (E2), accepts ubiquitin from E2, transfers ubiquitin to substrate lysine side chains, and transfers additional ...

cd00201
Location:447 → 477

WW; Two conserved tryptophans domain; also known as the WWP or rsp5 domain; around 40 amino acids; functions as an interaction module in a diverse set of signalling proteins; binds specific proline-rich sequences but at low affinities compared to other ...

pfam00397
Location:332 → 361

WW; WW domain

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCm39 C57BL/6J

Genomic

NC_000074.7 Reference GRCm39 C57BL/6J

Range

108162966..108285922

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006531299.5 → XP_006531362.1 NEDD4-like E3 ubiquitin-protein ligase WWP2 isoform X1

See identical proteins and their annotated locations for XP_006531362.1

UniProtKB/Swiss-Prot

Q8BTG4, Q923F6, Q9DBH0

UniProtKB/TrEMBL

A0A1D5RM92, I3RSH5

Related

ENSMUSP00000148679.2, ENSMUST00000212205.2

Conserved Domains (5) summary

cd04021
Location:17 → 142

C2_E3_ubiquitin_ligase; C2 domain present in E3 ubiquitin ligase

PRK07003
Location:149 → 299

PRK07003; DNA polymerase III subunit gamma/tau

cd00078
Location:516 → 868

HECTc; HECT domain; C-terminal catalytic domain of a subclass of Ubiquitin-protein ligase (E3). It binds specific ubiquitin-conjugating enzymes (E2), accepts ubiquitin from E2, transfers ubiquitin to substrate lysine side chains, and transfers additional ...

cd00201
Location:447 → 477

WW; Two conserved tryptophans domain; also known as the WWP or rsp5 domain; around 40 amino acids; functions as an interaction module in a diverse set of signalling proteins; binds specific proline-rich sequences but at low affinities compared to other ...

pfam00397
Location:332 → 361

WW; WW domain
XM_006531301.2 → XP_006531364.1 NEDD4-like E3 ubiquitin-protein ligase WWP2 isoform X2

See identical proteins and their annotated locations for XP_006531364.1

UniProtKB/TrEMBL

Q3TXI7

Related

ENSMUSP00000148813.2, ENSMUST00000212543.2

Conserved Domains (2) summary

cd00078
Location:77 → 429

HECTc; HECT domain; C-terminal catalytic domain of a subclass of Ubiquitin-protein ligase (E3). It binds specific ubiquitin-conjugating enzymes (E2), accepts ubiquitin from E2, transfers ubiquitin to substrate lysine side chains, and transfers additional ...

cd00201
Location:8 → 38

WW; Two conserved tryptophans domain; also known as the WWP or rsp5 domain; around 40 amino acids; functions as an interaction module in a diverse set of signalling proteins; binds specific proline-rich sequences but at low affinities compared to other ...