Wwp1 WW domain containing E3 ubiquitin protein ligase 1 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Wwp1provided by MGI
Official Full Name: WW domain containing E3 ubiquitin protein ligase 1provided by MGI
Primary source: MGI:MGI:1861728
See related: Ensembl:ENSMUSG00000041058 AllianceGenome:MGI:1861728
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: AIP5; SDRP1; Tiul1; 8030445B08Rik
Summary: Enables ubiquitin protein ligase activity. Involved in negative regulation of transcription, DNA-templated; proteasome-mediated ubiquitin-dependent protein catabolic process; and protein ubiquitination. Predicted to be located in cytosol. Predicted to be active in cytoplasm. Is expressed in limb and limb mesenchyme. Orthologous to human WWP1 (WW domain containing E3 ubiquitin protein ligase 1). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Ubiquitous expression in bladder adult (RPKM 6.5), cerebellum adult (RPKM 5.3) and 28 other tissues See more
Orthologs: human all
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Genomic context

Location:: 4 A3; 4 7.56 cM

Exon count:: 27

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	4	NC_000070.7 (19608296..19709004, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	4	NC_000070.6 (19608296..19709004, complement)

Chromosome 4 - NC_000070.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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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?

Systemic depletion of WWP1 improves insulin sensitivity and lowers triglyceride content in the liver of obese mice.
Title: Systemic depletion of WWP1 improves insulin sensitivity and lowers triglyceride content in the liver of obese mice.
WWP1 inactivation enhances efficacy of PI3K inhibitors while suppressing their toxicities in breast cancer models.
Title: WWP1 inactivation enhances efficacy of PI3K inhibitors while suppressing their toxicities in breast cancer models.
Targeting E3 Ubiquitin Ligase WWP1 Prevents Cardiac Hypertrophy Through Destabilizing DVL2 via Inhibition of K27-Linked Ubiquitination.
Title: Targeting E3 Ubiquitin Ligase WWP1 Prevents Cardiac Hypertrophy Through Destabilizing DVL2 via Inhibition of K27-Linked Ubiquitination.
E3 ubiquitin ligase Wwp1 regulates ciliary dynamics of the Hedgehog receptor Smoothened.
Title: E3 ubiquitin ligase Wwp1 regulates ciliary dynamics of the Hedgehog receptor Smoothened.
WWP1 knockout in mice exacerbates obesity-related phenotypes in white adipose tissue but improves whole-body glucose metabolism.
Title: WWP1 knockout in mice exacerbates obesity-related phenotypes in white adipose tissue but improves whole-body glucose metabolism.
The ubiquitin ligase WWP1 contributes to shifts in matrix proteolytic profiles and a myocardial aging phenotype with diastolic heart.
Title: The ubiquitin ligase WWP1 contributes to shifts in matrix proteolytic profiles and a myocardial aging phenotype with diastolic heart.
Abundance of KLF15 as well as the expression of genes related to muscle atrophy are increased in skeletal muscle of diabetic model mice, and mice with muscle-specific KLF15 deficiency are protected from the diabetes-induced decline of skeletal muscle mass. Hyperglycemia upregulates the KLF15 protein in skeletal muscle of diabetic animals, which is achieved via downregulation of the E3 ubiquitin ligase WWP1.
Title: Hyperglycemia induces skeletal muscle atrophy via a WWP1/KLF15 axis.
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.
WWP1 was upregulated in obese white adipose tissue in a p53-dependent manner. To investigate the functions of WWP1 in adipocytes, a proteome analysis of WWP1 overexpression (OE) and knockdown (KD) 3T3-L1 cells was performed. This analysis showed a positive correlation between WWP1 expression and the abundance of several antioxidative proteins.
Title: Identification of WWP1 as an obesity-associated E3 ubiquitin ligase with a protective role against oxidative stress in adipocytes.
Atypical ubiquitination by E3 ligase WWP1 inhibits the proteasome-mediated degradation of mutant huntingtin. This suggests that the E3 ligase WWP1 is involved in the pathogenesis of Huntington's disease; therefore, it may be a novel target for therapeutic intervention.
Title: Atypical ubiquitination by E3 ligase WWP1 inhibits the proteasome-mediated degradation of mutant huntingtin.

Submit: New GeneRIF Correction See all GeneRIFs (15)

Variation

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Alleles

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

Gene trapped (1)
Targeted (3) 1 citation
Endonuclease-mediated (5)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D4Dcr6 (e-PCR), detects polymorphism
- UniSTS:507708

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables transferase activity	IEA Inferred from Electronic Annotation more info
enables ubiquitin protein ligase activity	EXP Inferred from Experiment more info	PubMed
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	TAS Traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
involved_in T cell differentiation	TAS Traceable Author Statement more info	PubMed
involved_in lung development	TAS Traceable Author Statement more info	PubMed
involved_in negative regulation of DNA-templated transcription	IDA Inferred from Direct Assay 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 protein ubiquitination	IBA Inferred from Biological aspect of Ancestor more info
involved_in protein ubiquitination	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within protein ubiquitination	TAS Traceable Author Statement 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 cytosol	TAS Traceable Author Statement more info
located_in membrane	IEA Inferred from Electronic Annotation more info
located_in nucleus	IEA Inferred from Electronic Annotation more info
located_in plasma membrane	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: NEDD4-like E3 ubiquitin-protein ligase WWP1

Names: HECT-type E3 ubiquitin transferase WWP1; WW domain-containing protein 1

NP_001263221.1

EC 2.3.2.26

NP_001342151.1

EC 2.3.2.26

NP_796301.2

EC 2.3.2.26

XP_006537609.1

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_001276292.1 → NP_001263221.1 NEDD4-like E3 ubiquitin-protein ligase WWP1 isoform 2

See identical proteins and their annotated locations for NP_001263221.1

Status: VALIDATED

Description

Transcript Variant: This variant (2) has multiple coding region differences and initiates translation at a downstream start codon, compared to variant 1. The use of the start codon used in variant 1 would render the transcript a candidate for nonsense-mediated mRNA decay (NMD). Leaky scanning may allow translation initiation at the downstream AUG, which is associated with a strong Kozak sequence. The resulting isoform (2) is shorter and has a distinct N-terminus compared to isoform 1.

Source sequence(s)

AK031762, AK033138, AK168567, AL683894, CJ101217

UniProtKB/TrEMBL

B9EKB3, Q05CE4, Q3UV52

Conserved Domains (4) summary

smart00119
Location:456 → 784

HECTc; Domain Homologous to E6-AP Carboxyl Terminus with

cd00078
Location:433 → 785

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:364 → 393

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:216 → 245

WW; WW domain
NM_001355222.1 → NP_001342151.1 NEDD4-like E3 ubiquitin-protein ligase WWP1 isoform 3

Status: VALIDATED

Source sequence(s)

AK031762, AK032232, AK033138, AK168567, AL683894, BY739197, CJ101217

UniProtKB/TrEMBL

Q3UV52

Conserved Domains (3) summary

COG5021
Location:309 → 850

HUL4; Ubiquitin-protein ligase [Posttranslational modification, protein turnover, chaperones]

pfam00397
Location:279 → 308

WW; WW domain

cl14603
Location:8 → 72

C2; C2 domain
NM_177327.5 → NP_796301.2 NEDD4-like E3 ubiquitin-protein ligase WWP1 isoform 1

See identical proteins and their annotated locations for NP_796301.2

Status: VALIDATED

Description

Transcript Variant: This variant (1) represents the longr transcript and encodes the longer isoform (1).

Source sequence(s)

AK031762, AK033138, AK137588, AL683894, CJ101217

Consensus CDS

CCDS38697.1

UniProtKB/Swiss-Prot

Q8BIV9, Q8BZZ3, Q8VDP8

UniProtKB/TrEMBL

B9EKB3, Q3UV52

Related

ENSMUSP00000103881.3, ENSMUST00000108246.9

Conserved Domains (5) summary

cd04021
Location:17 → 140

C2_E3_ubiquitin_ligase; C2 domain present in E3 ubiquitin ligase

smart00119
Location:587 → 915

HECTc; Domain Homologous to E6-AP Carboxyl Terminus with

cd00078
Location:564 → 916

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:495 → 524

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:347 → 376

WW; WW domain

RNA

NR_074089.1 RNA Sequence

Status: VALIDATED

Description

Transcript Variant: This variant (3) lacks an alternate internal exon, compared to isoform 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AK031762, AK032232, AK033138, AL683894, CJ101217, CJ137158
NR_074090.1 RNA Sequence

Status: VALIDATED

Description

Transcript Variant: This variant (4) uses alternate splice sites at two internal exons, compared to isoform 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AK031762, AK033138, AK168567, AL683894, CJ101217

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_000070.7 Reference GRCm39 C57BL/6J

Range

19608296..19709004 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006537546.5 → XP_006537609.1 NEDD4-like E3 ubiquitin-protein ligase WWP1 isoform X1

Conserved Domains (2) summary

COG5021
Location:121 → 662

HUL4; Ubiquitin-protein ligase [Posttranslational modification, protein turnover, chaperones]

pfam00397
Location:91 → 120

WW; WW domain