InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Wtip

Summary

InnateDB Protein

IDBP-173032.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

Wtip

Protein Name

WT1-interacting protein

Synonyms

Species

Mus musculus

Ensembl Protein

ENSMUSP00000047623

InnateDB Gene

IDBG-173030 (Wtip)

Protein Structure

UniProt Annotation

Function

Adapter or scaffold protein which participates in the assembly of numerous protein complexes and is involved in several cellular processes such as cell fate determination, cytoskeletal organization, repression of gene transcription, cell-cell adhesion, cell differentiation, proliferation and migration. Positively regulates microRNA (miRNA)-mediated gene silencing. Negatively regulates Hippo signaling pathway and antagonizes phosphorylation of YAP1. Acts as a transcriptional corepressor for SNAI1 and SNAI2/SLUG-dependent repression of E-cadherin transcription. Acts as a hypoxic regulator by bridging an association between the prolyl hydroxylases and VHL enabling efficient degradation of HIF1A. In podocytes, may play a role in the regulation of actin dynamics and/or foot process cytoarchitecture. In the course of podocyte injury, shuttles into the nucleus and acts as a transcription regulator that represses WT1-dependent transcription regulation, thereby translating changes in slit diaphragm structure into altered gene expression and a less differentiated phenotype. {ECO:0000269PubMed:14736876, ECO:0000269PubMed:15798086, ECO:0000269PubMed:17909014, ECO:0000269PubMed:20086015}.

Subcellular Localization

Cell junction, focal adhesion. Cell junction, adherens junction. Nucleus. Cytoplasm, cytosol. Cell membrane. Note=In adherent but isolated podocytes, targets to focal adhesions and then shifts to adherens junctions after cells make homotypic contacts. Following podocyte injury, caused by treatment with LPS, puromycin aminonucleoside, ultraviolet or hydrogen peroxide, translocates from sites of cell-cell contacts into the cytosol and nucleus. Maximal nuclear localization is achieved 6 hours after LPS treatment. Nuclear translocation requires dynein motor activity and intact microtubule network (By similarity). Returns to cell-cell contacts several hours after LPS stimulation. In the presence of ROR2, localizes to the plasma membrane. {ECO:0000250}.

Disease Associations

Tissue Specificity

Expressed in kidney, lung, eye and ovary. In kidney, restricted to podocytes. {ECO:0000269PubMed:14736876, ECO:0000269PubMed:20086015}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 4 experimentally validated interaction(s) in this database.
They are also associated with 3 interaction(s) predicted by orthology.

Experimentally validated
Total	4 [view]
Protein-Protein	4 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	3 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003714	transcription corepressor activity
GO:0005515	protein binding
GO:0008270	zinc ion binding

Biological Process

GO:0001666	response to hypoxia
GO:0006351	transcription, DNA-templated
GO:0006355	regulation of transcription, DNA-templated
GO:0007010	cytoskeleton organization
GO:0022604	regulation of cell morphogenesis
GO:0035195	gene silencing by miRNA
GO:0035331	negative regulation of hippo signaling
GO:2000637	positive regulation of gene silencing by miRNA