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MGP004624

UniProt Annotations

Entry Information
Gene NameWW and C2 domain containing 1
Protein EntryKIBRA_HUMAN
UniProt IDQ8IX03
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=2; Name=1; IsoId=Q8IX03-1; Sequence=Displayed; Name=2; IsoId=Q8IX03-2; Sequence=VSP_019448;
DomainThe C2-domain mediates homodimerization. It is a calcium- sensitive lipid-binding domain with preference for PI(3)P. {ECO:0000269|PubMed:18672031}.
FunctionProbable regulator of the Hippo/SWH (Sav/Wts/Hpo) signaling pathway, a signaling pathway that plays a pivotal role in tumor suppression by restricting proliferation and promoting apoptosis. Along with NF2 can synergistically induce the phosphorylation of LATS1 and LATS2 and can probably function in the regulation of the Hippo/SWH (Sav/Wts/Hpo) signaling pathway. Acts as a transcriptional coactivator of ESR1 which plays an essential role in DYNLL1-mediated ESR1 transactivation. Regulates collagen-stimulated activation of the ERK/MAPK cascade. Modulates directional migration of podocytes. Acts as a substrate for PRKCZ. Plays a role in cognition and memory performance. {ECO:0000269|PubMed:15081397, ECO:0000269|PubMed:16684779, ECO:0000269|PubMed:18190796, ECO:0000269|PubMed:18596123, ECO:0000269|PubMed:18672031, ECO:0000269|PubMed:20159598, ECO:0000269|PubMed:23778582}.
InductionStrongly up-regulated by progestin treatment. {ECO:0000269|PubMed:18190796}.
PolymorphismGenetic variations in WWC1 define the memory quantitative trait locus (MEMRYQTL) [MIM:615602].
PtmPhosphorylation at Ser-542 and Ser-931 by CDK1 in response to spindle damage stress regulates mitotic exit, these two sites are dephosphorylated by CDC14B. {ECO:0000269|PubMed:15081397, ECO:0000269|PubMed:16684779, ECO:0000269|PubMed:18190796, ECO:0000269|PubMed:18669648, ECO:0000269|PubMed:20068231, ECO:0000269|PubMed:22784093}.
SimilarityBelongs to the WWC family. KIBRA subfamily. {ECO:0000305}.
SimilarityContains 1 C2 domain. {ECO:0000305}.
SimilarityContains 2 WW domains. {ECO:0000255|PROSITE- ProRule:PRU00224}.
Subcellular LocationCytoplasm. Cytoplasm, perinuclear region. Nucleus. Cell projection, ruffle membrane. Note=Colocalizes with PRKCZ in the perinuclear region.
SubunitHomodimer. Interacts with DDN. Interacts with DYNLL1 and histone H3. The interaction with DYNLL1 is mandatory for the recruitment and transactivation functions of ESR1 or DYNLL1 to the target chromatin and the interaction with histone H3 ensures proper regulatory interaction of WWC1-DYNLL1-ESR1 complexes with target chromatin. Interacts (via WW domains) with DDR1 (via PPxY motif) in a collagen-regulated manner. Interacts with PRKCZ (via the protein kinase domain). Forms a tripartite complex with DDR1 and PRKCZ, but predominantly in the absence of collagen. Interacts (via the ADDV motif) with INADL (via PDZ domain 8). Interacts (via WW domains) with SYNPO (via PPxY motifs). Interacts with NF2 and SNX4. {ECO:0000269|PubMed:12559952, ECO:0000269|PubMed:15081397, ECO:0000269|PubMed:16684779, ECO:0000269|PubMed:17994011, ECO:0000269|PubMed:18190796, ECO:0000269|PubMed:18596123, ECO:0000269|PubMed:18672031, ECO:0000269|PubMed:20159599}.
Tissue SpecificityExpressed in mammary epithelial cells and breast cancer cell lines. Found in the luminal epithelium surrounding the ducts in the normal breast. In the brain, expressed in somatodendritic compartment of neurons in the cortex and hippocampus and in the cerebellum it is found in the Purkinje cells and some granule cells (at protein level). Detected in brain, heart, colon and kidney. In the kidney, expressed in glomerular podocytes, in some tubules and in the collecting duct. {ECO:0000269|PubMed:12559952, ECO:0000269|PubMed:18190796, ECO:0000269|PubMed:18596123, ECO:0000269|PubMed:18672031}.
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