UniProt functional annotation for Q8VEB2



	UniProt functional annotation for Q8VEB2

UniProt code: Q8VEB2.

Organism: Mus musculus (Mouse).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.

Function: Regulator of STK3/MST2 and STK4/MST1 in the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Phosphorylation of YAP1 by LATS1/2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. SAV1 is required for STK3/MST2 and STK4/MST1 activation and promotes cell-cycle exit and terminal differentiation in developing epithelial tissues. Plays a role in centrosome disjunction by regulating the localization of NEK2 to centrosomes, and its ability to phosphorylate CROCC and CEP250. In conjunction with STK3/MST2, activates the transcriptional activity of ESR1 through the modulation of its phosphorylation (By similarity). {ECO:0000250, ECO:0000269|PubMed:18369314, ECO:0000269|PubMed:20080689}.

Subunit: Homodimer. Stabilized through interaction with STK3/MST2 or STK4/MST1. Interacts (via SARAH domain) with isoform 1 of NEK2. Interacts with ESR1 only in the presence of STK3/MST2. Interacts with WTIP and AJUBA. {ECO:0000250|UniProtKB:Q9H4B6}.

Subcellular location: Nucleus {ECO:0000250}. Cytoplasm {ECO:0000250}.

Tissue specificity: Ubiquitously expressed in adult tissues with the highest level found in testis.

Developmental stage: Expression was detected in 7 dpc embryos. Expression levels decreased at day 11 and remained low at days 15 and 17.

Ptm: Phosphorylated by STK3/MST2 and STK4/MST1. Phosphorylation is not required for SAV1 stability and may increase the number of protein binding sites on the scaffold molecule (By similarity). {ECO:0000250}.

Disruption phenotype: Mice show progressive hepatomegaly with a 2-fold increase in liver mass relative to total body mass at 1 month of age and a 3-fold increase by 3 months of age. Embryos display unchecked proliferation and defects in terminal differentiation of epithelial cells. {ECO:0000269|PubMed:18369314, ECO:0000269|PubMed:20080689}.

Annotations taken from UniProtKB at the EBI.


Organism:		Mus musculus (Mouse).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.



Function:		Regulator of STK3/MST2 and STK4/MST1 in the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Phosphorylation of YAP1 by LATS1/2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. SAV1 is required for STK3/MST2 and STK4/MST1 activation and promotes cell-cycle exit and terminal differentiation in developing epithelial tissues. Plays a role in centrosome disjunction by regulating the localization of NEK2 to centrosomes, and its ability to phosphorylate CROCC and CEP250. In conjunction with STK3/MST2, activates the transcriptional activity of ESR1 through the modulation of its phosphorylation (By similarity). {ECO:0000250, ECO:0000269\|PubMed:18369314, ECO:0000269\|PubMed:20080689}.


Subunit:		Homodimer. Stabilized through interaction with STK3/MST2 or STK4/MST1. Interacts (via SARAH domain) with isoform 1 of NEK2. Interacts with ESR1 only in the presence of STK3/MST2. Interacts with WTIP and AJUBA. {ECO:0000250\|UniProtKB:Q9H4B6}.
Subcellular location:		Nucleus {ECO:0000250}. Cytoplasm {ECO:0000250}.
Tissue specificity:		Ubiquitously expressed in adult tissues with the highest level found in testis.
Developmental stage:		Expression was detected in 7 dpc embryos. Expression levels decreased at day 11 and remained low at days 15 and 17.
Ptm:		Phosphorylated by STK3/MST2 and STK4/MST1. Phosphorylation is not required for SAV1 stability and may increase the number of protein binding sites on the scaffold molecule (By similarity). {ECO:0000250}.
Disruption phenotype:		Mice show progressive hepatomegaly with a 2-fold increase in liver mass relative to total body mass at 1 month of age and a 3-fold increase by 3 months of age. Embryos display unchecked proliferation and defects in terminal differentiation of epithelial cells. {ECO:0000269\|PubMed:18369314, ECO:0000269\|PubMed:20080689}.