SAV1

WW domain-containing proteins are found in all eukaryotes and play an important role in the regulation of a wide variety of cellular functions such as protein degradation, transcription, and RNA splicing. This gene encodes a protein with two WW domains, a SARAH domain, and a coiled-coil region and is ubiquitously expressed in adult tissues. This protein binds to MST1 (mammalian sterile 20-like kinase 1) and promotes MST1-induced apoptosis. It has also been shown to bind to HAX1 (hematopoietic cell-specific protein 1 (HS1)-associated protein X-1) and to attenuate the anti-apoptotic effects of HAX1. Studies in human and mouse suggest this gene acts as a tumor suppressor. [provided by RefSeq, Aug 2012]

Full Name

Salvador Family WW Domain Containing Protein 1

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.

Biological Process

Biological Process cardiac muscle cell proliferationIEA:Ensembl
Biological Process epithelial cell proliferationIEA:Ensembl
Biological Process hair follicle developmentIEA:Ensembl
Biological Process hippo signalingISS:UniProtKB
Biological Process intestinal epithelial cell differentiationIEA:Ensembl
Biological Process keratinocyte apoptotic processIEA:Ensembl
Biological Process keratinocyte differentiationIEA:Ensembl
Biological Process lung epithelial cell differentiationIEA:Ensembl
Biological Process negative regulation of cardiac muscle cell proliferationIEA:Ensembl
Biological Process negative regulation of epithelial cell proliferationIEA:Ensembl
Biological Process positive regulation of DNA-binding transcription factor activityIEA:Ensembl
Biological Process positive regulation of fat cell differentiationIEA:Ensembl
Biological Process positive regulation of keratinocyte apoptotic processIEA:Ensembl
Biological Process protein stabilizationIEA:Ensembl
Biological Process receptor clusteringManual Assertion Based On ExperimentIBA:GO_Central
Biological Process regulation of stem cell population maintenanceIEA:Ensembl
Biological Process signal transductionManual Assertion Based On ExperimentIBA:GO_Central
Biological Process ventricular septum morphogenesisIEA:Ensembl

Cellular Location

Nucleus
Cytoplasm

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.