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SAV1 (human)

Overview SAV1 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. 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. Ubiquitously expressed in adult tissues with highest expression in the pancreas, aorta and interventricular septum and lowest expression in skeletal muscle. Expression was higher in fetal than in the adult heart. Expressed in various cell lines. Note: This description may include information from UniProtKB. Protein type: Adaptor/scaffold Cellular Component: cytoplasm; cytosol; nucleus Molecular Function: protein binding Biological Process: keratinocyte differentiation; hair follicle development; negative regulation of cardiac muscle cell proliferation; positive regulation of apoptosis; negative regulation of epithelial cell proliferation Reference #:  Q9H4B6 (UniProtKB) Alt. Names/Synonyms: 1700040G09Rik; 45 kDa WW domain protein; hWW45; Protein salvador homolog 1; salvador homolog 1 (Drosophila); SAV; SAV1; WW domain-containing; WW45; WWP4 Gene Symbols: SAV1 Molecular weight: 44,634 Da Basal Isoelectric point: 9.12  Predict pI for various phosphorylation states CST Pathways:  Hippo Signaling Protein-Specific Antibodies or siRNAs from Cell Signaling Technology®

Select Structure to View Below SAV1 2DWV - A/B=229-270 (mouse) 2YSB - A=198-233 (mouse)

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	Sites Implicated In
apoptosis, induced: T26‑p, S27‑p, S36‑p, S269‑p protein conformation: T26‑p, S27‑p, S36‑p, S269‑p

	Modification Sites and Domains

	Modification Sites in Parent Protein, Orthologs, and Isoforms

SS  SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.	MS  MS: The number of records in which this modification site was assigned using ONLY proteomic discovery-mode mass spectrometry.			human
0	1		T26-p	GKYVKKEtsPLLRNL
0	1		S27-p	KYVKKEtsPLLRNLM
0	1		S36-p	LLRNLMPsFIRHGPT
0	1		S56-p	DICLPDSsPNAFSTS
0	1		S90-p	HEIMRREsNRLsAPS
0	2		S94-p	RREsNRLsAPSYLAR
0	1		S102	APSYLARSLADVPRE
0	1		Y135-p	DSGSRYYysDNFFDG
0	2		S136-p	SGSRYYysDNFFDGQ
0	1		S206-p	LPLPPGWsVDWtMRG
0	2		T210-p	PGWsVDWtMRGRKYY
0	1		Y357-p	IVKMYEAyRQALLTE

	mouse
T26	GKYVKKETSPLLRNL
S27	KYVKKETSPLLRNLM
S36	LLRNLMPSFIRHGPT
S56	DLCLPDSSATAFSAS
S91	HEVMRRESHRLsAPS
S95-p	RRESHRLsAPSYLVR
S103-p	APSYLVRsLADVPRE
F136	DSGSRYFFsDNFFDG
S137-p	SGSRYFFsDNFFDGQ
S207	LPLPPGWSVDWTMRG
T211	PGWSVDWTMRGRKYY
Y358	IVKLYEAYRQALLTE

	rat
T26	GKYVKKETSPLLRNL
S27	KYVKKETSPLLRNLM
S36	LLRNLMPSFIRHGPT
S56	DLCLPESSASAFSAS
S91	HEVMRRESNRLSAPS
S95	RRESNRLSAPSSYLV
S104	PSSYLVRSLADVPRE
Y137	DSGSRYFYSDNFFDG
S138	SGSRYFYSDNFFDGQ
S208	LPLPPGWSVDWTMRG
T212	PGWSVDWTMRGRKYY
Y359	IVKLYEAYRQALVTE

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