Tbio SAV1 Protein salvador homolog 1

Protein Summary

Description

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. 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]

Uniprot Accession IDs

• Q9H4B6
• A8K4B8
• D3DSB6
• Q6IA58
• Q9H949
• Q9HAK9

Gene Name

• SAV1

Ensembl ID

• ENST00000324679
• ENSP00000324729
• ENSG00000151748

Symbol

• WW45
• SAV
• WW45
• WWP4

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
kinase perturbation	0.91
histone modification site profile	0.77
virus perturbation	0.76
transcription factor binding site profile	0.69
disease perturbation	0.68

Protein Classes

No PANTHER Classes or DTO Classes found

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 101.61   (req: < 5)

Gene RIFs: 17   (req: <= 3)

Antibodies: 213   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 101.61   (req: >= 5)

Gene RIFs: 17   (req: > 3)

Antibodies: 213   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 16

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Expression Data (0 Tissues)

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No expression data found

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Target Illumination GWAS Analytics (TIGA)

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (0)

No approved drugs found

Active Ligands (0)

No active ligands found

Protein-Protein Interactions (81)

Explore Interacting Targets

1 – 10 of 81

• See Interactions on String-DB

STK4

Tchem

Family:  Kinase

Novelty:  0.02104423

p_int:  0.999988108

p_ni:  0.000011892

Score:  0.998

Data Source:  BioPlex,Reactome,STRINGDB

KIF2B

Tbio

Novelty:  0.09958244

p_int:  0.999982527

p_ni:  0.000017473

Data Source:  BioPlex

ZNF554

Tdark

Family:  TF

Novelty:  1.57478216

p_int:  0.999982276

p_ni:  0.000017724

Data Source:  BioPlex

STK3

Tchem

Family:  Kinase

Novelty:  0.0529257

p_int:  0.99981225

p_ni:  0.00018775

Score:  0.997

Data Source:  BioPlex,Reactome,STRINGDB

ADCYAP1

Tbio

Family:  Enzyme

Novelty:  0.00080219

p_int:  0.999803309

p_ni:  0.000196655

p_wrong:  3.6e-8

Score:  0.663

Data Source:  BioPlex,STRINGDB

ZNF420

Tbio

Family:  TF

Novelty:  0.20022795

p_int:  0.999790755

p_ni:  0.000209245

Score:  0.747

Data Source:  BioPlex,STRINGDB

ZNF695

Tdark

Family:  TF

Novelty:  0.37164664

p_int:  0.999479899

p_ni:  0.000520097

p_wrong:  4e-9

Score:  0.552

Data Source:  BioPlex,STRINGDB

ZIM2

Tbio

Family:  TF

Novelty:  0.08135678

p_int:  0.998928438

p_ni:  0.001071558

p_wrong:  4e-9

Score:  0.54

Data Source:  BioPlex,STRINGDB

IQCN

Tdark

Novelty:  2.74045479

p_int:  0.996911801

p_ni:  0.003088199

Data Source:  BioPlex

ZNF133

Tbio

Family:  TF

Novelty:  0.20117958

p_int:  0.996361192

p_ni:  0.003638808

Score:  0.665

Data Source:  BioPlex,STRINGDB

Nearest Tclin Targets

Nearest Tclin calculations are only available for targets with KEGG Pathway annotations.

Pathways (10)

Reactome (2)

KEGG (2)

WikiPathways (6)

Signal Transduction (R-HSA-162582)

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Signal Transduction	2704 targets	R-HSA-162582
Reactome	Signaling by Hippo	20 targets	R-HSA-2028269

Name	Explore in Pharos	Explore in Source
Signal Transduction	2704 targets	R-HSA-162582
Signaling by Hippo	20 targets	R-HSA-2028269

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (19)

Functions (2)

Components (3)

Processes (14)

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GO Term	Evidence	Assigned by
identical protein binding	Inferred from Physical Interaction (IPI)	IntAct
protein-containing complex scaffold activity	Inferred from Electronic Annotation (IEA)	InterPro

Disease Associations ()

No disease associations found

GWAS Traits (8)

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GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
mean platelet volume	EFO_0004584	3	5	5		98.2
Dupuytren Contracture	EFO_0004229	1	1	0	1.2	68.6
platelet count	EFO_0004309	1	2	2		68.4
serum alanine aminotransferase measurement	EFO_0004735	1	1	0	6.9	52.4
balding measurement	EFO_0007825	1	1	1		35

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
mean platelet volume	EFO_0004584	5		98.2
Dupuytren Contracture	EFO_0004229	0	1.2	68.6
platelet count	EFO_0004309	2		68.4
serum alanine aminotransferase measurement	EFO_0004735	0	6.9	52.4
balding measurement	EFO_0007825	1		35

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UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Coiled coil
Complete proteome
Cytoplasm
Nucleus
Phosphoprotein
Polymorphism
Reference proteome
Repeat

GWAS Trait Find Similar Targets

No Header	No Header
balding measurement
Dupuytren Contracture
heel bone mineral density
mean platelet volume
platelet count
schizophrenia
serum alanine aminotransferase measurement
serum albumin measurement

MGI Phenotype Find Similar Targets

No Header	No Header
cardiovascular system phenotype
cellular phenotype
digestive/alimentary phenotype
embryo phenotype
endocrine/exocrine gland phenotype
growth/size/body region phenotype
homeostasis/metabolism phenotype
integument phenotype
liver/biliary system phenotype
mortality/aging

IDG Resources

No IDG generated resources found

Orthologs (14)

1 – 5 of 14

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	salvador family WW domain containing protein 1	VGNC:12527	452899
Macaque	salvador family WW domain containing protein 1		706424
Mouse	salvador family WW domain containing 1	MGI:1927144	64010
Rat	salvador family WW domain containing protein 1	RGD:1307253	299116
Dog	salvador family WW domain containing protein 1	VGNC:45877	480319

Species	Name	OMA	EggNOG	Inparanoid
Chimp	salvador family WW domain containing protein 1
Macaque	salvador family WW domain containing protein 1
Mouse	salvador family WW domain containing 1
Rat	salvador family WW domain containing protein 1
Dog	salvador family WW domain containing protein 1

Publication Statistics

PubMed Score 101.61

PubMed score by year

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PubTator Score 40.35

PubTator score by year

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Related Publications

Text Mined References (41)

GeneRif Annotations (17)

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PMID	Year	Title