SAV1

Functionⁱ

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.4 Publications

GO - Molecular functionⁱ

protein complex scaffold Source: InterPro

Complete GO annotation...

GO - Biological processⁱ

apoptotic process Source: InterPro
hair follicle development Source: Ensembl
hippo signaling Source: UniProtKB
intestinal epithelial cell differentiation Source: Ensembl
keratinocyte differentiation Source: Ensembl
lung epithelial cell differentiation Source: Ensembl
negative regulation of cardiac muscle cell proliferation Source: Ensembl
negative regulation of epithelial cell proliferation Source: Ensembl
positive regulation of apoptotic process Source: Ensembl
positive regulation of fat cell differentiation Source: Ensembl
positive regulation of sequence-specific DNA binding transcription factor activity Source: Ensembl
protein stabilization Source: Ensembl
regulation of stem cell population maintenance Source: Ensembl
ventricular septum morphogenesis Source: Ensembl

Complete GO annotation...

Enzyme and pathway databases

Reactomeⁱ	R-HSA-2028269. Signaling by Hippo.
SignaLinkⁱ	Q9H4B6.
SIGNORⁱ	Q9H4B6.

Names & Taxonomyⁱ

Protein namesⁱ	Recommended name: Protein salvador homolog 1 Alternative name(s): 45 kDa WW domain protein Short name: hWW45
Gene namesⁱ	Name:SAV1 Synonyms:WW45
Organismⁱ	Homo sapiens (Human)
Taxonomic identifierⁱ	9606 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo
Proteomesⁱ	UP000005640 Componentⁱ: Chromosome 14

Organism-specific databases

Human Gene Nomenclature Database More...HGNCⁱ	HGNC:17795. SAV1.

HGNCⁱ

HGNC:17795. SAV1.

Subcellular locationⁱ

GO - Cellular componentⁱ

cytoplasm
Source: UniProtKB
Inferred from direct assayⁱ
- 19212654
cytosol Source: HPA
nucleus
Source: UniProtKB
Inferred from direct assayⁱ
- 19212654

Complete GO annotation...

Keywords - Cellular componentⁱ

Cytoplasm, Nucleus

Pathology & Biotechⁱ

Organism-specific databases

DisGeNET More...DisGeNETⁱ	60485.
Open Targets More...OpenTargetsⁱ	ENSG00000151748.
PharmGKBⁱ	PA134875018.

Polymorphism and mutation databases

BioMutaⁱ	SAV1.
DMDMⁱ	32699681.

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
ChainⁱPRO_0000076060	1 – 383	Protein salvador homolog 1Add BLAST		383

Amino acid modifications

Feature key	Position(s)	DescriptionActions	Length
Modified residueⁱ	94	PhosphoserineCombined sources	1
Modified residueⁱ	136	PhosphoserineBy similarity	1
Modified residueⁱ	210	PhosphothreonineCombined sources	1

Post-translational modificationⁱ

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.1 Publication

Keywords - PTMⁱ

Phosphoprotein

Proteomic databases

EPDⁱ	Q9H4B6.
MaxQB - The MaxQuant DataBase More...MaxQBⁱ	Q9H4B6.
PaxDbⁱ	Q9H4B6.
PeptideAtlas More...PeptideAtlasⁱ	Q9H4B6.
PRIDEⁱ	Q9H4B6.

PTM databases

iPTMnetⁱ	Q9H4B6.
PhosphoSitePlusⁱ	Q9H4B6.

Expressionⁱ

Tissue specificityⁱ

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.1 Publication

Gene expression databases

Bgeeⁱ	ENSG00000151748.
CleanExⁱ	HS_SAV1.
ExpressionAtlasⁱ	Q9H4B6. baseline and differential.
Genevisibleⁱ	Q9H4B6. HS.

Organism-specific databases

Human Protein Atlas More...HPAⁱ	HPA001808.

HPAⁱ

HPA001808.

Interactionⁱ

Subunit structureⁱ

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.7 Publications

Binary interactionsⁱ

With	Entry	#Exp.	IntAct	Notes
STK3	Q13188	19	EBI-1017775,EBI-992580
STK4	Q13043	18	EBI-1017775,EBI-367376

Show more details

GO - Molecular functionⁱ

protein complex scaffold Source: InterPro

Complete GO annotation...

Protein-protein interaction databases

BioGridⁱ	121917. 83 interactors.
Database of interacting proteins More...DIPⁱ	DIP-36127N.
IntActⁱ	Q9H4B6. 65 interactors.
Molecular INTeraction database More...MINTⁱ	MINT-2817789.
STRINGⁱ	9606.ENSP00000324729.

Structureⁱ

3D structure databases

ProteinModelPortalⁱ	Q9H4B6.
SMRⁱ	Q9H4B6.
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Family & Domainsⁱ

Domains and Repeats

Feature key	Position(s)	DescriptionActions	Length
Domainⁱ	199 – 232	WW 1PROSITE-ProRule annotationAdd BLAST	34
Domainⁱ	234 – 267	WW 2PROSITE-ProRule annotationAdd BLAST	34
Domainⁱ	321 – 368	SARAHPROSITE-ProRule annotationAdd BLAST	48

Coiled coil

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Coiled coilⁱ	344 – 373	Sequence analysisAdd BLAST		30

Keywords - Domainⁱ

Coiled coil, Repeat

Phylogenomic databases

eggNOGⁱ	KOG1891. Eukaryota. ENOG410ZK10. LUCA.
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00650000092997.
HOGENOMⁱ	HOG000013074.
HOVERGENⁱ	HBG044514.
InParanoidⁱ	Q9H4B6.
KEGG Orthology (KO) More...KOⁱ	K16686.
OMAⁱ	RQQWYAQ.
Database of Orthologous Groups More...OrthoDBⁱ	EOG091G09KI.
PhylomeDBⁱ	Q9H4B6.
TreeFamⁱ	TF317631.

Family and domain databases

InterProⁱ	View protein in InterPro IPR011524. SARAH_dom. IPR030030. Sav. IPR001202. WW_dom.
PANTHERⁱ	PTHR10316:SF59. PTHR10316:SF59. 1 hit.
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF00397. WW. 1 hit.
SMARTⁱ	View protein in SMART SM00456. WW. 2 hits.
SUPFAMⁱ	SSF51045. SSF51045. 2 hits.
PROSITEⁱ	View protein in PROSITE PS50951. SARAH. 1 hit. PS50020. WW_DOMAIN_2. 2 hits.

Sequenceⁱ

Sequence statusⁱ: Complete.

Q9H4B6-1 [UniParc]FASTA Add to basket

« Hide

        10         20         30         40         50
MLSRKKTKNE VSKPAEVQGK YVKKETSPLL RNLMPSFIRH GPTIPRRTDI 
        60         70         80         90        100
CLPDSSPNAF STSGDVVSRN QSFLRTPIQR TPHEIMRRES NRLSAPSYLA 
       110        120        130        140        150
RSLADVPREY GSSQSFVTEV SFAVENGDSG SRYYYSDNFF DGQRKRPLGD 
       160        170        180        190        200
RAHEDYRYYE YNHDLFQRMP QNQGRHASGI GRVAATSLGN LTNHGSEDLP 
       210        220        230        240        250
LPPGWSVDWT MRGRKYYIDH NTNTTHWSHP LEREGLPPGW ERVESSEFGT 
       260        270        280        290        300
YYVDHTNKKA QYRHPCAPSV PRYDQPPPVT YQPQQTERNQ SLLVPANPYH 
       310        320        330        340        350
TAEIPDWLQV YARAPVKYDH ILKWELFQLA DLDTYQGMLK LLFMKELEQI 
       360        370        380 
VKMYEAYRQA LLTELENRKQ RQQWYAQQHG KNF

Length:383

Mass (Da):44,634

Last modified:July 11, 2003 - v2

Checksum:ⁱ4012C40A8601417A

GO

Experimental Info

Feature key	Position(s)	DescriptionActions	Length
Sequence conflictⁱ	5	K → Q in CAC13972 (PubMed:11027580).Curated	1
Sequence conflictⁱ	18	Q → R in CAG33578 (Ref. 3) Curated	1
Sequence conflictⁱ	292	L → F in BAB13835 (PubMed:14702039).Curated	1

Natural variant

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Natural variantⁱVAR_015880	185	A → D in a colon cancer cell line. 1 Publication		1

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	AJ292969 mRNA. Translation: CAC13972.1. AK021500 mRNA. Translation: BAB13835.1. AK023071 mRNA. Translation: BAB14390.1. AK290883 mRNA. Translation: BAF83572.1. CR457297 mRNA. Translation: CAG33578.1. CH471078 Genomic DNA. Translation: EAW65702.1. CH471078 Genomic DNA. Translation: EAW65704.1. BC020537 mRNA. Translation: AAH20537.1.
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS9701.1.
PIRⁱ	JC7507.
NCBI Reference Sequences More...RefSeqⁱ	NP_068590.1. NM_021818.3.
UniGeneⁱ	Hs.642842. Hs.706933.

Genome annotation databases

Ensemblⁱ	ENST00000324679; ENSP00000324729; ENSG00000151748.
GeneIDⁱ	60485.
KEGGⁱ	hsa:60485.
UCSC genome browser More...UCSCⁱ	uc001wyh.3. human.

Keywords - Coding sequence diversityⁱ

Polymorphism

Similar proteinsⁱ

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:

100%	UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%	UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%	UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.

Cross-referencesⁱ

Web resourcesⁱ

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	AJ292969 mRNA. Translation: CAC13972.1. AK021500 mRNA. Translation: BAB13835.1. AK023071 mRNA. Translation: BAB14390.1. AK290883 mRNA. Translation: BAF83572.1. CR457297 mRNA. Translation: CAG33578.1. CH471078 Genomic DNA. Translation: EAW65702.1. CH471078 Genomic DNA. Translation: EAW65704.1. BC020537 mRNA. Translation: AAH20537.1.
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS9701.1.
PIRⁱ	JC7507.
NCBI Reference Sequences More...RefSeqⁱ	NP_068590.1. NM_021818.3.
UniGeneⁱ	Hs.642842. Hs.706933.

3D structure databases

ProteinModelPortalⁱ	Q9H4B6.
SMRⁱ	Q9H4B6.
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Protein-protein interaction databases

BioGridⁱ	121917. 83 interactors.
Database of interacting proteins More...DIPⁱ	DIP-36127N.
IntActⁱ	Q9H4B6. 65 interactors.
Molecular INTeraction database More...MINTⁱ	MINT-2817789.
STRINGⁱ	9606.ENSP00000324729.

PTM databases

iPTMnetⁱ	Q9H4B6.
PhosphoSitePlusⁱ	Q9H4B6.

Polymorphism and mutation databases

BioMutaⁱ	SAV1.
DMDMⁱ	32699681.

Proteomic databases

EPDⁱ	Q9H4B6.
MaxQB - The MaxQuant DataBase More...MaxQBⁱ	Q9H4B6.
PaxDbⁱ	Q9H4B6.
PeptideAtlas More...PeptideAtlasⁱ	Q9H4B6.
PRIDEⁱ	Q9H4B6.

Protocols and materials databases

The DNASU plasmid repository More...DNASUⁱ	60485.
Structural Biology Knowledgebase	Search...

Genome annotation databases

Ensemblⁱ	ENST00000324679; ENSP00000324729; ENSG00000151748.
GeneIDⁱ	60485.
KEGGⁱ	hsa:60485.
UCSC genome browser More...UCSCⁱ	uc001wyh.3. human.

Organism-specific databases

CTDⁱ	60485.
DisGeNET More...DisGeNETⁱ	60485.
GeneCardsⁱ	SAV1.
Human Gene Nomenclature Database More...HGNCⁱ	HGNC:17795. SAV1.
Human Protein Atlas More...HPAⁱ	HPA001808.
MIMⁱ	607203. gene.
neXtProtⁱ	NX_Q9H4B6.
Open Targets More...OpenTargetsⁱ	ENSG00000151748.
PharmGKBⁱ	PA134875018.
GenAtlas: human gene database More...GenAtlasⁱ	Search...

Phylogenomic databases

eggNOGⁱ	KOG1891. Eukaryota. ENOG410ZK10. LUCA.
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00650000092997.
HOGENOMⁱ	HOG000013074.
HOVERGENⁱ	HBG044514.
InParanoidⁱ	Q9H4B6.
KEGG Orthology (KO) More...KOⁱ	K16686.
OMAⁱ	RQQWYAQ.
Database of Orthologous Groups More...OrthoDBⁱ	EOG091G09KI.
PhylomeDBⁱ	Q9H4B6.
TreeFamⁱ	TF317631.

Enzyme and pathway databases

Reactomeⁱ	R-HSA-2028269. Signaling by Hippo.
SignaLinkⁱ	Q9H4B6.
SIGNORⁱ	Q9H4B6.

Miscellaneous databases

ChiTaRSⁱ	SAV1. human.
GeneWikiⁱ	SAV1.
GenomeRNAiⁱ	60485.
Protein Ontology More...PROⁱ	PR:Q9H4B6.
SOURCEⁱ	Search...

Gene expression databases

Bgeeⁱ	ENSG00000151748.
CleanExⁱ	HS_SAV1.
ExpressionAtlasⁱ	Q9H4B6. baseline and differential.
Genevisibleⁱ	Q9H4B6. HS.

Family and domain databases

InterProⁱ	View protein in InterPro IPR011524. SARAH_dom. IPR030030. Sav. IPR001202. WW_dom.
PANTHERⁱ	PTHR10316:SF59. PTHR10316:SF59. 1 hit.
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF00397. WW. 1 hit.
SMARTⁱ	View protein in SMART SM00456. WW. 2 hits.
SUPFAMⁱ	SSF51045. SSF51045. 2 hits.
PROSITEⁱ	View protein in PROSITE PS50951. SARAH. 1 hit. PS50020. WW_DOMAIN_2. 2 hits.
ProtoNetⁱ	Search...

Entry informationⁱ

Entry nameⁱ	SAV1_HUMAN
Accessionⁱ	Q9H4B6Primary (citable) accession number: Q9H4B6 Secondary accession number(s): A8K4B8 , D3DSB6, Q6IA58, Q9H949, Q9HAK9
Entry historyⁱ	Integrated into UniProtKB/Swiss-Prot:	July 11, 2003
	Last sequence update:	July 11, 2003
	Last modified:	June 7, 2017
	This is version 131 of the entry and version 2 of the sequence. See complete history.
Entry statusⁱ	Reviewed (UniProtKB/Swiss-Prot)
Annotation program	Chordata Protein Annotation Program
Disclaimer	Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousⁱ

Keywords - Technical termⁱ

Complete proteome, Reference proteome

Documents

Human chromosome 14
Human chromosome 14: entries, gene names and cross-references to MIM
Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations
Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations
MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

UniProtKB

UniParc

Help

UniRef

Proteomes

Annotation systems

Supporting data

UniProtKB - Q9H4B6 (SAV1_HUMAN)

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Protein salvador homolog 1

Select a section on the left to see content.

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Biological processi

Enzyme and pathway databases

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Cellular componenti

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Organism-specific databases

Polymorphism and mutation databases

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Amino acid modifications

Proteomic databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

Organism-specific databases

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

Protein-protein interaction databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

3D structure databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Coiled coil

Phylogenomic databases

Family and domain databases

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including length and molecular weight.<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequencei

Experimental Info

Natural variant

Sequence databases

Genome annotation databases

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

<p>This subsection of the <a href="http://www.uniprot.org/manual/cross_references_section">Cross-references</a> section provides links to various web resources that are relevant for a specific protein.<p><a href='/help/web_resource' target='_top'>More...</a></p>Web resourcesi

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Polymorphism and mutation databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Miscellaneous databases

Gene expression databases

Family and domain databases

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Documents

Functionⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

GO - Cellular componentⁱ

Pathology & Biotechⁱ

PTM / Processingⁱ

Expressionⁱ

Interactionⁱ

GO - Molecular functionⁱ

Structureⁱ

Family & Domainsⁱ

Sequenceⁱ

Cross-referencesⁱ

Web resourcesⁱ

Entry informationⁱ

Miscellaneousⁱ