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UniProtKB - Q9H4B6 (SAV1_HUMAN)

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Protein

Protein salvador homolog 1

Gene

SAV1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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

Complete GO annotation...

GO - Biological processi

Complete GO annotation...

Enzyme and pathway databases

ReactomeiR-HSA-2028269. Signaling by Hippo.
SignaLinkiQ9H4B6.
SIGNORiQ9H4B6.

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 14

Organism-specific databases

HGNCiHGNC:17795. SAV1.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: HPA
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi60485.
OpenTargetsiENSG00000151748.
PharmGKBiPA134875018.

Polymorphism and mutation databases

BioMutaiSAV1.
DMDMi32699681.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000760601 – 383Protein salvador homolog 1Add BLAST383

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei94PhosphoserineCombined sources1
Modified residuei136PhosphoserineBy similarity1
Modified residuei210PhosphothreonineCombined sources1

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

EPDiQ9H4B6.
MaxQBiQ9H4B6.
PaxDbiQ9H4B6.
PeptideAtlasiQ9H4B6.
PRIDEiQ9H4B6.

PTM databases

iPTMnetiQ9H4B6.
PhosphoSitePlusiQ9H4B6.

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

BgeeiENSG00000151748.
CleanExiHS_SAV1.
ExpressionAtlasiQ9H4B6. baseline and differential.
GenevisibleiQ9H4B6. HS.

Organism-specific databases

HPAiHPA001808.

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

Show more details

GO - Molecular functioni

Complete GO annotation...

Protein-protein interaction databases

BioGridi121917. 83 interactors.
DIPiDIP-36127N.
IntActiQ9H4B6. 65 interactors.
MINTiMINT-2817789.
STRINGi9606.ENSP00000324729.

Structurei

3D structure databases

ProteinModelPortaliQ9H4B6.
SMRiQ9H4B6.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini199 – 232WW 1PROSITE-ProRule annotationAdd BLAST34
Domaini234 – 267WW 2PROSITE-ProRule annotationAdd BLAST34
Domaini321 – 368SARAHPROSITE-ProRule annotationAdd BLAST48

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili344 – 373Sequence analysisAdd BLAST30

Keywords - Domaini

Coiled coil, Repeat

Phylogenomic databases

eggNOGiKOG1891. Eukaryota.
ENOG410ZK10. LUCA.
GeneTreeiENSGT00650000092997.
HOGENOMiHOG000013074.
HOVERGENiHBG044514.
InParanoidiQ9H4B6.
KOiK16686.
OMAiRQQWYAQ.
OrthoDBiEOG091G09KI.
PhylomeDBiQ9H4B6.
TreeFamiTF317631.

Family and domain databases

InterProiView protein in InterPro
IPR011524. SARAH_dom.
IPR030030. Sav.
IPR001202. WW_dom.
PANTHERiPTHR10316:SF59. PTHR10316:SF59. 1 hit.
PfamiView protein in Pfam
PF00397. WW. 1 hit.
SMARTiView protein in SMART
SM00456. WW. 2 hits.
SUPFAMiSSF51045. SSF51045. 2 hits.
PROSITEiView protein in PROSITE
PS50951. SARAH. 1 hit.
PS50020. WW_DOMAIN_2. 2 hits.

Sequencei

Sequence statusi: Complete.

Q9H4B6-1 [UniParc]FASTAAdd 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 keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti5K → Q in CAC13972 (PubMed:11027580).Curated1
Sequence conflicti18Q → R in CAG33578 (Ref. 3) Curated1
Sequence conflicti292L → F in BAB13835 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_015880185A → D in a colon cancer cell line. 1 Publication1

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.
CCDSiCCDS9701.1.
PIRiJC7507.
RefSeqiNP_068590.1. NM_021818.3.
UniGeneiHs.642842.
Hs.706933.

Genome annotation databases

EnsembliENST00000324679; ENSP00000324729; ENSG00000151748.
GeneIDi60485.
KEGGihsa:60485.
UCSCiuc001wyh.3. human.

Keywords - Coding sequence diversityi

Polymorphism

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.
CCDSiCCDS9701.1.
PIRiJC7507.
RefSeqiNP_068590.1. NM_021818.3.
UniGeneiHs.642842.
Hs.706933.

3D structure databases

ProteinModelPortaliQ9H4B6.
SMRiQ9H4B6.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi121917. 83 interactors.
DIPiDIP-36127N.
IntActiQ9H4B6. 65 interactors.
MINTiMINT-2817789.
STRINGi9606.ENSP00000324729.

PTM databases

iPTMnetiQ9H4B6.
PhosphoSitePlusiQ9H4B6.

Polymorphism and mutation databases

BioMutaiSAV1.
DMDMi32699681.

Proteomic databases

EPDiQ9H4B6.
MaxQBiQ9H4B6.
PaxDbiQ9H4B6.
PeptideAtlasiQ9H4B6.
PRIDEiQ9H4B6.

Protocols and materials databases

DNASUi60485.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000324679; ENSP00000324729; ENSG00000151748.
GeneIDi60485.
KEGGihsa:60485.
UCSCiuc001wyh.3. human.

Organism-specific databases

CTDi60485.
DisGeNETi60485.
GeneCardsiSAV1.
HGNCiHGNC:17795. SAV1.
HPAiHPA001808.
MIMi607203. gene.
neXtProtiNX_Q9H4B6.
OpenTargetsiENSG00000151748.
PharmGKBiPA134875018.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1891. Eukaryota.
ENOG410ZK10. LUCA.
GeneTreeiENSGT00650000092997.
HOGENOMiHOG000013074.
HOVERGENiHBG044514.
InParanoidiQ9H4B6.
KOiK16686.
OMAiRQQWYAQ.
OrthoDBiEOG091G09KI.
PhylomeDBiQ9H4B6.
TreeFamiTF317631.

Enzyme and pathway databases

ReactomeiR-HSA-2028269. Signaling by Hippo.
SignaLinkiQ9H4B6.
SIGNORiQ9H4B6.

Miscellaneous databases

ChiTaRSiSAV1. human.
GeneWikiiSAV1.
GenomeRNAii60485.
PROiPR:Q9H4B6.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000151748.
CleanExiHS_SAV1.
ExpressionAtlasiQ9H4B6. baseline and differential.
GenevisibleiQ9H4B6. HS.

Family and domain databases

InterProiView protein in InterPro
IPR011524. SARAH_dom.
IPR030030. Sav.
IPR001202. WW_dom.
PANTHERiPTHR10316:SF59. PTHR10316:SF59. 1 hit.
PfamiView protein in Pfam
PF00397. WW. 1 hit.
SMARTiView protein in SMART
SM00456. WW. 2 hits.
SUPFAMiSSF51045. SSF51045. 2 hits.
PROSITEiView protein in PROSITE
PS50951. SARAH. 1 hit.
PS50020. WW_DOMAIN_2. 2 hits.
ProtoNetiSearch...

Entry informationi

Entry nameiSAV1_HUMAN
AccessioniPrimary (citable) accession number: Q9H4B6
Secondary accession number(s): A8K4B8
, D3DSB6, Q6IA58, Q9H949, Q9HAK9
Entry historyiIntegrated 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 statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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

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

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.