UniProtKB - Q9H4B6 (SAV1_HUMAN)
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Protein
Protein salvador homolog 1
Gene
SAV1
Organism
Homo sapiens (Human)
Status
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
- identical protein binding Source: IntAct
- protein complex scaffold activity Source: InterPro
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 DNA binding transcription factor activity Source: Ensembl
- positive regulation of fat cell differentiation Source: Ensembl
- protein stabilization Source: Ensembl
- regulation of stem cell population maintenance Source: Ensembl
- ventricular septum morphogenesis Source: Ensembl
Enzyme and pathway databases
Reactomei | R-HSA-2028269. Signaling by Hippo. |
SignaLinki | Q9H4B6. |
SIGNORi | Q9H4B6. |
Names & Taxonomyi
Protein namesi | Recommended name: Protein salvador homolog 1Alternative 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 | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000151748.14. |
HGNCi | HGNC:17795. SAV1. |
MIMi | 607203. gene. |
neXtProti | NX_Q9H4B6. |
Pathology & Biotechi
Organism-specific databases
DisGeNETi | 60485. |
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 | Graphical view | 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
PhosphoproteinProteomic databases
EPDi | Q9H4B6. |
MaxQBi | Q9H4B6. |
PaxDbi | Q9H4B6. |
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
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
GO - Molecular functioni
- identical protein binding Source: IntAct
- protein complex scaffold activity Source: InterPro
Protein-protein interaction databases
BioGridi | 121917. 93 interactors. |
CORUMi | Q9H4B6. |
DIPi | DIP-36127N. |
IntActi | Q9H4B6. 80 interactors. |
MINTi | Q9H4B6. |
STRINGi | 9606.ENSP00000324729. |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more detailsFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Helixi | 298 – 300 | Combined sources | 3 | |
Helixi | 306 – 313 | Combined sources | 8 | |
Beta strandi | 316 – 319 | Combined sources | 4 | |
Helixi | 329 – 375 | Combined sources | 47 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
6AO5 | X-ray | 2.96 | B | 291-383 | [»] | |
ProteinModelPortali | Q9H4B6. | |||||
SMRi | Q9H4B6. | |||||
ModBasei | Search... | |||||
MobiDBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | 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, RepeatPhylogenomic databases
eggNOGi | KOG1891. Eukaryota. ENOG410ZK10. LUCA. |
GeneTreei | ENSGT00650000092997. |
HOGENOMi | HOG000013074. |
HOVERGENi | HBG044514. |
InParanoidi | Q9H4B6. |
KOi | K16686. |
OMAi | WYAQQHG. |
OrthoDBi | EOG091G09KI. |
PhylomeDBi | Q9H4B6. |
TreeFami | TF317631. |
Family and domain databases
CDDi | cd00201. WW. 2 hits. |
InterProi | View protein in InterPro IPR011524. SARAH_dom. IPR030030. Sav. IPR001202. WW_dom. IPR036020. WW_dom_sf. |
PANTHERi | PTHR10316:SF66. PTHR10316:SF66. 2 hits. |
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. |
i Sequence
Sequence statusi: Complete.
Q9H4B6-1 [UniParc]FASTAAdd to basket
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
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | 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. |
CCDSi | CCDS9701.1. |
PIRi | JC7507. |
RefSeqi | NP_068590.1. NM_021818.3. |
UniGenei | Hs.642842. Hs.706933. |
Genome annotation databases
Ensembli | ENST00000324679; ENSP00000324729; ENSG00000151748. |
GeneIDi | 60485. |
KEGGi | hsa:60485. |
UCSCi | uc001wyh.3. human. |
Keywords - Coding sequence diversityi
PolymorphismSimilar proteinsi
Entry informationi
Entry namei | SAV1_HUMAN | |
Accessioni | Q9H4B6Primary (citable) accession number: Q9H4B6 Secondary accession number(s): A8K4B8 Q9HAK9 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 11, 2003 |
Last sequence update: | July 11, 2003 | |
Last modified: | March 28, 2018 | |
This is version 138 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. |