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Protein

Protein salvador homolog 1

Gene

SAV1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

  • identical protein binding Source: IntAct
  • protein-containing complex scaffold activity Source: InterPro

GO - Biological processi

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 14

Organism-specific databases

EuPathDBiHostDB:ENSG00000151748.14
HGNCiHGNC:17795 SAV1
MIMi607203 gene
neXtProtiNX_Q9H4B6

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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
ProteomicsDBi80818

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

  • identical protein binding Source: IntAct
  • protein-containing complex scaffold activity Source: InterPro

Protein-protein interaction databases

BioGridi121917, 94 interactors
CORUMiQ9H4B6
DIPiDIP-36127N
IntActiQ9H4B6, 80 interactors
MINTiQ9H4B6
STRINGi9606.ENSP00000324729

Structurei

Secondary structure

1383
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi298 – 300Combined sources3
Helixi306 – 313Combined sources8
Beta strandi316 – 319Combined sources4
Helixi329 – 375Combined sources47

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
OMAiWYAQQHG
OrthoDBiEOG091G09KI
PhylomeDBiQ9H4B6
TreeFamiTF317631

Family and domain databases

CDDicd00201 WW, 2 hits
InterProiView protein in InterPro
IPR011524 SARAH_dom
IPR030030 Sav
IPR001202 WW_dom
IPR036020 WW_dom_sf
PANTHERiPTHR10316:SF66 PTHR10316:SF66, 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

Similar proteinsi

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: July 18, 2018
This is version 142 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

3D-structure, 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
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references

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