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Protein

Protein salvador homolog 1

Gene

Sav1

Organism
Mus musculus (Mouse)
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 (By similarity).By similarity2 Publications

GO - Biological processi

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

Enzyme and pathway databases

ReactomeiR-MMU-2028269. Signaling by Hippo.

Names & Taxonomyi

Protein namesi
Recommended name:
Protein salvador homolog 1
Alternative name(s):
45 kDa WW domain protein
Short name:
mWW45
Gene namesi
Name:Sav1
Synonyms:Ww45, Wwp3
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 12

Organism-specific databases

MGIiMGI:1927144. Sav1.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Disruption phenotypei

Mice show progressive hepatomegaly with a 2-fold increase in liver mass relative to total body mass at 1 month of age and a 3-fold increase by 3 months of age. Embryos display unchecked proliferation and defects in terminal differentiation of epithelial cells.2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 386386Protein salvador homolog 1PRO_0000076061Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei137 – 1371PhosphoserineCombined sources
Modified residuei211 – 2111PhosphothreonineBy similarity

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 (By similarity).By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ8VEB2.
PaxDbiQ8VEB2.
PRIDEiQ8VEB2.

PTM databases

iPTMnetiQ8VEB2.
PhosphoSiteiQ8VEB2.

Expressioni

Tissue specificityi

Ubiquitously expressed in adult tissues with the highest level found in testis.

Developmental stagei

Expression was detected in 7 dpc embryos. Expression levels decreased at day 11 and remained low at days 15 and 17.

Gene expression databases

BgeeiQ8VEB2.
CleanExiMM_SAV1.
GenevisibleiQ8VEB2. MM.

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 (By similarity). Interacts with WTIP and AJUBA (By similarity).By similarity

Protein-protein interaction databases

IntActiQ8VEB2. 5 interactions.
MINTiMINT-4133861.
STRINGi10090.ENSMUSP00000021467.

Structurei

Secondary structure

1
386
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi206 – 2105Combined sources
Beta strandi212 – 2143Combined sources
Beta strandi216 – 2205Combined sources
Turni221 – 2244Combined sources
Beta strandi225 – 2295Combined sources
Turni231 – 2333Combined sources
Beta strandi241 – 2466Combined sources
Turni247 – 2493Combined sources
Beta strandi250 – 2556Combined sources
Turni256 – 2594Combined sources
Beta strandi260 – 2645Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2DWVNMR-A/B231-266[»]
2YSBNMR-A198-233[»]
ProteinModelPortaliQ8VEB2.
SMRiQ8VEB2. Positions 198-270.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ8VEB2.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini200 – 23334WW 1PROSITE-ProRule annotationAdd
BLAST
Domaini235 – 26834WW 2PROSITE-ProRule annotationAdd
BLAST
Domaini322 – 36948SARAHPROSITE-ProRule annotationAdd
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili345 – 37430Sequence analysisAdd
BLAST

Sequence similaritiesi

Contains 1 SARAH domain.PROSITE-ProRule annotation
Contains 2 WW domains.PROSITE-ProRule annotation

Keywords - Domaini

Coiled coil, Repeat

Phylogenomic databases

eggNOGiKOG1891. Eukaryota.
ENOG410ZK10. LUCA.
GeneTreeiENSGT00650000092997.
HOGENOMiHOG000013074.
HOVERGENiHBG044514.
InParanoidiQ8VEB2.
KOiK16686.
OMAiWYAQQHG.
OrthoDBiEOG7K3TP1.
PhylomeDBiQ8VEB2.
TreeFamiTF317631.

Family and domain databases

InterProiIPR011524. SARAH_dom.
IPR001202. WW_dom.
[Graphical view]
PfamiPF00397. WW. 1 hit.
[Graphical view]
SMARTiSM00456. WW. 2 hits.
[Graphical view]
SUPFAMiSSF51045. SSF51045. 2 hits.
PROSITEiPS50951. SARAH. 1 hit.
PS50020. WW_DOMAIN_2. 2 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q8VEB2-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MLSRKKTKNE VSKPAEVQGK YVKKETSPLL RNLMPSFIRH GPTIPRRTDL
60 70 80 90 100
CLPDSSATAF SASGDGVVSR NQSFLRTAIQ RTPHEVMRRE SHRLSAPSYL
110 120 130 140 150
VRSLADVPRE CGSSQSFLTE VNFAVENGDS GSRYFFSDNF FDGQRRRPLG
160 170 180 190 200
DRAQEDYRYY EYNHDLFQRM PQSQGRHTSG IGRVTATSLG NLTNHGSEDL
210 220 230 240 250
PLPPGWSVDW TMRGRKYYID HNTNTTHWSH PLEREGLPPG WERVESSEFG
260 270 280 290 300
TYYVDHTNKR AQYRHPCAPS VPRYDQPPPI TYQPQQTERN QSLLVPANPY
310 320 330 340 350
HTAEIPDWLQ VYARAPVKYD HILKWELFQL ADLDTYQGML KLLFMKELEQ
360 370 380
IVKLYEAYRQ ALLTELENRK QRQQWYAQQH GKTFLS
Length:386
Mass (Da):44,845
Last modified:July 11, 2003 - v2
Checksum:i310F8E19F20257C2
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti67 – 671V → I in AAH19377 (PubMed:15489334).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ292968 mRNA. Translation: CAC13977.1.
BC019377 mRNA. Translation: AAH19377.1.
AK006655 mRNA. Translation: BAB24691.2.
CCDSiCCDS25956.1.
PIRiJC7508.
RefSeqiNP_071311.1. NM_022028.2.
UniGeneiMm.390480.

Genome annotation databases

EnsembliENSMUST00000021467; ENSMUSP00000021467; ENSMUSG00000021067.
GeneIDi64010.
KEGGimmu:64010.
UCSCiuc007nte.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ292968 mRNA. Translation: CAC13977.1.
BC019377 mRNA. Translation: AAH19377.1.
AK006655 mRNA. Translation: BAB24691.2.
CCDSiCCDS25956.1.
PIRiJC7508.
RefSeqiNP_071311.1. NM_022028.2.
UniGeneiMm.390480.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2DWVNMR-A/B231-266[»]
2YSBNMR-A198-233[»]
ProteinModelPortaliQ8VEB2.
SMRiQ8VEB2. Positions 198-270.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ8VEB2. 5 interactions.
MINTiMINT-4133861.
STRINGi10090.ENSMUSP00000021467.

PTM databases

iPTMnetiQ8VEB2.
PhosphoSiteiQ8VEB2.

Proteomic databases

MaxQBiQ8VEB2.
PaxDbiQ8VEB2.
PRIDEiQ8VEB2.

Protocols and materials databases

DNASUi64010.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000021467; ENSMUSP00000021467; ENSMUSG00000021067.
GeneIDi64010.
KEGGimmu:64010.
UCSCiuc007nte.2. mouse.

Organism-specific databases

CTDi60485.
MGIiMGI:1927144. Sav1.

Phylogenomic databases

eggNOGiKOG1891. Eukaryota.
ENOG410ZK10. LUCA.
GeneTreeiENSGT00650000092997.
HOGENOMiHOG000013074.
HOVERGENiHBG044514.
InParanoidiQ8VEB2.
KOiK16686.
OMAiWYAQQHG.
OrthoDBiEOG7K3TP1.
PhylomeDBiQ8VEB2.
TreeFamiTF317631.

Enzyme and pathway databases

ReactomeiR-MMU-2028269. Signaling by Hippo.

Miscellaneous databases

EvolutionaryTraceiQ8VEB2.
PROiQ8VEB2.
SOURCEiSearch...

Gene expression databases

BgeeiQ8VEB2.
CleanExiMM_SAV1.
GenevisibleiQ8VEB2. MM.

Family and domain databases

InterProiIPR011524. SARAH_dom.
IPR001202. WW_dom.
[Graphical view]
PfamiPF00397. WW. 1 hit.
[Graphical view]
SMARTiSM00456. WW. 2 hits.
[Graphical view]
SUPFAMiSSF51045. SSF51045. 2 hits.
PROSITEiPS50951. SARAH. 1 hit.
PS50020. WW_DOMAIN_2. 2 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Cloning, expression and mapping of hWW45, a novel WW-domain containing gene."
    Valverde P.
    Biochem. Biophys. Res. Commun. 276:990-998(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: Czech II.
    Tissue: Mammary gland.
  3. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 111-386.
    Strain: C57BL/6J.
    Tissue: Testis.
  4. "A crucial role of WW45 in developing epithelial tissues in the mouse."
    Lee J.H., Kim T.S., Yang T.H., Koo B.K., Oh S.P., Lee K.P., Oh H.J., Lee S.H., Kong Y.Y., Kim J.M., Lim D.S.
    EMBO J. 27:1231-1242(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE.
  5. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-137, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Kidney, Lung and Spleen.
  6. "Hippo signaling is a potent in vivo growth and tumor suppressor pathway in the mammalian liver."
    Lu L., Li Y., Kim S.M., Bossuyt W., Liu P., Qiu Q., Wang Y., Halder G., Finegold M.J., Lee J.S., Johnson R.L.
    Proc. Natl. Acad. Sci. U.S.A. 107:1437-1442(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE.
  7. "Solution structure of the first WW domain from the mouse salvador homolog 1 protein (Sav1)."
    RIKEN structural genomics initiative (RSGI)
    Submitted (OCT-2007) to the PDB data bank
    Cited for: STRUCTURE BY NMR OF 198-233.

Entry informationi

Entry nameiSAV1_MOUSE
AccessioniPrimary (citable) accession number: Q8VEB2
Secondary accession number(s): Q9D9N9, Q9ER46
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 11, 2003
Last sequence update: July 11, 2003
Last modified: June 8, 2016
This is version 109 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

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.