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Q9H4B6

- SAV1_HUMAN

UniProt

Q9H4B6 - SAV1_HUMAN

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Protein
Protein salvador homolog 1
Gene
SAV1, WW45
Organism
Homo sapiens (Human)
Status
Reviewed - 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

  1. protein binding Source: UniProtKB

GO - Biological processi

  1. hair follicle development Source: Ensembl
  2. hippo signaling Source: UniProtKB
  3. intestinal epithelial cell differentiation Source: Ensembl
  4. keratinocyte differentiation Source: Ensembl
  5. lung epithelial cell differentiation Source: Ensembl
  6. negative regulation of cardiac muscle cell proliferation Source: Ensembl
  7. negative regulation of epithelial cell proliferation Source: Ensembl
  8. positive regulation of apoptotic process Source: Ensembl
  9. regulation of stem cell maintenance Source: Ensembl
  10. ventricular septum morphogenesis Source: Ensembl
Complete GO annotation...

Enzyme and pathway databases

ReactomeiREACT_118607. Signaling by Hippo.
SignaLinkiQ9H4B6.

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
ProteomesiUP000005640: Chromosome 14

Organism-specific databases

HGNCiHGNC:17795. SAV1.

Subcellular locationi

Nucleus. Cytoplasm 1 Publication

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. cytosol Source: Reactome
  3. nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA134875018.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 383383Protein salvador homolog 1
PRO_0000076060Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei210 – 2101Phosphothreonine1 Publication

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

MaxQBiQ9H4B6.
PaxDbiQ9H4B6.
PRIDEiQ9H4B6.

PTM databases

PhosphoSiteiQ9H4B6.

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

ArrayExpressiQ9H4B6.
BgeeiQ9H4B6.
CleanExiHS_SAV1.
GenevestigatoriQ9H4B6.

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.6 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
STK3Q1318815EBI-1017775,EBI-992580
STK4Q1304316EBI-1017775,EBI-367376

Protein-protein interaction databases

BioGridi121917. 57 interactions.
IntActiQ9H4B6. 60 interactions.
MINTiMINT-2817789.
STRINGi9606.ENSP00000324729.

Structurei

3D structure databases

ProteinModelPortaliQ9H4B6.
SMRiQ9H4B6. Positions 197-269.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini199 – 23234WW 1
Add
BLAST
Domaini234 – 26734WW 2
Add
BLAST
Domaini321 – 36848SARAH
Add
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili344 – 37330 Reviewed prediction
Add
BLAST

Sequence similaritiesi

Contains 1 SARAH domain.
Contains 2 WW domains.

Keywords - Domaini

Coiled coil, Repeat

Phylogenomic databases

eggNOGiNOG314596.
HOGENOMiHOG000013074.
HOVERGENiHBG044514.
InParanoidiQ9H4B6.
KOiK16686.
OMAiHINKRAQ.
PhylomeDBiQ9H4B6.
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.

Q9H4B6-1 [UniParc]FASTAAdd to Basket

« Hide

MLSRKKTKNE VSKPAEVQGK YVKKETSPLL RNLMPSFIRH GPTIPRRTDI    50
CLPDSSPNAF STSGDVVSRN QSFLRTPIQR TPHEIMRRES NRLSAPSYLA 100
RSLADVPREY GSSQSFVTEV SFAVENGDSG SRYYYSDNFF DGQRKRPLGD 150
RAHEDYRYYE YNHDLFQRMP QNQGRHASGI GRVAATSLGN LTNHGSEDLP 200
LPPGWSVDWT MRGRKYYIDH NTNTTHWSHP LEREGLPPGW ERVESSEFGT 250
YYVDHTNKKA QYRHPCAPSV PRYDQPPPVT YQPQQTERNQ SLLVPANPYH 300
TAEIPDWLQV YARAPVKYDH ILKWELFQLA DLDTYQGMLK LLFMKELEQI 350
VKMYEAYRQA LLTELENRKQ RQQWYAQQHG KNF 383
Length:383
Mass (Da):44,634
Last modified:July 11, 2003 - v2
Checksum:i4012C40A8601417A
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti185 – 1851A → D in a colon cancer cell line. 1 Publication
VAR_015880

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti5 – 51K → Q in CAC13972. 1 Publication
Sequence conflicti18 – 181Q → R in CAG33578. 1 Publication
Sequence conflicti292 – 2921L → F in BAB13835. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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.2. human.

Polymorphism databases

DMDMi32699681.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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.

3D structure databases

ProteinModelPortali Q9H4B6.
SMRi Q9H4B6. Positions 197-269.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 121917. 57 interactions.
IntActi Q9H4B6. 60 interactions.
MINTi MINT-2817789.
STRINGi 9606.ENSP00000324729.

PTM databases

PhosphoSitei Q9H4B6.

Polymorphism databases

DMDMi 32699681.

Proteomic databases

MaxQBi Q9H4B6.
PaxDbi Q9H4B6.
PRIDEi Q9H4B6.

Protocols and materials databases

DNASUi 60485.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000324679 ; ENSP00000324729 ; ENSG00000151748 .
GeneIDi 60485.
KEGGi hsa:60485.
UCSCi uc001wyh.2. human.

Organism-specific databases

CTDi 60485.
GeneCardsi GC14M051100.
HGNCi HGNC:17795. SAV1.
HPAi HPA001808.
MIMi 607203. gene.
neXtProti NX_Q9H4B6.
PharmGKBi PA134875018.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG314596.
HOGENOMi HOG000013074.
HOVERGENi HBG044514.
InParanoidi Q9H4B6.
KOi K16686.
OMAi HINKRAQ.
PhylomeDBi Q9H4B6.
TreeFami TF317631.

Enzyme and pathway databases

Reactomei REACT_118607. Signaling by Hippo.
SignaLinki Q9H4B6.

Miscellaneous databases

ChiTaRSi SAV1. human.
GeneWikii SAV1.
GenomeRNAii 60485.
NextBioi 65363.
PROi Q9H4B6.
SOURCEi Search...

Gene expression databases

ArrayExpressi Q9H4B6.
Bgeei Q9H4B6.
CleanExi HS_SAV1.
Genevestigatori Q9H4B6.

Family and domain databases

InterProi IPR011524. SARAH_dom.
IPR001202. WW_dom.
[Graphical view ]
Pfami PF00397. WW. 1 hit.
[Graphical view ]
SMARTi SM00456. WW. 2 hits.
[Graphical view ]
SUPFAMi SSF51045. SSF51045. 2 hits.
PROSITEi PS50951. SARAH. 1 hit.
PS50020. WW_DOMAIN_2. 2 hits.
[Graphical view ]
ProtoNeti Search...

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. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Fetus and Neuron.
  3. "Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
    Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
    Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
  4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. "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].
    Tissue: Kidney.
  6. "The Ste20-like kinase Mst2 activates the human large tumor suppressor kinase Lats1."
    Chan E.H.Y., Nousiainen M., Chalamalasetty R.B., Schaefer A., Nigg E.A., Sillje H.H.W.
    Oncogene 24:2076-2086(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH STK3/MST2.
  7. "Association of mammalian sterile twenty kinases, Mst1 and Mst2, with hSalvador via C-terminal coiled-coil domains, leads to its stabilization and phosphorylation."
    Callus B.A., Verhagen A.M., Vaux D.L.
    FEBS J. 273:4264-4276(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, HOMODIMERIZATION, INTERACTION WITH STK3/MST2 AND STK4/MST1, PHOSPHORYLATION.
  8. "Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
    Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
    Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  9. "The human WW45 protein enhances MST1-mediated apoptosis in vivo."
    Luo X., Li Z., Yan Q., Li X., Tao D., Wang J., Leng Y., Gardner K., Judge S.I., Li Q.Q., Hu J., Gong J.
    Int. J. Mol. Med. 23:357-362(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH STK4/MST1, TISSUE SPECIFICITY.
  10. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-210, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  11. "Ajuba LIM proteins are negative regulators of the Hippo signaling pathway."
    Das Thakur M., Feng Y., Jagannathan R., Seppa M.J., Skeath J.B., Longmore G.D.
    Curr. Biol. 20:657-662(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH WTIP AND AJUBA.
  12. "Components of the Hippo pathway cooperate with Nek2 kinase to regulate centrosome disjunction."
    Mardin B.R., Lange C., Baxter J.E., Hardy T., Scholz S.R., Fry A.M., Schiebel E.
    Nat. Cell Biol. 12:1166-1176(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH NEK2.
  13. "Mammalian MST2 kinase and human Salvador activate and reduce estrogen receptor alpha in the absence of ligand."
    Park Y., Park J., Lee Y., Lim W., Oh B.C., Shin C., Kim W., Lee Y.
    J. Mol. Med. 89:181-191(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH ESR1.
  14. "Salvador promotes both cell cycle exit and apoptosis in Drosophila and is mutated in human cancer cell lines."
    Tapon N., Harvey K.F., Bell D.W., Wahrer D.C.R., Schiripo T.A., Haber D.A., Hariharan I.K.
    Cell 110:467-478(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT ASP-185.

Entry informationi

Entry nameiSAV1_HUMAN
AccessioniPrimary (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: September 3, 2014
This is version 105 of the entry and version 2 of the sequence. [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
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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