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Q9H4B6

- SAV1_HUMAN

UniProt

Q9H4B6 - SAV1_HUMAN

Protein

Protein salvador homolog 1

Gene

SAV1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 106 (01 Oct 2014)
      Sequence version 2 (11 Jul 2003)
      Previous versions | rss
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    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

    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 1 Publication. Cytoplasm 1 Publication

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB
    2. cytosol Source: Reactome
    3. nucleus Source: UniProtKB

    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 1PRO_0000076060Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei210 – 2101Phosphothreonine2 Publications

    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.2 Publications

    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.
    DIPiDIP-36127N.
    IntActiQ9H4B6. 60 interactions.
    MINTiMINT-2817789.
    STRINGi9606.ENSP00000324729.

    Structurei

    3D structure databases

    ProteinModelPortaliQ9H4B6.
    SMRiQ9H4B6. Positions 197-269.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini199 – 23234WW 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini234 – 26734WW 2PROSITE-ProRule annotationAdd
    BLAST
    Domaini321 – 36848SARAHPROSITE-ProRule annotationAdd
    BLAST

    Coiled coil

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Coiled coili344 – 37330Sequence 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

    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

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti5 – 51K → Q in CAC13972. (PubMed:11027580)Curated
    Sequence conflicti18 – 181Q → R in CAG33578. 1 PublicationCurated
    Sequence conflicti292 – 2921L → F in BAB13835. (PubMed:14702039)Curated

    Natural variant

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

    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.
    DIPi DIP-36127N.
    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

    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: October 1, 2014
    This is version 106 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