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Q9H4B6 (SAV1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 104. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Protein salvador homolog 1
Alternative name(s):
45 kDa WW domain protein
Short name=hWW45
Gene names
Name:SAV1
Synonyms:WW45
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length383 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.7 Ref.9 Ref.12 Ref.13

Subunit structure

Homodimer. Stabilized through interaction with STK3/MST2 or STK4/MST1. Interacts (via SARAH domain) with isoform 1of NEK2. Interacts with ESR1 only in the presence of STK3/MST2. Interacts with WTIP and AJUBA. Ref.6 Ref.7 Ref.9 Ref.11 Ref.12 Ref.13

Subcellular location

Nucleus. Cytoplasm Ref.9.

Tissue specificity

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. Ref.9

Post-translational modification

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. Ref.7

Sequence similarities

Contains 1 SARAH domain.

Contains 2 WW domains.

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 383383Protein salvador homolog 1
PRO_0000076060

Regions

Domain199 – 23234WW 1
Domain234 – 26734WW 2
Domain321 – 36848SARAH
Coiled coil344 – 37330 Potential

Amino acid modifications

Modified residue2101Phosphothreonine Ref.10

Natural variations

Natural variant1851A → D in a colon cancer cell line. Ref.14
VAR_015880

Experimental info

Sequence conflict51K → Q in CAC13972. Ref.1
Sequence conflict181Q → R in CAG33578. Ref.3
Sequence conflict2921L → F in BAB13835. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Q9H4B6 [UniParc].

Last modified July 11, 2003. Version 2.
Checksum: 4012C40A8601417A

FASTA38344,634
        10         20         30         40         50         60 
MLSRKKTKNE VSKPAEVQGK YVKKETSPLL RNLMPSFIRH GPTIPRRTDI CLPDSSPNAF 

        70         80         90        100        110        120 
STSGDVVSRN QSFLRTPIQR TPHEIMRRES NRLSAPSYLA RSLADVPREY GSSQSFVTEV 

       130        140        150        160        170        180 
SFAVENGDSG SRYYYSDNFF DGQRKRPLGD RAHEDYRYYE YNHDLFQRMP QNQGRHASGI 

       190        200        210        220        230        240 
GRVAATSLGN LTNHGSEDLP LPPGWSVDWT MRGRKYYIDH NTNTTHWSHP LEREGLPPGW 

       250        260        270        280        290        300 
ERVESSEFGT YYVDHTNKKA QYRHPCAPSV PRYDQPPPVT YQPQQTERNQ SLLVPANPYH 

       310        320        330        340        350        360 
TAEIPDWLQV YARAPVKYDH ILKWELFQLA DLDTYQGMLK LLFMKELEQI VKMYEAYRQA 

       370        380 
LLTELENRKQ RQQWYAQQHG KNF 

« Hide

References

« Hide 'large scale' references
[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. expand/collapse author list , 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]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
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]"Large-scale proteomics analysis of the human kinome."
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H.
Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS9701.1.
PIRJC7507.
RefSeqNP_068590.1. NM_021818.3.
UniGeneHs.642842.
Hs.706933.

3D structure databases

ProteinModelPortalQ9H4B6.
SMRQ9H4B6. Positions 197-269.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid121917. 57 interactions.
IntActQ9H4B6. 60 interactions.
MINTMINT-2817789.
STRING9606.ENSP00000324729.

PTM databases

PhosphoSiteQ9H4B6.

Polymorphism databases

DMDM32699681.

Proteomic databases

MaxQBQ9H4B6.
PaxDbQ9H4B6.
PRIDEQ9H4B6.

Protocols and materials databases

DNASU60485.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000324679; ENSP00000324729; ENSG00000151748.
GeneID60485.
KEGGhsa:60485.
UCSCuc001wyh.2. human.

Organism-specific databases

CTD60485.
GeneCardsGC14M051100.
HGNCHGNC:17795. SAV1.
HPAHPA001808.
MIM607203. gene.
neXtProtNX_Q9H4B6.
PharmGKBPA134875018.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG314596.
HOGENOMHOG000013074.
HOVERGENHBG044514.
InParanoidQ9H4B6.
KOK16686.
OMAHINKRAQ.
PhylomeDBQ9H4B6.
TreeFamTF317631.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
SignaLinkQ9H4B6.

Gene expression databases

ArrayExpressQ9H4B6.
BgeeQ9H4B6.
CleanExHS_SAV1.
GenevestigatorQ9H4B6.

Family and domain databases

InterProIPR011524. SARAH_dom.
IPR001202. WW_dom.
[Graphical view]
PfamPF00397. WW. 1 hit.
[Graphical view]
SMARTSM00456. WW. 2 hits.
[Graphical view]
SUPFAMSSF51045. SSF51045. 2 hits.
PROSITEPS50951. SARAH. 1 hit.
PS50020. WW_DOMAIN_2. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSSAV1. human.
GeneWikiSAV1.
GenomeRNAi60485.
NextBio65363.
PROQ9H4B6.
SOURCESearch...

Entry information

Entry nameSAV1_HUMAN
AccessionPrimary (citable) accession number: Q9H4B6
Secondary accession number(s): A8K4B8 expand/collapse secondary AC list , D3DSB6, Q6IA58, Q9H949, Q9HAK9
Entry history
Integrated into UniProtKB/Swiss-Prot: July 11, 2003
Last sequence update: July 11, 2003
Last modified: July 9, 2014
This is version 104 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 14

Human chromosome 14: entries, gene names and cross-references to MIM