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SAV1 (Salvador homolog 1 (Drosophila))

Written2007-06Bernard A Callus
Biochemistry Department, La Trobe University, Bundoora VIC 3086, Australia

(Note : for Links provided by Atlas : click)


Alias_namessalvador homolog 1 (Drosophila)
Alias_symbol (synonym)WW45
Other aliasSalvador
HGNC (Hugo) SAV1
LocusID (NCBI) 60485
Atlas_Id 42206
Location 14q22.1  [Link to chromosome band 14q22]
Location_base_pair Starts at 50633580 and ends at 50668353 bp from pter ( according to hg19-Feb_2009)  [Mapping SAV1.png]
Local_order telomeric to SPG3A and centromeric to ZF405P
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
MAP4K5 (14q21.3) / SAV1 (14q22.1)MAP4K5 (14q22.1) / SAV1 (14q22.1)SAV1 (14q22.1) / ATL1 (14q22.1)
USP11 (Xp11.23) / SAV1 (14q22.1)


  SAV1 is encoded by five exons represented by the boxes. The blue shaded region indicates the Sav1 coding region while the untranslated regions (UTR) are shown in white.
Description The Sav1 gene spans 34.7 kb.
Transcription The longest SAV1 mRNA transcript of 3.0 kb encodes an open reading frame (ORF) of 1152 bases and untranslated regions of 338 and 1541 bases at the 5' and 3' ends, respectively. No splice variants have been reported for SAV1. Smaller transcripts of 1.8 kb and 2.1 kb, encoding the identical ORF, have been isolated which may be the result of alternative sites of poly-adenylation.


  SAV1 contains two central proline-binding WW domains (red) and a C-terminal SARAH (for Salvador/Rassf/Hippo) domain (green).
Description Sav1 is 383 amino acids in length with an expected weight of 44,606 Da. WW1: residues 199-232; WW2: 234-267; SARAH domain: residues 321-368. The SARAH domain partially overlaps with a predicted coiled-coil domain: 344-373.
Expression SAV1 mRNA is ubiquitously expressed in adult tissues with highest expression in the placenta, pancreas, heart, kidney, lung and aorta and lowest expression in skeletal muscle. Expression was higher in fetal heart compared with adult heart.
Localisation SAV1 is localized to the centrosome during interphase and metaphase and localizes with the contractile ring during cytokinesis. SAV1 co-localizes with MST2, RASSF1A and LATS1 during anaphase, interphase, metaphase and cytokinesis.
Function Sav1 is a scaffold protein and able to homodimerize independently of its SARAH domain. Sav1 binds to MST1/2 kinases and RASSF1A in an interaction that requires their homologous SARAH domains. The binding of MST stabilizes SAV1 abundance and enhances the association of SAV1 with RASSF1A. SAV1 is phosphorylated by MST1/2 but the consequence of this is not known. The MST2/SAV1/RASSF1A complex can recruit LATS1 kinase resulting in the activation of LATS1 by MST2. The MST2/SAV1/RASSF1A/LATS1 complex may function in regulating cell-cycle exit. In Drosophila, dSav mutant tissue is more resistant to apoptosis and grows more quickly compared with wild type tissue suggesting dSav is a dual regulator of cell proliferation and apoptosis.
Homology mSav1 is 94% identical to hSav1. hSav1 is 31% identical and 44% similar to dSav from Drosophila melanogaster, however, the similarity increases to 59% if only the sequences comprising the WW and SARAH domains are compared. There is no recognizable orthologue of hSav1 in S.cerevisiae.


Note The cDNA sequence for SAV1 is conflicted at codons 5 (K/Q), 18 (Q/R), 292 (L/F) and 373 (Q/stop).
Germinal No germline mutations for SAV1 have been reported.
Somatic In one study of 52 cancer cell lines, SAV1 was deleted in two renal cancer cell lines (ACHN and 786-O) and a C to A mutation at nucleotide 554 (Ala185Asp) was detected in a colon cancer cell line (HCT15). A second study from the Korean population failed to detect the C554A polymorphism or any additional mutations of SAV1 in 324 cancer cell lines. A third study failed to detect hypermethylation the SAV1 promoter in 44 soft tissue sarcomas and 6 sarcoma cell lines. These results suggest that (1) the C554A mutation found in the colon cancer cell line might be a true mutation and (2) that SAV1 is not frequently mutated in human cancers.

Implicated in

Entity To date SAV1 is not implicated in any diseases.


Association of mammalian sterile twenty kinases, Mst1 and Mst2, with hSalvador via C-terminal coiled-coil domains, leads to its stabilization and phosphorylation.
Callus BA, Verhagen AM, Vaux DL
The FEBS journal. 2006 ; 273 (18) : 4264-4276.
PMID 16930133
The Ste20-like kinase Mst2 activates the human large tumor suppressor kinase Lats1.
Chan EH, Nousiainen M, Chalamalasetty RB, Schäfer A, Nigg EA, Silljé HH
Oncogene. 2005 ; 24 (12) : 2076-2086.
PMID 15688006
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
Direct submission GenBank database June. 2004.
RASSF1A is part of a complex similar to the Drosophila Hippo/Salvador/Lats tumor-suppressor network.
Guo C, Tommasi S, Liu L, Yee JK, Dammann R, Pfeifer GP
Current biology : CB. 2007 ; 17 (8) : 700-705.
PMID 17379520
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 TO, 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
Nature genetics. 2004 ; 36 (1) : 40-45.
PMID 14702039
Frequent hypermethylation of MST1 and MST2 in soft tissue sarcoma.
Seidel C, Schagdarsurengin U, Blümke K, Würl P, Pfeifer GP, Hauptmann S, Taubert H, Dammann R
Molecular carcinogenesis. 2007 ; 46 (10) : 865-871.
PMID 17538946
Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
Strausberg RL, Feingold EA, Grouse LH, Derge JG, Klausner RD, Collins FS, Wagner L, Shenmen CM, Schuler GD, Altschul SF, Zeeberg B, Buetow KH, Schaefer CF, Bhat NK, Hopkins RF, Jordan H, Moore T, Max SI, Wang J, Hsieh F, Diatchenko L, Marusina K, Farmer AA, Rubin GM, Hong L, Stapleton M, Soares MB, Bonaldo MF, Casavant TL, Scheetz TE, Brownstein MJ, Usdin TB, Toshiyuki S, Carninci P, Prange C, Raha SS, Loquellano NA, Peters GJ, Abramson RD, Mullahy SJ, Bosak SA, McEwan PJ, McKernan KJ, Malek JA, Gunaratne PH, Richards S, Worley KC, Hale S, Garcia AM, Gay LJ, Hulyk SW, Villalon DK, Muzny DM, Sodergren EJ, Lu X, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madan A, Young AC, Shevchenko Y, Bouffard GG, Blakesley RW, Touchman JW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Krzywinski MI, Skalska U, Smailus DE, Schnerch A, Schein JE, Jones SJ, Mammalian Gene Collection Program Team, Marra MA
Proceedings of the National Academy of Sciences of the United States of America. 2002 ; 99 (26) : 16899-16903.
PMID 12477932
Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library.
Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S
Gene. 1997 ; 200 (1-2) : 149-156.
PMID 9373149
salvador Promotes both cell cycle exit and apoptosis in Drosophila and is mutated in human cancer cell lines.
Tapon N, Harvey KF, Bell DW, Wahrer DC, Schiripo TA, Haber DA, Hariharan IK
Cell. 2002 ; 110 (4) : 467-478.
PMID 12202036
Cloning, expression, and mapping of hWW45, a novel human WW domain-containing gene.
Valverde P
Biochemical and biophysical research communications. 2000 ; 276 (3) : 990-998.
PMID 11027580
Mutational analysis of salvador gene in human carcinomas.
Yoo NJ, Soung YH, Lee JW, Park WS, Kim SY, Nam SW, Han JH, Kim SH, Lee JY, Lee SH
APMIS : acta pathologica, microbiologica, et immunologica Scandinavica. 2003 ; 111 (6) : 595-598.
PMID 12969014


This paper should be referenced as such :
Callus, BA
SAV1 (Salvador homolog 1 (Drosophila))
Atlas Genet Cytogenet Oncol Haematol. 2008;12(1):10-11.
Free journal version : [ pdf ]   [ DOI ]
On line version :

Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 2 ]
  MAP4K5/SAV1 (14q22)
SAV1/ATL1 (14q22)

External links

HGNC (Hugo)SAV1   17795
Entrez_Gene (NCBI)SAV1  60485  salvador family WW domain containing protein 1
AliasesSAV; WW45; WWP4
GeneCards (Weizmann)SAV1
Ensembl hg19 (Hinxton)ENSG00000151748 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000151748 [Gene_View]  ENSG00000151748 [Sequence]  chr14:50633580-50668353 [Contig_View]  SAV1 [Vega]
ICGC DataPortalENSG00000151748
TCGA cBioPortalSAV1
AceView (NCBI)SAV1
Genatlas (Paris)SAV1
SOURCE (Princeton)SAV1
Genetics Home Reference (NIH)SAV1
Genomic and cartography
GoldenPath hg38 (UCSC)SAV1  -     chr14:50633580-50668353 -  14q22.1   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)SAV1  -     14q22.1   [Description]    (hg19-Feb_2009)
GoldenPathSAV1 - 14q22.1 [CytoView hg19]  SAV1 - 14q22.1 [CytoView hg38]
Mapping of homologs : NCBISAV1 [Mapview hg19]  SAV1 [Mapview hg38]
Gene and transcription
Genbank (Entrez)AF088000 AJ292969 AK021500 AK023071 AK095903
RefSeq transcript (Entrez)NM_021818
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)SAV1
Cluster EST : UnigeneHs.706933 [ NCBI ]
CGAP (NCI)Hs.706933
Alternative Splicing GalleryENSG00000151748
Gene ExpressionSAV1 [ NCBI-GEO ]   SAV1 [ EBI - ARRAY_EXPRESS ]   SAV1 [ SEEK ]   SAV1 [ MEM ]
Gene Expression Viewer (FireBrowse)SAV1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevestigatorExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)60485
GTEX Portal (Tissue expression)SAV1
Human Protein AtlasENSG00000151748-SAV1 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ9H4B6   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ9H4B6  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ9H4B6
Splice isoforms : SwissVarQ9H4B6
Domaine pattern : Prosite (Expaxy)SARAH (PS50951)    WW_DOMAIN_2 (PS50020)   
Domains : Interpro (EBI)SARAH_dom    Sav    WW_dom    WW_dom_sf   
Domain families : Pfam (Sanger)WW (PF00397)   
Domain families : Pfam (NCBI)pfam00397   
Domain families : Smart (EMBL)WW (SM00456)  
Conserved Domain (NCBI)SAV1
DMDM Disease mutations60485
Blocks (Seattle)SAV1
PDB Europe6AO5   
PDB (PDBSum)6AO5   
PDB (IMB)6AO5   
Structural Biology KnowledgeBase6AO5   
SCOP (Structural Classification of Proteins)6AO5   
CATH (Classification of proteins structures)6AO5   
Human Protein Atlas [tissue]ENSG00000151748-SAV1 [tissue]
Peptide AtlasQ9H4B6
IPIIPI00301738   IPI01013281   IPI01025535   IPI01025178   IPI01024822   IPI01025034   
Protein Interaction databases
IntAct (EBI)Q9H4B6
Ontologies - Pathways
Ontology : AmiGOhair follicle development  protein binding  nucleus  cytoplasm  cytoplasm  cytosol  cytosol  apoptotic process  signal transduction  keratinocyte differentiation  hippo signaling  hippo signaling  hippo signaling  identical protein binding  positive regulation of apoptotic process  positive regulation of fat cell differentiation  negative regulation of epithelial cell proliferation  protein stabilization  positive regulation of DNA-binding transcription factor activity  negative regulation of cardiac muscle cell proliferation  molecular adaptor activity  ventricular septum morphogenesis  lung epithelial cell differentiation  intestinal epithelial cell differentiation  regulation of stem cell population maintenance  
Ontology : EGO-EBIhair follicle development  protein binding  nucleus  cytoplasm  cytoplasm  cytosol  cytosol  apoptotic process  signal transduction  keratinocyte differentiation  hippo signaling  hippo signaling  hippo signaling  identical protein binding  positive regulation of apoptotic process  positive regulation of fat cell differentiation  negative regulation of epithelial cell proliferation  protein stabilization  positive regulation of DNA-binding transcription factor activity  negative regulation of cardiac muscle cell proliferation  molecular adaptor activity  ventricular septum morphogenesis  lung epithelial cell differentiation  intestinal epithelial cell differentiation  regulation of stem cell population maintenance  
Pathways : KEGGHippo signaling pathway   
REACTOMEQ9H4B6 [protein]
REACTOME PathwaysR-HSA-2028269 [pathway]   
NDEx NetworkSAV1
Atlas of Cancer Signalling NetworkSAV1
Wikipedia pathwaysSAV1
Orthology - Evolution
GeneTree (enSembl)ENSG00000151748
Phylogenetic Trees/Animal Genes : TreeFamSAV1
Homologs : HomoloGeneSAV1
Homology/Alignments : Family Browser (UCSC)SAV1
Gene fusions - Rearrangements
Fusion : MitelmanMAP4K5/SAV1 [14q21.3/14q22.1]  [t(14;14)(q22;q22)]  
Fusion : MitelmanSAV1/ATL1 [14q22.1/14q22.1]  [t(14;14)(q22;q22)]  
Fusion PortalMAP4K5 14q21.3 SAV1 14q22.1 BRCA
Fusion PortalSAV1 14q22.1 ATL1 14q22.1 BRCA
Fusion : FusionGDB20916    24368    32684    40962    6522   
Fusion : Fusion_HubABHD12B--SAV1    ALS2--SAV1    CDK14--SAV1    CHST11--SAV1    FERMT2--SAV1    FRMD6--SAV1    GYPB--SAV1    IGSF9B--SAV1    KDM4C--SAV1    MAP4K5--SAV1    MKLN1--SAV1    NIN--SAV1    PRH2--SAV1    RB1--SAV1    SAV1--ATL1   
SAV1--B4GAT1    SAV1--CD55    SAV1--CDKL1    SAV1--DLG1    SAV1--GYPA    SAV1--GYPB    SAV1--GYPE    SAV1--MAP4    SAV1--MARK3    SAV1--MKLN1    SAV1--TXNL1    SLC36A1--SAV1    USP11--SAV1   
Fusion : QuiverSAV1
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerSAV1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)SAV1
Exome Variant ServerSAV1
ExAC (Exome Aggregation Consortium)ENSG00000151748
GNOMAD BrowserENSG00000151748
Varsome BrowserSAV1
Genetic variants : HAPMAP60485
Genomic Variants (DGV)SAV1 [DGVbeta]
DECIPHERSAV1 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisSAV1 
ICGC Data PortalSAV1 
TCGA Data PortalSAV1 
Broad Tumor PortalSAV1
OASIS PortalSAV1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICSAV1  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DSAV1
Mutations and Diseases : HGMDSAV1
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch SAV1
DgiDB (Drug Gene Interaction Database)SAV1
DoCM (Curated mutations)SAV1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)SAV1 (select a term)
NCG5 (London)SAV1
Cancer3DSAV1(select the gene name)
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Genetic Testing Registry SAV1
NextProtQ9H4B6 [Medical]
Target ValidationSAV1
Huge Navigator SAV1 [HugePedia]
snp3D : Map Gene to Disease60485
BioCentury BCIQSAV1
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD60485
Chemical/Pharm GKB GenePA134875018
Clinical trialSAV1
canSAR (ICR)SAV1 (select the gene name)
DataMed IndexSAV1
PubMed58 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Wed Nov 13 21:58:05 CET 2019

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