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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)

Identity

Other namesSalvador
WW45
WWP4
HGNC (Hugo) SAV1
LocusID (NCBI) 60485
Atlas_Id 42206
Location 14q22.1  [Link to chromosome band 14q22]
Location_base_pair Starts at 51100298 and ends at 51135071 bp from pter ( according to hg19-Feb_2009)  [Mapping SAV1.png]
Local_order telomeric to SPG3A and centromeric to ZF405P
Fusion genes
(updated 2016)
MAP4K5 (14q21.3) / SAV1 (14q22.1)SAV1 (14q22.1) / ATL1 (14q22.1)USP11 (Xp11.23) / SAV1 (14q22.1)

DNA/RNA

 
  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.

Protein

 
  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.

Mutations

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

Note
Entity To date SAV1 is not implicated in any diseases.
  

Bibliography

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
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PMID 12969014
 

Citation

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 : http://AtlasGeneticsOncology.org/Genes/SAV1ID42206ch14q13.html


External links

Nomenclature
HGNC (Hugo)SAV1   17795
Cards
AtlasSAV1ID42206ch14q13
Entrez_Gene (NCBI)SAV1  60485  salvador family WW domain containing protein 1
AliasesSAV; WW45; WWP4
GeneCards (Weizmann)SAV1
Ensembl hg19 (Hinxton)ENSG00000151748 [Gene_View]  chr14:51100298-51135071 [Contig_View]  SAV1 [Vega]
Ensembl hg38 (Hinxton)ENSG00000151748 [Gene_View]  chr14:51100298-51135071 [Contig_View]  SAV1 [Vega]
ICGC DataPortalENSG00000151748
TCGA cBioPortalSAV1
AceView (NCBI)SAV1
Genatlas (Paris)SAV1
WikiGenes60485
SOURCE (Princeton)SAV1
Genomic and cartography
GoldenPath hg19 (UCSC)SAV1  -     chr14:51100298-51135071 -  14q13-q23   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)SAV1  -     14q13-q23   [Description]    (hg38-Dec_2013)
EnsemblSAV1 - 14q13-q23 [CytoView hg19]  SAV1 - 14q13-q23 [CytoView hg38]
Mapping of homologs : NCBISAV1 [Mapview hg19]  SAV1 [Mapview hg38]
OMIM607203   
Gene and transcription
Genbank (Entrez)AF088000 AJ292969 AK021500 AK023071 AK095903
RefSeq transcript (Entrez)NM_021818
RefSeq genomic (Entrez)NC_000014 NC_018925 NT_026437 NW_004929393
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]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)60485
GTEX Portal (Tissue expression)SAV1
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ9H4B6 (Uniprot)
NextProtQ9H4B6  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ9H4B6
Splice isoforms : SwissVarQ9H4B6 (Swissvar)
PhosPhoSitePlusQ9H4B6
Domaine pattern : Prosite (Expaxy)SARAH (PS50951)    WW_DOMAIN_2 (PS50020)   
Domains : Interpro (EBI)SARAH_dom    WW_dom   
Domain families : Pfam (Sanger)WW (PF00397)   
Domain families : Pfam (NCBI)pfam00397   
Domain families : Smart (EMBL)WW (SM00456)  
DMDM Disease mutations60485
Blocks (Seattle)SAV1
SuperfamilyQ9H4B6
Human Protein AtlasENSG00000151748
Peptide AtlasQ9H4B6
HPRD06229
IPIIPI00301738   IPI01013281   IPI01025535   IPI01025178   IPI01024822   IPI01025034   
Protein Interaction databases
DIP (DOE-UCLA)Q9H4B6
IntAct (EBI)Q9H4B6
FunCoupENSG00000151748
BioGRIDSAV1
STRING (EMBL)SAV1
ZODIACSAV1
Ontologies - Pathways
QuickGOQ9H4B6
Ontology : AmiGOhair follicle development  protein binding  nucleus  cytoplasm  cytosol  keratinocyte differentiation  hippo signaling  hippo signaling  positive regulation of apoptotic process  positive regulation of fat cell differentiation  negative regulation of epithelial cell proliferation  protein stabilization  positive regulation of sequence-specific DNA binding transcription factor activity  negative regulation of cardiac muscle cell proliferation  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  cytosol  keratinocyte differentiation  hippo signaling  hippo signaling  positive regulation of apoptotic process  positive regulation of fat cell differentiation  negative regulation of epithelial cell proliferation  protein stabilization  positive regulation of sequence-specific DNA binding transcription factor activity  negative regulation of cardiac muscle cell proliferation  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 Signaling by Hippo [pathway]
NDEx Network
Atlas of Cancer Signalling NetworkSAV1
Wikipedia pathwaysSAV1
Orthology - Evolution
OrthoDB60485
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: TCGAMAP4K5 14q21.3 SAV1 14q22.1 BRCA
Fusion: TCGASAV1 14q22.1 ATL1 14q22.1 BRCA
Polymorphisms : SNP, variants
NCBI Variation ViewerSAV1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)SAV1
dbVarSAV1
ClinVarSAV1
1000_GenomesSAV1 
Exome Variant ServerSAV1
ExAC (Exome Aggregation Consortium)SAV1 (select the gene name)
Genetic variants : HAPMAP60485
Genomic Variants (DGV)SAV1 [DGVbeta]
Mutations
ICGC Data PortalSAV1 
TCGA Data PortalSAV1 
Broad Tumor PortalSAV1
OASIS PortalSAV1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICSAV1 
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)
intoGenSAV1
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] 
Diseases
DECIPHER (Syndromes)14:51100298-51135071  ENSG00000151748
CONAN: Copy Number AnalysisSAV1 
Mutations and Diseases : HGMDSAV1
OMIM607203   
MedgenSAV1
Genetic Testing Registry SAV1
NextProtQ9H4B6 [Medical]
TSGene60485
GENETestsSAV1
Huge Navigator SAV1 [HugePedia]
snp3D : Map Gene to Disease60485
BioCentury BCIQSAV1
ClinGenSAV1
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD60485
Chemical/Pharm GKB GenePA134875018
Clinical trialSAV1
Miscellaneous
canSAR (ICR)SAV1 (select the gene name)
Probes
Litterature
PubMed43 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineSAV1
EVEXSAV1
GoPubMedSAV1
iHOPSAV1
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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