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SAV1 (Salvador homolog 1 (Drosophila))

Identity

Other namesSalvador
WW45
WWP4
HGNC (Hugo) SAV1
LocusID (NCBI) 60485
Location 14q13-q23
Location_base_pair Starts at 51100360 and ends at 51135023 bp from pter ( according to hg19-Feb_2009)  [Mapping]
Local_order telomeric to SPG3A and centromeric to ZF405P

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 5¹ and 3¹ 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

Entity To date SAV1 is not implicated in any diseases.
  

External links

Nomenclature
HGNC (Hugo)SAV1   17795
Entrez_Gene (NCBI)SAV1  60485  salvador homolog 1 (Drosophila)
Cards
AtlasSAV1ID42206ch14q13
GeneCards (Weizmann)SAV1
Ensembl (Hinxton)ENSG00000151748 [Gene_View]  chr14:51100360-51135023 [Contig_View]  SAV1 [Vega]
AceView (NCBI)SAV1
Genatlas (Paris)SAV1
euGene (Indiana)60485
SOURCE (Stanford)NM_021818
Genomic and cartography
GoldenPath (UCSC)SAV1  -     chr14:51100360-51135023 -  14q13-q23   [Description]    (hg19-Feb_2009)
EnsemblSAV1 - 14q13-q23 [CytoView]
Mapping of homologs : NCBISAV1 [Mapview]
OMIM607203   
Gene and transcription
Genbank (Entrez)AF088000 AJ292969 AK021500 AK023071 AK095903
RefSeq transcript (SRS)NM_021818
RefSeq transcript (Entrez)NM_021818
RefSeq genomic (SRS)AC_000146 NC_000014 NG_009028 NT_026437 NW_001838111
RefSeq genomic (Entrez)AC_000146 NC_000014 NG_009028 NT_026437 NW_001838111
Consensus coding sequences : CCDS (NCBI)SAV1
Cluster EST : UnigeneHs.642842 [ SRS ] Hs.642842 [ NCBI ]
Alternative Splicing : Fast-db (Paris)208
Alternative Splicing GalleryENSG00000151748
Gene ExpressionSAV1 [ NCBI-GEO ]   SAV1 [ EBI - ARRAY_EXPRESS ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ9H4B6 (SRS) Q9H4B6 (Uniprot)
With graphics : InterProQ9H4B6
Splice isoforms : SwissVarQ9H4B6(Swissvar)
Domaine pattern : Prosite (SRS)SARAH (PS50951)    WW_DOMAIN_1 (PS01159)    WW_DOMAIN_2 (PS50020)   
Domaine pattern : Prosite (Expaxy)SARAH (PS50951)    WW_DOMAIN_1 (PS01159)    WW_DOMAIN_2 (PS50020)   
Domains : Interpro (SRS)SARAH    WW_Rsp5_WWP   
Domains : Interpro (EBI)SARAH    WW_Rsp5_WWP   
Related proteins : CluSTrQ9H4B6
Domain families : Pfam (SRS)WW (PF00397)   
Domain families : Pfam (Sanger)WW (PF00397)   
Domain families : Pfam (NCBI)pfam00397   
Domain families : Smart (EMBL)WW (SM00456)  
Blocks (Seattle)Q9H4B6
Human Protein AtlasENSG00000151748
HPRD06229
IPIIPI00301738   IPI01013281   IPI01025535   IPI01025178   IPI01024822   IPI01025034   
Protein Interaction databases
DIP (DOE-UCLA)Q9H4B6
IntAct (EBI)Q9H4B6
FunCoupENSG00000151748
REACTOMESAV1
BioGRIDSAV1
InParanoidQ9H4B6
Interologous Interaction database Q9H4B6
Polymorphism : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)SAV1
SNP (GeneSNP Utah)SAV1
SNP : HGBaseSAV1
Genetic variants : HAPMAPSAV1
Somatic Mutations in Cancer : COSMICSAV1 
CONAN: Copy Number AnalysisSAV1 
Mutations and Diseases : HGMDSAV1
OMIM607203   
GENETests607203   
Disease Genetic AssociationSAV1
Huge Navigator SAV1 [HugePedia]  SAV1 [HugeCancerGEM]
Genomic VariantsSAV1
snp3D : Map Gene to Disease60485
General knowledge
Homologs : HomoloGeneSAV1
Homology/Alignments : Family Browser (UCSC)SAV1
Phylogenetic Trees/Animal Genes : TreeFamSAV1
Chemical/Protein Interactions : CTD60485
Chemical/Pharm GKB GenePA134875018
Clinical trialSAV1
Cancer Resource (Charite)ENSG00000151748
Ontology : AmiGOhair follicle development  protein binding  nucleus  cytoplasm  signal transduction  keratinocyte differentiation  hippo signaling cascade  positive regulation of apoptotic process  regulation of organ growth  negative regulation of epithelial cell proliferation  negative regulation of cardiac muscle cell proliferation  ventricular septum morphogenesis  lung epithelial cell differentiation  intestinal epithelial cell differentiation  regulation of stem cell maintenance  
Ontology : EGO-EBIhair follicle development  protein binding  nucleus  cytoplasm  signal transduction  keratinocyte differentiation  hippo signaling cascade  positive regulation of apoptotic process  regulation of organ growth  negative regulation of epithelial cell proliferation  negative regulation of cardiac muscle cell proliferation  ventricular septum morphogenesis  lung epithelial cell differentiation  intestinal epithelial cell differentiation  regulation of stem cell maintenance  
Other databases
Probes
Probes : ImagenesSAV1 Related clones (RZPD - Berlin)
Litterature
PubMed20 Pubmed reference(s) in Entrez
PubGeneSAV1
iHOPSAV1

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Contributor(s)

Written06-2007Bernard A Callus
Biochemistry Department, La Trobe University, Bundoora VIC 3086, Australia

Citation

This paper should be referenced as such :
Callus BA . SAV1 (Salvador homolog 1 (Drosophila)). Atlas Genet Cytogenet Oncol Haematol. June 2007 .
URL : http://AtlasGeneticsOncology.org/Genes/SAV1ID42206ch14q13.html

This paper is referenced by INIST as such :
http://documents.irevues.inist.fr/bitstream/2042/38464/1/06-2007-SAV1ID42206ch14q13.pdf   [ Bibliographic record ]

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indexed on : Sat Apr 28 15:09:15 CEST 2012

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