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SAV1 (Salvador homolog 1 (Drosophila))

Identity

Other namesSalvador
WW45
WWP4
Hugo SAV1
Location 14q13-q23
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
HugoSAV1
GDBSAV1
Entrez_GeneSAV1  60485  salvador homolog 1 (Drosophila)
Cards
AtlasSAV1ID42206ch14q13
GeneCardsSAV1
EnsemblSAV1 [Search_View]   ENSG00000151748 [Gene_View]
GenatlasSAV1
GeneLynxSAV1
eGenomeSAV1
euGene60485
Genomic and cartography
GoldenPathSAV1  -     chr14:50170110-50204773 -  14q13-q23   [Description]    (hg18-Mar_2006)
EnsemblSAV1 - 14q13-q23 [CytoView]
NCBIMapview
OMIMDisease map [OMIM]
HomoloGeneSAV1
Gene and transcription
GenbankAF088000 [ ENTREZ ]
GenbankAJ292969 [ ENTREZ ]
GenbankAK021500 [ ENTREZ ]
GenbankAK023071 [ ENTREZ ]
GenbankAK095903 [ ENTREZ ]
RefSeqNM_021818 [ SRS ]    NM_021818 [ ENTREZ ]
RefSeqAC_000057 [ SRS ]    AC_000057 [ ENTREZ ]
RefSeqNC_000014 [ SRS ]    NC_000014 [ ENTREZ ]
RefSeqNT_026437 [ SRS ]    NT_026437 [ ENTREZ ]
RefSeqNW_925539 [ SRS ]    NW_925539 [ ENTREZ ]
AceViewSAV1 AceView - NCBI
UnigeneHs.642842 [ SRS ]    Hs.642842 [ NCBI ]     HS642842 [ spliceNest ]
Fast-db208 (alternative variants)
Protein : pattern, domain, 3D structure
SwissProtQ9H4B6 [ SRS]    Q9H4B6 [ EXPASY ]     Q9H4B6 [ INTERPRO ]
PrositePS50951 SARAH [ SRS ]    PS50951 SARAH [ Expasy ]
PrositePS01159 WW_DOMAIN_1 [ SRS ]    PS01159 WW_DOMAIN_1 [ Expasy ]
PrositePS50020 WW_DOMAIN_2 [ SRS ]    PS50020 WW_DOMAIN_2 [ Expasy ]
InterproIPR011524 SARAH [ SRS ]    IPR011524 SARAH [ EBI ]
InterproIPR001202 WW_Rsp5_WWP [ SRS ]    IPR001202 WW_Rsp5_WWP [ EBI ]
CluSTrQ9H4B6
PfamPF00397 WW [ SRS ]    PF00397 WW [ Sanger ]    pfam00397 [ NCBI-CDD ]
SmartSM00456 WW [EMBL]
BlocksQ9H4B6
HPRD06229
Protein Interaction databases
DIPQ9H4B6
IntActQ9H4B6
Polymorphism : SNP, mutations, diseases
OMIM607203    [ map ]   
GENECLINICS607203
SNPSAV1 [dbSNP-NCBI]  
SNPNM_021818 [SNP-NCI]  
SNPSAV1 [GeneSNPs - Utah]  SAV1] [HGBASE - SRS]
HAPMAPSAV1 [HAPMAP]  
COSMICSAV1 [Somatic mutation (COSMIC-CGP-Sanger)]  
HGMDSAV1
General knowledge
Family BrowserSAV1 [UCSC Family Browser]
SOURCENM_021818
SMDHs.642842
SAGEHs.642842
GOsignal transduction [Amigo]  signal transduction
GOidentical protein binding [Amigo]  identical protein binding
PubGeneSAV1
TreeFamSAV1
CTD60485 [Comparative ToxicoGenomics Database]
Other databases
Probes
ProbeSAV1 Related clones (RZPD - Berlin)
PubMed
PubMed11 Pubmed reference(s) in LocusLink

Bibliography

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
 
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
 
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
 
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 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.
 
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
 
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
 
The Ste20-like kinase Mst2 activates the human large tumor suppressor kinase Lats1.
Chan EH, Nousiainen M, Chalamalasetty RB, Schˆ§fer A, Nigg EA, Silljˆ© HH
Oncogene. 2005 ; 24 (12) : 2076-2086.
PMID 15688006
 
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
 
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
 
Frequent hypermethylation of MST1 and MST2 in soft tissue sarcoma.
Seidel C, Schagdarsurengin U, Blˆºmke K, Wˆºrl P, Pfeifer GP, Hauptmann S, Taubert H, Dammann R
Molecular carcinogenesis. 2007 ; 46 (10) : 865-871.
PMID 17538946
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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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

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Wed Jul 2 08:26:56 2008


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