ID SAV_DROME Reviewed; 608 AA.
AC Q9VCR6; Q8MQH6; Q8T9A6; Q9VCR5;
DT 19-JUL-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 2.
DT 24-JAN-2024, entry version 169.
DE RecName: Full=Scaffold protein salvador;
DE AltName: Full=Shar-pei;
GN Name=sav; Synonyms=SHRP; ORFNames=CG33193;
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227 {ECO:0000312|EMBL:AAL39999.1};
RN [1] {ECO:0000312|EMBL:AAM97280.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, AND INTERACTION
RP WITH WTS.
RX PubMed=12202036; DOI=10.1016/s0092-8674(02)00824-3;
RA Tapon N., Harvey K.F., Bell D.W., Wahrer D.C.R., Schiripo T.A., Haber D.A.,
RA Hariharan I.K.;
RT "Salvador promotes both cell cycle exit and apoptosis in Drosophila and is
RT mutated in human cancer cell lines.";
RL Cell 110:467-478(2002).
RN [2] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [3] {ECO:0000305}
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [4] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Embryo;
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [5]
RP FUNCTION.
RX PubMed=12421711; DOI=10.1242/dev.00168;
RA Kango-Singh M., Nolo R., Tao C., Verstreken P., Hiesinger P.R.,
RA Bellen H.J., Halder G.;
RT "Shar-pei mediates cell proliferation arrest during imaginal disc growth in
RT Drosophila.";
RL Development 129:5719-5730(2002).
RN [6]
RP FUNCTION WITH HPO.
RX PubMed=12941274; DOI=10.1016/s0092-8674(03)00557-9;
RA Harvey K.F., Pfleger C.M., Hariharan I.K.;
RT "The Drosophila Mst ortholog, hippo, restricts growth and cell
RT proliferation and promotes apoptosis.";
RL Cell 114:457-467(2003).
RN [7]
RP PHOSPHORYLATION BY HPO.
RX PubMed=12941273; DOI=10.1016/s0092-8674(03)00549-x;
RA Wu S., Huang J., Dong J., Pan D.;
RT "hippo encodes a Ste-20 family protein kinase that restricts cell
RT proliferation and promotes apoptosis in conjunction with salvador and
RT warts.";
RL Cell 114:445-456(2003).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-413 AND SER-416, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Embryo;
RX PubMed=18327897; DOI=10.1021/pr700696a;
RA Zhai B., Villen J., Beausoleil S.A., Mintseris J., Gygi S.P.;
RT "Phosphoproteome analysis of Drosophila melanogaster embryos.";
RL J. Proteome Res. 7:1675-1682(2008).
RN [9]
RP INTERACTION WITH JUB.
RX PubMed=20303269; DOI=10.1016/j.cub.2010.02.035;
RA Das Thakur M., Feng Y., Jagannathan R., Seppa M.J., Skeath J.B.,
RA Longmore G.D.;
RT "Ajuba LIM proteins are negative regulators of the Hippo signaling
RT pathway.";
RL Curr. Biol. 20:657-662(2010).
RN [10]
RP INTERACTION WITH KIBRA; MER AND HPO.
RX PubMed=20159598; DOI=10.1016/j.devcel.2009.12.012;
RA Yu J., Zheng Y., Dong J., Klusza S., Deng W.-M., Pan D.;
RT "Kibra functions as a tumor suppressor protein that regulates Hippo
RT signaling in conjunction with Merlin and Expanded.";
RL Dev. Cell 18:288-299(2010).
CC -!- FUNCTION: Plays a key role in the Hippo/SWH (Sav/Wts/Hpo) signaling
CC pathway, a signaling pathway that plays a pivotal role in organ size
CC control and tumor suppression by restricting proliferation and
CC promoting apoptosis. The core of this pathway is composed of a kinase
CC cascade wherein Hippo (Hpo), in complex with its regulatory protein
CC Salvador (Sav), phosphorylates and activates Warts (Wts) in complex
CC with its regulatory protein Mats, which in turn phosphorylates and
CC inactivates the Yorkie (Yki) oncoprotein. The Hippo/SWH signaling
CC pathway inhibits the activity of the transcriptional complex formed by
CC Scalloped (sd) and Yki and the target genes of this pathway include
CC cyclin-E (cycE), diap1 and bantam. Required for cell cycle exit in eye
CC imaginal disk and hid-induced apoptotic cell deaths that are part of
CC normal retinal development. Activation of Drice in eye imaginal disk by
CC either Hid or Rpr is almost completely blocked by Sav expression.
CC {ECO:0000269|PubMed:12202036, ECO:0000269|PubMed:12421711,
CC ECO:0000269|PubMed:12941274}.
CC -!- SUBUNIT: Interacts with Wts via its WW domains. Interacts (via FBM
CC motif) with Mer (via FERM domain). Interacts with Kibra. Interacts with
CC Hpo (via SARAH domain). Interacts with jub.
CC {ECO:0000269|PubMed:12202036, ECO:0000269|PubMed:20159598,
CC ECO:0000269|PubMed:20303269}.
CC -!- INTERACTION:
CC Q9VCR6; Q8T0S6: hpo; NbExp=3; IntAct=EBI-145004, EBI-101858;
CC Q9VCR6; Q6NPA6: par-1; NbExp=2; IntAct=EBI-145004, EBI-3415099;
CC -!- TISSUE SPECIFICITY: Third instar larvae eye disk, expressed in a stripe
CC in the morphogenetic furrow, decreases in the region of the second
CC mitotic wave (SMW) and increases once again posterior to the SMW.
CC {ECO:0000269|PubMed:12202036}.
CC -!- PTM: Phosphorylated by Hpo. {ECO:0000269|PubMed:12941273,
CC ECO:0000269|PubMed:18327897}.
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DR EMBL; AY131211; AAM97280.1; -; mRNA.
DR EMBL; AE014297; AAF56090.3; -; Genomic_DNA.
DR EMBL; AY069854; AAL39999.1; -; mRNA.
DR RefSeq; NP_788721.1; NM_176544.3.
DR PDB; 6BN1; X-ray; 2.60 A; B=531-600.
DR PDBsum; 6BN1; -.
DR AlphaFoldDB; Q9VCR6; -.
DR SMR; Q9VCR6; -.
DR BioGRID; 76064; 59.
DR DIP; DIP-18696N; -.
DR IntAct; Q9VCR6; 3.
DR STRING; 7227.FBpp0083749; -.
DR iPTMnet; Q9VCR6; -.
DR PaxDb; 7227-FBpp0083749; -.
DR EnsemblMetazoa; FBtr0084356; FBpp0083749; FBgn0053193.
DR GeneID; 252554; -.
DR KEGG; dme:Dmel_CG33193; -.
DR UCSC; CG33193-RA; d. melanogaster.
DR AGR; FB:FBgn0053193; -.
DR CTD; 252554; -.
DR FlyBase; FBgn0053193; sav.
DR VEuPathDB; VectorBase:FBgn0053193; -.
DR eggNOG; KOG1891; Eukaryota.
DR InParanoid; Q9VCR6; -.
DR OMA; VWTSDQR; -.
DR OrthoDB; 3673987at2759; -.
DR PhylomeDB; Q9VCR6; -.
DR Reactome; R-DME-2028269; Signaling by Hippo.
DR Reactome; R-DME-390089; Formation of the Hippo kinase cassette.
DR Reactome; R-DME-390098; Phosphorylation-dependent inhibition of YKI.
DR Reactome; R-DME-390150; DS ligand bound to FT receptor.
DR SignaLink; Q9VCR6; -.
DR BioGRID-ORCS; 252554; 0 hits in 1 CRISPR screen.
DR GenomeRNAi; 252554; -.
DR PRO; PR:Q9VCR6; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0053193; Expressed in saliva-secreting gland and 21 other cell types or tissues.
DR ExpressionAtlas; Q9VCR6; baseline and differential.
DR Genevisible; Q9VCR6; DM.
DR GO; GO:0045177; C:apical part of cell; IDA:FlyBase.
DR GO; GO:0106037; C:apicomedial cortex; IDA:FlyBase.
DR GO; GO:0005829; C:cytosol; IDA:FlyBase.
DR GO; GO:0060090; F:molecular adaptor activity; IGI:FlyBase.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0035329; P:hippo signaling; IDA:FlyBase.
DR GO; GO:0007444; P:imaginal disc development; IMP:FlyBase.
DR GO; GO:0072002; P:Malpighian tubule development; IMP:FlyBase.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IMP:FlyBase.
DR GO; GO:0040015; P:negative regulation of multicellular organism growth; IMP:FlyBase.
DR GO; GO:0046621; P:negative regulation of organ growth; TAS:FlyBase.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:FlyBase.
DR GO; GO:0045463; P:R8 cell development; IGI:FlyBase.
DR GO; GO:0045464; P:R8 cell fate specification; IMP:FlyBase.
DR GO; GO:0048814; P:regulation of dendrite morphogenesis; IGI:FlyBase.
DR GO; GO:0045570; P:regulation of imaginal disc growth; TAS:FlyBase.
DR GO; GO:0010212; P:response to ionizing radiation; IMP:FlyBase.
DR GO; GO:0046666; P:retinal cell programmed cell death; IMP:FlyBase.
DR GO; GO:0048863; P:stem cell differentiation; IMP:FlyBase.
DR GO; GO:0072089; P:stem cell proliferation; IMP:FlyBase.
DR CDD; cd21433; SARAH_Sav; 1.
DR CDD; cd00201; WW; 1.
DR Gene3D; 2.20.70.10; -; 1.
DR InterPro; IPR011524; SARAH_dom.
DR InterPro; IPR030030; Sav.
DR InterPro; IPR001202; WW_dom.
DR InterPro; IPR036020; WW_dom_sf.
DR PANTHER; PTHR47522:SF2; PROTEIN SALVADOR HOMOLOG 1; 1.
DR PANTHER; PTHR47522; SALVADOR FAMILY WW DOMAIN-CONTAINING PROTEIN 1; 1.
DR Pfam; PF00397; WW; 1.
DR SMART; SM00456; WW; 2.
DR SUPFAM; SSF51045; WW domain; 2.
DR PROSITE; PS50951; SARAH; 1.
DR PROSITE; PS50020; WW_DOMAIN_2; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Apoptosis; Coiled coil; Phosphoprotein; Reference proteome;
KW Repeat.
FT CHAIN 1..608
FT /note="Scaffold protein salvador"
FT /id="PRO_0000076062"
FT DOMAIN 423..456
FT /note="WW 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00224,
FT ECO:0000305"
FT DOMAIN 458..491
FT /note="WW 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00224,
FT ECO:0000305"
FT DOMAIN 552..599
FT /note="SARAH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00310"
FT REGION 17..37
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 64..145
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 157..202
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 220..243
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 264..293
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 345..425
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 274..294
FT /evidence="ECO:0000255"
FT MOTIF 32..38
FT /note="Ferm-binding motif (FBM)"
FT COMPBIAS 17..35
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 64..112
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 157..192
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 227..243
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 360..389
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 406..420
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 413
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 416
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT CONFLICT 119
FT /note="S -> A (in Ref. 4; AAL39999)"
FT /evidence="ECO:0000305"
FT CONFLICT 194
FT /note="L -> M (in Ref. 1; AAM97280)"
FT /evidence="ECO:0000305"
FT CONFLICT 275
FT /note="Missing (in Ref. 4; AAL39999)"
FT /evidence="ECO:0000305"
FT HELIX 537..544
FT /evidence="ECO:0007829|PDB:6BN1"
FT HELIX 555..557
FT /evidence="ECO:0007829|PDB:6BN1"
FT HELIX 560..599
FT /evidence="ECO:0007829|PDB:6BN1"
SQ SEQUENCE 608 AA; 68146 MW; 05DF47686EE3335E CRC64;
MNYLTILLCN RKPTMLSRRN KEKSQHKEGV VGKYMKKDTP PDISVINVWS DQRAKKKSLQ
RCASTSPSCE FHPRSSSTSR NTYSCTDSQP DYYHARRAQS QMPLQQHSHS HPHSLPHPSH
PHVRSHPPLP PHQFRASSNQ LSQNSSNYVN FEQIERMRRQ QSSPLLQTTS SPAPGAGGFQ
RSYSTTQRQH HPHLGGDSYD ADQGLLSASY ANMLQLPQRP HSPAHYAVPP QQQQHPQIHQ
QHASTPFGST LRFDRAAMSI RERQPRYQPT SSPMQQQQQQ QQQQQQQLQH TQLAAHLGGS
YSSDSYPIYE NPSRVISMRA TQSQRSESPI YSNTTASSAT LAVVPQHHHQ GHLAVPSGSG
GGSLSGSGRG GSSGSVRGAS TSVQSLYVPP RTPPSAVAGA GGSANGSLQK VPSQQSLTEP
EELPLPPGWA TQYTLHGRKY YIDHNAHTTH WNHPLEREGL PVGWRRVVSK MHGTYYENQY
TGQSQRQHPC LTSYYVYTTS AEPPKAIRPE ASLYAPPTHT HNALVPANPY LLEEIPKWLA
VYSEADSSKD HLLQFNMFSL PELEGFDSML VRLFKQELGT IVGFYERYRR ALILEKNRRA
GQNQNQNQ
//
