Q9VCR6 (SAV_DROME) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Scaffold protein salvador

Alternative name(s):
Shar-pei

Gene names

Name:	sav
Synonyms:	SHRP
ORF Names:	CG33193

Organism

Drosophila melanogaster (Fruit fly)

Taxonomic identifier

7227 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Arthropoda › Hexapoda › Insecta › Pterygota › Neoptera › Endopterygota › Diptera › Brachycera › Muscomorpha › Ephydroidea › Drosophilidae › Drosophila › Sophophora

Protein attributes

Sequence length	608 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Plays a key role in the Hippo/SWH (Sav/Wts/Hpo) signaling pathway, a signaling pathway that plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein Hippo (Hpo), in complex with its regulatory protein Salvador (Sav), phosphorylates and activates Warts (Wts) in complex with its regulatory protein Mats, which in turn phosphorylates and inactivates the Yorkie (Yki) oncoprotein. The Hippo/SWH signaling pathway inhibits the activity of the transcriptional complex formed by Scalloped (sd) and Yki and the target genes of this pathway include cyclin-E (cycE), diap1 and bantam. Required for cell cycle exit in eye imaginal disk and hid-induced apoptotic cell deaths that are part of normal retinal development. Activation of Ice in eye imaginal disk by either Hid or Rpr is almost completely blocked by Sav expression. Ref.1 Ref.5 Ref.6
Subunit structure	Interacts with Wts via its WW domains. Interacts (via FBM motif) with Mer (via FERM domain). Interacts with Kibra. Interacts with Hpo (via SARAH domain). Ref.1 Ref.9
Tissue specificity	Third instar larvae eye disk, expressed in a stripe in the morphogenetic furrow, decreases in the region of the second mitotic wave (SMW) and increases once again posterior to the SMW. Ref.1
Post-translational modification	Phosphorylated by Hpo. Ref.7 Ref.8
Sequence similarities	Contains 1 SARAH domain. Contains 2 WW domains.

Ontologies

Keywords
Biological process	Apoptosis
Domain	Coiled coil Repeat
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	Malpighian tubule development Inferred from mutant phenotype. Source: FlyBase R8 cell fate specification Inferred from mutant phenotype. Source: FlyBase apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW hippo signaling cascade Traceable author statement Ref.9. Source: UniProtKB imaginal disc development Inferred from mutant phenotype Ref.5. Source: FlyBase induction of apoptosis Inferred from mutant phenotype Ref.1. Source: FlyBase negative regulation of cell proliferation Inferred from mutant phenotype Ref.5. Source: FlyBase negative regulation of organ growth Traceable author statement. Source: FlyBase regulation of cell cycle Inferred from mutant phenotype Ref.1. Source: FlyBase regulation of dendrite morphogenesis Inferred from genetic interaction. Source: FlyBase regulation of imaginal disc growth Traceable author statement. Source: FlyBase response to ionizing radiation Inferred from mutant phenotype. Source: FlyBase retinal cell programmed cell death Inferred from mutant phenotype Ref.1. Source: FlyBase stem cell differentiation Inferred from mutant phenotype. Source: FlyBase stem cell proliferation Inferred from mutant phenotype. Source: FlyBase
Molecular function	protein binding Inferred from physical interaction Ref.9. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 608	608	Scaffold protein salvador		PRO_0000076062
Regions
	Domain	423 – 456	34	WW 1
	Domain	458 – 491	34	WW 2
	Domain	552 – 599	48	SARAH
	Coiled coil	274 – 294	21	Potential
	Motif	32 – 38	7	Ferm-binding motif (FBM)
	Compositional bias	107 – 132	26	His-rich
	Compositional bias	231 – 234	4	Poly-Gln
	Compositional bias	275 – 289	15	Poly-Gln
Amino acid modifications
	Modified residue	413	1	Phosphoserine Ref.8
	Modified residue	416	1	Phosphoserine Ref.8
Experimental info
	Sequence conflict	119	1	S → A in AAL39999. Ref.4
	Sequence conflict	194	1	L → M in AAM97280. Ref.1
	Sequence conflict	275	1	Missing in AAL39999. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Q9VCR6 [UniParc]. Last modified June 1, 2003. Version 2. Checksum: 05DF47686EE3335E	FASTA	608	68,146
	10 20 30 40 50 60 MNYLTILLCN RKPTMLSRRN KEKSQHKEGV VGKYMKKDTP PDISVINVWS DQRAKKKSLQ 70 80 90 100 110 120 RCASTSPSCE FHPRSSSTSR NTYSCTDSQP DYYHARRAQS QMPLQQHSHS HPHSLPHPSH 130 140 150 160 170 180 PHVRSHPPLP PHQFRASSNQ LSQNSSNYVN FEQIERMRRQ QSSPLLQTTS SPAPGAGGFQ 190 200 210 220 230 240 RSYSTTQRQH HPHLGGDSYD ADQGLLSASY ANMLQLPQRP HSPAHYAVPP QQQQHPQIHQ 250 260 270 280 290 300 QHASTPFGST LRFDRAAMSI RERQPRYQPT SSPMQQQQQQ QQQQQQQLQH TQLAAHLGGS 310 320 330 340 350 360 YSSDSYPIYE NPSRVISMRA TQSQRSESPI YSNTTASSAT LAVVPQHHHQ GHLAVPSGSG 370 380 390 400 410 420 GGSLSGSGRG GSSGSVRGAS TSVQSLYVPP RTPPSAVAGA GGSANGSLQK VPSQQSLTEP 430 440 450 460 470 480 EELPLPPGWA TQYTLHGRKY YIDHNAHTTH WNHPLEREGL PVGWRRVVSK MHGTYYENQY 490 500 510 520 530 540 TGQSQRQHPC LTSYYVYTTS AEPPKAIRPE ASLYAPPTHT HNALVPANPY LLEEIPKWLA 550 560 570 580 590 600 VYSEADSSKD HLLQFNMFSL PELEGFDSML VRLFKQELGT IVGFYERYRR ALILEKNRRA GQNQNQNQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Salvador promotes both cell cycle exit and apoptosis in Drosophila and is mutated in human cancer cell lines." Tapon N., Harvey K.F., Bell D.W., Wahrer D.C.R., Schiripo T.A., Haber D.A., Hariharan I.K. Cell 110:467-478(2002) [PubMed: 12202036] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, INTERACTION WITH WTS.
[2]	"The genome sequence of Drosophila melanogaster." Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D., Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F., George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N., Sutton G.G., Wortman J.R., Yandell M.D. , Zhang Q., Chen L.X., Brandon R.C., Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C., Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A., An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A., Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V., Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J., Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E., Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B., Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I., Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C., Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S., Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M., Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M., Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D., Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F., Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D., Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A., Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C., McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C., Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L., Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R., Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V., Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F., Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J., Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R., Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y., Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T., Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S., Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W., Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M., Venter J.C. Science 287:2185-2195(2000) [PubMed: 10731132] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: Berkeley.
[3]	"Annotation of the Drosophila melanogaster euchromatic genome: a systematic review." Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S., Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E., Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P., Bettencourt B.R., Celniker S.E., de Grey A.D.N.J. , Drysdale R.A., Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M., Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E. Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002) [PubMed: 12537572] [Abstract] Cited for: GENOME REANNOTATION. Strain: Berkeley.
[4]	"A Drosophila full-length cDNA resource." Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A., Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M., Celniker S.E. Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002) [PubMed: 12537569] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: Berkeley. Tissue: Embryo.
[5]	"Shar-pei mediates cell proliferation arrest during imaginal disc growth in Drosophila." Kango-Singh M., Nolo R., Tao C., Verstreken P., Hiesinger P.R., Bellen H.J., Halder G. Development 129:5719-5730(2002) [PubMed: 12421711] [Abstract] Cited for: FUNCTION.
[6]	"The Drosophila Mst ortholog, hippo, restricts growth and cell proliferation and promotes apoptosis." Harvey K.F., Pfleger C.M., Hariharan I.K. Cell 114:457-467(2003) [PubMed: 12941274] [Abstract] Cited for: FUNCTION WITH HPO.
[7]	"hippo encodes a Ste-20 family protein kinase that restricts cell proliferation and promotes apoptosis in conjunction with salvador and warts." Wu S., Huang J., Dong J., Pan D. Cell 114:445-456(2003) [PubMed: 12941273] [Abstract] Cited for: PHOSPHORYLATION BY HPO.
[8]	"Phosphoproteome analysis of Drosophila melanogaster embryos." Zhai B., Villen J., Beausoleil S.A., Mintseris J., Gygi S.P. J. Proteome Res. 7:1675-1682(2008) [PubMed: 18327897] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-413 AND SER-416, MASS SPECTROMETRY. Tissue: Embryo.
[9]	"Kibra functions as a tumor suppressor protein that regulates Hippo signaling in conjunction with Merlin and Expanded." Yu J., Zheng Y., Dong J., Klusza S., Deng W.-M., Pan D. Dev. Cell 18:288-299(2010) [PubMed: 20159598] [Abstract] Cited for: INTERACTION WITH KIBRA; MER AND HPO.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AY131211 mRNA. Translation: AAM97280.1. AE014297 Genomic DNA. Translation: AAF56090.3. AY069854 mRNA. Translation: AAL39999.1.
RefSeq	NP_788721.1. NM_176544.2.
3D structure databases
ProteinModelPortal	Q9VCR6.
SMR	Q9VCR6. Positions 421-493.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-18696N.
IntAct	Q9VCR6. 2 interactions.
MINT	MINT-311653.
STRING	Q9VCR6.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
EnsemblMetazoa	FBtr0084356; FBpp0083749; FBgn0053193.
GeneID	252554.
KEGG	dme:Dmel_CG33193.
NMPDR	fig|7227.3.peg.14174.
UCSC	CG33193-RA. d. melanogaster.
Organism-specific databases
CTD	252554.
FlyBase	FBgn0053193. sav.
Phylogenomic databases
eggNOG	inNOG10488.
GeneTree	EMGT00050000005502.
InParanoid	Q9VCR6.
OMA	KKDTPPE.
OrthoDB	EOG4NGF38.
PhylomeDB	Q9VCR6.
Gene expression databases
Bgee	Q9VCR6.
GermOnline	CG33193. Drosophila melanogaster.
Family and domain databases
InterPro	IPR011524. SARAH. IPR001202. WW_Rsp5_WWP. [Graphical view]
Gene3D	G3DSA:2.20.70.10. G3DSA:2.20.70.10. 2 hits.
Pfam	PF00397. WW. 1 hit. [Graphical view]
SMART	SM00456. WW. 2 hits. [Graphical view]
SUPFAM	SSF51045. WW_Rsp5_WWP. 2 hits.
PROSITE	PS50951. SARAH. 1 hit. PS01159. WW_DOMAIN_1. False negative. PS50020. WW_DOMAIN_2. 2 hits. [Graphical view]
ProtoNet	Search...
Other
NextBio	843605.

Entry information

Entry name

SAV_DROME

Accession

Primary (citable) accession number: Q9VCR6
Secondary accession number(s): Q8MQH6, Q8T9A6, Q9VCR5

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 19, 2003
Last sequence update:	June 1, 2003
Last modified:	January 25, 2012
This is version 83 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Drosophila annotation project