ID SSH_DROME Reviewed; 1045 AA. AC Q6NN85; Q7KS05; Q8IMU8; Q9NKY1; Q9VC04; DT 22-NOV-2005, integrated into UniProtKB/Swiss-Prot. DT 22-NOV-2005, sequence version 2. DT 27-MAR-2024, entry version 148. DE RecName: Full=Protein phosphatase Slingshot; DE EC=3.1.3.16; DE EC=3.1.3.48; GN Name=ssh; ORFNames=CG6238; 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; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, INTERACTION WITH ACTIN, RP AND MUTAGENESIS OF CYS-468. RX PubMed=11832213; DOI=10.1016/s0092-8674(01)00638-9; RA Niwa R., Nagata-Ohashi K., Takeichi M., Mizuno K., Uemura T.; RT "Control of actin reorganization by Slingshot, a family of phosphatases RT that dephosphorylate ADF/cofilin."; RL Cell 108:233-246(2002). RN [2] 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] 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] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC STRAIN=Berkeley; TISSUE=Testis; RA Stapleton M., Carlson J.W., Chavez C., Frise E., George R.A., Pacleb J.M., RA Park S., Wan K.H., Yu C., Rubin G.M., Celniker S.E.; RL Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases. RN [5] RP FUNCTION, AND MUTAGENESIS OF CYS-468. RX PubMed=15572110; DOI=10.1016/j.neuron.2004.11.014; RA Ng J., Luo L.; RT "Rho GTPases regulate axon growth through convergent and divergent RT signaling pathways."; RL Neuron 44:779-793(2004). RN [6] RP FUNCTION, AND DEVELOPMENTAL STAGE. RX PubMed=16169194; DOI=10.1016/j.mod.2005.07.002; RA Rogers E.M., Hsiung F., Rodrigues A.B., Moses K.; RT "Slingshot cofilin phosphatase localization is regulated by receptor RT tyrosine kinases and regulates cytoskeletal structure in the developing RT Drosophila eye."; RL Mech. Dev. 122:1194-1205(2005). RN [7] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-719, AND IDENTIFICATION BY RP 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). CC -!- FUNCTION: Protein phosphatase which regulates actin filament dynamics CC (PubMed:11832213, PubMed:16169194). Dephosphorylates and activates the CC actin binding/depolymerizing factor tsr/cofilin, which subsequently CC binds to actin filaments and stimulates their disassembly CC (PubMed:11832213). Required for axon growth (PubMed:15572110). CC {ECO:0000269|PubMed:11832213, ECO:0000269|PubMed:15572110, CC ECO:0000269|PubMed:16169194}. CC -!- CATALYTIC ACTIVITY: CC Reaction=H2O + O-phospho-L-tyrosyl-[protein] = L-tyrosyl-[protein] + CC phosphate; Xref=Rhea:RHEA:10684, Rhea:RHEA-COMP:10136, Rhea:RHEA- CC COMP:10137, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:46858, CC ChEBI:CHEBI:82620; EC=3.1.3.48; Evidence={ECO:0000255|PROSITE- CC ProRule:PRU10044}; CC -!- CATALYTIC ACTIVITY: CC Reaction=H2O + O-phospho-L-seryl-[protein] = L-seryl-[protein] + CC phosphate; Xref=Rhea:RHEA:20629, Rhea:RHEA-COMP:9863, Rhea:RHEA- CC COMP:11604, ChEBI:CHEBI:15377, ChEBI:CHEBI:29999, ChEBI:CHEBI:43474, CC ChEBI:CHEBI:83421; EC=3.1.3.16; CC -!- CATALYTIC ACTIVITY: CC Reaction=H2O + O-phospho-L-threonyl-[protein] = L-threonyl-[protein] + CC phosphate; Xref=Rhea:RHEA:47004, Rhea:RHEA-COMP:11060, Rhea:RHEA- CC COMP:11605, ChEBI:CHEBI:15377, ChEBI:CHEBI:30013, ChEBI:CHEBI:43474, CC ChEBI:CHEBI:61977; EC=3.1.3.16; CC -!- SUBUNIT: Interacts with actin. {ECO:0000269|PubMed:11832213}. CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q6NN85-1; Sequence=Displayed; CC Name=2; CC IsoId=Q6NN85-2; Sequence=VSP_016339; CC -!- DEVELOPMENTAL STAGE: Strongly expressed in apical regions of the CC assembling ommatidia of the eye-imaginal disk. Apical expression CC requires the receptor tyrosine kinases Egfr and sev/sevenless. CC {ECO:0000269|PubMed:16169194}. CC -!- MISCELLANEOUS: Tyrosine phosphatase activity has not been demonstrated CC for this protein to date. CC -!- SIMILARITY: Belongs to the protein-tyrosine phosphatase family. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAF56372.3; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; CC Sequence=AAN14027.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AB036834; BAA89534.1; -; mRNA. DR EMBL; AE014297; AAF56372.3; ALT_SEQ; Genomic_DNA. DR EMBL; AE014297; AAN14027.1; ALT_SEQ; Genomic_DNA. DR EMBL; BT011408; AAR96200.1; -; mRNA. DR RefSeq; NP_001163716.1; NM_001170245.1. [Q6NN85-2] DR RefSeq; NP_001163717.1; NM_001170246.1. [Q6NN85-1] DR RefSeq; NP_524492.2; NM_079768.4. DR RefSeq; NP_733063.1; NM_170184.2. DR AlphaFoldDB; Q6NN85; -. DR SMR; Q6NN85; -. DR BioGRID; 67907; 14. DR IntAct; Q6NN85; 4. DR STRING; 7227.FBpp0084175; -. DR iPTMnet; Q6NN85; -. DR PaxDb; 7227-FBpp0084175; -. DR DNASU; 42986; -. DR EnsemblMetazoa; FBtr0301612; FBpp0290827; FBgn0029157. [Q6NN85-2] DR EnsemblMetazoa; FBtr0301613; FBpp0290828; FBgn0029157. [Q6NN85-1] DR GeneID; 42986; -. DR KEGG; dme:Dmel_CG6238; -. DR UCSC; CG6238-RA; d. melanogaster. [Q6NN85-1] DR AGR; FB:FBgn0029157; -. DR CTD; 42986; -. DR FlyBase; FBgn0029157; ssh. DR VEuPathDB; VectorBase:FBgn0029157; -. DR eggNOG; KOG1716; Eukaryota. DR GeneTree; ENSGT00940000171707; -. DR HOGENOM; CLU_004876_0_0_1; -. DR InParanoid; Q6NN85; -. DR OMA; RIMRHNS; -. DR OrthoDB; 5490735at2759; -. DR PhylomeDB; Q6NN85; -. DR BioGRID-ORCS; 42986; 0 hits in 3 CRISPR screens. DR GenomeRNAi; 42986; -. DR PRO; PR:Q6NN85; -. DR Proteomes; UP000000803; Chromosome 3R. DR Bgee; FBgn0029157; Expressed in oviduct (Drosophila) and 25 other cell types or tissues. DR ExpressionAtlas; Q6NN85; baseline and differential. DR GO; GO:0045177; C:apical part of cell; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell. DR GO; GO:0003779; F:actin binding; IDA:UniProtKB. DR GO; GO:0017018; F:myosin phosphatase activity; IEA:UniProtKB-EC. DR GO; GO:0004721; F:phosphoprotein phosphatase activity; IDA:UniProtKB. DR GO; GO:0004725; F:protein tyrosine phosphatase activity; IEA:UniProtKB-EC. DR GO; GO:0008138; F:protein tyrosine/serine/threonine phosphatase activity; IEA:InterPro. DR GO; GO:0030036; P:actin cytoskeleton organization; IBA:GO_Central. DR GO; GO:0007409; P:axonogenesis; IMP:UniProtKB. DR GO; GO:0000902; P:cell morphogenesis; IMP:UniProtKB. DR GO; GO:0048749; P:compound eye development; IGI:FlyBase. DR GO; GO:0000278; P:mitotic cell cycle; IMP:FlyBase. DR GO; GO:0016319; P:mushroom body development; IMP:FlyBase. DR GO; GO:0030837; P:negative regulation of actin filament polymerization; IDA:UniProtKB. DR GO; GO:0007097; P:nuclear migration; IMP:UniProtKB. DR GO; GO:0006470; P:protein dephosphorylation; IMP:UniProtKB. DR GO; GO:0030833; P:regulation of actin filament polymerization; IMP:UniProtKB. DR GO; GO:0008064; P:regulation of actin polymerization or depolymerization; IMP:FlyBase. DR GO; GO:0050770; P:regulation of axonogenesis; IMP:FlyBase. DR GO; GO:0010591; P:regulation of lamellipodium assembly; IMP:FlyBase. DR CDD; cd14513; DSP_slingshot; 1. DR CDD; cd11652; SSH-N; 1. DR Gene3D; 1.10.10.60; Homeodomain-like; 1. DR Gene3D; 3.90.190.10; Protein tyrosine phosphatase superfamily; 1. DR InterPro; IPR014876; DEK_C. DR InterPro; IPR000340; Dual-sp_phosphatase_cat-dom. DR InterPro; IPR043587; Phosphatase_SSH-like. DR InterPro; IPR029021; Prot-tyrosine_phosphatase-like. DR InterPro; IPR043588; SSH-N. DR InterPro; IPR016130; Tyr_Pase_AS. DR InterPro; IPR000387; Tyr_Pase_dom. DR InterPro; IPR020422; TYR_PHOSPHATASE_DUAL_dom. DR PANTHER; PTHR45864:SF2; PROTEIN PHOSPHATASE SLINGSHOT; 1. DR PANTHER; PTHR45864; SLINGSHOT PROTEIN PHOSPHATASE HOMOLOG; 1. DR Pfam; PF08766; DEK_C; 1. DR Pfam; PF00782; DSPc; 1. DR SMART; SM00195; DSPc; 1. DR SUPFAM; SSF52799; (Phosphotyrosine protein) phosphatases II; 1. DR SUPFAM; SSF109715; DEK C-terminal domain; 1. DR PROSITE; PS51998; DEK_C; 1. DR PROSITE; PS00383; TYR_PHOSPHATASE_1; 1. DR PROSITE; PS50056; TYR_PHOSPHATASE_2; 1. DR PROSITE; PS50054; TYR_PHOSPHATASE_DUAL; 1. DR Genevisible; Q6NN85; DM. PE 1: Evidence at protein level; KW Actin-binding; Alternative splicing; Cytoplasm; Cytoskeleton; Hydrolase; KW Phosphoprotein; Protein phosphatase; Reference proteome. FT CHAIN 1..1045 FT /note="Protein phosphatase Slingshot" FT /id="PRO_0000094849" FT DOMAIN 324..379 FT /note="DEK-C" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01342" FT DOMAIN 383..524 FT /note="Tyrosine-protein phosphatase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160" FT REGION 1..35 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 58..80 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 143..194 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 306..325 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 529..631 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 699..799 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1001..1045 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1..19 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 59..80 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 146..175 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 310..325 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 556..570 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 597..628 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 699..729 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 733..748 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 761..778 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 468 FT /note="Phosphocysteine intermediate" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160" FT MOD_RES 719 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:18327897" FT VAR_SEQ 1..19 FT /note="MALVTVQRSPSVAGSCSNS -> MSMQVCSLPDDILIFSLTPR (in FT isoform 2)" FT /evidence="ECO:0000303|Ref.4" FT /id="VSP_016339" FT MUTAGEN 468 FT /note="C->S: Abrogates phosphatase activity." FT /evidence="ECO:0000269|PubMed:11832213, FT ECO:0000269|PubMed:15572110" SQ SEQUENCE 1045 AA; 114997 MW; 76620BB63EE58A8B CRC64; MALVTVQRSP SVAGSCSNSD GESEDDEGNS KGNDRSECFF AGKGTALVLA LKDIPPLTQS ERRLSTDSTR SSNSTQSNNS DIQLHLQSMF YLLQREDTLK MAVKLESQRS NRTRYLVIAS RSCCRSGTSD RRRHRIMRHH SVKVGGSAGT KSSTSPAVPT QRQLSVEQTA TEASSKCDKT ADKENATAAG DNKNTSGMEE SCLLGIDCNE RTTIGLVVPI LADTTIHLDG DGGFSVKVYE KTHIFKPVSV QAMWSALQTL HKVSKKAREN NFYASGPSHD WLSSYERRIE SDQSCLNEWN AMDALESRRP PSPDAIRNKP PEKEETESVI KMKLKAIMMS VDLDEVTSKY IRGRLEEILD MDLGEYKSFI DAEMLVILGQ MDAPTKIFEH VYLGSEWNAS NLEELQKNGV RHILNVTREI DNFFPGTFEY FNVRVYDDEK TNLLKYWDDT FRYITRAKAE GSKVLVHCKM GVSRSASVVI AYAMKAYQWE FQQALEHVKK RRSCIKPNKN FLNQLETYSG MLDAMKNKEK LQRSKSETNL KSTKDARLLP GSEPTPLIQA LNQAKSKSTG EAGVTPDGEE EDGSRMHRRS IAQKSQRRMV RRSSSTSPKT QTAVVTKQQS QSMENLTPER SVAEEPKNMR FPGSNGENYS VTQNQVLHIQ KHTPLSVRTR IHDLEAHRAD QLPQQPVWTS LTKLITQTSH LGKSVSGSSS GNIDSRRDSS CSDVFSSQVD SVFAKDEGEK RQRRKTHSWT ESLGPSGGIV LDPTPQQQKQ QSNAILRPRG TRQRELPSRH ASWGSGDNRC CLPQRTSSGS YYDSNRNTTA IFEGVIQDLK RSSNCNVIEG VAVAVEPIVG VGEGTVKRTK QKLEESTSLK KRCQEESQEL LLEAVDAGQR RCPSLYRSAS SAHSPRQRQP LRCNSEELMH TSDIENKNTT PGDHEATVVL RVQGQTLADD QRISGNVQIL KQNFEAKAGV VGTGGGGGGG TAAGSGSSST IATSVSAVAG ACSANPGKKT TSHQSLPSSP VAQHANHVSA ASNSNSSASN SSDSS //