DOS_DROME
ID DOS_DROME Reviewed; 878 AA.
AC Q9VZZ9; Q24452; Q9W000;
DT 02-SEP-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=Protein daughter of sevenless;
GN Name=dos; ORFNames=CG1044;
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), AND DEVELOPMENTAL STAGE.
RX PubMed=8681385; DOI=10.1016/s0092-8674(00)81274-x;
RA Raabe T., Riesgo-Escovar J., Liu X., Bausenwein B.S., Deak P., Maroy P.,
RA Hafen E.;
RT "Dos, a novel PH domain containing protein required for signal transduction
RT between Sevenless and Ras1 in Drosophila.";
RL Cell 85:911-920(1996).
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, AND ALTERNATIVE SPLICING.
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=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 PROTEIN SEQUENCE OF 818-829, AND PHOSPHORYLATION.
RX PubMed=8681384; DOI=10.1016/s0092-8674(00)81273-8;
RA Herbst R., Carroll P.M., Allard J.D., Schilling J., Raabe T., Simon M.A.;
RT "Daughter of sevenless is a substrate of the phosphotyrosine phosphatase
RT Corkscrew and functions during sevenless signaling.";
RL Cell 85:899-909(1996).
RN [6]
RP PHOSPHORYLATION AT TYR-801 AND TYR-854.
RX PubMed=10601017; DOI=10.1093/emboj/18.24.6950;
RA Herbst R., Zhang X., Qin J., Simon M.A.;
RT "Recruitment of the protein tyrosine phosphatase CSW by DOS is an essential
RT step during signaling by the sevenless receptor tyrosine kinase.";
RL EMBO J. 18:6950-6961(1999).
RN [7]
RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF TRP-104 AND TYR-801.
RX PubMed=10640704; DOI=10.1016/s0925-4773(99)00252-x;
RA Bausenwein B.S., Schmidt M., Mielke B., Raabe T.;
RT "In vivo functional analysis of the daughter of sevenless protein in
RT receptor tyrosine kinase signaling.";
RL Mech. Dev. 90:205-215(2000).
RN [8]
RP INTERACTION WITH DRK, AND MUTAGENESIS OF ARG-644 AND ARG-696.
RX PubMed=12128212; DOI=10.1016/s0925-4773(02)00147-8;
RA Feller S.M., Wecklein H., Lewitzky M., Kibler E., Raabe T.;
RT "SH3 domain-mediated binding of the Drk protein to Dos is an important step
RT in signaling of Drosophila receptor tyrosine kinases.";
RL Mech. Dev. 116:129-139(2002).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-481; THR-771 AND TYR-801, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=17372656; DOI=10.1039/b617545g;
RA Bodenmiller B., Mueller L.N., Pedrioli P.G.A., Pflieger D., Juenger M.A.,
RA Eng J.K., Aebersold R., Tao W.A.;
RT "An integrated chemical, mass spectrometric and computational strategy for
RT (quantitative) phosphoproteomics: application to Drosophila melanogaster
RT Kc167 cells.";
RL Mol. Biosyst. 3:275-286(2007).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-399, 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: Essential component for signaling from various receptor
CC tyrosine kinases such as Sevenless, TORSO and DER. Required for
CC photoreceptor cell and wing development.
CC -!- SUBUNIT: Interacts with DRK. {ECO:0000269|PubMed:12128212}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10640704}. Membrane
CC {ECO:0000269|PubMed:10640704}; Peripheral membrane protein
CC {ECO:0000269|PubMed:10640704}; Cytoplasmic side
CC {ECO:0000269|PubMed:10640704}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9VZZ9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9VZZ9-2; Sequence=VSP_035054;
CC -!- DEVELOPMENTAL STAGE: Present in larva (at protein level).
CC {ECO:0000269|PubMed:8681385}.
CC -!- PTM: Phosphorylated on Tyr-801 and Tyr-854 in response to sevenless
CC activation, which initiates the recruitment of the phosphatase CSW.
CC {ECO:0000269|PubMed:10601017, ECO:0000269|PubMed:17372656,
CC ECO:0000269|PubMed:18327897, ECO:0000269|PubMed:8681384}.
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DR EMBL; X97447; CAA66076.1; -; mRNA.
DR EMBL; AE014296; AAF47662.1; -; Genomic_DNA.
DR EMBL; AE014296; AAF47663.2; -; Genomic_DNA.
DR EMBL; AY122244; AAM52756.1; -; mRNA.
DR RefSeq; NP_523890.2; NM_079166.3. [Q9VZZ9-1]
DR RefSeq; NP_728757.1; NM_167956.2. [Q9VZZ9-2]
DR AlphaFoldDB; Q9VZZ9; -.
DR SMR; Q9VZZ9; -.
DR BioGRID; 63826; 54.
DR IntAct; Q9VZZ9; 2.
DR MINT; Q9VZZ9; -.
DR STRING; 7227.FBpp0072803; -.
DR iPTMnet; Q9VZZ9; -.
DR PaxDb; Q9VZZ9; -.
DR PRIDE; Q9VZZ9; -.
DR DNASU; 38321; -.
DR EnsemblMetazoa; FBtr0072926; FBpp0072803; FBgn0016794. [Q9VZZ9-1]
DR EnsemblMetazoa; FBtr0072927; FBpp0072804; FBgn0016794. [Q9VZZ9-2]
DR GeneID; 38321; -.
DR KEGG; dme:Dmel_CG1044; -.
DR UCSC; CG1044-RA; d. melanogaster. [Q9VZZ9-1]
DR UCSC; CG1044-RB; d. melanogaster.
DR CTD; 38321; -.
DR FlyBase; FBgn0016794; dos.
DR VEuPathDB; VectorBase:FBgn0016794; -.
DR eggNOG; KOG3751; Eukaryota.
DR GeneTree; ENSGT00940000175323; -.
DR HOGENOM; CLU_351684_0_0_1; -.
DR InParanoid; Q9VZZ9; -.
DR OMA; FYEGWLI; -.
DR PhylomeDB; Q9VZZ9; -.
DR Reactome; R-DME-109704; PI3K Cascade.
DR Reactome; R-DME-1257604; PIP3 activates AKT signaling.
DR Reactome; R-DME-180292; GAB1 signalosome.
DR Reactome; R-DME-2730905; Role of LAT2/NTAL/LAB on calcium mobilization.
DR Reactome; R-DME-5654689; PI-3K cascade:FGFR1.
DR Reactome; R-DME-5654695; PI-3K cascade:FGFR2.
DR Reactome; R-DME-5654710; PI-3K cascade:FGFR3.
DR Reactome; R-DME-5654720; PI-3K cascade:FGFR4.
DR Reactome; R-DME-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR Reactome; R-DME-9027276; Erythropoietin activates Phosphoinositide-3-kinase (PI3K).
DR SignaLink; Q9VZZ9; -.
DR BioGRID-ORCS; 38321; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 38321; -.
DR PRO; PR:Q9VZZ9; -.
DR Proteomes; UP000000803; Chromosome 3L.
DR Bgee; FBgn0016794; Expressed in cleaving embryo and 25 other tissues.
DR ExpressionAtlas; Q9VZZ9; baseline and differential.
DR Genevisible; Q9VZZ9; DM.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:FlyBase.
DR GO; GO:0042169; F:SH2 domain binding; IPI:FlyBase.
DR GO; GO:0035591; F:signaling adaptor activity; IBA:GO_Central.
DR GO; GO:0008595; P:anterior/posterior axis specification, embryo; TAS:FlyBase.
DR GO; GO:0042461; P:photoreceptor cell development; IMP:UniProtKB.
DR GO; GO:0007465; P:R7 cell fate commitment; IMP:FlyBase.
DR GO; GO:0046578; P:regulation of Ras protein signal transduction; IMP:UniProtKB.
DR GO; GO:0045500; P:sevenless signaling pathway; IDA:FlyBase.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR GO; GO:0008293; P:torso signaling pathway; IMP:FlyBase.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR046355; Gab1-4-like.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR PANTHER; PTHR45960; PTHR45960; 1.
DR Pfam; PF00169; PH; 1.
DR SMART; SM00233; PH; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Coiled coil; Cytoplasm; Developmental protein;
KW Direct protein sequencing; Membrane; Phosphoprotein; Reference proteome.
FT CHAIN 1..878
FT /note="Protein daughter of sevenless"
FT /id="PRO_0000347179"
FT DOMAIN 3..113
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT REGION 132..176
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 391..437
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 638..650
FT /note="Interaction with DRK 1"
FT REGION 686..721
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 690..702
FT /note="Interaction with DRK 2"
FT REGION 749..773
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 246..275
FT /evidence="ECO:0000255"
FT COMPBIAS 132..173
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 402..431
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 705..719
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 755..773
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 399
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 481
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:17372656"
FT MOD_RES 771
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:17372656"
FT MOD_RES 801
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:10601017,
FT ECO:0000269|PubMed:17372656"
FT MOD_RES 854
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:10601017"
FT VAR_SEQ 1..80
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12537569"
FT /id="VSP_035054"
FT MUTAGEN 104
FT /note="W->A: Abolishes function in photoreceptor cell
FT development."
FT /evidence="ECO:0000269|PubMed:10640704"
FT MUTAGEN 644
FT /note="R->K: Impairs interaction with DRK."
FT /evidence="ECO:0000269|PubMed:12128212"
FT MUTAGEN 696
FT /note="R->K: Impairs interaction with DRK."
FT /evidence="ECO:0000269|PubMed:12128212"
FT MUTAGEN 801
FT /note="Y->F: Abolishes function in photoreceptor cell
FT development."
FT /evidence="ECO:0000269|PubMed:10640704"
FT CONFLICT 474
FT /note="P -> A (in Ref. 1; CAA66076)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 878 AA; 95536 MW; 5BE89F16EA5E6177 CRC64;
MDRTFYEGWL IKSPPTKRIW RARWRRRYFT LKQGEIPEQF CLEYYTDHNC RKLKGVIDLD
QCEQVDCGLR LENRKQKFQY MFDIKTPKRT YYLAAETEAD MRDWVNCICQ VCHLHDTKQS
NELPLGAVGA DENRTQHTSS SGGLSNSTQN TTTTSLHSSA GTTAPQASVP NAGGSAQLRR
PAVIEEQPMP SNAGNNNSDS VYVNTEYSNR ETMLCDANFD QQELLSAAQQ QPPPSPATAL
YLNHSALIQA QAAAAAAEQL QQQQQQAARL AVSANGVVRK LPEHLVLTQQ TLAEAAAQQH
SSVQASPALS TASGPYIPIS ECFSGSPRFL PGVPLPGADL AIPNNPTTPL NNLDPKFYDT
PRSHNNIGLN LTNDQSYSPK ITNLSLQQLA NNNASKQRSD SDSESVFTDD DEWAHPLPLR
ENVDRSTRPS DSSIENESFV LTYSQRFSKM PEEGGAIVPP AEKSSKLAGA ASLPEAGDQG
TLDKLAKVLK NKNNLILDFK ENEKIPRDLP QLSDTENTSP AIVARRNAHS AFIEESYDIP
RSHQQPYYNV NQLLGERPVT SPHNSNPIAA STPNLMAADL GAVAAISAAA NPGLMGEAQA
VASSPTSART LPRHCYTNAA PTKMEGNVFR YDFMEQADCP PVNRKLKPKV AGGLPVVEDK
PPEEFPAKPP VGVDQLTNKL GAAQLQQPIG PPSVDRKCKP NAYKLGNSAT MSPATRRSSG
APLSMVLPHE TDVHSPAAAN AFFHETRTLP RQQHRHHPNS PGSMSVQHQR TASAAAAMMS
LTAAAAPKQQ AAAQTEHKLQ YFDLDVTNKP PLLNRSSMSV GNLYSQGGNG ASGMRFAGVE
AGGARAPVPS SVVYRSVDFV KTEAFKRIRE ERESSGNK
