GAP1_DROME
ID GAP1_DROME Reviewed; 1163 AA.
AC P48423; A4V1S6; Q6NP17; Q9VT58;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 21-JUN-2005, sequence version 2.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=GTPase-activating protein;
DE AltName: Full=Ras GTPase-activating protein 1;
GN Name=RasGAP1; Synonyms=Gap1; ORFNames=CG6721;
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], FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=1547500; DOI=10.1016/0092-8674(92)90073-l;
RA Gaul U., Mardon G., Rubin G.M.;
RT "A putative Ras GTPase activating protein acts as a negative regulator of
RT signaling by the Sevenless receptor tyrosine kinase.";
RL Cell 68:1007-1019(1992).
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].
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 629-1163.
RC STRAIN=Berkeley; TISSUE=Embryo;
RA Stapleton M., Brokstein P., Hong L., Agbayani A., Carlson J.W., Champe M.,
RA Chavez C., Dorsett V., Dresnek D., Farfan D., Frise E., George R.A.,
RA Gonzalez M., Guarin H., Kronmiller B., Li P.W., Liao G., Miranda A.,
RA Mungall C.J., Nunoo J., Pacleb J.M., Paragas V., Park S., Patel S.,
RA Phouanenavong S., Wan K.H., Yu C., Lewis S.E., Rubin G.M., Celniker S.E.;
RL Submitted (DEC-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP INTERACTION WITH STY.
RX PubMed=10089881; DOI=10.1016/s0092-8674(00)80576-0;
RA Casci T., Vinos J., Freeman M.;
RT "Sprouty, an intracellular inhibitor of Ras signaling.";
RL Cell 96:655-665(1999).
CC -!- FUNCTION: Inhibitory regulator of the Ras-cyclic AMP pathway. May
CC function as a negative regulator of Ras85D/Ras1 in the sev signaling
CC pathway. Acts cell autonomously in cone cell precursors as a negative
CC regulator of R7 photoreceptor cell determination.
CC {ECO:0000269|PubMed:1547500}.
CC -!- SUBUNIT: Interacts with sty. {ECO:0000269|PubMed:10089881}.
CC -!- TISSUE SPECIFICITY: In third instar larvae eye imaginal disk, expressed
CC in cells posterior to the morphogenetic furrow, in all photoreceptor
CC and cone cell precursors as well as in still uncommitted cells.
CC {ECO:0000269|PubMed:1547500}.
CC -!- DISRUPTION PHENOTYPE: Mutant flies display a highly irregular eye
CC pattern, with ommatidia improperly oriented and occasionally fused.
CC Most of these ommatidia contain extra cells that resemble R7
CC photoreceptor cell, characterized by small rhabdomere diameter, a
CC central position in the distal half of the retina and expression of the
CC R7-specific rhodopsin Rh4. The extra R7 cells are derived from cone
CC cell precursors. In mutant wing, an additional longitudinal vein
CC branches off the posterior crossvein, the wing veins widen at their
CC junctions with the wing margins and wing vein material is found in
CC between the longitudinal veins. {ECO:0000269|PubMed:1547500}.
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DR EMBL; M86655; AAA28595.1; -; mRNA.
DR EMBL; AE014296; AAF50196.1; -; Genomic_DNA.
DR EMBL; AE014296; AAN11935.1; -; Genomic_DNA.
DR EMBL; AY051747; AAK93171.1; -; mRNA.
DR EMBL; BT011114; AAR82781.1; -; mRNA.
DR PIR; A42142; S27809.
DR RefSeq; NP_524014.2; NM_079290.3.
DR RefSeq; NP_729562.1; NM_168382.2.
DR AlphaFoldDB; P48423; -.
DR BioGRID; 64545; 40.
DR IntAct; P48423; 1.
DR STRING; 7227.FBpp0076097; -.
DR PaxDb; P48423; -.
DR DNASU; 39158; -.
DR EnsemblMetazoa; FBtr0076367; FBpp0076096; FBgn0004390.
DR EnsemblMetazoa; FBtr0076368; FBpp0076097; FBgn0004390.
DR GeneID; 39158; -.
DR KEGG; dme:Dmel_CG6721; -.
DR CTD; 39158; -.
DR FlyBase; FBgn0004390; RasGAP1.
DR VEuPathDB; VectorBase:FBgn0004390; -.
DR eggNOG; KOG2059; Eukaryota.
DR GeneTree; ENSGT00940000167058; -.
DR HOGENOM; CLU_008096_1_0_1; -.
DR InParanoid; P48423; -.
DR OMA; FDHSLNN; -.
DR OrthoDB; 145372at2759; -.
DR PhylomeDB; P48423; -.
DR SignaLink; P48423; -.
DR BioGRID-ORCS; 39158; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 39158; -.
DR PRO; PR:P48423; -.
DR Proteomes; UP000000803; Chromosome 3L.
DR Bgee; FBgn0004390; Expressed in wing disc and 30 other tissues.
DR ExpressionAtlas; P48423; baseline and differential.
DR Genevisible; P48423; DM.
DR GO; GO:0005886; C:plasma membrane; IDA:FlyBase.
DR GO; GO:0005096; F:GTPase activator activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008595; P:anterior/posterior axis specification, embryo; TAS:FlyBase.
DR GO; GO:0007476; P:imaginal disc-derived wing morphogenesis; IMP:FlyBase.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR GO; GO:0045792; P:negative regulation of cell size; IMP:FlyBase.
DR GO; GO:0042059; P:negative regulation of epidermal growth factor receptor signaling pathway; IMP:FlyBase.
DR GO; GO:0045677; P:negative regulation of R7 cell differentiation; IGI:FlyBase.
DR GO; GO:0045873; P:negative regulation of sevenless signaling pathway; IGI:FlyBase.
DR GO; GO:0120177; P:negative regulation of torso signaling pathway; IMP:FlyBase.
DR GO; GO:0030948; P:negative regulation of vascular endothelial growth factor receptor signaling pathway; IMP:FlyBase.
DR GO; GO:0045678; P:positive regulation of R7 cell differentiation; IGI:FlyBase.
DR GO; GO:0043087; P:regulation of GTPase activity; IEA:InterPro.
DR Gene3D; 1.10.506.10; -; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR Gene3D; 2.60.40.150; -; 2.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR InterPro; IPR039360; Ras_GTPase.
DR InterPro; IPR023152; RasGAP_CS.
DR InterPro; IPR001936; RasGAP_dom.
DR InterPro; IPR008936; Rho_GTPase_activation_prot.
DR InterPro; IPR001562; Znf_Btk_motif.
DR PANTHER; PTHR10194; PTHR10194; 1.
DR Pfam; PF00779; BTK; 1.
DR Pfam; PF00168; C2; 2.
DR Pfam; PF00169; PH; 1.
DR Pfam; PF00616; RasGAP; 1.
DR SMART; SM00107; BTK; 1.
DR SMART; SM00239; C2; 2.
DR SMART; SM00233; PH; 1.
DR SMART; SM00323; RasGAP; 1.
DR SUPFAM; SSF48350; SSF48350; 1.
DR SUPFAM; SSF49562; SSF49562; 2.
DR PROSITE; PS50004; C2; 2.
DR PROSITE; PS50003; PH_DOMAIN; 1.
DR PROSITE; PS00509; RAS_GTPASE_ACTIV_1; 1.
DR PROSITE; PS50018; RAS_GTPASE_ACTIV_2; 1.
DR PROSITE; PS51113; ZF_BTK; 1.
PE 1: Evidence at protein level;
KW GTPase activation; Metal-binding; Reference proteome; Repeat; Zinc;
KW Zinc-finger.
FT CHAIN 1..1163
FT /note="GTPase-activating protein"
FT /id="PRO_0000056661"
FT DOMAIN 26..148
FT /note="C2 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 261..419
FT /note="C2 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 504..698
FT /note="Ras-GAP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00167"
FT DOMAIN 762..860
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT ZN_FING 862..898
FT /note="Btk-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00432"
FT REGION 1026..1051
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1091..1163
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1091..1153
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 870
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00432"
FT BINDING 881
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00432"
FT BINDING 882
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00432"
FT BINDING 892
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00432"
FT CONFLICT 4
FT /note="K -> N (in Ref. 1; AAA28595)"
FT /evidence="ECO:0000305"
FT CONFLICT 765
FT /note="G -> GEG (in Ref. 1; AAA28595)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1163 AA; 132087 MW; 5E70011CEC269984 CRC64;
MLLKKKRYMF DERDDNNINS PVAVEPSSNN NKMADTREVR IEEQLKVKIG EAKNLSSRNA
ANTSCSTQGT RDVYCTIALD QEEICRTPTI ERTLTPFFGE EHQFKIPRRF RYLTIYLWDR
DMKQDKPIGK IAIKREELHM YNHKDHWFSL RPVDQDSEVQ GMVNVEVAFT EAQQTQSLSE
GIDLGQHTLR HHQNLPHHSH QQRAHLNDYK ENSELSNIQR ASAAAASSSS AAMTLKTRAA
GLFGHVHHPP SQTQHFPIIN TTSTSSDQLS NWKSHGRFVG VTIKVPACVD LAKKQGTCDP
FVVCTAHYSN KHQVTRRTKQ RKKTVDPEFD EAMYFDLHID ADAGSTNTTG SNKSAGSLES
SANKGYSIYP VGGADLVEIV VSVWHDAHGA MSDKVFLGEV RLPMLNKQEQ QAVNPSAWYY
LQPRSMTHSS RSLNATPRSC ATPPGTRLSV DSTIGSLRLN LNYTADHVFP LATYDDLMNL
LLESVDQRPI TVSAVSILGE LVSGKTEVAQ PLVRLFTHTE RIAPIIKALA DHEISHLTDP
TTIFRGNTLV SKMMDEAMRL SGLHYLHQTL RPVLSQIVAE KKPCEIDPSK IKDRSAVDTN
LHNLQDYVER VFEAITKSAD RCPKVLCQIF HDLRECAGEH FPSNREVRYS VVSGFIFLRF
FAPAILGPKL FDLTTERLDA QTSRTLTLIS KTIQSLGNLV SSRSSQQTCK EEFTVELYKK
FCTEQHVDAV KHFLEVISTP SHASSSVHPA AAAATPLEPV LLKEGLMTKY PTSRKRFGRQ
FKQRHFRLTT HSLSYAKSKG KQPICDIPLQ EIASVEQLKD KSFKMQNCFK IVHNDRSLIV
QTTNCVEERE WFDLLHKICL MNSIRMQYFH PSAFVSGFYS CCGRSDENSP GCKKVLDKTM
DYFQMDLVTA LDPALDLQRI HTLIMSNMSV LESLLDPLTY HQSLSQTQHQ QHNPLVPLAT
DLQKHSPQAF AEFKRTIEKL REKAYAIDRD HRDYKQGITR QLKYGSRQAP IGDDNYWHMM
RAAGQLNQQH HQQQQHQQQQ QQQQQQQLQQ FQPQPVLPQM QNVRAYPYQP ATSNMNAYCL
HNMQYQQQRL PFHQQQQQHH QQLQQQQSQF QPLRSHQLQR HNNNLNNNNC GNGSSSSPSS
TTSSVVAAPP STTSSSQPAP PIY
