GAP2_DROME
ID GAP2_DROME Reviewed; 1580 AA.
AC Q8T498; A8JV42; Q95TL0; Q9VX23;
DT 19-JUL-2003, integrated into UniProtKB/Swiss-Prot.
DT 20-JAN-2009, sequence version 3.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=Ras GTPase-activating protein raskol {ECO:0000303|PubMed:30763317};
GN Name=raskol {ECO:0000303|PubMed:30763317};
GN ORFNames=CG42684 {ECO:0000312|FlyBase:FBgn0261570};
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 [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 [2]
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A).
RC STRAIN=Berkeley; TISSUE=Embryo, and Testis;
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 [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-164; THR-167; SER-221;
RP SER-224; SER-1158; SER-1164; SER-1401 AND SER-1403, 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).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=30763317; DOI=10.1371/journal.pgen.1007720;
RA Raza Q., Choi J.Y., Li Y., O'Dowd R.M., Watkins S.C., Chikina M., Hong Y.,
RA Clark N.L., Kwiatkowski A.V.;
RT "Evolutionary rate covariation analysis of E-cadherin identifies Raskol as
RT a regulator of cell adhesion and actin dynamics in Drosophila.";
RL PLoS Genet. 15:E1007720-E1007720(2019).
CC -!- FUNCTION: GTPase-activating protein, which acts as a negative regulator
CC for some members of the Ras family (By similarity). Probably decreases
CC their signaling activity by stimulating their intrinsic GTPase
CC activity, thereby lowering the levels of the GTP-bound active form (By
CC similarity). Functions with DE-cadherin (shg) to promote embryonic
CC border cell (BC) migration and adhesion by regulating the distribution
CC of actin protrusions in BCs (PubMed:30763317). Promotes shg-mediated
CC adhesion at the BC interfaces and likely maintains BC cluster adhesion
CC during BC detachment from the follicular epithelium and subsequent BC
CC migration (PubMed:30763317). Also required for restricting the
CC development of actin-rich protrusions to the front of migrating BC
CC clusters thus ensuring unidirectional BC migration (PubMed:30763317).
CC Possibly functions by suppressing Rac1 signaling in non-leading BCs,
CC thus limiting its activity to leading BCs where it initiates localized
CC actin cytoskeleton remodeling to produce the polarized protrusions
CC (PubMed:30763317). {ECO:0000250|UniProtKB:Q8MLZ5,
CC ECO:0000269|PubMed:30763317}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:30763317}. Cell
CC membrane; Peripheral membrane protein {ECO:0000269|PubMed:30763317}.
CC Apical cell membrane; Peripheral membrane protein
CC {ECO:0000269|PubMed:30763317}. Note=In embryos before border cell (BC)
CC delamination and during BC migration (stage 8 and stage 9 egg
CC chambers), colocalizes with E-cad/shg at the cell membranes of BCs and
CC polar cells (PCs), and is enriched at the PC apical membrane. Also
CC colocalizes with shg in the aminoserosa cell contacts and the dorsal
CC most ectodermal cells at the zippering interface. Cytoplasmic levels
CC are higher in PCs compared to BCs. {ECO:0000269|PubMed:30763317}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=B;
CC IsoId=Q8T498-1; Sequence=Displayed;
CC Name=A;
CC IsoId=Q8T498-2; Sequence=VSP_036230;
CC -!- DEVELOPMENTAL STAGE: Detected in stage 8 and stage 9 egg chambers (at
CC protein level). {ECO:0000269|PubMed:30763317}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown in both the border cells
CC (BCs) and follicle cells (FCs), results in the abnormal distribution of
CC F-actin protrusions which extend from the BC cluster. However, the
CC number of actin protrusions is not significantly affected. RNAi-
CC mediated knockdown in the embryonic polar cells (PCs) results in BC
CC dissociation in 63 percent of egg chambers.
CC {ECO:0000269|PubMed:30763317}.
CC -!- MISCELLANEOUS: The name 'raskol' means 'to split' in Russian, and is
CC based upon its role in maintaining cell adhesion in the polar and
CC border cells of embryos. {ECO:0000269|PubMed:30763317}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAL90028.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AE014298; AAF48759.2; -; Genomic_DNA.
DR EMBL; AE014298; ABW09442.1; -; Genomic_DNA.
DR EMBL; AY058706; AAL13935.1; -; mRNA.
DR EMBL; AY089290; AAL90028.1; ALT_INIT; mRNA.
DR RefSeq; NP_001097012.1; NM_001103542.4. [Q8T498-1]
DR RefSeq; NP_573240.1; NM_133012.5. [Q8T498-2]
DR AlphaFoldDB; Q8T498; -.
DR SMR; Q8T498; -.
DR BioGRID; 59077; 7.
DR DIP; DIP-19744N; -.
DR IntAct; Q8T498; 5.
DR STRING; 7227.FBpp0291973; -.
DR iPTMnet; Q8T498; -.
DR PaxDb; Q8T498; -.
DR PRIDE; Q8T498; -.
DR DNASU; 32754; -.
DR EnsemblMetazoa; FBtr0302834; FBpp0291974; FBgn0261570. [Q8T498-2]
DR EnsemblMetazoa; FBtr0302835; FBpp0291975; FBgn0261570. [Q8T498-1]
DR GeneID; 32754; -.
DR KEGG; dme:Dmel_CG42684; -.
DR UCSC; CG42270-RB; d. melanogaster. [Q8T498-1]
DR CTD; 32754; -.
DR FlyBase; FBgn0261570; raskol.
DR VEuPathDB; VectorBase:FBgn0261570; -.
DR eggNOG; KOG3508; Eukaryota.
DR GeneTree; ENSGT00940000172132; -.
DR InParanoid; Q8T498; -.
DR BioGRID-ORCS; 32754; 0 hits in 3 CRISPR screens.
DR ChiTaRS; CG42684; fly.
DR GenomeRNAi; 32754; -.
DR PRO; PR:Q8T498; -.
DR Proteomes; UP000000803; Chromosome X.
DR Bgee; FBgn0261570; Expressed in egg cell and 21 other tissues.
DR ExpressionAtlas; Q8T498; baseline and differential.
DR Genevisible; Q8T498; DM.
DR GO; GO:0045179; C:apical cortex; HDA:FlyBase.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005096; F:GTPase activator activity; IEA:UniProtKB-KW.
DR GO; GO:0046580; P:negative regulation of Ras protein signal transduction; ISS:UniProtKB.
DR GO; GO:0043087; P:regulation of GTPase activity; IEA:InterPro.
DR GO; GO:0007165; P:signal transduction; IEA:InterPro.
DR Gene3D; 1.10.506.10; -; 2.
DR Gene3D; 2.60.40.150; -; 1.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR021887; DAB2P_C.
DR InterPro; IPR039360; Ras_GTPase.
DR InterPro; IPR023152; RasGAP_CS.
DR InterPro; IPR001936; RasGAP_dom.
DR InterPro; IPR008936; Rho_GTPase_activation_prot.
DR PANTHER; PTHR10194; PTHR10194; 1.
DR Pfam; PF00168; C2; 1.
DR Pfam; PF12004; DUF3498; 1.
DR Pfam; PF00616; RasGAP; 2.
DR SMART; SM00239; C2; 1.
DR SMART; SM00323; RasGAP; 1.
DR SUPFAM; SSF48350; SSF48350; 1.
DR SUPFAM; SSF49562; SSF49562; 1.
DR PROSITE; PS50004; C2; 1.
DR PROSITE; PS00509; RAS_GTPASE_ACTIV_1; 1.
DR PROSITE; PS50018; RAS_GTPASE_ACTIV_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Cytoplasm; GTPase activation;
KW Membrane; Phosphoprotein; Reference proteome.
FT CHAIN 1..1580
FT /note="Ras GTPase-activating protein raskol"
FT /id="PRO_0000056662"
FT DOMAIN 233..291
FT /note="PH"
FT DOMAIN 282..400
FT /note="C2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 474..668
FT /note="Ras-GAP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00167"
FT REGION 197..223
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 764..819
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 857..892
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 904..1023
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1112..1218
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1284..1313
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1334..1443
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1561..1580
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 200..217
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 773..819
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 904..942
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 980..1023
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1140..1171
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1182..1218
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1284..1307
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1334..1362
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1378..1411
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 164
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 167
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 221
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 224
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 1158
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 1164
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 1401
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 1403
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT VAR_SEQ 129..152
FT /note="Missing (in isoform A)"
FT /evidence="ECO:0000303|PubMed:12537569"
FT /id="VSP_036230"
FT CONFLICT 1370
FT /note="H -> P (in Ref. 3; AAL90028)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1580 AA; 173530 MW; 0125FC61292A76BA CRC64;
MGRRTYLSRS STISYPSRIE GWLDVCETEG ELTRLIKTLP WGPLYCVLQQ DDQTFTAYCS
EEISLGDVCY EDIPRVRLDR VRRPAKALWD GPPTLVEENE DSDSCVGGSG GMSGINDIVL
NTTLYSELGE YKSKTLPRIH FDTALNDTSL NEDTSYEKAC RRGSAPTTPI LGSKQHQTEH
NATSRFTNFF SKKSNPLKRT KSVTKLERTK RGSGGLRGSR SHESLLSSHA VMSTIDLSCT
GAVGVAPVHQ SVLGRRHCFQ VRGGPRGERY YSCGSRQERD LWIYSLRKSI APNAEHTRRT
DNSLKMWVYE AKNLPPKKRY FCELQLDKTL YGRTSVKLQT DLLFWGEHFD FPDIPEINVI
TVNVFREVDK KKKRDKYQFV GSVKIPVHDV TSRLPCEQWY PILSDKAGDS LGRTSGGGGS
GSKDKEQLPT LRIKCRFQST DILPINVYGN FLTYLKENYK RVCETLEPVI GVKAKEDIGQ
ALVLLMHAQG LAGAFLTDVV ALDLLRVGDQ RLTFRGNSLA TKSMEAFLKL TGEQYLQDTL
SAPINELIQS ERDCEVDPTK TSGSSAGSLQ RQQAALRGAV RGAWQCIFES HKHFPAQLRN
CFATFRERLQ QLGRQDMADN LISASIFLRF LCPAILSPSL FNITSELPSA RATRNLTLVA
KTLQTLANFT RFQGKENFME FLNDFLEQEA ARMQQFLEII STRPEHPAPD SILDWAGYID
QGKQLSILHS LLSESLAKLP EARQHELDPL QHILDEISRA KEHGMGTALP GGYLPATSST
HSIASENQEN RNPGSSGSHA GSNSEQLLPQ QSQLAQPQHA IVSKPLSAER GIMRGVLTPN
SLEKNIFRYN DPTVNGLLQQ QQQQQQQQQQ QQQQHQQLQQ HGHQQQPHHQ HPLQMLSNSQ
TSIAGNQYMS SPGGLQHAQS QTSMASSSLN GSSSNLLHGH QQHAHHPQQL HPHHCPPAPQ
TSASSTMERM DRMNYPYMSH NGNDYETSTP SSTRSRTLPR NGNPNANGNV GSSNNNQSGS
YDDMHGEFQI QISGFDTSSA FVCKSPTPMM KSSLGPAGAG RSHHKLNLGI PDHSGGYVRG
NNLNPNSNMP KNLEDLDDLF KYAEEHDVAE PANHHNHNQG QQNHQGHLKP AAVPGKEQLS
AKSSHCSSGY QSISTNPSPS QSSSPVESQL KAAMGSHNAP LAFKNPSYQL QPQTGSSRSS
AQSNTHQQQQ QQQQQQFGSR LKPIGGGLVA ARAAFLNSGG ALEAATLTPS SSDEQLSADN
YFSYAAAAAA GAGIATKLEA QRSLSGGSSS STSASASTSN LGKSGGSSAY GRLNGPLKRE
DVYGSGYGGS SGNVGYGLST SSAAGHHQHP HQQQQNPMQQ QQQRERDQEH KQYAGSVAGS
VGSATSAAQR RLSLDSARTL SDSSTDTEGH CNQLQEGKRR RQLRSSGGSG GGGAGSEQGL
GKSYDQNGEI QLLQQTLDTL CHTLDRDEAE LRDSSDELFG LQRPAGSNGS NNLSLQSEST
MRSIIDRLIT MEEELRREQL KMSLALSHKQ RVIEEQGQQI AALDAANSRL LSALTALRQR
YETQQQQQQH QAPPKTQKPQ
