CONU_DROME
ID CONU_DROME Reviewed; 629 AA.
AC Q8T0G4; Q0E9Q3;
DT 10-MAY-2017, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=Rho GTPase-activating protein conundrum {ECO:0000303|PubMed:23468526};
GN Name=conu {ECO:0000303|PubMed:23468526, ECO:0000312|FlyBase:FBgn0039994};
GN ORFNames=CG17082 {ECO:0000312|FlyBase:FBgn0039994};
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 {ECO:0000312|Proteomes:UP000000803};
RN [1] {ECO:0000312|Proteomes:UP000000803}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
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] {ECO:0000312|Proteomes:UP000000803}
RP GENOME REANNOTATION.
RC STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
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] {ECO:0000312|EMBL:AAL39479.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley {ECO:0000312|EMBL:AAL39479.1};
RC TISSUE=Embryo {ECO:0000312|EMBL:AAL39479.1};
RA Stapleton M., Carlson J., Chavez C., Frise E., George R., Pacleb J.,
RA Park S., Wan K., Yu C., Celniker S.;
RL Submitted (JUN-2006) to the EMBL/GenBank/DDBJ databases.
RN [4] {ECO:0000305}
RP FUNCTION, INTERACTION WITH MOE, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE,
RP AND MUTAGENESIS OF ARG-402.
RX PubMed=23468526; DOI=10.1091/mbc.e12-11-0800;
RA Neisch A.L., Formstecher E., Fehon R.G.;
RT "Conundrum, an ARHGAP18 orthologue, regulates RhoA and proliferation
RT through interactions with Moesin.";
RL Mol. Biol. Cell 24:1420-1433(2013).
CC -!- FUNCTION: GTPase-activating protein (GAP) for Rho1; functions with the
CC ERM protein Moe to regulate Rho1 and control proliferation in the
CC developing epithelium. Recruited by Moe to the cell cortex where it
CC negatively regulates Rho1 activity. Can also promote cell proliferation
CC independently of its GAP activity, perhaps by acting with Arf51F (Arf6)
CC to positively regulate Rac1. {ECO:0000269|PubMed:23468526}.
CC -!- SUBUNIT: Interacts with Moe (via FERM domain).
CC {ECO:0000269|PubMed:23468526}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:23468526}. Cell
CC membrane {ECO:0000269|PubMed:23468526}; Peripheral membrane protein
CC {ECO:0000269|PubMed:23468526}. Cytoplasm, cell cortex
CC {ECO:0000269|PubMed:23468526}. Cell junction
CC {ECO:0000269|PubMed:23468526}. Note=Recruited by Moe to the cell
CC cortex. In the epithelium, predominately expressed at the apical
CC cortex. {ECO:0000269|PubMed:23468526}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown does not affect
CC epithelial integrity or apoptosis. {ECO:0000269|PubMed:23468526}.
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DR EMBL; AE013599; EAA45990.1; -; Genomic_DNA.
DR EMBL; AE013599; EAA45991.3; -; Genomic_DNA.
DR EMBL; AE013599; EAA45992.1; -; Genomic_DNA.
DR EMBL; AE013599; EAA45993.1; -; Genomic_DNA.
DR EMBL; AE013599; EAA45994.1; -; Genomic_DNA.
DR EMBL; AY069334; AAL39479.1; -; mRNA.
DR RefSeq; NP_001036454.1; NM_001042989.3.
DR RefSeq; NP_001036455.2; NM_001042990.3.
DR RefSeq; NP_001036456.3; NM_001042991.3.
DR RefSeq; NP_001036457.1; NM_001042992.2.
DR RefSeq; NP_001036458.1; NM_001042993.3.
DR AlphaFoldDB; Q8T0G4; -.
DR SMR; Q8T0G4; -.
DR DIP; DIP-23652N; -.
DR STRING; 7227.FBpp0110582; -.
DR PaxDb; Q8T0G4; -.
DR EnsemblMetazoa; FBtr0111285; FBpp0110582; FBgn0039994.
DR EnsemblMetazoa; FBtr0111287; FBpp0110498; FBgn0039994.
DR EnsemblMetazoa; FBtr0111288; FBpp0110554; FBgn0039994.
DR EnsemblMetazoa; FBtr0302385; FBpp0291580; FBgn0039994.
DR EnsemblMetazoa; FBtr0345008; FBpp0311259; FBgn0039994.
DR GeneID; 3355133; -.
DR KEGG; dme:Dmel_CG17082; -.
DR UCSC; CG17082-RA; d. melanogaster.
DR UCSC; CG17082-RC; d. melanogaster.
DR CTD; 3355133; -.
DR FlyBase; FBgn0039994; conu.
DR VEuPathDB; VectorBase:FBgn0039994; -.
DR eggNOG; KOG2200; Eukaryota.
DR GeneTree; ENSGT00940000168361; -.
DR HOGENOM; CLU_023268_1_0_1; -.
DR OMA; CKPKEMD; -.
DR OrthoDB; 700544at2759; -.
DR PhylomeDB; Q8T0G4; -.
DR Reactome; R-DME-8980692; RHOA GTPase cycle.
DR Reactome; R-DME-9013106; RHOC GTPase cycle.
DR Reactome; R-DME-9013148; CDC42 GTPase cycle.
DR BioGRID-ORCS; 3355133; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 3355133; -.
DR PRO; PR:Q8T0G4; -.
DR Proteomes; UP000000803; Chromosome 2R.
DR Bgee; FBgn0039994; Expressed in adult abdomen and 21 other tissues.
DR ExpressionAtlas; Q8T0G4; baseline and differential.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-SubCell.
DR GO; GO:0045179; C:apical cortex; IDA:FlyBase.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005096; F:GTPase activator activity; IDA:FlyBase.
DR GO; GO:0034260; P:negative regulation of GTPase activity; IGI:FlyBase.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IGI:FlyBase.
DR GO; GO:0043547; P:positive regulation of GTPase activity; IGI:FlyBase.
DR GO; GO:0030833; P:regulation of actin filament polymerization; IBA:GO_Central.
DR GO; GO:0051056; P:regulation of small GTPase mediated signal transduction; IBA:GO_Central.
DR GO; GO:0007165; P:signal transduction; IEA:InterPro.
DR Gene3D; 1.10.555.10; -; 1.
DR InterPro; IPR008936; Rho_GTPase_activation_prot.
DR InterPro; IPR000198; RhoGAP_dom.
DR Pfam; PF00620; RhoGAP; 1.
DR SMART; SM00324; RhoGAP; 1.
DR SUPFAM; SSF48350; SSF48350; 1.
DR PROSITE; PS50238; RHOGAP; 1.
PE 1: Evidence at protein level;
KW Cell junction; Cell membrane; Cytoplasm; GTPase activation; Membrane;
KW Reference proteome.
FT CHAIN 1..629
FT /note="Rho GTPase-activating protein conundrum"
FT /id="PRO_0000439857"
FT DOMAIN 359..565
FT /note="Rho-GAP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00172"
FT REGION 185..294
FT /note="Required for interaction with Moe"
FT /evidence="ECO:0000269|PubMed:23468526"
FT REGION 237..261
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 240..261
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 402
FT /note="R->A: Required for activity. Inhibits negative
FT regulation of Rho1 but has no effect on the positive
FT regulation of Rac1."
FT /evidence="ECO:0000269|PubMed:23468526"
SQ SEQUENCE 629 AA; 71697 MW; CB3882B8DB95B348 CRC64;
MNSNTDLHHS DDQDFSEFLN EYYLQSNSQS IEPEASYEDG EMEAEWLVSA GYPELTKPFE
QGLEVSKKDL EPILTTLSKP HAEAIVQLVR TLNKTVRVRT KSRPKRKPDI RDVFREFDEQ
GTVTRSRSAT PDSLDSLQID EAWTNNSLPT FVNVYEKNTE TAIQCVEQSN EIYLKQNLRR
TPSAPPKSGT YADIFRGSQV RCDIPLYSAD GVELLGYSRI GTIQFPRNRS VSDPFCSIGR
SKESRSENDA RSQKKKSSEV LSASENECGR LLPMPYNVLS FESICRDSSS LDSCEVLDTC
DIPSTLFTDV VLISETDMKR LQTILWLELA TIFDRNKVSL DKRKPFKRRR KEEGNLFGVS
INALIRRDQQ VTGTDSSLVP LFLEKLIGEL LRRGSREEGL LRIGGHKQKT ELLYNELEST
FYQNPDNLDN LFRTATVHEL SSLLKRWLRE LPQPLLTNEL IQLFYQCHTL PSIDQMNALS
ILCHLLPPEN RNTLRSLLSF FNIIINLKDI NKMNVHNVAT IMAPSMFPPR YIHPSDNNSI
AEQVRMAAQC CRLTNILILR GEKLFQVPNN LIVESQKTMM GKKGWHRHRN SNEITAKPSG
KASNVGVGHD STVINKYSTN LKHLHPFVI
