GEK_DROME
ID GEK_DROME Reviewed; 1637 AA.
AC Q9W1B0; O44368;
DT 02-SEP-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 177.
DE RecName: Full=Serine/threonine-protein kinase Genghis Khan;
DE EC=2.7.11.1;
GN Name=gek; ORFNames=CG4012;
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], ENZYME ACTIVITY, DISRUPTION PHENOTYPE,
RP INTERACTION WITH CDC42, AND MUTAGENESIS OF 1546-ILE--PRO-1548.
RX PubMed=9371783; DOI=10.1073/pnas.94.24.12963;
RA Luo L., Lee T., Tsai L., Tang G., Jan L.Y., Jan Y.N.;
RT "Genghis Khan (Gek) as a putative effector for Drosophila Cdc42 and
RT regulator of actin polymerization.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:12963-12968(1997).
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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1584, AND IDENTIFICATION BY
RP 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 [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-895, 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: Acts as a downstream effector for the regulation of actin
CC polymerization by Cdc42.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC Evidence={ECO:0000269|PubMed:9371783};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1; Evidence={ECO:0000269|PubMed:9371783};
CC -!- SUBUNIT: Interacts tightly with GTP-bound but not GDP-bound Cdc42.
CC {ECO:0000269|PubMed:9371783}.
CC -!- DISRUPTION PHENOTYPE: Flies are defective in producing fertilized eggs.
CC Egg chambers exhibit abnormal accumulation of F-actin.
CC {ECO:0000269|PubMed:9371783}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC protein kinase family. DMPK subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB96643.1; Type=Frameshift; 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; AF029395; AAB96643.1; ALT_FRAME; mRNA.
DR EMBL; AE013599; AAF47163.1; -; Genomic_DNA.
DR EMBL; AY051698; AAK93122.1; -; mRNA.
DR RefSeq; NP_523837.2; NM_079113.3.
DR AlphaFoldDB; Q9W1B0; -.
DR SMR; Q9W1B0; -.
DR BioGRID; 63437; 2.
DR STRING; 7227.FBpp0072194; -.
DR iPTMnet; Q9W1B0; -.
DR PaxDb; Q9W1B0; -.
DR PRIDE; Q9W1B0; -.
DR DNASU; 37858; -.
DR EnsemblMetazoa; FBtr0072287; FBpp0072194; FBgn0023081.
DR GeneID; 37858; -.
DR KEGG; dme:Dmel_CG4012; -.
DR UCSC; CG4012-RA; d. melanogaster.
DR CTD; 37858; -.
DR FlyBase; FBgn0023081; gek.
DR VEuPathDB; VectorBase:FBgn0023081; -.
DR eggNOG; KOG0612; Eukaryota.
DR GeneTree; ENSGT01030000234517; -.
DR HOGENOM; CLU_000288_140_3_1; -.
DR InParanoid; Q9W1B0; -.
DR OMA; EFTIGYM; -.
DR OrthoDB; 759391at2759; -.
DR PhylomeDB; Q9W1B0; -.
DR Reactome; R-DME-5625900; RHO GTPases activate CIT.
DR Reactome; R-DME-8980692; RHOA GTPase cycle.
DR Reactome; R-DME-9013026; RHOB GTPase cycle.
DR Reactome; R-DME-9013106; RHOC GTPase cycle.
DR Reactome; R-DME-9013149; RAC1 GTPase cycle.
DR SignaLink; Q9W1B0; -.
DR BioGRID-ORCS; 37858; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 37858; -.
DR PRO; PR:Q9W1B0; -.
DR Proteomes; UP000000803; Chromosome 2R.
DR Bgee; FBgn0023081; Expressed in oviduct (Drosophila) and 26 other tissues.
DR Genevisible; Q9W1B0; DM.
DR GO; GO:0030424; C:axon; IDA:FlyBase.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005856; C:cytoskeleton; IBA:GO_Central.
DR GO; GO:0030426; C:growth cone; IDA:FlyBase.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004672; F:protein kinase activity; IDA:FlyBase.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0008154; P:actin polymerization or depolymerization; IMP:FlyBase.
DR GO; GO:0031032; P:actomyosin structure organization; IBA:GO_Central.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; IBA:GO_Central.
DR GO; GO:0030833; P:regulation of actin filament polymerization; IMP:UniProtKB.
DR GO; GO:0008039; P:synaptic target recognition; IMP:FlyBase.
DR CDD; cd00029; C1; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR000961; AGC-kinase_C.
DR InterPro; IPR046349; C1-like_sf.
DR InterPro; IPR001180; CNH_dom.
DR InterPro; IPR000095; CRIB_dom.
DR InterPro; IPR031597; KELK.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR002219; PE/DAG-bd.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR InterPro; IPR017892; Pkinase_C.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00130; C1_1; 1.
DR Pfam; PF00780; CNH; 1.
DR Pfam; PF15796; KELK; 1.
DR Pfam; PF00069; Pkinase; 1.
DR Pfam; PF00433; Pkinase_C; 1.
DR SMART; SM00109; C1; 1.
DR SMART; SM00036; CNH; 1.
DR SMART; SM00285; PBD; 1.
DR SMART; SM00233; PH; 1.
DR SMART; SM00133; S_TK_X; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR SUPFAM; SSF57889; SSF57889; 1.
DR PROSITE; PS51285; AGC_KINASE_CTER; 1.
DR PROSITE; PS50219; CNH; 1.
DR PROSITE; PS50108; CRIB; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
DR PROSITE; PS00479; ZF_DAG_PE_1; 1.
DR PROSITE; PS50081; ZF_DAG_PE_2; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Coiled coil; Kinase; Metal-binding; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Serine/threonine-protein kinase;
KW Transferase; Zinc; Zinc-finger.
FT CHAIN 1..1637
FT /note="Serine/threonine-protein kinase Genghis Khan"
FT /id="PRO_0000348214"
FT DOMAIN 100..369
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 370..440
FT /note="AGC-kinase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT DOMAIN 1059..1177
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 1203..1489
FT /note="CNH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00795"
FT DOMAIN 1546..1559
FT /note="CRIB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00057"
FT ZN_FING 989..1039
FT /note="Phorbol-ester/DAG-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT REGION 538..575
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 952..971
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1611..1637
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 473..587
FT /evidence="ECO:0000255"
FT COILED 643..688
FT /evidence="ECO:0000255"
FT COILED 839..881
FT /evidence="ECO:0000255"
FT ACT_SITE 224
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 106..114
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 129
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 895
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 1584
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:17372656"
FT MUTAGEN 1546..1549
FT /note="Missing: Abolishes interaction with Cdc42."
FT CONFLICT 41
FT /note="G -> D (in Ref. 1; AAB96643)"
FT /evidence="ECO:0000305"
FT CONFLICT 879..880
FT /note="LQ -> FE (in Ref. 1; AAB96643)"
FT /evidence="ECO:0000305"
FT CONFLICT 1300
FT /note="R -> G (in Ref. 1; AAB96643)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1637 AA; 186724 MW; 6FB1641362CEA4B2 CRC64;
MEYESSEISD ITTGSCKKRL TFLKCILSDT TSDQKWAAEF GEDTEGHQFS LDYLLDTFIV
LYDECSNSSL RREKGVSDFL KLSKPFVHIV RKLRLSRDDF DILKIIGRGA FGEVCVVQMI
STEKVYAMKI LNKWEMLKRA ETACFREERD VLVFGDRQWI TNLHYAFQDN INLYLVMDYY
CGGDLLTLLS KFEDKLPEDM AKFYITEMIL AINSIHQIRY VHRDIKPDNV LLDKRGHVRL
ADFGSCLRLD KDGTVQSNVA VGTPDYISPE ILRAMEDGKG RYGTECDWWS LGVCMYEMLY
GETPFYAESL VETYGKIMNH QNCFNLPSQE TLNYKVSETS QDLLCKLICI PENRLGQNGI
QDFMDHPWFV GIDWKNIRQG PAPYVPEVSS PTDTSNFDVD DNDVRLTDSI PPSANPAFSG
FHLPFIGFTF SLTSSSTLDS KKNQSSGFGD DTLDTISSPQ LAILPSNNSE TPVDSVQLKA
LNDQLAALKQ EKAELSKQHN EVFERLKTQD SELQDAISQR NIAMMEYSEV TEKLSELRNQ
KQKLSRQVRD KEEELDGAMQ KNDSLRNELR KSDKTRRELE LHIEDAVIEA AKEKKLREHA
EDCCRQLQME LRKGSSSVET TMPLSISSEM SSYEIERLEL QFSEKLSHQQ TRHNMELEAL
REQFSELENA NLALTKELQQ TQERLKYTQM ESITDSAETL LELKKQHDLE KSSWFEEKQR
LSSEVNLKSK SLKELQAEDD EIFKELRMKR EAITLWERQM AEIIQWVSDE KDARGYLQAL
ATKMTEELEY LKHVGTFNNN GVDNKNWRNR RSQKLDKMEL LNLQSALQRE IQAKNMISDE
LSQTRSDLIS TQKEVRDYKK RYDSILHDFQ KKETELRDLQ KGGLEYSESF LNKSTHHGLS
SAFFRDMSKN SEIIDSAESF GNESGDNFTP NFFQSGNSGM LFNYEPKYAG KNNKDHSSMK
EASVSDLSRE ESDQLVKESQ KKVPGNTAIH QFLVRTFSSP TKCNHCTSLM VGLTRQGVVC
EICGFACHTI CCQKVPTTCP VPMDQTKRPL GIDPTRGIGT AYEGYVKVPK SGVIKRGWIR
QFVVVCDFKL FLYDISPDRC ALPSVSVSQV LDMRDPEFSV GSVRESDVIH AAKKDVPCIF
KIKTALIDGG LSLNTLMLAD NESEKSKWVI ALGELHRILK RNSLPNTAIF KVNEILDNTL
SLIRNALCSV IIYPNQILLG TEDGLFYINL DQYEIARIGE SKKILQLWYI EEEQILVILC
GKQRNLRLLP IRALEASDVE WIKVVESKNC ISACTGIIRR FPNIVYSFII ALKRPNNHTQ
IVVYEINRTR TRHQKTCEFT IGYMAQHLQI LSDMRLVVAH QSGFTAYFLR GEATAMSLVH
PENQLCAFLN YSGVDAVRVI EILCPSGGNF GEYLLVFQTL AIYVDLQGRK SRDREIMYPA
FPTYITFCDG HLLVFSDTHL DIFNTQTAEW VQSIGLKQSL PLNNLGNVVL SSVNDTPLIV
YLSNIHTKGL LQYRDGNRKG LPSIKRRFSI REINKTIKSD RRSKMISAPT NFNHISHMGP
GDGIQNQRLL DLPTTLETAD QACSPIIHSL SCIPQSRKSN FLEQVDANSD DYGNDNIISR
TPSPMASSFM DGLSNND
