PAKM_DROME
ID PAKM_DROME Reviewed; 639 AA.
AC Q9VXE5; O96372; Q960J8; Q9TYH2;
DT 09-NOV-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 2.
DT 03-AUG-2022, entry version 178.
DE RecName: Full=Serine/threonine-protein kinase PAK mbt;
DE EC=2.7.11.1;
DE AltName: Full=Protein mushroom bodies tiny;
DE AltName: Full=p21-activated kinase-related protein;
GN Name=mbt {ECO:0000312|EMBL:AAF48629.2}; ORFNames=CG18582;
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] {ECO:0000305, ECO:0000312|EMBL:CAA09699.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL
RP STAGE, AND DISRUPTION PHENOTYPE.
RC TISSUE=Embryo {ECO:0000269|PubMed:9811608};
RX PubMed=9811608; DOI=10.1016/s0960-9822(07)00514-3;
RA Melzig J., Rein K.-H., Schaefer U., Pfister H., Jaeckle H., Heisenberg M.,
RA Raabe T.;
RT "A protein related to p21-activated kinase (PAK) that is involved in
RT neurogenesis in the Drosophila adult central nervous system.";
RL Curr. Biol. 8:1223-1226(1998).
RN [2] {ECO:0000312|EMBL:AAD01935.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Melnick M.B.;
RT "New Drosophila member of the Ste20 serine/threonine kinase family.";
RL Submitted (OCT-1997) to the EMBL/GenBank/DDBJ databases.
RN [3] {ECO:0000312|EMBL:AAF48629.2}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000269|PubMed:10731132};
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 [4] {ECO:0000305, ECO:0000312|EMBL:AAF48629.2}
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 [5] {ECO:0000312|EMBL:AAK93447.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley {ECO:0000312|EMBL:AAK93447.1};
RC TISSUE=Embryo {ECO:0000269|PubMed:12537569};
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 [6] {ECO:0000305}
RP FUNCTION, INTERACTION WITH CDC42, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP DEVELOPMENTAL STAGE, AND MUTAGENESIS OF HIS-19; HIS-22 AND THR-525.
RX PubMed=12490550; DOI=10.1242/dev.00248;
RA Schneeberger D., Raabe T.;
RT "Mbt, a Drosophila PAK protein, combines with Cdc42 to regulate
RT photoreceptor cell morphogenesis.";
RL Development 130:427-437(2003).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-521 AND THR-525, AND
RP IDENTIFICATION BY 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: Involved in neurogenesis of the adult central nervous system,
CC and together with Cdc42, regulates photoreceptor cell morphogenesis.
CC Phosphorylates exogenous substrates when activated by Cdc42.
CC {ECO:0000269|PubMed:12490550, ECO:0000269|PubMed:9811608}.
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:12490550};
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:12490550};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC -!- SUBUNIT: Interacts tightly with GTP-bound but not GDP-bound Cdc42 and
CC weakly with Rac1. {ECO:0000269|PubMed:12490550}.
CC -!- INTERACTION:
CC Q9VXE5; P40793: Cdc42; NbExp=2; IntAct=EBI-75994, EBI-114324;
CC -!- SUBCELLULAR LOCATION: Cell junction, adherens junction
CC {ECO:0000269|PubMed:12490550}. Cell membrane
CC {ECO:0000269|PubMed:12490550}; Peripheral membrane protein
CC {ECO:0000269|PubMed:12490550}. Note=Apical membrane sites of adherens
CC junctions of developing photoreceptor cells.
CC -!- TISSUE SPECIFICITY: Expressed in adult brain and eye. High levels
CC detected in developing photoreceptor cells and future bristle cells,
CC and lower levels in cone and pigment cells, as detected in third instar
CC eye imaginal disks (at protein level). {ECO:0000269|PubMed:12490550,
CC ECO:0000269|PubMed:9811608}.
CC -!- DEVELOPMENTAL STAGE: Expressed throughout development.
CC {ECO:0000269|PubMed:12490550, ECO:0000269|PubMed:9811608}.
CC -!- PTM: Autophosphorylated when activated by Cdc42.
CC {ECO:0000269|PubMed:12490550, ECO:0000269|PubMed:18327897}.
CC -!- DISRUPTION PHENOTYPE: In the adult brain of mutants, the calyx,
CC peduncle and the lobe system of the mushroom bodies are reduced, along
CC with other neuropil structures in the central brain. The Kenyon cell
CC body layer above and behind the calyces is thinner. Additionally these
CC mutants have a rough eye phenotype and bristle malformations.
CC {ECO:0000269|PubMed:9811608}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr
CC protein kinase family. STE20 subfamily. {ECO:0000305}.
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DR EMBL; AJ011578; CAA09699.1; -; mRNA.
DR EMBL; AF031517; AAD01935.1; -; mRNA.
DR EMBL; AE014298; AAF48629.2; -; Genomic_DNA.
DR EMBL; AY052023; AAK93447.1; -; mRNA.
DR RefSeq; NP_523375.2; NM_078651.4.
DR AlphaFoldDB; Q9VXE5; -.
DR SMR; Q9VXE5; -.
DR BioGRID; 58968; 26.
DR DIP; DIP-20519N; -.
DR IntAct; Q9VXE5; 11.
DR STRING; 7227.FBpp0074060; -.
DR iPTMnet; Q9VXE5; -.
DR PaxDb; Q9VXE5; -.
DR PRIDE; Q9VXE5; -.
DR DNASU; 32631; -.
DR EnsemblMetazoa; FBtr0074285; FBpp0074060; FBgn0025743.
DR GeneID; 32631; -.
DR KEGG; dme:Dmel_CG18582; -.
DR CTD; 32631; -.
DR FlyBase; FBgn0025743; mbt.
DR VEuPathDB; VectorBase:FBgn0025743; -.
DR eggNOG; KOG0578; Eukaryota.
DR GeneTree; ENSGT00940000169130; -.
DR HOGENOM; CLU_000288_26_6_1; -.
DR InParanoid; Q9VXE5; -.
DR OMA; CLKPLAY; -.
DR OrthoDB; 757766at2759; -.
DR PhylomeDB; Q9VXE5; -.
DR Reactome; R-DME-9013149; RAC1 GTPase cycle.
DR Reactome; R-DME-9013405; RHOD GTPase cycle.
DR Reactome; R-DME-9013407; RHOH GTPase cycle.
DR Reactome; R-DME-9013420; RHOU GTPase cycle.
DR Reactome; R-DME-9013424; RHOV GTPase cycle.
DR SignaLink; Q9VXE5; -.
DR BioGRID-ORCS; 32631; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 32631; -.
DR PRO; PR:Q9VXE5; -.
DR Proteomes; UP000000803; Chromosome X.
DR Bgee; FBgn0025743; Expressed in ovary and 11 other tissues.
DR ExpressionAtlas; Q9VXE5; baseline and differential.
DR Genevisible; Q9VXE5; DM.
DR GO; GO:0005912; C:adherens junction; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:FlyBase.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IMP:UniProtKB.
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:FlyBase.
DR GO; GO:0031267; F:small GTPase binding; IPI:FlyBase.
DR GO; GO:0048749; P:compound eye development; IMP:FlyBase.
DR GO; GO:0001751; P:compound eye photoreceptor cell differentiation; IMP:UniProtKB.
DR GO; GO:0007010; P:cytoskeleton organization; TAS:UniProtKB.
DR GO; GO:0007030; P:Golgi organization; IMP:FlyBase.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0016319; P:mushroom body development; IMP:UniProtKB.
DR GO; GO:0045792; P:negative regulation of cell size; IMP:FlyBase.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:FlyBase.
DR GO; GO:0045315; P:positive regulation of compound eye photoreceptor development; IMP:UniProtKB.
DR GO; GO:0048639; P:positive regulation of developmental growth; IMP:FlyBase.
DR GO; GO:0006468; P:protein phosphorylation; IMP:UniProtKB.
DR GO; GO:2000047; P:regulation of cell-cell adhesion mediated by cadherin; IMP:FlyBase.
DR GO; GO:0043408; P:regulation of MAPK cascade; IMP:UniProtKB.
DR CDD; cd01093; CRIB_PAK_like; 1.
DR Gene3D; 3.90.810.10; -; 1.
DR InterPro; IPR000095; CRIB_dom.
DR InterPro; IPR036936; CRIB_dom_sf.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR033923; PAK_BD.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR Pfam; PF00786; PBD; 1.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00285; PBD; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50108; CRIB; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cell junction; Cell membrane; Developmental protein;
KW Differentiation; Kinase; Magnesium; Membrane; Neurogenesis;
KW Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..639
FT /note="Serine/threonine-protein kinase PAK mbt"
FT /id="PRO_0000086479"
FT DOMAIN 11..24
FT /note="CRIB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00057"
FT DOMAIN 368..619
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 25..367
FT /note="Linker"
FT REGION 79..195
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 222..345
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 81..100
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 136..150
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 222..292
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 311..337
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 487
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:O96013,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 374..382
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:O96013,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 397
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:O96013,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 521
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 525
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MUTAGEN 19
FT /note="H->L: Inhibits binding to Cdc42; when associated
FT with L-22."
FT /evidence="ECO:0000269|PubMed:12490550"
FT MUTAGEN 22
FT /note="H->L: Inhibits binding to Cdc42; when associated
FT with L-19."
FT /evidence="ECO:0000269|PubMed:12490550"
FT MUTAGEN 525
FT /note="T->A: Strongly reduces autophosphorylation and
FT substrate phosphorylation."
FT /evidence="ECO:0000269|PubMed:12490550"
FT CONFLICT 394
FT /note="V -> A (in Ref. 5; AAK93447)"
FT /evidence="ECO:0000305"
FT CONFLICT 596
FT /note="L -> F (in Ref. 2; AAD01935)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 639 AA; 69620 MW; 414D217F0AEEC1C6 CRC64;
MFSKKKKKPL ISMPSNFEHR VHTGFDKREN KYVGLPLQWA SIVGNNQILK SSNRPLPLVD
PSEITPTEIL DLKTIVRPHH NNNKADTTSL NSSSTMMMGS MAPMNPMAPG AHPMMSHGPG
MMMPPETGGI VLPKTSHVAR SNSLRSSSPP RVRRVANVPP SVPEEEGPPA AGTPGVGGAS
SGGFKPPGAH PSLLYNSQHA HANGATGPLA VRTDQTNLQQ YRSNLAPPSG GSMPQQQQTS
PVGSVASGTR SNHSHTNNGN SGGSYPPMYP TSHQQQQQQQ QQAKQGGDQN QNPLHPHAHP
HPHHHQHLAK SASRASSSSG GASSAAQQAS GASGGAAGQP KQDQRLTHEQ FRAALQMVVS
AGDPRENLDH FNKIGEGSTG TVCIATDKST GRQVAVKKMD LRKQQRRELL FNEVVIMRDY
HHPNIVETYS SFLVNDELWV VMEYLEGGAL TDIVTHSRMD EEQIATVCKQ CLKALAYLHS
QGVIHRDIKS DSILLAADGR VKLSDFGFCA QVSQELPKRK SLVGTPYWMS PEVISRLPYG
PEVDIWSLGI MVIEMVDGEP PFFNEPPLQA MRRIRDMQPP NLKNAHKVSP RLQSFLDRML
VRDPAQRATA AELLAHPFLR QAGPPSLLVP LMRNARHHP
