PAK_DROME
ID PAK_DROME Reviewed; 704 AA.
AC Q9VI13; Q24190; Q24213;
DT 02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 204.
DE RecName: Full=Serine/threonine-protein kinase Pak;
DE EC=2.7.11.1 {ECO:0000250|UniProtKB:Q13153};
GN Name=Pak;
GN Synonyms=DPAK {ECO:0000303|PubMed:8628256}, Dpak1 {ECO:0000303|Ref.4};
GN ORFNames=CG10295;
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.
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 [MRNA], INTERACTION WITH CDC42 AND RAC1, DEVELOPMENTAL
RP STAGE, AND SUBCELLULAR LOCATION.
RC STRAIN=Canton-S; TISSUE=Embryo;
RX PubMed=8628256; DOI=10.1128/mcb.16.5.1896;
RA Harden N., Lee J., Loh H.Y., Ong Y.M., Tan I., Leung T., Manser E., Lim L.;
RT "A Drosophila homolog of the Rac- and Cdc42-activated serine/threonine
RT kinase PAK is a potential focal adhesion and focal complex protein that
RT colocalizes with dynamic actin structures.";
RL Mol. Cell. Biol. 16:1896-1908(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Chernoff J.;
RL Submitted (APR-1996) to the EMBL/GenBank/DDBJ databases.
RN [5]
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 [6]
RP FUNCTION, INTERACTION WITH GIT AND PAK, AND DISRUPTION PHENOTYPE.
RX PubMed=18996366; DOI=10.1016/j.ydbio.2008.09.001;
RA Bahri S.M., Choy J.M., Manser E., Lim L., Yang X.;
RT "The Drosophila homologue of Arf-GAP GIT1, dGIT, is required for proper
RT muscle morphogenesis and guidance during embryogenesis.";
RL Dev. Biol. 325:15-23(2009).
CC -!- FUNCTION: Protein kinase involved in intracellular signaling pathways
CC downstream of integrins and receptor-type kinases that plays an
CC important role in cytoskeleton dynamics, in cell adhesion, migration,
CC proliferation, apoptosis, mitosis, and in vesicle-mediated transport
CC processes. May be required for the formation of dendritic spines and
CC excitatory synapses (By similarity). During muscle embryogenesis,
CC promotes proper muscle morphogenesis, as well as guidance and targeting
CC of subsets of myotubes (PubMed:18996366).
CC {ECO:0000250|UniProtKB:Q61036, ECO:0000269|PubMed:18996366}.
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:0000250|UniProtKB:Q13153};
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:0000250|UniProtKB:Q13153};
CC -!- SUBUNIT: Interacts with activated, GTP-bound Cdc42 and Rac1
CC (PubMed:8628256). Forms a complex with pix and Git; the interaction
CC with Git may be mediated by pix (PubMed:18996366).
CC {ECO:0000269|PubMed:18996366, ECO:0000269|PubMed:8628256}.
CC -!- INTERACTION:
CC Q9VI13; P40792: Rac1; NbExp=3; IntAct=EBI-74826, EBI-74845;
CC Q9VI13; P48554: Rac2; NbExp=3; IntAct=EBI-74826, EBI-74869;
CC Q9VI13; O44924: robo1; NbExp=5; IntAct=EBI-74826, EBI-74797;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:8628256}. Cell
CC junction, focal adhesion {ECO:0000305|PubMed:8628256}.
CC -!- DEVELOPMENTAL STAGE: Widely expressed throughout embryonic development,
CC with some cells showing increased levels (at protein level). Such an
CC increased level is observed in stage 11 in the epidermal cells
CC immediately flanking the amnioserosa. This increase is particularly
CC pronounced in stage 14 embryos around the time of dorsal closure
CC initiation. Dorsal epidermal cells in the first row of cells adjacent
CC to the amnioserosa show increased expression levels relative to the
CC rest of the epidermis, with at least two cells flanking each segment
CC border having particularly high levels. During dorsal closure,
CC accumulates in the cells of the leading edge (at protein level).
CC Expression is also higher in the abdominal segments than in the thorax,
CC but in later embryos increased RNA levels are seen in the thorax and in
CC more ventrally located epidermal cells flanking the segment borders.
CC Following the completion of dorsal closure, high expression levels were
CC detected in the dorsal vessel, in the central nervous system and in the
CC epidermal cells at 3 thoracic muscle attachment sites in the epidermis.
CC At the end of embryogenesis, elevated transcript levels are seen in
CC muscle attachment sites throughout the epidermis.
CC {ECO:0000269|PubMed:8628256}.
CC -!- DISRUPTION PHENOTYPE: Homozygous knockout flies show defective wing
CC morphology. Mutant embryos show guidance phenotypes in ventral oblique
CC muscle 5 (VO5), ventral oblique muscle 6 (VO6) and ventral acute muscle
CC 3 (VA3). The affected muscles bypass their normal ventral attachment
CC sites and mistarget toward or crossing the ventral midline. Mutant
CC embryos exhibit additional muscle phenotypes, such as increase in
CC lateral transverse (LT) muscles and VA3 numbers and defective lateral
CC oblique muscle 1 (LO1) and ventral oblique muscle 1 (VO1) shape.
CC {ECO:0000269|PubMed:18996366}.
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; AE014297; AAF54131.1; -; Genomic_DNA.
DR EMBL; AE014297; AAF54132.1; -; Genomic_DNA.
DR EMBL; AE014297; AAN13373.1; -; Genomic_DNA.
DR EMBL; AE014297; AGB95692.1; -; Genomic_DNA.
DR EMBL; AE014297; AGB95696.1; -; Genomic_DNA.
DR EMBL; U49446; AAC47094.1; -; mRNA.
DR EMBL; U56080; AAB01209.1; -; mRNA.
DR EMBL; BT010291; AAQ23609.1; -; mRNA.
DR RefSeq; NP_001262309.1; NM_001275380.2.
DR RefSeq; NP_001262313.1; NM_001275384.1.
DR RefSeq; NP_524681.1; NM_079942.4.
DR RefSeq; NP_731073.1; NM_169136.3.
DR RefSeq; NP_731074.1; NM_169137.3.
DR AlphaFoldDB; Q9VI13; -.
DR SMR; Q9VI13; -.
DR IntAct; Q9VI13; 32.
DR MINT; Q9VI13; -.
DR EnsemblMetazoa; FBtr0081714; FBpp0081211; FBgn0267698.
DR EnsemblMetazoa; FBtr0081715; FBpp0081212; FBgn0267698.
DR EnsemblMetazoa; FBtr0081716; FBpp0081213; FBgn0267698.
DR EnsemblMetazoa; FBtr0334539; FBpp0306606; FBgn0267698.
DR EnsemblMetazoa; FBtr0334544; FBpp0306611; FBgn0267698.
DR GeneID; 44039; -.
DR KEGG; dme:Dmel_CG10295; -.
DR UCSC; CG10295-RA; d. melanogaster.
DR CTD; 44039; -.
DR FlyBase; FBgn0267698; Pak.
DR VEuPathDB; VectorBase:FBgn0267698; -.
DR GeneTree; ENSGT00950000182988; -.
DR HOGENOM; CLU_000288_26_2_1; -.
DR PhylomeDB; Q9VI13; -.
DR SignaLink; Q9VI13; -.
DR BioGRID-ORCS; 44039; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 44039; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0267698; Expressed in adult midgut (Drosophila) and 44 other tissues.
DR ExpressionAtlas; Q9VI13; baseline and differential.
DR GO; GO:0031252; C:cell leading edge; IDA:FlyBase.
DR GO; GO:0005737; C:cytoplasm; IDA:FlyBase.
DR GO; GO:0005856; C:cytoskeleton; IMP:FlyBase.
DR GO; GO:0005925; C:focal adhesion; IEA:UniProtKB-SubCell.
DR GO; GO:0016328; C:lateral plasma membrane; IDA:FlyBase.
DR GO; GO:0097482; C:muscle cell postsynaptic specialization; IDA:FlyBase.
DR GO; GO:0031594; C:neuromuscular junction; IDA:SynGO.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:FlyBase.
DR GO; GO:0017124; F:SH3 domain binding; IPI:FlyBase.
DR GO; GO:0031267; F:small GTPase binding; IPI:FlyBase.
DR GO; GO:0007411; P:axon guidance; IMP:FlyBase.
DR GO; GO:0007155; P:cell adhesion; IDA:FlyBase.
DR GO; GO:0007391; P:dorsal closure; IMP:FlyBase.
DR GO; GO:0007395; P:dorsal closure, spreading of leading edge cells; IEP:FlyBase.
DR GO; GO:0035072; P:ecdysone-mediated induction of salivary gland cell autophagic cell death; IMP:FlyBase.
DR GO; GO:0007480; P:imaginal disc-derived leg morphogenesis; IMP:FlyBase.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0045887; P:positive regulation of synaptic assembly at neuromuscular junction; IMP:FlyBase.
DR GO; GO:0006468; P:protein phosphorylation; IMP:FlyBase.
DR GO; GO:0050770; P:regulation of axonogenesis; IGI:FlyBase.
DR GO; GO:0043408; P:regulation of MAPK cascade; IBA:GO_Central.
DR GO; GO:0098696; P:regulation of neurotransmitter receptor localization to postsynaptic specialization membrane; IDA:SynGO.
DR GO; GO:0043067; P:regulation of programmed cell death; IMP:FlyBase.
DR GO; GO:0090128; P:regulation of synapse maturation; IMP:SynGO.
DR GO; GO:0050803; P:regulation of synapse structure or activity; IMP:FlyBase.
DR GO; GO:0019991; P:septate junction assembly; IMP:FlyBase.
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 InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00786; PBD; 1.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00285; PBD; 1.
DR SMART; SM00220; S_TKc; 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.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cell junction; Cytoplasm; Developmental protein; Kinase;
KW Nucleotide-binding; Reference proteome; Serine/threonine-protein kinase;
KW Transferase.
FT CHAIN 1..704
FT /note="Serine/threonine-protein kinase Pak"
FT /id="PRO_0000452605"
FT DOMAIN 83..96
FT /note="CRIB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00057"
FT DOMAIN 430..681
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..87
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 80..171
FT /note="Autoregulatory region"
FT /evidence="ECO:0000250|UniProtKB:Q13153"
FT REGION 83..113
FT /note="GTPase-binding"
FT /evidence="ECO:0000250|UniProtKB:Q13153"
FT REGION 97..429
FT /note="Linker"
FT REGION 159..188
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 254..292
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 49..64
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 254..275
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 549
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q13153"
FT BINDING 436..444
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 459
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT CONFLICT 338
FT /note="A -> T (in Ref. 3; AAC47094 and 4; AAB01209)"
FT /evidence="ECO:0000305"
FT CONFLICT 446
FT /note="T -> S (in Ref. 4; AAB01209)"
FT /evidence="ECO:0000305"
FT CONFLICT 528
FT /note="A -> G (in Ref. 4; AAB01209)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 704 AA; 76187 MW; A5A095564A9A2453 CRC64;
MSSEEDKPPA PPVRLTSNRG GNERSGGGVG VGGGGLGGGG MGDVPPDMRP LPKEPDDSDR
KKKTLKSKIK GSKPSHTDSK PNISYPTNFE HTVHVGFDAV TGEFTGMPEA WARLLMNSNI
SKQEQKKNPQ AVLDVLKWFD NTTKQRPSSK YMTNAITTHS GSSLSRVSSS SPSSTPTDSE
LHGSNSGGNL IGVQLGSMTL GPNANNVAVA GQILGNHYQQ QQQHLLQQQQ PLLHQNHNQH
HMGISQSHSY NFVGHTVSSS TSQHSSANED DMLGPQHPQQ QPPPPPVASR PERTKSIYTR
PIEDLQPAII PMPVAPATTP ATPLQNHRTP GGISAPAASP MMHNNATTTL DKNKNNANLY
TPEPTVAQVS AGGPSSQVAG NQIAVPQAAV APAATPNTRA ANAKKKKMSD EEILEKLRTI
VSVGDPNRKY TKMEKIGQGA SGTVYTAIES STGMEVAIKQ MNLSQQPKKE LIINEILVMR
ENKHPNVVNY LDSYLVSEEL WVVMEYLPGG SLTDVVTETC MDEGQIAAVC REVLQALEFL
HANQVIHRDI KSDNILLGLD GSVKLTDFGF CAQISPEQSK RTTMVGTPYW MAPEVVTRKQ
YGPKVDLWSL GIMAIEMVEG EPPYLNENPL KALYLIATNG KPEIKEKDKL SSAFQDFLDQ
CLEVEVDRRA SALDLLKHPF LKLARPLASL TPLIMAAKEA TKGN
