ACKL_DROME
ID ACKL_DROME Reviewed; 1337 AA.
AC Q9I7F7; Q24316; Q960Z6; Q9V6K0;
DT 27-JAN-2003, integrated into UniProtKB/Swiss-Prot.
DT 27-JAN-2003, sequence version 3.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=Activated Cdc42 kinase-like {ECO:0000312|FlyBase:FBgn0263998};
DE EC=2.7.10.2;
DE AltName: Full=Tyrosine-protein kinase PR2 {ECO:0000303|PubMed:8112607};
GN Name=Ack-like {ECO:0000312|FlyBase:FBgn0263998};
GN Synonyms=PR2 {ECO:0000312|FlyBase:FBgn0263998};
GN ORFNames=CG43741 {ECO:0000312|FlyBase:FBgn0263998};
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}
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 [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 [4] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] OF 13-917.
RC STRAIN=Oregon-R; TISSUE=Embryo;
RX PubMed=8112607; DOI=10.1016/0378-1119(94)90758-7;
RA Ito M., Matsui T., Taniguchi T., Chihara K.;
RT "Alternative splicing generates two distinct transcripts for the Drosophila
RT melanogaster fibroblast growth factor receptor homolog.";
RL Gene 139:215-218(1994).
RN [5] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 266-321.
RX PubMed=9731193; DOI=10.1006/bbrc.1998.9003;
RA Oates A.C., Wollberg P., Achen M.G., Wilks A.F.;
RT "Sampling the genomic pool of protein tyrosine kinase genes using the
RT polymerase chain reaction with genomic DNA.";
RL Biochem. Biophys. Res. Commun. 249:660-667(1998).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-831, 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 [7]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=18816840; DOI=10.1002/dvdy.21722;
RA Zahedi B., Shen W., Xu X., Chen X., Mahey M., Harden N.;
RT "Leading edge-secreted Dpp cooperates with ACK-dependent signaling from the
RT amnioserosa to regulate myosin levels during dorsal closure.";
RL Dev. Dyn. 237:2936-2946(2008).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-71; TYR-291; TYR-292;
RP SER-764; SER-778; SER-918 AND SER-924, AND IDENTIFICATION BY MASS
RP 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 [9]
RP DISRUPTION PHENOTYPE.
RX PubMed=22615583; DOI=10.1371/journal.pgen.1002725;
RA Schoenherr J.A., Drennan J.M., Martinez J.S., Chikka M.R., Hall M.C.,
RA Chang H.C., Clemens J.C.;
RT "Drosophila activated Cdc42 kinase has an anti-apoptotic function.";
RL PLoS Genet. 8:E1002725-E1002725(2012).
CC -!- FUNCTION: Likely to act as a downstream effector of Cdc42 during dorsal
CC closure, acting in a kinase independent manner with the other ACK
CC family member Ack to positively regulate expression of the myosin zip
CC by promoting the endocytosis of Egfr in the amnioserosa (AS).
CC {ECO:0000269|PubMed:18816840}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.2;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10028};
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown results in a low
CC frequency of dorsal defects in the developing embryo (PubMed:18816840).
CC RNAi-mediated knockdown does not rescue the small eye phenotypes
CC induced by hid and rpr overexpression (PubMed:22615583). Simultaneous
CC knockdown of Ack and Ack-like results in many embryos failing to
CC properly secrete the cuticle likely due to the loss of zip expression
CC (PubMed:18816840). Mutants also display defects in the dorsal surface
CC including holes in the cuticle and germband retraction failure
CC (PubMed:18816840). {ECO:0000269|PubMed:18816840,
CC ECO:0000269|PubMed:22615583}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. {ECO:0000255|PROSITE-ProRule:PRU00159}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAF58423.5; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=BAA04489.1; 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; AE013599; AAF58423.5; ALT_SEQ; Genomic_DNA.
DR EMBL; AE013599; AAG22275.3; -; Genomic_DNA.
DR EMBL; AY051755; AAK93179.1; -; mRNA.
DR EMBL; D17551; BAA04489.1; ALT_FRAME; mRNA.
DR EMBL; AJ002909; CAA05744.1; -; Genomic_DNA.
DR RefSeq; NP_477086.2; NM_057738.4.
DR RefSeq; NP_477087.3; NM_057739.4.
DR AlphaFoldDB; Q9I7F7; -.
DR SMR; Q9I7F7; -.
DR BioGRID; 62210; 1.
DR IntAct; Q9I7F7; 3.
DR STRING; 7227.FBpp0303362; -.
DR iPTMnet; Q9I7F7; -.
DR PaxDb; Q9I7F7; -.
DR PRIDE; Q9I7F7; -.
DR EnsemblMetazoa; FBtr0330329; FBpp0303361; FBgn0263998.
DR EnsemblMetazoa; FBtr0330331; FBpp0303363; FBgn0263998.
DR GeneID; 36442; -.
DR KEGG; dme:Dmel_CG43741; -.
DR CTD; 36442; -.
DR FlyBase; FBgn0263998; Ack-like.
DR VEuPathDB; VectorBase:FBgn0263998; -.
DR eggNOG; KOG0199; Eukaryota.
DR GeneTree; ENSGT00940000173732; -.
DR InParanoid; Q9I7F7; -.
DR PhylomeDB; Q9I7F7; -.
DR SignaLink; Q9I7F7; -.
DR BioGRID-ORCS; 36442; 0 hits in 1 CRISPR screen.
DR ChiTaRS; Ack-like; fly.
DR GenomeRNAi; 36442; -.
DR PRO; PR:Q9I7F7; -.
DR Proteomes; UP000000803; Chromosome 2R.
DR Bgee; FBgn0263998; Expressed in eye disc (Drosophila) and 42 other tissues.
DR ExpressionAtlas; Q9I7F7; baseline and differential.
DR Genevisible; Q9I7F7; DM.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; ISS:FlyBase.
DR GO; GO:0004713; F:protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0005102; F:signaling receptor binding; IBA:GO_Central.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0046664; P:dorsal closure, amnioserosa morphology change; IGI:UniProtKB.
DR GO; GO:0008258; P:head involution; IGI:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IBA:GO_Central.
DR GO; GO:0031034; P:myosin filament assembly; IMP:UniProtKB.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; ISS:FlyBase.
DR GO; GO:0006468; P:protein phosphorylation; NAS:UniProtKB.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR InterPro; IPR000095; CRIB_dom.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR InterPro; IPR020635; Tyr_kinase_cat_dom.
DR Pfam; PF00786; PBD; 1.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR SMART; SM00285; PBD; 1.
DR SMART; SM00326; SH3; 1.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF50044; SSF50044; 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; PS00109; PROTEIN_KINASE_TYR; 1.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Kinase; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; SH3 domain; Transferase; Tyrosine-protein kinase.
FT CHAIN 1..1337
FT /note="Activated Cdc42 kinase-like"
FT /id="PRO_0000088132"
FT DOMAIN 133..399
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 399..460
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 488..502
FT /note="CRIB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00057"
FT REGION 714..739
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 786..822
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 906..969
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1024..1045
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 788..819
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 910..925
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 943..957
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1029..1043
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 260
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 139..147
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 164
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 71
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 291
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 292
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 764
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 778
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 831
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:17372656"
FT MOD_RES 918
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 924
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT CONFLICT 450
FT /note="F -> FSTPFWKGVLSTGKTGYF (in Ref. 4; BAA04489)"
FT /evidence="ECO:0000305"
FT CONFLICT 484
FT /note="R -> A (in Ref. 4; BAA04489)"
FT /evidence="ECO:0000305"
FT CONFLICT 906
FT /note="A -> P (in Ref. 4; BAA04489)"
FT /evidence="ECO:0000305"
FT CONFLICT 913
FT /note="D -> V (in Ref. 4; BAA04489)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1337 AA; 147477 MW; 12650E9DF5A82724 CRC64;
MEYPQIDLYE FLTESELQQY YNAVKNELKI TNAAQFKYAA DEDLRFIGLS RPEIRRLRKF
YEKHFPHSYL SKIKRLLQAP GTMVKREEAP GGGSQVALDG SSASACSSLA AKNGASSPSK
VPNNKHIIPA DSISVNKQLG TGEFGIVQQG VWSNGNERIQ VAIKCLCRER MQSNPMEFLK
EAAIMHSIEH ENIVRLYGVV LATDSLMLVT ELAHLRSLLE CLKDSGLRVS FLTIPTLCEF
ALQICNGMRY LEQKRLIHRD LAARNILVFS KDKVKISDFG LSRALGVGKD YYKTNFNVNL
KLPIAWCAPE CINYLRFTNA SDVWAFGVCL WEMFSYGFQP WAALTGLQIL EAIDAPNYQR
LEQPDCCPSE YYTLMMKCWQ DDAAKRPRFG EIYDQLPDMK PEQLKAVVNC TEPKKDHLLY
RQGDIISVLD RNTGTPFWKG VLSTGKTGYF NPSNTVAFLE GLPSSTRDSF SRVSDHRISK
RKLRTEMISK PQNDFKHTGH VGIDGATFGD IAFLGSSQNY NHVPKQIVTP YKPSEDIEQT
PLLLPPTPTS PDSLQTASGY FPEGANSGGA MGTSMNPTFI PSAEHTPKLI ATNGQSSFDF
ASGSTNPFFP NRGDDELEFG LHNYGADGKS VHSETGWRPT SRSIVDDPHE YHEISDDEIA
ADKLDFGPSL LDEINSMFGS ISAATGSHPK SPGFDHVNNK NEITEMSAKL GQKSGDTNGN
KHGHGLLPTL SKKKSSGTVK PISVKDEKIL NHAIEIANEI SARSMIDLVS DQTPVIHSPK
RKFSFRFPHL SNNGSGDKSG GLGTSGSAHT PTHGNASPFP KKKNFTEELQ SIPDIQSLIG
KEGLEAYNSL IERKALLDIG PSPAATLLRH LDTDEFDLQS LHQSQRPMTL PTRGATQRVR
KAELAAGLSR HNDENSNSLE ACESPSYMTH GSYKFPEAQP TEQLPEPESP NPIPLPPREG
KKQVKTSTKR HVRKYPLIIP ANGLQRTLSK LADFGDEAAK SPEISTSSQP QPGRAIEVVA
AVRPSGMRRP SRPSEREYEN MPTVGKESAH TYQNLDKLTP ADAAGLTDTA SLQFESIMEA
DTSKEGILQS PDVTDGFYNF SIQKEHYNKG KDAEFEATQI SGLYVNDDEL RNLDIESSRR
TATPCSSCSA LESEHSQPDA LPSTESVSEV SRFSSVDNEL AGNALFKKVR ASVNMAMNRK
SVAETSLTSN QPGGASAKPQ TEAEYFAATA ARLADSNSVS CEDLLEFSDK KPKGCERGVD
SDEVRIMVKV LGKDSTPNRC LGALEFINWD VHKSIKLIKL QNLVSEANLS LEASFEALQQ
HEWDLHTTAH KLNGLKL
