PKN_DROME
ID PKN_DROME Reviewed; 1190 AA.
AC A1Z7T0; C7LA81;
DT 25-JAN-2012, integrated into UniProtKB/Swiss-Prot.
DT 06-FEB-2007, sequence version 1.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=Serine/threonine-protein kinase N;
DE EC=2.7.11.13;
DE AltName: Full=Protein kinase related to PKN;
GN Name=Pkn; Synonyms=Dpkn; ORFNames=CG2049;
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 [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=Berkeley; TISSUE=Head;
RA Carlson J., Booth B., Frise E., Park S., Wan K., Yu C., Celniker S.;
RL Submitted (AUG-2009) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP DEVELOPMENTAL STAGE.
RX PubMed=9125115; DOI=10.1006/bbrc.1997.6229;
RA Ueno N., Oishi I., Sugiyama S., Nishida Y., Minami Y., Yamamura H.;
RT "Identification of a novel Drosophila protein kinase highly homologous to
RT protein kinase N (PKN).";
RL Biochem. Biophys. Res. Commun. 232:126-129(1997).
RN [5]
RP FUNCTION, ACTIVITY REGULATION, INTERACTION WITH RHO1; RAC1 AND RAC2,
RP DISRUPTION PHENOTYPE, AUTOPHOSPHORYLATION, MUTAGENESIS OF GLY-58, AND
RP DEVELOPMENTAL STAGE.
RX PubMed=10323867; DOI=10.1101/gad.13.9.1168;
RA Lu Y., Settleman J.;
RT "The Drosophila Pkn protein kinase is a Rho/Rac effector target required
RT for dorsal closure during embryogenesis.";
RL Genes Dev. 13:1168-1180(1999).
RN [6]
RP FUNCTION, ACTIVITY REGULATION, INTERACTION WITH RHO1 AND RAC1, MUTAGENESIS
RP OF GLY-58 AND LYS-892, AND SUBCELLULAR LOCATION.
RX PubMed=17507675; DOI=10.1534/genetics.107.072967;
RA Betson M., Settleman J.;
RT "A rho-binding protein kinase C-like activity is required for the function
RT of protein kinase N in Drosophila development.";
RL Genetics 176:2201-2212(2007).
CC -!- FUNCTION: Pkc-related serine/threonine-protein kinase and Rho/Rac
CC effector protein that participates in specific signal transduction
CC responses in the cell. May play a role in the regulation of cell cycle
CC progression, actin cytoskeleton assembly, cell migration, cell adhesion
CC and transcription activation signaling processes (By similarity). Plays
CC a role in regulating Rho-mediated dorsal closure during embryogenesis.
CC {ECO:0000250, ECO:0000269|PubMed:10323867,
CC ECO:0000269|PubMed:17507675}.
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=2.7.11.13;
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=2.7.11.13;
CC -!- ACTIVITY REGULATION: Activated by lipids, particularly cardiolipin and
CC to a lesser extent by other acidic phospholipids and unsaturated fatty
CC acids. Two specific sites, Thr-1022 (activation loop of the kinase
CC domain) and Thr-1164 (turn motif), may be needed to be phosphorylated
CC for its full activation (By similarity). Kinase activity is activated
CC upon binding to GTP-bound Rho/Rac GTPases. {ECO:0000250,
CC ECO:0000269|PubMed:10323867, ECO:0000269|PubMed:17507675}.
CC -!- SUBUNIT: Interacts (via N-terminus) with Rho1 (via REM repeats), Rac1
CC (via REM 1 repeat) and Rac2. {ECO:0000269|PubMed:10323867,
CC ECO:0000269|PubMed:17507675}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17507675}. Nucleus
CC {ECO:0000250}. Membrane {ECO:0000250}. Cell projection, lamellipodium
CC {ECO:0000250}. Cytoplasm, cytoskeleton {ECO:0000250}. Cleavage furrow
CC {ECO:0000250}. Midbody {ECO:0000250}. Cell junction {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=A1Z7T0-1; Sequence=Displayed;
CC Name=2; Synonyms=Pkn-RB;
CC IsoId=A1Z7T0-2; Sequence=VSP_042188;
CC -!- DEVELOPMENTAL STAGE: Expressed at the leading edge (LE) cells and in
CC two pairs of discontinuous stripes on the epidermis of each segment at
CC stage 13. Expressed in the anterior and posterior spiracles, the
CC pharynx and the mouth tip at stage 16. {ECO:0000269|PubMed:10323867,
CC ECO:0000269|PubMed:9125115}.
CC -!- PTM: Phosphorylated (By similarity). Autophosphorylated;
CC autophosphorylation is stimulated by GTP-bound Rho/Rac GTPases.
CC {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Embryonic lethal due to defects in dorsal
CC closure. {ECO:0000269|PubMed:10323867}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein
CC kinase family. {ECO:0000255|PROSITE-ProRule:PRU00159}.
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DR EMBL; AE013599; AAF58958.2; -; Genomic_DNA.
DR EMBL; BT099631; ACU64820.1; -; mRNA.
DR EMBL; BT099751; ACV82450.1; -; mRNA.
DR RefSeq; NP_788290.1; NM_176110.2. [A1Z7T0-1]
DR AlphaFoldDB; A1Z7T0; -.
DR SMR; A1Z7T0; -.
DR BioGRID; 61787; 12.
DR IntAct; A1Z7T0; 14.
DR PaxDb; A1Z7T0; -.
DR PRIDE; A1Z7T0; -.
DR EnsemblMetazoa; FBtr0088601; FBpp0087682; FBgn0020621. [A1Z7T0-1]
DR EnsemblMetazoa; FBtr0308206; FBpp0300526; FBgn0020621. [A1Z7T0-2]
DR GeneID; 35950; -.
DR KEGG; dme:Dmel_CG2049; -.
DR UCSC; CG2049-RB; d. melanogaster. [A1Z7T0-1]
DR CTD; 35950; -.
DR FlyBase; FBgn0020621; Pkn.
DR VEuPathDB; VectorBase:FBgn0020621; -.
DR eggNOG; KOG0694; Eukaryota.
DR GeneTree; ENSGT00940000168432; -.
DR InParanoid; A1Z7T0; -.
DR Reactome; R-DME-5625740; RHO GTPases activate PKNs.
DR Reactome; R-DME-5625886; Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3.
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; A1Z7T0; -.
DR BioGRID-ORCS; 35950; 0 hits in 3 CRISPR screens.
DR ChiTaRS; Pkn; fly.
DR GenomeRNAi; 35950; -.
DR PRO; PR:A1Z7T0; -.
DR Proteomes; UP000000803; Chromosome 2R.
DR Bgee; FBgn0020621; Expressed in head capsule and 34 other tissues.
DR ExpressionAtlas; A1Z7T0; baseline and differential.
DR Genevisible; A1Z7T0; DM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-SubCell.
DR GO; GO:0045179; C:apical cortex; IDA:FlyBase.
DR GO; GO:0032154; C:cleavage furrow; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; HDA:FlyBase.
DR GO; GO:0030027; C:lamellipodium; IEA:UniProtKB-SubCell.
DR GO; GO:0030496; C:midbody; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004698; F:calcium-dependent protein kinase C activity; IEA:UniProtKB-EC.
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; ISS:FlyBase.
DR GO; GO:0031267; F:small GTPase binding; IEA:InterPro.
DR GO; GO:0031532; P:actin cytoskeleton reorganization; IMP:FlyBase.
DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR GO; GO:0007391; P:dorsal closure; IMP:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0000281; P:mitotic cytokinesis; IMP:FlyBase.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IBA:GO_Central.
DR GO; GO:0090303; P:positive regulation of wound healing; IMP:FlyBase.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
DR GO; GO:1901648; P:regulation of actomyosin contractile ring localization; IMP:FlyBase.
DR GO; GO:0007472; P:wing disc morphogenesis; IMP:UniProtKB.
DR CDD; cd11622; HR1_PKN_1; 1.
DR InterPro; IPR000961; AGC-kinase_C.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR011072; HR1_rho-bd.
DR InterPro; IPR036274; HR1_rpt_sf.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR017892; Pkinase_C.
DR InterPro; IPR037313; PKN_HR1_1.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF02185; HR1; 3.
DR Pfam; PF00069; Pkinase; 1.
DR Pfam; PF00433; Pkinase_C; 1.
DR SMART; SM00239; C2; 1.
DR SMART; SM00742; Hr1; 3.
DR SMART; SM00133; S_TK_X; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF46585; SSF46585; 3.
DR SUPFAM; SSF49562; SSF49562; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS51285; AGC_KINASE_CTER; 1.
DR PROSITE; PS50004; C2; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
DR PROSITE; PS51860; REM_1; 3.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Cell adhesion; Cell cycle;
KW Cell division; Cell junction; Cell projection; Coiled coil; Cytoplasm;
KW Cytoskeleton; Developmental protein; Kinase; Membrane; Nucleotide-binding;
KW Nucleus; Phosphoprotein; Reference proteome; Repeat;
KW Serine/threonine-protein kinase; Transcription; Transcription regulation;
KW Transferase.
FT CHAIN 1..1190
FT /note="Serine/threonine-protein kinase N"
FT /id="PRO_0000415277"
FT DOMAIN 28..102
FT /note="REM-1 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01207"
FT DOMAIN 142..219
FT /note="REM-1 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01207"
FT DOMAIN 242..322
FT /note="REM-1 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01207"
FT DOMAIN 359..515
FT /note="C2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 863..1122
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 1123..1190
FT /note="AGC-kinase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT REGION 395..415
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 572..715
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 757..787
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 811..832
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 575..607
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 988
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 869..877
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 892
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT VAR_SEQ 729
FT /note="E -> EARISLVHITLEPINASRTTSCLIEEVAEPDSQPEIKPVAEAQSAKV
FT SEACVESILPETVEKLETADQVQQ (in isoform 2)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_042188"
FT MUTAGEN 58
FT /note="G->A: Inhibits interaction with Rac1 but not Rho1,
FT does not alter subcellular localization and is able to
FT rescue loss-of-function phenotype lethality."
FT /evidence="ECO:0000269|PubMed:10323867,
FT ECO:0000269|PubMed:17507675"
FT MUTAGEN 892
FT /note="K->D: Shows some nuclear localization."
FT /evidence="ECO:0000269|PubMed:17507675"
FT CONFLICT 680
FT /note="A -> V (in Ref. 3; ACV82450/ACU64820)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1190 AA; 131791 MW; D989403290E75B9B CRC64;
MSDSYYQGEY IKHPVLYELS HKYGFTENLP ESCMSIRLEE IKEAIRREIR KELKIKEGAE
KLREVAKDRR SLSDVAVLVK KSKSKLAELK SELQELESQI LLTSANTAVN SNGQESITAC
IDPNGGFLVS GAVGGLGGGN TALEGGAPAT ANDKVLASLE KQLQIEMKVK TGAENMIQSL
GIGCDKKLLA EAHQMLADSK AKIEFLRLRI IKVKQNREQA DRLKASRQMI DEHGQTIGGN
NSSQPQSLET TLEERIEELR HRLRIEAAVV DGAKNVIRTL QTANRAPDKK ALQEAHGRLS
ESSRKLDLLR YSLDLRRQEL PADSPAAQQL KTELQIVQLS TSPAPVTYTS LQSGQAGILG
GKPYQSVSSL GRCASVTGKL EVRLLGCQDL LEDVPGRSRR DKDNNSSPGD LRSFVKGVTS
RSSSKSYSVK DETSIEIMAV IKLDNITVGQ TSWKQCSQQA WDQRFSIDLD RSRELEIGVY
WRDWRSLCAV KVLRLEEFID DVRHGMALQL EPQGLLFAEV KFLNPMISQK PKLRRQRMIF
NRQQAKNISR AKQMNINVAT WGRLLKRNAP NHVHMGSAGS GSSLTGSSPM VVGGSRDSES
PISRTPSSDA LVEPEPYTPG EQAQNLEFDP DAGINEHVET PGEYPDPAAS GLSGMRPLSM
HMQGISVLPP ESPPVATGAA GRPNTLSLQM PGASKGQVIQ GGRTAAPTTA PPPPPVLKAT
STTPILDQEV IPQLGKLYVG SSQQQYAQQS SPIIQEPATP TIYGNSAAAG APQFPQPAQR
QEKQPPQQQP IYANQYELNV AKAAAAASVY SPSSSTTSNS NQQQQQQRRN VARGLQYRES
GGLETGRAGK QPPNAGMLSM DNFRLLSVLG RGHFGKVILS QLRSNNQYYA IKALKKGDII
ARDEVESLLS EKRIFEVANA MRHPFLVNLY SCFQTEQHVC FVMEYAAGGD LMMHIHTDVF
LEPRAVFYAA CVVLGLQYLH ENKIIYRDLK LDNLLLDTEG YVKIADFGLC KEGMGFGDRT
GTFCGTPEFL APEVLTETSY TRAVDWWGLG VLIFEMLVGE SPFPGDDEEE VFDSIVNDEV
RYPRFLSLEA IAVMRRLLRK NPERRLGSSE RDAEDVKKQA FFRSIVWDDL LLRKVKPPFV
PTINHLEDVS NFDEEFTSEK AQLTPPKEPR HLTEEEQLLF QDFSYTAEWC
