PK1_CAEEL
ID PK1_CAEEL Reviewed; 572 AA.
AC Q17850; Q22041; Q86GT8; Q86GT9; Q86GU0; Q94133;
DT 31-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2001, sequence version 2.
DT 03-AUG-2022, entry version 178.
DE RecName: Full=Serine/threonine-protein kinase pak-1;
DE EC=2.7.11.1 {ECO:0000269|PubMed:8824291};
DE AltName: Full=CePAK;
DE AltName: Full=p21-activated kinase 1;
DE Short=PAK1;
GN Name=pak-1; ORFNames=C09B8.7;
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1] {ECO:0000305, ECO:0000312|EMBL:AAC47308.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), FUNCTION, CATALYTIC ACTIVITY,
RP COFACTOR, INTERACTION WITH CDC-42 AND CED-10, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, AND DEVELOPMENTAL STAGE.
RC STRAIN=Bristol N2 {ECO:0000312|EMBL:AAC47308.1};
RC TISSUE=Embryo {ECO:0000269|PubMed:8824291};
RX PubMed=8824291; DOI=10.1074/jbc.271.42.26362;
RA Chen W., Chen S., Yap S.F., Lim L.;
RT "The Caenorhabditis elegans p21-activated kinase (CePAK) colocalizes with
RT CeRac1 and CDC42Ce at hypodermal cell boundaries during embryo
RT elongation.";
RL J. Biol. Chem. 271:26362-26368(1996).
RN [2] {ECO:0000305, ECO:0000312|EMBL:BAA11844.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B), SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RC STRAIN=Bristol N2 {ECO:0000312|EMBL:BAA11844.1}; TISSUE=Embryo;
RX PubMed=9535804; DOI=10.1006/bbrc.1998.8380;
RA Iino Y., Yamamoto M.;
RT "Expression pattern of the C. elegans p21-activated protein kinase,
RT CePAK.";
RL Biochem. Biophys. Res. Commun. 245:177-184(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND ALTERNATIVE SPLICING.
RC STRAIN=Bristol N2;
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [4]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=17050621; DOI=10.1242/dev.02648;
RA Lucanic M., Kiley M., Ashcroft N., L'Etoile N., Cheng H.J.;
RT "The Caenorhabditis elegans P21-activated kinases are differentially
RT required for UNC-6/netrin-mediated commissural motor axon guidance.";
RL Development 133:4549-4559(2006).
RN [5]
RP FUNCTION.
RX PubMed=18499456; DOI=10.1016/j.cub.2008.04.050;
RA Quinn C.C., Pfeil D.S., Wadsworth W.G.;
RT "CED-10/Rac1 mediates axon guidance by regulating the asymmetric
RT distribution of MIG-10/lamellipodin.";
RL Curr. Biol. 18:808-813(2008).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE,
RP AND MUTAGENESIS OF SER-68.
RX PubMed=19023419; DOI=10.1371/journal.pgen.1000269;
RA Lucanic M., Cheng H.J.;
RT "A RAC/CDC-42-independent GIT/PIX/PAK signaling pathway mediates cell
RT migration in C. elegans.";
RL PLoS Genet. 4:E1000269-E1000269(2008).
RN [7]
RP FUNCTION.
RX PubMed=19675126; DOI=10.1242/dev.039412;
RA Gally C., Wissler F., Zahreddine H., Quintin S., Landmann F., Labouesse M.;
RT "Myosin II regulation during C. elegans embryonic elongation: LET-502/ROCK,
RT MRCK-1 and PAK-1, three kinases with different roles.";
RL Development 136:3109-3119(2009).
RN [8]
RP FUNCTION, AND MUTAGENESIS OF 234-ARG-PRO-235 AND LYS-324.
RX PubMed=19797046; DOI=10.1534/genetics.109.106880;
RA Locke C.J., Kautu B.B., Berry K.P., Lee S.K., Caldwell K.A., Caldwell G.A.;
RT "Pharmacogenetic analysis reveals a post-developmental role for Rac GTPases
RT in Caenorhabditis elegans GABAergic neurotransmission.";
RL Genetics 183:1357-1372(2009).
CC -!- FUNCTION: Required for hypodermal cell fusion, together with cdc-42 and
CC ced-10, leading to embryonic body elongation, which involves dramatic
CC cytoskeletal reorganization (PubMed:8824291). Plays a redundant role
CC with max-2 in dorsal axonal guidance in ventral cord commissural
CC motoneurons and in P neuroblast migration. Acts probably downstream of
CC Rho GTPases mig-2 and ced-10 to regulate these 2 processes
CC (PubMed:17050621). Involved in orientating axonal growth of HSN neurons
CC (PubMed:18499456). During gonad morphogenesis and probably in
CC association with pix-1 and git-1, involved in the migration of distal
CC tip cell (DTC) and in maintaining their sharp tapering morphology. In
CC addition, plays a redundant role with max-2 in DTC-mediated guidance of
CC gonad elongation (PubMed:19023419, PubMed:19797046). May phosphorylate
CC mlc-4 (PubMed:19675126). {ECO:0000269|PubMed:17050621,
CC ECO:0000269|PubMed:18499456, ECO:0000269|PubMed:19023419,
CC ECO:0000269|PubMed:19797046, ECO:0000269|PubMed:8824291,
CC ECO:0000305|PubMed:19675126}.
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:8824291};
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:8824291};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:8824291};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:8824291};
CC Note=Divalent cations such as magnesium or manganese.
CC {ECO:0000269|PubMed:8824291};
CC -!- SUBUNIT: Interacts with cdc-42 (GTP-bound form) and cedd-10 (GTP-bound
CC form). {ECO:0000269|PubMed:8824291}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:8824291,
CC ECO:0000269|PubMed:9535804}; Peripheral membrane protein
CC {ECO:0000269|PubMed:8824291, ECO:0000269|PubMed:9535804}. Cytoplasm
CC {ECO:0000269|PubMed:19023419}. Cell projection, axon
CC {ECO:0000269|PubMed:9535804}. Perikaryon {ECO:0000269|PubMed:9535804}.
CC Note=Co-localizes with ced-10/rac-1 and cdc-42 at hypodermal cell
CC boundaries during embryo elongation (PubMed:8824291). Preferentially
CC enriched at pharyngeal muscle cells boundaries (PubMed:9535804). In CAN
CC neurons, detected in the cell bodies and along the axons
CC (PubMed:9535804). Remains diffused in the cytoplasm during distal tip
CC cell (DTC) migration (PubMed:19023419). {ECO:0000269|PubMed:19023419,
CC ECO:0000269|PubMed:8824291, ECO:0000269|PubMed:9535804}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=a {ECO:0000269|PubMed:8824291};
CC IsoId=Q17850-1; Sequence=Displayed;
CC Name=b {ECO:0000269|PubMed:9535804};
CC IsoId=Q17850-2; Sequence=VSP_051596, VSP_042128;
CC Name=c;
CC IsoId=Q17850-3; Sequence=VSP_051593, VSP_051596;
CC Name=e;
CC IsoId=Q17850-5; Sequence=VSP_051595;
CC -!- TISSUE SPECIFICITY: Specifically colocalized with cdc-42 and ced-10 at
CC all hypodermal cell boundaries during embryo elongation throughout the
CC second phase of embryogenesis. Expressed mainly in pharyngeal muscles,
CC the CAN neurons, motor neurons in the ventral nerve cord, several cells
CC in the tail region (including the B and Y cells from L1 to adult, the
CC hypodermal blast cell T in the L1 and some of its progeny in later
CC stages), and the distal tip cells. {ECO:0000269|PubMed:17050621,
CC ECO:0000269|PubMed:19023419, ECO:0000269|PubMed:8824291,
CC ECO:0000269|PubMed:9535804}.
CC -!- DEVELOPMENTAL STAGE: Highly expressed at the embryonic stage, with
CC decreasing expression from L1 onwards. {ECO:0000269|PubMed:8824291}.
CC -!- DISRUPTION PHENOTYPE: In pak-1 and pak-2 double mutants, defects in
CC embryogenesis and L1 stage lethality. The few animals reaching
CC adulthood have normal ventral cord commissural motoneuron axonal
CC guidance and are relatively coordinated. In max-2 and pak-1 double
CC mutants, DD and DC motoneuron axons fail to reach the dorsal cord
CC (PubMed:17050621). Animals are also uncoordinated, defective in egg
CC laying and in distal tip cell (DTC) migration, guidance and morphology,
CC and exhibit ventral enclosure defects (PubMed:17050621,
CC PubMed:19023419). {ECO:0000269|PubMed:17050621,
CC ECO:0000269|PubMed:19023419}.
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; U63744; AAC47308.1; -; mRNA.
DR EMBL; D83215; BAA11844.1; -; mRNA.
DR EMBL; FO080450; CCD63804.1; -; Genomic_DNA.
DR EMBL; FO080450; CCD63805.1; -; Genomic_DNA.
DR EMBL; FO080450; CCD63806.1; -; Genomic_DNA.
DR EMBL; FO080450; CCD63807.1; -; Genomic_DNA.
DR PIR; T15467; T15467.
DR RefSeq; NP_001024377.1; NM_001029206.2. [Q17850-1]
DR RefSeq; NP_001024378.1; NM_001029207.2. [Q17850-2]
DR RefSeq; NP_001024379.1; NM_001029208.3.
DR RefSeq; NP_001024380.1; NM_001029209.3.
DR AlphaFoldDB; Q17850; -.
DR SMR; Q17850; -.
DR BioGRID; 45805; 27.
DR DIP; DIP-26715N; -.
DR IntAct; Q17850; 1.
DR STRING; 6239.C09B8.7a; -.
DR EPD; Q17850; -.
DR PaxDb; Q17850; -.
DR PeptideAtlas; Q17850; -.
DR EnsemblMetazoa; C09B8.7a.1; C09B8.7a.1; WBGene00003911. [Q17850-1]
DR EnsemblMetazoa; C09B8.7b.1; C09B8.7b.1; WBGene00003911. [Q17850-2]
DR EnsemblMetazoa; C09B8.7c.1; C09B8.7c.1; WBGene00003911.
DR GeneID; 180873; -.
DR KEGG; cel:CELE_C09B8.7; -.
DR UCSC; C09B8.7e.2; c. elegans. [Q17850-1]
DR CTD; 180873; -.
DR WormBase; C09B8.7a; CE27670; WBGene00003911; pak-1. [Q17850-1]
DR WormBase; C09B8.7b; CE06792; WBGene00003911; pak-1. [Q17850-2]
DR WormBase; C09B8.7c; CE33559; WBGene00003911; pak-1.
DR WormBase; C09B8.7e; CE33561; WBGene00003911; pak-1. [Q17850-5]
DR eggNOG; KOG0578; Eukaryota.
DR GeneTree; ENSGT00940000165560; -.
DR InParanoid; Q17850; -.
DR OMA; WYDASAT; -.
DR OrthoDB; 757766at2759; -.
DR PhylomeDB; Q17850; -.
DR Reactome; R-CEL-2029482; Regulation of actin dynamics for phagocytic cup formation.
DR Reactome; R-CEL-376172; DSCAM interactions.
DR Reactome; R-CEL-389359; CD28 dependent Vav1 pathway.
DR Reactome; R-CEL-3928662; EPHB-mediated forward signaling.
DR Reactome; R-CEL-3928664; Ephrin signaling.
DR Reactome; R-CEL-399954; Sema3A PAK dependent Axon repulsion.
DR Reactome; R-CEL-445144; Signal transduction by L1.
DR Reactome; R-CEL-5218920; VEGFR2 mediated vascular permeability.
DR Reactome; R-CEL-5621575; CD209 (DC-SIGN) signaling.
DR Reactome; R-CEL-5627123; RHO GTPases activate PAKs.
DR Reactome; R-CEL-5687128; MAPK6/MAPK4 signaling.
DR Reactome; R-CEL-8964616; G beta:gamma signalling through CDC42.
DR Reactome; R-CEL-9013149; RAC1 GTPase cycle.
DR Reactome; R-CEL-9013407; RHOH GTPase cycle.
DR Reactome; R-CEL-9013420; RHOU GTPase cycle.
DR Reactome; R-CEL-9013424; RHOV GTPase cycle.
DR PRO; PR:Q17850; -.
DR Proteomes; UP000001940; Chromosome X.
DR Bgee; WBGene00003911; Expressed in pharyngeal muscle cell (C elegans) and 9 other tissues.
DR GO; GO:0030424; C:axon; IDA:WormBase.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:WormBase.
DR GO; GO:0030056; C:hemidesmosome; IDA:WormBase.
DR GO; GO:0016021; C:integral component of membrane; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IDA:WormBase.
DR GO; GO:0043025; C:neuronal cell body; IDA:WormBase.
DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:WormBase.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005525; F:GTP binding; IDA:UniProtKB.
DR GO; GO:0004672; F:protein kinase activity; IDA:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IBA:GO_Central.
DR GO; GO:0016477; P:cell migration; IGI:UniProtKB.
DR GO; GO:0010172; P:embryonic body morphogenesis; IGI:WormBase.
DR GO; GO:0048598; P:embryonic morphogenesis; IGI:WormBase.
DR GO; GO:0035262; P:gonad morphogenesis; IMP:WormBase.
DR GO; GO:0031581; P:hemidesmosome assembly; IGI:WormBase.
DR GO; GO:0040039; P:inductive cell migration; IMP:WormBase.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0008045; P:motor neuron axon guidance; IGI:UniProtKB.
DR GO; GO:0002119; P:nematode larval development; IMP:WormBase.
DR GO; GO:0006468; P:protein phosphorylation; IBA:GO_Central.
DR GO; GO:0050770; P:regulation of axonogenesis; IBA:GO_Central.
DR GO; GO:0043408; P:regulation of MAPK cascade; IBA:GO_Central.
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 Alternative splicing; ATP-binding; Cell membrane; Cell projection;
KW Cytoplasm; Developmental protein; Kinase; Magnesium; Manganese; Membrane;
KW Neurogenesis; Nucleotide-binding; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..572
FT /note="Serine/threonine-protein kinase pak-1"
FT /id="PRO_0000086463"
FT DOMAIN 67..80
FT /note="CRIB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00057"
FT DOMAIN 295..546
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..71
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 81..294
FT /note="Linker"
FT REGION 156..195
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 36..65
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 174..195
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 414
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q13153,
FT ECO:0000255|PROSITE-ProRule:PRU00159, ECO:0000255|PROSITE-
FT ProRule:PRU10027"
FT BINDING 301..309
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q13153,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 324
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q13153,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT VAR_SEQ 1..448
FT /note="Missing (in isoform e)"
FT /evidence="ECO:0000305"
FT /id="VSP_051595"
FT VAR_SEQ 1..46
FT /note="Missing (in isoform c)"
FT /evidence="ECO:0000305"
FT /id="VSP_051593"
FT VAR_SEQ 139..141
FT /note="Missing (in isoform b and isoform c)"
FT /evidence="ECO:0000303|PubMed:9535804"
FT /id="VSP_051596"
FT VAR_SEQ 142
FT /note="D -> N (in isoform b)"
FT /evidence="ECO:0000303|PubMed:9535804"
FT /id="VSP_042128"
FT MUTAGEN 68
FT /note="S->P: May prevent interaction with Rho GTPases.
FT Defect in commissural axon guidance in ventral motoneurons
FT in an RNAi-mediated max-2 knockdown background. Rescues
FT anterior gonad morphology defects in pax-1 ok488 mutants."
FT /evidence="ECO:0000269|PubMed:19023419"
FT MUTAGEN 234..235
FT /note="RP->AA: May prevent interaction with pix-1. Fails to
FT rescue distal tip cell migration defect in an RNAi-mediated
FT max-2 knockdown background."
FT /evidence="ECO:0000269|PubMed:19797046"
FT MUTAGEN 324
FT /note="K->R: Probable loss of activity. Fails to rescue
FT distal tip cell migration defect in an RNAi-mediated max-2
FT knockdown background."
FT /evidence="ECO:0000269|PubMed:19797046"
FT CONFLICT 435
FT /note="F -> L (in Ref. 1; AAC47308)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 572 AA; 63881 MW; B8D74B0386343B78 CRC64;
MKAFSSYDEK PPAPPIRFSS SATRENQVVG LKPLPKEPEA TKKKKTMPNP FMKKNKDKKE
ASEKPVISRP SNFEHTIHVG YDPKTGEFTG MPEAWARLLT DSQISKQEQQ QNPQAVLDAL
KYYTQGESSG QKWLQYDMMF IDDAPSRTPS YGLKPQPYST SSLPYHGNKI QDPRKMNPMT
TSTSSAGYNS KQGVPPTTFS VNENRSSMPP SYAPPPVPHG ETPADIVPPA IPDRPARTLS
IYTKPKEEEE KIPDLSKGQF GVQARGQKAK KKMTDAEVLT KLRTIVSIGN PDRKYRKVDK
IGSGASGSVY TAIEISTEAE VAIKQMNLKD QPKKELIINE ILVMRENKHA NIVNYLDSYL
VCDELWVVME YLAGGSLTDV VTECQMEDGI IAAVCREVLQ ALEFLHSRHV IHRDIKSDNI
LLGMDGSVKL TDFGFCAQLS PEQRKRTTMV GTPYWMAPEV VTRKQYGPKV DVWSLGIMAI
EMVEGEPPYL NENPLRAIYL IATNGKPDFP GRDSMTLLFK DFVDSALEVQ VENRWSASQL
LTHPFLRCAK PLASLYYLIV AAKKSIAEAS NS
