PAR4_CAEEL
ID PAR4_CAEEL Reviewed; 617 AA.
AC Q9GN62; G5EES7; G5EGA8; Q9Y0C1;
DT 22-SEP-2009, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2001, sequence version 2.
DT 03-AUG-2022, entry version 168.
DE RecName: Full=Serine/threonine-protein kinase par-4 {ECO:0000303|PubMed:10704392, ECO:0000312|EMBL:AAD45355.1};
DE EC=2.7.11.1;
GN Name=par-4; ORFNames=Y59A8B.14;
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:AAD45355.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), FUNCTION, SUBCELLULAR LOCATION,
RP TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RC STRAIN=Bristol N2 {ECO:0000312|EMBL:AAD45355.1};
RX PubMed=10704392; DOI=10.1242/dev.127.7.1467;
RA Watts J.L., Morton D.G., Bestman J., Kemphues K.J.;
RT "The Caenorhabditis elegans par-4 gene encodes a putative serine-threonine
RT kinase required for establishing embryonic asymmetry.";
RL Development 127:1467-1475(2000).
RN [2] {ECO:0000312|EMBL:CAC14418.2}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND ALTERNATIVE SPLICING.
RC STRAIN=Bristol N2 {ECO:0000312|EMBL:CAC14418.2};
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 [3] {ECO:0000305}
RP DISRUPTION PHENOTYPE.
RX PubMed=3345562; DOI=10.1016/s0092-8674(88)80024-2;
RA Kemphues K.J., Priess J.R., Morton D.G., Cheng N.S.;
RT "Identification of genes required for cytoplasmic localization in early C.
RT elegans embryos.";
RL Cell 52:311-320(1988).
RN [4] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=15574588; DOI=10.1101/gad.1255404;
RA Apfeld J., O'Connor G., McDonagh T., DiStefano P.S., Curtis R.;
RT "The AMP-activated protein kinase AAK-2 links energy levels and insulin-
RT like signals to lifespan in C. elegans.";
RL Genes Dev. 18:3004-3009(2004).
RN [5] {ECO:0000305}
RP FUNCTION.
RX PubMed=18842813; DOI=10.1242/dev.027060;
RA Tenlen J.R., Molk J.N., London N., Page B.D., Priess J.R.;
RT "MEX-5 asymmetry in one-cell C. elegans embryos requires PAR-4- and PAR-1-
RT dependent phosphorylation.";
RL Development 135:3665-3675(2008).
RN [6] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=18408008; DOI=10.1074/jbc.m709115200;
RA Lee H., Cho J.S., Lambacher N., Lee J., Lee S.J., Lee T.H., Gartner A.,
RA Koo H.S.;
RT "The Caenorhabditis elegans AMP-activated protein kinase AAK-2 is
RT phosphorylated by LKB1 and is required for resistance to oxidative stress
RT and for normal motility and foraging behavior.";
RL J. Biol. Chem. 283:14988-14993(2008).
RN [7]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=20023164; DOI=10.1242/dev.041459;
RA Kim J.S., Hung W., Narbonne P., Roy R., Zhen M.;
RT "C. elegans STRADalpha and SAD cooperatively regulate neuronal polarity and
RT synaptic organization.";
RL Development 137:93-102(2010).
RN [8]
RP FUNCTION, AND INTERACTION WITH STRD-1.
RX PubMed=20110331; DOI=10.1242/dev.042044;
RA Narbonne P., Hyenne V., Li S., Labbe J.C., Roy R.;
RT "Differential requirements for STRAD in LKB1-dependent functions in C.
RT elegans.";
RL Development 137:661-670(2010).
RN [9]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=21276723; DOI=10.1016/j.cub.2011.01.010;
RA Chartier N.T., Salazar Ospina D.P., Benkemoun L., Mayer M., Grill S.W.,
RA Maddox A.S., Labbe J.C.;
RT "PAR-4/LKB1 mobilizes nonmuscle myosin through anillin to regulate C.
RT elegans embryonic polarization and cytokinesis.";
RL Curr. Biol. 21:259-269(2011).
RN [10]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=21186357; DOI=10.1038/nn.2717;
RA Teichmann H.M., Shen K.;
RT "UNC-6 and UNC-40 promote dendritic growth through PAR-4 in Caenorhabditis
RT elegans neurons.";
RL Nat. Neurosci. 14:165-172(2011).
RN [11]
RP FUNCTION.
RX PubMed=22801495; DOI=10.1038/nature11240;
RA Denning D.P., Hatch V., Horvitz H.R.;
RT "Programmed elimination of cells by caspase-independent cell extrusion in
RT C. elegans.";
RL Nature 488:226-230(2012).
RN [12]
RP FUNCTION.
RX PubMed=23267054; DOI=10.1534/genetics.112.148106;
RA Chien S.C., Brinkmann E.M., Teuliere J., Garriga G.;
RT "Caenorhabditis elegans PIG-1/MELK acts in a conserved PAR-4/LKB1 polarity
RT pathway to promote asymmetric neuroblast divisions.";
RL Genetics 193:897-909(2013).
CC -!- FUNCTION: Required for cytoplasmic partitioning and asymmetric cell
CC division in early embryogenesis (PubMed:10704392). Controls the
CC asymmetric cell division of the Q.p neuroblast lineage
CC (PubMed:23267054). Involved in mediating cell polarization via
CC regulation of anillin family scaffold proteins (PubMed:21276723).
CC Phosphorylates and restricts the asymmetry effectors mex-5 and mex-6 to
CC the anterior cytoplasm of the zygote and maintains these
CC phosphorylations until fertilization (PubMed:18842813). May
CC phosphorylate par-1. Required for strd-1 localization to the cell
CC cortex of early embryos and may be required for strd-1 protein
CC stabilization. May regulate the integrity of the early embryonic cortex
CC in a strd-1-dependent manner (PubMed:20110331). Phosphorylates and
CC regulates aak-2 in response to oxidative stress and during dauer
CC development (PubMed:18408008, PubMed:20110331). May also play a role in
CC motility, behavioral response, regulation of lifespan and dauer
CC formation through this pathway (PubMed:15574588, PubMed:18408008).
CC Required to establish germline stem cell (GSC) quiescence during dauer
CC development (PubMed:20110331). Acts downstream of unc-40 in dendrite
CC outgrowth (PubMed:21186357). May play a role in cell shedding during
CC embryogenesis, probably by phosphorylating pig-1 (PubMed:22801495).
CC {ECO:0000269|PubMed:10704392, ECO:0000269|PubMed:15574588,
CC ECO:0000269|PubMed:18408008, ECO:0000269|PubMed:18842813,
CC ECO:0000269|PubMed:20023164, ECO:0000269|PubMed:20110331,
CC ECO:0000269|PubMed:21186357, ECO:0000269|PubMed:21276723,
CC ECO:0000269|PubMed:22801495, ECO:0000269|PubMed:23267054}.
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:Q15831};
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:Q15831};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q15831};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:Q15831};
CC -!- SUBUNIT: Interacts with strd-1. {ECO:0000269|PubMed:20110331}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cell cortex
CC {ECO:0000269|PubMed:10704392}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=a;
CC IsoId=Q9GN62-1; Sequence=Displayed;
CC Name=b;
CC IsoId=Q9GN62-2; Sequence=VSP_043926;
CC Name=c;
CC IsoId=Q9GN62-3; Sequence=VSP_043927;
CC -!- TISSUE SPECIFICITY: Expressed in the gonads, oocytes and early embryos
CC (at protein level). {ECO:0000269|PubMed:10704392}.
CC -!- DEVELOPMENTAL STAGE: Cortical distribution begins at the late 1-cell
CC stage, is more pronounced at the 2- and 4-cell stages and is reduced at
CC late stages of embryonic development. {ECO:0000269|PubMed:10704392}.
CC -!- DISRUPTION PHENOTYPE: Maternal effect lethality. Blastomeres cleave
CC synchronously until the fourth or fifth round, when synchrony breaks
CC down. Cells also fail to segregate P granules, with the posteriormost
CC blastomere tending to contain more P granules than other blastomeres.
CC Terminal stage embryos fail to produce intestinal cells. Adult worms
CC exhibit temperature-dependent reduction of oxidative-stress induced
CC aak-2 phosphorylation, hypersensitivity to oxidative stress, slow body
CC bending, abnormal modulation of head oscillation, and partially
CC suppress the lifespan extension and dauer-constitutive phenotypes of
CC aak-2 mutants. Cytokinesis cell polarity defeats; mispositioning of
CC anterior PAR proteins and defects in contractile ring ingression during
CC cytokinesis due to abnormal actomyosin contractility. Shortened
CC dendrites. {ECO:0000269|PubMed:10704392, ECO:0000269|PubMed:15574588,
CC ECO:0000269|PubMed:18408008, ECO:0000269|PubMed:20023164,
CC ECO:0000269|PubMed:21186357, ECO:0000269|PubMed:21276723,
CC ECO:0000269|PubMed:3345562}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. LKB1 subfamily. {ECO:0000255}.
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DR EMBL; AF160189; AAD45355.1; -; mRNA.
DR EMBL; AL132898; CAC14418.2; -; Genomic_DNA.
DR EMBL; AL132863; CAC14418.2; JOINED; Genomic_DNA.
DR EMBL; AL132898; CCA65681.1; -; Genomic_DNA.
DR EMBL; AL132863; CCA65681.1; JOINED; Genomic_DNA.
DR EMBL; AL132898; CCA65682.1; -; Genomic_DNA.
DR EMBL; AL132863; CCA65682.1; JOINED; Genomic_DNA.
DR RefSeq; NP_001256778.1; NM_001269849.1.
DR RefSeq; NP_001256779.1; NM_001269850.1.
DR RefSeq; NP_001256780.1; NM_001269851.1.
DR AlphaFoldDB; Q9GN62; -.
DR SMR; Q9GN62; -.
DR BioGRID; 45156; 2.
DR STRING; 6239.Y59A8B.14a; -.
DR EPD; Q9GN62; -.
DR PaxDb; Q9GN62; -.
DR PeptideAtlas; Q9GN62; -.
DR EnsemblMetazoa; Y59A8B.14a.1; Y59A8B.14a.1; WBGene00003919. [Q9GN62-1]
DR EnsemblMetazoa; Y59A8B.14b.1; Y59A8B.14b.1; WBGene00003919. [Q9GN62-2]
DR EnsemblMetazoa; Y59A8B.14c.1; Y59A8B.14c.1; WBGene00003919. [Q9GN62-3]
DR UCSC; Y59A8B.14; c. elegans. [Q9GN62-1]
DR WormBase; Y59A8B.14a; CE27410; WBGene00003919; par-4. [Q9GN62-1]
DR WormBase; Y59A8B.14b; CE46046; WBGene00003919; par-4. [Q9GN62-2]
DR WormBase; Y59A8B.14c; CE46081; WBGene00003919; par-4. [Q9GN62-3]
DR eggNOG; KOG0583; Eukaryota.
DR GeneTree; ENSGT00940000158050; -.
DR InParanoid; Q9GN62; -.
DR OMA; RIMERMR; -.
DR OrthoDB; 856506at2759; -.
DR PhylomeDB; Q9GN62; -.
DR PRO; PR:Q9GN62; -.
DR Proteomes; UP000001940; Chromosome V.
DR Bgee; WBGene00003919; Expressed in adult organism and 3 other tissues.
DR GO; GO:0005938; C:cell cortex; IDA:WormBase.
DR GO; GO:0005737; C:cytoplasm; IDA:WormBase.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005516; F:calmodulin binding; IPI:WormBase.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IMP:WormBase.
DR GO; GO:0008356; P:asymmetric cell division; IMP:WormBase.
DR GO; GO:0055059; P:asymmetric neuroblast division; IMP:WormBase.
DR GO; GO:0045167; P:asymmetric protein localization involved in cell fate determination; IMP:WormBase.
DR GO; GO:0030154; P:cell differentiation; IMP:WormBase.
DR GO; GO:0008340; P:determination of adult lifespan; IGI:WormBase.
DR GO; GO:0030010; P:establishment of cell polarity; IMP:WormBase.
DR GO; GO:0007163; P:establishment or maintenance of cell polarity; IMP:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; IMP:WormBase.
DR GO; GO:0061066; P:positive regulation of dauer larval development; IGI:WormBase.
DR GO; GO:0040017; P:positive regulation of locomotion; IMP:WormBase.
DR GO; GO:0006468; P:protein phosphorylation; IBA:GO_Central.
DR GO; GO:0031991; P:regulation of actomyosin contractile ring contraction; IMP:UniProtKB.
DR GO; GO:0006979; P:response to oxidative stress; IMP:WormBase.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 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; Cytoplasm; Developmental protein;
KW Kinase; Magnesium; Manganese; Metal-binding; Nucleotide-binding;
KW Reference proteome; Serine/threonine-protein kinase; Stress response;
KW Transferase.
FT CHAIN 1..617
FT /note="Serine/threonine-protein kinase par-4"
FT /id="PRO_0000383653"
FT DOMAIN 183..446
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..59
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 523..617
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 17..32
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 564..579
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 310
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P28523,
FT ECO:0000255|PROSITE-ProRule:PRU00159, ECO:0000255|PROSITE-
FT ProRule:PRU10027"
FT BINDING 189..197
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P28523,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 212
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P28523,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT VAR_SEQ 1..141
FT /note="Missing (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_043926"
FT VAR_SEQ 161..164
FT /note="Missing (in isoform c)"
FT /evidence="ECO:0000305"
FT /id="VSP_043927"
SQ SEQUENCE 617 AA; 69648 MW; 9E8451AE18BE5DCA CRC64;
MDAPSTSSGA QSKLLMPGDD EADEDHQNRG DPNLQQKQKI QLNVDPDYDD DEDDDCFIDG
CEASAPITRE LVDGAIERRS KDRNVKMSIG VYDEYDDDDD DEEETEEDQR RRFVEGIRNI
RHKQQESFDL EEHPIPVESE AMRQFINQQV NNAMMFNQDN SEFQHIEFEP IVKQKGPKII
EGYMWGGQIG TGSYGKVKEC IDMYTLTRRA VKIMKYDKLR KITNGWENIR SEMSILRRMN
HRNVIKLIEI FNIPAKGKVY MVFEYCIGSV QQLLDMEPAR RLTIGESHAI FIELCQGLNY
LHSKRVSHKD IKPGNLLVSI DFTVKICDFG VAEQINLFQR DGRCTKVNGT PKFQPPECIY
GNHDFFDGYK ADMWSAGVTL YNLVSGKYPF EKPVLLKLYE CIGTEPLQMP TNVQLTKDLQ
DLLTKLLEKD FNERPTCLET MIHPWFLSTF PEDQGLGRIM ERMRTGDRPL TMLSSMTALY
DGITPEDELI IEDNLGIIQQ ILPINLTSEA VLERGSFPGF KFLEAKPGDG PDGVEGSEDS
AAPLGPQRRP SSRSMPTCAP PGPAAGNAQN STAENGAETD GVASASDPPP TAAPGAPPRR
RKRNFFSCIF RSRTDSA
