CHK1_CAEEL
ID CHK1_CAEEL Reviewed; 503 AA.
AC Q9N3Z3; Q17375; Q86FM7;
DT 27-SEP-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2001, sequence version 2.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=Serine/threonine-protein kinase chk-1;
DE EC=2.7.11.1;
GN Name=chk-1 {ECO:0000312|WormBase:Y39H10A.7a};
GN ORFNames=Y39H10A.7 {ECO:0000312|WormBase:Y39H10A.7a};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A).
RA Winge P., Goebel V., Fleming J.T.;
RL Submitted (JAN-1996) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
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 [3]
RP FUNCTION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=15326393;
RA Kalogeropoulos N., Christoforou C., Green A.J., Gill S., Ashcroft N.R.;
RT "chk-1 is an essential gene and is required for an S-M checkpoint during
RT early embryogenesis.";
RL Cell Cycle 3:1196-1200(2004).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE,
RP AND PHOSPHORYLATION AT SER-344.
RX PubMed=26073019; DOI=10.1016/j.devcel.2015.04.019;
RA Butuci M., Williams A.B., Wong M.M., Kramer B., Michael W.M.;
RT "Zygotic genome activation triggers chromosome damage and checkpoint
RT signaling in C. elegans primordial germ cells.";
RL Dev. Cell 34:85-95(2015).
RN [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=27956467; DOI=10.1083/jcb.201604112;
RA Lawrence K.S., Tapley E.C., Cruz V.E., Li Q., Aung K., Hart K.C.,
RA Schwartz T.U., Starr D.A., Engebrecht J.;
RT "LINC complexes promote homologous recombination in part through inhibition
RT of nonhomologous end joining.";
RL J. Cell Biol. 215:801-821(2016).
CC -!- FUNCTION: Serine/threonine-protein kinase which is required for
CC checkpoint-mediated cell cycle arrest and activation of DNA repair in
CC response to the presence of DNA damage or unreplicated DNA
CC (PubMed:15326393). May also negatively regulate cell cycle progression
CC during unperturbed cell cycles (PubMed:15326393). Required for
CC checkpoint mediated cell cycle arrest in response to DNA damage in
CC germline cells (PubMed:15326393, PubMed:27956467). Delays cell-cycle
CC reentry of the Z2 and Z3 primordial germ cells in response to
CC transcription-induced DNA damage as they emerge from cell cycle arrest
CC in L1 larvae (PubMed:26073019). Essential for embryogenesis
CC (PubMed:15326393). {ECO:0000269|PubMed:15326393,
CC ECO:0000269|PubMed:26073019, ECO:0000269|PubMed:27956467}.
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 -!- 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;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:26073019}. Nucleus
CC {ECO:0000250|UniProtKB:O61661}. Cytoplasm, perinuclear region
CC {ECO:0000269|PubMed:26073019}. Note=The Ser-344 phosphorylated form
CC colocalizes with P granules in a perinuclear manner in embryonic
CC germline precursor cells and in Z2/Z3 primordial germ cells in L1 stage
CC larvae. {ECO:0000269|PubMed:26073019}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=a {ECO:0000312|WormBase:Y39H10A.7a};
CC IsoId=Q9N3Z3-1; Sequence=Displayed;
CC Name=b {ECO:0000312|WormBase:Y39H10A.7b};
CC IsoId=Q9N3Z3-2; Sequence=VSP_015771;
CC -!- TISSUE SPECIFICITY: Expressed in the germline.
CC {ECO:0000269|PubMed:15326393, ECO:0000269|PubMed:26073019}.
CC -!- DEVELOPMENTAL STAGE: Highly expressed in the embryo.
CC {ECO:0000269|PubMed:15326393}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown leads to premature cell-
CC cycle reentry of the Z2/Z3 primordial germ cells in L1 stage larvae
CC (PubMed:26073019). RNAi-mediated knockdown and DNA damage induced by
CC the ribonucleotide reductase inhibitor hydroxyurea in germ cells
CC results in impaired DNA repair, but does allow for nuclear division
CC (PubMed:27956467). In the proliferative zone of these germ cells,
CC nuclei do not arrest following DNA damage, but prematurely divide and
CC are smaller compared to wild-type (PubMed:27956467).
CC {ECO:0000269|PubMed:26073019, ECO:0000269|PubMed:27956467}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. NIM1 subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA93318.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=CCD73288.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; U44902; AAA93318.1; ALT_FRAME; mRNA.
DR EMBL; BX284605; CCD73287.1; -; Genomic_DNA.
DR EMBL; BX284605; CCD73288.1; ALT_INIT; Genomic_DNA.
DR RefSeq; NP_001024233.1; NM_001029062.3.
DR RefSeq; NP_001024234.1; NM_001029063.2.
DR AlphaFoldDB; Q9N3Z3; -.
DR SMR; Q9N3Z3; -.
DR BioGRID; 533239; 14.
DR IntAct; Q9N3Z3; 2.
DR MINT; Q9N3Z3; -.
DR STRING; 6239.Y39H10A.7a.2; -.
DR iPTMnet; Q9N3Z3; -.
DR EPD; Q9N3Z3; -.
DR PaxDb; Q9N3Z3; -.
DR PeptideAtlas; Q9N3Z3; -.
DR EnsemblMetazoa; Y39H10A.7a.1; Y39H10A.7a.1; WBGene00000498. [Q9N3Z3-1]
DR EnsemblMetazoa; Y39H10A.7b.1; Y39H10A.7b.1; WBGene00000498.
DR GeneID; 3565921; -.
DR UCSC; Y39H10A.7a; c. elegans. [Q9N3Z3-1]
DR CTD; 3565921; -.
DR WormBase; Y39H10A.7a; CE26076; WBGene00000498; chk-1. [Q9N3Z3-1]
DR WormBase; Y39H10A.7b; CE33867; WBGene00000498; chk-1. [Q9N3Z3-2]
DR eggNOG; KOG0590; Eukaryota.
DR GeneTree; ENSGT00940000167959; -.
DR InParanoid; Q9N3Z3; -.
DR OMA; PPWDRLF; -.
DR OrthoDB; 698464at2759; -.
DR PhylomeDB; Q9N3Z3; -.
DR Reactome; R-CEL-5693616; Presynaptic phase of homologous DNA pairing and strand exchange.
DR PRO; PR:Q9N3Z3; -.
DR Proteomes; UP000001940; Chromosome V.
DR Bgee; WBGene00000498; Expressed in germ line (C elegans) and 4 other tissues.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP 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; IBA:GO_Central.
DR GO; GO:0000077; P:DNA damage checkpoint signaling; IEA:InterPro.
DR GO; GO:0009792; P:embryo development ending in birth or egg hatching; IGI:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0033314; P:mitotic DNA replication checkpoint signaling; IMP:WormBase.
DR GO; GO:0006468; P:protein phosphorylation; IBA:GO_Central.
DR CDD; cd14069; STKc_Chk1; 1.
DR InterPro; IPR034670; Chk1_catalytic_dom.
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; Cell cycle; Cytoplasm;
KW Developmental protein; DNA damage; Kinase; Nucleotide-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Serine/threonine-protein kinase;
KW Transferase.
FT CHAIN 1..503
FT /note="Serine/threonine-protein kinase chk-1"
FT /id="PRO_0000085854"
FT DOMAIN 24..286
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 320..346
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 150
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 30..38
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 54
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 344
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:26073019"
FT VAR_SEQ 1..89
FT /note="Missing (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_015771"
FT CONFLICT 402
FT /note="V -> L (in Ref. 1; AAA93318)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 503 AA; 56935 MW; D9634ABE7F433CB7 CRC64;
MSAASTTSTP AAAAVAPQQP ESLYRVVQTL GEGAFGEVLL IVNTKNPEVA AAMKKINIAN
KSKDFIDNIR KEYLLQKRVS AVGHDNVIRM IGMRNDPQFY YLFLEYADGG ELFDKIEPDC
GMSPVFAQFY FKQLICGLKF IHDNDVVHRD IKPENLLLTG THVLKISDFG MATLYRNKGE
ERLLDLSCGT IPYAAPELCA GKKYRGPPVD VWSSGIVLIA MLTGELPWDR ASDASQSYMG
WISNTSLDER PWKKIDVRAL CMLRKIVTDK TDKRATIEQI QADPWYQHNF GQVETPNGRP
LKRARNNDEN ITCTQQAECS AKRRHLETPN EKSTLAERQN ASFSQPTKTE DLLLTQHIDM
SQTNSNLLQR MVCRMTRFCV VTDIRSTYQK VARASEHAGF GVRETDDYRL LVTWREVSMM
VSLYTMGDIP DKPRVMVDFR RSRGDGIQFK KMFMDVRNRM HEWICTDGNN WLANLGYVPR
NPQIVNGGGV NVEHSASSIN VDV
