CHK1_CHICK
ID CHK1_CHICK Reviewed; 476 AA.
AC Q8AYC9;
DT 27-SEP-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 128.
DE RecName: Full=Serine/threonine-protein kinase Chk1;
DE EC=2.7.11.1 {ECO:0000250|UniProtKB:O14757};
DE AltName: Full=CHK1 checkpoint homolog;
DE AltName: Full=Checkpoint kinase-1;
GN Name=CHEK1; Synonyms=CHK1;
OS Gallus gallus (Chicken).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC Phasianinae; Gallus.
OX NCBI_TaxID=9031;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND PHOSPHORYLATION AT SER-345.
RX PubMed=12554671; DOI=10.1093/emboj/cdg060;
RA Zachos G., Rainey M.D., Gillespie D.A.F.;
RT "Chk1-deficient tumour cells are viable but exhibit multiple checkpoint and
RT survival defects.";
RL EMBO J. 22:713-723(2003).
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:12554671). May also negatively regulate cell cycle progression
CC during unperturbed cell cycles. This regulation is achieved by a number
CC of mechanisms that together help to preserve the integrity of the
CC genome. Recognizes the substrate consensus sequence [R-X-X-S/T]. Binds
CC to and phosphorylates CDC25A, CDC25B and CDC25C. This inhibits their
CC activity through proteasomal degradation, nucleo-cytoplasmic shuttling
CC and inhibition by proteins of the 13-3-3 family. Inhibition of CDC25
CC leads to increased inhibitory tyrosine phosphorylation of CDK-cyclin
CC complexes and blocks cell cycle progression. May promote DNA repair,
CC regulate chromatin assembly and the transcription of genes that
CC regulate cell-cycle progression. May also play a role in replication
CC fork maintenance (By similarity). {ECO:0000250|UniProtKB:O14757,
CC ECO:0000269|PubMed:12554671}.
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:O14757};
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:O14757};
CC -!- ACTIVITY REGULATION: Activated through phosphorylation by atr or atm in
CC response to DNA damage or inhibition of DNA replication.
CC {ECO:0000250|UniProtKB:O14757}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:O14757}.
CC Chromosome {ECO:0000250|UniProtKB:O14757}. Cytoplasm
CC {ECO:0000250|UniProtKB:O14757}. Cytoplasm, cytoskeleton, microtubule
CC organizing center, centrosome {ECO:0000250|UniProtKB:O14757}.
CC -!- DOMAIN: The autoinhibitory region (AIR) inhibits the activity of the
CC kinase domain. {ECO:0000250|UniProtKB:Q6DE87}.
CC -!- PTM: Phosphorylated by ATR in a RAD17-dependent manner in response to
CC ultraviolet irradiation and inhibition of DNA replication.
CC Phosphorylated by ATM in response to ionizing irradiation (By
CC similarity). Phosphorylation at Ser-345 induces a change in the
CC conformation of the protein and activates the kinase activity.
CC Phosphorylation at Ser-345 also increases binding to 14-3-3 proteins
CC and promotes nuclear retention (PubMed:12554671).
CC {ECO:0000250|UniProtKB:O14757, ECO:0000269|PubMed:12554671}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. NIM1 subfamily. {ECO:0000305}.
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DR EMBL; AF525027; AAN33019.1; -; mRNA.
DR RefSeq; NP_989676.1; NM_204345.1.
DR AlphaFoldDB; Q8AYC9; -.
DR SMR; Q8AYC9; -.
DR BioGRID; 675270; 1.
DR STRING; 9031.ENSGALP00000001432; -.
DR iPTMnet; Q8AYC9; -.
DR PaxDb; Q8AYC9; -.
DR GeneID; 374260; -.
DR KEGG; gga:374260; -.
DR CTD; 1111; -.
DR VEuPathDB; HostDB:geneid_374260; -.
DR eggNOG; KOG0590; Eukaryota.
DR InParanoid; Q8AYC9; -.
DR OrthoDB; 698464at2759; -.
DR PhylomeDB; Q8AYC9; -.
DR Reactome; R-GGA-217106; Chk1-controlled and DNA-damage induced centrosome duplication.
DR Reactome; R-GGA-351433; ATM mediated phosphorylation of repair proteins.
DR Reactome; R-GGA-351451; Homologous recombination repair of replication-dependent double-strand breaks.
DR PRO; PR:Q8AYC9; -.
DR Proteomes; UP000000539; Unplaced.
DR GO; GO:0005813; C:centrosome; ISS:UniProtKB.
DR GO; GO:0000785; C:chromatin; ISS:UniProtKB.
DR GO; GO:0000794; C:condensed nuclear chromosome; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0035402; F:histone kinase activity (H3-T11 specific); ISS:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISS:UniProtKB.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISS:UniProtKB.
DR GO; GO:0000077; P:DNA damage checkpoint signaling; ISS:UniProtKB.
DR GO; GO:0006975; P:DNA damage induced protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR GO; GO:0045815; P:epigenetic maintenance of chromatin in transcription-competent conformation; ISS:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0007095; P:mitotic G2 DNA damage checkpoint signaling; ISS:UniProtKB.
DR GO; GO:0045839; P:negative regulation of mitotic nuclear division; ISS:UniProtKB.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; ISS:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IBA:GO_Central.
DR GO; GO:0010569; P:regulation of double-strand break repair via homologous recombination; ISS:UniProtKB.
DR GO; GO:2000615; P:regulation of histone H3-K9 acetylation; ISS:UniProtKB.
DR GO; GO:0046602; P:regulation of mitotic centrosome separation; ISS:UniProtKB.
DR GO; GO:0010767; P:regulation of transcription from RNA polymerase II promoter in response to UV-induced DNA damage; ISS:UniProtKB.
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 ATP-binding; Cell cycle; Chromosome; Cytoplasm; Cytoskeleton; DNA damage;
KW DNA repair; Kinase; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..476
FT /note="Serine/threonine-protein kinase Chk1"
FT /id="PRO_0000085851"
FT DOMAIN 9..265
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 272..329
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 391..476
FT /note="Autoinhibitory region"
FT /evidence="ECO:0000250"
FT COMPBIAS 310..329
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 130
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 15..23
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 38
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 280
FT /note="Phosphoserine; by PKB/AKT1"
FT /evidence="ECO:0000250|UniProtKB:O14757"
FT MOD_RES 296
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O14757"
FT MOD_RES 317
FT /note="Phosphoserine; by ATM and ATR"
FT /evidence="ECO:0000250|UniProtKB:O14757"
FT MOD_RES 345
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:12554671"
SQ SEQUENCE 476 AA; 53849 MW; 0E54EE2196EF0C15 CRC64;
MAVPFVEDWD LVQTLGEGAY GEVQLAVNRR TEEAVAVKIV DMKRAADCPE NIKKEICINK
MLNHENVVKF YGHRREGATQ YLFLEYCSGG ELFDRIEPDI GMPEPEAQRF FQQLIAGVVY
LHSMGITHRD LKPENLLLDE RDNLKISDFG LATVFKHNGR ERLLNKMCGT LPYVAPELLR
RPEFRAEPVD VWACGVVLTA MLAGELPWDQ PSDSCQEYSD WKERKTYLAP WRKIDSAPLA
LLHKILTENP TARITIPDIK KDRWYCRPLK KGTKRGRVSS GGVTESPGAL PKHIRSDTDF
SPVKSALGED KASYSTSQPE PGTGGALWDS STGSIDRLVQ GISFSQPACP EHMLLNSQLL
GTPGSSQSPW QRLVRRMTRF FTKLDADGSY RSLRDVCEKM GYGWKQSCTN QVTISTTDRR
NNKLIFKVNL LEMESRILVD FRLSKGDGLE FKRHFLKIKG KLSDVVSTQK VWLPPP
