Q8AYC9 (CHK1_CHICK) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Serine/threonine-protein kinase Chk1
EC=2.7.11.1

Alternative name(s):
CHK1 checkpoint homolog
Checkpoint kinase-1

Gene names

Name:	CHEK1
Synonyms:	CHK1

Organism

Gallus gallus (Chicken) [Reference proteome]

Taxonomic identifier

9031 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Sauropsida › Sauria › Archosauria › Dinosauria › Saurischia › Theropoda › Coelurosauria › Aves › Neognathae › Galliformes › Phasianidae › Phasianinae › Gallus

Protein attributes

Sequence length	476 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest and activation of DNA repair in response to the presence of DNA damage or unreplicated DNA. May also negatively regulate cell cycle progression during unperturbed cell cycles. This regulation is achieved by a number of mechanisms that together help to preserve the integrity of the genome. Recognizes the substrate consensus sequence [R-X-X-S/T]. Binds to and phosphorylates CDC25A, CDC25B and CDC25C. This inhibits their activity through proteasomal degradation, nucleo-cytoplasmic shuttling and inhibition by proteins of the 13-3-3 family. Inhibition of CDC25 leads to increased inhibitory tyrosine phosphorylation of CDK-cyclin complexes and blocks cell cycle progression. May promote DNA repair, regulate chromatin assembly and the transcription of genes that regulate cell-cycle progression. May also play a role in replication fork maintenance By similarity. Ref.1
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Enzyme regulation	Activated through phosphorylation by ATR or ATM in response to DNA damage or inhibition of DNA replication By similarity.
Subunit structure	Interacts with and phosphorylates CLSPN, an adapter protein that regulates the ATR-dependent phosphorylation of CHEK1 By similarity.
Subcellular location	Nucleus By similarity. Cytoplasm By similarity. Cytoplasm › cytoskeleton › centrosome By similarity.
Domain	The autoinhibitory region (AIR) inhibits the activity of the kinase domain By similarity.
Post-translational modification	Phosphorylated by ATR in a RAD17-dependent manner in response to ultraviolet irradiation and inhibition of DNA replication. Phosphorylated by ATM in response to ionizing irradiation By similarity. Phosphorylation at Ser-345 induces a change in the conformation of the protein and activates the kinase activity. Phosphorylation at Ser-345 also increases binding to 14-3-3 proteins and promotes nuclear retention. Ref.1
Sequence similarities	Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. NIM1 subfamily. Contains 1 protein kinase domain.

Ontologies

Keywords
Biological process	Cell cycle DNA damage DNA repair
Cellular component	Cytoplasm Cytoskeleton Nucleus
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	DNA damage induced protein phosphorylation Inferred from sequence or structural similarity. Source: UniProtKB G2 DNA damage checkpoint Inferred from sequence or structural similarity. Source: UniProtKB chromatin-mediated maintenance of transcription Inferred from sequence or structural similarity. Source: UniProtKB double-strand break repair via homologous recombination Traceable author statement. Source: Reactome negative regulation of mitosis Inferred from sequence or structural similarity. Source: UniProtKB regulation of double-strand break repair via homologous recombination Inferred from sequence or structural similarity. Source: UniProtKB regulation of histone H3-K9 acetylation Inferred from sequence or structural similarity. Source: UniProtKB regulation of mitotic centrosome separation Inferred from sequence or structural similarity. Source: UniProtKB regulation of transcription from RNA polymerase II promoter in response to UV-induced DNA damage Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	centrosome Inferred from sequence or structural similarity. Source: UniProtKB chromatin Inferred from sequence or structural similarity. Source: UniProtKB condensed nuclear chromosome Inferred from sequence or structural similarity. Source: UniProtKB cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nucleoplasm Traceable author statement. Source: Reactome
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW histone kinase activity (H3-T11 specific) Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 476	476	Serine/threonine-protein kinase Chk1		PRO_0000085851
Regions
	Domain	9 – 265	257	Protein kinase
	Nucleotide binding	15 – 23	9	ATP By similarity
	Region	1 – 265	265	Interaction with CLSPN By similarity
	Region	391 – 476	86	Autoinhibitory region By similarity
Sites
	Active site	130	1	Proton acceptor By similarity
	Binding site	38	1	ATP By similarity
Amino acid modifications
	Modified residue	280	1	Phosphoserine; by PKB/AKT1 By similarity
	Modified residue	296	1	Phosphoserine By similarity
	Modified residue	317	1	Phosphoserine; by ATM and ATR By similarity
	Modified residue	345	1	Phosphoserine Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q8AYC9 [UniParc]. Last modified March 1, 2003. Version 1. Checksum: 0E54EE2196EF0C15	FASTA	476	53,849
	10 20 30 40 50 60 MAVPFVEDWD LVQTLGEGAY GEVQLAVNRR TEEAVAVKIV DMKRAADCPE NIKKEICINK 70 80 90 100 110 120 MLNHENVVKF YGHRREGATQ YLFLEYCSGG ELFDRIEPDI GMPEPEAQRF FQQLIAGVVY 130 140 150 160 170 180 LHSMGITHRD LKPENLLLDE RDNLKISDFG LATVFKHNGR ERLLNKMCGT LPYVAPELLR 190 200 210 220 230 240 RPEFRAEPVD VWACGVVLTA MLAGELPWDQ PSDSCQEYSD WKERKTYLAP WRKIDSAPLA 250 260 270 280 290 300 LLHKILTENP TARITIPDIK KDRWYCRPLK KGTKRGRVSS GGVTESPGAL PKHIRSDTDF 310 320 330 340 350 360 SPVKSALGED KASYSTSQPE PGTGGALWDS STGSIDRLVQ GISFSQPACP EHMLLNSQLL 370 380 390 400 410 420 GTPGSSQSPW QRLVRRMTRF FTKLDADGSY RSLRDVCEKM GYGWKQSCTN QVTISTTDRR 430 440 450 460 470 NNKLIFKVNL LEMESRILVD FRLSKGDGLE FKRHFLKIKG KLSDVVSTQK VWLPPP

References

[1]	"Chk1-deficient tumour cells are viable but exhibit multiple checkpoint and survival defects." Zachos G., Rainey M.D., Gillespie D.A.F. EMBO J. 22:713-723(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, PHOSPHORYLATION AT SER-345.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF525027 mRNA. Translation: AAN33019.1.
IPI	IPI00589773.
RefSeq	NP_989676.1. NM_204345.1.
UniGene	Gga.4288. Gga.48286.
3D structure databases
ProteinModelPortal	Q8AYC9.
SMR	Q8AYC9. Positions 3-272.
ModBase	Search...
Protein-protein interaction databases
STRING	9031.ENSGALP00000040314.
Proteomic databases
PaxDb	Q8AYC9.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	374260.
KEGG	gga:374260.
Organism-specific databases
CTD	3703.
Phylogenomic databases
eggNOG	COG0515.
HOGENOM	HOG000216658.
HOVERGEN	HBG002590.
InParanoid	Q8AYC9.
KO	K02216.
OrthoDB	EOG4001JD.
Enzyme and pathway databases
Reactome	REACT_115612. DNA replication and repair.
Family and domain databases
InterPro	IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR002290. Ser/Thr_dual-sp_kinase_dom. IPR008271. Ser/Thr_kinase_AS. [Graphical view]
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
SMART	SM00220. S_TKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit.
PROSITE	PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	20813751.

Entry information

Entry name

CHK1_CHICK

Accession

Primary (citable) accession number: Q8AYC9

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 27, 2005
Last sequence update:	March 1, 2003
Last modified:	May 1, 2013
This is version 76 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program