Home
GeneCards Guide
Suite
- MalaCards
- GeneALaCart
- GeneDecks
- GeneIP
- GeneLoc
Terms and Conditions
- Terms of Use
- 3rd Party Notice
About Us
User Feedback
Mirror sites

Set Analyses:

Generates a file of GeneCards annotations for your list of genes

Advanced Search

Search By

Section (entire)

for

All GeneCards Within gene subset (to enable gene prioritization):
or upload a file of gene symbols

Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

CHEK1 Gene

protein-coding GIFtS: 74
GCID: GC11P125495

checkpoint kinase 1

(Previous names: CHK1 (checkpoint, S.pombe) homolog, CHK1 checkpoint homolog...)

Explore 60 diseases affiliated with
CHEK1 via

MalaCards

our new
Human Malady Compendium

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, and/or ¹⁰fRNAdb)
About This Section

Aliases
Checkpoint Kinase 1¹ ²		CHK1 (Checkpoint, S.Pombe) Homolog¹
CHK1¹ ² ³ ⁵		CHK1 Checkpoint Homolog (S. Pombe)¹
Cell Cycle Checkpoint Kinase² ³		Chk1-S²
Checkpoint Kinase-1² ³		Checkpoint, S. Pombe, Homolog Of, 1²
CHK1 Checkpoint Homolog² ³		Serine/Threonine-Protein Kinase Chk1²
EC 2.7.11.1³ ⁸		EC 2.7.11⁸

External Ids:	HGNC: 1925¹	Entrez Gene: 1111²	Ensembl: ENSG00000149554⁷	OMIM: 603078⁵	UniProtKB: O14757³

Export aliases for CHEK1 gene to outside databases

Previous GC identifers: GC11P127497 GC11P127009 GC11P125529 GC11P125033 GC11P125001 GC11P121436

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for CHEK1:

The protein encoded by this gene belongs to the Ser/Thr protein kinase family. It is required for checkpoint mediated

cell cycle arrest in response to DNA damage or the presence of unreplicated DNA. This protein acts to integrate

signals from ATM and ATR, two cell cycle proteins involved in DNA damage responses, that also associate with chromatin

in meiotic prophase I. Phosphorylation of CDC25A protein phosphatase by this protein is required for cells to delay

cell cycle progression in response to double-strand DNA breaks. Several alternatively spliced transcript variants have

been found for this gene. (provided by RefSeq, Oct 2011)

UniProtKB/Swiss-Prot: CHK1_HUMAN, O14757

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. Phosphorylation of CDC25A at 'Ser-178' and 'Thr-507' and phosphorylation of

CDC25C at 'Ser-216' creates binding sites for 14-3-3 proteins which inhibit CDC25A and CDC25C. Phosphorylation of

CDC25A at 'Ser-76', 'Ser-124', 'Ser-178', 'Ser-279' and 'Ser-293' promotes proteolysis of CDC25A. Phosphorylation of

CDC25A at 'Ser-76' primes the protein for subsequent phosphorylation at 'Ser-79', 'Ser-82' and 'Ser-88' by NEK11,

which is required for polyubiquitination and degradation of CDCD25A. Inhibition of CDC25 leads to increased inhibitory

tyrosine phosphorylation of CDK-cyclin complexes and blocks cell cycle progression. Also phosphorylates NEK6. Binds to

and phosphorylates RAD51 at 'Thr-309', which promotes the release of RAD51 from BRCA2 and enhances the association of

RAD51 with chromatin, thereby promoting DNA repair by homologous recombination. Phosphorylates multiple sites within

the C-terminus of TP53, which promotes activation of TP53 by acetylation and promotes cell cycle arrest and

suppression of cellular proliferation. Also promotes repair of DNA cross-links through phosphorylation of FANCE. Binds

to and phosphorylates TLK1 at 'Ser-743', which prevents the TLK1-dependent phosphorylation of the chromatin assembly

factor ASF1A. This may enhance chromatin assembly both in the presence or absence of DNA damage. May also play a role

in replication fork maintenance through regulation of PCNA. May regulate the transcription of genes that regulate

cell-cycle progression through the phosphorylation of histones. Phosphorylates histone H3.1 (to form H3T11ph), which

leads to epigenetic inhibition of a subset of genes. May also phosphorylate RB1 to promote its interaction with the

E2F family of transcription factors and subsequent cell cycle arrest

Function: Isoform 2: Endogenous repressor of isoform 1, interacts with, and antagonizes CHK1 to promote the S to G2/M

phase transition

summary for CHEK1:

Checkpoint kinases (Chks) are serine/threonine kinases that are involved in the control of the cell cycle.

Two subtypes have so far been identified, Chk1 and Chk2. They are essential components to delay cell cycle

progression in normal and damaged cells and can act at all three cell cycle checkpoints. Chks are activated

by phosphorylation. ATR kinase phosphorylates Chk1 in response to single strand DNA breaks and ATM kinase

phosphorylates Chk2 in response to double strand breaks. Chks phosphorylate Cdc25 phosphatase at Ser216,

which leads to Cdc25 sequestration in the cytoplasm. Therefore Cdc25 cannot remove the inhibitory

phosphorylation on mitotic promoting factor (MPF) and entry into mitosis is prohibited. In addition, Chks

have a role in the physiological stress of hypoxia/reoxygenation.

Gene Wiki entry for CHEK1

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000011.9 NC_018922.1 NT_033899.8

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the CHEK1 gene promoter:
AP-1 p53 ATF-2 c-Jun NF-AT1
Other transcription factors

SwitchGear Promoter luciferase reporter plasmid: CHEK1 promoter sequence

Search SABiosciences Chromatin IP Primers for CHEK1

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat CHEK1

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 11q24.2 Ensembl cytogenetic band: 11q24.2 HGNC cytogenetic band: 11q24.2

CHEK1 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
CHEK1 gene location

GeneLoc information about chromosome 11 GeneLoc Exon Structure

GeneLoc location for GC11P125495: view genomic region (about GC identifiers)

Start:	125,495,036 bp from pter	End:	125,546,150 bp from pter
Size:	51,115 bases	Orientation:	plus strand

(According to ¹UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: CHK1_HUMAN, O14757 (See protein sequence)

Recommended Name: Serine/threonine-protein kinase Chk1

Size: 476 amino acids; 54434 Da

Subunit: Interacts (phosphorylated by ATR) with RAD51. Interacts with and phosphorylates CLSPN, an adapter protein that

regulates the ATR-dependent phosphorylation of CHEK1. Interacts with BRCA1. Interacts with and phosphorylates CDC25A,

CDC25B and CDC25C. Interacts with FBXO6, which regulates CHEK1. Interacts with PPM1D, which regulates CHEK1 through

dephosphorylation. Interacts with TIMELESS; DNA damage-dependent. Interacts with FEM1B; activates CHEK1 in response to

stress. Interacts with TLK1. Interacts with XPO1 and YWHAZ. Isoform 1 associates with isoform 2, the interaction is

disrupted upon phosphorylation by ATR

Subcellular location: Nucleus. Cytoplasm. Cytoplasm, cytoskeleton, centrosome. Note=Nuclear export is mediated at least

in part by XPO1/CRM1. Also localizes to the centrosome specifically during interphase, where it may protect

centrosomal CDC2 kinase from inappropriate activation by cytoplasmic CDC25B

6/101 PDB 3D structures from and Proteopedia for CHEK1 (see all 101):

1IA8 (3D)

1NVQ (3D)

1NVR (3D)

1NVS (3D)

1ZLT (3D)

1ZYS (3D)

Secondary accessions: A8K934 B4DDD0 B4DSK3 B5BTY6 F5H7S4 H2BI51

Alternative splicing: 3 isoforms: O14757-1 O14757-2 O14757-3 (No experimental confirmation available)

Explore the universe of human proteins at neXtProt for CHEK1: NX_O14757

Post-translational modifications:

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. ATM and ATR can both phosphorylate Ser-317 and

Ser-345 and this results in enhanced kinase activity. Phosphorylation at Ser-345 induces a change in the conformation

of the protein, activates the kinase activity and is a prerequisite for interaction with FBXO6 and subsequent

ubiquitination at Lys-436. Phosphorylation at Ser-345 also increases binding to 14-3-3 proteins and promotes nuclear

retention. Conversely, dephosphorylation at Ser-345 by PPM1D may contribute to exit from checkpoint mediated cell

cycle arrest. Phosphorylation at Ser-280 by AKT1/PKB, may promote mono and/or diubiquitination. Also phosphorylated at

undefined residues during mitotic arrest, resulting in decreased activity¹

Ubiquitinated. Mono or diubiquitination promotes nuclear exclusion (By similarity). The activated form (phosphorylated

on Ser-345) is polyubiquitinated at Lys-436 by some SCF-type E3 ubiquitin ligase complex containing FBXO6 promoting

its degradation. Ubiquitination and degradation are required to terminate the checkpoint and ensure that activated

CHEK1 does not accumulate as cells progress through S phase, when replication forks encounter transient impediments

during normal DNA replication¹

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_O14757

4/15 DME Specific Peptides for CHEK1 (O14757) (see all 15)

GGELFDR

YVAPELL

HRDIKPEN

KPENLLLDE

CHEK1 Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins (4 alternative transcripts):

NP_001107593.1 NP_001107594.1 NP_001231775.1 NP_001265.2

ENSEMBL proteins:

ENSP00000434141 ENSP00000391090 ENSP00000412504 ENSP00000431525 ENSP00000431815

ENSP00000432470 ENSP00000433103 ENSP00000435371 ENSP00000432890 ENSP00000434646

ENSP00000278916 ENSP00000388648 ENSP00000442317

Reactome Protein details: O14757
Human Recombinant Protein Products:

	EMD Millipore Purified and/or Recombinant CHEK1 Protein
	R&D Systems Recombinant & Natural Proteins for CHEK1 (Chk1)
	Enzo Life Sciences proteins for CHEK1
	Browse OriGene full length recombinant human proteins expressed in human HEK293 cells OriGene Protein Over-expression Lysate (see all 3): CHEK1 OriGene Custom Protein Services for CHEK1
	GenScript Custom Purified and Recombinant Proteins Services for CHEK1
	Novus Biologicals CHEK1 Proteins Novus Biologicals CHEK1 Lysates
	Browse Sino Biological Recombinant Proteins
	Browse ProSpec Recombinant Proteins
	Uscn Proteins for CHEK1

Gene Ontology (GO): 5/8 cellular component terms (GO ID links to tree view) (see all 8): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0000781	colocalizes with chromosome, telomeric region	IDA	15149599
GO:0000785	chromatin	ISS	--
GO:0000794	condensed nuclear chromosome	IDA	9382850
GO:0005634	nucleus	IDA	--
GO:0005654	nucleoplasm	TAS	--

CHEK1 for ontologies About GeneDecksing

CHEK1 Antibody Products:

	EMD Millipore Mono- and Polyclonal Antibodies for the study of CHEK1
	R&D Systems Antibodies for CHEK1 (Chk1)
	Cell Signaling Technology (CST) Antibodies for CHEK1 (Chk1)
	OriGene Antibodies (see all 6): CHEK1 OriGene Custom Antibody Services for CHEK1
	GenScript Superior Antibodies for CHEK1
	Novus Biologicals CHEK1 Antibodies
	Abcam antibodies for CHEK1
	Uscn Antibodies for CHEK1
	ThermoFisher Antibodies for CHEK1

Assay Products for CHEK1:

	Browse Kits and Assays available from EMD Millipore
	OriGene Custom Immunoassay Development Browse OriGene Fluorogenic Cell Assay Kits
	Browse R&D Systems for biochemical assays
	GenScript Custom Assay Services for CHEK1
	Cell Signaling Technology (CST) Sandwich ELISA Kits for CHEK1 (Chk1)
	Browse Enzo Life Sciences for kits & assays
	Uscn ELISAs and CLIAs for CHEK1

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

CHEK1 for domains About GeneDecksing

5 InterPro domains/families:

IPR017441 Protein_kinase_ATP_BS

IPR002290 Ser/Thr_dual-sp_kinase_dom

IPR011009 Kinase-like_dom

IPR008271 Ser/Thr_kinase_AS

IPR000719 Prot_kinase_cat_dom

Graphical View of Domain Structure for InterPro Entry O14757

ProtoNet protein and cluster: O14757

UniProtKB/Swiss-Prot: CHK1_HUMAN, O14757

Domain: The autoinhibitory region (AIR) inhibits the activity of the kinase domain

Similarity: Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. NIM1 subfamily

Similarity: Contains 1 protein kinase domain

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Function Summary: