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O14757 (CHK1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 167. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Serine/threonine-protein kinase Chk1

EC=2.7.11.1
Alternative name(s):
CHK1 checkpoint homolog
Cell cycle checkpoint kinase
Checkpoint kinase-1
Gene names
Name:CHEK1
Synonyms:CHK1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length476 AA.
Sequence statusComplete.
Protein existenceEvidence 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. 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. Ref.1 Ref.11 Ref.14 Ref.18 Ref.20 Ref.21 Ref.22 Ref.23 Ref.25 Ref.27 Ref.29 Ref.32 Ref.34 Ref.38 Ref.40 Ref.41 Ref.42 Ref.43 Ref.44 Ref.45 Ref.48 Ref.49 Ref.50 Ref.52 Ref.57 Ref.60

Isoform 2:Endogenous repressor of isoform 1, interacts with, and antagonizes CHK1 to promote the S to G2/M phase transition. Ref.1 Ref.11 Ref.14 Ref.18 Ref.20 Ref.21 Ref.22 Ref.23 Ref.25 Ref.27 Ref.29 Ref.32 Ref.34 Ref.38 Ref.40 Ref.41 Ref.42 Ref.43 Ref.44 Ref.45 Ref.48 Ref.49 Ref.50 Ref.52 Ref.57 Ref.60

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulation

Activated through phosphorylation predominantly by ATR but also by ATM in response to DNA damage or inhibition of DNA replication. Activation is modulated by several mediators including CLSPN, BRCA1 and FEM1B.

Subunit structure

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. Ref.1 Ref.19 Ref.26 Ref.28 Ref.35 Ref.37 Ref.39 Ref.40 Ref.43 Ref.55 Ref.58

Subcellular location

Nucleus. Cytoplasm. Cytoplasmcytoskeletonmicrotubule organizing centercentrosome. 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. Ref.1 Ref.2 Ref.19 Ref.26 Ref.34 Ref.36

Tissue specificity

Expressed ubiquitously with the most abundant expression in thymus, testis, small intestine and colon. Ref.1 Ref.2

Domain

The autoinhibitory region (AIR) inhibits the activity of the kinase domain. Ref.33

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. 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 activity. Ref.13 Ref.14 Ref.15 Ref.18 Ref.21 Ref.22 Ref.24 Ref.25 Ref.26 Ref.31 Ref.32 Ref.33 Ref.35 Ref.37 Ref.41 Ref.55

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 replication. Ref.13 Ref.14 Ref.15 Ref.18 Ref.21 Ref.22 Ref.24 Ref.25 Ref.26 Ref.31 Ref.32 Ref.33 Ref.35 Ref.37 Ref.41 Ref.55

Sequence similarities

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

Contains 1 protein kinase domain.

Ontologies

Keywords
   Biological processCell cycle
DNA damage
DNA repair
   Cellular componentCytoplasm
Cytoskeleton
Nucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMIsopeptide bond
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processDNA damage checkpoint

Inferred from direct assay Ref.43. Source: UniProtKB

DNA damage induced protein phosphorylation

Inferred from direct assay Ref.43. Source: UniProtKB

DNA repair

Inferred from mutant phenotype Ref.55. Source: UniProtKB

DNA replication

Traceable author statement. Source: Reactome

G2 DNA damage checkpoint

Inferred from mutant phenotype PubMed 20932473. Source: UniProtKB

G2/M transition of mitotic cell cycle

Inferred from electronic annotation. Source: Ensembl

cellular response to DNA damage stimulus

Inferred from mutant phenotype PubMed 20932473. Source: UniProtKB

cellular response to caffeine

Inferred from electronic annotation. Source: Ensembl

cellular response to mechanical stimulus

Inferred from expression pattern PubMed 19593445. Source: UniProtKB

chromatin-mediated maintenance of transcription

Inferred from sequence or structural similarity. Source: UniProtKB

histone H3-T11 phosphorylation

Inferred from direct assay PubMed 18243098. Source: GOC

negative regulation of mitosis

Inferred from direct assay Ref.34. Source: UniProtKB

peptidyl-threonine phosphorylation

Inferred from direct assay Ref.40. Source: UniProtKB

regulation of cell proliferation

Inferred from electronic annotation. Source: Ensembl

regulation of double-strand break repair via homologous recombination

Inferred from direct assay Ref.40. Source: UniProtKB

regulation of histone H3-K9 acetylation

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of mitotic centrosome separation

Inferred from direct assay Ref.34. 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

replicative senescence

Non-traceable author statement PubMed 15149599. Source: BHF-UCL

   Cellular_componentcentrosome

Inferred from direct assay Ref.34. Source: UniProtKB

chromatin

Inferred from sequence or structural similarity. Source: UniProtKB

condensed nuclear chromosome

Inferred from direct assay Ref.2. Source: UniProtKB

cytosol

Traceable author statement. Source: Reactome

extracellular space

Inferred from direct assay PubMed 23580065. Source: UniProt

intracellular membrane-bounded organelle

Inferred from direct assay. Source: HPA

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay Ref.34PubMed 20932473. Source: UniProtKB

replication fork

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

histone kinase activity (H3-T11 specific)

Inferred from direct assay PubMed 18243098. Source: UniProtKB

protein serine/threonine kinase activity

Inferred from direct assay Ref.43. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O14757-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: O14757-2)

Also known as: Chk1-short; Chk1-S;

The sequence of this isoform differs from the canonical sequence as follows:
     1-94: Missing.
     95-97: RIE → MEK
Isoform 3 (identifier: O14757-3)

The sequence of this isoform differs from the canonical sequence as follows:
     412-445: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 476476Serine/threonine-protein kinase Chk1
PRO_0000085848

Regions

Domain9 – 265257Protein kinase
Nucleotide binding15 – 239ATP By similarity
Region1 – 265265Interaction with CLSPN By similarity
Region391 – 47686Autoinhibitory region

Sites

Active site1301Proton acceptor
Binding site381ATP By similarity

Amino acid modifications

Modified residue2801Phosphoserine; by PKB/AKT1 By similarity
Modified residue2861Phosphoserine Ref.53 Ref.61
Modified residue2961Phosphoserine Ref.35 Ref.53 Ref.56 Ref.61
Modified residue3011Phosphoserine Ref.51 Ref.53 Ref.59 Ref.61
Modified residue3171Phosphoserine; by ATM and ATR Ref.15 Ref.18 Ref.21 Ref.22 Ref.24 Ref.26 Ref.31 Ref.35 Ref.37
Modified residue3451Phosphoserine; by ATM and ATR Ref.13 Ref.15 Ref.18 Ref.21 Ref.25 Ref.26 Ref.32 Ref.33 Ref.35 Ref.37 Ref.41 Ref.55
Cross-link436Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.46 Ref.55

Natural variations

Alternative sequence1 – 9494Missing in isoform 2.
VSP_044008
Alternative sequence95 – 973RIE → MEK in isoform 2.
VSP_044009
Alternative sequence412 – 44534Missing in isoform 3.
VSP_045075
Natural variant1561R → Q. Ref.6
Corresponds to variant rs3731410 [ dbSNP | Ensembl ].
VAR_021123
Natural variant2231E → V. Ref.67
Corresponds to variant rs35817404 [ dbSNP | Ensembl ].
VAR_040407
Natural variant3121V → M. Ref.67
Corresponds to variant rs34097480 [ dbSNP | Ensembl ].
VAR_040408
Natural variant4711I → V. Ref.1 Ref.2 Ref.3 Ref.5 Ref.6 Ref.7 Ref.9 Ref.10
Corresponds to variant rs506504 [ dbSNP | Ensembl ].
VAR_024571

Experimental info

Mutagenesis381K → R: Abolishes kinase activity. Ref.18 Ref.33
Mutagenesis1301D → A: Abolishes kinase activity. Ref.1 Ref.11 Ref.14 Ref.15 Ref.16 Ref.23 Ref.24 Ref.34
Mutagenesis3171S → A: Abrogates interaction with RAD51; when associated with A-345. Reduces phosphorylation and impairs activation by hydroxyurea and ionizing radiation. Abrogates nuclear retention upon checkpoint activation. Impairs interaction with FBXO6. Ref.15 Ref.21 Ref.24 Ref.26 Ref.40
Mutagenesis3171S → E: Enhances interaction with RAD51; when associated with E-345. Ref.15 Ref.21 Ref.24 Ref.26 Ref.40
Mutagenesis3441F → A: Impairs nuclear export. Ref.26
Mutagenesis3451S → A: Abrogates interaction with RAD51; when associated with A-317. Reduces phosphorylation and impairs activation by hydroxyurea and ionizing radiation. Impairs interaction with YWHAZ which is required for nuclear retention after checkpoint activation. Ref.15 Ref.21 Ref.24 Ref.26 Ref.40 Ref.55
Mutagenesis3451S → E: Enhances interaction with RAD51; when associated with E-317. Ref.15 Ref.21 Ref.24 Ref.26 Ref.40 Ref.55
Mutagenesis3531M → A: Impairs nuclear export. Ref.26
Mutagenesis3571S → A: No effect on phosphorylation induced by hydroxyurea. Ref.15
Mutagenesis3661S → A: No effect on phosphorylation induced by hydroxyurea. Ref.15
Mutagenesis3721R → E in 3RE mutant. Disrupts the folding and/or conformation, allowing increased accessibility to FBXO6 component of SCF-type E3 ubiquitin ligase complex; when associated with E-376 and E-379. Ref.55
Mutagenesis3761R → E in 3RE mutant. Disrupts the folding and/or conformation, allowing increased accessibility to FBXO6 component of SCF-type E3 ubiquitin ligase complex; when associated with E-372 and E-379. Ref.55
Mutagenesis3791R → E in 3RE mutant. Disrupts the folding and/or conformation, allowing increased accessibility to FBXO6 component of SCF-type E3 ubiquitin ligase complex; when associated with E-372 and E-376. Ref.55
Mutagenesis4361K → R: Enhances stability of the protein, probably by preventing ubiquitination at this site. Ref.55
Mutagenesis4681S → A: No effect on phosphorylation induced by hydroxyurea. Ref.15
Sequence conflict1631L → S in BAG56691. Ref.5
Sequence conflict2201D → G in BAG61665. Ref.4
Sequence conflict3811F → L in BAG61665. Ref.4

Secondary structure

........................................................... 476
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified January 11, 2011. Version 2.
Checksum: 0ABD0FAB67E60F67

FASTA47654,434
        10         20         30         40         50         60 
MAVPFVEDWD LVQTLGEGAY GEVQLAVNRV TEEAVAVKIV DMKRAVDCPE NIKKEICINK 

        70         80         90        100        110        120 
MLNHENVVKF YGHRREGNIQ YLFLEYCSGG ELFDRIEPDI GMPEPDAQRF FHQLMAGVVY 

       130        140        150        160        170        180 
LHGIGITHRD IKPENLLLDE RDNLKISDFG LATVFRYNNR ERLLNKMCGT LPYVAPELLK 

       190        200        210        220        230        240 
RREFHAEPVD VWSCGIVLTA MLAGELPWDQ PSDSCQEYSD WKEKKTYLNP WKKIDSAPLA 

       250        260        270        280        290        300 
LLHKILVENP SARITIPDIK KDRWYNKPLK KGAKRPRVTS GGVSESPSGF SKHIQSNLDF 

       310        320        330        340        350        360 
SPVNSASSEE NVKYSSSQPE PRTGLSLWDT SPSYIDKLVQ GISFSQPTCP DHMLLNSQLL 

       370        380        390        400        410        420 
GTPGSSQNPW QRLVKRMTRF FTKLDADKSY QCLKETCEKL GYQWKKSCMN QVTISTTDRR 

       430        440        450        460        470 
NNKLIFKVNL LEMDDKILVD FRLSKGDGLE FKRHFLKIKG KLIDIVSSQK IWLPAT 

« Hide

Isoform 2 (Chk1-short) (Chk1-S) [UniParc].

Checksum: 3ECD01BEC168F007
Show »

FASTA38243,703
Isoform 3 [UniParc].

Checksum: 05680C63BD1287B6
Show »

FASTA44250,415

References

« Hide 'large scale' references
[1]"Conservation of the Chk1 checkpoint pathway in mammals: linkage of DNA damage to Cdk regulation through Cdc25."
Sanchez Y., Wong C., Thoma R.S., Richman R., Wu Z., Piwnica-Worms H., Elledge S.J.
Science 277:1497-1501(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION IN PHOSPHORYLATION OF CDC25A; CDC25B AND CDC25C, INTERACTION WITH CDC25A; CDC25B AND CDC25C, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, MUTAGENESIS OF ASP-130, VARIANT VAL-471.
[2]"Atm-dependent interactions of a mammalian chk1 homolog with meiotic chromosomes."
Flaggs G., Plug A.W., Dunks K.M., Mundt K.E., Ford J.C., Quiggle M.R.E., Taylor E.M., Westphal C.H., Ashley T., Hoekstra M.F., Carr A.M.
Curr. Biol. 7:977-986(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, SUBCELLULAR LOCATION, VARIANT VAL-471.
[3]"Analysis of the candidate target genes for mutation in microsatellite instability-positive cancers of the colorectum, stomach, and endometrium."
Semba S., Ouyang H., Han S.-Y., Kato Y., Horii A.
Int. J. Oncol. 16:731-737(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT VAL-471.
[4]"Checkpoint kinase 1 (Chk1)-short is a splice variant and endogenous inhibitor of Chk1 that regulates cell cycle and DNA damage checkpoints."
Pabla N., Bhatt K., Dong Z.
Proc. Natl. Acad. Sci. U.S.A. 109:197-202(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), ALTERNATIVE SPLICING.
Tissue: Fetal thymus.
[5]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3), VARIANT VAL-471.
Tissue: Brain and Testis.
[6]NIEHS SNPs program
Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS GLN-156 AND VAL-471.
[7]"Human protein factory for converting the transcriptome into an in vitro-expressed proteome."
Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R., Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y., Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B. expand/collapse author list , Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H., Maruyama Y., Matsuo K., Minami K., Mitsubori M., Mori M., Morishita R., Murase A., Nishikawa A., Nishikawa S., Okamoto T., Sakagami N., Sakamoto Y., Sasaki Y., Seki T., Sono S., Sugiyama A., Sumiya T., Takayama T., Takayama Y., Takeda H., Togashi T., Yahata K., Yamada H., Yanagisawa Y., Endo Y., Imamoto F., Kisu Y., Tanaka S., Isogai T., Imai J., Watanabe S., Nomura N.
Nat. Methods 5:1011-1017(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT VAL-471.
[8]"Human chromosome 11 DNA sequence and analysis including novel gene identification."
Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. expand/collapse author list , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y.
Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT VAL-471.
[10]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT VAL-471.
Tissue: Bone marrow and Muscle.
[11]"The human homologs of checkpoint kinases Chk1 and Cds1 (Chk2) phosphorylate p53 at multiple DNA damage-inducible sites."
Shieh S.-Y., Ahn J., Tamai K., Taya Y., Prives C.
Genes Dev. 14:289-300(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF TP53, MUTAGENESIS OF ASP-130.
[12]Erratum
Shieh S.-Y., Ahn J., Tamai K., Taya Y., Prives C.
Genes Dev. 14:750-750(2000)
[13]"Chk1 is an essential kinase that is regulated by Atr and required for the G(2)/M DNA damage checkpoint."
Liu Q., Guntuku S., Cui X.-S., Matsuoka S., Cortez D., Tamai K., Luo G., Carattini-Rivera S., DeMayo F., Bradley A., Donehower L.A., Elledge S.J.
Genes Dev. 14:1448-1459(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-345 BY ATR.
[14]"Activation of mammalian Chk1 during DNA replication arrest: a role for Chk1 in the intra-S phase checkpoint monitoring replication origin firing."
Feijoo C., Hall-Jackson C., Wu R., Jenkins D., Leitch J., Gilbert D.M., Smythe C.
J. Cell Biol. 154:913-923(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DNA REPLICATION, PHOSPHORYLATION BY ATR, MUTAGENESIS OF ASP-130.
[15]"ATR-mediated checkpoint pathways regulate phosphorylation and activation of human Chk1."
Zhao H., Piwnica-Worms H.
Mol. Cell. Biol. 21:4129-4139(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-317 AND SER-345, MUTAGENESIS OF ASP-130; SER-317; SER-345; SER-357; SER-366 AND SER-468.
[16]"Determination of substrate motifs for human Chk1 and hCds1/Chk2 by the oriented peptide library approach."
O'Neill T., Giarratani L., Chen P., Iyer L., Lee C.-H., Bobiak M., Kanai F., Zhou B.-B., Chung J.H., Rathbun G.A.
J. Biol. Chem. 277:16102-16115(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBSTRATE SPECIFICITY, MUTAGENESIS OF ASP-130.
[17]Erratum
O'Neill T., Giarratani L., Chen P., Iyer L., Lee C.-H., Bobiak M., Kanai F., Zhou B.-B., Chung J.H., Rathbun G.A.
J. Biol. Chem. 277:35776-35777(2002)
[18]"An ATR- and Chk1-dependent S checkpoint inhibits replicon initiation following UVC-induced DNA damage."
Heffernan T.P., Simpson D.A., Frank A.R., Heinloth A.N., Paules R.S., Cordeiro-Stone M., Kaufmann W.K.
Mol. Cell. Biol. 22:8552-8561(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DNA DAMAGE RESPONSE, PHOSPHORYLATION AT SER-317 AND SER-345, MUTAGENESIS OF LYS-38.
[19]"BRCA1 regulates the G2/M checkpoint by activating Chk1 kinase upon DNA damage."
Yarden R.I., Pardo-Reoyo S., Sgagias M., Cowan K.H., Brody L.C.
Nat. Genet. 30:285-289(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, INTERACTION WITH BRCA1.
[20]"Disruption of the checkpoint kinase 1/cell division cycle 25A pathway abrogates ionizing radiation-induced S and G2 checkpoints."
Zhao H., Watkins J.L., Piwnica-Worms H.
Proc. Natl. Acad. Sci. U.S.A. 99:14795-14800(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DNA DAMAGE RESPONSE.
[21]"Chk1 regulates the S phase checkpoint by coupling the physiological turnover and ionizing radiation-induced accelerated proteolysis of Cdc25A."
Soerensen C.S., Syljuaesen R.G., Falck J., Schroeder T., Roennstrand L., Khanna K.K., Zhou B.-B., Bartek J., Lukas J.
Cancer Cell 3:247-258(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN CDC25A TURNOVER, PHOSPHORYLATION AT SER-317 AND SER-345, MUTAGENESIS OF SER-317 AND SER-345.
[22]"Human tousled like kinases are targeted by an ATM- and Chk1-dependent DNA damage checkpoint."
Groth A., Lukas J., Nigg E.A., Sillje H.H.W., Wernstedt C., Bartek J., Hansen K.
EMBO J. 22:1676-1687(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF TLK1, PHOSPHORYLATION AT SER-317.
[23]"SCFbeta-TRCP links Chk1 signaling to degradation of the Cdc25A protein phosphatase."
Jin J., Shirogane T., Xu L., Nalepa G., Qin J., Elledge S.J., Harper J.W.
Genes Dev. 17:3062-3074(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN CDC25A TURNOVER, MUTAGENESIS OF ASP-130.
[24]"Ataxia-telangiectasia-mutated (ATM) and NBS1-dependent phosphorylation of Chk1 on ser-317 in response to ionizing radiation."
Gatei M., Sloper K., Soerensen C., Syljuaesen R., Falck J., Hobson K., Savage K., Lukas J., Zhou B.-B., Bartek J., Khanna K.K.
J. Biol. Chem. 278:14806-14811(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-317, MUTAGENESIS OF ASP-130; SER-317 AND SER-345.
[25]"Chk1 mediates S and G2 arrests through Cdc25A degradation in response to DNA-damaging agents."
Xiao Z., Chen Z., Gunasekera A.H., Sowin T.J., Rosenberg S.H., Fesik S., Zhang H.
J. Biol. Chem. 278:21767-21773(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN CDC25A TURNOVER, PHOSPHORYLATION AT SER-345.
[26]"Regulation of Chk1 includes chromatin association and 14-3-3 binding following phosphorylation on ser-345."
Jiang K., Pereira E., Maxfield M., Russell B., Goudelock D.M., Sanchez Y.
J. Biol. Chem. 278:25207-25217(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH YWHAZ AND XPO1, SUBCELLULAR LOCATION, ASSOCIATION WITH CHROMATIN, PHOSPHORYLATION AT SER-317 AND SER-345, MUTAGENESIS OF SER-317; PHE-344; SER-345 AND MET-353.
[27]"Phosphorylation at serine 75 is required for UV-mediated degradation of human Cdc25A phosphatase at the S-phase checkpoint."
Hassepass I., Voit R., Hoffmann I.
J. Biol. Chem. 278:29824-29829(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN CDC25A TURNOVER.
[28]"Human claspin is required for replication checkpoint control."
Chini C.C.S., Chen J.
J. Biol. Chem. 278:30057-30062(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CLSPN.
[29]"Chk1 kinase negatively regulates mitotic function of Cdc25A phosphatase through 14-3-3 binding."
Chen M.-S., Ryan C.E., Piwnica-Worms H.
Mol. Cell. Biol. 23:7488-7497(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN MITOSIS, FUNCTION IN PHOSPHORYLATION OF CDC25A.
[30]"Suppression of tousled-like kinase activity after DNA damage or replication block requires ATM, NBS1 and Chk1."
Krause D.R., Jonnalagadda J.C., Gatei M.H., Sillje H.H.W., Zhou B.-B., Nigg E.A., Khanna K.
Oncogene 22:5927-5937(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: REGULATION OF TLK1.
[31]"MSH2 and ATR form a signaling module and regulate two branches of the damage response to DNA methylation."
Wang Y., Qin J.
Proc. Natl. Acad. Sci. U.S.A. 100:15387-15392(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-317.
[32]"The DNA crosslink-induced S-phase checkpoint depends on ATR-CHK1 and ATR-NBS1-FANCD2 pathways."
Pichierri P., Rosselli F.
EMBO J. 23:1178-1187(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, PHOSPHORYLATION AT SER-345.
[33]"Differential mode of regulation of the checkpoint kinases CHK1 and CHK2 by their regulatory domains."
Ng C.-P., Lee H.C., Ho C.W., Arooz T., Siu W.Y., Lau A., Poon R.Y.C.
J. Biol. Chem. 279:8808-8819(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: DOMAIN, MITOTIC PHOSPHORYLATION, PHOSPHORYLATION AT SER-345, MUTAGENESIS OF LYS-38.
[34]"Centrosome-associated Chk1 prevents premature activation of cyclin-B-Cdk1 kinase."
Kraemer A., Mailand N., Lukas C., Syljuaesen R.G., Wilkinson C.J., Nigg E.A., Bartek J., Lukas J.
Nat. Cell Biol. 6:884-891(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN MITOSIS, SUBCELLULAR LOCATION, MUTAGENESIS OF ASP-130.
[35]"DNA-dependent phosphorylation of Chk1 and claspin in a human cell-free system."
Clarke C.A.L., Clarke P.R.
Biochem. J. 388:705-712(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CLSPN, PHOSPHORYLATION AT SER-296; SER-317 AND SER-345.
[36]"Lack of PTEN sequesters CHK1 and initiates genetic instability."
Puc J., Keniry M., Li H.S., Pandita T.K., Choudhury A.D., Memeo L., Mansukhani M., Murty V.V.V.S., Gaciong Z., Meek S.E.M., Piwnica-Worms H., Hibshoosh H., Parsons R.
Cancer Cell 7:193-204(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[37]"PPM1D dephosphorylates Chk1 and p53 and abrogates cell cycle checkpoints."
Lu X., Nannenga B., Donehower L.A.
Genes Dev. 19:1162-1174(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PPM1D, PHOSPHORYLATION AT SER-317 AND SER-345, DEPHOSPHORYLATION BY PPM1D.
[38]"p53 C-terminal phosphorylation by CHK1 and CHK2 participates in the regulation of DNA-damage-induced C-terminal acetylation."
Ou Y.-H., Chung P.-H., Sun T.-P., Shieh S.-Y.
Mol. Biol. Cell 16:1684-1695(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF TP53, FUNCTION IN TP53-DEPENDENT TRANSCRIPTION.
[39]"Coupling of human circadian and cell cycles by the timeless protein."
Uensal-Kacmaz K., Mullen T.E., Kaufmann W.K., Sancar A.
Mol. Cell. Biol. 25:3109-3116(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TIMELESS.
[40]"The cell-cycle checkpoint kinase Chk1 is required for mammalian homologous recombination repair."
Soerensen C.S., Hansen L.T., Dziegielewski J., Syljuaesen R.G., Lundin C., Bartek J., Helleday T.
Nat. Cell Biol. 7:195-201(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN HOMOLOGOUS RECOMBINATION REPAIR, FUNCTION IN PHOSPHORYLATION OF RAD51, INTERACTION WITH RAD51, MUTAGENESIS OF SER-317 AND SER-345.
[41]"DNA damage-induced mitotic catastrophe is mediated by the Chk1-dependent mitotic exit DNA damage checkpoint."
Huang X., Tran T., Zhang L., Hatcher R., Zhang P.
Proc. Natl. Acad. Sci. U.S.A. 102:1065-1070(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN MITOTIC EXIT, PHOSPHORYLATION AT SER-345.
[42]"14-3-3gamma binds to MDMX that is phosphorylated by UV-activated Chk1, resulting in p53 activation."
Jin Y., Dai M.S., Lu S.Z., Xu Y., Luo Z., Zhao Y., Lu H.
EMBO J. 25:1207-1218(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN TP53 ACTIVATION, FUNCTION IN PHOSPHORYLATION OF MDM4.
[43]"Repeated phosphopeptide motifs in human Claspin are phosphorylated by Chk1 and mediate Claspin function."
Chini C.C., Chen J.
J. Biol. Chem. 281:33276-33282(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF CLSPN, INTERACTION WITH CLSPN.
[44]"Phosphorylation of pRB at Ser612 by Chk1/2 leads to a complex between pRB and E2F-1 after DNA damage."
Inoue Y., Kitagawa M., Taya Y.
EMBO J. 26:2083-2093(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF RB1.
[45]"Chk1-mediated phosphorylation of FANCE is required for the Fanconi anemia/BRCA pathway."
Wang X., Kennedy R.D., Ray K., Stuckert P., Ellenberger T., D'Andrea A.D.
Mol. Cell. Biol. 27:3098-3108(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DNA CROSS-LINKS REPAIR, FUNCTION IN PHOSPHORYLATION OF FANCE.
[46]"Tryptic digestion of ubiquitin standards reveals an improved strategy for identifying ubiquitinated proteins by mass spectrometry."
Denis N.J., Vasilescu J., Lambert J.-P., Smith J.C., Figeys D.
Proteomics 7:868-874(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-436.
Tissue: Mammary cancer.
[47]"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage."
Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.
Science 316:1160-1166(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Embryonic kidney.
[48]"Chk1 suppresses a caspase-2 apoptotic response to DNA damage that bypasses p53, Bcl-2, and caspase-3."
Sidi S., Sanda T., Kennedy R.D., Hagen A.T., Jette C.A., Hoffmans R., Pascual J., Imamura S., Kishi S., Amatruda J.F., Kanki J.P., Green D.R., D'Andrea A.A., Look A.T.
Cell 133:864-877(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN APOPTOSIS.
[49]"Nek6 is involved in G2/M phase cell cycle arrest through DNA damage-induced phosphorylation."
Lee M.Y., Kim H.J., Kim M.A., Jee H.J., Kim A.J., Bae Y.S., Park J.I., Chung J.H., Yun J.
Cell Cycle 7:2705-2709(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF NEK6.
[50]"Chk1 and Claspin potentiate PCNA ubiquitination."
Yang X.H., Shiotani B., Classon M., Zou L.
Genes Dev. 22:1147-1152(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN REPLICATION FORK MAINTENANCE, FUNCTION IN PCNA UBIQUITINATION.
[51]"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-301, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[52]"The checkpoint kinases Chk1 and Chk2 regulate the functional associations between hBRCA2 and Rad51 in response to DNA damage."
Bahassi E.M., Ovesen J.L., Riesenberg A.L., Bernstein W.Z., Hasty P.E., Stambrook P.J.
Oncogene 27:3977-3985(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN RAD51-MEDIATED DNA REPAIR, FUNCTION IN PHOSPHORYLATION OF BRCA2 AND RAD51.
[53]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-286; SER-296 AND SER-301, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[54]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[55]"The F box protein Fbx6 regulates Chk1 stability and cellular sensitivity to replication stress."
Zhang Y.-W., Brognard J., Coughlin C., You Z., Dolled-Filhart M., Aslanian A., Manning G., Abraham R.T., Hunter T.
Mol. Cell 35:442-453(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-345, UBIQUITINATION AT LYS-436, INTERACTION WITH FBXO6, MUTAGENESIS OF SER-345; ARG-372; ARG-376; ARG-379 AND LYS-436.
[56]"Large-scale proteomics analysis of the human kinome."
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H.
Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-296, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[57]"NEK11 regulates CDC25A degradation and the IR-induced G2/M checkpoint."
Melixetian M., Klein D.K., Soerensen C.S., Helin K.
Nat. Cell Biol. 11:1247-1253(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN NEK11 PHOSPHORYLATION.
[58]"Human FEM1B is required for Rad9 recruitment and CHK1 activation in response to replication stress."
Sun T.P., Shieh S.Y.
Oncogene 28:1971-1981(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH FEM1B.
[59]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-301, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[60]"NEK11: linking CHK1 and CDC25A in DNA damage checkpoint signaling."
Soerensen C.S., Melixetian M., Klein D.K., Helin K.
Cell Cycle 9:450-455(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN CDC25A DEGRADATION.
[61]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-286; SER-296 AND SER-301, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[62]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[63]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[64]"The 1.7 A crystal structure of human cell cycle checkpoint kinase Chk1: implications for Chk1 regulation."
Chen P., Luo C., Deng Y., Ryan K., Register J., Margosiak S., Tempczyk-Russell A., Nguyen B., Myers P., Lundgren K., Kan C.-C., O'Connor P.M.
Cell 100:681-692(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 1-289.
[65]"Structural basis for Chk1 inhibition by UCN-01."
Zhao B., Bower M.J., McDevitt P.J., Zhao H., Davis S.T., Johanson K.O., Green S.M., Concha N.O., Zhou B.-B.S.
J. Biol. Chem. 277:46609-46615(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 1-289.
[66]"Structure-based design of novel Chk1 inhibitors: insights into hydrogen bonding and protein-ligand affinity."
Foloppe N., Fisher L.M., Howes R., Kierstan P., Potter A., Robertson A.G.S., Surgenor A.E.
J. Med. Chem. 48:4332-4345(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 1-289.
[67]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] VAL-223 AND MET-312.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF016582 mRNA. Translation: AAC51736.1.
AF032874 mRNA. Translation: AAB88852.1.
AB032387 Genomic DNA. Translation: BAA84577.1.
JF289264 mRNA. Translation: AEB71796.1.
AK292549 mRNA. Translation: BAF85238.1.
AK293143 mRNA. Translation: BAG56691.1.
AK299783 mRNA. Translation: BAG61665.1.
AF527555 Genomic DNA. Translation: AAM78553.1.
AB451222 mRNA. Translation: BAG70036.1.
AB451345 mRNA. Translation: BAG70159.1.
AP001132 Genomic DNA. No translation available.
CH471065 Genomic DNA. Translation: EAW67644.1.
BC004202 mRNA. Translation: AAH04202.1.
BC017575 mRNA. Translation: AAH17575.1.
RefSeqNP_001107593.1. NM_001114121.2.
NP_001107594.1. NM_001114122.2.
NP_001231775.1. NM_001244846.1.
NP_001265.2. NM_001274.5.
UniGeneHs.24529.
Hs.595920.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1IA8X-ray1.70A1-289[»]
1NVQX-ray2.00A1-289[»]
1NVRX-ray1.80A1-289[»]
1NVSX-ray1.80A1-289[»]
1ZLTX-ray1.74A1-289[»]
1ZYSX-ray1.70A1-273[»]
2AYPX-ray2.90A1-269[»]
2BR1X-ray2.00A1-289[»]
2BRBX-ray2.10A1-289[»]
2BRGX-ray2.10A1-289[»]
2BRHX-ray2.10A1-289[»]
2BRMX-ray2.20A1-289[»]
2BRNX-ray2.80A1-289[»]
2BROX-ray2.20A1-289[»]
2C3JX-ray2.10A1-289[»]
2C3KX-ray2.60A1-289[»]
2C3LX-ray2.35A1-289[»]
2CGUX-ray2.50A1-289[»]
2CGVX-ray2.60A1-289[»]
2CGWX-ray2.20A1-289[»]
2CGXX-ray2.20A1-289[»]
2E9NX-ray2.50A2-270[»]
2E9OX-ray2.10A2-270[»]
2E9PX-ray2.60A2-270[»]
2E9UX-ray2.00A2-270[»]
2E9VX-ray2.00A/B2-269[»]
2GDOX-ray3.00A1-289[»]
2GHGX-ray3.50A2-270[»]
2HOGX-ray1.90A2-307[»]
2HXLX-ray1.80A2-307[»]
2HXQX-ray2.00A2-307[»]
2HY0X-ray1.70A2-307[»]
2QHMX-ray2.00A1-307[»]
2QHNX-ray1.70A1-307[»]
2R0UX-ray1.90A1-307[»]
2WMQX-ray2.48A1-289[»]
2WMRX-ray2.43A1-289[»]
2WMSX-ray2.70A1-289[»]
2WMTX-ray2.55A1-289[»]
2WMUX-ray2.60A1-289[»]
2WMVX-ray2.01A1-289[»]
2WMWX-ray2.43A1-289[»]
2WMXX-ray2.45A1-289[»]
2X8DX-ray1.90A1-289[»]
2X8EX-ray2.50A1-276[»]
2X8IX-ray1.92A1-289[»]
2XEYX-ray2.70A1-289[»]
2XEZX-ray2.25A1-289[»]
2XF0X-ray2.40A1-289[»]
2YDIX-ray1.60A1-289[»]
2YDJX-ray1.85A/B1-276[»]
2YDKX-ray1.90A1-276[»]
2YERX-ray1.83A1-276[»]
2YEXX-ray1.30A1-276[»]
2YM3X-ray2.01A1-289[»]
2YM4X-ray2.35A1-289[»]
2YM5X-ray2.03A1-289[»]
2YM6X-ray2.01A1-289[»]
2YM7X-ray1.81A1-289[»]
2YM8X-ray2.07A1-289[»]
2YWPX-ray2.90A2-270[»]
3F9NX-ray1.90A2-307[»]
3JVRX-ray1.76A2-272[»]
3JVSX-ray1.90A2-272[»]
3NLBX-ray1.90A1-289[»]
3OT3X-ray1.44A2-274[»]
3OT8X-ray1.65A2-274[»]
3PA3X-ray1.40A2-274[»]
3PA4X-ray1.59A2-274[»]
3PA5X-ray1.70A2-274[»]
3TKHX-ray1.79A1-307[»]
3TKIX-ray1.60A1-307[»]
3U9NX-ray1.85A2-274[»]
4FSMX-ray2.30A2-280[»]
4FSNX-ray2.10A4-280[»]
4FSQX-ray2.40A2-280[»]
4FSRX-ray2.50A2-280[»]
4FSTX-ray1.90A2-270[»]
4FSUX-ray2.10A2-280[»]
4FSWX-ray2.30A2-280[»]
4FSYX-ray2.30A2-280[»]
4FSZX-ray2.30A2-280[»]
4FT0X-ray2.30A2-280[»]
4FT3X-ray2.50A2-280[»]
4FT5X-ray2.40A2-280[»]
4FT7X-ray2.20A2-280[»]
4FT9X-ray2.20A2-280[»]
4FTAX-ray2.40A2-280[»]
4FTCX-ray2.00A2-280[»]
4FTIX-ray2.20A2-280[»]
4FTJX-ray2.20A2-280[»]
4FTKX-ray2.30A2-280[»]
4FTLX-ray2.50A2-280[»]
4FTMX-ray1.90A2-280[»]
4FTNX-ray2.02A2-280[»]
4FTOX-ray2.10A2-280[»]
4FTQX-ray2.00A2-280[»]
4FTRX-ray2.25A2-280[»]
4FTTX-ray2.30A2-280[»]
4FTUX-ray2.10A2-280[»]
4GH2X-ray2.03A2-280[»]
4HYHX-ray1.70A1-289[»]
4HYIX-ray1.40A1-289[»]
4JIKX-ray1.90A2-274[»]
ProteinModelPortalO14757.
SMRO14757. Positions 2-447.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107536. 61 interactions.
DIPDIP-24182N.
IntActO14757. 30 interactions.
MINTMINT-1179072.
STRING9606.ENSP00000278916.

Chemistry

BindingDBO14757.
ChEMBLCHEMBL4630.
GuidetoPHARMACOLOGY1987.

PTM databases

PhosphoSiteO14757.

Proteomic databases

PaxDbO14757.
PRIDEO14757.

Protocols and materials databases

DNASU1111.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000428830; ENSP00000412504; ENSG00000149554. [O14757-1]
ENST00000438015; ENSP00000388648; ENSG00000149554. [O14757-1]
ENST00000524737; ENSP00000432890; ENSG00000149554. [O14757-1]
ENST00000534070; ENSP00000435371; ENSG00000149554. [O14757-1]
ENST00000544373; ENSP00000442317; ENSG00000149554. [O14757-3]
GeneID1111.
KEGGhsa:1111.
UCSCuc001qcf.4. human. [O14757-1]

Organism-specific databases

CTD1111.
GeneCardsGC11P125495.
H-InvDBHIX0201657.
HGNCHGNC:1925. CHEK1.
HPACAB002049.
HPA044364.
MIM603078. gene.
neXtProtNX_O14757.
PharmGKBPA110.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000216658.
HOVERGENHBG002590.
InParanoidO14757.
KOK02216.
OMAGGFSKHI.
PhylomeDBO14757.
TreeFamTF351441.

Enzyme and pathway databases

BRENDA2.7.11.1. 2681.
ReactomeREACT_111102. Signal Transduction.
REACT_115566. Cell Cycle.
SignaLinkO14757.

Gene expression databases

ArrayExpressO14757.
BgeeO14757.
CleanExHS_CHEK1.
GenevestigatorO14757.

Family and domain databases

InterProIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 2 hits.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSCHEK1. human.
EvolutionaryTraceO14757.
GeneWikiCHEK1.
GenomeRNAi1111.
NextBio4608.
PROO14757.
SOURCESearch...

Entry information

Entry nameCHK1_HUMAN
AccessionPrimary (citable) accession number: O14757
Secondary accession number(s): A8K934 expand/collapse secondary AC list , B4DDD0, B4DSK3, B5BTY6, F5H7S4, H2BI51
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: January 11, 2011
Last modified: April 16, 2014
This is version 167 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM