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Protein

Serine/threonine-protein kinase Chk1

Gene

CHEK1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulationi

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.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei38 – 381ATPPROSITE-ProRule annotation
Active sitei130 – 1301Proton acceptor

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi15 – 239ATPPROSITE-ProRule annotation

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • histone kinase activity (H3-T11 specific) Source: UniProtKB
  • kinase activity Source: Reactome
  • protein kinase activity Source: CACAO
  • protein serine/threonine kinase activity Source: UniProtKB

GO - Biological processi

  • cellular response to DNA damage stimulus Source: UniProtKB
  • cellular response to mechanical stimulus Source: UniProtKB
  • chromatin-mediated maintenance of transcription Source: UniProtKB
  • DNA damage checkpoint Source: UniProtKB
  • DNA damage induced protein phosphorylation Source: UniProtKB
  • DNA repair Source: UniProtKB
  • DNA replication Source: Reactome
  • G2/M transition of mitotic cell cycle Source: Ensembl
  • G2 DNA damage checkpoint Source: UniProtKB
  • negative regulation of mitotic nuclear division Source: UniProtKB
  • peptidyl-threonine phosphorylation Source: UniProtKB
  • regulation of cell proliferation Source: Ensembl
  • regulation of double-strand break repair via homologous recombination Source: UniProtKB
  • regulation of histone H3-K9 acetylation Source: UniProtKB
  • regulation of mitotic centrosome separation Source: UniProtKB
  • regulation of signal transduction by p53 class mediator Source: Reactome
  • regulation of transcription from RNA polymerase II promoter in response to UV-induced DNA damage Source: UniProtKB
  • replicative senescence Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Cell cycle, DNA damage, DNA repair

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.1. 2681.
ReactomeiR-HSA-1433557. Signaling by SCF-KIT.
R-HSA-176187. Activation of ATR in response to replication stress.
R-HSA-5693607. Processing of DNA double-strand break ends.
R-HSA-5693616. Presynaptic phase of homologous DNA pairing and strand exchange.
R-HSA-6796648. TP53 Regulates Transcription of DNA Repair Genes.
R-HSA-6804756. Regulation of TP53 Activity through Phosphorylation.
R-HSA-69473. G2/M DNA damage checkpoint.
R-HSA-69601. Ubiquitin Mediated Degradation of Phosphorylated Cdc25A.
R-HSA-75035. Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex.
SignaLinkiO14757.
SIGNORiO14757.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:CHEK1
Synonyms:CHK1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:1925. CHEK1.

Subcellular locationi

GO - Cellular componenti

  • centrosome Source: UniProtKB
  • chromatin Source: UniProtKB
  • condensed nuclear chromosome Source: UniProtKB
  • cytosol Source: Reactome
  • extracellular space Source: UniProtKB
  • intracellular membrane-bounded organelle Source: HPA
  • nucleoplasm Source: HPA
  • nucleus Source: UniProtKB
  • replication fork Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi38 – 381K → R: Abolishes kinase activity. 2 Publications
Mutagenesisi130 – 1301D → A: Abolishes kinase activity. 8 Publications
Mutagenesisi317 – 3171S → 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. 5 Publications
Mutagenesisi317 – 3171S → E: Enhances interaction with RAD51; when associated with E-345. 5 Publications
Mutagenesisi344 – 3441F → A: Impairs nuclear export. 1 Publication
Mutagenesisi345 – 3451S → 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. 6 Publications
Mutagenesisi345 – 3451S → E: Enhances interaction with RAD51; when associated with E-317. 6 Publications
Mutagenesisi353 – 3531M → A: Impairs nuclear export. 1 Publication
Mutagenesisi357 – 3571S → A: No effect on phosphorylation induced by hydroxyurea. 1 Publication
Mutagenesisi366 – 3661S → A: No effect on phosphorylation induced by hydroxyurea. 1 Publication
Mutagenesisi372 – 3721R → 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. 1 Publication
Mutagenesisi376 – 3761R → 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. 1 Publication
Mutagenesisi379 – 3791R → 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. 1 Publication
Mutagenesisi436 – 4361K → R: Enhances stability of the protein, probably by preventing ubiquitination at this site. 1 Publication
Mutagenesisi468 – 4681S → A: No effect on phosphorylation induced by hydroxyurea. 1 Publication

Organism-specific databases

PharmGKBiPA110.

Chemistry

ChEMBLiCHEMBL4630.
GuidetoPHARMACOLOGYi1987.

Polymorphism and mutation databases

BioMutaiCHEK1.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 476476Serine/threonine-protein kinase Chk1PRO_0000085848Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei280 – 2801PhosphoserineCombined sources
Modified residuei286 – 2861PhosphoserineCombined sources
Modified residuei296 – 2961PhosphoserineCombined sources1 Publication
Modified residuei301 – 3011PhosphoserineCombined sources
Modified residuei317 – 3171Phosphoserine; by ATM and ATR9 Publications
Modified residuei331 – 3311PhosphoserineCombined sources
Modified residuei345 – 3451Phosphoserine; by ATM and ATR12 Publications
Cross-linki436 – 436Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)2 Publications
Modified residuei467 – 4671PhosphoserineCombined sources
Modified residuei468 – 4681PhosphoserineCombined sources

Post-translational modificationi

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.16 Publications
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.By similarity13 Publications

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiO14757.
MaxQBiO14757.
PaxDbiO14757.
PeptideAtlasiO14757.
PRIDEiO14757.

PTM databases

iPTMnetiO14757.
PhosphoSiteiO14757.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSG00000149554.
CleanExiHS_CHEK1.
ExpressionAtlasiO14757. baseline and differential.
GenevisibleiO14757. HS.

Organism-specific databases

HPAiHPA044364.

Interactioni

Subunit structurei

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. Interacts with CDK5RAP3; antagonizes CHEK1 (PubMed:19223857).12 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
BRCA1P383983EBI-974488,EBI-349905
CDC25CP303072EBI-974488,EBI-974439
CHUKQ95KV13EBI-974488,EBI-7669068From a different organism.
CLSPNQ9HAW45EBI-974488,EBI-1369377
ERRFI1Q9UJM32EBI-974488,EBI-2941912
HSP90AB1P082383EBI-974488,EBI-352572
MEN1O002552EBI-974488,EBI-592789
RAD51Q066093EBI-974488,EBI-297202
RB1P064003EBI-974488,EBI-491274
SMURF1Q9HCE7-24EBI-974488,EBI-9845742
TIMELESSQ9UNS12EBI-974488,EBI-2212315
YWHAGP619817EBI-974488,EBI-359832

Protein-protein interaction databases

BioGridi107536. 88 interactions.
DIPiDIP-24182N.
IntActiO14757. 36 interactions.
MINTiMINT-1179072.
STRINGi9606.ENSP00000388648.

Chemistry

BindingDBiO14757.

Structurei

Secondary structure

1
476
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi3 – 86Combined sources
Beta strandi9 – 179Combined sources
Beta strandi19 – 2810Combined sources
Turni29 – 313Combined sources
Beta strandi34 – 418Combined sources
Helixi42 – 443Combined sources
Helixi48 – 6013Combined sources
Beta strandi70 – 767Combined sources
Beta strandi79 – 857Combined sources
Beta strandi88 – 914Combined sources
Helixi92 – 954Combined sources
Turni98 – 1003Combined sources
Helixi104 – 12320Combined sources
Beta strandi125 – 1273Combined sources
Helixi133 – 1353Combined sources
Beta strandi136 – 1383Combined sources
Beta strandi144 – 1463Combined sources
Helixi149 – 1513Combined sources
Beta strandi153 – 1575Combined sources
Helixi171 – 1733Combined sources
Helixi176 – 1794Combined sources
Beta strandi182 – 1843Combined sources
Helixi186 – 20318Combined sources
Beta strandi209 – 2113Combined sources
Beta strandi213 – 2153Combined sources
Helixi216 – 2227Combined sources
Beta strandi227 – 2293Combined sources
Helixi231 – 2333Combined sources
Helixi236 – 24510Combined sources
Turni250 – 2523Combined sources
Helixi256 – 2594Combined sources
Turni263 – 2664Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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[»]
4QYEX-ray2.05A1-289[»]
4QYFX-ray2.15A1-289[»]
4QYGX-ray1.75A/B1-289[»]
4QYHX-ray1.90A/B1-289[»]
4RVKX-ray1.85A1-289[»]
4RVLX-ray1.85A1-289[»]
4RVMX-ray1.86A1-289[»]
5DLSX-ray2.15A1-289[»]
5F4NX-ray1.91A1-273[»]
ProteinModelPortaliO14757.
SMRiO14757. Positions 2-310.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO14757.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini9 – 265257Protein kinasePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 265265Interaction with CLSPNBy similarityAdd
BLAST
Regioni391 – 47686Autoinhibitory regionAdd
BLAST

Domaini

The autoinhibitory region (AIR) inhibits the activity of the kinase domain.1 Publication

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0590. Eukaryota.
ENOG410XQ0D. LUCA.
GeneTreeiENSGT00680000099954.
HOGENOMiHOG000216658.
HOVERGENiHBG002590.
InParanoidiO14757.
KOiK02216.
OMAiGGFSKHI.
PhylomeDBiO14757.
TreeFamiTF351441.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 2 hits.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O14757-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MAVPFVEDWD LVQTLGEGAY GEVQLAVNRV TEEAVAVKIV DMKRAVDCPE
60 70 80 90 100
NIKKEICINK MLNHENVVKF YGHRREGNIQ YLFLEYCSGG ELFDRIEPDI
110 120 130 140 150
GMPEPDAQRF FHQLMAGVVY LHGIGITHRD IKPENLLLDE RDNLKISDFG
160 170 180 190 200
LATVFRYNNR ERLLNKMCGT LPYVAPELLK RREFHAEPVD VWSCGIVLTA
210 220 230 240 250
MLAGELPWDQ PSDSCQEYSD WKEKKTYLNP WKKIDSAPLA LLHKILVENP
260 270 280 290 300
SARITIPDIK KDRWYNKPLK KGAKRPRVTS GGVSESPSGF SKHIQSNLDF
310 320 330 340 350
SPVNSASSEE NVKYSSSQPE PRTGLSLWDT SPSYIDKLVQ GISFSQPTCP
360 370 380 390 400
DHMLLNSQLL GTPGSSQNPW QRLVKRMTRF FTKLDADKSY QCLKETCEKL
410 420 430 440 450
GYQWKKSCMN QVTISTTDRR NNKLIFKVNL LEMDDKILVD FRLSKGDGLE
460 470
FKRHFLKIKG KLIDIVSSQK IWLPAT
Length:476
Mass (Da):54,434
Last modified:January 11, 2011 - v2
Checksum:i0ABD0FAB67E60F67
GO
Isoform 2 (identifier: O14757-2) [UniParc]FASTAAdd to basket
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

Show »
Length:382
Mass (Da):43,703
Checksum:i3ECD01BEC168F007
GO
Isoform 3 (identifier: O14757-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     412-445: Missing.

Note: No experimental confirmation available.
Show »
Length:442
Mass (Da):50,415
Checksum:i05680C63BD1287B6
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti163 – 1631L → S in BAG56691 (PubMed:14702039).Curated
Sequence conflicti220 – 2201D → G in BAG61665 (PubMed:22184239).Curated
Sequence conflicti381 – 3811F → L in BAG61665 (PubMed:22184239).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti156 – 1561R → Q.1 Publication
Corresponds to variant rs3731410 [ dbSNP | Ensembl ].
VAR_021123
Natural varianti223 – 2231E → V.1 Publication
Corresponds to variant rs35817404 [ dbSNP | Ensembl ].
VAR_040407
Natural varianti312 – 3121V → M.1 Publication
Corresponds to variant rs34097480 [ dbSNP | Ensembl ].
VAR_040408
Natural varianti471 – 4711I → V.8 Publications
Corresponds to variant rs506504 [ dbSNP | Ensembl ].
VAR_024571

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 9494Missing in isoform 2. 2 PublicationsVSP_044008Add
BLAST
Alternative sequencei95 – 973RIE → MEK in isoform 2. 2 PublicationsVSP_044009
Alternative sequencei412 – 44534Missing in isoform 3. 1 PublicationVSP_045075Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS58191.1. [O14757-3]
CCDS8459.1. [O14757-1]
RefSeqiNP_001107593.1. NM_001114121.2. [O14757-1]
NP_001107594.1. NM_001114122.2. [O14757-1]
NP_001231775.1. NM_001244846.1. [O14757-3]
NP_001265.2. NM_001274.5. [O14757-1]
XP_011540865.1. XM_011542563.2. [O14757-2]
UniGeneiHs.24529.
Hs.595920.

Genome annotation databases

EnsembliENST00000428830; ENSP00000412504; ENSG00000149554. [O14757-1]
ENST00000438015; ENSP00000388648; ENSG00000149554. [O14757-1]
ENST00000524737; ENSP00000432890; ENSG00000149554. [O14757-1]
ENST00000532449; ENSP00000481616; ENSG00000149554. [O14757-3]
ENST00000534070; ENSP00000435371; ENSG00000149554. [O14757-1]
ENST00000544373; ENSP00000442317; ENSG00000149554. [O14757-2]
GeneIDi1111.
KEGGihsa:1111.
UCSCiuc001qcf.5. human. [O14757-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS58191.1. [O14757-3]
CCDS8459.1. [O14757-1]
RefSeqiNP_001107593.1. NM_001114121.2. [O14757-1]
NP_001107594.1. NM_001114122.2. [O14757-1]
NP_001231775.1. NM_001244846.1. [O14757-3]
NP_001265.2. NM_001274.5. [O14757-1]
XP_011540865.1. XM_011542563.2. [O14757-2]
UniGeneiHs.24529.
Hs.595920.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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[»]
4QYEX-ray2.05A1-289[»]
4QYFX-ray2.15A1-289[»]
4QYGX-ray1.75A/B1-289[»]
4QYHX-ray1.90A/B1-289[»]
4RVKX-ray1.85A1-289[»]
4RVLX-ray1.85A1-289[»]
4RVMX-ray1.86A1-289[»]
5DLSX-ray2.15A1-289[»]
5F4NX-ray1.91A1-273[»]
ProteinModelPortaliO14757.
SMRiO14757. Positions 2-310.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107536. 88 interactions.
DIPiDIP-24182N.
IntActiO14757. 36 interactions.
MINTiMINT-1179072.
STRINGi9606.ENSP00000388648.

Chemistry

BindingDBiO14757.
ChEMBLiCHEMBL4630.
GuidetoPHARMACOLOGYi1987.

PTM databases

iPTMnetiO14757.
PhosphoSiteiO14757.

Polymorphism and mutation databases

BioMutaiCHEK1.

Proteomic databases

EPDiO14757.
MaxQBiO14757.
PaxDbiO14757.
PeptideAtlasiO14757.
PRIDEiO14757.

Protocols and materials databases

DNASUi1111.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000428830; ENSP00000412504; ENSG00000149554. [O14757-1]
ENST00000438015; ENSP00000388648; ENSG00000149554. [O14757-1]
ENST00000524737; ENSP00000432890; ENSG00000149554. [O14757-1]
ENST00000532449; ENSP00000481616; ENSG00000149554. [O14757-3]
ENST00000534070; ENSP00000435371; ENSG00000149554. [O14757-1]
ENST00000544373; ENSP00000442317; ENSG00000149554. [O14757-2]
GeneIDi1111.
KEGGihsa:1111.
UCSCiuc001qcf.5. human. [O14757-1]

Organism-specific databases

CTDi1111.
GeneCardsiCHEK1.
H-InvDBHIX0201657.
HGNCiHGNC:1925. CHEK1.
HPAiHPA044364.
MIMi603078. gene.
neXtProtiNX_O14757.
PharmGKBiPA110.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0590. Eukaryota.
ENOG410XQ0D. LUCA.
GeneTreeiENSGT00680000099954.
HOGENOMiHOG000216658.
HOVERGENiHBG002590.
InParanoidiO14757.
KOiK02216.
OMAiGGFSKHI.
PhylomeDBiO14757.
TreeFamiTF351441.

Enzyme and pathway databases

BRENDAi2.7.11.1. 2681.
ReactomeiR-HSA-1433557. Signaling by SCF-KIT.
R-HSA-176187. Activation of ATR in response to replication stress.
R-HSA-5693607. Processing of DNA double-strand break ends.
R-HSA-5693616. Presynaptic phase of homologous DNA pairing and strand exchange.
R-HSA-6796648. TP53 Regulates Transcription of DNA Repair Genes.
R-HSA-6804756. Regulation of TP53 Activity through Phosphorylation.
R-HSA-69473. G2/M DNA damage checkpoint.
R-HSA-69601. Ubiquitin Mediated Degradation of Phosphorylated Cdc25A.
R-HSA-75035. Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex.
SignaLinkiO14757.
SIGNORiO14757.

Miscellaneous databases

ChiTaRSiCHEK1. human.
EvolutionaryTraceiO14757.
GeneWikiiCHEK1.
GenomeRNAii1111.
PROiO14757.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000149554.
CleanExiHS_CHEK1.
ExpressionAtlasiO14757. baseline and differential.
GenevisibleiO14757. HS.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 2 hits.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCHK1_HUMAN
AccessioniPrimary (citable) accession number: O14757
Secondary accession number(s): A8K934
, B4DDD0, B4DSK3, B5BTY6, F5H7S4, H2BI51
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: January 11, 2011
Last modified: September 7, 2016
This is version 192 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.