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O14757

- CHK1_HUMAN

UniProt

O14757 - CHK1_HUMAN

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Protein

Serine/threonine-protein kinase Chk1

Gene

CHEK1

Organism
Homo sapiens (Human)
Status
Reviewed - 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

  1. ATP binding Source: UniProtKB-KW
  2. histone kinase activity (H3-T11 specific) Source: UniProtKB
  3. protein serine/threonine kinase activity Source: UniProtKB

GO - Biological processi

  1. cellular response to caffeine Source: Ensembl
  2. cellular response to DNA damage stimulus Source: UniProtKB
  3. cellular response to mechanical stimulus Source: UniProtKB
  4. chromatin-mediated maintenance of transcription Source: UniProtKB
  5. DNA damage checkpoint Source: UniProtKB
  6. DNA damage induced protein phosphorylation Source: UniProtKB
  7. DNA repair Source: UniProtKB
  8. DNA replication Source: Reactome
  9. G2/M transition of mitotic cell cycle Source: Ensembl
  10. G2 DNA damage checkpoint Source: UniProtKB
  11. negative regulation of mitosis Source: UniProtKB
  12. peptidyl-threonine phosphorylation Source: UniProtKB
  13. regulation of cell proliferation Source: Ensembl
  14. regulation of double-strand break repair via homologous recombination Source: UniProtKB
  15. regulation of histone H3-K9 acetylation Source: UniProtKB
  16. regulation of mitotic centrosome separation Source: UniProtKB
  17. regulation of transcription from RNA polymerase II promoter in response to UV-induced DNA damage Source: UniProtKB
  18. 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.
ReactomeiREACT_111040. Signaling by SCF-KIT.
REACT_1614. Ubiquitin Mediated Degradation of Phosphorylated Cdc25A.
REACT_407. Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex.
REACT_6769. Activation of ATR in response to replication stress.
REACT_897. G2/M DNA damage checkpoint.
SignaLinkiO14757.

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
ProteomesiUP000005640: Chromosome 11

Organism-specific databases

HGNCiHGNC:1925. CHEK1.

Subcellular locationi

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.

GO - Cellular componenti

  1. centrosome Source: UniProtKB
  2. chromatin Source: UniProtKB
  3. condensed nuclear chromosome Source: UniProtKB
  4. cytosol Source: Reactome
  5. extracellular space Source: UniProt
  6. intracellular membrane-bounded organelle Source: HPA
  7. nucleoplasm Source: Reactome
  8. nucleus Source: UniProtKB
  9. 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.

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 – 2801Phosphoserine; by PKB/AKT1By similarity
Modified residuei286 – 2861Phosphoserine2 Publications
Modified residuei296 – 2961Phosphoserine4 Publications
Modified residuei301 – 3011Phosphoserine4 Publications
Modified residuei317 – 3171Phosphoserine; by ATM and ATR9 Publications
Modified residuei345 – 3451Phosphoserine; by ATM and ATR12 Publications
Cross-linki436 – 436Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)2 Publications

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

MaxQBiO14757.
PaxDbiO14757.
PRIDEiO14757.

PTM databases

PhosphoSiteiO14757.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiO14757.
CleanExiHS_CHEK1.
ExpressionAtlasiO14757. baseline and differential.
GenevestigatoriO14757.

Organism-specific databases

HPAiCAB002049.
HPA044364.

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.11 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
TIMELESSQ9UNS12EBI-974488,EBI-2212315
YWHAGP619817EBI-974488,EBI-359832

Protein-protein interaction databases

BioGridi107536. 69 interactions.
DIPiDIP-24182N.
IntActiO14757. 31 interactions.
MINTiMINT-1179072.
STRINGi9606.ENSP00000278916.

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[»]
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

eggNOGiCOG0515.
GeneTreeiENSGT00730000111032.
HOGENOMiHOG000216658.
HOVERGENiHBG002590.
InParanoidiO14757.
KOiK02216.
OMAiGGFSKHI.
PhylomeDBiO14757.
TreeFamiTF351441.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase.
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. Align

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_006718822.1. XM_006718759.1. [O14757-1]
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.4. 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 .
CCDSi CCDS58191.1. [O14757-3 ]
CCDS8459.1. [O14757-1 ]
RefSeqi NP_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_006718822.1. XM_006718759.1. [O14757-1 ]
UniGenei Hs.24529.
Hs.595920.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1IA8 X-ray 1.70 A 1-289 [» ]
1NVQ X-ray 2.00 A 1-289 [» ]
1NVR X-ray 1.80 A 1-289 [» ]
1NVS X-ray 1.80 A 1-289 [» ]
1ZLT X-ray 1.74 A 1-289 [» ]
1ZYS X-ray 1.70 A 1-273 [» ]
2AYP X-ray 2.90 A 1-269 [» ]
2BR1 X-ray 2.00 A 1-289 [» ]
2BRB X-ray 2.10 A 1-289 [» ]
2BRG X-ray 2.10 A 1-289 [» ]
2BRH X-ray 2.10 A 1-289 [» ]
2BRM X-ray 2.20 A 1-289 [» ]
2BRN X-ray 2.80 A 1-289 [» ]
2BRO X-ray 2.20 A 1-289 [» ]
2C3J X-ray 2.10 A 1-289 [» ]
2C3K X-ray 2.60 A 1-289 [» ]
2C3L X-ray 2.35 A 1-289 [» ]
2CGU X-ray 2.50 A 1-289 [» ]
2CGV X-ray 2.60 A 1-289 [» ]
2CGW X-ray 2.20 A 1-289 [» ]
2CGX X-ray 2.20 A 1-289 [» ]
2E9N X-ray 2.50 A 2-270 [» ]
2E9O X-ray 2.10 A 2-270 [» ]
2E9P X-ray 2.60 A 2-270 [» ]
2E9U X-ray 2.00 A 2-270 [» ]
2E9V X-ray 2.00 A/B 2-269 [» ]
2GDO X-ray 3.00 A 1-289 [» ]
2GHG X-ray 3.50 A 2-270 [» ]
2HOG X-ray 1.90 A 2-307 [» ]
2HXL X-ray 1.80 A 2-307 [» ]
2HXQ X-ray 2.00 A 2-307 [» ]
2HY0 X-ray 1.70 A 2-307 [» ]
2QHM X-ray 2.00 A 1-307 [» ]
2QHN X-ray 1.70 A 1-307 [» ]
2R0U X-ray 1.90 A 1-307 [» ]
2WMQ X-ray 2.48 A 1-289 [» ]
2WMR X-ray 2.43 A 1-289 [» ]
2WMS X-ray 2.70 A 1-289 [» ]
2WMT X-ray 2.55 A 1-289 [» ]
2WMU X-ray 2.60 A 1-289 [» ]
2WMV X-ray 2.01 A 1-289 [» ]
2WMW X-ray 2.43 A 1-289 [» ]
2WMX X-ray 2.45 A 1-289 [» ]
2X8D X-ray 1.90 A 1-289 [» ]
2X8E X-ray 2.50 A 1-276 [» ]
2X8I X-ray 1.92 A 1-289 [» ]
2XEY X-ray 2.70 A 1-289 [» ]
2XEZ X-ray 2.25 A 1-289 [» ]
2XF0 X-ray 2.40 A 1-289 [» ]
2YDI X-ray 1.60 A 1-289 [» ]
2YDJ X-ray 1.85 A/B 1-276 [» ]
2YDK X-ray 1.90 A 1-276 [» ]
2YER X-ray 1.83 A 1-276 [» ]
2YEX X-ray 1.30 A 1-276 [» ]
2YM3 X-ray 2.01 A 1-289 [» ]
2YM4 X-ray 2.35 A 1-289 [» ]
2YM5 X-ray 2.03 A 1-289 [» ]
2YM6 X-ray 2.01 A 1-289 [» ]
2YM7 X-ray 1.81 A 1-289 [» ]
2YM8 X-ray 2.07 A 1-289 [» ]
2YWP X-ray 2.90 A 2-270 [» ]
3F9N X-ray 1.90 A 2-307 [» ]
3JVR X-ray 1.76 A 2-272 [» ]
3JVS X-ray 1.90 A 2-272 [» ]
3NLB X-ray 1.90 A 1-289 [» ]
3OT3 X-ray 1.44 A 2-274 [» ]
3OT8 X-ray 1.65 A 2-274 [» ]
3PA3 X-ray 1.40 A 2-274 [» ]
3PA4 X-ray 1.59 A 2-274 [» ]
3PA5 X-ray 1.70 A 2-274 [» ]
3TKH X-ray 1.79 A 1-307 [» ]
3TKI X-ray 1.60 A 1-307 [» ]
3U9N X-ray 1.85 A 2-274 [» ]
4FSM X-ray 2.30 A 2-280 [» ]
4FSN X-ray 2.10 A 4-280 [» ]
4FSQ X-ray 2.40 A 2-280 [» ]
4FSR X-ray 2.50 A 2-280 [» ]
4FST X-ray 1.90 A 2-270 [» ]
4FSU X-ray 2.10 A 2-280 [» ]
4FSW X-ray 2.30 A 2-280 [» ]
4FSY X-ray 2.30 A 2-280 [» ]
4FSZ X-ray 2.30 A 2-280 [» ]
4FT0 X-ray 2.30 A 2-280 [» ]
4FT3 X-ray 2.50 A 2-280 [» ]
4FT5 X-ray 2.40 A 2-280 [» ]
4FT7 X-ray 2.20 A 2-280 [» ]
4FT9 X-ray 2.20 A 2-280 [» ]
4FTA X-ray 2.40 A 2-280 [» ]
4FTC X-ray 2.00 A 2-280 [» ]
4FTI X-ray 2.20 A 2-280 [» ]
4FTJ X-ray 2.20 A 2-280 [» ]
4FTK X-ray 2.30 A 2-280 [» ]
4FTL X-ray 2.50 A 2-280 [» ]
4FTM X-ray 1.90 A 2-280 [» ]
4FTN X-ray 2.02 A 2-280 [» ]
4FTO X-ray 2.10 A 2-280 [» ]
4FTQ X-ray 2.00 A 2-280 [» ]
4FTR X-ray 2.25 A 2-280 [» ]
4FTT X-ray 2.30 A 2-280 [» ]
4FTU X-ray 2.10 A 2-280 [» ]
4GH2 X-ray 2.03 A 2-280 [» ]
4HYH X-ray 1.70 A 1-289 [» ]
4HYI X-ray 1.40 A 1-289 [» ]
4JIK X-ray 1.90 A 2-274 [» ]
ProteinModelPortali O14757.
SMRi O14757. Positions 2-310.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 107536. 69 interactions.
DIPi DIP-24182N.
IntActi O14757. 31 interactions.
MINTi MINT-1179072.
STRINGi 9606.ENSP00000278916.

Chemistry

BindingDBi O14757.
ChEMBLi CHEMBL4630.
GuidetoPHARMACOLOGYi 1987.

PTM databases

PhosphoSitei O14757.

Proteomic databases

MaxQBi O14757.
PaxDbi O14757.
PRIDEi O14757.

Protocols and materials databases

DNASUi 1111.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000428830 ; 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 ]
GeneIDi 1111.
KEGGi hsa:1111.
UCSCi uc001qcf.4. human. [O14757-1 ]

Organism-specific databases

CTDi 1111.
GeneCardsi GC11P125495.
H-InvDB HIX0201657.
HGNCi HGNC:1925. CHEK1.
HPAi CAB002049.
HPA044364.
MIMi 603078. gene.
neXtProti NX_O14757.
PharmGKBi PA110.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG0515.
GeneTreei ENSGT00730000111032.
HOGENOMi HOG000216658.
HOVERGENi HBG002590.
InParanoidi O14757.
KOi K02216.
OMAi GGFSKHI.
PhylomeDBi O14757.
TreeFami TF351441.

Enzyme and pathway databases

BRENDAi 2.7.11.1. 2681.
Reactomei REACT_111040. Signaling by SCF-KIT.
REACT_1614. Ubiquitin Mediated Degradation of Phosphorylated Cdc25A.
REACT_407. Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex.
REACT_6769. Activation of ATR in response to replication stress.
REACT_897. G2/M DNA damage checkpoint.
SignaLinki O14757.

Miscellaneous databases

ChiTaRSi CHEK1. human.
EvolutionaryTracei O14757.
GeneWikii CHEK1.
GenomeRNAii 1111.
NextBioi 4608.
PROi O14757.
SOURCEi Search...

Gene expression databases

Bgeei O14757.
CleanExi HS_CHEK1.
ExpressionAtlasi O14757. baseline and differential.
Genevestigatori O14757.

Family and domain databases

InterProi IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view ]
Pfami PF00069. Pkinase. 1 hit.
[Graphical view ]
SMARTi SM00220. S_TKc. 1 hit.
[Graphical view ]
SUPFAMi SSF56112. SSF56112. 2 hits.
PROSITEi PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. 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.
    , 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.
    , 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. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  9. 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. "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.
  18. "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.
  19. "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.
  20. "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.
  21. "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.
  22. "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.
  23. "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.
  24. "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.
  25. "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.
  26. "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.
  27. "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.
  28. "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.
  29. "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.
  30. "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.
  31. "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.
  32. "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.
  33. "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.
  34. "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.
  35. Cited for: SUBCELLULAR LOCATION.
  36. "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.
  37. "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.
  38. "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.
  39. "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.
  40. "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.
  41. "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.
  42. "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.
  43. "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.
  44. "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.
  45. "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.
  46. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Embryonic kidney.
  47. "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.
  48. "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.
  49. "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.
  50. "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.
  51. "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.
  52. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-286; SER-296 AND SER-301, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  53. "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].
  54. "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.
  55. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-296, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  56. "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.
  57. "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.
  58. "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.
  59. "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.
  60. "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.
  61. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  62. "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].
  63. "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.
  64. Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 1-289.
  65. "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.
  66. "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.
    , 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.

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: October 29, 2014
This is version 173 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

External Data

Dasty 3