Homo sapiens L. (human) [HSA]

FULL NAME: Serine/threonine-protein kinase Chk1


DESCRIPTION:
Required for checkpoint mediated cell cycle arrest in response to DNA damage or the presence of unreplicated DNA. May also negatively regulate cell cycle progression during unperturbed cell cycles. 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. Inhibition of CDC25 activity leads to increased inhibitory tyrosine phosphorylation of CDK-cyclin complexes and blocks cell cycle progression. Binds to and phosphorylates RAD51 at 'Thr-309', which may enhance the association of RAD51 with chromatin and promote DNA repair by homologous recombination. Binds to and phosphorylates TLK1 at 'Ser-743', which prevents the TLK1-dependent phosphorylation of the chromatin assembly factor ASF1A. This may affect chromatin assembly during S phase or DNA repair. May also phosphorylate multiple sites within the C-terminus of TP53, which promotes activation of TP53 by acetylation and enhances suppression of cellular proliferation. Phosphorylates NEK6 and NEK11. Phosphorylation of CDC25A at Ser-76 primes it for subsequent phosphorylation at Ser-79, Ser-82 and Ser-88 by NEK11.

STRUCTURE SIMILARITY:
Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. NIM1 subfamily.
Contains 1 protein kinase domain.


CATALYTIC ACTIVITY:
ATP + a protein = ADP + a phosphoprotein.


POST-TRANSLATIONAL MODIFICATION:
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 of activated form is required to insure that activated CHK1 does not accumulate as cells progress through S phase, or when replication forks encounter transient impediments during normal DNA replication.
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. May also be phosphorylated at Ser-280 by AKT1/PKB, which may promote mono and/or diubiquitination. Also phosphorylated at undefined residues during mitotic arrest, which results in decreased activity.


PROTEIN TYPE(S):
kinase


RELATED PATHWAY(S):
DNA damage response (DDR)


Amino acids sequence

        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

Encoded by CHEK1 gene

FULL NAME: CHK1 checkpoint homolog (S. pombe)


OTHER NAME(S):
CHK1


Nucleic acid sequence

        10         20         30         40         50         60
atggcagtgc cctttgtgga agactgggac ttggtgcaaa ccctgggaga aggtgcctat
        70         80         90        100        110        120
ggagaagttc aacttgctgt gaatagagta actgaagaag cagtcgcagt gaagattgta
       130        140        150        160        170        180
gatatgaagc gtgccgtaga ctgtccagaa aatattaaga aagagatctg tatcaataaa
       190        200        210        220        230        240
atgctaaatc atgaaaatgt agtaaaattc tatggtcaca ggagagaagg caatatccaa
       250        260        270        280        290        300
tatttatttc tggagtactg tagtggagga gagctttttg acagaataga gccagacata
       310        320        330        340        350        360
ggcatgcctg aaccagatgc tcagagattc ttccatcaac tcatggcagg ggtggtttat
       370        380        390        400        410        420
ctgcatggta ttggaataac tcacagggat attaaaccag aaaatcttct gttggatgaa
       430        440        450        460        470        480
agggataacc tcaaaatctc agactttggc ttggcaacag tatttcggta taataatcgt
       490        500        510        520        530        540
gagcgtttgt tgaacaagat gtgtggtact ttaccatatg ttgctccaga acttctgaag
       550        560        570        580        590        600
agaagagaat ttcatgcaga accagttgat gtttggtcct gtggaatagt acttactgca
       610        620        630        640        650        660
atgctcgctg gagaattgcc atgggaccaa cccagtgaca gctgtcagga gtattctgac
       670        680        690        700        710        720
tggaaagaaa aaaaaacata cctcaaccct tggaaaaaaa tcgattctgc tcctctagct
       730        740        750        760        770        780
ctgctgcata aaatcttagt tgagaatcca tcagcaagaa ttaccattcc agacatcaaa
       790        800        810        820        830        840
aaagatagat ggtacaacaa acccctcaag aaaggggcaa aaaggccccg agtcacttca
       850        860        870        880        890        900
ggtggtgtgt cagagtctcc cagtggattt tctaagcaca ttcaatccaa tttggacttc
       910        920        930        940        950        960
tctccagtaa acagtgcttc tagtgaagaa aatgtgaagt actccagttc tcagccagaa
       970        980        990       1000       1010       1020
ccccgcacag gtctttcctt atgggatacc agcccctcat acattgataa attggtacaa
      1030       1040       1050       1060       1070       1080
gggatcagct tttcccagcc cacatgtcct gatcatatgc ttttgaatag tcagttactt
      1090       1100       1110       1120       1130       1140
ggcaccccag gatcctcaca gaacccctgg cagcggttgg tcaaaagaat gacacgattc
      1150       1160       1170       1180       1190       1200
tttaccaaat tggatgcaga caaatcttat caatgcctga aagagacttg tgagaagttg
      1210       1220       1230       1240       1250       1260
ggctatcaat ggaagaaaag ttgtatgaat caggttacta tatcaacaac tgataggaga
      1270       1280       1290       1300       1310       1320
aacaataaac tcattttcaa agtgaatttg ttagaaatgg atgataaaat attggttgac
      1330       1340       1350       1360       1370       1380
ttccggcttt ctaagggtga tggattggag ttcaagagac acttcctgaa gattaaaggg
      1390       1400       1410       1420       1430
aagctgattg atattgtgag cagccagaag atttggcttc ctgccacatg a

Last modification date: Oct. 2, 2011