Tag | Content |
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EKPD ID | EKS-HOS-00263 |
Classification | Group/Family | Score | E-Value | Start | End | Domain Length |
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CAMK/CAMKL | 287.2 | 5.0E-85 | 9 | 265 | 257 |
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Status | Reviewed |
Ensembl Protein | ENSP00000278916 |
UniProt Accession | O14757; A8K934; B4DSK3; B5BTY6; H2BI51; |
Protein Name | Serine/threonine-protein kinase Chk1 |
Protein Synonyms/Alias | CHK1 checkpoint homolog; Cell cycle checkpoint kinase; Checkpoint kinase-1; |
Gene Name | CHEK1 |
Gene Synonyms/Alias | CHEK1; CHK1; |
Ensembl Information | |
Organism | Homo sapiens |
Functional Description | Serine/threonine-protein kinase which is required forcheckpoint-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, interactswith, and antagonizes CHK1 to promote the S to G2/M phase transition. |
Protein Length | 432 |
Protein Sequence (FASTA) | MAVPFVEDWD LVQTLGEGAY GEVQLAVNRV TEEAVAVKIV DMKRAVDCPE NIKKEICINK 60 | MLNHENVVKF YGHRREGNIQ YLFLEYCSGG ELFDRIEPDI GMPEPDAQRF FHQLMAGVVY 120 | LHGIGITHRD IKPENLLLDE RDNLKISDFG LATVFRYNNR ERLLNKMCGT LPYVAPELLK 180 | RREFHAEPVD VWSCGIVLTA MLAGELPWDQ PSDSCQEYSD WKEKKTYLNP WKKIDSAPLA 240 | LLHKILVENP SARITIPDIK KDRWYNKPLK KGAKRPRVTS GGVSESPSGF SKHIQSNLDF 300 | SPVNSASSEE NVKYSSSQPE PRTGLSLWDT SPSYIDKLVQ GISFSQPTCP DHMLLNSQLL 360 | GTPGSSQVTI STTDRRNNKL IFKVNLLEMD DKILVDFRLS KGDGLEFKRH FLKIKGKLID 420 | IVSSQKIWLP AT 432 |
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Nucleotide Sequence (FASTA) | ATGGCAGTGC CCTTTGTGGA AGACTGGGAC TTGGTGCAAA CCCTGGGAGA AGGTGCCTAT 60 | GGAGAAGTTC AACTTGCTGT GAATAGAGTA ACTGAAGAAG CAGTCGCAGT GAAGATTGTA 120 | GATATGAAGC GTGCCGTAGA CTGTCCAGAA AATATTAAGA AAGAGATCTG TATCAATAAA 180 | ATGCTAAATC ATGAAAATGT AGTAAAATTC TATGGTCACA GGAGAGAAGG CAATATCCAA 240 | TATTTATTTC TGGAGTACTG TAGTGGAGGA GAGCTTTTTG ACAGAATAGA GCCAGACATA 300 | GGCATGCCTG AACCAGATGC TCAGAGATTC TTCCATCAAC TCATGGCAGG GGTGGTTTAT 360 | CTGCATGGTA TTGGAATAAC TCACAGGGAT ATTAAACCAG AAAATCTTCT GTTGGATGAA 420 | AGGGATAACC TCAAAATCTC AGACTTTGGC TTGGCAACAG TATTTCGGTA TAATAATCGT 480 | GAGCGTTTGT TGAACAAGAT GTGTGGTACT TTACCATATG TTGCTCCAGA ACTTCTGAAG 540 | AGAAGAGAAT TTCATGCAGA ACCAGTTGAT GTTTGGTCCT GTGGAATAGT ACTTACTGCA 600 | ATGCTCGCTG GAGAATTGCC ATGGGACCAA CCCAGTGACA GCTGTCAGGA GTATTCTGAC 660 | TGGAAAGAAA AAAAAACATA CCTCAACCCT TGGAAAAAAA TCGATTCTGC TCCTCTAGCT 720 | CTGCTGCATA AAATCTTAGT TGAGAATCCA TCAGCAAGAA TTACCATTCC AGACATCAAA 780 | AAAGATAGAT GGTACAACAA ACCCCTCAAG AAAGGGGCAA AAAGGCCCCG AGTCACTTCA 840 | GGTGGTGTGT CAGAGTCTCC CAGTGGATTT TCTAAGCACA TTCAATCCAA TTTGGACTTC 900 | TCTCCAGTAA ACAGTGCTTC TAGTGAAGAA AATGTGAAGT ACTCCAGTTC TCAGCCAGAA 960 | CCCCGCACAG GTCTTTCCTT ATGGGATACC AGCCCCTCAT ACATTGATAA ATTGGTACAA 1020 | GGGATCAGCT TTTCCCAGCC CACATGTCCT GATCATATGC TTTTGAATAG TCAGTTACTT 1080 | GGCACCCCAG GATCCTCACA GGTTACTATA TCAACAACTG ATAGGAGAAA CAATAAACTC 1140 | ATTTTCAAAG TGAATTTGTT AGAAATGGAT GATAAAATAT TGGTTGACTT CCGGCTTTCT 1200 | AAGGGTGATG GATTGGAGTT CAAGAGACAC TTCCTGAAGA TTAAAGGGAA GCTGATTGAT 1260 | ATTGTGAGCA GCCAGAAGAT TTGGCTTCCT GCCACATGA 1299 |
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Domain Profile | S: 1 ykllktlGegsfgkVklakhketkekvavKiikkkklseeslekikrEieilkklkhpni 60 | ++l++tlGeg++g+V+la+++ t+e+vavKi++ k++ + e+ik+Ei i k+l+h+n+ | Q: 9 WDLVQTLGEGAYGEVQLAVNRVTEEAVAVKIVDMKRAV-DCPENIKKEICINKMLNHENV 67 | 7899******************************7765.5579***************** |
| S: 61 ikllevietkkklylvleyasggeLfdyieekgrlkekearklfkqlvsavkYlhskgiv 120 | +k++ ++ + yl+ley+sggeLfd+ie + ++e +a+++f+ql+++v Ylh gi+ | Q: 68 VKFYGHRREGNIQYLFLEYCSGGELFDRIEPDIGMPEPDAQRFFHQLMAGVVYLHGIGIT 127 | ************************************************************ |
| S: 121 HrDlKpeNllldkkenikiaDFGlanlfkeg...klletfcGsppYaaPellkgkkYegp 177 | HrD+KpeNllld+++n+ki+DFGla++f+++ +ll+++cG++pY+aPellk+++++++ | Q: 128 HRDIKPENLLLDERDNLKISDFGLATVFRYNnreRLLNKMCGTLPYVAPELLKRREFHAE 187 | **************************9988777799************************ |
| S: 178 kvDvWslGvvLyalvtgklPfdee..nlkellekilkgkleipkk.lskelesLlrklLv 234 | +vDvWs+G+vL a+++g+lP+d++ +++e++++ +k+++ p k +++ Ll+k+Lv | Q: 188 PVDVWSCGIVLTAMLAGELPWDQPsdSCQEYSDWKEKKTYLNPWKkIDSAPLALLHKILV 247 | ***********************97679999999999999888778************** |
| S: 235 vdpekRatieeilkhewl 252 | ++p+ R+ti +i+k++w+ | Q: 248 ENPSARITIPDIKKDRWY 265 | *****************5 |
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Domain Sequence (FASTA) | WDLVQTLGEG AYGEVQLAVN RVTEEAVAVK IVDMKRAVDC PENIKKEICI NKMLNHENVV 60 | KFYGHRREGN IQYLFLEYCS GGELFDRIEP DIGMPEPDAQ RFFHQLMAGV VYLHGIGITH 120 | RDIKPENLLL DERDNLKISD FGLATVFRYN NRERLLNKMC GTLPYVAPEL LKRREFHAEP 180 | VDVWSCGIVL TAMLAGELPW DQPSDSCQEY SDWKEKKTYL NPWKKIDSAP LALLHKILVE 240 | NPSARITIPD IKKDRWY 257 |
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Keyword | 3D-structure; Alternative splicing; ATP-binding; Cell cycle; Complete proteome; Cytoplasm; Cytoskeleton; DNA damage; DNA repair; Isopeptide bond; Kinase; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Serine/threonine-protein kinase; Transferase; Ubl conjugation. |
Sequence Source | Ensembl |
Orthology | |
Gene Ontology | |
KEGG | |
InterPros | |
Pfam | |
SMARTs | |
Prosites | |
Prints | |
Created Date | 20-Feb-2013 |