EKS-MUM-00038

Eukaryotic Protein Kinase & Protein Phosphatase Database

Tag

Content

EKPD ID

EKS-MUM-00038

Classification

Group/Family	Score	E-Value	Start	End	Domain Length
CAMK/RAD53	443.0	8.4E-133	224	490	267

Status

Reviewed

Ensembl Protein

ENSMUSP00000066679

UniProt Accession

Q9Z265;

Protein Name

Serine/threonine-protein kinase Chk2

Protein Synonyms/Alias

CHK2 checkpoint homolog; Checkpoint kinase 2;

Gene Name

Chek2

Gene Synonyms/Alias

Chek2; Chk2, Rad53;

Ensembl Information

Ensembl Gene ID	Ensembl Protein ID	Ensembl Transcript ID
ENSMUSG00000029521	ENSMUSP00000066679	ENSMUST00000066160

Organism

Mus musculus

Functional Description

Serine/threonine-protein kinase which is required forcheckpoint-mediated cell cycle arrest, activation of DNA repair and apoptosis in response to the presence of DNA double-strand breaks. May also negatively regulate cell cycle progression during unperturbed cell cycles. Following activation, phosphorylates numerous effectors preferentially at the consensus sequence [L-X- R-X-X-S/T]. Regulates cell cycle checkpoint arrest through phosphorylation of CDC25A, CDC25B and CDC25C, inhibiting their activity. Inhibition of CDC25 phosphatase activity leads to increased inhibitory tyrosine phosphorylation of CDK-cyclin complexes and blocks cell cycle progression. May also phosphorylate NEK6 which is involved in G2/M cell cycle arrest. Regulates DNA repair through phosphorylation of BRCA2, enhancing the association of RAD51 with chromatin which promotes DNA repair by homologous recombination. Also stimulates the transcription of genes involved in DNA repair (including BRCA2) through the phosphorylation and activation of the transcription factor FOXM1. Regulates apoptosis through the phosphorylation of p53/TP53, MDM4 and PML. Phosphorylation of p53/TP53 at 'Ser-20' by CHEK2 may alleviate inhibition by MDM2, leading to accumulation of active p53/TP53. Phosphorylation of MDM4 may also reduce degradation of p53/TP53. Also controls the transcription of pro-apoptotic genes through phosphorylation of the transcription factor E2F1. Tumor suppressor, it may also have a DNA damage-independent function in mitotic spindle assembly by phosphorylating BRCA1. Its absence may be a cause of the chromosomal instability observed in some cancer cells.

Protein Length

546

Protein Sequence
(FASTA)

MKSHHQSHSS TSSKAHDSAS CSQSQGGFSQ PQGTPSQLHE LSQYQGSSSS STGTVPSSSQ 60

SSHSSSGTLS SLETVSTQEL CSIPEDQEPE EPGPAPWARL WALQDGFSNL DCVNDNYWFG 120

RDKSCEYCFD GPLLRRTDKY RTYSKKHFRI FREMGPKNCY IVYIEDHSGN GTFVNTELIG 180

KGKRCPLSNN SEIALSLCRN KVFVFFDLTV DDQSVYPKEL RDEYIMSKTL GSGACGEVKM 240

AFERKTCQKV AIKIISKRRF ALGSSREADT APSVETEIEI LKKLNHPCII KIKDVFDAED 300

YYIVLELMEG GELFDRVVGN KRLKEATCKL YFYQMLVAVQ YLHENGIIHR DLKPENVLLS 360

SQEEDCLIKI TDFGQSKILG ETSLMRTLCG TPTYLAPEVL VSNGTAGYSR AVDCWSLGVI 420

LFICLSGYPP FSEHKTQVSL KDQITSGKYN FIPEVWTDVS EEALDLVKKL LVVDPKARLT 480

TEEALNHPWL QDEYMKKKFQ DLLVQEKNSV TLPVAPAQTS SQKRPLELEV EGMPSTKRLS 540

VCGAVL 546

Nucleotide Sequence
(FASTA)

ATGAAGAGTC ATCATCAGTC CCACAGCAGC ACCTCCTCGA AGGCTCATGA CAGTGCTTCC 60

TGTTCACAGT CCCAGGGTGG CTTCAGCCAG CCCCAAGGCA CTCCTTCTCA GTTGCACGAG 120

CTCTCACAGT ATCAGGGTTC GTCCAGCTCC TCTACCGGCA CAGTGCCGTC CTCCAGCCAG 180

TCCTCGCACT CCAGTTCTGG GACTCTGAGC TCGCTGGAGA CAGTGTCTAC CCAGGAACTC 240

TGTTCTATTC CTGAGGACCA AGAACCTGAA GAACCTGGTC CTGCCCCTTG GGCTCGGCTA 300

TGGGCTCTTC AGGATGGATT CTCCAATCTA GACTGTGTTA ACGACAACTA CTGGTTTGGG 360

AGAGATAAAA GCTGTGAATA TTGCTTCGAT GGACCACTGT TGAGAAGGAC GGACAAGTAC 420

CGGACTTACA GCAAGAAGCA TTTTCGTATT TTCAGGGAAA TGGGCCCTAA AAATTGTTAC 480

ATCGTATACA TAGAGGATCA CAGTGGAAAT GGAACCTTCG TAAATACCGA GCTTATTGGG 540

AAAGGCAAAC GCTGTCCTCT GAGTAACAAC TCTGAAATCG CACTTTCACT ATGTAGAAAT 600

AAAGTTTTTG TATTTTTTGA TCTGACTGTA GATGATCAGT CAGTTTATCC TAAGGAATTA 660

AGAGACGAAT ACATCATGTC AAAAACTCTT GGAAGTGGTG CGTGTGGGGA GGTAAAGATG 720

GCTTTTGAGA GGAAGACATG TCAGAAAGTG GCCATAAAGA TCATTAGCAA GCGGAGGTTT 780

GCTCTTGGCT CATCGAGAGA AGCCGACACA GCTCCCAGTG TGGAAACTGA AATAGAAATT 840

TTGAAGAAAC TAAATCATCC ATGCATCATC AAGATTAAAG ATGTTTTTGA TGCGGAAGAT 900

TATTACATTG TTCTGGAACT GATGGAAGGA GGAGAACTAT TTGACCGGGT GGTGGGGAAC 960

AAGCGCCTGA AAGAAGCCAC CTGTAAGCTC TACTTCTACC AGATGCTTGT AGCTGTACAG 1020

TACCTTCACG AAAATGGGAT CATACATCGG GACTTAAAGC CGGAGAATGT TCTTTTATCA 1080

TCTCAGGAAG AGGATTGTCT AATCAAGATC ACTGACTTTG GGCAGTCCAA GATCTTGGGG 1140

GAGACCTCCT TGATGAGAAC CTTATGTGGT ACGCCCACTT ATCTGGCTCC TGAGGTTCTT 1200

GTCTCCAACG GGACTGCTGG GTACAGCCGC GCTGTGGACT GCTGGAGTTT AGGAGTTATT 1260

CTTTTCATCT GCCTAAGTGG GTATCCACCT TTCTCTGAGC ATAAGACCCA AGTGTCCCTG 1320

AAGGATCAGA TCACCAGTGG AAAGTACAAC TTTATTCCTG AAGTCTGGAC AGATGTCTCA 1380

GAGGAGGCTC TGGACCTTGT CAAGAAACTG TTAGTTGTAG ACCCAAAGGC TCGGCTTACC 1440

ACAGAGGAGG CCTTAAATCA TCCGTGGCTT CAGGATGAGT ACATGAAGAA GAAATTTCAG 1500

GATCTCCTGG TGCAGGAAAA GAACTCGGTG ACCCTCCCTG TGGCTCCCGC CCAGACTTCC 1560

AGTCAAAAGC GGCCCCTGGA ACTGGAGGTG GAGGGTATGC CGAGCACAAA ACGCCTGTCT 1620

GTGTGTGGGG CTGTGTTGTG A 1641

Domain Profile

S: 1     yilskelGkGafgkvklayekktgkkvavkilskrk.sirssreikkakeveeeveilkk  59

         yi+sk+lG+Ga+g+vk+a+e+kt++kva+ki+skr+ +++ssre+++a +ve+e+eilkk

Q: 224   YIMSKTLGSGACGEVKMAFERKTCQKVAIKIISKRRfALGSSREADTAPSVETEIEILKK  283

         89********************************9989**********************

S: 60    lshPnivklkdvfeeeeskylvlelvegGelldkvvakkllkedlskllfkqlltavkyl  119

         l+hP+i+k+kdvf++e++ y+vlel+egGel+d+vv +k+lke+++kl+f+q+l av+yl

Q: 284   LNHPCIIKIKDVFDAEDY-YIVLELMEGGELFDRVVGNKRLKEATCKLYFYQMLVAVQYL  342

         *****************9.*****************************************

S: 120   hekgiihrDlkPeniLlsekeedvlvkitDfGlakvlgevslmktlCGtpsyvaPevlvk  179

         he+giihrDlkPen+Lls++eed+l+kitDfG++k+lge+slm+tlCGtp+y+aPevlv+

Q: 343   HENGIIHRDLKPENVLLSSQEEDCLIKITDFGQSKILGETSLMRTLCGTPTYLAPEVLVS  402

         ************************************************************

S: 180   kgraeytskvDiWslGvvlfvilsGypPfseeltqvslkeqilkgkyafieekwkkisee  239

         +g+a+y+++vD+WslGv+lf++lsGypPfse++tqvslk+qi++gky+fi+e+w+++see

Q: 403   NGTAGYSRAVDCWSLGVILFICLSGYPPFSEHKTQVSLKDQITSGKYNFIPEVWTDVSEE  462

         ************************************************************

S: 240   akdlikklLvvdPeerlsieealnhpWl  267

         a+dl+kklLvvdP++rl++eealnhpWl

Q: 463   ALDLVKKLLVVDPKARLTTEEALNHPWL  490

         ***************************8

Domain Sequence
(FASTA)

YIMSKTLGSG ACGEVKMAFE RKTCQKVAIK IISKRRFALG SSREADTAPS VETEIEILKK 60

LNHPCIIKIK DVFDAEDYYI VLELMEGGEL FDRVVGNKRL KEATCKLYFY QMLVAVQYLH 120

ENGIIHRDLK PENVLLSSQE EDCLIKITDF GQSKILGETS LMRTLCGTPT YLAPEVLVSN 180

GTAGYSRAVD CWSLGVILFI CLSGYPPFSE HKTQVSLKDQ ITSGKYNFIP EVWTDVSEEA 240

LDLVKKLLVV DPKARLTTEE ALNHPWL 267

Keyword

Apoptosis; ATP-binding; Cell cycle; Cell division; Complete proteome; DNA damage; DNA repair; Kinase; Magnesium; Metal-binding; Mitosis; Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; Serine/threonine-protein kinase; Transcription; Transcription regulation; Transferase; Ubl conjugation.

Sequence Source

Ensembl

Orthology

Ortholog group

Ailuropoda melanoleuca"; ?>Bos taurus"; ?>Caenorhabditis elegans"; ?>Callithrix jacchus"; ?>Canis familiaris"; ?>Cavia porcellus"; ?>Ciona intestinalis"; ?>Ciona savignyi"; ?>Danio rerio"; ?>Drosophila melanogaster"; ?>Equus caballus"; ?>Felis catus"; ?>Gallus gallus"; ?>Gorilla gorilla"; ?>Homo sapiens"; ?>Ictidomys tridecemlineatus"; ?>Latimeria chalumnae"; ?>Loxodonta africana"; ?>Macaca mulatta"; ?>Meleagris gallopavo"; ?>Monodelphis domestica"; ?>Mustela putorius furo"; ?>Myotis lucifugus"; ?>Nomascus leucogenys"; ?>Oreochromis niloticus"; ?>Ornithorhynchus anatinus"; ?>Oryctolagus cuniculus"; ?>Oryzias latipes"; ?>Otolemur garnettii"; ?>Pan troglodytes"; ?>Pelodiscus sinensis"; ?>Pongo abelii"; ?>Rattus norvegicus"; ?>Sarcophilus harrisii"; ?>Taeniopygia guttata"; ?>Takifugu rubripes"; ?>Tetraodon nigroviridis"; ?>Xenopus tropicalis"; ?>Xiphophorus maculatus"; ?>Saccharomyces cerevisiae"; ?>Schizosaccharomyces pombe"; ?>

Gene Ontology

GO:0000781	; C:chromosome, telomeric region
GO:0016605	; C:PML body
GO:0005524	; F:ATP binding
GO:0046872	; F:metal ion binding
GO:0042803	; F:protein homodimerization activity
GO:0004674	; F:protein serine/threonine kinase activity
GO:0051301	; P:cell division
GO:0044257	; P:cellular protein catabolic process
GO:0006975	; P:DNA damage induced protein phosphorylation
GO:0006302	; P:double-strand break repair
GO:0000086	; P:G2/M transition of mitotic cell cycle
GO:0008630	; P:intrinsic apoptotic signaling pathway in response to DNA damage response
GO:0045893	; P:positive regulation of transcription, DNA-dependent
GO:0046777	; P:protein autophosphorylation
GO:0042176	; P:regulation of protein catabolic process
GO:0010332	; P:response to gamma radiation
GO:0072428	; P:signal transduction involved in intra-S DNA damage checkpoint
GO:0090307	; P:spindle assembly involved in mitosis
GO:0006351	; P:transcription, DNA-dependent

KEGG

mmu:50883

;

InterPros

IPR000253	; FHA_dom.
IPR011009	; Kinase-like_dom.
IPR000719	; Prot_kinase_cat_dom.
IPR002290	; Ser/Thr_dual-sp_kinase_dom.
IPR008271	; Ser/Thr_kinase_AS.
IPR008984	; SMAD_FHA_domain.

Pfam

PF00498	; FHA; 1.
PF00069	; Pkinase; 1.

SMARTs

SM00240	; FHA; 1.
SM00220	; S_TKc; 1.

Prosites

PS50006	; FHA_DOMAIN; 1.
PS00107	; PROTEIN_KINASE_ATP; FALSE_NEG.
PS50011	; PROTEIN_KINASE_DOM; 1.
PS00108	; PROTEIN_KINASE_ST; 1.

Prints

Created Date

20-Feb-2013