InnateDB Protein
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IDBP-369682.5
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Last Modified
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2014-10-13 [Report errors or provide feedback]
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Gene Symbol
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CHEK2
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Protein Name
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CHK2 checkpoint homolog (S. pombe)
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Synonyms
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CDS1; CHK2; hCds1; HuCds1; LFS2; PP1425; RAD53;
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Species
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Homo sapiens
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Ensembl Protein
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ENSP00000404567
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InnateDB Gene
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IDBG-3314 (CHEK2)
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Protein Structure
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Function |
Serine/threonine-protein kinase which is required for checkpoint-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. {ECO:0000269PubMed:10097108, ECO:0000269PubMed:10724175, ECO:0000269PubMed:11298456, ECO:0000269PubMed:12402044, ECO:0000269PubMed:12607004, ECO:0000269PubMed:12717439, ECO:0000269PubMed:12810724, ECO:0000269PubMed:16163388, ECO:0000269PubMed:17101782, ECO:0000269PubMed:17380128, ECO:0000269PubMed:17715138, ECO:0000269PubMed:18317453, ECO:0000269PubMed:18644861, ECO:0000269PubMed:18728393, ECO:0000269PubMed:20364141, ECO:0000269PubMed:9836640, ECO:0000269PubMed:9889122}.
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Subcellular Localization |
Isoform 2: Nucleus. Note=Isoform 10 is present throughout the cell.Isoform 4: Nucleus.Isoform 7: Nucleus.Isoform 9: Nucleus.Isoform 12: Nucleus.Nucleus, PML body. Nucleus, nucleoplasm. Note=Recruited into PML bodies together with TP53.
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Disease Associations |
Li-Fraumeni syndrome 2 (LFS2) [MIM:609265]: A highly penetrant familial cancer syndrome that in its classic form is defined by the existence of a proband affected by a sarcoma before 45 years with a first degree relative affected by any tumor before 45 years and another first degree relative with any tumor before 45 years or a sarcoma at any age. Other clinical definitions for LFS have been proposed (PubMed:8118819 and PubMed:8718514) and called Li-Fraumeni like syndrome (LFL). In these families affected relatives develop a diverse set of malignancies at unusually early ages. Four types of cancers account for 80% of tumors occurring in TP53 germline mutation carriers: breast cancers, soft tissue and bone sarcomas, brain tumors (astrocytomas) and adrenocortical carcinomas. Less frequent tumors include choroid plexus carcinoma or papilloma before the age of 15, rhabdomyosarcoma before the age of 5, leukemia, Wilms tumor, malignant phyllodes tumor, colorectal and gastric cancers. {ECO:0000269PubMed:11719428}. Note=The disease is caused by mutations affecting the gene represented in this entry.Prostate cancer (PC) [MIM:176807]: A malignancy originating in tissues of the prostate. Most prostate cancers are adenocarcinomas that develop in the acini of the prostatic ducts. Other rare histopathologic types of prostate cancer that occur in approximately 5% of patients include small cell carcinoma, mucinous carcinoma, prostatic ductal carcinoma, transitional cell carcinoma, squamous cell carcinoma, basal cell carcinoma, adenoid cystic carcinoma (basaloid), signet-ring cell carcinoma and neuroendocrine carcinoma. {ECO:0000269PubMed:12533788}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.Osteogenic sarcoma (OSRC) [MIM:259500]: A sarcoma originating in bone-forming cells, affecting the ends of long bones. Note=The gene represented in this entry may be involved in disease pathogenesis.Breast cancer (BC) [MIM:114480]: A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case. {ECO:0000269PubMed:12094328, ECO:0000269PubMed:21618645}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. {ECO:0000269PubMed:12094328}.
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Tissue Specificity |
High expression is found in testis, spleen, colon and peripheral blood leukocytes. Low expression is found in other tissues.
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Comments |
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Number of Interactions
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This gene and/or its encoded proteins are associated with 109 experimentally validated interaction(s) in this database.
They are also associated with 2 interaction(s) predicted by orthology.
Experimentally validated |
Total |
109
[view]
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Protein-Protein |
103
[view]
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Protein-DNA |
3
[view]
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Protein-RNA |
0
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DNA-DNA |
3
[view]
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RNA-RNA |
0
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DNA-RNA |
0
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Predicted by orthology |
Total |
2 [view]
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Molecular Function |
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Biological Process |
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Cellular Component |
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PDB ID |
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InterPro |
IPR008984
SMAD/FHA domain
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PFAM |
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PRINTS |
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PIRSF |
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SMART |
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TIGRFAMs |
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Modification |
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SwissProt |
O96017
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PhosphoSite |
PhosphoSite-O96017
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TrEMBL |
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UniProt Splice Variant |
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Entrez Gene |
11200
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UniGene |
Hs.505297
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RefSeq |
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HUGO |
HGNC:16627
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OMIM |
604373
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CCDS |
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HPRD |
05084
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IMGT |
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EMBL |
AB040105
AF086904
AF096279
AF174135
AF217975
AJ131197
AK290754
AL117330
AL121825
AY551295
AY551296
AY551297
AY551298
AY551299
AY551300
AY551301
AY551302
AY551303
AY551304
AY551305
AY800241
BC004207
CH471095
CR456418
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GenPept |
AAC83693
AAD11784
AAD48504
AAG17218
AAH04207
AAS58456
AAS58457
AAS58458
AAS58459
AAS58460
AAS58461
AAS58462
AAS58463
AAS58464
AAS58465
AAS58466
AAV41895
BAB17231
BAF83443
CAA10319
CAG30304
CAH73823
CAH73875
CAX11957
CAX11958
CAX11959
CAX14026
CAX14027
CAX14028
EAW59755
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