Tag | Content |
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EKPD ID | EKS-HOS-00056 |
Classification | Group/Family | Score | E-Value | Start | End | Domain Length |
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CMGC/CDK | 450.3 | 1.3E-134 | 4 | 286 | 283 |
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Status | Reviewed |
Ensembl Protein | ENSP00000266970 |
UniProt Accession | P24941; A8K7C6; O75100; |
Protein Name | Cyclin-dependent kinase 2 |
Protein Synonyms/Alias | Cell division protein kinase 2; p33 protein kinase; |
Gene Name | CDK2 |
Gene Synonyms/Alias | CDK2; CDKN2; |
Ensembl Information | |
Organism | Homo sapiens |
Functional Description | Serine/threonine-protein kinase involved in the controlof the cell cycle; essential for meiosis, but dispensable for mitosis. Phosphorylates CTNNB1, USP37, p53/TP53, NPM1, CDK7, RB1, BRCA2, MYC, NPAT, EZH2. Interacts with cyclins A, B1, B3, D, or E. Triggers duplication of centrosomes and DNA. Acts at the G1-S transition to promote the E2F transcriptional program and the initiation of DNA synthesis, and modulates G2 progression; controls the timing of entry into mitosis/meiosis by controlling the subsequent activation of cyclin B/CDK1 by phosphorylation, and coordinates the activation of cyclin B/CDK1 at the centrosome and in the nucleus. Crucial role in orchestrating a fine balance between cellular proliferation, cell death, and DNA repair in human embryonic stem cells (hESCs). Activity of CDK2 is maximal during S phase and G2; activated by interaction with cyclin E during the early stages of DNA synthesis to permit G1-S transition, and subsequently activated by cyclin A2 (cyclin A1 in germ cells) during the late stages of DNA replication to drive the transition from S phase to mitosis, the G2 phase. EZH2 phosphorylation promotes H3K27me3 maintenance and epigenetic gene silencing. Phosphorylates CABLES1 (By similarity). Cyclin E/CDK2 prevents oxidative stress-mediated Ras-induced senescence by phosphorylating MYC. Involved in G1-S phase DNA damage checkpoint that prevents cells with damaged DNA from initiating mitosis; regulates homologous recombination-dependent repair by phosphorylating BRCA2, this phosphorylation is low in S phase when recombination is active, but increases as cells progress towards mitosis. In response to DNA damage, double-strand break repair by homologous recombination a reduction of CDK2-mediated BRCA2 phosphorylation. Phosphorylation of RB1 disturbs its interaction with E2F1. NPM1 phosphorylation by cyclin E/CDK2 promotes its dissociates from unduplicated centrosomes, thus initiating centrosome duplication. Cyclin E/CDK2-mediated phosphorylation of NPAT at G1-S transition and until prophase stimulates the NPAT- mediated activation of histone gene transcription during S phase. Required for vitamin D-mediated growth inhibition by being itself inactivated. Involved in the nitric oxide- (NO) mediated signaling in a nitrosylation/activation-dependent manner. USP37 is activated by phosphorylation and thus triggers G1-S transition. CTNNB1 phosphorylation regulates insulin internalization. |
Protein Length | 298 |
Protein Sequence (FASTA) | MENFQKVEKI GEGTYGVVYK ARNKLTGEVV ALKKIRLDTE TEGVPSTAIR EISLLKELNH 60 | PNIVKLLDVI HTENKLYLVF EFLHQDLKKF MDASALTGIP LPLIKSYLFQ LLQGLAFCHS 120 | HRVLHRDLKP QNLLINTEGA IKLADFGLAR AFGVPVRTYT HEVVTLWYRA PEILLGCKYY 180 | STAVDIWSLG CIFAEMVTRR ALFPGDSEID QLFRIFRTLG TPDEVVWPGV TSMPDYKPSF 240 | PKWARQDFSK VVPPLDEDGR SLLSQMLHYD PNKRISAKAA LAHPFFQDVT KPVPHLRL 298 |
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Nucleotide Sequence (FASTA) | ATGGAGAACT TCCAAAAGGT GGAAAAGATC GGAGAGGGCA CGTACGGAGT TGTGTACAAA 60 | GCCAGAAACA AGTTGACGGG AGAGGTGGTG GCGCTTAAGA AAATCCGCCT GGACACTGAG 120 | ACTGAGGGTG TGCCCAGTAC TGCCATCCGA GAGATCTCTC TGCTTAAGGA GCTTAACCAT 180 | CCTAATATTG TCAAGCTGCT GGATGTCATT CACACAGAAA ATAAACTCTA CCTGGTTTTT 240 | GAATTTCTGC ACCAAGATCT CAAGAAATTC ATGGATGCCT CTGCTCTCAC TGGCATTCCT 300 | CTTCCCCTCA TCAAGAGCTA TCTGTTCCAG CTGCTCCAGG GCCTAGCTTT CTGCCATTCT 360 | CATCGGGTCC TCCACCGAGA CCTTAAACCT CAGAATCTGC TTATTAACAC AGAGGGGGCC 420 | ATCAAGCTAG CAGACTTTGG ACTAGCCAGA GCTTTTGGAG TCCCTGTTCG TACTTACACC 480 | CATGAGGTGG TGACCCTGTG GTACCGAGCT CCTGAAATCC TCCTGGGCTG CAAATATTAT 540 | TCCACAGCTG TGGACATCTG GAGCCTGGGC TGCATCTTTG CTGAGATGGT GACTCGCCGG 600 | GCCCTATTCC CTGGAGATTC TGAGATTGAC CAGCTCTTCC GGATCTTTCG GACTCTGGGG 660 | ACCCCAGATG AGGTGGTGTG GCCAGGAGTT ACTTCTATGC CTGATTACAA GCCAAGTTTC 720 | CCCAAGTGGG CCCGGCAAGA TTTTAGTAAA GTTGTACCTC CCCTGGATGA AGATGGACGG 780 | AGCTTGTTAT CGCAAATGCT GCACTACGAC CCTAACAAGC GGATTTCGGC CAAGGCAGCC 840 | CTGGCTCACC CTTTCTTCCA GGATGTGACC AAGCCAGTAC CCCATCTTCG ACTCTGA 897 |
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Domain Profile | S: 1 yeklekigeGtygkvykakdketgevvAlKkirlekekegvpitalrEisllkelkhkni 60 | ++k+ekigeGtyg+vyka++k tgevvAlKkirl++e+egvp+ta+rEisllkel+h+ni | Q: 4 FQKVEKIGEGTYGVVYKARNKLTGEVVALKKIRLDTETEGVPSTAIREISLLKELNHPNI 63 | 89********************************************************** |
| S: 61 vkLlevvakdkkklyLvfefleqdLkkllkkkkkkklsleevkslllqlleglaylHsnk 120 | vkLl+v++ +++klyLvfefl+qdLkk++++++ ++++l +ks+l+qll+gla++Hs++ | Q: 64 VKLLDVIH-TENKLYLVFEFLHQDLKKFMDASALTGIPLPLIKSYLFQLLQGLAFCHSHR 122 | ********.99************************************************* |
| S: 121 ilHRDlKpqNlLiskegklklaDfGlarafssplktytkevvTlwYraPelLlgakeYst 180 | +lHRDlKpqNlLi++eg +klaDfGlaraf++p++tyt+evvTlwYraPe+Llg+k+Yst | Q: 123 VLHRDLKPQNLLINTEGAIKLADFGLARAFGVPVRTYTHEVVTLWYRAPEILLGCKYYST 182 | ************************************************************ |
| S: 181 avDiWsvgcilaelltrkplfqgkseidqlerifkllgtpsekvwpevsklpeykksfpk 240 | avDiWs+gci+ae++tr++lf+g+seidql+rif++lgtp+e vwp+v+++p+yk sfpk | Q: 183 AVDIWSLGCIFAEMVTRRALFPGDSEIDQLFRIFRTLGTPDEVVWPGVTSMPDYKPSFPK 242 | ************************************************************ |
| S: 241 kkkkklkekvkklkekaldllekllaldpkkRisakealqhkyf 284 | +++++++++v+ l+e++++ll+++l++dp+kRisak+al+h++f | Q: 243 WARQDFSKVVPPLDEDGRSLLSQMLHYDPNKRISAKAALAHPFF 286 | ******************************************98 |
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Domain Sequence (FASTA) | FQKVEKIGEG TYGVVYKARN KLTGEVVALK KIRLDTETEG VPSTAIREIS LLKELNHPNI 60 | VKLLDVIHTE NKLYLVFEFL HQDLKKFMDA SALTGIPLPL IKSYLFQLLQ GLAFCHSHRV 120 | LHRDLKPQNL LINTEGAIKL ADFGLARAFG VPVRTYTHEV VTLWYRAPEI LLGCKYYSTA 180 | VDIWSLGCIF AEMVTRRALF PGDSEIDQLF RIFRTLGTPD EVVWPGVTSM PDYKPSFPKW 240 | ARQDFSKVVP PLDEDGRSLL SQMLHYDPNK RISAKAALAH PFF 283 |
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Keyword | 3D-structure; Acetylation; Alternative splicing; ATP-binding; Cell cycle; Cell division; Complete proteome; Cytoplasm; Cytoskeleton; DNA damage; DNA repair; Endosome; Kinase; Magnesium; Meiosis; Metal-binding; Mitosis; Nitration; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Serine/threonine-protein kinase; Transferase. |
Sequence Source | Ensembl |
Orthology | |
Gene Ontology | |
KEGG | |
InterPros | |
Pfam | |
SMARTs | |
Prosites | |
Prints | |
Created Date | 20-Feb-2013 |