Cyclin K

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CCNK
Protein CCNK PDB 2i53.png
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesCCNK, CPR4, Cyclin K
External IDsMGI: 1276106 HomoloGene: 14748 GeneCards: CCNK
Gene location (Human)
Chromosome 14 (human)
Chr.Chromosome 14 (human)[1]
Chromosome 14 (human)
Genomic location for CCNK
Genomic location for CCNK
Band14q32.2Start99,481,169 bp[1]
End99,535,044 bp[1]
RNA expression pattern
PBB GE CCNK 219273 at fs.png
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001099402
NM_003858

NM_009832

RefSeq (protein)

NP_001092872

NP_033962

Location (UCSC)Chr 14: 99.48 – 99.54 MbChr 12: 108.18 – 108.2 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Cyclin-K is a protein that in humans is encoded by the CCNK gene.[5][6][7]

Function[edit]

The protein encoded by this gene is a member of the transcription cyclin family. These cyclins may regulate transcription through their association with and activation of cyclin-dependent kinases (CDKs) through conformational changes.[8][9] Activation of CDKs through their cyclin partner, creates kinase complexes that will activate target proteins through phosphorylation. Targeted proteins can then ultimately regulate decisions of a cell’s progression within the cell cycle to occur. This gene product may be seen to play a dual role in both regulating CDK and RNA polymerase II (RNAP2) activities.[7] Cyclin K only uses RNA recruitment to activate transcription.[10]

Interactions[edit]

Cyclin K has been shown to interact with multiple CDKs including CDK9 and latest CDK12 and CDK13.[6][9] Roles include helping to phosphorylate C-terminal domains of subunits of RNAP2.[11] Cyclin K is most noted for its associated induction of processive elongation.[8] Also, identified with G1 and S phase cyclin activity, however functions are not deeply understood.[5][12]

Cyclin K also interacts with HIV nef protein.[13] In the presence of overexpressed Nef protein, Cyclin k and CDK9 binding is induced, inhibiting the positive elongation factor of other CDK9 binding complexes, resulting in an inhibition of specific HIV-1 gene expression.[9][13] CDK 13 may also be characterized to interact with HIV mRNA splicing, alongside Nef, and the underexpression of Gag and Env related proteins. [12][10]

Cyclin K is indispensable for Leukemia growth. SETD1A, is also known to bind Cyclin K through its FLOS domain.[14] The interaction is shown to be important to DNA damage response genes and for Leukemia proliferation.[10][14]

References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000090061 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000021258 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". 
  4. ^ "Mouse PubMed Reference:". 
  5. ^ a b Edwards MC, Wong C, Elledge SJ (July 1998). "Human cyclin K, a novel RNA polymerase II-associated cyclin possessing both carboxy-terminal domain kinase and Cdk-activating kinase activity". Molecular and Cellular Biology. 18 (7): 4291–300. PMC 109013Freely accessible. PMID 9632813. 
  6. ^ a b Fu TJ, Peng J, Lee G, Price DH, Flores O (December 1999). "Cyclin K functions as a CDK9 regulatory subunit and participates in RNA polymerase II transcription". The Journal of Biological Chemistry. 274 (49): 34527–30. doi:10.1074/jbc.274.49.34527. PMID 10574912. 
  7. ^ a b "Entrez Gene: CCNK cyclin K". 
  8. ^ a b Baek K, Brown RS, Birrane G, Ladias JA (February 2007). "Crystal structure of human cyclin K, a positive regulator of cyclin-dependent kinase 9". Journal of Molecular Biology. 366 (2): 563–73. doi:10.1016/j.jmb.2006.11.057. PMC 1852425Freely accessible. PMID 17169370. 
  9. ^ a b c Greifenberg AK, Hönig D, Pilarova K, Düster R, Bartholomeeusen K, Bösken CA, Anand K, Blazek D, Geyer M (January 2016). "Structural and Functional Analysis of the Cdk13/Cyclin K Complex". Cell Reports. 14 (2): 320–31. doi:10.1016/j.celrep.2015.12.025. PMID 26748711. 
  10. ^ a b c Kohoutek J, Blazek D (April 2012). "Cyclin K goes with Cdk12 and Cdk13". Cell Division. 7: 12. doi:10.1186/1747-1028-7-12. PMC 3348076Freely accessible. PMID 22512864. 
  11. ^ Edwards MC, Wong C, Elledge SJ (July 1998). "Human cyclin K, a novel RNA polymerase II-associated cyclin possessing both carboxy-terminal domain kinase and Cdk-activating kinase activity". Molecular and Cellular Biology. 18 (7): 4291–300. PMC 109013Freely accessible. PMID 9632813. 
  12. ^ a b Berro R, Pedati C, Kehn-Hall K, Wu W, Klase Z, Even Y, Genevière AM, Ammosova T, Nekhai S, Kashanchi F (July 2008). "CDK13, a new potential human immunodeficiency virus type 1 inhibitory factor regulating viral mRNA splicing". Journal of Virology. 82 (14): 7155–66. doi:10.1128/JVI.02543-07. PMC 2446983Freely accessible. PMID 18480452. 
  13. ^ a b Khan SZ, Mitra D (July 2011). "Cyclin K inhibits HIV-1 gene expression and replication by interfering with cyclin-dependent kinase 9 (CDK9)-cyclin T1 interaction in Nef-dependent manner". The Journal of Biological Chemistry. 286 (26): 22943–54. doi:10.1074/jbc.M110.201194. PMC 3123062Freely accessible. PMID 21555514. 
  14. ^ a b Hoshii T, Cifani P, Feng Z, Huang CH, Koche R, Chen CW, Delaney CD, Lowe SW, Kentsis A, Armstrong SA (February 2018). "A Non-catalytic Function of SETD1A Regulates Cyclin K and the DNA Damage Response". Cell. 172 (5): 1007–1021.e17. doi:10.1016/j.cell.2018.01.032. PMID 29474905. 

Further reading[edit]