Cyclin K

Last updated
CCNK
Protein CCNK PDB 2i53.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases CCNK , CPR4, Cyclin K, IDDHDF
External IDs OMIM: 603544 MGI: 1276106 HomoloGene: 14748 GeneCards: CCNK
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 Mb Chr 12: 108.15 – 108.17 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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

Contents

Function

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

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]

Related Research Articles

<span class="mw-page-title-main">Cyclin-dependent kinase</span> Class of enzymes

Cyclin-dependent kinases (CDKs) are the families of protein kinases first discovered for their role in regulating the cell cycle. They are also involved in regulating transcription, mRNA processing, and the differentiation of nerve cells. They are present in all known eukaryotes, and their regulatory function in the cell cycle has been evolutionarily conserved. In fact, yeast cells can proliferate normally when their CDK gene has been replaced with the homologous human gene. CDKs are relatively small proteins, with molecular weights ranging from 34 to 40 kDa, and contain little more than the kinase domain. By definition, a CDK binds a regulatory protein called a cyclin. Without cyclin, CDK has little kinase activity; only the cyclin-CDK complex is an active kinase but its activity can be typically further modulated by phosphorylation and other binding proteins, like p27. CDKs phosphorylate their substrates on serines and threonines, so they are serine-threonine kinases. The consensus sequence for the phosphorylation site in the amino acid sequence of a CDK substrate is [S/T*]PX[K/R], where S/T* is the phosphorylated serine or threonine, P is proline, X is any amino acid, K is lysine, and R is arginine.

<span class="mw-page-title-main">Cyclin-dependent kinase 2</span> Protein-coding gene in the species Homo sapiens

Cyclin-dependent kinase 2, also known as cell division protein kinase 2, or Cdk2, is an enzyme that in humans is encoded by the CDK2 gene. The protein encoded by this gene is a member of the cyclin-dependent kinase family of Ser/Thr protein kinases. This protein kinase is highly similar to the gene products of S. cerevisiae cdc28, and S. pombe cdc2, also known as Cdk1 in humans. It is a catalytic subunit of the cyclin-dependent kinase complex, whose activity is restricted to the G1-S phase of the cell cycle, where cells make proteins necessary for mitosis and replicate their DNA. This protein associates with and is regulated by the regulatory subunits of the complex including cyclin E or A. Cyclin E binds G1 phase Cdk2, which is required for the transition from G1 to S phase while binding with Cyclin A is required to progress through the S phase. Its activity is also regulated by phosphorylation. Multiple alternatively spliced variants and multiple transcription initiation sites of this gene have been reported. The role of this protein in G1-S transition has been recently questioned as cells lacking Cdk2 are reported to have no problem during this transition.

<span class="mw-page-title-main">7SK RNA</span> Small nuclear RNA found in metazoans

In molecular biology 7SK is an abundant small nuclear RNA found in metazoans. It plays a role in regulating transcription by controlling the positive transcription elongation factor P-TEFb. 7SK is found in a small nuclear ribonucleoprotein complex (snRNP) with a number of other proteins that regulate the stability and function of the complex.

<span class="mw-page-title-main">Cyclin-dependent kinase 9</span> Protein-coding gene in the species Homo sapiens

Cyclin-dependent kinase 9 or CDK9 is a cyclin-dependent kinase associated with P-TEFb.

<span class="mw-page-title-main">Cyclin T1</span> Protein-coding gene in humans

Cyclin-T1 is a protein that in humans is encoded by the CCNT1 gene.

<span class="mw-page-title-main">POLR2B</span> Protein-coding gene in the species Homo sapiens

DNA-directed RNA polymerase II subunit RPB2 is an enzyme that in humans is encoded by the POLR2B gene.

<span class="mw-page-title-main">POLR2G</span> Protein-coding gene in the species Homo sapiens

DNA-directed RNA polymerase II subunit RPB7 is an enzyme that in humans is encoded by the POLR2G gene.

<span class="mw-page-title-main">Cyclin-dependent kinase 7</span> Protein-coding gene in the species Homo sapiens

Cyclin-dependent kinase 7, or cell division protein kinase 7, is an enzyme that in humans is encoded by the CDK7 gene.

<span class="mw-page-title-main">RNA polymerase II subunit B4</span> Protein-coding gene in the species Homo sapiens

DNA-directed RNA polymerase II subunit RPB4 is an enzyme that in humans is encoded by the POLR2D gene.

<span class="mw-page-title-main">POLR2I</span> Protein-coding gene in the species Homo sapiens

DNA-directed RNA polymerase II subunit RPB9 is an enzyme that in humans is encoded by the POLR2I gene.

<span class="mw-page-title-main">MYBL2</span> Protein-coding gene in the species Homo sapiens

Myb-related protein B is a protein that in humans is encoded by the MYBL2 gene.

<span class="mw-page-title-main">MNAT1</span> Protein-coding gene in the species Homo sapiens

CDK-activating kinase assembly factor MAT1 is an enzyme that in humans is encoded by the MNAT1 gene.

<span class="mw-page-title-main">SUPT5H</span> Protein-coding gene in the species Homo sapiens

Transcription elongation factor SPT5 is a protein that in humans is encoded by the SUPT5H gene.

<span class="mw-page-title-main">Cyclin A2</span> Protein-coding gene in the species Homo sapiens

Cyclin-A2 is a protein that in humans is encoded by the CCNA2 gene. It is one of the two types of cyclin A: cyclin A1 is expressed during meiosis and embryogenesis while cyclin A2 is expressed in the mitotic division of somatic cells.

<span class="mw-page-title-main">Cyclin H</span> Protein-coding gene in the species Homo sapiens

Cyclin-H is a protein that in humans is encoded by the CCNH gene.

<span class="mw-page-title-main">Cyclin-dependent kinase 8</span> Protein-coding gene in the species Homo sapiens

Cell division protein kinase 8 is an enzyme that in humans is encoded by the CDK8 gene.

<span class="mw-page-title-main">HEXIM1</span> Protein-coding gene in the species Homo sapiens

Protein HEXIM1 is a protein that in humans is encoded by the HEXIM1 gene.

<span class="mw-page-title-main">Cyclin T2</span> Protein-coding gene in the species Homo sapiens

Cyclin-T2 is a protein that in humans is encoded by the CCNT2 gene.

<span class="mw-page-title-main">GTF2H1</span> Protein-coding gene in the species Homo sapiens

General transcription factor IIH subunit 1 is a protein that in humans is encoded by the GTF2H1 gene.

<span class="mw-page-title-main">CTDSPL</span> Protein-coding gene in the species Homo sapiens

CTD small phosphatase-like protein is an enzyme that in humans is encoded by the CTDSPL gene.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000090061 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000021258 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 1 2 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. doi:10.1128/MCB.18.7.4291. PMC   109013 . PMID   9632813.
  6. 1 2 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. 1 2 "Entrez Gene: CCNK cyclin K".
  8. 1 2 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   1852425 . PMID   17169370.
  9. 1 2 3 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 . hdl: 11858/00-001M-0000-0029-567D-5 . PMID   26748711.
  10. 1 2 3 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   3348076 . 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. doi:10.1128/mcb.18.7.4291. PMC   109013 . PMID   9632813.
  12. 1 2 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   2446983 . PMID   18480452.
  13. 1 2 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   3123062 . PMID   21555514.
  14. 1 2 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. PMC   6052445 . PMID   29474905.

Further reading