Cyclin H

Cyclin H
PDB rendering based on 1jkw.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1JKW​, 1KXU​
Identifiers
Symbols	CCNH ; CAK; CycH; p34; p37
External IDs	OMIM: 601953 MGI: 1913921 HomoloGene: 946 ChEMBL: 2165 GeneCards: CCNH Gene
Gene ontology Molecular function • protein binding • DNA-dependent ATPase activity • RNA polymerase II carboxy-terminal domain kinase activity • cyclin-dependent protein serine/threonine kinase regulator activity • protein kinase binding Cellular component • nucleus • nucleoplasm • holo TFIIH complex • cyclin-dependent protein kinase activating kinase holoenzyme complex • TFIIK complex Biological process • regulation of cyclin-dependent protein serine/threonine kinase activity • G1/S transition of mitotic cell cycle • G2/M transition of mitotic cell cycle • mitotic cell cycle • nucleotide-excision repair, DNA damage removal • DNA repair • transcription-coupled nucleotide-excision repair • nucleotide-excision repair • transcription from RNA polymerase I promoter • transcription initiation from RNA polymerase I promoter • transcription elongation from RNA polymerase I promoter • termination of RNA polymerase I transcription • transcription from RNA polymerase II promoter • transcription initiation from RNA polymerase II promoter • transcription elongation from RNA polymerase II promoter • 7-methylguanosine mRNA capping • protein phosphorylation • gene expression • viral process • regulation of gene expression, epigenetic • negative regulation of gene expression, epigenetic • positive regulation of transcription from RNA polymerase II promoter • positive regulation of viral transcription Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	902	66671
Ensembl	ENSG00000134480	ENSMUSG00000021548
UniProt	P51946	Q61458
RefSeq (mRNA)	NM_001199189	NM_023243
RefSeq (protein)	NP_001186118	NP_075732
Location (UCSC)	Chr 5: 87.39 – 87.41 Mb	Chr 13: 85.19 – 85.22 Mb
PubMed search

Cyclin-H is a protein that in humans is encoded by the CCNH gene.^[1][2]

Function

The protein encoded by this gene belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance through the cell cycle. Cyclins function as regulators of CDK kinases. Different cyclins exhibit distinct expression and degradation patterns which contribute to the temporal coordination of each mitotic event. This cyclin forms a complex with CDK7 kinase and ring finger protein MAT1. The kinase complex is able to phosphorylate CDK2 and CDC2 kinases, thus functions as a CDK-activating kinase (CAK). This cyclin and its kinase partner are components of TFIIH, as well as RNA polymerase II protein complexes. They participate in two different transcriptional regulation processes, suggesting an important link between basal transcription control and the cell cycle machinery.^[2]

Interactions

Cyclin H has been shown to interact with P53,^[3] Cyclin-dependent kinase 7^[4][5][6] and MNAT1.^[7][8]

References

1. Eki T, Okumura K, Abe M, Kagotani K, Taguchi H, Murakami Y, Pan ZQ, Hanaoka F (Jan 1998). "Mapping of the human genes encoding cyclin H (CCNH) and the CDK-activating kinase (CAK) assembly factor MAT1 (MNAT1) to chromosome bands 5q13.3-q14 and 14q23, respectively". Genomics 47 (1): 115–20. doi:10.1006/geno.1997.5053. PMID 9465303.
2. "Entrez Gene: CCNH cyclin H".
3. Schneider E, Montenarh M, Wagner P (Nov 1998). "Regulation of CAK kinase activity by p53". Oncogene 17 (21): 2733–41. doi:10.1038/sj.onc.1202504. PMID 9840937.
4. Mäkelä TP, Tassan JP, Nigg EA, Frutiger S, Hughes GJ, Weinberg RA (Sep 1994). "A cyclin associated with the CDK-activating kinase MO15". Nature 371 (6494): 254–7. doi:10.1038/371254a0. PMID 8078587.
5. Yee A, Nichols MA, Wu L, Hall FL, Kobayashi R, Xiong Y (Dec 1995). "Molecular cloning of CDK7-associated human MAT1, a cyclin-dependent kinase-activating kinase (CAK) assembly factor". Cancer Research 55 (24): 6058–62. PMID 8521393.
6. Garber ME, Mayall TP, Suess EM, Meisenhelder J, Thompson NE, Jones KA (Sep 2000). "CDK9 autophosphorylation regulates high-affinity binding of the human immunodeficiency virus type 1 tat-P-TEFb complex to TAR RNA". Molecular and Cellular Biology 20 (18): 6958–69. doi:10.1128/MCB.20.18.6958-6969.2000. PMC 88771. PMID 10958691.
7. Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Molecular Systems Biology 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931.
8. Talukder AH, Mishra SK, Mandal M, Balasenthil S, Mehta S, Sahin AA, Barnes CJ, Kumar R (Mar 2003). "MTA1 interacts with MAT1, a cyclin-dependent kinase-activating kinase complex ring finger factor, and regulates estrogen receptor transactivation functions". The Journal of Biological Chemistry 278 (13): 11676–85. doi:10.1074/jbc.M209570200. PMID 12527756.

Further reading

• Jeang KT (1998). "Tat, Tat-associated kinase, and transcription". Journal of Biomedical Science 5 (1): 24–7. doi:10.1007/BF02253352. PMID 9570510.
• Yankulov K, Bentley D (Jun 1998). "Transcriptional control: Tat cofactors and transcriptional elongation". Current Biology 8 (13): R447–9. doi:10.1016/S0960-9822(98)70289-1. PMID 9651670.
• Shiekhattar R, Mermelstein F, Fisher RP, Drapkin R, Dynlacht B, Wessling HC, Morgan DO, Reinberg D (Mar 1995). "Cdk-activating kinase complex is a component of human transcription factor TFIIH". Nature 374 (6519): 283–7. doi:10.1038/374283a0. PMID 7533895.
• Darbon JM, Devault A, Taviaux S, Fesquet D, Martinez AM, Galas S, Cavadore JC, Dorée M, Blanchard JM (Nov 1994). "Cloning, expression and subcellular localization of the human homolog of p40MO15 catalytic subunit of cdk-activating kinase". Oncogene 9 (11): 3127–38. PMID 7936635.
• Feaver WJ, Svejstrup JQ, Henry NL, Kornberg RD (Dec 1994). "Relationship of CDK-activating kinase and RNA polymerase II CTD kinase TFIIH/TFIIK". Cell 79 (6): 1103–9. doi:10.1016/0092-8674(94)90040-X. PMID 8001136. Check date values in: |year= / |date= mismatch (help)
• Fisher RP, Morgan DO (Aug 1994). "A novel cyclin associates with MO15/CDK7 to form the CDK-activating kinase". Cell 78 (4): 713–24. doi:10.1016/0092-8674(94)90535-5. PMID 8069918.
• Mäkelä TP, Tassan JP, Nigg EA, Frutiger S, Hughes GJ, Weinberg RA (Sep 1994). "A cyclin associated with the CDK-activating kinase MO15". Nature 371 (6494): 254–7. doi:10.1038/371254a0. PMID 8078587.
• Perez JL, Shen X, Finkernagel S, Sciorra L, Jenkins NA, Gilbert DJ, Copeland NG, Wong TW (Jan 1994). "Identification and chromosomal mapping of a receptor tyrosine kinase with a putative phospholipid binding sequence in its ectodomain". Oncogene 9 (1): 211–9. PMID 8302582.
• Tassan JP, Jaquenoud M, Fry AM, Frutiger S, Hughes GJ, Nigg EA (Nov 1995). "In vitro assembly of a functional human CDK7-cyclin H complex requires MAT1, a novel 36 kDa RING finger protein". The EMBO Journal 14 (22): 5608–17. PMC 394676. PMID 8521818. Check date values in: |year= / |date= mismatch (help)
• Adamczewski JP, Rossignol M, Tassan JP, Nigg EA, Moncollin V, Egly JM (Apr 1996). "MAT1, cdk7 and cyclin H form a kinase complex which is UV light-sensitive upon association with TFIIH". The EMBO Journal 15 (8): 1877–84. PMC 450106. PMID 8617234.
• Blau J, Xiao H, McCracken S, O'Hare P, Greenblatt J, Bentley D (May 1996). "Three functional classes of transcriptional activation domain". Molecular and Cellular Biology 16 (5): 2044–55. PMC 231191. PMID 8628270.
• Reardon JT, Ge H, Gibbs E, Sancar A, Hurwitz J, Pan ZQ (Jun 1996). "Isolation and characterization of two human transcription factor IIH (TFIIH)-related complexes: ERCC2/CAK and TFIIH". Proceedings of the National Academy of Sciences of the United States of America 93 (13): 6482–7. doi:10.1073/pnas.93.13.6482. PMC 39049. PMID 8692841.
• Drapkin R, Le Roy G, Cho H, Akoulitchev S, Reinberg D (Jun 1996). "Human cyclin-dependent kinase-activating kinase exists in three distinct complexes". Proceedings of the National Academy of Sciences of the United States of America 93 (13): 6488–93. doi:10.1073/pnas.93.13.6488. PMC 39050. PMID 8692842.
• Kim KK, Chamberlin HM, Morgan DO, Kim SH (Oct 1996). "Three-dimensional structure of human cyclin H, a positive regulator of the CDK-activating kinase". Nature Structural Biology 3 (10): 849–55. doi:10.1038/nsb1096-849. PMID 8836101.
• Zhou Q, Sharp PA (Oct 1996). "Tat-SF1: cofactor for stimulation of transcriptional elongation by HIV-1 Tat". Science 274 (5287): 605–10. doi:10.1126/science.274.5287.605. PMID 8849451.
• Parada CA, Roeder RG (Nov 1996). "Enhanced processivity of RNA polymerase II triggered by Tat-induced phosphorylation of its carboxy-terminal domain". Nature 384 (6607): 375–8. doi:10.1038/384375a0. PMID 8934526.
• García-Martínez LF, Ivanov D, Gaynor RB (Mar 1997). "Association of Tat with purified HIV-1 and HIV-2 transcription preinitiation complexes". The Journal of Biological Chemistry 272 (11): 6951–8. doi:10.1074/jbc.272.11.6951. PMID 9054383.
• Poterszman A, Andersen G, Busso D, Rossignol M, Egly JM, Thierry JC (Mar 1997). "Expression in Escherichia coli: purification and characterization of cyclin H, a subunit of the human general transcription/DNA repair factor TFIIH". Protein Expression and Purification 9 (2): 153–8. doi:10.1006/prep.1996.0693. PMID 9056480.
• Marinoni JC, Roy R, Vermeulen W, Miniou P, Lutz Y, Weeda G, Seroz T, Gomez DM, Hoeijmakers JH, Egly JM (Mar 1997). "Cloning and characterization of p52, the fifth subunit of the core of the transcription/DNA repair factor TFIIH". The EMBO Journal 16 (5): 1093–102. doi:10.1093/emboj/16.5.1093. PMC 1169708. PMID 9118947.
• Andersen G, Busso D, Poterszman A, Hwang JR, Wurtz JM, Ripp R, Thierry JC, Egly JM, Moras D (Mar 1997). "The structure of cyclin H: common mode of kinase activation and specific features". The EMBO Journal 16 (5): 958–67. doi:10.1093/emboj/16.5.958. PMC 1169696. PMID 9118957.