CYCLIN H

CCNH
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	1JKW, 1KXU
Identifiers
Aliases	CCNH, CAK, CycH, p34, p37, Cyclin H
External IDs	OMIM: 601953; MGI: 1913921; HomoloGene: 946; GeneCards: CCNH; OMA: CCNH - orthologs
Gene location ( Human)
Chr.	Chromosome 5 (human)
End	87,412,930 bp
Gene location ( Mouse)
Chr.	Chromosome 13 (mouse)
End	85,371,588 bp
RNA expression pattern
	Top expressed in
	Achilles tendon; ; left testis; ; right testis; ; ventricular zone; ; epithelium of colon; ; ganglionic eminence; ; anterior pituitary; ; right lung; ; sperm; ; C1 segment;
	Top expressed in
	interventricular septum; ; fossa; ; condyle; ; endothelial cell of lymphatic vessel; ; vas deferens; ; primitive streak; ; facial motor nucleus; ; otic placode; ; efferent ductule; ; Paneth cell;
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	ATP-dependent activity, acting on DNA; kinase activity; cyclin-dependent protein serine/threonine kinase regulator activity; protein binding; RNA polymerase II CTD heptapeptide repeat kinase activity;
Cellular component	nucleoplasm; transcription factor TFIIH holo complex; transcription factor TFIIK complex; nucleus; cyclin-dependent protein kinase activating kinase holoenzyme complex; cyclin-dependent protein kinase holoenzyme complex;
Biological process	termination of RNA polymerase I transcription; regulation of transcription, DNA-templated; phosphorylation; transcription initiation from RNA polymerase I promoter; transcription elongation from RNA polymerase II promoter; 7-methylguanosine mRNA capping; transcription by RNA polymerase II; transcription, DNA-templated; positive regulation of phosphorylation of RNA polymerase II C-terminal domain; positive regulation of cyclin-dependent protein serine/threonine kinase activity; cell cycle; transcription-coupled nucleotide-excision repair; transcription initiation from RNA polymerase II promoter; positive regulation of transcription by RNA polymerase II; protein phosphorylation; nucleotide-excision repair, preincision complex assembly; protein stabilization; regulation of cyclin-dependent protein serine/threonine kinase activity; regulation of transcription by RNA polymerase II; G1/S transition of mitotic cell cycle; G2/M transition of mitotic cell cycle; transcription elongation from RNA polymerase I promoter;
	Sources: Amigo / QuickGO
Orthologs
	902
	66671
	ENSG00000134480
	ENSMUSG00000021548
	P51946
	Q61458
	NM_001199189; NM_001239; NM_001363539; NM_001364075; NM_001364076
	NM_023243; NM_001347587; NM_001347588
	NP_001186118; NP_001230; NP_001350468; NP_001351004; NP_001351005
	NP_001334516; NP_001334517; NP_075732
	Wikidata
View/Edit Human	View/Edit Mouse

Cyclin-H is a protein that in humans is encoded by the CCNH gene.^[5]^[6]

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.^[6]

Interactions

Cyclin H has been shown to interact with P53,^[7] Cyclin-dependent kinase 7^[8]^[9]^[10] and MNAT1.^[11]^[12]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000134480 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000021548 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ 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.
^ ^a ^b "Entrez Gene: CCNH cyclin H".
^ Schneider E, Montenarh M, Wagner P (November 1998). "Regulation of CAK kinase activity by p53". Oncogene. 17 (21): 2733–41. doi: 10.1038/sj.onc.1202504. PMID 9840937. S2CID 6281777.
^ 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. Bibcode: 1994Natur.371..254M. doi: 10.1038/371254a0. PMID 8078587. S2CID 4369898.
^ Yee A, Nichols MA, Wu L, Hall FL, Kobayashi R, Xiong Y (December 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.
^ 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.
^ 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.
^ 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.

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. Bibcode: 1998CBio....8.R447Y. doi: 10.1016/S0960-9822(98)70289-1. PMID 9651670. S2CID 15480646.
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. Bibcode: 1995Natur.374..283S. doi: 10.1038/374283a0. PMID 7533895. S2CID 4282418.
Darbon JM, Devault A, Taviaux S, Fesquet D, Martinez AM, Galas S, Cavadore JC, Dorée M, Blanchard JM (November 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 (December 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. S2CID 205021029.
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. S2CID 2996948.
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. Bibcode: 1994Natur.371..254M. doi: 10.1038/371254a0. PMID 8078587. S2CID 4369898.
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 (November 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. doi: 10.1002/j.1460-2075.1995.tb00248.x. PMC 394676. PMID 8521818.
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. doi: 10.1002/j.1460-2075.1996.tb00538.x. 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. doi: 10.1128/MCB.16.5.2044. 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. Bibcode: 1996PNAS...93.6482R. 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. Bibcode: 1996PNAS...93.6488D. 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. S2CID 8880795.
Zhou Q, Sharp PA (Oct 1996). "Tat-SF1: cofactor for stimulation of transcriptional elongation by HIV-1 Tat". Science. 274 (5287): 605–10. Bibcode: 1996Sci...274..605Z. doi: 10.1126/science.274.5287.605. PMID 8849451. S2CID 13266489.
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. Bibcode: 1996Natur.384..375P. doi: 10.1038/384375a0. PMID 8934526. S2CID 4278432.
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.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000134480 – Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000021548 – 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.

[pmid9465303-5] 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.

[entrez-6] "Entrez Gene: CCNH cyclin H".

[pmid9840937-7] Schneider E, Montenarh M, Wagner P (November 1998). "Regulation of CAK kinase activity by p53". Oncogene. 17 (21): 2733–41. doi: 10.1038/sj.onc.1202504. PMID 9840937. S2CID 6281777.

[pmid8078587-8] 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. Bibcode: 1994Natur.371..254M. doi: 10.1038/371254a0. PMID 8078587. S2CID 4369898.

[pmid8521393-9] Yee A, Nichols MA, Wu L, Hall FL, Kobayashi R, Xiong Y (December 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.

[pmid10958691-10] 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.

[pmid17353931-11] 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.

[pmid12527756-12] 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.

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Function

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References

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