KAT5
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| Location (UCSC) | Chr 11: 65.71 – 65.72 Mb | Chr 19: 5.65 – 5.66 Mb | |||||||
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Histone acetyltransferase KAT5 is an enzyme that in humans is encoded by the KAT5 gene.[5][6] It is also commonly identified as TIP60.
The protein encoded by this gene belongs to the MYST family of histone acetyl transferases (HATs) and was originally isolated as an HIV-1 TAT-interactive protein. HATs play important roles in regulating chromatin remodeling, transcription and other nuclear processes by acetylating histone and nonhistone proteins. This protein is a histone acetylase that has a role in DNA repair and apoptosis and is thought to play an important role in signal transduction. Alternative splicing of this gene results in multiple transcript variants.[6]
Structure
The structure of KAT5 includes an acetyl CoA binding domain and a zinc finger in the MYST domain, and a CHROMO domain.[7] Excess acetyl CoA is necessary for acetylation of histones. The zinc finger domain has been shown to aid in the acetylation process as well.[8] The CHROMO domain aids in KAT5 ability to bind chromatin, which is important for DNA repair.[9]
Function
KAT5 enzyme is known for acetylating
Transcription
DNA repair
KAT5 is an important enzyme for repairing DNA and returning cellular function to normal through its regulation of
KAT5 also works later in the DNA repair process, as it serves as a cofactor for
near broken double stranded DNA sequences. KAT5 aids this recognition.Apoptosis
P53 is well known for causing cell apoptosis after DNA damage. Acetylation of p53 by KAT5 induces this cell death.[11] Therefore, lack of KAT5 allows cells with damaged DNA to avoid apoptosis and continue dividing.
Regulation
KAT5 catalytic activity is regulated by the phosphorylation of its histones during the
Clinical relevance
KAT5 has many clinically significant implications that make it a useful target for diagnostic or therapeutic approaches. Most notably, KAT5 helps to regulate cancers, HIV, and neurodegenerative diseases.[7]
Cancer
As mentioned above, KAT5 helps to repair DNA and upregualte tumor suppressors such as p53. Therefore, many cancers are marked by a reduction of KAT5 mRNA. KAT5 also is linked to metastasis and malignancy.[16]
- Colon cancer[17]
- Lung cancer[11]
- Breast cancer[18]
- Pancreatic[18]
- Gastric cancer[19]
- Metastatic melanoma[16]
Studies have also shown that KAT5 augmented the ability of chemotherapy to stop tumor growth, demonstrating its potential for use in combination therapy.[18]
However, KAT5 isn't always anti-cancer. It can enhance the activity of proteins for viruses that cause cancer such as
Other proteins that KAT5 promotes may lead to cancer as well. For example, overexpressed E2F1, a transcriptional factor, is implicated in melanoma progression.[22] More research needs to be performed to clearly elucidate the overall role KAT5 has in cancer.
HIV
KAT5 binds to
Aging and Neurodegeneration
TIP60 regulates diverse cellular pathways including autophagy, DNA repair, neuronal survival, learning/memory, sleep/wake patterns, and protein turnover, all of which contribute to cellular homeostasis and organismal health so as to counteract aging and neurodegeneration.[24]
Interactions
HTATIP has been shown to
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000172977 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000024926 – 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.
- PMID 8607265.
- ^ a b "Entrez Gene: HTATIP HIV-1 Tat interacting protein, 60kDa". Archived from the original on 2024-04-27. Retrieved 2024-04-27.
- ^ hdl:2042/38522.)
{{cite journal}}: CS1 maint: DOI inactive as of April 2024 (link - PMID 17636029.
- PMID 7501439.
- ^ Lee F. "Gene Transcription: Histone Acetylation, DNA Methylation and Epigenetics". Molecular Biology Web Book. Web Books Publishing. Archived from the original on 2015-05-04. Retrieved 2015-05-06.
- ^ PMID 22159227.
- PMID 15572685.
- PMID 16141325.
- S2CID 25051471.
- from the original on 2022-01-11. Retrieved 2024-04-27.
- ^ PMID 22673729.
- PMID 24287617.
- ^ .
- PMID 21273583.
- PMID 15988028.
- PMID 25673709.
- PMID 20026813.
- PMID 8607265.
- from the original on 2023-03-04. Retrieved 2024-04-27.
- S2CID 9930504.
- S2CID 2356435.
- PMID 10720489.
- PMID 12737628.
- S2CID 38498534.
- PMID 18263878.
- S2CID 6317335.
- PMID 11927554.
- PMID 12776177.
- PMID 11416127.
- ^ Bakshi, K., Ranjitha, B., Dubey, S. et al. Novel complex of HAT protein TIP60 and nuclear receptor PXR promotes cell migration and adhesion. Sci Rep 7, 3635 (2017). https://doi.org/10.1038/s41598-017-03783-w
Further reading
- Doyon Y, Côté J (Apr 2004). "The highly conserved and multifunctional NuA4 HAT complex". Current Opinion in Genetics & Development. 14 (2): 147–54. PMID 15196461.
- Sapountzi V, Logan IR, Robson CN (2006). "Cellular functions of TIP60". The International Journal of Biochemistry & Cell Biology. 38 (9): 1496–509. PMID 16698308.
- Maruyama K, Sugano S (Jan 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. PMID 8125298.
- Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (Oct 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. PMID 9373149.
- Yamamoto T, Horikoshi M (Dec 1997). "Novel substrate specificity of the histone acetyltransferase activity of HIV-1-Tat interactive protein Tip60". The Journal of Biological Chemistry. 272 (49): 30595–8. S2CID 21873080.
- Kimura A, Horikoshi M (Dec 1998). "Tip60 acetylates six lysines of a specific class in core histones in vitro". Genes to Cells. 3 (12): 789–800. S2CID 41070266.
- Dechend R, Hirano F, Lehmann K, Heissmeyer V, Ansieau S, Wulczyn FG, Scheidereit C, Leutz A (Jun 1999). "The Bcl-3 oncoprotein acts as a bridging factor between NF-kappaB/Rel and nuclear co-regulators". Oncogene. 18 (22): 3316–23. S2CID 2356435.
- Brady ME, Ozanne DM, Gaughan L, Waite I, Cook S, Neal DE, Robson CN (Jun 1999). "Tip60 is a nuclear hormone receptor coactivator". The Journal of Biological Chemistry. 274 (25): 17599–604. S2CID 38058299.
- Creaven M, Hans F, Mutskov V, Col E, Caron C, Dimitrov S, Khochbin S (Jul 1999). "Control of the histone-acetyltransferase activity of Tip60 by the HIV-1 transactivator protein, Tat". Biochemistry. 38 (27): 8826–30. PMID 10393559.
- Sliva D, Zhu YX, Tsai S, Kamine J, Yang YC (Sep 1999). "Tip60 interacts with human interleukin-9 receptor alpha-chain". Biochemical and Biophysical Research Communications. 263 (1): 149–55. PMID 10486269.
- Gavaravarapu S, Kamine J (Mar 2000). "Tip60 inhibits activation of CREB protein by protein kinase A". Biochemical and Biophysical Research Communications. 269 (3): 758–66. PMID 10720489.
- Husi H, Ward MA, Choudhary JS, Blackstock WP, Grant SG (Jul 2000). "Proteomic analysis of NMDA receptor-adhesion protein signaling complexes". Nature Neuroscience. 3 (7): 661–9. S2CID 14392630.
- Ikura T, Ogryzko VV, Grigoriev M, Groisman R, Wang J, Horikoshi M, Scully R, Qin J, Nakatani Y (Aug 2000). "Involvement of the TIP60 histone acetylase complex in DNA repair and apoptosis". Cell. 102 (4): 463–73. S2CID 18047169.
- Ran Q, Pereira-Smith OM (Nov 2000). "Identification of an alternatively spliced form of the Tat interactive protein (Tip60), Tip60(beta)". Gene. 258 (1–2): 141–6. PMID 11111051.
- Lee HJ, Chun M, Kandror KV (May 2001). "Tip60 and HDAC7 interact with the endothelin receptor a and may be involved in downstream signaling". The Journal of Biological Chemistry. 276 (20): 16597–600. S2CID 38498534.
- Hlubek F, Löhberg C, Meiler J, Jung A, Kirchner T, Brabletz T (Apr 2001). "Tip60 is a cell-type-specific transcriptional regulator". Journal of Biochemistry. 129 (4): 635–41. PMID 11275565.
- Sheridan AM, Force T, Yoon HJ, O'Leary E, Choukroun G, Taheri MR, Bonventre JV (Jul 2001). "PLIP, a novel splice variant of Tip60, interacts with group IV cytosolic phospholipase A(2), induces apoptosis, and potentiates prostaglandin production". Molecular and Cellular Biology. 21 (14): 4470–81. PMID 11416127.
- Cao X, Südhof TC (Jul 2001). "A transcriptionally [correction of transcriptively] active complex of APP with Fe65 and histone acetyltransferase Tip60". Science. 293 (5527): 115–20. S2CID 43920642.
- Legube G, Linares LK, Lemercier C, Scheffner M, Khochbin S, Trouche D (Apr 2002). "Tip60 is targeted to proteasome-mediated degradation by Mdm2 and accumulates after UV irradiation". The EMBO Journal. 21 (7): 1704–12. PMID 11927554.
External links
- Overview of all the structural information available in the PDB for UniProt: Q92993 (Histone acetyltransferase KAT5) at the PDBe-KB.
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