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Literature summary for 2.3.1.48 extracted from
- Deciphering structure, function and mechanism of lysine acetyltransferase HBO1 in protein acetylation, transcription regulation, DNA replication and its oncogenic properties in cancer (2020), Cell. Mol. Life Sci., 77, 637-649 .
Activating Compound
| Activating Compound | Comment | Organism | Structure |
|---|---|---|---|
| BRPF2 | i.e. BRD1, BRPF2 is a cofactor directing HBO1 binding to the histone and binds to HBO1 in a cervical-loop structure proximity to the MYST domain to facilitate histone binding | Homo sapiens | |
| BRPF2 | i.e. BRD1, BRPF2 is a cofactor directing HBO1 binding to the histone and binds to HBO1 in a cervical-loop structure proximity to the MYST domain to facilitate histone binding. BRPF2 binds to HBO1 on the hinge connecting the NTD and MYST domain, thus it is reasonable to develop BRPF2-mimic peptides or molecules for disrupting HBO1-BRPF2 interaction andsubsequently prevent the binding of HBO1 to chromatin | Mus musculus |
Application
| Application | Comment | Organism |
|---|---|---|
| drug development | HBO1 is a potential anti-cancer target, design of HBO1-targeting molecules and their applications | Homo sapiens |
Cloned(Commentary)
| Cloned (Comment) | Organism |
|---|---|
| gene KAT7, sequence comparisons, expression analysis | Homo sapiens |
| gene KAT7, sequence comparisons, expression analysis | Mus musculus |
Protein Variants
| Protein Variants | Comment | Organism |
|---|---|---|
| additional information | in vitro-expressed full-length HBO1 exerts less acetylation activity compared to that of the separate MYST domain | Homo sapiens |
| additional information | in vitro-expressed full-length HBO1 exerts less acetylation activity compared to that of the separate MYST domain | Mus musculus |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| protein HBZ | HTLV-1 (basic zipper factor, from a human T cell leukemia virus), interacts with HBO1 during pathogenesis and inhibits its acetylation activity to reduce p53-mediated transcription activation of p21/CDKN1A and Gadd45a, and subsequently delays G2-cell cycle arrest. BRPF2 binds to HBO1 on the hinge connecting the NTD and MYST domain, thus it is reasonable to develop BRPF2-mimic peptides or molecules for disrupting HBO1-BRPF2 interaction and subsequently prevent the binding of HBO1 to chromatin | Homo sapiens | |
| protein HBZ | HTLV-1 (basic zipper factor, from a human T cell leukemia virus), interacts with HBO1 during pathogenesis and inhibits its acetylation activity to reduce p53-mediated transcription activation of p21/CDKN1A and Gadd45a, and subsequently delays G2-cell cycle arrest | Mus musculus |
Localization
| Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|
| nucleus | - |
Mus musculus | 5634 | - |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| acetyl-CoA + [histone H3]-L-lysine14 | Homo sapiens | - |
CoA + [histone H3]-N6-acetyl-L-lysine14 | - |
? |  |
| acetyl-CoA + [histone H3]-L-lysine14 | Mus musculus | - |
CoA + [histone H3]-N6-acetyl-L-lysine14 | - |
? | |
| acetyl-CoA + [histone H4]-L-lysine | Homo sapiens | - |
CoA + [histone H4]-N6-acetyl-L-lysine | - |
? | |
| acetyl-CoA + [histone H4]-L-lysine | Mus musculus | - |
CoA + [histone H4]-N6-acetyl-L-lysine | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | O95251 | - |
- |
| Mus musculus | Q5SVQ0 | - |
- |
Posttranslational Modification
| Posttranslational Modification | Comment | Organism |
|---|---|---|
| acetylation | acetylation and autoacetylation regulates HBO1 activity. This regulation mainly occurs on Lys199 (K199) within the residues HLTGK (ac) HER in humans. In contrast, acetylation occurs at conserve site Lys277 in humans | Homo sapiens |
| acetylation | acetylation and autoacetylation regulates HBO1 activity. This regulation mainly occurs on Lys201. In contrast, acetylation occurs at another conserve site Lys279 in RNSGLSK(ac)EQ is downregulated in response to heat or X-ray treatments in mouse testis, indicating its functions in spermatogenesis | Mus musculus |
| additional information | HBO1 can be either ubiquitinated or act as an ubiquitin ligase | Homo sapiens |
| additional information | HBO1 can be either ubiquitinated or act as an ubiquitin ligase | Mus musculus |
| phosphoprotein | phosphorylations regulate HBO1 activity and connect it to the cell cycle | Homo sapiens |
| phosphoprotein | phosphorylations regulate HBO1 activity and connect it to the cell cycle | Mus musculus |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| fibroblast | - |
Mus musculus | - |
| additional information | HBO1 is highly expressed in testis or ovary. Tissue-specific acetyltransferase activity of HBO1 | Homo sapiens | - |
| ovary | - |
Homo sapiens | - |
| synovial fibroblast | in immune-related disease, HBO1 is upregulated in synovial fibroblasts, which are the key pathogenic factors contributing to the development and progression of rheumatoid arthritis | Homo sapiens | - |
| testis | - |
Homo sapiens | - |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| acetyl-CoA + [CDC6]-L-lysine14 | - |
Homo sapiens | CoA + [CDC6]-N6-acetyl-L-lysine14 | - |
? | |
| acetyl-CoA + [CDC6]-L-lysine14 | - |
Mus musculus | CoA + [CDC6]-N6-acetyl-L-lysine14 | - |
? | |
| acetyl-CoA + [Geminin]-L-lysine14 | - |
Homo sapiens | CoA + [Geminin]-N6-acetyl-L-lysine14 | - |
? | |
| acetyl-CoA + [Geminin]-L-lysine14 | - |
Mus musculus | CoA + [Geminin]-N6-acetyl-L-lysine14 | - |
? | |
| acetyl-CoA + [histone H3]-L-lysine14 | - |
Homo sapiens | CoA + [histone H3]-N6-acetyl-L-lysine14 | - |
? | |
| acetyl-CoA + [histone H3]-L-lysine14 | - |
Mus musculus | CoA + [histone H3]-N6-acetyl-L-lysine14 | - |
? | |
| acetyl-CoA + [histone H4]-L-lysine | - |
Homo sapiens | CoA + [histone H4]-N6-acetyl-L-lysine | - |
? | |
| acetyl-CoA + [histone H4]-L-lysine | - |
Mus musculus | CoA + [histone H4]-N6-acetyl-L-lysine | - |
? | |
| acetyl-CoA + [MCM2]-L-lysine14 | - |
Homo sapiens | CoA + [MCM2]-N6-acetyl-L-lysine14 | - |
? | |
| acetyl-CoA + [MCM2]-L-lysine14 | - |
Mus musculus | CoA + [MCM2]-N6-acetyl-L-lysine14 | - |
? | |
| acetyl-CoA + [ORC2]-L-lysine14 | - |
Homo sapiens | CoA + [ORC2]-N6-acetyl-L-lysine14 | - |
? | |
| acetyl-CoA + [ORC2]-L-lysine14 | - |
Mus musculus | CoA + [ORC2]-N6-acetyl-L-lysine14 | - |
? | |
| additional information | HBO1 exerts significant acetyltransferase activity on proteins such as ORC2, MCM2, CDC6, and Geminin in in vitro assays | Homo sapiens | ? | - |
- |
|
| additional information | HBO1 exerts significant acetyltransferase activity on proteins such as ORC2, MCM2, CDC6, and Geminin in in vitro assays | Mus musculus | ? | - |
- |
|
Subunits
| Subunits | Comment | Organism |
|---|---|---|
| More | HBO1 consists of the N-terminal domain (NTD) and the conserved C-terminal MYST domain. The NTD of HBO1 consists of a number of loops and a small part of the helix. The structure is highly flexible, which may provide abundant conformation changes for HBO1 activity regulation or protein binding. The MYST domain of HBO1 contains two typical sites for molecule binding, the acetyl-CoA-binding site and histone tail binding site | Homo sapiens |
| More | HBO1 consists of the N-terminal domain (NTD) and the conserved C-terminal MYST domain. The NTD of HBO1 consists of a number of loops and a small part of the helix. The structure is highly flexible, which may provide abundant conformation changes for HBO1 activity regulation or protein binding. The MYST domain of HBO1 contains two typical sites for molecule binding, the acetyl-CoA-binding site and histone tail binding site | Mus musculus |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| HBO1 | - |
Homo sapiens |
| HBO1 | - |
Mus musculus |
| KAT7 | - |
Homo sapiens |
| KAT7 | - |
Mus musculus |
| lysine acetyltransferase | - |
Homo sapiens |
| lysine acetyltransferase | - |
Mus musculus |
| MYST2 | - |
Homo sapiens |
| MYST2 | - |
Mus musculus |
Cofactor
| Cofactor | Comment | Organism | Structure |
|---|---|---|---|
| acetyl-CoA | - |
Homo sapiens | |
| acetyl-CoA | - |
Mus musculus | |
Expression
| Organism | Comment | Expression |
|---|---|---|
| Homo sapiens | in immune-related disease, HBO1 is upregulated in synovial fibroblasts, which are the key pathogenic factors contributing to the development and progression of rheumatoid arthritis | up |
| Mus musculus | in immune-related disease, HBO1 is upregulated in synovial fibroblasts, which are the key pathogenic factors contributing to the development and progression of rheumatoid arthritis | up |
General Information
| General Information | Comment | Organism |
|---|---|---|
| evolution | HBO1 (also known as KAT7, MYST2) is a canonical member of the MYST (MOZ, Ybf1/Sas3, Sas2 and Tip60) acetyltransferase family. HBO1 contains the MYST domain that is a highly conserved acetyltransferase domain shared by the MYST family such as MYST1 (MOF/KAT8), MYST2 (HBO1/KAT7), and MYST3 (MOZ/KAT6A). HBO1 comprises a cervical-loop structure proximity to the MYST domain that mediates the interaction with the N-terminal region (residues 31-80) of BRPF2 (also known as BRD1), for BRPF2 is a cofactor directing HBO1 binding to the histone | Homo sapiens |
| evolution | HBO1 (also known as KAT7, MYST2) is a canonical member of the MYST (MOZ, Ybf1/Sas3, Sas2 and Tip60) acetyltransferase family. HBO1 contains the MYST domain that is a highly conserved acetyltransferase domain shared by the MYST family such as MYST1 (MOF/KAT8), MYST2 (HBO1/KAT7), and MYST3 (MOZ/KAT6A). HBO1 comprises a cervical-loop structure proximity to the MYST domain that mediates the interaction with the N-terminal region (residues 31-80) of BRPF2 (also known as BRD1), for BRPF2 is a cofactor directing HBO1 binding to the histone | Mus musculus |
| malfunction | abrogation of HBO1 activity caused by either RNA interference or dominant negative mutation (e.g. S57A) does not affect the recruitment of ORC, CDC6 and CDT1 to replication origins, but remarkably impairs the loading of MCMs to the origins and subsequently delays DNA replication licensing. In immune-related disease, HBO1 is upregulated in synovial fibroblasts, which are the key pathogenic factors contributing to the development and progression of rheumatoid arthritis. Protein HBZ (HTLV-1 basic zipper factor, from a human T cell leukemia virus) interacts with HBO1 during pathogenesis and inhibits its acetylation activity to reduce p53-mediated transcription activation of p21/CDKN1A and Gadd45a, and subsequently delays G2-cell cycle arrest | Homo sapiens |
| malfunction | abrogation of HBO1 activity caused by either RNA interference or dominant negative mutation (e.g. S57A) does not affect the recruitment of ORC, CDC6 and CDT1 to replication origins, but remarkably impairs the loading of MCMs to the origins and subsequently delays DNA replication licensing. In immune-related disease, HBO1 is upregulated in synovial fibroblasts, which are the key pathogenic factors contributing to the development and progression of rheumatoid arthritis. Protein HBZ (HTLV-1 basic zipper factor, from a human T cell leukemia virus) interacts with HBO1 during pathogenesis and inhibits its acetylation activity to reduce p53-mediated transcription activation of p21/CDKN1A and Gadd45a, and subsequently delays G2-cell cycle arrest | Mus musculus |
| metabolism | HBO1 can be either ubiquitinated or act as an ubiquitin ligase. HBO1 acetyltransferase complexes and activity regulation, overview. The tumor suppressor p53, adipogenesis regulator FAD24 (factor for adipocyte differentiation 24, also called NOC3L) and cell cycle kinases CDK1, CDK2, CDK11 and PLK1 are linked to HBO1. Moreover, cell growth inhibitor Niam and homeobox protein SIX1 that potentiates the Warburg effect by interaction with HBO1 are also presented. HBO1 complexes mainly consist of accessory proteins MEAF6, ING4 or ING5, and two types of cofactors for chromatin binding: Jade-1/2/3 and BRPF1/2/3. HBO1 is associated with the key events of the cell cycle, especially in mitosis through physical interaction with PLK1 and CDK1. Acetylation and autoacetylation regulates HBO1 activity | Homo sapiens |
| metabolism | HBO1 can be either ubiquitinated or act as an ubiquitin ligase. HBO1 acetyltransferase complexes and activity regulation, overview. The tumor suppressor p53, adipogenesis regulator FAD24 (factor for adipocyte differentiation 24, also called NOC3L) and cell cycle kinases CDK1, CDK2, CDK11 and PLK1 are linked to HBO1. Moreover, cell growth inhibitor Niam and homeobox protein SIX1 that potentiates the Warburg effect by interaction with HBO1 are also presented. HBO1 complexes mainly consist of accessory proteins MEAF6, ING4 or ING5, and two types of cofactors for chromatin binding: Jade-1/2/3 and BRPF1/2/3. HBO1 is associated with the key events of the cell cycle, especially in mitosis through physical interaction with PLK1 and CDK1. Acetylation and autoacetylation regulates HBO1 activity | Mus musculus |
| additional information | in vitro-expressed full-length HBO1 exerts less acetylation activity compared to that of the separate MYST domain. The N-terminal domain may provide a regulatory switch for HBO1 activity | Homo sapiens |
| additional information | in vitro-expressed full-length HBO1 exerts less acetylation activity compared to that of the separate MYST domain. The N-terminal domain may provide a regulatory switch for HBO1 activity | Mus musculus |
| physiological function | enzyme HBO1 is responsible for the bulk acetylation of histone H4 and H3K14. HBO1 functions as the core catalytic subunit in multimeric complexes established by cofactors and accessory proteins. HBO1 affords multiple functions in various processes such as DNA replication, gene transcription, protein ubiquitination, immune regulation, stem cell pluripotent and self-renewal maintenance as well as embryonic development. HBO1 functions as the core catalytic subunit in multimeric complexes established by cofactors and accessory proteins. HBO1 is reported to participate in transcriptional regulation in alternative complexes such as HBO1-SIX1 and HBO1-Niam. HBO1 encourages tissue-specific gene expression, for it participates in intragenic histone acetylation and mediated Pol II binding in regulating the expression of endothelial VEGFR-2. HBO1-mediated histone acetylation enables the accession of transcriptional factors to the chromatin and regulates the initiation of transcription. Alternatively, HBO1 complexes occupies the coding region to afford a direct role in transcriptional elongation. HBO1 might acetylate the transcriptional factors and change their protein-protein interactions. HBO1 facilitates chromatin loading of minichromosome maintenance (MCM) complexes and promotes DNA replication licensing. Loading of MCM complexes to chromatin is the final step of the prereplicative complexes assembly. Indispensable roles of HBO1 in chromosome remodeling and DNA replication, the mechanism regarding how HBO1 facilitates MCM loading and the involved protein-protein interactions is analyzed. HBO1 is required for T cell development and immune regulation. HBO1 acetyltransferase complexes and activity regulation, overview. Multiple functions of HBO1 are realized by the formation of protein complexes with different cofactors or partner proteins. The components of HBO1 acetyltransferase complexes and related downstream pathways may also contribute to the activity of HBO1 in cell proliferation. For example, Jade-2-mediated HBO1 acetylation activity enhances the expression of mechano-transductor signaling factor YAP1 to modulate cell elasticity in ovarian cancer. Besides, mutations in ING4 or ING5 destabilize the protein and contribute to tumorigenesis. HBO1 is essential for global acetylation of histone H3K4 and H4, thus the acetylation activity of HBO1 may also induce the expression of anti-cancer genes such as Brahma. In acute myeloid leukemia, HBO1 expression is suppressed associated with the decease of global H4K5 acetylation. Interestingly, a fusion of nucleoporin-98 (NUP98)-HBO1 is identified in a patient with chronic myelomonocytic leukemia (CMML). NUP98-HBO1 is sufficient to generate CMML pathogenesis through aberrant histone acetylation on the promoter of oncogene such as HOXA9 | Homo sapiens |
| physiological function | enzyme HBO1 is responsible for the bulk acetylation of histone H4 and H3K14. HBO1 functions as the core catalytic subunit in multimeric complexes established by cofactors and accessory proteins. HBO1 affords multiple functions in various processes such as DNA replication, gene transcription, protein ubiquitination, immune regulation, stem cell pluripotent and self-renewal maintenance as well as embryonic development. HBO1 functions as the core catalytic subunit in multimeric complexes established by cofactors and accessory proteins. HBO1 is reported to participate in transcriptional regulation in alternative complexes such as HBO1-SIX1 and HBO1-Niam. HBO1 encourages tissue-specific gene expression, for it participates in intragenic histone acetylation and mediated Pol II binding in regulating the expression of endothelial VEGFR-2. HBO1-mediated histone acetylation enables the accession of transcriptional factors to the chromatin and regulates the initiation of transcription. Alternatively, HBO1 complexes occupies the coding region to afford a direct role in transcriptional elongation. HBO1 might acetylate the transcriptional factors and change their protein-protein interactions. HBO1 facilitates chromatin loading of minichromosome maintenance (MCM) complexes and promotes DNA replication licensing. Loading of MCM complexes to chromatin is the final step of the prereplicative complexes assembly. Indispensable roles of HBO1 in chromosome remodeling and DNA replication, the mechanism regarding how HBO1 facilitates MCM loading and the involved protein-protein interactions is analyzed. HBO1 is required for T cell development and immune regulation. HBO1 acetyltransferase complexes and activity regulation, overview. Multiple functions of HBO1 are realized by the formation of protein complexes with different cofactors or partner proteins. HBO1 functions in spermatogenesis | Mus musculus |
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