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654  structures 6020  species 0  interactions 25207  sequences 266  architectures

Family: Hist_deacetyl (PF00850)

Summary: Histone deacetylase domain

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This is the Wikipedia entry entitled "Histone deacetylase". More...

Histone deacetylase Edit Wikipedia article

histone deacetylase
Catalytic domain of Human histone deacetylase 4 with bound inhibitor. PDB rendering based on 2vqj.[1]
EC number3.5.1.98
CAS number9076-57-7
IntEnzIntEnz view
ExPASyNiceZyme view
MetaCycmetabolic pathway
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO
Histone deacetylase superfamily

Histone deacetylases (EC, HDAC) are a class of enzymes that remove acetyl groups (O=C-CH3) from an ε-N-acetyl lysine amino acid on a histone, allowing the histones to wrap the DNA more tightly. This is important because DNA is wrapped around histones, and DNA expression is regulated by acetylation and de-acetylation. Its action is opposite to that of histone acetyltransferase. HDAC proteins are now also called lysine deacetylases (KDAC), to describe their function rather than their target, which also includes non-histone proteins.[2]

HDAC super family

Together with the acetylpolyamine amidohydrolases and the acetoin utilization proteins, the histone deacetylases form an ancient protein superfamily known as the histone deacetylase superfamily.[3]

Classes of HDACs in higher eukaryotes

HDACs, are classified in four classes depending on sequence homology to the yeast original enzymes and domain organization:[4]

Class Members Catalytic sites Subcellular localization Tissue distribution Substrates Binding partners Knockout phenotype
I HDAC1 1 Nucleus Ubiquitous Androgen receptor, SHP, p53, MyoD, E2F1, STAT3 – embryonic lethal, increased histone acetylation, increase in p21 and p27
HDAC2 1 Nucleus Ubiquitous Glucocorticoid receptor, YY1, BCL6, STAT3 – Cardiac defect
HDAC3 1 Nucleus Ubiquitous SHP, YY1, GATA1, RELA, STAT3, MEF2D – –
HDAC8 1 Nucleus/cytoplasm Ubiquitous? – EST1B –
IIA HDAC4 1 Nucleus / cytoplasm heart, skeletal muscle, brain GCMA, GATA1, HP1 RFXANK Defects in chondrocyte differentiation
HDAC5 1 Nucleus / cytoplasm heart, skeletal muscle, brain GCMA, SMAD7, HP1 REA, estrogen receptor Cardiac defect
HDAC7 1 Nucleus / cytoplasm / mitochondria heart, skeletal muscle, pancreas, placenta PLAG1, PLAG2 HIF1A, BCL6, endothelin receptor, ACTN1, ACTN4, androgen receptor, Tip60 Maintenance of vascular integrity, increase in MMP10
HDAC9 1 Nucleus / cytoplasm brain, skeletal muscle – FOXP3 Cardiac defect
IIB HDAC6 2 Mostly cytoplasm heart, liver, kidney, placenta α-Tubulin, HSP90, SHP, SMAD7 RUNX2 –
HDAC10 1 Mostly cytoplasm liver, spleen, kidney – – –
III sirtuins in mammals (SIRT1, SIRT2, SIRT3, SIRT4, SIRT5, SIRT6, SIRT7) – – – – – –
Sir2 in the yeast S. cerevisiae – – – – – –
IV HDAC11 2 Nucleus / cytoplasm brain, heart, skeletal muscle, kidney – – –

HDAC (except class III) contain zinc and are known as Zn2+-dependent histone deacetylases.[5] They feature a classical Arginase fold and are structurally and mechanistically distinct from sirtuins (class III), which fold into a Rossmann architecture and are NAD+ dependent.[6]


HDAC proteins are grouped into four classes (see above) based on function and DNA sequence similarity. Class I, II and IV are considered "classical" HDACs whose activities are inhibited by trichostatin A (TSA) and have a zinc dependent active site, whereas Class III enzymes are a family of NAD+-dependent proteins known as sirtuins and are not affected by TSA.[7] Homologues to these three groups are found in yeast having the names: reduced potassium dependency 3 (Rpd3), which corresponds to Class I; histone deacetylase 1 (hda1), corresponding to Class II; and silent information regulator 2 (Sir2), corresponding to Class III. Class IV contains just one isoform (HDAC11), which is not highly homologous with either Rpd3 or hda1 yeast enzymes,[8] and therefore HDAC11 is assigned to its own class. The Class III enzymes are considered a separate type of enzyme and have a different mechanism of action; these enzymes are NAD+-dependent, whereas HDACs in other classes require Zn2+ as a cofactor.[9]

Subcellular distribution

Within the Class I HDACs, HDAC 1, 2, and 3 are found primarily in the nucleus, whereas HDAC8 is found in both the nucleus and the cytoplasm, and is also membrane-associated. Class II HDACs (HDAC4, 5, 6, 7 9, and 10) are able to shuttle in and out of the nucleus, depending on different signals.[10][11]

HDAC6 is a cytoplasmic, microtubule-associated enzyme. HDAC6 deacetylates tubulin, Hsp90, and cortactin, and forms complexes with other partner proteins, and is, therefore, involved in a variety of biological processes.[12]


Histone modification

Histone tails are normally positively charged due to amine groups present on their lysine and arginine amino acids. These positive charges help the histone tails to interact with and bind to the negatively charged phosphate groups on the DNA backbone. Acetylation, which occurs normally in a cell, neutralizes the positive charges on the histone by changing amines into amides and decreases the ability of the histones to bind to DNA. This decreased binding allows chromatin expansion, permitting genetic transcription to take place. Histone deacetylases remove those acetyl groups, increasing the positive charge of histone tails and encouraging high-affinity binding between the histones and DNA backbone. The increased DNA binding condenses DNA structure, preventing transcription.

Histone deacetylase is involved in a series of pathways within the living system. According to the Kyoto Encyclopedia of Genes and Genomes (KEGG), these are:

Histone acetylation plays an important role in the regulation of gene expression. Hyperacetylated chromatin is transcriptionally active, and hypoacetylated chromatin is silent. A study on mice found that a specific subset of mouse genes (7%) was deregulated in the absence of HDAC1.[13] Their study also found a regulatory crosstalk between HDAC1 and HDAC2 and suggest a novel function for HDAC1 as a transcriptional coactivator. HDAC1 expression was found to be increased in the prefrontal cortex of schizophrenia subjects,[14] negatively correlating with the expression of GAD67 mRNA.

Non-histone effects

It is a mistake to regard HDACs solely in the context of regulating gene transcription by modifying histones and chromatin structure, although that appears to be the predominant function. The function, activity, and stability of proteins can be controlled by post-translational modifications. Protein phosphorylation is perhaps the most widely studied and understood modification in which certain amino acid residues are phosphorylated by the action of protein kinases or dephosphorylated by the action of phosphatases. The acetylation of lysine residues is emerging as an analogous mechanism, in which non-histone proteins are acted on by acetylases and deacetylases.[15] It is in this context that HDACs are being found to interact with a variety of non-histone proteins—some of these are transcription factors and co-regulators, some are not. Note the following four examples:

  • HDAC6 is associated with aggresomes. Misfolded protein aggregates are tagged by ubiquitination and removed from the cytoplasm by dynein motors via the microtubule network to an organelle termed the aggresome. HDAC 6 binds polyubiquitinated misfolded proteins and links to dynein motors, thereby allowing the misfolded protein cargo to be physically transported to chaperones and proteasomes for subsequent destruction.[16] HDAC6 is important regulator of HSP90 function and its inhibitor proposed to treat metabolic disorders.[17]
  • PTEN is an important phosphatase involved in cell signaling via phosphoinositols and the AKT/PI3 kinase pathway. PTEN is subject to complex regulatory control via phosphorylation, ubiquitination, oxidation and acetylation. Acetylation of PTEN by the histone acetyltransferase p300/CBP-associated factor (PCAF) can repress its activity; on the converse, deacetylation of PTEN by SIRT1 deacetylase and, by HDAC1, can stimulate its activity.[18][19]
  • APE1/Ref-1 (APEX1) is a multifunctional protein possessing both DNA repair activity (on abasic and single-strand break sites) and transcriptional regulatory activity associated with oxidative stress. APE1/Ref-1 is acetylated by PCAF; on the converse, it is stably associated with and deacetylated by Class I HDACs. The acetylation state of APE1/Ref-1 does not appear to affect its DNA repair activity, but it does regulate its transcriptional activity such as its ability to bind to the PTH promoter and initiate transcription of the parathyroid hormone gene.[20][21]
  • NF-κB is a key transcription factor and effector molecule involved in responses to cell stress, consisting of a p50/p65 heterodimer. The p65 subunit is controlled by acetylation via PCAF and by deacetylation via HDAC3 and HDAC6.[22]

These are just some examples of constantly emerging non-histone, non-chromatin roles for HDACs.

Neurodegenerative diseases

Inherited mutations in the gene encoding FUS, an RNA/DNA binding protein, are causally linked to amyotrophic lateral sclerosis (ALS).[23] FUS has a pivotal role in the DNA damage response involving its direct interaction with histone deacetylase 1 (HDAC1). ALS mutant FUS proteins are defective in the DNA damage response and in recombinational DNA repair, and also show reduced interaction with HDAC1.[23]

Ataxia-telangiectasia is due to mutation in the Atm gene. Wild-type Atm encodes a protein kinase employed in chromatin remodeling and in epigenetic alterations that are required for repairing DNA double-strand breaks.[24] Atm mutation causes neurons to accumulate nuclear histone deacetylase 4 (HDAC4) resulting in increased histone deacetylation and altered neuronal gene expression that likely contributes to the neurodegeneration characteristic of ataxia-telangiectasia.[25]

HDAC inhibitors

Histone deacetylase inhibitors (HDIs) have a long history of use in psychiatry and neurology as mood stabilizers and anti-epileptics, for example, valproic acid. In more recent times, HDIs are being studied as a mitigator or treatment for neurodegenerative diseases.[26][27] Also in recent years, there has been an effort to develop HDIs for cancer therapy.[28][29] Vorinostat (SAHA) was FDA approved in 2006 for the treatment of cutaneous manifestations in patients with cutaneous T cell lymphoma (CTCL) that have failed previous treatments. A second HDI, Istodax (romidepsin), was approved in 2009 for patients with CTCL. The exact mechanisms by which the compounds may work are unclear, but epigenetic pathways are proposed.[30] In addition, a clinical trial is studying valproic acid effects on the latent pools of HIV in infected persons.[31] HDIs are currently being investigated as chemosensitizers for cytotoxic chemotherapy or radiation therapy, or in association with DNA methylation inhibitors based on in vitro synergy.[32] Isoform selective HDIs which can aid in elucidating role of individual HDAC isoforms have been developed.[33][34][35]

HDAC inhibitors have effects on non-histone proteins that are related to acetylation. HDIs can alter the degree of acetylation of these molecules and, therefore, increase or repress their activity. For the four examples given above (see Function) on HDACs acting on non-histone proteins, in each of those instances the HDAC inhibitor Trichostatin A (TSA) blocks the effect. HDIs have been shown to alter the activity of many transcription factors, including ACTR, cMyb, E2F1, EKLF, FEN 1, GATA, HNF-4, HSP90, Ku70, NFκB, PCNA, p53, RB, Runx, SF1 Sp3, STAT, TFIIE, TCF, YY1.[36][37]

Histone deacetylase inhibitors may modulate the latency of some viruses, resulting in reactivation.[38] This has been shown to occur, for instance, with a latent human herpesvirus-6 infection.

See also


  1. ^ Bottomley MJ, Lo Surdo P, Di Giovine P, Cirillo A, Scarpelli R, Ferrigno F, Jones P, Neddermann P, et al. (September 2008). "Structural and functional analysis of the human HDAC4 catalytic domain reveals a regulatory structural zinc-binding domain". The Journal of Biological Chemistry. 283 (39): 26694–704. doi:10.1074/jbc.M803514200. PMC 3258910. PMID 18614528.
  2. ^ Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M (Aug 2009). "Lysine acetylation targets protein complexes and co-regulates major cellular functions". Science. 325 (5942): 834–40. doi:10.1126/science.1175371. PMID 19608861.
  3. ^ Leipe DD, Landsman D (Sep 1997). "Histone deacetylases, acetoin utilization proteins and acetylpolyamine amidohydrolases are members of an ancient protein superfamily". Nucleic Acids Research. 25 (18): 3693–7. doi:10.1093/nar/25.18.3693. PMC 146955. PMID 9278492.
  4. ^ Dokmanovic M, Clarke C, Marks PA (Oct 2007). "Histone deacetylase inhibitors: overview and perspectives". Molecular Cancer Research. 5 (10): 981–9. doi:10.1158/1541-7786.MCR-07-0324. PMID 17951399.
  5. ^ Marks PA, Xu WS (Jul 2009). "Histone deacetylase inhibitors: Potential in cancer therapy". Journal of Cellular Biochemistry. 107 (4): 600–8. doi:10.1002/jcb.22185. PMC 2766855. PMID 19459166.
  6. ^ Bürger M, Chory J (2018). "Structural and chemical biology of deacetylases for carbohydrates, proteins, small molecules and histones". Communications Biology. 1: 217. doi:10.1038/s42003-018-0214-4. PMC 6281622. PMID 30534609.
  7. ^ Imai S, Armstrong CM, Kaeberlein M, Guarente L (Feb 2000). "Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase". Nature. 403 (6771): 795–800. doi:10.1038/35001622. PMID 10693811.
  8. ^ Yang XJ, Seto E (Mar 2008). "The Rpd3/Hda1 family of lysine deacetylases: from bacteria and yeast to mice and men". Nature Reviews Molecular Cell Biology. 9 (3): 206–18. doi:10.1038/nrm2346. PMC 2667380. PMID 18292778.
  9. ^ Barneda-Zahonero B, Parra M (Dec 2012). "Histone deacetylases and cancer". Molecular Oncology. 6 (6): 579–89. doi:10.1016/j.molonc.2012.07.003. PMC 5528343. PMID 22963873.
  10. ^ de Ruijter AJ, van Gennip AH, Caron HN, Kemp S, van Kuilenburg AB (Mar 2003). "Histone deacetylases (HDACs): characterization of the classical HDAC family". The Biochemical Journal. 370 (Pt 3): 737–49. doi:10.1042/BJ20021321. PMC 1223209. PMID 12429021.
  11. ^ Longworth MS, Laimins LA (Jul 2006). "Histone deacetylase 3 localizes to the plasma membrane and is a substrate of Src". Oncogene. 25 (32): 4495–500. doi:10.1038/sj.onc.1209473. PMID 16532030.
  12. ^ Valenzuela-Fernández A, Cabrero JR, Serrador JM, Sánchez-Madrid F (Jun 2008). "HDAC6: a key regulator of cytoskeleton, cell migration and cell-cell interactions". Trends in Cell Biology. 18 (6): 291–7. doi:10.1016/j.tcb.2008.04.003. PMID 18472263.
  13. ^ Zupkovitz G, Tischler J, Posch M, Sadzak I, Ramsauer K, Egger G, Grausenburger R, Schweifer N, Chiocca S, Decker T, Seiser C (Nov 2006). "Negative and positive regulation of gene expression by mouse histone deacetylase 1". Molecular and Cellular Biology. 26 (21): 7913–28. doi:10.1128/MCB.01220-06. PMC 1636735. PMID 16940178.
  14. ^ Sharma RP, Grayson DR, Gavin DP (Jan 2008). "Histone deactylase 1 expression is increased in the prefrontal cortex of schizophrenia subjects: analysis of the National Brain Databank microarray collection". Schizophrenia Research. 98 (1–3): 111–7. doi:10.1016/j.schres.2007.09.020. PMC 2254186. PMID 17961987.
  15. ^ Glozak MA, Sengupta N, Zhang X, Seto E (Dec 2005). "Acetylation and deacetylation of non-histone proteins". Gene. 363: 15–23. doi:10.1016/j.gene.2005.09.010. PMID 16289629.
  16. ^ Rodriguez-Gonzalez A, Lin T, Ikeda AK, Simms-Waldrip T, Fu C, Sakamoto KM (Apr 2008). "Role of the aggresome pathway in cancer: targeting histone deacetylase 6-dependent protein degradation". Cancer Research. 68 (8): 2557–60. doi:10.1158/0008-5472.CAN-07-5989. PMID 18413721.
  17. ^ Mahla, RS (2012). "Comment on: Winkler et al. Histone Deacetylase 6 (HDAC6) Is an Essential Modifier of Glucocorticoid-Induced Hepatic Gluconeogenesis". Diabetes. 61 (7): e10. doi:10.2337/db12-0323. PMC 3379673. PMID 22723278.
  18. ^ Ikenoue T, Inoki K, Zhao B, Guan KL (Sep 2008). "PTEN acetylation modulates its interaction with PDZ domain". Cancer Research. 68 (17): 6908–12. doi:10.1158/0008-5472.CAN-08-1107. PMID 18757404.
  19. ^ Yao XH, Nyomba BL (Jun 2008). "Hepatic insulin resistance induced by prenatal alcohol exposure is associated with reduced PTEN and TRB3 acetylation in adult rat offspring". American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. 294 (6): R1797–806. doi:10.1152/ajpregu.00804.2007. PMID 18385463.
  20. ^ Bhakat KK, Izumi T, Yang SH, Hazra TK, Mitra S (Dec 2003). "Role of acetylated human AP-endonuclease (APE1/Ref-1) in regulation of the parathyroid hormone gene". The EMBO Journal. 22 (23): 6299–309. doi:10.1093/emboj/cdg595. PMC 291836. PMID 14633989.
  21. ^ Fantini D, Vascotto C, Deganuto M, Bivi N, Gustincich S, Marcon G, Quadrifoglio F, Damante G, Bhakat KK, Mitra S, Tell G (Jan 2008). "APE1/Ref-1 regulates PTEN expression mediated by Egr-1". Free Radical Research. 42 (1): 20–9. doi:10.1080/10715760701765616. PMC 2677450. PMID 18324520.
  22. ^ Hasselgren PO (Dec 2007). "Ubiquitination, phosphorylation, and acetylation--triple threat in muscle wasting". Journal of Cellular Physiology. 213 (3): 679–89. doi:10.1002/jcp.21190. PMID 17657723.
  23. ^ a b Wang WY, Pan L, Su SC, Quinn EJ, Sasaki M, Jimenez JC, Mackenzie IR, Huang EJ, Tsai LH (October 2013). "Interaction of FUS and HDAC1 regulates DNA damage response and repair in neurons". Nat. Neurosci. 16 (10): 1383–91. doi:10.1038/nn.3514. PMC 5564396. PMID 24036913.
  24. ^ Berger ND, Stanley FK, Moore S, Goodarzi AA (October 2017). "ATM-dependent pathways of chromatin remodelling and oxidative DNA damage responses". Philos. Trans. R. Soc. Lond., B, Biol. Sci. 372 (1731). doi:10.1098/rstb.2016.0283. PMC 5577461. PMID 28847820.
  25. ^ Li J, Chen J, Ricupero CL, Hart RP, Schwartz MS, Kusnecov A, Herrup K (May 2012). "Nuclear accumulation of HDAC4 in ATM deficiency promotes neurodegeneration in ataxia telangiectasia". Nat. Med. 18 (5): 783–90. doi:10.1038/nm.2709. PMC 3378917. PMID 22466704.
  26. ^ Hahnen E, Hauke J, Tränkle C, Eyüpoglu IY, Wirth B, Blümcke I (Feb 2008). "Histone deacetylase inhibitors: possible implications for neurodegenerative disorders". Expert Opinion on Investigational Drugs. 17 (2): 169–84. doi:10.1517/13543784.17.2.169. PMID 18230051.
  27. ^ "Scientists 'reverse' memory loss". BBC News. 2007-04-29. Retrieved 2007-07-08.
  28. ^ Mwakwari SC, Patil V, Guerrant W, Oyelere AK (2010). "Macrocyclic histone deacetylase inhibitors". Curr Top Med Chem. 10 (14): 1423–40. doi:10.2174/156802610792232079. PMC 3144151. PMID 20536416.
  29. ^ Miller TA, Witter DJ, Belvedere S (Nov 2003). "Histone deacetylase inhibitors". Journal of Medicinal Chemistry. 46 (24): 5097–116. doi:10.1021/jm0303094. PMID 14613312.
  30. ^ Monneret C (Apr 2007). "Histone deacetylase inhibitors for epigenetic therapy of cancer". Anti-Cancer Drugs. 18 (4): 363–70. doi:10.1097/CAD.0b013e328012a5db. PMID 17351388.
  31. ^ Depletion of Latent HIV in CD4 Cells - Full Text View -
  32. ^ Batty N, Malouf GG, Issa JP (Aug 2009). "Histone deacetylase inhibitors as anti-neoplastic agents". Cancer Letters. 280 (2): 192–200. doi:10.1016/j.canlet.2009.03.013. PMID 19345475.
  33. ^ Patil V, Sodji QH, Kornacki JR, Mrksich M, Oyelere AK (May 2013). "3-Hydroxypyridin-2-thione as novel zinc binding group for selective histone deacetylase inhibition". Journal of Medicinal Chemistry. 56 (9): 3492–506. doi:10.1021/jm301769u. PMC 3657749. PMID 23547652.
  34. ^ Mwakwari SC, Guerrant W, Patil V, Khan SI, Tekwani BL, Gurard-Levin ZA, Mrksich M, Oyelere AK (Aug 2010). "Non-peptide macrocyclic histone deacetylase inhibitors derived from tricyclic ketolide skeleton". Journal of Medicinal Chemistry. 53 (16): 6100–11. doi:10.1021/jm100507q. PMC 2924451. PMID 20669972.
  35. ^ Butler KV, Kalin J, Brochier C, Vistoli G, Langley B, Kozikowski AP (Aug 2010). "Rational design and simple chemistry yield a superior, neuroprotective HDAC6 inhibitor, tubastatin A". Journal of the American Chemical Society. 132 (31): 10842–6. doi:10.1021/ja102758v. PMC 2916045. PMID 20614936.
  36. ^ Drummond DC, Noble CO, Kirpotin DB, Guo Z, Scott GK, Benz CC (2005). "Clinical development of histone deacetylase inhibitors as anticancer agents". Annual Review of Pharmacology and Toxicology. 45: 495–528. doi:10.1146/annurev.pharmtox.45.120403.095825. PMID 15822187.
  37. ^ Yang XJ, Seto E (Aug 2007). "HATs and HDACs: from structure, function and regulation to novel strategies for therapy and prevention". Oncogene. 26 (37): 5310–8. doi:10.1038/sj.onc.1210599. PMID 17694074.
  38. ^ Arbuckle JH, Medveczky PG (Aug 2011). "The molecular biology of human herpesvirus-6 latency and telomere integration". Microbes and Infection / Institut Pasteur. 13 (8–9): 731–41. doi:10.1016/j.micinf.2011.03.006. PMC 3130849. PMID 21458587.

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Histone deacetylase domain Provide feedback

Histones can be reversibly acetylated on several lysine residues. Regulation of transcription is caused in part by this mechanism. Histone deacetylases catalyse the removal of the acetyl group. Histone deacetylases are related to other proteins [1].

Literature references

  1. Leipe DD, Landsman D; , Nucleic Acids Res 1997;25:3693-3697.: Histone deacetylases, acetoin utilization proteins and acetylpolyamine amidohydrolases are members of an ancient protein superfamily. PUBMED:9278492 EPMC:9278492

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR023801

Regulation of transcription is, in part, modulated by reversible histone acetylation on several lysine. Histone deacetylases (HDA) catalyse the removal of the acetyl group. Histone deacetylases, acetoin utilization proteins and acetylpolyamine amidohydrolases are all members of this ancient protein superfamily [ PUBMED:9278492 ].

HDAs function in multi-subunit complexes, reversing the acetylation of histones by histone acetyltransferases [ PUBMED:10322454 , PUBMED:10072350 ], and are also believed to deacetylate general transcription factors such as TFIIF and sequence-specific transcription factors such as p53 [ PUBMED:10322454 ]. Thus, HDAs contribute to the regulation of transcription, in particular transcriptional repression [ PUBMED:10072350 ]. At N-terminal tails of histones, removal of the acetyl group from the epsilon-amino group of a lysine side chain will restore its positivecharge, which may stabilise the histone-DNA interaction and prevent activating transcription factors binding to promoter elements [ PUBMED:9278492 ]. HDAs play important roles in the cell cycle and differentiation, and their deregulation can contribute to the development of cancer [ PUBMED:10072350 , PUBMED:10322142 ].

This entry represents the structural domain found in histone deacetylases. It consists of a 3-layer(alpha-beta-alpha) sandwich.

Domain organisation

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Pfam Clan

This family is a member of clan Arginase (CL0302), which has the following description:

This superfamily includes arginase enzymes as well as histone deacetylases and related enzymes [1].

The clan contains the following 3 members:

Arginase Hist_deacetyl UPF0489


We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB sequence database. More...

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Curation and family details

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Seed source: Pfam-B_343 (release 3.0)
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: Bateman A
Number in seed: 68
Number in full: 25207
Average length of the domain: 277.70 aa
Average identity of full alignment: 29 %
Average coverage of the sequence by the domain: 55.10 %

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HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 27.9 27.9
Trusted cut-off 27.9 27.9
Noise cut-off 27.7 27.8
Model length: 307
Family (HMM) version: 22
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Species distribution

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Colour assignments

Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence


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For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Hist_deacetyl domain has been found. There are 654 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.

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AlphaFold Structure Predictions

The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.

Protein Predicted structure External Information
A0A0G2KIA0 View 3D Structure Click here
A0A0P0XZX1 View 3D Structure Click here
A0A0R0FIH2 View 3D Structure Click here
A0A0R0H2W2 View 3D Structure Click here
A0A0R0JIQ9 View 3D Structure Click here
A0A0R0JU82 View 3D Structure Click here
A0A0R0K0I2 View 3D Structure Click here
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