Summary: Histone deacetylase domain
Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.
This is the Wikipedia entry entitled "Histone deacetylase". More...
The Wikipedia text that you see displayed here is a download from Wikipedia. This means that the information we display is a copy of the information from the Wikipedia database. The button next to the article title ("Edit Wikipedia article") takes you to the edit page for the article directly within Wikipedia. You should be aware you are not editing our local copy of this information. Any changes that you make to the Wikipedia article will not be displayed here until we next download the article from Wikipedia. We currently download new content on a nightly basis.
Does Pfam agree with the content of the Wikipedia entry ?
Pfam has chosen to link families to Wikipedia articles. In some case we have created or edited these articles but in many other cases we have not made any direct contribution to the content of the article. The Wikipedia community does monitor edits to try to ensure that (a) the quality of article annotation increases, and (b) vandalism is very quickly dealt with. However, we would like to emphasise that Pfam does not curate the Wikipedia entries and we cannot guarantee the accuracy of the information on the Wikipedia page.
Editing Wikipedia articles
Before you edit for the first time
Wikipedia is a free, online encyclopedia. Although anyone can edit or contribute to an article, Wikipedia has some strong editing guidelines and policies, which promote the Wikipedia standard of style and etiquette. Your edits and contributions are more likely to be accepted (and remain) if they are in accordance with this policy.
You should take a few minutes to view the following pages:
How your contribution will be recorded
Anyone can edit a Wikipedia entry. You can do this either as a new user or you can register with Wikipedia and log on. When you click on the "Edit Wikipedia article" button, your browser will direct you to the edit page for this entry in Wikipedia. If you are a registered user and currently logged in, your changes will be recorded under your Wikipedia user name. However, if you are not a registered user or are not logged on, your changes will be logged under your computer's IP address. This has two main implications. Firstly, as a registered Wikipedia user your edits are more likely seen as valuable contribution (although all edits are open to community scrutiny regardless). Secondly, if you edit under an IP address you may be sharing this IP address with other users. If your IP address has previously been blocked (due to being flagged as a source of 'vandalism') your edits will also be blocked. You can find more information on this and creating a user account at Wikipedia.
If you have problems editing a particular page, contact us at firstname.lastname@example.org and we will try to help.
The community annotation is a new facility of the Pfam web site. If you have problems editing or experience problems with these pages please contact us.
Histone deacetylase Edit Wikipedia article
|PDB structures||RCSB PDB PDBe PDBsum|
|Gene Ontology||AmiGO / EGO|
|Histone deacetylase superfamily|
Histone deacetylases (EC 126.96.36.199, 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.
HDAC super family
Classes of HDACs in higher eukaryotes
HDACs, are classified in four classes depending on sequence homology to the yeast original enzymes and domain organization:
|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||–||–|
|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 Zn-dependent histone deacetylases.
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. 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, 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.
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.
HDAC6 is a cytoplasmic, microtuble-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.
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:
- Environmental information processing; signal transduction; notch signaling pathway PATH:ko04330
- Cellular processes; cell growth and death; cell cycle PATH:ko04110
- Human diseases; cancers; chronic myeloid leukemia PATH:ko05220
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. 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, negatively correlating with the expression of GAD67 mRNA.
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. 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. HDAC6 is important regulator of HSP90 function and its inhibitor proposed to treat metabolic disorders.
- 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.
- 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.
- 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.
These are just some examples of constantly emerging non-histone, non-chromatin roles for HDACs.
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. Also in recent years, there has been an effort to develop HDIs for cancer therapy. Vorinostat (SAHA) was 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. In addition, a clinical trial is studying valproic acid effects on the latent pools of HIV in infected persons. 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. Isoform selective HDIs which can aid in elucidating role of individual HDAC isoforms have been developed.
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.
- Histone acetyltransferase (HAT)
- Histone deacetylase inhibitor
- Histone methyltransferase (HMT)
- Histone-modifying enzymes
- RNA polymerase control by chromatin structure
- Bottomley, M. J.; Lo Surdo, P.; Di Giovine, P.; Cirillo, A.; Scarpelli, R.; Ferrigno, F.; Jones, P.; Neddermann, P.; De Francesco, R.; Steinkühler, C.; Gallinari, P.; Carfí, A. (2008). "Structural and Functional Analysis of the Human HDAC4 Catalytic Domain Reveals a Regulatory Structural Zinc-binding Domain". Journal of Biological Chemistry. 283 (39): 26694–26704. doi:10.1074/jbc.M803514200. PMC . PMID 18614528.
- 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.
- 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 . PMID 9278492.
- 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.
- 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 . PMID 19459166.
- 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.
- 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 . PMID 18292778.
- 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. PMID 22963873.
- 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 . PMID 12429021.
- 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.
- 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.
- 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 . PMID 16940178.
- 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 . PMID 17961987.
- 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.
- 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.
- 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 . PMID 22723278.
- 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.
- 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.
- 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 . PMID 14633989.
- 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 . PMID 18324520.
- 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.
- 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:10.1517/135437188.8.131.52. PMID 18230051.
- "Scientists 'reverse' memory loss". BBC News. 2007-04-29. Retrieved 2007-07-08.
- 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 . PMID 20536416.
- 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.
- 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.
- Depletion of Latent HIV in CD4 Cells - Full Text View - ClinicalTrials.gov
- 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.
- 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 . PMID 23547652.
- 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 . PMID 20669972.
- 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 . PMID 20614936.
- 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.
- 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.
- 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 . PMID 21458587.
This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.
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 .
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.
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
The graphic that is shown by default represents the longest sequence with a given architecture. Each row contains the following information:
- the number of sequences which exhibit this architecture
a textual description of the architecture, e.g. Gla, EGF x 2, Trypsin.
This example describes an architecture with one
Gladomain, followed by two consecutive
EGFdomains, and finally a single
- a link to the page in the Pfam site showing information about the sequence that the graphic describes
- the UniProt description of the protein sequence
- the number of residues in the sequence
- the Pfam graphic itself.
Note that you can see the family page for a particular domain by clicking on the graphic. You can also choose to see all sequences which have a given architecture by clicking on the Show link in each row.
Finally, because some families can be found in a very large number of architectures, we load only the first fifty architectures by default. If you want to see more architectures, click the button at the bottom of the page to load the next set.
Loading domain graphics...
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, the UniProtKB sequence database, the NCBI sequence database, and our metagenomics sequence database. More...
There are various ways to view or download the sequence alignments that we store. We provide several sequence viewers and a plain-text Stockholm-format file for download.
We make a range of alignments for each Pfam-A family:
- the curated alignment from which the HMM for the family is built
- the alignment generated by searching the sequence database using the HMM
- Representative Proteomes (RPs) at 15%, 35%, 55% and 75% co-membership thresholds
- alignment generated by searching the UniProtKB sequence database using the family HMM
- alignment generated by searching the NCBI sequence database using the family HMM
- alignment generated by searching the metagenomics sequence database using the family HMM
You can see the alignments as HTML or in three different sequence viewers:
- a Java applet developed at the University of Dundee. You will need Java installed before running jalview
- an HTML page showing the whole alignment.Please note: full Pfam alignments can be very large. These HTML views are extremely large and often cause problems for browsers. Please use either jalview or the Pfam viewer if you have trouble viewing the HTML version
- an HTML-based representation of the alignment, coloured according to the posterior-probability (PP) values from the HMM. As for the standard HTML view, heatmap alignments can also be very large and slow to render.
You can download (or view in your browser) a text representation of a Pfam alignment in various formats:
You can also change the order in which sequences are listed in the alignment, change how insertions are represented, alter the characters that are used to represent gaps in sequences and, finally, choose whether to download the alignment or to view it in your browser directly.
You may find that large alignments cause problems for the viewers and the reformatting tool, so we also provide all alignments in Stockholm format. You can download either the plain text alignment, or a gzipped version of it.
We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key: available, not generated, — not available.
Format an alignment
We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.
You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.
HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...
If you find these logos useful in your own work, please consider citing the following article:
This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.
Note: You can also download the data file for the tree.
Curation and family details
This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.
|Seed source:||Pfam-B_343 (release 3.0)|
|Number in seed:||79|
|Number in full:||16021|
|Average length of the domain:||282.20 aa|
|Average identity of full alignment:||28 %|
|Average coverage of the sequence by the domain:||60.60 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null --hand HMM SEED
search method: hmmsearch -Z 45638612 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||19|
|Download:||download the raw HMM for this family|
Weight segments by...
Change the size of the sunburst
selected sequences to HMM
a FASTA-format file
- 0 sequences
- 0 species
This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the More....
This chart is a modified "sunburst" visualisation of the species tree for this family. It shows each node in the tree as a separate arc, arranged radially with the superkingdoms at the centre and the species arrayed around the outermost ring.
How the sunburst is generated
The tree is built by considering the taxonomic lineage of each sequence that has a match to this family. For each node in the resulting tree, we draw an arc in the sunburst. The radius of the arc, its distance from the root node at the centre of the sunburst, shows the taxonomic level ("superkingdom", "kingdom", etc). The length of the arc represents either the number of sequences represented at a given level, or the number of species that are found beneath the node in the tree. The weighting scheme can be changed using the sunburst controls.
In order to reduce the complexity of the representation, we reduce the number of taxonomic levels that we show. We consider only the following eight major taxonomic levels:
Colouring and labels
Segments of the tree are coloured approximately according to their superkingdom. For example, archeal branches are coloured with shades of orange, eukaryotes in shades of purple, etc. The colour assignments are shown under the sunburst controls. Where space allows, the name of the taxonomic level will be written on the arc itself.
As you move your mouse across the sunburst, the current node will be highlighted. In the top section of the controls panel we show a summary of the lineage of the currently highlighed node. If you pause over an arc, a tooltip will be shown, giving the name of the taxonomic level in the title and a summary of the number of sequences and species below that node in the tree.
Anomalies in the taxonomy tree
There are some situations that the sunburst tree cannot easily handle and for which we have work-arounds in place.
Missing taxonomic levels
Some species in the taxonomic tree may not have one or more of the main eight levels that we display. For example, Bos taurus is not assigned an order in the NCBI taxonomic tree. In such cases we mark the omitted level with, for example, "No order", in both the tooltip and the lineage summary.
Unmapped species names
The tree is built by looking at each sequence in the full alignment for the family. We take the name of the species given by UniProt and try to map that to the full taxonomic tree from NCBI. In some cases, the name chosen by UniProt does not map to any node in the NCBI tree, perhaps because the chosen name is listed as a synonym or a misspelling in the NCBI taxonomy.
So that these nodes are not simply omitted from the sunburst tree, we group them together in a separate branch (or segment of the sunburst tree). Since we cannot determine the lineage for these unmapped species, we show all levels between the superkingdom and the species as "uncategorised".
Since we reduce the species tree to only the eight main taxonomic levels, sequences that are mapped to the sub-species level in the tree would not normally be shown. Rather than leave out these species, we map them instead to their parent species. So, for example, for sequences belonging to one of the Vibrio cholerae sub-species in the NCBI taxonomy, we show them instead as belonging to the species Vibrio cholerae.
Too many species/sequences
For large species trees, you may see blank regions in the outer layers of the sunburst. These occur when there are large numbers of arcs to be drawn in a small space. If an arc is less than approximately one pixel wide, it will not be drawn and the space will be left blank. You may still be able to get some information about the species in that region by moving your mouse across the area, but since each arc will be very small, it will be difficult to accurately locate a particular species.
The tree shows the occurrence of this domain across different species. More...
We show the species tree in one of two ways. For smaller trees we try to show an interactive representation, which allows you to select specific nodes in the tree and view them as an alignment or as a set of Pfam domain graphics.
Unfortunately we have found that there are problems viewing the interactive tree when the it becomes larger than a certain limit. Furthermore, we have found that Internet Explorer can become unresponsive when viewing some trees, regardless of their size. We therefore show a text representation of the species tree when the size is above a certain limit or if you are using Internet Explorer to view the site.
If you are using IE you can still load the interactive tree by clicking the "Generate interactive tree" button, but please be aware of the potential problems that the interactive species tree can cause.
For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.
We also count the number of unique sequences on which each domain is found, which is shown in green. Note that a domain may appear multiple times on the same sequence, leading to the difference between these two numbers.
Finally, we group sequences from the same organism according to the NCBI code that is assigned by UniProt, allowing us to count the number of distinct sequences on which the domain is found. This value is shown in the pink boxes.
We use the NCBI species tree to group organisms according to their taxonomy and this forms the structure of the displayed tree. Note that in some cases the trees are too large (have too many nodes) to allow us to build an interactive tree, but in most cases you can still view the tree in a plain text, non-interactive representation. Those species which are represented in the seed alignment for this domain are highlighted.
You can use the tree controls to manipulate how the interactive tree is displayed:
- show/hide the summary boxes
- highlight species that are represented in the seed alignment
- expand/collapse the tree or expand it to a given depth
- select a sub-tree or a set of species within the tree and view them graphically or as an alignment
- save a plain text representation of the tree
Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.
There are 3 interactions for this family. More...
We determine these interactions using iPfam, which considers the interactions between residues in three-dimensional protein structures and maps those interactions back to Pfam families. You can find more information about the iPfam algorithm in the journal article that accompanies the website.
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 326 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.
Loading structure mapping...