Summary: SNF2-related 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 "SWI/SNF". 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.
SWI/SNF Edit Wikipedia article
|Snf2 ATPase bound to a nucleosome|
|SCOP2||5x0x / SCOPe / SUPFAM|
In molecular biology, SWI/SNF (SWItch/Sucrose Non-Fermentable), is a subfamily of ATP-dependent chromatin remodeling complexes, which is found in eukaryotes. In other words, it is a group of proteins that associate to remodel the way DNA is packaged. This complex is composed of several proteins â€“ products of the SWI and SNF genes (SWI1, SWI2/SNF2, SWI3, SWI5, SWI6), as well as other polypeptides. It possesses a DNA-stimulated ATPase activity that can destabilize histone-DNA interactions in reconstituted nucleosomes in an ATP-dependent manner, though the exact nature of this structural change is unknown. The SWI/SNF subfamily provides crucial nucleosome rearrangement, which is seen as ejection and/or sliding. The movement of nucleosomes provides easier access to the chromatin, allowing genes to be activated or repressed.
The human analogs of SWI/SNF are "BRG1- or BRM-associated factors", or BAF (SWI/SNF-A) and "Polybromo-associated BAF", which is also known as PBAF (SWI/SNF-B). There are also Drosophila analogs of SWI/SNF, known as "Brahma Associated Protein", or BAP and "Polybromo-associated BAP", also known as PBAP.
Mechanism of action
It has been found that the SWI/SNF complex (in yeast) is capable of altering the position of nucleosomes along DNA. These alterations are classified in three different ways, and they are seen as the processes of sliding nucleosomes, ejecting nucleosomes, and ejecting only certain components of the nucleosome. Due to the actions performed by the SWI/SNF subfamily, they are referred to as "access remodellers" and promote gene expression by exposing binding sites so that transcription factors can bind more easily. Two mechanisms for nucleosome remodeling by SWI/SNF have been proposed. The first model contends that a unidirectional diffusion of a twist defect within the nucleosomal DNA results in a corkscrew-like propagation of DNA over the octamer surface that initiates at the DNA entry site of the nucleosome. The other is known as the "bulge" or "loop-recapture" mechanism and it involves the dissociation of DNA at the edge of the nucleosome with re-association of DNA inside the nucleosome, forming a DNA bulge on the octamer surface. The DNA loop would then propagate across the surface of the histone octamer in a wave-like manner, resulting in the re-positioning of DNA without changes in the total number of histone-DNA contacts. A recent study has provided strong evidence against the twist diffusion mechanism and has further strengthened the loop-recapture model.
Role as a tumor suppressor
The mammalian SWI/SNF (mSWI/SNF) complex functions as a tumor suppressor in many human malignant cancers. Early studies identified that SWI/SNF subunits were frequently absent in cancer cell lines. SWI/SNF was first identified in 1998 as a tumor suppressor in rhabdoid tumors, a rare pediatric malignant cancer. Other instances of SWI/SNF acting as a tumor suppressor comes from the heterozygous deletion of BAF47 or alteration of BAF47. These instances result in cases of chronic and acute CML and in rarer cases, Hodgkin's lymphoma, respectively. To prove that BAF47, also known as SMARCB1, acts as a tumor suppressor, experiments resulting in the formation of rhabdoid tumors in mice were conducted via total knockout of BAF47. As DNA sequencing costs diminished, many tumors were sequenced for the first time around 2010. Several of these studies revealed SWI/SNF to be a tumor suppressor in a number of diverse malignancies. Several studies revealed that subunits of the mammalian complex, including ARID1A, PBRM1, SMARCB1, SMARCA4, and ARID2, are frequently mutated in human cancers. It has been noted that total loss of BAF47 is extremely rare and instead, most cases of tumors that resulted from SWI/SNF subunits come from BRG1 deletion, BRM deletion, or total loss of both subunits. Further analysis concluded that total loss of both subunits was present in about 10% of tumor cell lines after 100 cell lines were looked at. A meta-analysis of many sequencing studies demonstrated SWI/SNF to be mutated in approximately 20% of human malignancies.
Structure of the SWI/SNF complex
Electron microscopy studies of SWI/SNF and RSC (SWI/SNF-B) reveal large, lobed 1.1-1.3 MDa structures. These structures resemble RecA and cover both sides of a conserved section of the ATPase domain. The domain also contains a separate domain, HSA, that is capable of binding actin, and resides on the N-terminus. The bromo domain present is responsible for recognizing and binding lysines that have been acetylated. No atomic-resolution structures of the entire SWI/SNF complex have been obtained to date, due to the protein complex being highly dynamic and composed of many subunits. However, domains and several individual subunits from yeast and mammals have been described. In particular, the cryo-EM structure of the ATPase Snf2 in complex with a nucleosome shows that nucleosomal DNA is locally deformed at the site of binding. A model of the mammalian ATPase SMARCA4 shows similar features, based on the high degree of sequence homology with yeast Snf2. The interface between two subunits, BAF155 (SMARCC1) and BAF47 (SMARCB1) was also resolved, providing important insights into the mechanisms of the SWI/SNF complex assembly pathway.
SWIB/MDM2 protein domain
The protein domain, SWIB/MDM2, short for SWI/SNF complex B/MDM2 is an important domain. This protein domain has been found in both SWI/SNF complex B and in the negative regulator of the p53 tumor suppressor MDM2. It has been shown that MDM2 is homologous to the SWIB complex.
The primary function of the SWIB protein domain is to aid gene expression. In yeast, this protein domain expresses certain genes, in particular BADH2, GAL1, GAL4, and SUC2. It works by increasing transcription. It has ATPase activity, meaning it breaks down ATP, the basic unit of energy currency. This destabilizes the interaction between DNA and histones. The destabilization that occurs disrupts chromatin and opens up the transcription-binding domains. Transcription factors can then bind to this site, leading to an increase in transcription.
The interactions between the proteins of the SWI/SNF complex and the chromatin allows binding of transcription factors, therefore causing an increase in transcription.
This protein domain is known to contain one short alpha helix.
|SWI1||ARID1A, ARID1B||OSA||Contains LXXLL nuclear receptor binding motifs|
|SWI2/SNF2||SMARCA2, SMARCA4||BRM||ATP dependent chromatin remodeling|
|SWI3||SMARCC1, SMARCC2||Moira/BAP155||Similar sequence; function unknown|
|SWP73/SNF12||SMARCD1, SMARCD2, SMARCD3||BAP60||Similar sequence; function unknown|
|SWP61/ARP7||ACTL6A, ACTL6B||Actin-like protein|
|SNF5||SMARCB1||SNR1||ATP dependent chromatin remodeling|
The SWI/SNF complex was first discovered in the yeast, Saccharomyces cerevisiae. It was named after initially screening for mutations that would affect the pathways for both yeast mating types switching (SWI) and sucrose non-fermenting (SNF).
- Neigeborn L, Carlson M (December 1984). "Genes affecting the regulation of SUC2 gene expression by glucose repression in Saccharomyces cerevisiae". Genetics. 108 (4): 845â€“58. doi:10.1093/genetics/108.4.845. PMCÂ 1224269. PMIDÂ 6392017.
- Stern M, Jensen R, Herskowitz I (October 1984). "Five SWI genes are required for expression of the HO gene in yeast". Journal of Molecular Biology. 178 (4): 853â€“68. doi:10.1016/0022-2836(84)90315-2. PMIDÂ 6436497.
- Pazin MJ, Kadonaga JT (March 1997). "SWI2/SNF2 and related proteins: ATP-driven motors that disrupt protein-DNA interactions?". Cell. 88 (6): 737â€“40. doi:10.1016/S0092-8674(00)81918-2. PMIDÂ 9118215.
- Clapier CR, Iwasa J, Cairns BR, Peterson CL (July 2017). "Mechanisms of action and regulation of ATP-dependent chromatin-remodelling complexes". Nature Reviews. Molecular Cell Biology. 18 (7): 407â€“422. doi:10.1038/nrm.2017.26. PMCÂ 8127953. PMIDÂ 28512350.
- Nie Z, Yan Z, Chen EH, Sechi S, Ling C, Zhou S, etÂ al. (April 2003). "Novel SWI/SNF chromatin-remodeling complexes contain a mixed-lineage leukemia chromosomal translocation partner". Molecular and Cellular Biology. 23 (8): 2942â€“52. doi:10.1128/MCB.23.8.2942-2952.2003. PMCÂ 152562. PMIDÂ 12665591.
- Tang L, Nogales E, Ciferri C (June 2010). "Structure and function of SWI/SNF chromatin remodeling complexes and mechanistic implications for transcription". Progress in Biophysics and Molecular Biology. 102 (2â€“3): 122â€“8. doi:10.1016/j.pbiomolbio.2010.05.001. PMCÂ 2924208. PMIDÂ 20493208.
- Whitehouse I, Flaus A, Cairns BR, White MF, Workman JL, Owen-Hughes T (August 1999). "Nucleosome mobilization catalysed by the yeast SWI/SNF complex". Nature. 400 (6746): 784â€“7. Bibcode:1999Natur.400..784W. doi:10.1038/23506. PMIDÂ 10466730. S2CIDÂ 2841873.
- van Holde K, Yager T (June 2003). "Models for chromatin remodeling: a critical comparison". Biochemistry and Cell Biology. 81 (3): 169â€“72. doi:10.1139/o03-038. PMIDÂ 12897850.
- Flaus A, Owen-Hughes T (April 2003). "Mechanisms for nucleosome mobilization". Biopolymers. 68 (4): 563â€“78. doi:10.1002/bip.10323. PMIDÂ 12666181.
- Zofall M, Persinger J, Kassabov SR, Bartholomew B (April 2006). "Chromatin remodeling by ISW2 and SWI/SNF requires DNA translocation inside the nucleosome". Nature Structural & Molecular Biology. 13 (4): 339â€“46. doi:10.1038/nsmb1071. PMIDÂ 16518397. S2CIDÂ 24163324.
- Hodges C, Kirkland JG, Crabtree GR (August 2016). "The Many Roles of BAF (mSWI/SNF) and PBAF Complexes in Cancer". Cold Spring Harbor Perspectives in Medicine. 6 (8): a026930. doi:10.1101/cshperspect.a026930. PMCÂ 4968166. PMIDÂ 27413115.
- Dunaief JL, Strober BE, Guha S, Khavari PA, Alin K, Luban J, etÂ al. (October 1994). "The retinoblastoma protein and BRG1 form a complex and cooperate to induce cell cycle arrest". Cell. 79 (1): 119â€“30. doi:10.1016/0092-8674(94)90405-7. PMIDÂ 7923370. S2CIDÂ 7058539.
- Versteege I, SÃ©venet N, Lange J, Rousseau-Merck MF, Ambros P, Handgretinger R, etÂ al. (July 1998). "Truncating mutations of hSNF5/INI1 in aggressive paediatric cancer". Nature. 394 (6689): 203â€“6. Bibcode:1998Natur.394..203V. doi:10.1038/28212. PMIDÂ 9671307. S2CIDÂ 6019090.
- Melo JV, Gordon DE, Cross NC, Goldman JM (January 1993). "The ABL-BCR fusion gene is expressed in chronic myeloid leukemia". Blood. 81 (1): 158â€“65. doi:10.1182/blood.v81.1.158.bloodjournal811158. PMIDÂ 8417787.
- Yuge M, Nagai H, Uchida T, Murate T, Hayashi Y, Hotta T, etÂ al. (October 2000). "HSNF5/INI1 gene mutations in lymphoid malignancy". Cancer Genetics and Cytogenetics. 122 (1): 37â€“42. doi:10.1016/s0165-4608(00)00274-0. PMIDÂ 11104031.
- Reisman D, Glaros S, Thompson EA (April 2009). "The SWI/SNF complex and cancer". Oncogene. 28 (14): 1653â€“68. doi:10.1038/onc.2009.4. PMIDÂ 19234488.
- Wiegand KC, Shah SP, Al-Agha OM, Zhao Y, Tse K, Zeng T, etÂ al. (October 2010). "ARID1A mutations in endometriosis-associated ovarian carcinomas". The New England Journal of Medicine. 363 (16): 1532â€“43. doi:10.1056/NEJMoa1008433. PMCÂ 2976679. PMIDÂ 20942669.
- Li M, Zhao H, Zhang X, Wood LD, Anders RA, Choti MA, etÂ al. (August 2011). "Inactivating mutations of the chromatin remodeling gene ARID2 in hepatocellular carcinoma". Nature Genetics. 43 (9): 828â€“9. doi:10.1038/ng.903. PMCÂ 3163746. PMIDÂ 21822264.
- Shain AH, Giacomini CP, Matsukuma K, Karikari CA, Bashyam MD, Hidalgo M, etÂ al. (January 2012). "Convergent structural alterations define SWItch/Sucrose NonFermentable (SWI/SNF) chromatin remodeler as a central tumor suppressive complex in pancreatic cancer". Proceedings of the National Academy of Sciences of the United States of America. 109 (5): E252-9. doi:10.1073/pnas.1114817109. PMCÂ 3277150. PMIDÂ 22233809.
- Varela I, Tarpey P, Raine K, Huang D, Ong CK, Stephens P, etÂ al. (January 2011). "Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma". Nature. 469 (7331): 539â€“42. Bibcode:2011Natur.469..539V. doi:10.1038/nature09639. PMCÂ 3030920. PMIDÂ 21248752.
- Mathur R, Alver BH, San Roman AK, Wilson BG, Wang X, Agoston AT, etÂ al. (February 2017). "ARID1A loss impairs enhancer-mediated gene regulation and drives colon cancer in mice". Nature Genetics. 49 (2): 296â€“302. doi:10.1038/ng.3744. PMCÂ 5285448. PMIDÂ 27941798.
- Isakoff MS, Sansam CG, Tamayo P, Subramanian A, Evans JA, Fillmore CM, etÂ al. (December 2005). "Inactivation of the Snf5 tumor suppressor stimulates cell cycle progression and cooperates with p53 loss in oncogenic transformation". Proceedings of the National Academy of Sciences of the United States of America. 102 (49): 17745â€“50. Bibcode:2005PNAS..10217745I. doi:10.1073/pnas.0509014102. PMCÂ 1308926. PMIDÂ 16301525.
- Hodges HC, Stanton BZ, Cermakova K, Chang CY, Miller EL, Kirkland JG, etÂ al. (January 2018). "Dominant-negative SMARCA4 mutants alter the accessibility landscape of tissue-unrestricted enhancers". Nature Structural & Molecular Biology. 25 (1): 61â€“72. doi:10.1038/s41594-017-0007-3. PMCÂ 5909405. PMIDÂ 29323272.
- Muchardt C, Yaniv M (May 2001). "When the SWI/SNF complex remodels...the cell cycle". Oncogene. 20 (24): 3067â€“75. doi:10.1038/sj.onc.1204331. PMIDÂ 11420722.
- Decristofaro MF, Betz BL, Rorie CJ, Reisman DN, Wang W, Weissman BE (January 2001). "Characterization of SWI/SNF protein expression in human breast cancer cell lines and other malignancies". Journal of Cellular Physiology. 186 (1): 136â€“45. doi:10.1002/1097-4652(200101)186:1<136::aid-jcp1010>3.0.co;2-4. PMIDÂ 11147808.
- Shain AH, Pollack JR (2013). "The spectrum of SWI/SNF mutations, ubiquitous in human cancers". PLOS ONE. 8 (1): e55119. Bibcode:2013PLoSO...855119S. doi:10.1371/journal.pone.0055119. PMCÂ 3552954. PMIDÂ 23355908.
- Asturias FJ, Chung WH, Kornberg RD, Lorch Y (October 2002). "Structural analysis of the RSC chromatin-remodeling complex". Proceedings of the National Academy of Sciences of the United States of America. 99 (21): 13477â€“80. Bibcode:2002PNAS...9913477A. doi:10.1073/pnas.162504299. PMCÂ 129698. PMIDÂ 12368485.
- Leschziner AE, Saha A, Wittmeyer J, Zhang Y, Bustamante C, Cairns BR, Nogales E (March 2007). "Conformational flexibility in the chromatin remodeler RSC observed by electron microscopy and the orthogonal tilt reconstruction method". Proceedings of the National Academy of Sciences of the United States of America. 104 (12): 4913â€“8. Bibcode:2007PNAS..104.4913L. doi:10.1073/pnas.0700706104. PMCÂ 1820885. PMIDÂ 17360331.
- Smith CL, Horowitz-Scherer R, Flanagan JF, Woodcock CL, Peterson CL (February 2003). "Structural analysis of the yeast SWI/SNF chromatin remodeling complex". Nature Structural Biology. 10 (2): 141â€“5. doi:10.1038/nsb888. PMIDÂ 12524530. S2CIDÂ 3140088.
- Chaban Y, Ezeokonkwo C, Chung WH, Zhang F, Kornberg RD, Maier-Davis B, Lorch Y, Asturias FJ (December 2008). "Structure of a RSC-nucleosome complex and insights into chromatin remodeling". Nature Structural & Molecular Biology. 15 (12): 1272â€“7. doi:10.1038/nsmb.1524. PMCÂ 2659406. PMIDÂ 19029894.
- Liu X, Li M, Xia X, Li X, Chen Z (April 2017). "Mechanism of chromatin remodelling revealed by the Snf2-nucleosome structure". Nature. 544 (7651): 440â€“445. Bibcode:2017Natur.544..440L. doi:10.1038/nature22036. PMIDÂ 28424519.
- Yan L, Xie S, Du Y, Qian C (June 2017). "Structural Insights into BAF47 and BAF155 Complex Formation". Journal of Molecular Biology. 429 (11): 1650â€“1660. doi:10.1016/j.jmb.2017.04.008. PMIDÂ 28438634.
- Bennett-Lovsey R, Hart SE, Shirai H, Mizuguchi K (April 2002). "The SWIB and the MDM2 domains are homologous and share a common fold". Bioinformatics. 18 (4): 626â€“30. doi:10.1093/bioinformatics/18.4.626. PMIDÂ 12016060.
- Decristofaro MF, Betz BL, Rorie CJ, Reisman DN, Wang W, Weissman BE (January 2001). "Characterization of SWI/SNF protein expression in human breast cancer cell lines and other malignancies". Journal of Cellular Physiology. 186 (1): 136â€“45. doi:10.1002/1097-4652(200101)186:1<136::AID-JCP1010>3.0.CO;2-4. PMIDÂ 11147808.
- "Table 1 The different components in the yeast, Drosophila and mammalian SWI/SNF complex". Oncogene Including Oncogene Reviews. ISSNÂ 1476-5594.
- Collingwood TN, Urnov FD, Wolffe AP (December 1999). "Nuclear receptors: coactivators, corepressors and chromatin remodeling in the control of transcription". Journal of Molecular Endocrinology. 23 (3): 255â€“75. doi:10.1677/jme.0.0230255. PMIDÂ 10601972.
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.
SNF2-related domain Provide feedback
This domain is found in proteins involved in a variety of processes including transcription regulation (e.g., SNF2, STH1, brahma, MOT1), DNA repair (e.g., ERCC6, RAD16, RAD5), DNA recombination (e.g., RAD54), and chromatin unwinding (e.g., ISWI) as well as a variety of other proteins with little functional information (e.g., lodestar, ETL1)[1,2,3]. SNF2 functions as the ATPase component of the SNF2/SWI multisubunit complex, which utilises energy derived from ATP hydrolysis to disrupt histone-DNA interactions, resulting in the increased accessibility of DNA to transcription factors.
Linder B, Cabot RA, Schwickert T, Rupp RA;, Gene. 2004;326:59-66.: The SNF2 domain protein family in higher vertebrates displays dynamic expression patterns in Xenopus laevis embryos. PUBMED:14729263 EPMC:14729263
Rowbotham SP, Barki L, Neves-Costa A, Santos F, Dean W, Hawkes N, Choudhary P, Will WR, Webster J, Oxley D, Green CM, Varga-Weisz P, Mermoud JE;, Mol Cell. 2011;42:285-296.: Maintenance of silent chromatin through replication requires SWI/SNF-like chromatin remodeler SMARCAD1. PUBMED:21549307 EPMC:21549307
Internal database links
|SCOOP:||AAA_19 AAA_22 AAA_30 AAA_34 Chromo CMS1 DEAD DEAD_2 DUF2075 ERCC3_RAD25_C Flavi_DEAD HDA2-3 Helicase_C Helicase_C_3 Helicase_RecD LAGLIDADG_3 Linker_histone PHD ResIII SecA_DEAD SWI2_SNF2 zf-CW|
|Similarity to PfamA using HHSearch:||DEAD ResIII AAA_34 SWI2_SNF2|
This tab holds annotation information from the InterPro database.
InterPro entry IPR000330
This domain is found in proteins involved in a variety of processes including transcription regulation (e.g., SNF2, STH1, brahma, MOT1), DNA repair (e.g., ERCC6, RAD16, RAD5), DNA recombination (e.g., RAD54), and chromatin unwinding (e.g., ISWI) as well as a variety of other proteins with little functional information (e.g., lodestar, ETL1) [ PUBMED:7651832 , PUBMED:14729263 , PUBMED:21549307 ]. SNF2 functions as the ATPase component of the SNF2/SWI multisubunit complex, which utilises energy derived from ATP hydrolysis to disrupt histone-DNA interactions, resulting in the increased accessibility of DNA to transcription factors [ PUBMED:16935875 ].
Proteins that contain this domain appear to be distantly related to the DEAX box helicases.
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Molecular function||ATP binding (GO:0005524)|
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...
AAA family proteins often perform chaperone-like functions that assist in the assembly, operation, or disassembly of protein complexes .
The clan contains the following 245 members:6PF2K AAA AAA-ATPase_like AAA_10 AAA_11 AAA_12 AAA_13 AAA_14 AAA_15 AAA_16 AAA_17 AAA_18 AAA_19 AAA_2 AAA_21 AAA_22 AAA_23 AAA_24 AAA_25 AAA_26 AAA_27 AAA_28 AAA_29 AAA_3 AAA_30 AAA_31 AAA_32 AAA_33 AAA_34 AAA_35 AAA_5 AAA_6 AAA_7 AAA_8 AAA_9 AAA_PrkA ABC_ATPase ABC_tran ABC_tran_Xtn Adeno_IVa2 Adenylsucc_synt ADK AFG1_ATPase AIG1 APS_kinase Arf ArsA_ATPase ATP-synt_ab ATP_bind_1 ATP_bind_2 ATPase ATPase_2 Bac_DnaA BCA_ABC_TP_C Beta-Casp bpMoxR BrxC_BrxD BrxL_ATPase Cas_Csn2 Cas_St_Csn2 CbiA CBP_BcsQ CDC73_C CENP-M CFTR_R CLP1_P CMS1 CoaE CobA_CobO_BtuR CobU cobW CPT CSM2 CTP_synth_N Cytidylate_kin Cytidylate_kin2 DAP3 DEAD DEAD_2 divDNAB DLIC DNA_pack_C DNA_pack_N DNA_pol3_delta DNA_pol3_delta2 DnaB_C dNK DO-GTPase1 DO-GTPase2 DUF1611 DUF2075 DUF2326 DUF2478 DUF257 DUF2813 DUF3584 DUF463 DUF4914 DUF5906 DUF6079 DUF815 DUF835 DUF87 DUF927 Dynamin_N Dynein_heavy Elong_Iki1 ELP6 ERCC3_RAD25_C Exonuc_V_gamma FeoB_N Fer4_NifH Flavi_DEAD FTHFS FtsK_SpoIIIE G-alpha Gal-3-0_sulfotr GBP GBP_C GpA_ATPase GpA_nuclease GTP_EFTU Gtr1_RagA Guanylate_kin GvpD_P-loop HDA2-3 Helicase_C Helicase_C_2 Helicase_C_4 Helicase_RecD HerA_C Herpes_Helicase Herpes_ori_bp Herpes_TK HydF_dimer HydF_tetramer Hydin_ADK IIGP IPPT IPT iSTAND IstB_IS21 KAP_NTPase KdpD Kinase-PPPase Kinesin KTI12 LAP1_C LpxK MCM MeaB MEDS Mg_chelatase Microtub_bd MipZ MMR_HSR1 MMR_HSR1_C MobB MukB Mur_ligase_M MutS_V Myosin_head NACHT NAT_N NB-ARC NOG1 NTPase_1 NTPase_P4 ORC3_N P-loop_TraG ParA Parvo_NS1 PAXNEB PduV-EutP PhoH PIF1 Ploopntkinase1 Ploopntkinase2 Ploopntkinase3 Podovirus_Gp16 Polyoma_lg_T_C Pox_A32 PPK2 PPV_E1_C PRK PSY3 Rad17 Rad51 Ras RecA ResIII RHD3_GTPase RhoGAP_pG1_pG2 RHSP RNA12 RNA_helicase Roc RsgA_GTPase RuvB_N SbcC_Walker_B SecA_DEAD Senescence Septin Sigma54_activ_2 Sigma54_activat SKI SMC_N SNF2-rel_dom SpoIVA_ATPase Spore_III_AA SRP54 SRPRB SulA Sulfotransfer_1 Sulfotransfer_2 Sulfotransfer_3 Sulfotransfer_4 Sulfotransfer_5 Sulphotransf SWI2_SNF2 T2SSE T4SS-DNA_transf TerL_ATPase Terminase_3 Terminase_6N Thymidylate_kin TIP49 TK TmcA_N TniB Torsin TraG-D_C tRNA_lig_kinase TrwB_AAD_bind TsaE UvrB UvrD-helicase UvrD_C UvrD_C_2 Viral_helicase1 VirC1 VirE YqeC Zeta_toxin Zot
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...
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
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.
|Number in seed:||19|
|Number in full:||69218|
|Average length of the domain:||295.60 aa|
|Average identity of full alignment:||24 %|
|Average coverage of the sequence by the domain:||23.77 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null --hand HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||26|
|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.
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 SNF2-rel_dom domain has been found. There are 79 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...
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.