ADA2/YDR448W Summary Help

ADA2 BASIC INFORMATION

Standard Name ADA2
Systematic Name YDR448W
Alias SWI8
Feature Type ORF, Verified
Description Transcription coactivator, component of the ADA and SAGA transcriptional adaptor/HAT (histone acetyltransferase) complexes (1, 2 and see Summary Paragraph)
Name Description transcriptional ADAptor 3
GO Annotations All ADA2 GO evidence and references
    View Computational GO annotations for ADA2
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Mutant Phenotype All ADA2 Phenotype details and references
Classical genetics
null
reduction of function
unspecified
Large-scale survey
null
overexpression
Interactions ADA2 All interactions details and references
444 total interaction(s) for 158 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 174
  • Affinity Capture-Western: 76
  • Co-fractionation: 1
  • Co-localization: 4
  • Co-purification: 21
  • Reconstituted Complex: 18
  • Two-hybrid: 28
Genetic Interactions
  • Phenotypic Suppression: 1
  • Synthetic Growth Defect: 101
  • Synthetic Lethality: 18
  • Synthetic Rescue: 2
Sequence Information
ChrIV:1356058 to 1357362 | ORF Map | GBrowse
Gbrowse
Last Update Coordinates: 2008-06-05 | Sequence: 1996-07-31
Subfeature details
Relative
Coordinates		 Chromosomal
Coordinates		 Most Recent Updates
Coordinates Sequence
CDS 1..1305 1356058..1357362 2008-06-05 1996-07-31
External Links All Associated Seq | Entrez Gene | Entrez RefSeq Protein | MIPS | UniProtKB
Primary SGDIDS000002856

ADA2 RESOURCES

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Expression Summary histogram

ADDITIONAL INFORMATION for ADA2

SUMMARY PARAGRAPH for ADA2

ADA2 encodes a component of three chromatin modifying histone acetyltransferase (HAT) complexes: SAGA, SLIK, and ADA (4, 5, 6; reviewed in 7). These complexes function in positive and negative transcriptional regulation of numerous RNA polymerase II-transcribed genes; in addition, SLIK plays a role in the retrograde response (6, 8; reviewed in 9). The three complexes each contain the histone acetyltransferase catalytic subunit Gcn5p, which interacts directly with Ada2p and preferentially modifies histones H3 and H2B (10; reviewed in 9). In vitro, Gcn5p acetylates N-terminal lysines on free histones, but acetylation of nucleosomal histone substrates also requires Ada2p and Ngg1p (also called Ada3p), which are found in a complex with Gcn5p (1). Ada2p has been shown to increase the HAT activity of Gcn5p, while Ngg1p plays a role in expanding the range of lysines that undergo acetylation (1).

Independently of its interaction with Gcn5p, Ada2p has also been shown to function in transcriptional silencing at telomeres and ribosomal DNA (11). Ada2p binds telomeric chromatin and Sir2p to prevent the spread of silencing proteins Sir2p and Sir3p into subtelomeric regions (11).

Null mutations in ADA2 confer slow growth in minimal glucose media, resistance to the toxic effect of the chimeric transcriptional activator GAL4-VP16, and silencing defects (3, 11). The null mutant also grows poorly on low phosphate medium, and exhibits increased sensitivity to ethanol or caffeine (12). Microarray analysis indicates that 2.5% of S. cerevisiae open reading frames show a twofold or greater change in expression in the null mutant (12).

The amino terminal region of Ada2p contains a ZZ-type zinc finger and a SANT domain (13), which is found in other proteins involved in chromatin remodeling, such as Swi3p (a component of the SWI/SNF complex) and Rsc8p (a subunit of the RSC complex). Ada2p also contains a conserved central region, and a C-terminal SWIRM domain (14, 12). Mutations in the Ada2p SANT domain confer growth and histone acetylation defects, indicating that this region is essential for the function of the HAT complexes (15, 2). The amino terminal region of Ada2p is required for interaction with Gcn5p, whereas interaction with Ngg1p is mediated by the central region (16). Mutant analysis indicates that the central region is also required for full Gcn5p acetyltransferase activity and substrate specificity; in addition, it has been shown to bind phosphatidylserine (12).

Ada2p is evolutionarily conserved among eukaryotes and orthologs have been described in several organisms, including Arabidopsis (17), Drosophila (18), and humans (19). The human ortholog ADA2b is a component of the SAGA-like complex STAGA and is recruited to p53-dependent promoters (19).

Last updated: 2009-11-13

REFERENCES CITED ON THIS PAGE [View Complete Literature Guide for ADA2]

1) Balasubramanian R, et al.  (2002) Role of the Ada2 and Ada3 transcriptional coactivators in histone acetylation. J Biol Chem 277(10):7989-95
2) Sterner DE, et al.  (2002) The SANT domain of Ada2 is required for normal acetylation of histones by the yeast SAGA complex. J Biol Chem 277(10):8178-86
3) Berger SL, et al.  (1992) Genetic isolation of ADA2: a potential transcriptional adaptor required for function of certain acidic activation domains. Cell 70(2):251-65
4) Horiuchi J, et al.  (1995) ADA3, a putative transcriptional adaptor, consists of two separable domains and interacts with ADA2 and GCN5 in a trimeric complex. Mol Cell Biol 15(3):1203-9
5) Eberharter A, et al.  (1999) The ADA complex is a distinct histone acetyltransferase complex in Saccharomyces cerevisiae. Mol Cell Biol 19(10):6621-31
6) Pray-Grant MG, et al.  (2002) The novel SLIK histone acetyltransferase complex functions in the yeast retrograde response pathway. Mol Cell Biol 22(24):8774-86
7) Sterner DE and Berger SL  (2000) Acetylation of histones and transcription-related factors. Microbiol Mol Biol Rev 64(2):435-59
8) Grant PA, et al.  (1997) Yeast Gcn5 functions in two multisubunit complexes to acetylate nucleosomal histones: characterization of an Ada complex and the SAGA (Spt/Ada) complex. Genes Dev 11(13):1640-50
9) Daniel JA and Grant PA  (2007) Multi-tasking on chromatin with the SAGA coactivator complexes. Mutat Res 618(1-2):135-48
10) Marcus GA, et al.  (1994) Functional similarity and physical association between GCN5 and ADA2: putative transcriptional adaptors. EMBO J 13(20):4807-15
11) Jacobson S and Pillus L  (2009) The SAGA subunit Ada2 functions in transcriptional silencing. Mol Cell Biol 29(22):6033-45
12) Hoke SM, et al.  (2008) A conserved central region of yeast ada2 regulates the histone acetyltransferase activity of gcn5 and interacts with phospholipids. J Mol Biol 384(4):743-55
13) Aasland R, et al.  (1996) The SANT domain: a putative DNA-binding domain in the SWI-SNF and ADA complexes, the transcriptional co-repressor N-CoR and TFIIIB. Trends Biochem Sci 21(3):87-8
14) Aravind L and Iyer LM  (2002) The SWIRM domain: a conserved module found in chromosomal proteins points to novel chromatin-modifying activities. Genome Biol 3(8):RESEARCH0039
15) Boyer LA, et al.  (2002) Essential role for the SANT domain in the functioning of multiple chromatin remodeling enzymes. Mol Cell 10(4):935-42
16) Candau R and Berger SL  (1996) Structural and functional analysis of yeast putative adaptors. Evidence for an adaptor complex in vivo. J Biol Chem 271(9):5237-45
17) Hark AT, et al.  (2009) Two Arabidopsis orthologs of the transcriptional coactivator ADA2 have distinct biological functions. Biochim Biophys Acta 1789(2):117-24
18) Muratoglu S, et al.  (2003) Two different Drosophila ADA2 homologues are present in distinct GCN5 histone acetyltransferase-containing complexes. Mol Cell Biol 23(1):306-21
19) Gamper AM, et al.  (2009) The STAGA subunit ADA2b is an important regulator of human GCN5 catalysis. Mol Cell Biol 29(1):266-80