IRA1/YBR140C Summary Help

Standard Name IRA1 1
Systematic Name YBR140C
Alias GLC1 , PPD1
Feature Type ORF, Verified
Description GTPase-activating protein; negatively regulates RAS by converting it from the GTP- to the GDP-bound inactive form, required for reducing cAMP levels under nutrient limiting conditions, mediates membrane association of adenylate cyclase; mutations cause catalase T deficiency, defective glycogen synthesis and defective trehalose accumulation; IRA1 has a paralog, IRA2, that arose from the whole genome duplication (1, 2, 3, 4 and see Summary Paragraph)
Name Description Inhibitory Regulator of the RAS-cAMP pathway 1
Chromosomal Location
ChrII:526628 to 517350 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Gbrowse
Genetic position: 78 cM
Gene Ontology Annotations All IRA1 GO evidence and references
  View Computational GO annotations for IRA1
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
High-throughput
Regulators 3 genes
Resources
Classical genetics
null
reduction of function
unspecified
Large-scale survey
null
reduction of function
Resources
48 total interaction(s) for 34 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 9
  • Affinity Capture-RNA: 1
  • Affinity Capture-Western: 3
  • Co-fractionation: 1
  • Co-purification: 1
  • Two-hybrid: 1

Genetic Interactions
  • Dosage Lethality: 2
  • Dosage Rescue: 9
  • Phenotypic Enhancement: 3
  • Phenotypic Suppression: 1
  • Synthetic Growth Defect: 7
  • Synthetic Lethality: 6
  • Synthetic Rescue: 4

Resources
Expression Summary
histogram
Resources
Length (a.a.) 3,092
Molecular Weight (Da) 350,976
Isoelectric Point (pI) 6.54
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrII:526628 to 517350 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
SGD ORF map
Genetic position: 78 cM
Last Update Coordinates: 2011-02-03 | Sequence: 1997-01-28
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..9279 526628..517350 2011-02-03 1997-01-28
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
Resources
External Links All Associated Seq | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000000344
SUMMARY PARAGRAPH for IRA1

Ira1p and Ira2p are Ras GTPase activating proteins (GAP) that act as negative regulators of the Ras-cAMP signaling pathway by increasing the rate Ras proteins (encoded by RAS1 and RAS2) hydrolyze GTP to GDP (reviewed in 5, 6, 7, 8, 1). In addition to regulating the Ras-cAMP pathway via the GTPase activity of Ras2p, Ira1p may regulate the localization of Cyr1p, the catalytic subunit of adenylate cyclase (2).

Consistent with their role as negative regulators of the Ras-cAMP pathway, disruption of IRA1 or IRA2 results in the increase of intracellular cAMP levels (1). In addition, ira1 or ira2 mutants have phenotypes consistent with phenotypes of a constitutively active Ras2p mutant, which has reduced GTPase activity. These phenotypes include sensitivity to heat shock or nitrogen starvation, aberrant response to glucose, sporulation defects, pseudohyphal growth defects, filamentous growth defects, and aberrant colony morphology (8, 1, 9, 10, 11, 12). Although both Ira1p and Ira2p regulate Ras2p, biochemical and genetic evidence suggest Ira1p and Ira2p are not functionally redundant and may be involved in responding to different environmental stresses (8, 13, 14).

The C-terminal regions of Ira1p and Ira2p are important for their activity as well as regulation by the kelch proteins Gpb1p and Gpb2p, which are involved in Gpr1p-coupled receptor signaling (9, 11). In addition, Ira2p activity can be inhibited by arachidonic acid (7). Expression of IRA1 and IRA2 increases under conditions when cAMP levels decrease (15).

Ira1p and Ira2p belong to a large family of GAPs which include the S. pombe gap1 gene and the human disease gene NF1, which causes neurofibromatosis type 1 (OMIM) (16, 17, 18, 19). Mutations in Ira1p based on mutations identified in patients with neurofibromatosis effect the Ira1p GAP activity, confirming that yeast is an effective model system for studying the function of NF1 (20).

Last updated: 2007-02-01 Contact SGD

References cited on this page View Complete Literature Guide for IRA1
1) Tanaka K, et al.  (1989) IRA1, an inhibitory regulator of the RAS-cyclic AMP pathway in Saccharomyces cerevisiae. Mol Cell Biol 9(2):757-68
2) Mitts MR, et al.  (1991) Interactions between adenylate cyclase and the yeast GTPase-activating protein IRA1. Mol Cell Biol 11(9):4591-8
3) Byrne KP and Wolfe KH  (2005) The Yeast Gene Order Browser: combining curated homology and syntenic context reveals gene fate in polyploid species. Genome Res 15(10):1456-61
4) Chvojka A, et al.  (1981) A regulatory mutation in yeast which affects catalase T formation and metabolism of carbohydrate reserves. Curr Genet 4(1):47-50
5) Broach JR  (1991) Ras-regulated signaling processes in Saccharomyces cerevisiae. Curr Opin Genet Dev 1(3):370-7
6) Tanaka K, et al.  (1990) S. cerevisiae genes IRA1 and IRA2 encode proteins that may be functionally equivalent to mammalian ras GTPase activating protein. Cell 60(5):803-7
7) Golubic M, et al.  (1991) The GTPase stimulatory activities of the neurofibromatosis type 1 and the yeast IRA2 proteins are inhibited by arachidonic acid. EMBO J 10(10):2897-903
8) Tanaka K, et al.  (1990) IRA2, a second gene of Saccharomyces cerevisiae that encodes a protein with a domain homologous to mammalian ras GTPase-activating protein. Mol Cell Biol 10(8):4303-13
9) Halme A, et al.  (2004) Genetic and epigenetic regulation of the FLO gene family generates cell-surface variation in yeast. Cell 116(3):405-15
10) Colombo S, et al.  (2004) Activation state of the Ras2 protein and glucose-induced signaling in Saccharomyces cerevisiae. J Biol Chem 279(45):46715-22
11) Harashima T, et al.  (2006) The kelch proteins Gpb1 and Gpb2 inhibit Ras activity via association with the yeast RasGAP neurofibromin homologs Ira1 and Ira2. Mol Cell 22(6):819-30
12) Broach JR  (1991) RAS genes in Saccharomyces cerevisiae: signal transduction in search of a pathway. Trends Genet 7(1):28-33
13) Park JI, et al.  (2005) The high-affinity cAMP phosphodiesterase of Saccharomyces cerevisiae is the major determinant of cAMP levels in stationary phase: involvement of different branches of the Ras-cyclic AMP pathway in stress responses. Biochem Biophys Res Commun 327(1):311-9
14) Magherini F, et al.  (2006) In Saccharomyces cerevisiae an unbalanced level of tyrosine phosphorylation down-regulates the Ras/PKA pathway. Int J Biochem Cell Biol 38(3):444-60
15) Russell M, et al.  (1993) Changes in gene expression in the Ras/adenylate cyclase system of Saccharomyces cerevisiae: correlation with cAMP levels and growth arrest. Mol Biol Cell 4(7):757-65
16) Bernards A  (2003) GAPs galore! A survey of putative Ras superfamily GTPase activating proteins in man and Drosophila. Biochim Biophys Acta 1603(2):47-82
17) Imai Y, et al.  (1991) Identification of a GTPase-activating protein homolog in Schizosaccharomyces pombe. Mol Cell Biol 11(6):3088-94
18) Ballester R, et al.  (1990) The NF1 locus encodes a protein functionally related to mammalian GAP and yeast IRA proteins. Cell 63(4):851-9
19) Buchberg AM, et al.  (1990) Sequence homology shared by neurofibromatosis type-1 gene and IRA-1 and IRA-2 negative regulators of the RAS cyclic AMP pathway. Nature 347(6290):291-4
20) Gil R and Seeling JM  (1999) Characterization of Saccharomyces cerevisiae strains expressing ira1 mutant alleles modeled after disease-causing mutations in NF1. Mol Cell Biochem 202(1-2):109-18