ARG82/YDR173C Summary Help

Standard Name ARG82 1
Systematic Name YDR173C
Alias ARGR3 , IPK2 2
Feature Type ORF, Verified
Description Inositol polyphosphate multikinase (IPMK); sequentially phosphorylates Ins(1,4,5)P3 to form Ins(1,3,4,5,6)P5; also has diphosphoinositol polyphosphate synthase activity; regulates arginine-, phosphate-, and nitrogen-responsive genes (2, 3, 4, 5, 6, 7 and see Summary Paragraph)
Also known as: ARGRIII 8
Name Description ARGinine requiring
Chromosomal Location
ChrIV:811632 to 810565 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Genetic position: 95 cM
Gene Ontology Annotations All ARG82 GO evidence and references
  View Computational GO annotations for ARG82
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 6 genes
Classical genetics
Large-scale survey
47 total interaction(s) for 36 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 2
  • Affinity Capture-RNA: 2
  • Reconstituted Complex: 4
  • Two-hybrid: 8

Genetic Interactions
  • Dosage Growth Defect: 1
  • Dosage Rescue: 3
  • Negative Genetic: 16
  • Phenotypic Enhancement: 2
  • Phenotypic Suppression: 2
  • Positive Genetic: 1
  • Synthetic Growth Defect: 4
  • Synthetic Lethality: 1
  • Synthetic Rescue: 1

Expression Summary
Length (a.a.) 355
Molecular Weight (Da) 40,353
Isoelectric Point (pI) 4.41
Phosphorylation PhosphoGRID | PhosphoPep Database
sequence information
ChrIV:811632 to 810565 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Genetic position: 95 cM
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Most Recent Updates
Coordinates Sequence
CDS 1..1068 811632..810565 2011-02-03 1996-07-31
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
External Links All Associated Seq | E.C. | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000002580

ARG82 (also commonly referred to as IPK2 and IPMK) encodes an inositol polyphosphate multikinase involved in inositol phosphorylation (2). Soluble inositol polyphosphates have emerged as important signaling molecules for regulating processes such as transcription, mRNA export, DNA repair, chromatin remodeling, glucose-induced calcium signaling, and telomere elongation (6, 9, 10, and reviewed in 11). Arg82p is able to phosphorylate inositol 1,4,5-trisphosphate (IP3) on both the carbon-3 and carbon-6 positions to synthesize inositol 1,3,4,5-tetrakisphosphate and inositol 1,4,5,6-tetrakisphosphate (IP4), and then to subsequently phosphorylate and convert either isomer of IP4 to inositol 1,3,4,5,6-pentakisphosphate (IP5) (5, 4). Arg82p is also able to use IP5 as a substrate and act as a diphosphoinositol polyphosphate synthase to generate two isomers of PP-IP4 (4). Additionally, Arg82p is able to phosphorylate inositol molecules that are part of the lipid phophatidylinositol (12).

ARG82 was initially identified as an important regulator of arginine metabolism (8). Arg82p is involved in regulating this process by stabilizing the transcription factors Mcm1p and Arg80p (13, 6). Together with Arg81p, Mcm1p and Arg80p form a complex that binds to "arginine boxes" in the promoters of arginine anabolic and catabolic genes (14). Arg82p kinase activity is not required for its protein chaperoning function (6, 2), however the kinase activity of Arg82p may still be required for other aspects of arginine metabolism regulation (2, 3).

An ipk2 null mutant strain displays pleiotropic defects which include temperature sensitivity, sterility, defective sporulation, arginine and ornithine auxotrophy, and impaired mRN A export (15, 16).

Inositol polyphosphate multikinase activity is conserved from yeast to humans, and expression of either the D. melanogaster or A. thaliana homolog, Ipk2p, phenotypically rescues an arg82 null mutant (17, 18, 19). Knockouts of the mouse ortholog of yeast IPK2 result in developmental defects and early embryonic lethality, implicating the importance of inositol polyphosphates in the development of higher organisms (reviewed in 11).

Last updated: 2008-01-22 Contact SGD

References cited on this page View Complete Literature Guide for ARG82
1) Deschamps J and Wiame JM  (1979) Mating-type effect on cis mutations leading to constitutivity of ornithine transaminase in diploid cells of Saccharomyces cerevisiae. Genetics 92(3):749-58
2) Odom AR, et al.  (2000) A role for nuclear inositol 1,4,5-trisphosphate kinase in transcriptional control. Science 287(5460):2026-9
3) Dubois E, et al.  (2000) Inositol polyphosphate kinase activity of Arg82/ArgRIII is not required for the regulation of the arginine metabolism in yeast. FEBS Lett 486(3):300-4
4) Zhang T, et al.  (2001) The transcriptional regulator, Arg82, is a hybrid kinase with both monophosphoinositol and diphosphoinositol polyphosphate synthase activity. FEBS Lett 494(3):208-12
5) Saiardi A, et al.  (1999) Synthesis of diphosphoinositol pentakisphosphate by a newly identified family of higher inositol polyphosphate kinases. Curr Biol 9(22):1323-6
6) El Alami M, et al.  (2003) Arg82p is a bifunctional protein whose inositol polyphosphate kinase activity is essential for nitrogen and PHO gene expression but not for Mcm1p chaperoning in yeast. Mol Microbiol 49(2):457-68
7) Qui HF, et al.  (1991) Dissection of the bifunctional ARGRII protein involved in the regulation of arginine anabolic and catabolic pathways. Mol Cell Biol 11(4):2169-79
8) Bechet J, et al.  (1970) Mutations affecting the repressibility of arginine biosynthetic enzymes in Saccharomyces cerevisiae. Eur J Biochem 12(1):31-9
9) Steger DJ, et al.  (2003) Regulation of chromatin remodeling by inositol polyphosphates. Science 299(5603):114-6
10) Tisi R, et al.  (2004) Evidence for inositol triphosphate as a second messenger for glucose-induced calcium signalling in budding yeast. Curr Genet 45(2):83-9
11) York JD  (2006) Regulation of nuclear processes by inositol polyphosphates. Biochim Biophys Acta 1761(5-6):552-9
12) Resnick AC, et al.  (2005) Inositol polyphosphate multikinase is a nuclear PI3-kinase with transcriptional regulatory activity. Proc Natl Acad Sci U S A 102(36):12783-8
13) El Bakkoury M, et al.  (2000) Recruitment of the yeast MADS-box proteins, ArgRI and Mcm1 by the pleiotropic factor ArgRIII is required for their stability. Mol Microbiol 35(1):15-31
14) Dubois E and Messenguy F  (1991) In vitro studies of the binding of the ARGR proteins to the ARG5,6 promoter. Mol Cell Biol 11(4):2162-8
15) Dubois E and Messenguy F  (1994) Pleiotropic function of ArgRIIIp (Arg82p), one of the regulators of arginine metabolism in Saccharomyces cerevisiae. Role in expression of cell-type-specific genes. Mol Gen Genet 243(3):315-24
16) Saiardi A, et al.  (2000) Inositol polyphosphate multikinase (ArgRIII) determines nuclear mRNA export in Saccharomyces cerevisiae. FEBS Lett 468(1):28-32
17) Xia HJ, et al.  (2003) Arabidopsis inositol polyphosphate 6-/3-kinase is a nuclear protein that complements a yeast mutant lacking a functional ArgR-Mcm1 transcription complex. Plant Cell 15(2):449-63
18) Seeds AM, et al.  (2004) A molecular basis for inositol polyphosphate synthesis in Drosophila melanogaster. J Biol Chem 279(45):47222-32
19) Nalaskowski MM, et al.  (2002) The human homologue of yeast ArgRIII protein is an inositol phosphate multikinase with predominantly nuclear localization. Biochem J 366(Pt 2):549-56