HOG1/YLR113W Summary Help

Standard Name HOG1 1
Systematic Name YLR113W
Alias SSK3 2
Feature Type ORF, Verified
Description Mitogen-activated protein kinase involved in osmoregulation; controls global reallocation of RNAPII in osmotic shock; activates CDC28 by stimulating antisense RNA transcription; mediates recruitment/activation of RNAPII at Hot1p-dependent promoters; with Mrc1p defines novel S-phase checkpoint that prevent conflicts between DNA replication and transcription; nuclear form represses pseudohyphal growth; autophosphorylates; protein abundance increases under DNA replication stress (1, 3, 4, 5, 6, 7, 8, 9, 10, 11 and see Summary Paragraph)
Name Description High Osmolarity Glycerol response 1
Chromosomal Location
ChrXII:371620 to 372927 | ORF Map | GBrowse
Gene Ontology Annotations All HOG1 GO evidence and references
  View Computational GO annotations for HOG1
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 6 genes
Classical genetics
Large-scale survey
581 total interaction(s) for 331 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 31
  • Affinity Capture-Western: 55
  • Biochemical Activity: 24
  • Co-localization: 6
  • PCA: 9
  • Reconstituted Complex: 5
  • Two-hybrid: 14

Genetic Interactions
  • Dosage Growth Defect: 79
  • Dosage Lethality: 1
  • Dosage Rescue: 9
  • Negative Genetic: 177
  • Phenotypic Enhancement: 16
  • Phenotypic Suppression: 71
  • Positive Genetic: 3
  • Synthetic Growth Defect: 32
  • Synthetic Haploinsufficiency: 2
  • Synthetic Lethality: 8
  • Synthetic Rescue: 39

Expression Summary
Length (a.a.) 435
Molecular Weight (Da) 48,858
Isoelectric Point (pI) 5.31
Phosphorylation PhosphoGRID | PhosphoPep Database
sequence information
ChrXII:371620 to 372927 | ORF Map | GBrowse
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Most Recent Updates
Coordinates Sequence
CDS 1..1308 371620..372927 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 SGDIDS000004103

Hog1p is a mitogen-activated protein kinase (MAPK) integral to the osmoregulatory signal transduction cascade (HOG signaling pathway) which affects gene expression, G1 and G2 cell cycle progression, and cellular ion levels in response to hyperosmotic stress (1 and a comprehensive review of the HOG pathway can be found in 12). Loss of Hog1p activity results in reduced growth on high osmolarity media, abnormal cell and budding morphology, and osmolarity-induced activation of the pheromone response pathway (1, 13). Constitutive activation of Hog1p has been shown to be lethal (14). HOG1 is the yeast homolog of the mammalian MAPK p38, which is involved in the inflammatory and stress responses (15, 16).

Shortly after S. cerevisiae cells are exposed to hyperosmotic stress, Hog1p is phosphorylated on Thr174 and Tyr176 by the MAPKK Pbs2p (1). Activation of Hog1p leads to its Nmd5p-dependent nuclear import (17). After the cell has equilibrated to the hyperosmotic environment, Hog1p is dephosphorylated by the phosphatases Ptc1p, Ptc2p, Ptc3p, Ptp2p, and Ptp3p (18, 19, 20) and then exported from the nucleus by the karyopherin, Crm1p (17).

Nuclear-localized Hog1p mediates the upregulation of nearly 600 genes by phosphorylating osmoresponsive transcription factors, such as Msn2p/Msn4p, Sko1p, Hot1p, and Smp1p (reviewed in 12 and 21). Phosphorylation of target proteins can lead to the recruitment of other transcription factors that enlist the transcription machinery, but Hog1p has been shown to directly recruit Pol II as well (4, 22). Interaction between Hog1p and the histone deactylase Rpd3p targets the Rpd3p/Sin3p/Sap30p complex to the promoters of osmotic stress genes, resulting in chromatin modification and transcription initiation (23). Additional non-transcription factor targets of Hog1p include the Na+/H+ antiporter Nha1p; the potassium channel Tok1p; the cell cycle regulators Sic1p and Hsl1p; the osmosensor Sho1p; and the protein kinase regulator Ste50p (24, 25, 26, 27, 28).

Last updated: 2010-01-04 Contact SGD

References cited on this page View Complete Literature Guide for HOG1
1) Brewster JL, et al.  (1993) An osmosensing signal transduction pathway in yeast. Science 259(5102):1760-3
2) Maeda T, et al.  (1994) A two-component system that regulates an osmosensing MAP kinase cascade in yeast. Nature 369(6477):242-5
3) O'Rourke SM and Herskowitz I  (2002) A third osmosensing branch in Saccharomyces cerevisiae requires the Msb2 protein and functions in parallel with the Sho1 branch. Mol Cell Biol 22(13):4739-49
4) Alepuz PM, et al.  (2003) Osmostress-induced transcription by Hot1 depends on a Hog1-mediated recruitment of the RNA Pol II. EMBO J 22(10):2433-42
5) Mao K, et al.  (2011) Two MAPK-signaling pathways are required for mitophagy in Saccharomyces cerevisiae. J Cell Biol 193(4):755-67
6) Tkach JM, et al.  (2012) Dissecting DNA damage response pathways by analysing protein localization and abundance changes during DNA replication stress. Nat Cell Biol 14(9):966-76
7) Cook KE and O'Shea EK  (2012) Hog1 Controls Global Reallocation of RNA Pol II upon Osmotic Shock in Saccharomyces cerevisiae. G3 (Bethesda) 2(9):1129-36
8) Maayan I, et al.  (2012) Osmostress Induces Autophosphorylation of Hog1 via a C-Terminal Regulatory Region That Is Conserved in p38alpha. PLoS One 7(9):e44749
9) Duch A, et al.  (2013) Coordinated control of replication and transcription by a SAPK protects genomic integrity. Nature 493(7430):116-9
10) Shively CA, et al.  (2013) Genetic networks inducing invasive growth in Saccharomyces cerevisiae identified through systematic genome-wide overexpression. Genetics 193(4):1297-310
11) Nadal-Ribelles M, et al.  (2014) Control of Cdc28 CDK1 by a Stress-Induced lncRNA. Mol Cell 53(4):549-61
12) Westfall PJ, et al.  (2004) When the stress of your environment makes you go HOG wild. Science 306(5701):1511-2
13) O'Rourke SM and Herskowitz I  (1998) The Hog1 MAPK prevents cross talk between the HOG and pheromone response MAPK pathways in Saccharomyces cerevisiae. Genes Dev 12(18):2874-86
14) Wurgler-Murphy SM, et al.  (1997) Regulation of the Saccharomyces cerevisiae HOG1 mitogen-activated protein kinase by the PTP2 and PTP3 protein tyrosine phosphatases. Mol Cell Biol 17(3):1289-97
15) Han J, et al.  (1994) A MAP kinase targeted by endotoxin and hyperosmolarity in mammalian cells. Science 265(5173):808-11
16) Raingeaud J, et al.  (1995) Pro-inflammatory cytokines and environmental stress cause p38 mitogen-activated protein kinase activation by dual phosphorylation on tyrosine and threonine. J Biol Chem 270(13):7420-6
17) Ferrigno P, et al.  (1998) Regulated nucleo/cytoplasmic exchange of HOG1 MAPK requires the importin beta homologs NMD5 and XPO1. EMBO J 17(19):5606-14
18) Warmka J, et al.  (2001) Ptc1, a type 2C Ser/Thr phosphatase, inactivates the HOG pathway by dephosphorylating the mitogen-activated protein kinase Hog1. Mol Cell Biol 21(1):51-60
19) Young C, et al.  (2002) Role of Ptc2 type 2C Ser/Thr phosphatase in yeast high-osmolarity glycerol pathway inactivation. Eukaryot Cell 1(6):1032-40
20) Mattison CP and Ota IM  (2000) Two protein tyrosine phosphatases, Ptp2 and Ptp3, modulate the subcellular localization of the Hog1 MAP kinase in yeast. Genes Dev 14(10):1229-35
21) Hohmann S  (2002) Osmotic stress signaling and osmoadaptation in yeasts. Microbiol Mol Biol Rev 66(2):300-72
22) Proft M and Struhl K  (2002) Hog1 kinase converts the Sko1-Cyc8-Tup1 repressor complex into an activator that recruits SAGA and SWI/SNF in response to osmotic stress. Mol Cell 9(6):1307-17
23) De Nadal E, et al.  (2004) The MAPK Hog1 recruits Rpd3 histone deacetylase to activate osmoresponsive genes. Nature 427(6972):370-4
24) Proft M and Struhl K  (2004) MAP kinase-mediated stress relief that precedes and regulates the timing of transcriptional induction. Cell 118(3):351-61
25) Escote X, et al.  (2004) Hog1 mediates cell-cycle arrest in G1 phase by the dual targeting of Sic1. Nat Cell Biol 6(10):997-1002
26) Clotet J, et al.  (2006) Phosphorylation of Hsl1 by Hog1 leads to a G2 arrest essential for cell survival at high osmolarity. EMBO J 25(11):2338-46
27) Hao N, et al.  (2007) A systems-biology analysis of feedback inhibition in the Sho1 osmotic-stress-response pathway. Curr Biol 17(8):659-67
28) Hao N, et al.  (2008) Control of MAPK specificity by feedback phosphorylation of shared adaptor protein ste50. J Biol Chem 283(49):33798-802