KSR1 Gene

Name	kinase suppressor of ras 1
Description	Enables 14-3-3 protein binding activity and ATP binding activity. Involved in positive regulation of MAPK cascade. Located in cytosol; endoplasmic reticulum; and membrane. Part of protein-containing complex. Implicated in breast adenocarcinoma. Biomarker of breast cancer. [provided by Alliance of Genome Resources, Mar 2025]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Kinase suppressor of Ras 1 (KSR1) functions as a noncatalytic scaffold that orchestrates the assembly and regulation of the Raf/MEK/ERK signaling cascade in response to diverse extracellular cues. By preassembling high‐molecular‐weight complexes containing MEK, ERK, and Raf, KSR1 enhances both the intensity and duration of ERK activation, thereby impacting cell proliferation, differentiation, and survival."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Its activity is finely regulated by post‐translational modifications; for instance, phosphorylation at key residues such as Ser392 and Thr274 modulates KSR1’s stability, subcellular localization, and its association with other signaling mediators, thus endowing the cascade with stimulus‐specific responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " \n Structural analyses further reveal that KSR1 interacts directly with MEK and, upon heterodimerization with RAF kinases, facilitates a conformational switch that renders MEK a better substrate for phosphorylation by activated Raf."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition, KSR1 is integrated into specialized signaling modules. In dendritic cells, for example, it associates with partners such as LSP1, CNK, and Raf-1 within the DC-SIGN signalosome to dynamically regulate proinflammatory cytokine production in response to carbohydrate-specific pathogen cues."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Moreover, its dephosphorylation mediated by adaptor molecules (via interactions with proteins like GEF-H1 that recruit PP2A) contributes to positive feedback amplification of MAPK signaling in oncogenic contexts."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, in the nervous system KSR1 functions in neural-specific MAPK signaling—helping to restrict ERK pathway activation within distinct subcellular compartments, thereby influencing synaptic plasticity, learning, and memory formation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies underscore the multifaceted role of KSR1 as a critical scaffold that not only heightens the efficiency and specificity of Raf/MEK/ERK signal relay but also integrates regulatory feedback and context-dependent modulation, with profound implications in normal physiology and disease.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "AnhCo Nguyen, W Richard Burack, Jeffrey L Stock, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Kinase suppressor of Ras (KSR) is a scaffold which facilitates mitogen-activated protein kinase activation in vivo."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.22.9.3035-3045.2002"}], "href": "https://doi.org/10.1128/MCB.22.9.3035-3045.2002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11940661"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11940661"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Robert L Kortum, Robert E Lewis "}, {"type": "b", "children": [{"type": "t", "text": "The molecular scaffold KSR1 regulates the proliferative and oncogenic potential of cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.24.10.4407-4416.2004"}], "href": "https://doi.org/10.1128/MCB.24.10.4407-4416.2004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15121859"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15121859"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Gina L Razidlo, Robert L Kortum, Jamie L Haferbier, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Phosphorylation regulates KSR1 stability, ERK activation, and cell proliferation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M406395200"}], "href": "https://doi.org/10.1074/jbc.M406395200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15371409"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15371409"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Damian F Brennan, Arvin C Dar, Nicholas T Hertz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A Raf-induced allosteric transition of KSR stimulates phosphorylation of MEK."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature09860"}], "href": "https://doi.org/10.1038/nature09860"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21441910"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21441910"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Melissa M McKay, Daniel A Ritt, Deborah K Morrison "}, {"type": "b", "children": [{"type": "t", "text": "Signaling dynamics of the KSR1 scaffold complex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0901590106"}], "href": "https://doi.org/10.1073/pnas.0901590106"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19541618"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19541618"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Sonja I Gringhuis, Jeroen den Dunnen, Manja Litjens, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Carbohydrate-specific signaling through the DC-SIGN signalosome tailors immunity to Mycobacterium tuberculosis, HIV-1 and Helicobacter pylori."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Immunol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ni.1778"}], "href": "https://doi.org/10.1038/ni.1778"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19718030"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19718030"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Jane Cullis, David Meiri, Maria Jose Sandi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The RhoGEF GEF-H1 is required for oncogenic RAS signaling via KSR-1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Cell (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ccr.2014.01.025"}], "href": "https://doi.org/10.1016/j.ccr.2014.01.025"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24525234"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24525234"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Sara C Shalin, Caterina M Hernandez, Michele K Dougherty, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Kinase suppressor of Ras1 compartmentalizes hippocampal signal transduction and subserves synaptic plasticity and memory formation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuron (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neuron.2006.04.029"}], "href": "https://doi.org/10.1016/j.neuron.2006.04.029"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16731514"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16731514"}]}]}]}
Synonyms	KSR, RSU2
Proteins	KSR1_HUMAN
NCBI Gene ID	8844
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

KSR1 has 7,414 functional associations with biological entities spanning 9 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 128 datasets.

Click the + buttons to view associations for KSR1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

KSR1 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of KSR1 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of KSR1 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of KSR1 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of KSR1 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of KSR1 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	Biocarta Pathways	pathways involving KSR1 protein from the Biocarta Pathways dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of KSR1 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of KSR1 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of KSR1 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of KSR1 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of KSR1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with KSR1 gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with KSR1 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with KSR1 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of KSR1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of KSR1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of KSR1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing KSR1 protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of KSR1 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing KSR1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing KSR1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with KSR1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with KSR1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing KSR1 protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of KSR1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with KSR1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with KSR1 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with KSR1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of KSR1 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by KSR1 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with KSR1 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with KSR1 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with KSR1 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with KSR1 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with KSR1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with KSR1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at KSR1 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of KSR1 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of KSR1 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing KSR1 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.