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    KSR2 kinase suppressor of ras 2 [ Homo sapiens (human) ]

    Gene ID: 283455, updated on 2-Nov-2024

    Summary

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    Official Symbol
    KSR2provided by HGNC
    Official Full Name
    kinase suppressor of ras 2provided by HGNC
    Primary source
    HGNC:HGNC:18610
    See related
    Ensembl:ENSG00000171435 MIM:610737; AllianceGenome:HGNC:18610
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Summary
    Enables protein serine/threonine kinase activity. Predicted to be involved in Ras protein signal transduction; calcium-mediated signaling; and positive regulation of cold-induced thermogenesis. Predicted to act upstream of or within positive regulation of MAPK cascade. Predicted to be located in membrane. Predicted to be active in cytosol and plasma membrane. [provided by Alliance of Genome Resources, Nov 2024]
    Expression
    Biased expression in brain (RPKM 1.7), adrenal (RPKM 0.5) and 7 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See KSR2 in Genome Data Viewer
    Location:
    12q24.22-q24.23
    Exon count:
    26
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (117453012..117968990, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (117440139..117956270, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (117890817..118406795, complement)

    Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr12:117580597-117581796 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4913 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4914 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7104 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4915 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4916 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4917 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:117645205-117645705 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:117657550-117658106 Neighboring gene F-box protein 21 Neighboring gene MPRA-validated peak1985 silencer Neighboring gene ReSE screen-validated silencer GRCh37_chr12:117670646-117670812 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:117674186-117674690 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:117674691-117675195 Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:117718941-117719440 Neighboring gene elongin C pseudogene 32 Neighboring gene nitric oxide synthase 1 Neighboring gene NOS1 1f and 1g alternate promoter region Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:117826376-117826876 Neighboring gene NOS1 1c alternate promoter Neighboring gene uncharacterized LOC105370012 Neighboring gene Sharpr-MPRA regulatory region 11046 Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:118021615-118022115 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:118066793-118067293 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:118066292-118066792 Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:118078225-118078724 Neighboring gene uncharacterized LOC105370011 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:118274024-118274569 Neighboring gene OCT4-NANOG-H3K4me1 hESC enhancer GRCh37_chr12:118284773-118285290 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:118312867-118313667 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4918 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4919 Neighboring gene ReSE screen-validated silencer GRCh37_chr12:118442171-118442363 Neighboring gene MPRA-validated peak1990 silencer Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_24987 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_24992 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4920 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7105 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7106 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr12:118489679-118490878 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4921 Neighboring gene uncharacterized LOC124903030 Neighboring gene replication factor C subunit 5 Neighboring gene WD repeat and SOCS box containing 2 Neighboring gene V-set and immunoglobulin domain containing 10

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Expression of human kinase suppressor of Ras 2 (hKSR-2) gene in HL60 leukemia cells is directly upregulated by 1,25-dihydroxyvitamin D(3) and is required for optimal cell differentiation. Wang X, et al. Exp Cell Res, 2007 Aug 15. PMID 17599832, Free PMC Article
    2. Kinase suppressor of Ras 2 is involved in regulation of cell proliferation and is up-regulated in human invasive ductal carcinomas of breast. Jia M, et al. Exp Oncol, 2010 Sep. PMID 21403620
    3. The KSR2-rs7973260 Polymorphism is Associated with Metabolic Phenotypes, but Not Psychological Phenotypes, in Chinese Elders. Wang Y, et al. Genet Test Mol Biomarkers, 2017 Jul. PMID 28537769
    4. KSR2 mutations are associated with obesity, insulin resistance, and impaired cellular fuel oxidation. Pearce LR, et al. Cell, 2013 Nov 7. PMID 24209692, Free PMC Article
    5. Splicing factor SF3B1 promotes endometrial cancer progression via regulating KSR2 RNA maturation. Popli P, et al. Cell Death Dis, 2020 Oct 10. PMID 33040078, Free PMC Article

    See all (40) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. MiR-3138 deteriorates the insulin resistance of HUVECs via KSR2/AMPK/GLUT4 signaling pathway.
      Title: MiR-3138 deteriorates the insulin resistance of HUVECs via KSR2/AMPK/GLUT4 signaling pathway.
    2. Splicing factor SF3B1 promotes endometrial cancer progression via regulating KSR2 RNA maturation.
      Title: Splicing factor SF3B1 promotes endometrial cancer progression via regulating KSR2 RNA maturation.
    3. These observations suggest that, in the brain, KSR2 regulates energy balance via control of feeding behavior and adaptive thermogenesis, while a second KSR2-dependent mechanism, functioning through one or more other tissues, modulates sensitivity to leptin and activators of the energy sensor AMPK.
      Title: Kinase Suppressor of Ras 2 (KSR2) expression in the brain regulates energy balance and glucose homeostasis.
    4. A pleiotropic effect of KSR2-rs7973260 was found on the risk of metabolic syndrome, severe hypertriglyceridemia, and diabetes.
      Title: The KSR2-rs7973260 Polymorphism is Associated with Metabolic Phenotypes, but Not Psychological Phenotypes, in Chinese Elders.
    5. KSR2 deficiency affects stromal interaction molecule 1 (STIM1)/ORAI1 puncta formation, which is correlated with cytoskeleton disorganization.
      Title: The KSR2-calcineurin complex regulates STIM1-ORAI1 dynamics and store-operated calcium entry (SOCE).
    6. Study explored the role of KSR2 in humans by sequencing 2,101 individuals with severe early-onset obesity and identified multiple rare variants in KSR2 that disrupt signaling through the Raf-MEKERK pathway and impair cellular fatty acid oxidation and glucose oxidation in transfected cells.
      Title: KSR2 mutations are associated with obesity, insulin resistance, and impaired cellular fuel oxidation.
    7. study demonstrated that miR-31 upregulated IL-2 expression via reduction of its up-stream kinase suppressor, KSR2, and is a component of T cell activation
      Title: miR-31 regulates interleukin 2 and kinase suppressor of ras 2 during T cell activation.
    8. The involvement of KSR2 in regulation of cell proliferation was predicted by a KSR2-centered network analysis.
      Title: Kinase suppressor of Ras 2 is involved in regulation of cell proliferation and is up-regulated in human invasive ductal carcinomas of breast.
    9. KSR interacts with a regulatory Raf molecule in cis to induce a conformational switch of MEK, facilitating MEK's phosphorylation by a separate catalytic Raf molecule in trans
      Title: A Raf-induced allosteric transition of KSR stimulates phosphorylation of MEK.
    10. Oncoprotein Cot1 represses kinase suppressors of Ras1/2 and 1,25-dihydroxyvitamin D3-induced differentiation of human acute myeloid leukemia cells.
      Title: Oncoprotein Cot1 represses kinase suppressors of Ras1/2 and 1,25-dihydroxyvitamin D3-induced differentiation of human acute myeloid leukemia cells.
    Submit: New GeneRIF Correction See all GeneRIFs (17)

    Phenotypes

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    Review eQTL and phenotype association data in this region using PheGenI

    EBI GWAS Catalog

    Description
    Genome-wide association for abdominal subcutaneous and visceral adipose reveals a novel locus for visceral fat in women.
    EBI GWAS Catalog
    Genome-wide association study link novel loci to endometriosis.
    EBI GWAS Catalog
    Genome-wide association study of biochemical traits in Korcula Island, Croatia.
    EBI GWAS Catalog
    Genome-wide meta-analysis identifies new susceptibility loci for migraine.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • FLJ25965

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables ATP binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables MAP-kinase scaffold activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables histone H2AS1 kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables mitogen-activated protein kinase kinase binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein kinase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables protein serine kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein serine/threonine kinase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in MAPK cascade IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in Ras protein signal transduction IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in calcium-mediated signaling IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in chromatin remodeling IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of MAPK cascade IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of cold-induced thermogenesis ISS
    Inferred from Sequence or Structural Similarity
    more info
    		 PubMed 
    involved_in protein phosphorylation IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    is_active_in cytosol IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    is_active_in plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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    Preferred Names
    kinase suppressor of Ras 2
    NP_775869.4
    XP_011536526.1
    XP_011536527.1
    XP_011536528.1
    XP_011536531.1
    XP_016874697.1
    XP_016874698.1
    XP_016874699.1
    XP_054227814.1
    XP_054227815.1
    XP_054227816.1
    XP_054227817.1
    XP_054227818.1
    XP_054227819.1
    XP_054227820.1

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_173598.6 → NP_775869.4  kinase suppressor of Ras 2

      Status: VALIDATED

      Source sequence(s)
      AC073864, AC079127, AC084291, AC092936
      Consensus CDS
      CCDS61250.2
      UniProtKB/Swiss-Prot
      A0PJT2, Q3B828, Q6VAB6, Q8N775
      Related
      ENSP00000339952.4, ENST00000339824.7
      Conserved Domains (3) summary
      cd14153
      Location:665 → 934
      PK_KSR2; Pseudokinase domain of Kinase Suppressor of Ras 2
      pfam13543
      Location:24 → 152
      KSR1-SAM; SAM like domain present in kinase suppressor RAS 1
      cl00040
      Location:408 → 464
      C1; protein kinase C conserved region 1 (C1 domain) superfamily

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000012.12 Reference GRCh38.p14 Primary Assembly

      Range
      117453012..117968990 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011538224.4 → XP_011536526.1  kinase suppressor of Ras 2 isoform X1

      See identical proteins and their annotated locations for XP_011536526.1

      Conserved Domains (3) summary
      cd00029
      Location:413 → 455
      C1; Protein kinase C conserved region 1 (C1) . Cysteine-rich zinc binding domain. Some members of this domain family bind phorbol esters and diacylglycerol, some are reported to bind RasGTP. May occur in tandem arrangement. Diacylglycerol (DAG) is a second ...
      cd14153
      Location:663 → 932
      PK_KSR2; Pseudokinase domain of Kinase Suppressor of Ras 2
      pfam13543
      Location:24 → 152
      KSR1-SAM; SAM like domain present in kinase suppressor RAS 1

    2. XM_011538225.4 → XP_011536527.1  kinase suppressor of Ras 2 isoform X3

      See identical proteins and their annotated locations for XP_011536527.1

      Conserved Domains (2) summary
      cd00029
      Location:292 → 334
      C1; Protein kinase C conserved region 1 (C1) . Cysteine-rich zinc binding domain. Some members of this domain family bind phorbol esters and diacylglycerol, some are reported to bind RasGTP. May occur in tandem arrangement. Diacylglycerol (DAG) is a second ...
      cd14153
      Location:544 → 813
      PK_KSR2; Pseudokinase domain of Kinase Suppressor of Ras 2

    3. XM_017019210.3 → XP_016874699.1  kinase suppressor of Ras 2 isoform X7

    4. XM_017019208.3 → XP_016874697.1  kinase suppressor of Ras 2 isoform X2

    5. XM_011538226.4 → XP_011536528.1  kinase suppressor of Ras 2 isoform X4

      Conserved Domains (3) summary
      cd00029
      Location:413 → 455
      C1; Protein kinase C conserved region 1 (C1) . Cysteine-rich zinc binding domain. Some members of this domain family bind phorbol esters and diacylglycerol, some are reported to bind RasGTP. May occur in tandem arrangement. Diacylglycerol (DAG) is a second ...
      pfam13543
      Location:24 → 152
      KSR1-SAM; SAM like domain present in kinase suppressor RAS 1
      cl21453
      Location:665 → 739
      PKc_like; Protein Kinases, catalytic domain

    6. XM_011538229.4 → XP_011536531.1  kinase suppressor of Ras 2 isoform X6

      Conserved Domains (2) summary
      cd00029
      Location:413 → 455
      C1; Protein kinase C conserved region 1 (C1) . Cysteine-rich zinc binding domain. Some members of this domain family bind phorbol esters and diacylglycerol, some are reported to bind RasGTP. May occur in tandem arrangement. Diacylglycerol (DAG) is a second ...
      pfam13543
      Location:24 → 152
      KSR1-SAM; SAM like domain present in kinase suppressor RAS 1

    7. XM_017019209.3 → XP_016874698.1  kinase suppressor of Ras 2 isoform X5

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060936.1 Alternate T2T-CHM13v2.0

      Range
      117440139..117956270 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054371839.1 → XP_054227814.1  kinase suppressor of Ras 2 isoform X1

    2. XM_054371841.1 → XP_054227816.1  kinase suppressor of Ras 2 isoform X3

    3. XM_054371845.1 → XP_054227820.1  kinase suppressor of Ras 2 isoform X7

    4. XM_054371840.1 → XP_054227815.1  kinase suppressor of Ras 2 isoform X2

    5. XM_054371842.1 → XP_054227817.1  kinase suppressor of Ras 2 isoform X4

    6. XM_054371844.1 → XP_054227819.1  kinase suppressor of Ras 2 isoform X6

    7. XM_054371843.1 → XP_054227818.1  kinase suppressor of Ras 2 isoform X5

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q6VAB6.2 GenPept UniProtKB/Swiss-Prot:Q6VAB6

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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