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

Summary

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, Dec 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

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_000012.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: 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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
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).
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.
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.
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.
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.
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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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

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 EBI GWAS CatalogPubMed
Genome-wide association study link novel loci to endometriosis. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of biochemical traits in Korcula Island, Croatia. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide meta-analysis identifies new susceptibility loci for migraine. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-147582 (e-PCR)
- UniSTS:175890

D12S1974 (e-PCR)
- UniSTS:54290

G17626 (e-PCR)
- UniSTS:11549

SHGC-110659 (e-PCR)
- UniSTS:167966

D8S2109 (e-PCR)
- UniSTS:67878

SHGC-152266 (e-PCR)
- UniSTS:177452

D12S1720 (e-PCR)
- UniSTS:50222

WI-7483 (e-PCR)
- UniSTS:66869

SHGC-149743 (e-PCR)
- UniSTS:182581

SHGC-110724 (e-PCR)
- UniSTS:167990

SHGC-111879 (e-PCR)
- UniSTS:168798

G64754 (e-PCR)
- UniSTS:164714

G64753 (e-PCR)
- UniSTS:164739

SHGC-151170 (e-PCR)
- UniSTS:173458

G64589 (e-PCR)
- UniSTS:163732

D12S810 (e-PCR)
- UniSTS:149148

G64860 (e-PCR)
- UniSTS:164767

G64843 (e-PCR)
- UniSTS:164768

SHGC-144516 (e-PCR)
- UniSTS:174264

D12S1246E (e-PCR)
- UniSTS:151494

AFMa184zf5 (e-PCR)
- UniSTS:29664

SHGC-144921 (e-PCR)
- UniSTS:174325

D12S1780 (e-PCR)
- UniSTS:36599

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables 3-phosphoinositide-dependent protein kinase activity	IEA Inferred from Electronic Annotation more info
enables AMP-activated protein kinase activity	IEA Inferred from Electronic Annotation more info
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables DNA-dependent protein kinase activity	IEA Inferred from Electronic Annotation more info
enables MAP-kinase scaffold activity	IEA Inferred from Electronic Annotation more info
enables Rho-dependent protein serine/threonine kinase activity	IEA Inferred from Electronic Annotation more info
enables eukaryotic translation initiation factor 2alpha kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H2AS1 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H2AS121 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H2AT120 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H2AXS139 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H2BS14 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H2BS36 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3S10 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3S28 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3S57 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3T11 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3T3 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3T45 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3T6 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H4S1 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
enables ribosomal protein S6 kinase activity	IEA Inferred from Electronic Annotation more info

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

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

EC 2.7.11.1

XP_011536526.1

EC 2.7.11.1

XP_011536527.1

EC 2.7.11.1

XP_011536528.1

EC 2.7.11.1

XP_011536531.1

EC 2.7.11.1

XP_016874697.1

EC 2.7.11.1

XP_016874698.1

EC 2.7.11.1

XP_016874699.1

EC 2.7.11.1

XP_054227814.1

EC 2.7.11.1

XP_054227815.1

EC 2.7.11.1

XP_054227816.1

EC 2.7.11.1

XP_054227817.1

EC 2.7.11.1

XP_054227818.1

EC 2.7.11.1

XP_054227819.1

EC 2.7.11.1

XP_054227820.1

EC 2.7.11.1

NCBI Reference Sequences (RefSeq)

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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)

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

NC_000012.12 Reference GRCh38.p14 Primary Assembly

Range

117453012..117968990 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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
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
XM_017019210.3 → XP_016874699.1 kinase suppressor of Ras 2 isoform X7
XM_017019208.3 → XP_016874697.1 kinase suppressor of Ras 2 isoform X2
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
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
XM_017019209.3 → XP_016874698.1 kinase suppressor of Ras 2 isoform X5