Ksr2 kinase suppressor of ras 2 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Ksr2provided by MGI
Official Full Name: kinase suppressor of ras 2provided by MGI
Primary source: MGI:MGI:3610315
See related: Ensembl:ENSMUSG00000061578 AllianceGenome:MGI:3610315
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Summary: Enables MAP-kinase scaffold activity and mitogen-activated protein kinase kinase binding activity. Involved in positive regulation of cold-induced thermogenesis. Acts upstream of or within calcium-mediated signaling and positive regulation of MAPK cascade. Located in cytosol and plasma membrane. Orthologous to human KSR2 (kinase suppressor of ras 2). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Biased expression in cerebellum adult (RPKM 2.9), frontal lobe adult (RPKM 2.1) and 10 other tissues See more
Orthologs: human all
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Genomic context

Location:: 5 F; 5 56.88 cM

Exon count:: 22

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	5	NC_000071.7 (117552067..117906061)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	5	NC_000071.6 (117414002..117767996)

Chromosome 5 - NC_000071.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Contrasting effects of <i>Ksr2</i>, an obesity gene, on trabecular bone volume and bone marrow adiposity.
Title: Contrasting effects of Ksr2, an obesity gene, on trabecular bone volume and bone marrow adiposity.
These data indicate that KSR2 functions in a cell non-autonomous fashion to regulate GH-stimulated IGF-1 expression in the liver of neonatal mice, which plays a key role in the development of body length.
Title: Cell non-autonomous regulation of hepatic IGF-1 and neonatal growth by Kinase Suppressor of Ras 2 (KSR2).
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).
KSR2 is essential to tumor cell energy homeostasis and critical to the integration of mitogenic and metabolic signaling pathways
Title: Kinase suppressor of Ras 2 (KSR2) regulates tumor cell transformation via AMPK.
The metabolic phenotype of KSR2 heterozygous (KSR2(+/minus;)) and KSR2(-/-) mice suggests that human KSR2 variants may contribute to a similar phenotype linked to human chromosome 12q24
Title: Profound obesity secondary to hyperphagia in mice lacking kinase suppressor of ras 2.
KSR2 regulates AMPK-dependent glucose uptake and fatty acid oxidation in mouse embryonic fibroblasts and glycolysis in a neuronal cell line.
Title: KSR2 is an essential regulator of AMP kinase, energy expenditure, and insulin sensitivity.
The protein phosphatase calcineurin selectively interacts with KSR2 and KSR2 uniquely contributes to Ca2+-mediated ERK signaling.
Title: KSR2 is a calcineurin substrate that promotes ERK cascade activation in response to calcium signals.

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Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Spontaneous (1) 1 citation
Targeted (5) 1 citation
Chemically induced (ENU) (1)
Endonuclease-mediated (1)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables MAP-kinase scaffold activity	IDA Inferred from Direct Assay more info	PubMed
enables 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	IDA Inferred from Direct Assay more info	PubMed
enables nucleotide 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/threonine kinase activity	ISO Inferred from Sequence Orthology more info
enables transferase activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
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
acts_upstream_of_or_within calcium-mediated signaling	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within phosphorylation	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within positive regulation of MAPK cascade	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of cold-induced thermogenesis	IMP Inferred from Mutant Phenotype 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
located_in cytosol	IDA Inferred from Direct Assay more info	PubMed
located_in membrane	IEA Inferred from Electronic Annotation more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: kinase suppressor of Ras 2

NP_001299843.1

EC 2.7.11.1

XP_006530456.1

EC 2.7.11.1

XP_006530457.1

EC 2.7.11.1

XP_006530458.1

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_001312914.1 → NP_001299843.1 kinase suppressor of Ras 2

Status: VALIDATED

Source sequence(s)

AC113299, AK137433, BC068233, KJ719253

UniProtKB/Swiss-Prot

M0QW59, Q3UVC0

UniProtKB/TrEMBL

A5X3G4

Related

ENSMUSP00000137670.2, ENSMUST00000180430.2

Conserved Domains (4) summary

cd00029
Location:414 → 456

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:666 → 935

PK_KSR2; Pseudokinase domain of Kinase Suppressor of Ras 2

pfam07714
Location:667 → 929

Pkinase_Tyr; Protein tyrosine kinase

pfam13543
Location:24 → 152

KSR1-SAM; SAM like domain present in kinase suppressor RAS 1

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

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

Reference GRCm39 C57BL/6J

Genomic

NC_000071.7 Reference GRCm39 C57BL/6J

Range

117552067..117906061

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006530393.4 → XP_006530456.1 kinase suppressor of Ras 2 isoform X1

UniProtKB/TrEMBL

A0A8V5L0Q6, A5X3G4

Related

ENSMUSP00000159519.1, ENSMUST00000240758.1

Conserved Domains (3) summary

cd00029
Location:414 → 456

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:664 → 933

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_006530394.5 → XP_006530457.1 kinase suppressor of Ras 2 isoform X2

Conserved Domains (2) summary

cd00029
Location:117 → 159

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:369 → 638

PK_KSR2; Pseudokinase domain of Kinase Suppressor of Ras 2
XM_006530395.5 → XP_006530458.1 kinase suppressor of Ras 2 isoform X3

See identical proteins and their annotated locations for XP_006530458.1

UniProtKB/TrEMBL

A0A075EIS2

Conserved Domains (2) summary

cd00029
Location:41 → 83

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:293 → 562

PK_KSR2; Pseudokinase domain of Kinase Suppressor of Ras 2

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_001034873.2: Suppressed sequence

Description

NM_001034873.2: This RefSeq was permanently suppressed because currently there is support for the transcript but not for the protein.
NM_001114545.2: Suppressed sequence

Description

NM_001114545.2: This RefSeq was removed because currently there is insufficient support for the transcript and the protein.