Sesn1 sestrin 1 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Sesn1provided by MGI
Official Full Name: sestrin 1provided by MGI
Primary source: MGI:MGI:2155278
See related: Ensembl:ENSMUSG00000038332 AllianceGenome:MGI:2155278
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
Also known as: Pa26; Sest1; 1110002G11Rik
Summary: Predicted to enable L-leucine binding activity and oxidoreductase activity, acting on peroxide as acceptor. Involved in cellular response to amino acid stimulus; negative regulation of TORC1 signaling; and negative regulation of cell growth. Acts upstream of or within regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction. Predicted to be located in cytoplasm; fibrillar center; and nucleoplasm. Predicted to be part of GATOR2 complex. Is expressed in several structures, including alimentary system; brain; genitourinary system; hemolymphoid system; and integumental system. Orthologous to human SESN1 (sestrin 1). [provided by Alliance of Genome Resources, Nov 2024]
Expression: Ubiquitous expression in heart adult (RPKM 16.1), large intestine adult (RPKM 14.7) and 28 other tissues See more
Orthologs: human all
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Genomic context

Location:: 10 B2; 10 22.77 cM

Exon count:: 11

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	10	NC_000076.7 (41686570..41784432)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	10	NC_000076.6 (41810574..41908436)

Chromosome 10 - NC_000076.7 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: 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?

Sestrin1, 2, and 3 are dispensable for female fertility in mice.
Title: Sestrin1, 2, and 3 are dispensable for female fertility in mice.
Zonated leucine sensing by Sestrin-mTORC1 in the liver controls the response to dietary leucine.
Title: Zonated leucine sensing by Sestrin-mTORC1 in the liver controls the response to dietary leucine.
MiR-200c-3p targets SESN1 and represses the IL-6/AKT loop to prevent cholangiocyte activation and cholestatic liver fibrosis.
Title: MiR-200c-3p targets SESN1 and represses the IL-6/AKT loop to prevent cholangiocyte activation and cholestatic liver fibrosis.
Forkhead box protein 1 transcriptionally activates sestrin1 to alleviate oxidized low-density lipoprotein-induced inflammation and lipid accumulation in macrophages.
Title: Forkhead box protein 1 transcriptionally activates sestrin1 to alleviate oxidized low-density lipoprotein-induced inflammation and lipid accumulation in macrophages.
Aerobic exercise inhibits inflammatory response in atherosclerosis via Sestrin1 protein.
Title: Aerobic exercise inhibits inflammatory response in atherosclerosis via Sestrin1 protein.
Sestrin1 exerts a cytoprotective role against oxygen-glucose deprivation/reoxygenation-induced neuronal injury by potentiating Nrf2 activation via the modulation of Keap1.
Title: Sestrin1 exerts a cytoprotective role against oxygen-glucose deprivation/reoxygenation-induced neuronal injury by potentiating Nrf2 activation via the modulation of Keap1.
Sestrins are critical mediators of exercise benefits. Genetic ablation of Sestrins prevents mice from acquiring metabolic benefits of exercise and improving their endurance through training. Sestrin upregulation mimics both molecular and physiological effects of exercise, suggesting that it is a major effector of exercise metabolism. AKT and PGC1alpha are critical for the Sestrin effects in extending endurance.
Title: Sestrins are evolutionarily conserved mediators of exercise benefits.
By upregulating AMPK and autophagic activities and suppressing mammalian target of rapamycin complex 1 and oxidative stress, sestrins counteract detrimental effects of doxorubicin on cardiomyocytes.
Title: Cardioprotective roles of sestrin 1 and sestrin 2 against doxorubicin cardiotoxicity.
Sestrin 1 targets at the AMPK/mTORC1/autophagy pathway to inhibit cardiac hypertrophy by interaction with AMPK which is responsible for autophagy regulation. Taken together, our data indicate that Sestrin 1 regulates AMPK/mTORC1/autophagy axis to attenuate cardiac hypertrophy.
Title: Sestrin 1 ameliorates cardiac hypertrophy via autophagy activation.
Study found that Sestrins (1,2 and 3) can inhibit mTORC1 signaling in the absence of AMPK or TSC2. Surprisingly, when coexpressed with a GTP-bound constitutively active form of RagB (RagBQ99L), Sestrins potentiate mTORC1 signaling in the absence of amino acids.
Title: Sestrins function as guanine nucleotide dissociation inhibitors for Rag GTPases to control mTORC1 signaling.

Submit: New GeneRIF Correction See all GeneRIFs (12)

Variation

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Alleles

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

Endonuclease-mediated (3)
Targeted (5) 1 citation

General gene information

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Markers

NoName (e-PCR)
- UniSTS:236340

AU044290 (e-PCR)
- UniSTS:159970

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables L-leucine binding	IBA Inferred from Biological aspect of Ancestor more info
enables L-leucine binding	ISO Inferred from Sequence Orthology more info
enables L-leucine binding	ISS Inferred from Sequence or Structural Similarity more info
enables oxidoreductase activity	IEA Inferred from Electronic Annotation more info
enables oxidoreductase activity, acting on peroxide as acceptor	IBA Inferred from Biological aspect of Ancestor more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in cellular oxidant detoxification	ISO Inferred from Sequence Orthology more info
involved_in cellular oxidant detoxification	ISS Inferred from Sequence or Structural Similarity more info
involved_in cellular response to L-leucine	IBA Inferred from Biological aspect of Ancestor more info
involved_in cellular response to amino acid starvation	ISO Inferred from Sequence Orthology more info
involved_in cellular response to amino acid starvation	ISS Inferred from Sequence or Structural Similarity more info
involved_in cellular response to amino acid stimulus	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular response to glucose starvation	ISO Inferred from Sequence Orthology more info
involved_in cellular response to leucine starvation	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of TORC1 signaling	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of TORC1 signaling	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of TORC1 signaling	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of TORC1 signaling	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of cell growth	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of macroautophagy	IBA Inferred from Biological aspect of Ancestor more info
involved_in reactive oxygen species metabolic process	ISO Inferred from Sequence Orthology more info
involved_in reactive oxygen species metabolic process	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of response to reactive oxygen species	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
part_of GATOR2 complex	ISO Inferred from Sequence Orthology more info
part_of GATOR2 complex	ISS Inferred from Sequence or Structural Similarity more info
located_in cytoplasm	ISO Inferred from Sequence Orthology more info
located_in cytoplasm	ISS Inferred from Sequence or Structural Similarity more info
located_in fibrillar center	ISO Inferred from Sequence Orthology more info
located_in nucleoplasm	ISO Inferred from Sequence Orthology more info
located_in nucleus	ISO Inferred from Sequence Orthology more info
located_in nucleus	ISS Inferred from Sequence or Structural Similarity more info

General protein information

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Preferred Names: sestrin-1

Names: p53 regulated Pa26 nuclear protein; p53-regulated protein PA26

NP_001013388.2

EC 1.11.1.15

NP_001156380.1

EC 1.11.1.15

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_001013370.2 → NP_001013388.2 sestrin-1 isoform 2

See identical proteins and their annotated locations for NP_001013388.2

Status: VALIDATED

Description

Transcript Variant: This variant (2) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at an alternate start codon, compared to variant 1. The encoded isoform (2) has a distinct N-terminus and is shorter than isoform 1.

Source sequence(s)

AK160083, BB338086, BC055753, BY126656

Consensus CDS

CCDS23809.1

UniProtKB/Swiss-Prot

E9QPK0, P58006, Q7TNF3

UniProtKB/TrEMBL

V5QRJ1

Related

ENSMUSP00000043034.7, ENSMUST00000041438.7

Conserved Domains (1) summary

pfam04636
Location:47 → 491

PA26; PA26 p53-induced protein (sestrin)
NM_001162908.1 → NP_001156380.1 sestrin-1 isoform 1

Status: VALIDATED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).

Source sequence(s)

AK160083, BB338086, BC100403

Consensus CDS

CCDS48550.1

UniProtKB/TrEMBL

E9PXR3, Q497S6

Related

ENSMUSP00000097515.4, ENSMUST00000099931.11

Conserved Domains (1) summary

pfam04636
Location:106 → 550

PA26; PA26 p53-induced protein (sestrin)