SESN1 sestrin 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: SESN1provided by HGNC
Official Full Name: sestrin 1provided by HGNC
Primary source: HGNC:HGNC:21595
See related: Ensembl:ENSG00000080546 MIM:606103; AllianceGenome:HGNC:21595
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: PA26; SEST1
Summary: This gene encodes a member of the sestrin family. Sestrins are induced by the p53 tumor suppressor protein and play a role in the cellular response to DNA damage and oxidative stress. The encoded protein mediates p53 inhibition of cell growth by activating AMP-activated protein kinase, which results in the inhibition of the mammalian target of rapamycin protein. The encoded protein also plays a critical role in antioxidant defense by regenerating overoxidized peroxiredoxins, and the expression of this gene is a potential marker for exposure to radiation. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2010]
Expression: Ubiquitous expression in testis (RPKM 26.4), ovary (RPKM 22.9) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 6q21

Exon count:: 12

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	6	NC_000006.12 (108984309..109094846, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	6	NC_060930.1 (110161725..110272953, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	6	NC_000006.11 (109305512..109416049, complement)

Chromosome 6 - NC_000006.12 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?

Metformin Caused Radiosensitivity of Breast Cancer Cells through the Expression Modulation of miR-21-5p/SESN1axis.
Title: Metformin Caused Radiosensitivity of Breast Cancer Cells through the Expression Modulation of miR-21-5p/SESN1axis.
SESN1 is a FOXO3 effector that counteracts human skeletal muscle ageing.
Title: SESN1 is a FOXO3 effector that counteracts human skeletal muscle ageing.
SESN1 attenuates the OxLDLinduced inflammation, apoptosis and endothelialmesenchymal transition of human umbilical vein endothelial cells by regulating AMPK/SIRT1/LOX1 signaling.
Title: SESN1 attenuates the Ox‑LDL‑induced inflammation, apoptosis and endothelial‑mesenchymal transition of human umbilical vein endothelial cells by regulating AMPK/SIRT1/LOX1 signaling.
SESN1, negatively regulated by miR-377-3p, suppresses invasive growth of head and neck squamous cell carcinoma by interaction with SMAD3.
Title: SESN1, negatively regulated by miR-377-3p, suppresses invasive growth of head and neck squamous cell carcinoma by interaction with SMAD3.
The functions and roles of sestrins in regulating human diseases.
Title: The functions and roles of sestrins in regulating human diseases.
Serum Sestrin-1 Concentration Is Higher in Frail than Non-Frail Older People Living in Nursing Homes.
Title: Serum Sestrin-1 Concentration Is Higher in Frail than Non-Frail Older People Living in Nursing Homes.
Integrating Mouse and Human Genetic Data to Move beyond GWAS and Identify Causal Genes in Cholesterol Metabolism.
Title: Integrating Mouse and Human Genetic Data to Move beyond GWAS and Identify Causal Genes in Cholesterol Metabolism.
Inhibition of sestrin 1 alleviates polycystic ovary syndrome by decreasing autophagy.
Title: Inhibition of sestrin 1 alleviates polycystic ovary syndrome by decreasing autophagy.
Circulating Sestrin Levels Are Increased in Hypertension Patients.
Title: Circulating Sestrin Levels Are Increased in Hypertension Patients.
Sestrin expression decreases during inactivity and its genetic deficiency exacerbates muscle wasting; conversely, sestrin overexpression suffices to prevent atrophy. This protection occurs through mTORC1 inhibition, which upregulates autophagy, and AKT activation, which in turn inhibits FoxO-regulated ubiquitin-proteasome-mediated proteolysis. Sestrin protects muscles against aging-induced atrophy(sarcopenia).
Title: Sestrin prevents atrophy of disused and aging muscles by integrating anabolic and catabolic signals.

Submit: New GeneRIF Correction See all GeneRIFs (20)

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
Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array. 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

G54662 (e-PCR)
- UniSTS:117767

RH46717 (e-PCR)
- UniSTS:25611

RH37402 (e-PCR)
- UniSTS:74778

RH69830 (e-PCR)
- UniSTS:64796

A007I12 (e-PCR)
- UniSTS:1835

RH46062 (e-PCR)
- UniSTS:23106

RH102290 (e-PCR)
- UniSTS:96624

RH36549 (e-PCR)
- UniSTS:43124

RH75369 (e-PCR)
- UniSTS:87295

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables L-leucine binding	IBA Inferred from Biological aspect of Ancestor more info
enables L-leucine binding	IDA Inferred from Direct Assay more info	PubMed
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	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular response to L-leucine	IBA Inferred from Biological aspect of Ancestor more info
involved_in cellular response to amino acid starvation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular response to glucose starvation	IMP Inferred from Mutant Phenotype more info	PubMed
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 positive regulation of macroautophagy	IBA Inferred from Biological aspect of Ancestor more info
involved_in reactive oxygen species metabolic process	IMP Inferred from Mutant Phenotype 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	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info
located_in fibrillar center	IDA Inferred from Direct Assay more info
located_in nucleoplasm	IDA Inferred from Direct Assay more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: sestrin-1

Names: p53 activated gene 26; p53 regulated PA26 nuclear protein

NP_001186862.1

EC 1.11.1.15

NP_001186863.1

EC 1.11.1.15

NP_055269.1

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.

Genomic

NG_029518.2 RefSeqGene

Range

5001..115538

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001199933.2 → NP_001186862.1 sestrin-1 isoform 2

See identical proteins and their annotated locations for NP_001186862.1

Status: REVIEWED

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)

AF033120, AL390208, BI549226, BU740021

Consensus CDS

CCDS56445.1

UniProtKB/Swiss-Prot

Q2M2B7, Q5T316, Q9NV00, Q9UPD5, Q9Y6P5, Q9Y6P6

UniProtKB/TrEMBL

A8K3D6

Related

ENSP00000349061.7, ENST00000356644.7

Conserved Domains (1) summary

pfam04636
Location:47 → 491

PA26; PA26 p53-induced protein (sestrin)
NM_001199934.2 → NP_001186863.1 sestrin-1 isoform 3

See identical proteins and their annotated locations for NP_001186863.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) 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 (3) has a distinct N-terminus and is shorter than isoform 1.

Source sequence(s)

AF033121, AL390208, BU740021

Consensus CDS

CCDS56444.1

UniProtKB/TrEMBL

A8K3D6

Related

ENSP00000306734.2, ENST00000302071.6

Conserved Domains (1) summary

pfam04636
Location:1 → 425

PA26; PA26 p53-induced protein (sestrin)
NM_014454.3 → NP_055269.1 sestrin-1 isoform 1

See identical proteins and their annotated locations for NP_055269.1

Status: REVIEWED

Description

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

Source sequence(s)

AF033122, AL355305, AL390208

Consensus CDS

CCDS5070.1

UniProtKB/TrEMBL

A8K292

Related

ENSP00000393762.2, ENST00000436639.7

Conserved Domains (1) summary

pfam04636
Location:106 → 550

PA26; PA26 p53-induced protein (sestrin)