Insig2 insulin induced gene 2 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Insig2provided by MGI
Official Full Name: insulin induced gene 2provided by MGI
Primary source: MGI:MGI:1920249
See related: Ensembl:ENSMUSG00000003721 AllianceGenome:MGI:1920249
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: Insig-2; 2900053I11Rik; C730043J18Rik
Summary: Predicted to enable oxysterol binding activity. Acts upstream of or within several processes, including cholesterol biosynthetic process; ear morphogenesis; and negative regulation of lipid biosynthetic process. Predicted to be located in membrane. Predicted to be integral component of membrane. Predicted to be part of SREBP-SCAP-Insig complex. Predicted to be active in endoplasmic reticulum. Is expressed in central nervous system; jaw bone; and retina. Orthologous to human INSIG2 (insulin induced gene 2). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Ubiquitous expression in liver adult (RPKM 40.0), large intestine adult (RPKM 16.4) and 26 other tissues See more
Orthologs: human all
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Genomic context

Location:: 1 E2.3; 1 52.91 cM

Exon count:: 7

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	1	NC_000067.7 (121232082..121260391, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	1	NC_000067.6 (121304353..121332662, complement)

Chromosome 1 - NC_000067.7 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?

Insulin-induced gene 2 protects against hepatic ischemia-reperfusion injury via metabolic remodeling.
Title: Insulin-induced gene 2 protects against hepatic ischemia-reperfusion injury via metabolic remodeling.
CD36 promotes de novo lipogenesis in hepatocytes through INSIG2-dependent SREBP1 processing.
Title: CD36 promotes de novo lipogenesis in hepatocytes through INSIG2-dependent SREBP1 processing.
Insig-2 is an ER membrane protein negatively controlling lipid biosynthesis. The stabilized Insig-2 downregulates lipogenesis through inhibiting the SREBP pathway, helping to channel the carbon flux to ATP generation and protecting myotubes from lipid over-accumulation.
Title: Competitive oxidation and ubiquitylation on the evolutionarily conserved cysteine confer tissue-specific stabilization of Insig-2.
CRTC2 modulates hepatic SREBP1c cleavage by controlling Insig2a expression during fasting
Title: CRTC2 modulates hepatic SREBP1c cleavage by controlling Insig2a expression during fasting.
These results suggest that PPARalpha is a trans-acting factor that enhances Insig2a gene expression, thereby suppressing SREBP-1c processing during fasting.
Title: PPARα-dependent Insig2a overexpression inhibits SREBP-1c processing during fasting.
Intracellular biosynthesis of lipids and cholesterol by Scap and Insig in mesenchymal cells regulates long bone growth and chondrocyte homeostasis.
Title: Intracellular biosynthesis of lipids and cholesterol by Scap and Insig in mesenchymal cells regulates long bone growth and chondrocyte homeostasis.
INSIG2 is a negative regulator of SREBP, and acute glucocorticoid treatment decreased active SREBP during refeeding or in livers of Ob/Ob mice, both systems of elevated SREBP-1c-driven lipogenesis.
Title: SETDB2 Links Glucocorticoid to Lipid Metabolism through Insig2a Regulation.
These results indicate that HIF-mediated induction of Insig-2 and degradation of HMGCR are physiologically relevant events that guard against wasteful oxygen consumption and inappropriate cell growth during hypoxia.
Title: Hypoxia-inducible factor 1α activates insulin-induced gene 2 (Insig-2) transcription for degradation of 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase in the liver.
the essential role of Insig1,2 proteins in the sterol homeostasis of enterocytes.
Title: Insig proteins mediate feedback inhibition of cholesterol synthesis in the intestine.
Insig deficiency in skin causes accumulation of cholesterol precursors, and this impairs normal hair development
Title: Hair growth defects in Insig-deficient mice caused by cholesterol precursor accumulation and reversed by simvastatin.

Submit: New GeneRIF Correction See all GeneRIFs (19)

Variation

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Alleles

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

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

General gene information

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Markers

PMC303355P2 (e-PCR)
- UniSTS:272505

AU027072 (e-PCR)
- UniSTS:113660

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables lipid binding	IEA Inferred from Electronic Annotation more info
enables oxysterol binding	ISO Inferred from Sequence Orthology more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein sequestering activity	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
involved_in SREBP signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in SREBP signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in SREBP-SCAP complex retention in endoplasmic reticulum	IBA Inferred from Biological aspect of Ancestor more info
involved_in SREBP-SCAP complex retention in endoplasmic reticulum	ISO Inferred from Sequence Orthology more info
involved_in cellular response to insulin stimulus	IBA Inferred from Biological aspect of Ancestor more info
involved_in cholesterol biosynthetic process	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within cholesterol biosynthetic process	IGI Inferred from Genetic Interaction more info	PubMed
involved_in cholesterol biosynthetic process	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within cholesterol metabolic process	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within cranial suture morphogenesis	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within inner ear morphogenesis	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within lipid metabolic process	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within middle ear morphogenesis	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within negative regulation of fatty acid biosynthetic process	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within negative regulation of steroid biosynthetic process	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within response to sterol depletion	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within roof of mouth development	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within steroid metabolic process	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within sterol biosynthetic process	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within triglyceride metabolic process	IGI Inferred from Genetic Interaction more info	PubMed

Component	Evidence Code	Pubs
part_of SREBP-SCAP-Insig complex	IBA Inferred from Biological aspect of Ancestor more info
part_of SREBP-SCAP-Insig complex	ISO Inferred from Sequence Orthology more info
is_active_in endoplasmic reticulum	IBA Inferred from Biological aspect of Ancestor more info
located_in endoplasmic reticulum	ISO Inferred from Sequence Orthology more info
is_active_in endoplasmic reticulum membrane	ISO Inferred from Sequence Orthology more info
located_in membrane	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: insulin-induced gene 2 protein

Names: INSIG-2 membrane protein

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_001271531.1 → NP_001258460.1 insulin-induced gene 2 protein isoform 1

See identical proteins and their annotated locations for NP_001258460.1

Status: VALIDATED

Description

Transcript Variant: This variant (3) differs in the 5' UTR compared to variant 1. Variants 1, 2 and 3 encode the same isoform (1).

Source sequence(s)

AK050394, BC023067

Consensus CDS

CCDS15236.1

UniProtKB/Swiss-Prot

Q3TMY2, Q8BWP1, Q91WG1

Related

ENSMUSP00000124345.2, ENSMUST00000159085.8

Conserved Domains (1) summary

pfam07281
Location:31 → 211

INSIG; Insulin-induced protein (INSIG)
NM_001271532.1 → NP_001258461.1 insulin-induced gene 2 protein isoform 2

Status: VALIDATED

Description

Transcript Variant: This variant (4) lacks an exon which contains a portion of the 5' UTR and 5' coding region including the start codon, compared to variant 1. These differences cause translation initiation at a downstream start codon and result in an isoform (2) with a shorter N-terminus, compared to isoform 1.

Source sequence(s)

AC163333

Consensus CDS

CCDS78670.1

UniProtKB/TrEMBL

A0A087WQP7

Related

ENSMUSP00000140292.2, ENSMUST00000186915.2

Conserved Domains (1) summary

pfam07281
Location:1 → 103

INSIG; Insulin-induced protein (INSIG)
NM_001357251.1 → NP_001344180.1 insulin-induced gene 2 protein isoform 1

Status: VALIDATED

Source sequence(s)

AC163333

Consensus CDS

CCDS15236.1

UniProtKB/Swiss-Prot

Q3TMY2, Q8BWP1, Q91WG1

Conserved Domains (1) summary

pfam07281
Location:31 → 211

INSIG; Insulin-induced protein (INSIG)
NM_133748.2 → NP_598509.1 insulin-induced gene 2 protein isoform 1

See identical proteins and their annotated locations for NP_598509.1

Status: VALIDATED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longer isoform (1). Variants 1, 2 and 3 encode the same isoform (1).

Source sequence(s)

AC163333, BC023067

Consensus CDS

CCDS15236.1

UniProtKB/Swiss-Prot

Q3TMY2, Q8BWP1, Q91WG1

Related

ENSMUSP00000003818.8, ENSMUST00000003818.14

Conserved Domains (1) summary

pfam07281
Location:31 → 211

INSIG; Insulin-induced protein (INSIG)
NM_178082.3 → NP_835183.1 insulin-induced gene 2 protein isoform 1

See identical proteins and their annotated locations for NP_835183.1

Status: VALIDATED

Description

Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Variants 1, 2 and 3 encode the same isoform (1).

Source sequence(s)

AK040703, AY156084, BC023067

Consensus CDS

CCDS15236.1

UniProtKB/Swiss-Prot

Q3TMY2, Q8BWP1, Q91WG1

Related

ENSMUSP00000065485.7, ENSMUST00000071064.13

Conserved Domains (1) summary

pfam07281
Location:31 → 211

INSIG; Insulin-induced protein (INSIG)