INSIG1 insulin induced gene 1 [Homo sapiens] - Gene

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Summary

Official Symbol: INSIG1provided by HGNC
Official Full Name: insulin induced gene 1provided by HGNC
Primary source: HGNC:6083
See related: Ensembl:ENSG00000186480; HPRD:03633; MIM:602055; Vega:OTTHUMG00000151330
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: CL6; CL-6; MGC1405
Summary: Oxysterols regulate cholesterol homeostasis through the liver X receptor (LXR)- and sterol regulatory element-binding protein (SREBP)-mediated signaling pathways. This gene is an insulin-induced gene. It encodes an endoplasmic reticulum (ER) membrane protein that plays a critical role in regulating cholesterol concentrations in cells. This protein binds to the sterol-sensing domains of SREBP cleavage-activating protein (SCAP) and HMG CoA reductase, and is essential for the sterol-mediated trafficking of the two proteins. Alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Jun 2009]

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Genomic context

Location :: 7q36

Sequence :: Chromosome: 7; NC_000007.13 (155089486..155101945)

See INSIG1 in Epigenomics, MapViewer

Chromosome 7 - NC_000007.13 Genomic Context describing neighboring genes

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Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

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Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

Observational study of gene-disease association, gene-gene interaction, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
Title: Gene-gene interactions of the INSIG1 and INSIG2 in metabolic syndrome in schizophrenic patients treated with atypical antipsychotics.
From genetic association studies, SNPs in INSIG1 (including the promoter region) influence hypertriglyceridemia.
Title: INSIG1 influences obesity-related hypertriglyceridemia in humans.
Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
Title: Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
Common variation in INSIG1 is unlikely to have a major effect on risk of type 2 diabetes risk in white Europeans.
Title: No association between polymorphisms in the INSIG1 gene and the risk of type 2 diabetes and related traits.
These data suggest that p97 recruits proteasomes to polytopic ER proteins, such as Insig-1, even before they are extracted from membranes.
Title: Regulated endoplasmic reticulum-associated degradation of a polytopic protein: p97 recruits proteasomes to Insig-1 before extraction from membranes.
Studies define Insig-1 and Insig-2 as the minimal requirement for sterol-accelerated degradation of the membrane domain of reductase.
Title: Insig-mediated, sterol-accelerated degradation of the membrane domain of hamster 3-hydroxy-3-methylglutaryl-coenzyme A reductase in insect cells.
Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator)
Title: Interactions among genetic variants from SREBP2 activating-related pathway on risk of coronary heart disease in Chinese Han population.
Unsaturated fatty acid-mediated stabilization of Insig-1 enhances the ability of sterols to inhibit proteolytic activation of SREBP-1, which activates transcription of genes involved in fatty acid synthesis
Title: Unsaturated fatty acids inhibit proteasomal degradation of Insig-1 at a postubiquitination step.
Under conditions of mild steroid depletion, the failure to ubiquinate Insig-1 causes a delay in release of the Scap/sterol regulatory element binding protein-2, but it does not abolish it.
Title: Sterol-regulated ubiquitination and degradation of Insig-1 creates a convergent mechanism for feedback control of cholesterol synthesis and uptake.
The INSIG1 gene, not the INSIG2 gene, associated with coronary heart disease: tagSNPs and haplotype-based association study.
Title: The INSIG1 gene, not the INSIG2 gene, associated with coronary heart disease: tagSNPs and haplotype-based association study. The Beijing Atherosclerosis Study.

Submit: New GeneRIF Correction See all (27)

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Phenotypes

Review eQTL and phenotype association data in this region using PheGenI

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Products	Interactant	Other Gene	Source	Pubs	Description
O15503	P04035	HMGCR	HPRD	PubMed
O15503	Q12770	SCAP	HPRD	PubMed
O15503	Q12772	SREBF2	HPRD	PubMed
BioGRID:109850	BioGRID:106764	AMFR	BioGRID	PubMed	Affinity Capture-Western
BioGRID:109850	BioGRID:116331	ERLIN2	BioGRID	PubMed	Affinity Capture-Western
BioGRID:109850	BioGRID:116806	FAF2	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:109850	BioGRID:109399	HMGCR	BioGRID	PubMed	Affinity Capture-Western
BioGRID:109850	BioGRID:109850	INSIG1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:109850	BioGRID:119325	INSIG2	BioGRID	PubMed	Affinity Capture-Western
	NP_006658.1	PGRMC1	BIND	PubMed	PGRMC1 interacts with an unspecified isoform of INSIG1.
BioGRID:109850	BioGRID:111661	PSMA7	BioGRID	PubMed	Reconstituted Complex
BioGRID:109850	BioGRID:111675	PSMC3	BioGRID	PubMed	Reconstituted Complex
BioGRID:109850	BioGRID:116401	RNF139	BioGRID	PubMed	Affinity Capture-Western
	NP_036367.1	SCAP	BIND	PubMed	An unspecified isoform of INSIG-1 interacts with SCAP, as a part of the SCAP-SREBP-2 complex. This interaction was modelled on a demonstrated interaction between human INSIG-1 and hamster SCAP.
BioGRID:109850	BioGRID:116596	SCAP	BioGRID	PubMed	Affinity Capture-Western
BioGRID:109850	BioGRID:112599	SREBF2	BioGRID	PubMed	Affinity Capture-Western
BioGRID:109850	BioGRID:231694	Scap	BioGRID	PubMed	Affinity Capture-Western; Co-localization
BioGRID:109850	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS; Affinity Capture-Western
BioGRID:109850	BioGRID:114651	VAPA	BioGRID	PubMed	Affinity Capture-Western
BioGRID:109850	BioGRID:114650	VAPB	BioGRID	PubMed	Affinity Capture-Western
BioGRID:109850	BioGRID:113258	VCP	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex

Function	Evidence Code	Pubs
protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
ER-nuclear sterol response pathway	IDA Inferred from Direct Assay more info	PubMed
cell proliferation	TAS Traceable Author Statement more info	PubMed
cholesterol biosynthetic process	IEA Inferred from Electronic Annotation more info
cranial suture morphogenesis	IEA Inferred from Electronic Annotation more info
inner ear morphogenesis	IEA Inferred from Electronic Annotation more info
metabolic process	TAS Traceable Author Statement more info	PubMed
middle ear morphogenesis	IEA Inferred from Electronic Annotation more info
negative regulation of fat cell differentiation	IEA Inferred from Electronic Annotation more info
negative regulation of fatty acid biosynthetic process	IEA Inferred from Electronic Annotation more info
negative regulation of steroid biosynthetic process	IEA Inferred from Electronic Annotation more info
palate development	IEA Inferred from Electronic Annotation more info
response to sterol depletion	IEA Inferred from Electronic Annotation more info
steroid metabolic process	IEA Inferred from Electronic Annotation more info
triglyceride metabolic process	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
endoplasmic reticulum	IDA Inferred from Direct Assay more info	PubMed
endoplasmic reticulum membrane	IEA Inferred from Electronic Annotation more info
integral to membrane	IEA Inferred from Electronic Annotation more info
membrane	IEA Inferred from Electronic Annotation more info

General protein information

Preferred Names: insulin-induced gene 1 protein

Names: insulin-induced gene 1 protein; INSIG-1 membrane protein

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NCBI Reference Sequences (RefSeq)

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_005542.4 → NP_005533.2 insulin-induced gene 1 protein isoform 1

Status: REVIEWED

Description

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

Source sequence(s)

AL541939, BC001880, BM995866, DA738378

Consensus CDS

CCDS5938.1

UniProtKB/Swiss-Prot

O15503

Related

ENSP00000344741, OTTHUMP00000216469, ENST00000340368, OTTHUMT00000322244

Conserved Domains (1) summary

pfam07281
Location:84 – 267
Blast Score: 583

INSIG; Insulin-induced protein (INSIG)
NM_198336.2 → NP_938150.2 insulin-induced gene 1 protein isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate in-frame splice site in the 5' coding region, and includes an alternate exon in the 3' coding region that causes a frameshift, compared to variant 1. The resulting isoform (2) has a distinct C-terminus and is shorter than isoform 1.

Source sequence(s)

AC144652, AL541939, BC001880, BM995866, DA590854, DA738378

UniProtKB/TrEMBL

F5H6P3

UniProtKB/Swiss-Prot

O15503

Related

ENSP00000340010, ENST00000344756

Conserved Domains (1) summary

pfam07281
Location:28 – 115
Blast Score: 273

INSIG; Insulin-induced protein (INSIG)
NM_198337.2 → NP_938151.1 insulin-induced gene 1 protein isoform 3

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks two exons in the mid-coding region that causes a frameshift, compared to variant 1. The resulting isoform (3) has a distinct C-terminus and is shorter than isoform 1.

Source sequence(s)

AL541939, BC001880, BM995866, DA738378, DN996424

Consensus CDS

CCDS5939.1

UniProtKB/TrEMBL

A4D2N1

UniProtKB/Swiss-Prot

O15503

Related

ENSP00000344035, OTTHUMP00000216470, ENST00000342407, OTTHUMT00000322246

Conserved Domains (1) summary

pfam07281
Location:84 – 139
Blast Score: 138

INSIG; Insulin-induced protein (INSIG)

RefSeqs of Annotated Genomes: Build 37.3

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

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000007.13 Reference GRCh37.p5 Primary Assembly

Range

155089486..155101945

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000139.1 Alternate HuRef

Range

148822074..148834485

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CRA_TCAGchr7v2

Genomic

AC_000068.1 Alternate CRA_TCAGchr7v2

Range

154316806..154329270

Download

GenBank, FASTA, Sequence Viewer (Graphics)

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AC144438.2	None
genomic	AC144652.1 (21938..23787)	None
genomic	AC231970.2 (7381..15934)	None
genomic	CH236962.1	EAL23728.1
		EAL23729.1
		EAL23730.1
genomic	CH471149.1	EAX04529.1
		EAX04530.1
		EAX04531.1
		EAX04532.1
genomic	U96876.1	AAB69121.1
mRNA	AA565248.1	None
mRNA	AF086365.1	None
mRNA	AK095977.1	None
mRNA	AK291675.1	BAF84364.1
mRNA	AL541939.3	None
mRNA	AY112745.1	AAM44086.1
mRNA	BC001880.1	AAH01880.1
mRNA	BI550548.1	None
mRNA	BI918342.1	None
mRNA	BM995866.1	None
mRNA	BQ059075.1	None
mRNA	BT007227.1	AAP35891.1
mRNA	DA590854.1	None
mRNA	DA738378.1	None
mRNA	DN996424.1	None