INSIG1 insulin induced gene 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: INSIG1provided by HGNC
Official Full Name: insulin induced gene 1provided by HGNC
Primary source: HGNC:HGNC:6083
See related: Ensembl:ENSG00000186480 MIM:602055; AllianceGenome:HGNC:6083
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
Summary: This gene encodes an endoplasmic reticulum membrane protein that regulates cholesterol metabolism, lipogenesis, and glucose homeostasis. The encoded protein has six transmembrane helices which contain an effector protein binding site. It binds the sterol-sensing domains of sterol regulatory element-binding protein (SREBP) cleavage-activating protein (SCAP) and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase), and is essential for the sterol-mediated trafficking of these two proteins. It promotes the endoplasmic reticulum retention of SCAP and the ubiquitin-mediated degradation of HMG-CoA reductase. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2016]
Expression: Ubiquitous expression in liver (RPKM 104.0), fat (RPKM 35.8) and 24 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 7q36.3

Exon count:: 7

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	7	NC_000007.14 (155297878..155310235)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	7	NC_060931.1 (156473431..156485788)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	7	NC_000007.13 (155089588..155101945)

Chromosome 7 - NC_000007.14 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?

A novel protein encoded by circINSIG1 reprograms cholesterol metabolism by promoting the ubiquitin-dependent degradation of INSIG1 in colorectal cancer.
Title: A novel protein encoded by circINSIG1 reprograms cholesterol metabolism by promoting the ubiquitin-dependent degradation of INSIG1 in colorectal cancer.
Suppression of insulin-induced gene 1 (INSIG1) function promotes hepatic lipid remodelling and restrains NASH progression.
Title: Suppression of insulin-induced gene 1 (INSIG1) function promotes hepatic lipid remodelling and restrains NASH progression.
Insulin-induced genes INSIG1 and INSIG2 mediate oxysterol-dependent activation of the PERK-eIF2alpha-ATF4 axis.
Title: Insulin-induced genes INSIG1 and INSIG2 mediate oxysterol-dependent activation of the PERK-eIF2α-ATF4 axis.
The Propensity of the Human Liver to Form Large Lipid Droplets Is Associated with PNPLA3 Polymorphism, Reduced INSIG1 and NPC1L1 Expression and Increased Fibrogenetic Capacity.
Title: The Propensity of the Human Liver to Form Large Lipid Droplets Is Associated with PNPLA3 Polymorphism, Reduced INSIG1 and NPC1L1 Expression and Increased Fibrogenetic Capacity.
Investigation of the association between obesity and insulin-induced gene 1 polymorphism at 7q36.3 region in Uygur population in Xinjiang, China.
Title: Investigation of the association between obesity and insulin-induced gene 1 polymorphism at 7q36.3 region in Uygur population in Xinjiang, China.
the gluconeogenic enzyme PCK1 phosphorylates INSIG1/2 for lipogenesis; findings highlight the importance of the protein kinase activity of PCK1 in the activation of SREBPs, lipogenesis and the development of hepatocellular carcinoma
Title: The gluconeogenic enzyme PCK1 phosphorylates INSIG1/2 for lipogenesis.
INSIG1 functions as a sentinel responsive to HIV-1 production and inhibits HIV-1 replication by degrading Gag, a process occurring at intracellular membrane sites such as the endoplasmic reticulum and endosomes where both INSIG1 and Gag may be located.
Title: Insulin-induced gene 1 (INSIG1) inhibits HIV-1 production by degrading Gag via activity of the ubiquitin ligase TRC8.
Knock down of FADS1 did not significantly change cholesterol efflux (p=0.70), but knockdown of INSIG1 and LDLR resulted in highly significant reduction of the efflux to HDL (67% and 75% of control, respectively, p<0.001).
Title: HDL activates expression of genes stimulating cholesterol efflux in human monocyte-derived macrophages.
INSIG1 variation may contribute to statin-induced changes in plasma triglycerides in a sex-specific manner.
Title: Statin-induced expression change of INSIG1 in lymphoblastoid cell lines correlates with plasma triglyceride statin response in a sex-specific manner.
argue that precursor miR-122 molecules modulate polyadenylation site usage in Insig1 mRNAs, resulting in down-regulation of Insig1 protein abundance
Title: Precursor microRNA-122 inhibits synthesis of Insig1 isoform mRNA by modulating polyadenylation site usage.

Submit: New GeneRIF Correction See all GeneRIFs (42)

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
Genome-wide interaction study of smoking and bladder cancer risk. EBI GWAS Catalog EBI GWAS CatalogPubMed
PKNOX2 is associated with formal thought disorder in schizophrenia: a meta-analysis of two genome-wide association studies. 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)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Vif	vif	HIV-1 Vif upregulates the expression of insulin induced gene 1 (INSIG1) in Vif-expression T cells	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

WI-13602 (e-PCR)
- UniSTS:45347

D7S2171E (e-PCR)
- UniSTS:151158

D7S2172E (e-PCR)
- UniSTS:151159

WI-11991 (e-PCR)
- UniSTS:6079

RH47239 (e-PCR)
- UniSTS:5066

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables oxysterol binding	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein sequestering activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in SREBP signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in SREBP signaling pathway	IDA Inferred from Direct Assay more info	PubMed
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	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to insulin stimulus	IBA Inferred from Biological aspect of Ancestor more info
involved_in cellular response to sterol	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cholesterol biosynthetic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in cholesterol biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
involved_in cholesterol homeostasis	IDA Inferred from Direct Assay more info	PubMed
involved_in cranial suture morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in inner ear morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in middle ear morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of cargo loading into COPII-coated vesicle	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of fat cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of fatty acid biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of protein exit from endoplasmic reticulum	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of steroid biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in roof of mouth development	IEA Inferred from Electronic Annotation more info
involved_in triglyceride metabolic process	IEA Inferred from Electronic Annotation more info

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	IDA Inferred from Direct Assay more info	PubMed
is_active_in endoplasmic reticulum	IBA Inferred from Biological aspect of Ancestor more info
located_in endoplasmic reticulum	IDA Inferred from Direct Assay more info	PubMed
is_active_in endoplasmic reticulum membrane	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: insulin-induced gene 1 protein

Names: INSIG-1 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_001346590.2 → NP_001333519.1 insulin-induced gene 1 protein isoform 4

Status: REVIEWED

Description

Transcript Variant: This variant (4) contains an alternate exon in the 3' coding region which results in a frameshift, compared to variant 1. The encoded isoform (4) has a distinct C-terminus and is longer than isoform 1. Variants 4 and 5 encode the same protein.

Source sequence(s)

AC231970, AK095977, BC001880, BM995866, DA590854

UniProtKB/TrEMBL

A0A2Z2EKN2, A4D2M9
NM_001346591.2 → NP_001333520.1 insulin-induced gene 1 protein isoform 4

Status: REVIEWED

Description

Transcript Variant: This variant (5) differs in the 5' UTR and contains an alternate exon in the 3' coding region which results in a frameshift, compared to variant 1. The encoded isoform (4) has a distinct C-terminus and is longer than isoform 1. Variants 4 and 5 encode the same protein.

Source sequence(s)

AC231970, AK095977, BC001880, BM995866, DA590854, DB034358, HY070608

UniProtKB/TrEMBL

A0A2Z2EKN2, A4D2M9
NM_001346592.2 → NP_001333521.1 insulin-induced gene 1 protein isoform 1

Status: REVIEWED

Description

Transcript Variant: This variant (6) differs in the 5' UTR, compared to variant 1. Variants 1 and 6 encode the same protein.

Source sequence(s)

AC144652, AC231970, AK095977, BC001880, BM995866, BT007227, HY070608

Consensus CDS

CCDS5938.1

UniProtKB/Swiss-Prot

A4D2N1, A8K6L0, O15503, Q53XW8, Q9BUV5

UniProtKB/TrEMBL

A0A2Z2EKN2

Conserved Domains (1) summary

pfam07281
Location:87 → 267

INSIG; Insulin-induced protein (INSIG)
NM_001346593.2 → NP_001333522.1 insulin-induced gene 1 protein isoform 3

Status: REVIEWED

Description

Transcript Variant: This variant (7) differs in the 5' UTR, and lacks two exons in the coding region which results in a frameshift and an early stop codon, compared to variant 1. The encoded isoform (3) has a distinct C-terminus and is shorter than isoform 1. Variants 3 and 7 encode the same protein.

Source sequence(s)

AC144652, AC231970, AK095977, BC001880, BM995866, BT007227, BU177114, HY070608

Consensus CDS

CCDS5939.1

UniProtKB/Swiss-Prot

O15503
NM_001346594.2 → NP_001333523.1 insulin-induced gene 1 protein isoform 5

Status: REVIEWED

Description

Transcript Variant: This variant (8) uses an alternate in-frame splice site in the coding region, compared to variant 1. The encoded isoform (5) is longer than isoform 1.

Source sequence(s)

AC144652, AC231970, AK095977, BC001880, BI460711, BM995866

UniProtKB/TrEMBL

A0A2Z2EKN2
NM_005542.6 → NP_005533.2 insulin-induced gene 1 protein isoform 1

See identical proteins and their annotated locations for NP_005533.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes isoform 1. Variants 1 and 6 encode the same protein.

Source sequence(s)

AC231970, AK095977, BC001880, BM995866

Consensus CDS

CCDS5938.1

UniProtKB/Swiss-Prot

A4D2N1, A8K6L0, O15503, Q53XW8, Q9BUV5

UniProtKB/TrEMBL

A0A2Z2EKN2

Related

ENSP00000344741.4, ENST00000340368.9

Conserved Domains (1) summary

pfam07281
Location:87 → 267

INSIG; Insulin-induced protein (INSIG)
NM_198336.4 → NP_938150.2 insulin-induced gene 1 protein isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) has multiple coding region differences, compared to variant 1, one of which results in a frameshift. The encoded isoform (2) has a distinct C-terminus and is shorter than isoform 1.

Source sequence(s)

AC144652, AC231970, AK095977, BC001880, BM995866, DA590854, DA775024

Consensus CDS

CCDS94240.1

UniProtKB/TrEMBL

F5H6P3

Related

ENSP00000340010.4, ENST00000344756.8

Conserved Domains (1) summary

pfam07281
Location:25 → 115

INSIG; Insulin-induced protein (INSIG)
NM_198337.4 → NP_938151.1 insulin-induced gene 1 protein isoform 3

See identical proteins and their annotated locations for NP_938151.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks two exons in the coding region which results in a frameshift and an early stop codon, compared to variant 1. The encoded isoform (3) has a distinct C-terminus and is shorter than isoform 1. Variants 3 and 7 encode the same protein.

Source sequence(s)

AC231970, AK095977, BC001880, BM995866, DA738378, DN996424

Consensus CDS

CCDS5939.1

UniProtKB/Swiss-Prot

O15503

Related

ENSP00000344035.5, ENST00000342407.5