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Aliases for INSIG1 Gene

Aliases for INSIG1 Gene

  • Insulin Induced Gene 1 2 3 5
  • INSIG-1 Membrane Protein 2 3
  • Insulin-Induced Gene 1 Protein 3
  • INSIG-1 4
  • CL6 3

External Ids for INSIG1 Gene

Previous GeneCards Identifiers for INSIG1 Gene

  • GC07U990053
  • GC07P154481
  • GC07P154527
  • GC07P154720
  • GC07P155089
  • GC07P148822

Summaries for INSIG1 Gene

Entrez Gene Summary for INSIG1 Gene

  • 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]

GeneCards Summary for INSIG1 Gene

INSIG1 (Insulin Induced Gene 1) is a Protein Coding gene. Among its related pathways are Metabolism and Chks in Checkpoint Regulation. An important paralog of this gene is INSIG2.

UniProtKB/Swiss-Prot for INSIG1 Gene

  • Mediates feedback control of cholesterol synthesis by controlling SCAP and HMGCR. Functions by blocking the processing of sterol regulatory element-binding proteins (SREBPs). Capable of retaining the SCAP-SREBF2 complex in the ER thus preventing it from escorting SREBPs to the Golgi. Initiates the sterol-mediated ubiquitin-mediated endoplasmic reticulum-associated degradation (ERAD) of HMGCR via recruitment of the reductase to the ubiquitin ligase, AMFR/gp78. May play a role in growth and differentiation of tissues involved in metabolic control. May play a regulatory role during G0/G1 transition of cell growth.

Gene Wiki entry for INSIG1 Gene

Additional gene information for INSIG1 Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for INSIG1 Gene

Genomics for INSIG1 Gene

Regulatory Elements for INSIG1 Gene

Enhancers for INSIG1 Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH07H155213 1.8 FANTOM5 Ensembl ENCODE dbSUPER 17.1 -83.5 -83457 1 HDAC1 ATF1 NFIB ZNF76 KLF17 RAD21 YY1 GLIS2 GATA2 EGR1 INSIG1 LOC105375586 SHH ENSG00000278998
GH07H155344 1.6 FANTOM5 Ensembl ENCODE 13.5 +47.2 47209 1 TBP HDGF TBL1XR1 RB1 SIN3A NFXL1 ZNF2 RAD21 GLIS2 EGR1 INSIG1 BLACE LOC105375591 GC07P155346 LOC105375592
GH07H155203 1.7 Ensembl ENCODE dbSUPER 7.7 -91.0 -90992 5 HDGF PKNOX1 ARNT SIN3A FEZF1 YBX1 ZNF2 YY1 ZNF766 CBX5 PAXIP1-AS2 PAXIP1 ENSG00000227365 LOC105375589 BLACE RBM33 LOC105375580 ENSG00000273183 PAXIP1-AS1 LOC105375586
GH07H155324 1 ENCODE 12.1 +26.4 26380 0 PKNOX1 ATF1 ARNT YBX1 TCF12 ZNF766 GATA2 ELK1 ATF7 CAVIN1 INSIG1 LOC105375592 GC07P155307
GH07H155193 0.6 FANTOM5 dbSUPER 18.8 -104.3 -104338 0 INSIG1 BLACE ENSG00000217825 RN7SKP280
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around INSIG1 on UCSC Golden Path with GeneCards custom track

Promoters for INSIG1 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00000220058 524 2601 HDGF PKNOX1 ARNT SIN3A ZNF2 YY1 CBX5 ZNF207 FOS SP3

Genomic Location for INSIG1 Gene

Chromosome:
7
Start:
155,297,776 bp from pter
End:
155,310,235 bp from pter
Size:
12,460 bases
Orientation:
Plus strand

Genomic View for INSIG1 Gene

Genes around INSIG1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
INSIG1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for INSIG1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for INSIG1 Gene

Proteins for INSIG1 Gene

  • Protein details for INSIG1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O15503-INSI1_HUMAN
    Recommended name:
    Insulin-induced gene 1 protein
    Protein Accession:
    O15503
    Secondary Accessions:
    • A4D2N1
    • A8K6L0
    • Q53XW8
    • Q9BUV5

    Protein attributes for INSIG1 Gene

    Size:
    277 amino acids
    Molecular mass:
    29987 Da
    Quaternary structure:
    • Binds to the SCAP-SREBF2 complex only in the presence of sterols. Interacts with RNF139. Interacts with HMGCR (via its SSD); the interaction, accelerated by sterols, leads to the recruitment of HMGCR to AMFR/gp78 for its ubiquitination by the sterol-mediated ERAD pathway. Interacts with AMFR/gp78 (via its membrane domain); the interaction recruits HMCR at the ER membrane for its ubiquitination and degradation by the sterol-mediated ERAD pathway.
    Miscellaneous:
    • Expressed at high levels when nuclear SREBP levels are high as a result of sterol deprivation.

    Three dimensional structures from OCA and Proteopedia for INSIG1 Gene

    Alternative splice isoforms for INSIG1 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for INSIG1 Gene

Post-translational modifications for INSIG1 Gene

  • Ubiquitinated. Subsequent to sterol deprivation, the SCAP-SREBF2 complex becomes dissociated from INSIG1, is then ubiquitinated and degraded in proteasomes. Although ubiquitination is required for rapid INSIG1 degradation, it is not required for release of the SCAP-SREBP complex. Ubiquitinated by RNF139.
  • Ubiquitination at isoforms=233, isoforms=156, isoforms=158, and posLast=273273
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for INSIG1 Gene

Domains & Families for INSIG1 Gene

Gene Families for INSIG1 Gene

Human Protein Atlas (HPA):
  • Plasma proteins
  • Predicted membrane proteins

Protein Domains for INSIG1 Gene

InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for INSIG1 Gene

Graphical View of Domain Structure for InterPro Entry

O15503

UniProtKB/Swiss-Prot:

INSI1_HUMAN :
  • Belongs to the INSIG family.
Family:
  • Belongs to the INSIG family.
genes like me logo Genes that share domains with INSIG1: view

Function for INSIG1 Gene

Molecular function for INSIG1 Gene

GENATLAS Biochemistry:
insulin induced gene 1,playing a role in growth and differention of tissues involved in metabolic control
UniProtKB/Swiss-Prot Function:
Mediates feedback control of cholesterol synthesis by controlling SCAP and HMGCR. Functions by blocking the processing of sterol regulatory element-binding proteins (SREBPs). Capable of retaining the SCAP-SREBF2 complex in the ER thus preventing it from escorting SREBPs to the Golgi. Initiates the sterol-mediated ubiquitin-mediated endoplasmic reticulum-associated degradation (ERAD) of HMGCR via recruitment of the reductase to the ubiquitin ligase, AMFR/gp78. May play a role in growth and differentiation of tissues involved in metabolic control. May play a regulatory role during G0/G1 transition of cell growth.
UniProtKB/Swiss-Prot Induction:
By insulin.

Phenotypes From GWAS Catalog for INSIG1 Gene

Gene Ontology (GO) - Molecular Function for INSIG1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 12202038
genes like me logo Genes that share ontologies with INSIG1: view
genes like me logo Genes that share phenotypes with INSIG1: view

Animal Models for INSIG1 Gene

MGI Knock Outs for INSIG1:

Animal Model Products

CRISPR Products

miRNA for INSIG1 Gene

miRTarBase miRNAs that target INSIG1

Inhibitory RNA Products

Clone Products

  • Applied Biological Materials Clones for INSIG1
  • Vectors and viruses for ORF, Lenti, Retro, Adenovirus, AAV, and more

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for INSIG1 Gene

Localization for INSIG1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for INSIG1 Gene

Endoplasmic reticulum membrane; Multi-pass membrane protein.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for INSIG1 gene
Compartment Confidence
endoplasmic reticulum 5
plasma membrane 3
peroxisome 2
cytosol 2
extracellular 1
mitochondrion 1
nucleus 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for INSIG1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005783 endoplasmic reticulum IEA,IDA 12202038
GO:0005789 endoplasmic reticulum membrane TAS --
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IEA --
GO:0032937 SREBP-SCAP-Insig complex IDA 15899885
genes like me logo Genes that share ontologies with INSIG1: view

Pathways & Interactions for INSIG1 Gene

genes like me logo Genes that share pathways with INSIG1: view

Pathways by source for INSIG1 Gene

Gene Ontology (GO) - Biological Process for INSIG1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006629 lipid metabolic process IEA --
GO:0006641 triglyceride metabolic process IEA --
GO:0006695 cholesterol biosynthetic process IEA --
GO:0006991 response to sterol depletion IEA --
GO:0008152 metabolic process TAS 9268630
genes like me logo Genes that share ontologies with INSIG1: view

No data available for SIGNOR curated interactions for INSIG1 Gene

Drugs & Compounds for INSIG1 Gene

(1) Drugs for INSIG1 Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(2) Additional Compounds for INSIG1 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with INSIG1: view

Transcripts for INSIG1 Gene

Unigene Clusters for INSIG1 Gene

Insulin induced gene 1:
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

Clone Products

  • Applied Biological Materials Clones for INSIG1
  • Vectors and viruses for ORF, Lenti, Retro, Adenovirus, AAV, and more

Alternative Splicing Database (ASD) splice patterns (SP) for INSIG1 Gene

ExUns: 1a · 1b · 1c · 1d · 1e · 1f ^ 2 ^ 3 ^ 4a · 4b ^ 5a · 5b ^ 6 ^ 7 ^ 8a · 8b · 8c · 8d
SP1: - - -
SP2: -
SP3: - - - -
SP4: - - - - - -
SP5: -
SP6: -

Relevant External Links for INSIG1 Gene

GeneLoc Exon Structure for
INSIG1
ECgene alternative splicing isoforms for
INSIG1

Expression for INSIG1 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for INSIG1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for INSIG1 Gene

This gene is overexpressed in Liver (x10.2).

Protein differential expression in normal tissues from HIPED for INSIG1 Gene

This gene is overexpressed in Adipocyte (39.1) and Fetal ovary (29.9).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, and MOPED for INSIG1 Gene



Protein tissue co-expression partners for INSIG1 Gene

NURSA nuclear receptor signaling pathways regulating expression of INSIG1 Gene:

INSIG1

SOURCE GeneReport for Unigene cluster for INSIG1 Gene:

Hs.520819

mRNA Expression by UniProt/SwissProt for INSIG1 Gene:

O15503-INSI1_HUMAN
Tissue specificity: Expressed in all tissues tested with highest expression in the liver.

Evidence on tissue expression from TISSUES for INSIG1 Gene

  • Skin(4.6)
  • Nervous system(4.4)
  • Liver(4)
  • Blood(3)
  • Lung(2.1)
genes like me logo Genes that share expression patterns with INSIG1: view

Primer Products

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for INSIG1 Gene

Orthologs for INSIG1 Gene

This gene was present in the common ancestor of chordates.

Orthologs for INSIG1 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia INSIG1 33 34
  • 99.64 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia INSIG1 34
  • 83 (a)
OneToOne
cow
(Bos Taurus)
Mammalia INSIG1 33 34
  • 81.52 (n)
mouse
(Mus musculus)
Mammalia Insig1 33 16 34
  • 81.34 (n)
oppossum
(Monodelphis domestica)
Mammalia INSIG1 34
  • 81 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Insig1 33
  • 80.57 (n)
dog
(Canis familiaris)
Mammalia INSIG1 33 34
  • 80.44 (n)
chicken
(Gallus gallus)
Aves INSIG1 33 34
  • 78.49 (n)
lizard
(Anolis carolinensis)
Reptilia INSIG1 34
  • 79 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia insig1 33
  • 71.07 (n)
zebrafish
(Danio rerio)
Actinopterygii insig1 33 34
  • 67.86 (n)
wufi35b10 33
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.2198 33
Species where no ortholog for INSIG1 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for INSIG1 Gene

ENSEMBL:
Gene Tree for INSIG1 (if available)
TreeFam:
Gene Tree for INSIG1 (if available)

Paralogs for INSIG1 Gene

Paralogs for INSIG1 Gene

(1) SIMAP similar genes for INSIG1 Gene using alignment to 5 proteins:

genes like me logo Genes that share paralogs with INSIG1: view

Variants for INSIG1 Gene

Sequence variations from dbSNP and Humsavar for INSIG1 Gene

SNP ID Clin Chr 07 pos Sequence Context AA Info Type
rs1000353028 -- 155,299,280(+) TAAGG(A/G)AAAGA intron-variant, upstream-variant-2KB
rs1000957797 -- 155,305,604(+) CGAGA(A/G)TGAAG intron-variant
rs1001354055 -- 155,306,932(+) GGTCC(A/G)CCCGG intron-variant
rs1001400348 -- 155,310,274(+) TTGGG(A/G)TGGTG downstream-variant-500B
rs1001631094 -- 155,298,722(+) CTTCT(A/G)GAAGT intron-variant, upstream-variant-2KB

Structural Variations from Database of Genomic Variants (DGV) for INSIG1 Gene

Variant ID Type Subtype PubMed ID
nsv1144204 CNV deletion 24896259
nsv609124 CNV loss 21841781
nsv609126 CNV loss 21841781

Variation tolerance for INSIG1 Gene

Residual Variation Intolerance Score: 62.7% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.39; 8.58% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for INSIG1 Gene

Human Gene Mutation Database (HGMD)
INSIG1
SNPedia medical, phenotypic, and genealogical associations of SNPs for
INSIG1

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for INSIG1 Gene

Disorders for INSIG1 Gene

Relevant External Links for INSIG1

Genetic Association Database (GAD)
INSIG1
Human Genome Epidemiology (HuGE) Navigator
INSIG1
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
INSIG1

No disorders were found for INSIG1 Gene.

No data available for MalaCards , UniProtKB/Swiss-Prot and Genatlas for INSIG1 Gene

Publications for INSIG1 Gene

  1. Interactions among genetic variants from SREBP2 activating-related pathway on risk of coronary heart disease in Chinese Han population. (PMID: 19740467) Liu X … Gu D (Atherosclerosis 2010) 3 22 45 60
  2. The INSIG1 gene, not the INSIG2 gene, associated with coronary heart disease: tagSNPs and haplotype-based association study. The Beijing Atherosclerosis Study. (PMID: 18989534) Liu X … Gu D (Thrombosis and haemostasis 2008) 3 22 45 60
  3. Sterol-regulated ubiquitination and degradation of Insig-1 creates a convergent mechanism for feedback control of cholesterol synthesis and uptake. (PMID: 16399501) Gong Y … Ye J (Cell metabolism 2006) 3 4 22 60
  4. Gp78, a membrane-anchored ubiquitin ligase, associates with Insig-1 and couples sterol-regulated ubiquitination to degradation of HMG CoA reductase. (PMID: 16168377) Song BL … DeBose-Boyd RA (Molecular cell 2005) 3 4 22 60
  5. Crucial step in cholesterol homeostasis: sterols promote binding of SCAP to INSIG-1, a membrane protein that facilitates retention of SREBPs in ER. (PMID: 12202038) Yang T … Brown MS (Cell 2002) 3 4 22 60

Products for INSIG1 Gene

Sources for INSIG1 Gene

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