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    INSIG2 insulin induced gene 2 [ Homo sapiens (human) ]

    Gene ID: 51141, updated on 7-Apr-2024

    Summary

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    Official Symbol
    INSIG2provided by HGNC
    Official Full Name
    insulin induced gene 2provided by HGNC
    Primary source
    HGNC:HGNC:20452
    See related
    Ensembl:ENSG00000125629 MIM:608660; AllianceGenome:HGNC:20452
    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
    INSIG-2
    Summary
    The protein encoded by this gene is highly similar to the protein product encoded by gene INSIG1. Both INSIG1 protein and this protein are endoplasmic reticulum proteins that block the processing of sterol regulatory element binding proteins (SREBPs) by binding to SREBP cleavage-activating protein (SCAP), and thus prevent SCAP from escorting SREBPs to the Golgi. [provided by RefSeq, Jul 2008]
    Expression
    Ubiquitous expression in liver (RPKM 12.3), lung (RPKM 10.5) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See INSIG2 in Genome Data Viewer
    Location:
    2q14.1-q14.2
    Exon count:
    7
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (118088471..118110997)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (118521717..118544171)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (118846047..118868573)

    Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC102723413 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16438 Neighboring gene uncharacterized LOC107985940 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16439 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16440 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr2:118873325-118874524 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr2:118880595-118881794 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16441 Neighboring gene uncharacterized LOC124907879 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:118899713-118900386 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16442 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16443 Neighboring gene testis associated oncogenic lncRNA

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • 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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    Related articles in PubMed

    1. Insulin-induced gene 2 expression is associated with cervical adenocarcinoma malignant behavior. Qian Y, et al. Mol Biol Rep, 2023 Feb. PMID 36515824
    2. Insulin-Induced Gene 2 Expression Is Associated with Breast Cancer Metastasis. Lu N, et al. Am J Pathol, 2021 Feb. PMID 33321090
    3. The CC Genotype of Insulin-Induced Gene 2 rs7566605 Is a Protective Factor of Hypercholesteremia Susceptible to Mild Cognitive Impairment, Especially to the Executive Function of Patients with Type 2 Diabetes Mellitus. Zhang H, et al. Biomed Res Int, 2020. PMID 32596317, Free PMC Article
    4. INSIG2 gene polymorphism is associated with higher blood pressure and triglyceride levels in Brazilian obese subjects. Nicoletti CF, et al. Nutr Hosp, 2019 Jul 1. PMID 31144980
    5. INSIG2 rs7566605 single nucleotide variant and global DNA methylation index levels are associated with weight loss in a personalized weight reduction program. Pirini F, et al. Mol Med Rep, 2018 Jan. PMID 29138870, Free PMC Article

    See all (111) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Genome-wide loss-of-function genetic screen identifies INSIG2 as the vulnerability of hepatitis B virus-integrated hepatoma cells.
      Title: Genome-wide loss-of-function genetic screen identifies INSIG2 as the vulnerability of hepatitis B virus-integrated hepatoma cells.
    2. Insulin-induced gene 2 expression is associated with cervical adenocarcinoma malignant behavior.
      Title: Insulin-induced gene 2 expression is associated with cervical adenocarcinoma malignant behavior.
    3. Structural basis for sterol sensing by Scap and Insig.
      Title: Structural basis for sterol sensing by Scap and Insig.
    4. 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.
    5. Association of CNR1 and INSIG2 polymorphisms with antipsychotics-induced weight gain: a prospective nested case-control study.
      Title: Association of CNR1 and INSIG2 polymorphisms with antipsychotics-induced weight gain: a prospective nested case-control study.
    6. Polymorphic variants INSIG2 rs6726538, HLA-DRB1 rs9272143, and GCNT1P5 rs7780883 contribute to the susceptibility of cervical cancer in the Bangladeshi women.
      Title: Polymorphic variants INSIG2 rs6726538, HLA-DRB1 rs9272143, and GCNT1P5 rs7780883 contribute to the susceptibility of cervical cancer in the Bangladeshi women.
    7. A structure of human Scap bound to Insig-2 suggests how their interaction is regulated by sterols.
      Title: A structure of human Scap bound to Insig-2 suggests how their interaction is regulated by sterols.
    8. The CC Genotype of Insulin-Induced Gene 2 rs7566605 Is a Protective Factor of Hypercholesteremia Susceptible to Mild Cognitive Impairment, Especially to the Executive Function of Patients with Type 2 Diabetes Mellitus.
      Title: The CC Genotype of Insulin-Induced Gene 2 rs7566605 Is a Protective Factor of Hypercholesteremia Susceptible to Mild Cognitive Impairment, Especially to the Executive Function of Patients with Type 2 Diabetes Mellitus.
    9. Insulin-Induced Gene 2 Expression Is Associated with Breast Cancer Metastasis.
      Title: Insulin-Induced Gene 2 Expression Is Associated with Breast Cancer Metastasis.
    10. 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.
    Submit: New GeneRIF Correction See all GeneRIFs (86)

    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
    Discovery and refinement of loci associated with lipid levels.
    EBI GWAS Catalog
    Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • MGC26273

    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 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 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 fatty acid biosynthetic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    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 2 protein
    Names
    INSIG2 membrane protein
    insulin induced protein 2

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    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)

    1. NM_001321329.2 → NP_001308258.1  insulin-induced gene 2 protein isoform a

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) and variant 1 both encode the same isoform (a).
      Source sequence(s)
      AC009303, AF527632, AW264638, BE888848
      Consensus CDS
      CCDS2122.1
      UniProtKB/Swiss-Prot
      A8K5W8, Q8TBI8, Q9Y5U4
      Conserved Domains (1) summary
      pfam07281
      Location:31 → 211
      INSIG; Insulin-induced protein (INSIG)

    2. NM_001321330.2 → NP_001308259.1  insulin-induced gene 2 protein isoform b

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) and variants 4 and 5 all encode the same isoform (b).
      Source sequence(s)
      AC009303, AF527632, AW264638, DC364733, HY053967
      UniProtKB/TrEMBL
      B4DQ23
      Conserved Domains (1) summary
      pfam07281
      Location:1 → 103
      INSIG; Insulin-induced protein (INSIG)

    3. NM_001321331.2 → NP_001308260.1  insulin-induced gene 2 protein isoform b

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) and variants 3 and 5 all encode the same isoform (b).
      Source sequence(s)
      AC009303, AF527632, AW264638, BX647805, HY053967
      UniProtKB/TrEMBL
      B4DQ23
      Related
      ENST00000485520.5
      Conserved Domains (1) summary
      pfam07281
      Location:1 → 103
      INSIG; Insulin-induced protein (INSIG)

    4. NM_001321332.2 → NP_001308261.1  insulin-induced gene 2 protein isoform b

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) and variants 3 and 4 all encode the same isoform (b).
      Source sequence(s)
      AC009303, AF527632, AW264638, BE888848, BX647805
      UniProtKB/TrEMBL
      B4DQ23
      Conserved Domains (1) summary
      pfam07281
      Location:1 → 103
      INSIG; Insulin-induced protein (INSIG)

    5. NM_001321333.2 → NP_001308262.1  insulin-induced gene 2 protein isoform c

      Status: REVIEWED

      Source sequence(s)
      AC009303, AF527632, AK021692, AW264638, HY053967
      UniProtKB/Swiss-Prot
      Q9Y5U4
      Conserved Domains (1) summary
      pfam07281
      Location:1 → 67
      INSIG; Insulin-induced protein (INSIG)

    6. NM_016133.4 → NP_057217.2  insulin-induced gene 2 protein isoform a

      See identical proteins and their annotated locations for NP_057217.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) and variant 2 both encode the same isoform (a).
      Source sequence(s)
      AC009303, AF527632, AW264638, HY053967
      Consensus CDS
      CCDS2122.1
      UniProtKB/Swiss-Prot
      A8K5W8, Q8TBI8, Q9Y5U4
      Related
      ENSP00000245787.4, ENST00000245787.9
      Conserved Domains (1) summary
      pfam07281
      Location:31 → 211
      INSIG; Insulin-induced protein (INSIG)

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000002.12 Reference GRCh38.p14 Primary Assembly

      Range
      118088471..118110997
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047444640.1 → XP_047300596.1  insulin-induced gene 2 protein isoform X1

      UniProtKB/Swiss-Prot
      A8K5W8, Q8TBI8, Q9Y5U4

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060926.1 Alternate T2T-CHM13v2.0

      Range
      118521717..118544171
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054342404.1 → XP_054198379.1  insulin-induced gene 2 protein isoform X1

      UniProtKB/Swiss-Prot
      A8K5W8, Q8TBI8, Q9Y5U4

    2. XM_054342405.1 → XP_054198380.1  insulin-induced gene 2 protein isoform X1

      UniProtKB/Swiss-Prot
      A8K5W8, Q8TBI8, Q9Y5U4
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9Y5U4.2 GenPept UniProtKB/Swiss-Prot:Q9Y5U4

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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