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    INS insulin [ Homo sapiens (human) ]

    Gene ID: 3630, updated on 16-Jul-2017
    Official Symbol
    INSprovided by HGNC
    Official Full Name
    insulinprovided by HGNC
    Primary source
    HGNC:HGNC:6081
    See related
    Ensembl:ENSG00000254647 MIM:176730; Vega:OTTHUMG00000009558
    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
    IDDM; ILPR; IRDN; IDDM1; IDDM2; MODY10
    Summary
    After removal of the precursor signal peptide, proinsulin is post-translationally cleaved into three peptides: the B chain and A chain peptides, which are covalently linked via two disulfide bonds to form insulin, and C-peptide. Binding of insulin to the insulin receptor (INSR) stimulates glucose uptake. A multitude of mutant alleles with phenotypic effects have been identified. There is a read-through gene, INS-IGF2, which overlaps with this gene at the 5' region and with the IGF2 gene at the 3' region. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2010]
    Orthologs
    Location:
    11p15.5
    Exon count:
    3
    Annotation release Status Assembly Chr Location
    108 current GRCh38.p7 (GCF_000001405.33) 11 NC_000011.10 (2159779..2161209, complement)
    105 previous assembly GRCh37.p13 (GCF_000001405.25) 11 NC_000011.9 (2181009..2182439, complement)

    Chromosome 11 - NC_000011.10Genomic Context describing neighboring genes Neighboring gene INS-IGF2 readthrough Neighboring gene insulin like growth factor 2 Neighboring gene microRNA 483 Neighboring gene IGF2 antisense RNA Neighboring gene microRNA 4686 Neighboring gene tyrosine hydroxylase Neighboring gene achaete-scute family bHLH transcription factor 2

    • 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 Jun 15 11:32:44 2016

    GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

    Associated conditions

    Description Tests
    Diabetes mellitus, insulin-dependent, 2
    MedGen: C1852092 OMIM: 125852 GeneReviews: Not available
    Compare labs
    Hyperproinsulinemia
    MedGen: C0342283 OMIM: 616214 GeneReviews: Not available
    Compare labs
    Maturity-onset diabetes of the young, type 10
    MedGen: C3150617 OMIM: 613370 GeneReviews: Not available
    Compare labs
    Permanent neonatal diabetes mellitus Compare labs

    Copy number response

    Description
    Copy number response
    Haploinsufficency

    No evidence available (Last evaluated (2012-03-22)

    ClinGen Genome Curation Page
    Triplosensitivity

    No evidence available (Last evaluated (2012-03-22)

    ClinGen Genome Curation Page

    NHGRI GWAS Catalog

    Description
    A genome-wide association study identifies KIAA0350 as a type 1 diabetes gene.
    NHGRI GWA Catalog
    A possible mechanism behind autoimmune disorders discovered by genome-wide linkage and association analysis in celiac disease.
    NHGRI GWA Catalog
    Genome-wide association analysis of autoantibody positivity in type 1 diabetes cases.
    NHGRI GWA Catalog
    Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes.
    NHGRI GWA Catalog
    Identification of seven new prostate cancer susceptibility loci through a genome-wide association study.
    NHGRI GWA Catalog
    Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes.
    NHGRI GWA Catalog

    Protein interactions

    Protein Gene Interaction Pubs
    Vpr vpr HIV-1 Vpr antagonizes insulin's effect on the expression of glucose 6-phosphatase, manganese superoxide dismutase, and sterol carrier protein 2 genes in HepG2 cells PubMed
    vpr HIV-1 Vpr inhibits insulin-induced association of 14-3-3 and Foxo3a in HeLa cells PubMed
    vpr HIV-1 Vpr inhibits insulin-induced cytoplasmic translocation of Foxo3a, a subtype of the forkhead transcription factors PubMed

    Go to the HIV-1, Human Interaction Database

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    • Signal attenuation, organism-specific biosystem (from REACTOME)
      Signal attenuation, organism-specific biosystemNow with the complete receptor-ligand dissociation and subsequent degradation of insulin in the endosomal lumen, the endosomally associated protein tyrosine phosphatases (PTPs) complete the receptor ...
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    • Signaling by Insulin receptor, organism-specific biosystem (from REACTOME)
      Signaling by Insulin receptor, organism-specific biosystemInsulin binding to its receptor results in receptor autophosphorylation on tyrosine residues and the tyrosine phosphorylation of insulin receptor substrates (e.g. IRS and Shc) by the insulin receptor...
    • Signaling by PDGF, organism-specific biosystem (from REACTOME)
      Signaling by PDGF, organism-specific biosystemPlatelet-derived Growth Factor (PDGF) is a potent stimulator of growth and motility of connective tissue cells such as fibroblasts and smooth muscle cells as well as other cells such as capillary end...
    • Signaling by SCF-KIT, organism-specific biosystem (from REACTOME)
      Signaling by SCF-KIT, organism-specific biosystemStem cell factor (SCF) is a growth factor with membrane bound and soluble forms. It is expressed by fibroblasts and endothelial cells throughout the body, promoting proliferation, migration, survival...
    • Signaling by the B Cell Receptor (BCR), organism-specific biosystem (from REACTOME)
      Signaling by the B Cell Receptor (BCR), organism-specific biosystemMature B cells express IgM and IgD immunoglobulins which are complexed at the plasma membrane with Ig-alpha (CD79A, MB-1) and Ig-beta (CD79B, B29) to form the B cell receptor (BCR) (Fu et al. 1974, F...
    • Signaling events mediated by PTP1B, organism-specific biosystem (from Pathway Interaction Database)
      Signaling events mediated by PTP1B, organism-specific biosystem
      Signaling events mediated by PTP1B
    • Signaling events mediated by TCPTP, organism-specific biosystem (from Pathway Interaction Database)
      Signaling events mediated by TCPTP, organism-specific biosystem
      Signaling events mediated by TCPTP
    • Signalling by NGF, organism-specific biosystem (from REACTOME)
      Signalling by NGF, organism-specific biosystemNeurotrophins (NGF, BDNF, NT-3, NT-4/5) play pivotal roles in survival, differentiation, and plasticity of neurons in the peripheral and central nervous system. They are produced, and secreted in mi...
    • Sterol Regulatory Element-Binding Proteins (SREBP) signalling, organism-specific biosystem (from WikiPathways)
      Sterol Regulatory Element-Binding Proteins (SREBP) signalling, organism-specific biosystemSterol regulatory element-binding proteins (SREBPs) are membrane-bound proteins that act as transcription factors. They regulate lipid, especially cholesterol, biosynthesis and uptake at a transcript...
    • Synthesis, secretion, and deacylation of Ghrelin, organism-specific biosystem (from REACTOME)
      Synthesis, secretion, and deacylation of Ghrelin, organism-specific biosystemGhrelin is a peptide hormone of 28 amino acid residues which is acylated at the serine-3 of the mature peptide. Ghrelin is synthesized in several tissues: X/A-like cells of the gastric mucosa (the ma...
    • Transport to the Golgi and subsequent modification, organism-specific biosystem (from REACTOME)
      Transport to the Golgi and subsequent modification, organism-specific biosystemAt least two mechanisms of transport of proteins from the ER to the Golgi have been described. One is a general flow requiring no export signals (Wieland et al, 1987; Martinez-Menarguez et al, 1999)....
    • Type I diabetes mellitus, organism-specific biosystem (from KEGG)
      Type I diabetes mellitus, organism-specific biosystemType I diabetes mellitus is a disease that results from autoimmune destruction of the insulin-producing beta-cells. Certain beta-cell proteins act as autoantigens after being processed by antigen-pre...
    • Type I diabetes mellitus, conserved biosystem (from KEGG)
      Type I diabetes mellitus, conserved biosystemType I diabetes mellitus is a disease that results from autoimmune destruction of the insulin-producing beta-cells. Certain beta-cell proteins act as autoantigens after being processed by antigen-pre...
    • Type II diabetes mellitus, organism-specific biosystem (from KEGG)
      Type II diabetes mellitus, organism-specific biosystemInsulin resistance is strongly associated with type II diabetes. "Diabetogenic" factors including FFA, TNFalpha and cellular stress induce insulin resistance through inhibition of IRS1 functions. Ser...
    • Type II diabetes mellitus, conserved biosystem (from KEGG)
      Type II diabetes mellitus, conserved biosystemInsulin resistance is strongly associated with type II diabetes. "Diabetogenic" factors including FFA, TNFalpha and cellular stress induce insulin resistance through inhibition of IRS1 functions. Ser...
    • Vesicle-mediated transport, organism-specific biosystem (from REACTOME)
      Vesicle-mediated transport, organism-specific biosystemThe transit of proteins and other cargo through the cell requires a cellular transport process in which transported substances are moved in membrane-bounded vesicles. Transported substances are enclo...
    • Vitamin B12 Metabolism, organism-specific biosystem (from WikiPathways)
      Vitamin B12 Metabolism, organism-specific biosystem
      Vitamin B12 Metabolism
    • cGMP-PKG signaling pathway, organism-specific biosystem (from KEGG)
      cGMP-PKG signaling pathway, organism-specific biosystemCyclic GMP (cGMP) is the intracellular second messenger that mediates the action of nitric oxide (NO) and natriuretic peptides (NPs), regulating a broad array of physiologic processes. The elevated i...
    • cGMP-PKG signaling pathway, conserved biosystem (from KEGG)
      cGMP-PKG signaling pathway, conserved biosystemCyclic GMP (cGMP) is the intracellular second messenger that mediates the action of nitric oxide (NO) and natriuretic peptides (NPs), regulating a broad array of physiologic processes. The elevated i...
    • mTOR signaling pathway, organism-specific biosystem (from KEGG)
      mTOR signaling pathway, organism-specific biosystemThe mammalian (mechanistic) target of rapamycin (mTOR) is a highly conserved serine/threonine protein kinase, which exists in two complexes termed mTOR complex 1 (mTORC1) and 2 (mTORC2). mTORC1 conta...
    • mTOR signaling pathway, conserved biosystem (from KEGG)
      mTOR signaling pathway, conserved biosystemThe mammalian (mechanistic) target of rapamycin (mTOR) is a highly conserved serine/threonine protein kinase, which exists in two complexes termed mTOR complex 1 (mTORC1) and 2 (mTORC2). mTORC1 conta...
    Products Interactant Other Gene Complex Source Pubs Description

    Markers

    Readthrough INS-IGF2

    Readthrough gene: INS-IGF2, Included gene: IGF2

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    hormone activity IC
    Inferred by Curator
    more info
    PubMed 
    hormone activity IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    hormone activity NAS
    Non-traceable Author Statement
    more info
    PubMed 
    identical protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    insulin receptor binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    insulin receptor binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    insulin-like growth factor receptor binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    protease binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    Process Evidence Code Pubs
    ER to Golgi vesicle-mediated transport TAS
    Traceable Author Statement
    more info
     
    G-protein coupled receptor signaling pathway IDA
    Inferred from Direct Assay
    more info
    PubMed 
    MAPK cascade IDA
    Inferred from Direct Assay
    more info
    PubMed 
    activation of protein kinase B activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    acute-phase response IDA
    Inferred from Direct Assay
    more info
    PubMed 
    alpha-beta T cell activation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    cell-cell signaling IC
    Inferred by Curator
    more info
    PubMed 
    cellular protein metabolic process TAS
    Traceable Author Statement
    more info
     
    cognition TAS
    Traceable Author Statement
    more info
    PubMed 
    fatty acid homeostasis IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    glucose homeostasis IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    glucose metabolic process IEA
    Inferred from Electronic Annotation
    more info
     
    glucose transport IDA
    Inferred from Direct Assay
    more info
    PubMed 
    insulin receptor signaling pathway IDA
    Inferred from Direct Assay
    more info
    PubMed 
    insulin receptor signaling pathway TAS
    Traceable Author Statement
    more info
     
    negative regulation of NAD(P)H oxidase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    negative regulation of acute inflammatory response IDA
    Inferred from Direct Assay
    more info
    PubMed 
    negative regulation of blood vessel diameter NAS
    Non-traceable Author Statement
    more info
    PubMed 
    negative regulation of fatty acid metabolic process IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    negative regulation of feeding behavior IDA
    Inferred from Direct Assay
    more info
    PubMed 
    negative regulation of gluconeogenesis NAS
    Non-traceable Author Statement
    more info
    PubMed 
    negative regulation of glycogen catabolic process IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    negative regulation of lipid catabolic process IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    negative regulation of lipid catabolic process NAS
    Non-traceable Author Statement
    more info
    PubMed 
    negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway NAS
    Non-traceable Author Statement
    more info
    PubMed 
    negative regulation of protein catabolic process IDA
    Inferred from Direct Assay
    more info
    PubMed 
    negative regulation of protein oligomerization IDA
    Inferred from Direct Assay
    more info
    PubMed 
    negative regulation of protein secretion IDA
    Inferred from Direct Assay
    more info
    PubMed 
    negative regulation of proteolysis IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    negative regulation of reactive oxygen species biosynthetic process IGI
    Inferred from Genetic Interaction
    more info
    PubMed 
    negative regulation of respiratory burst involved in inflammatory response IDA
    Inferred from Direct Assay
    more info
    PubMed 
    neuron projection maintenance IGI
    Inferred from Genetic Interaction
    more info
    PubMed 
    positive regulation of DNA replication IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of MAPK cascade IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of NF-kappaB transcription factor activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of blood vessel diameter NAS
    Non-traceable Author Statement
    more info
    PubMed 
    positive regulation of brown fat cell differentiation TAS
    Traceable Author Statement
    more info
    PubMed 
    positive regulation of cell differentiation NAS
    Non-traceable Author Statement
    more info
    PubMed 
    positive regulation of cell growth NAS
    Non-traceable Author Statement
    more info
    PubMed 
    positive regulation of cell migration ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    positive regulation of cell proliferation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of cellular protein metabolic process IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    positive regulation of cytokine secretion IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of dendritic spine maintenance IGI
    Inferred from Genetic Interaction
    more info
    PubMed 
    positive regulation of gene expression IGI
    Inferred from Genetic Interaction
    more info
    PubMed 
    positive regulation of glucose import IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of glycogen biosynthetic process IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of glycolytic process IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of glycolytic process IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    positive regulation of insulin receptor signaling pathway IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of lipid biosynthetic process NAS
    Non-traceable Author Statement
    more info
    PubMed 
    positive regulation of long-term synaptic potentiation TAS
    Traceable Author Statement
    more info
    PubMed 
    positive regulation of mitotic nuclear division IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of nitric oxide biosynthetic process NAS
    Non-traceable Author Statement
    more info
    PubMed 
    positive regulation of nitric-oxide synthase activity NAS
    Non-traceable Author Statement
    more info
    PubMed 
    positive regulation of peptide hormone secretion TAS
    Traceable Author Statement
    more info
    PubMed 
    positive regulation of peptidyl-tyrosine phosphorylation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of phosphatidylinositol 3-kinase signaling IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of protein autophosphorylation ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    positive regulation of protein kinase B signaling IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of protein localization to nucleus IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of respiratory burst IDA
    Inferred from Direct Assay
    more info
    PubMed 
    regulation of cellular amino acid metabolic process IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    regulation of protein localization IDA
    Inferred from Direct Assay
    more info
    PubMed 
    regulation of protein localization to plasma membrane IGI
    Inferred from Genetic Interaction
    more info
    PubMed 
    regulation of protein secretion IDA
    Inferred from Direct Assay
    more info
    PubMed 
    regulation of synaptic plasticity TAS
    Traceable Author Statement
    more info
    PubMed 
    regulation of transcription, DNA-templated NAS
    Non-traceable Author Statement
    more info
    PubMed 
    regulation of transmembrane transporter activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    wound healing IDA
    Inferred from Direct Assay
    more info
    PubMed 
    Component Evidence Code Pubs
    Golgi lumen TAS
    Traceable Author Statement
    more info
     
    Golgi membrane TAS
    Traceable Author Statement
    more info
     
    endoplasmic reticulum lumen TAS
    Traceable Author Statement
    more info
     
    endoplasmic reticulum-Golgi intermediate compartment membrane TAS
    Traceable Author Statement
    more info
     
    endosome lumen TAS
    Traceable Author Statement
    more info
     
    extracellular region IC
    Inferred by Curator
    more info
    PubMed 
    extracellular region TAS
    Traceable Author Statement
    more info
     
    extracellular space IDA
    Inferred from Direct Assay
    more info
    PubMed 
    secretory granule lumen TAS
    Traceable Author Statement
    more info
     
    transport vesicle TAS
    Traceable Author Statement
    more info
     
    Preferred Names
    insulin
    Names
    preproinsulin
    proinsulin

    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.

    Genomic

    1. NG_007114.1 RefSeqGene

      Range
      4986..6416
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_000207.2NP_000198.1  insulin preproprotein

      See identical proteins and their annotated locations for NP_000198.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the shortest variant. All variants encode the same protein.
      Source sequence(s)
      BC005255, BM510748
      Consensus CDS
      CCDS7729.1
      UniProtKB/Swiss-Prot
      P01308
      UniProtKB/TrEMBL
      I3WAC9
      Related
      ENSP00000370731.4, OTTHUMP00000011161, ENST00000381330.4, OTTHUMT00000026393
      Conserved Domains (1) summary
      cd04367
      Location:26110
      IlGF_insulin_like; IlGF_like family, insulin_like subgroup, specific to vertebrates. Members include a number of peptides including insulin and insulin-like growth factors I and II, which play a variety of roles in controlling processes such as metabolism, growth and ...
    2. NM_001185097.1NP_001172026.1  insulin preproprotein

      See identical proteins and their annotated locations for NP_001172026.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR, compared to variant 1. All variants encode the same protein.
      Source sequence(s)
      AY899304, BM510347, BP322143
      Consensus CDS
      CCDS7729.1
      UniProtKB/Swiss-Prot
      P01308
      UniProtKB/TrEMBL
      I3WAC9
      Related
      ENSP00000250971.3, OTTHUMP00000011162, ENST00000250971.7, OTTHUMT00000026394
      Conserved Domains (1) summary
      cd04367
      Location:26110
      IlGF_insulin_like; IlGF_like family, insulin_like subgroup, specific to vertebrates. Members include a number of peptides including insulin and insulin-like growth factors I and II, which play a variety of roles in controlling processes such as metabolism, growth and ...
    3. NM_001185098.1NP_001172027.1  insulin preproprotein

      See identical proteins and their annotated locations for NP_001172027.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) differs in the 5' UTR, compared to variant 1. All variants encode the same protein.
      Source sequence(s)
      AC132217, BM510347, BP322143
      Consensus CDS
      CCDS7729.1
      UniProtKB/Swiss-Prot
      P01308
      UniProtKB/TrEMBL
      I3WAC9
      Related
      ENSP00000380432.1, OTTHUMP00000196038, ENST00000397262.5, OTTHUMT00000026395
      Conserved Domains (1) summary
      cd04367
      Location:26110
      IlGF_insulin_like; IlGF_like family, insulin_like subgroup, specific to vertebrates. Members include a number of peptides including insulin and insulin-like growth factors I and II, which play a variety of roles in controlling processes such as metabolism, growth and ...
    4. NM_001291897.1NP_001278826.1  insulin preproprotein

      See identical proteins and their annotated locations for NP_001278826.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) differs in the 5' UTR, compared to variant 1. All variants encode the same protein.
      Source sequence(s)
      AC132217, BM510347
      Consensus CDS
      CCDS7729.1
      UniProtKB/Swiss-Prot
      P01308
      UniProtKB/TrEMBL
      I3WAC9
      Conserved Domains (1) summary
      cd04367
      Location:26110
      IlGF_insulin_like; IlGF_like family, insulin_like subgroup, specific to vertebrates. Members include a number of peptides including insulin and insulin-like growth factors I and II, which play a variety of roles in controlling processes such as metabolism, growth and ...

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 108 details...Open this link in a new tab

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

    Reference GRCh38.p7 Primary Assembly

    Genomic

    1. NC_000011.10 Reference GRCh38.p7 Primary Assembly

      Range
      2159779..2161209 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate CHM1_1.1

    Genomic

    1. NC_018922.2 Alternate CHM1_1.1

      Range
      2179957..2181387 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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