Q5F3W2 · INSI2_CHICK

  • Protein
    Insulin-induced gene 2 protein
  • Gene
    INSIG2
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at transcript level
  • Annotation score
    3/5

Function

function

Oxysterol-binding protein that mediates feedback control of cholesterol synthesis by controlling both endoplasmic reticulum to Golgi transport of SCAP and degradation of HMGCR. Acts as a negative regulator of cholesterol biosynthesis by mediating the retention of the SCAP-SREBP complex in the endoplasmic reticulum, thereby blocking the processing of sterol regulatory element-binding proteins (SREBPs). Binds oxysterol, including 22-hydroxycholesterol, 24-hydroxycholesterol, 25-hydroxycholesterol and 27-hydroxycholesterol, regulating interaction with SCAP and retention of the SCAP-SREBP complex in the endoplasmic reticulum. In presence of oxysterol, interacts with SCAP, retaining the SCAP-SREBP complex in the endoplasmic reticulum, thereby preventing SCAP from escorting SREBPs to the Golgi. Sterol deprivation reduces oxysterol-binding, disrupting the interaction between INSIG2 and SCAP, thereby promoting Golgi transport of the SCAP-SREBP complex, followed by processing and nuclear translocation of SREBPs. Also regulates cholesterol synthesis by regulating degradation of HMGCR.

Features

Showing features for site.

122520406080100120140160180200220
TypeIDPosition(s)Description
Site115Required for the recognition of 25-hydroxycholesterol

GO annotations

all annotationsall molecular functionvirus receptor activitydna bindingrna bindingcytoskeletal motor activitycatalytic activitygtpase activitystructural molecule activitytransporter activitycytoskeletal protein bindinglipid bindingcyclase activityantioxidant activityoxidoreductase activitytransferase activityhydrolase activitylyase activityisomerase activityligase activityprotein tag activitycargo receptor activityhistone bindingprotein folding chaperonetranslation regulator activitynutrient reservoir activityreceptor ligand activitymolecular transducer activitymolecular adaptor activitytoxin activitycell adhesion mediator activitymolecular function regulator activityvirus coreceptor activitycatalytic activity, acting on a proteincatalytic activity, acting on dnacatalytic activity, acting on rnamolecular carrier activitytranscription regulator activitygeneral transcription initiation factor activitymolecular sensor activitymolecular sequestering activityatp-dependent activityother molecular functionall biological processmitotic cell cyclecytokinesiscytoplasmic translationimmune system processmuscle system processcirculatory system processrenal system processrespiratory system processcarbohydrate metabolic processgeneration of precursor metabolites and energydna replicationdna repairdna recombinationchromatin organizationdna-templated transcriptionregulation of dna-templated transcriptiontrna metabolic processprotein foldingprotein glycosylationamino acid metabolic processmodified amino acid metabolic processlipid metabolic processvitamin metabolic processsulfur compound metabolic processintracellular protein transportnucleocytoplasmic transportautophagyinflammatory responsemitochondrion organizationcytoskeleton organizationmicrotubule-based movementperoxisome organizationlysosome organizationchromosome segregationcell adhesionestablishment or maintenance of cell polarityprogrammed cell deathphotosynthesismrna metabolic processsnrna metabolic processvesicle-mediated transportreproductive processdigestive system processsignalingcell differentiationprotein catabolic processextracellular matrix organizationregulatory ncrna-mediated gene silencingtelomere organizationcell junction organizationwound healingribosome biogenesiscilium organizationanatomical structure developmentcell motilitynervous system processendocrine processprotein maturationtransmembrane transportnucleobase-containing small molecule metabolic processhepaticobiliary system processmembrane organizationprotein-containing complex assemblycell wall organization or biogenesisnitrogen cycle metabolic processprotein localization to plasma membranedefense response to other organismdetoxificationmeiotic nuclear divisionmitotic nuclear divisionmitochondrial gene expressioncarbohydrate derivative metabolic processother biological processall cellular componentnuclear chromosomeextracellular regionextracellular spacecell wallnucleusnuclear envelopenucleoplasmchromosomenucleolusmitochondrionlysosomeendosomevacuoleperoxisomeendoplasmic reticulumgolgi apparatuslipid dropletmicrotubule organizing centercytosolribosomecytoskeletonplasma membraneciliumplastidthylakoidexternal encapsulating structureextracellular matrixcytoplasmic vesicleorganelleother cellular component
Cell color indicative of number of GO terms
AspectTerm
Cellular Componentendoplasmic reticulum
Cellular ComponentSREBP-SCAP-Insig complex
Molecular Functionoxysterol binding
Biological Processcellular response to insulin stimulus
Biological Processcholesterol biosynthetic process
Biological ProcessSREBP signaling pathway
Biological ProcessSREBP-SCAP complex retention in endoplasmic reticulum

Keywords

Names & Taxonomy

Protein names

  • Recommended name
    Insulin-induced gene 2 protein
  • Short names
    INSIG-2

Gene names

    • Name
      INSIG2
    • ORF names
      RCJMB04_5j21

Organism names

  • Taxonomic identifier
  • Strains
    • CB
    • Red jungle fowl
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Archelosauria > Archosauria > Dinosauria > Saurischia > Theropoda > Coelurosauria > Aves > Neognathae > Galloanserae > Galliformes > Phasianidae > Phasianinae > Gallus

Accessions

  • Primary accession
    Q5F3W2
  • Secondary accessions
    • R4GK90

Proteomes

Organism-specific databases

Subcellular Location

Features

Showing features for topological domain, transmembrane.

TypeIDPosition(s)Description
Topological domain1-28Cytoplasmic
Transmembrane29-51Helical; Name=1
Topological domain52-70Lumenal
Transmembrane71-88Helical; Name=2
Topological domain89-103Cytoplasmic
Transmembrane104-126Helical; Name=3
Topological domain127-129Lumenal
Transmembrane130-148Helical; Name=4
Topological domain149-153Cytoplasmic
Transmembrane154-175Helical; Name=5
Topological domain176-189Lumenal
Transmembrane190-207Helical; Name=6
Topological domain208-225Cytoplasmic

Keywords

PTM/Processing

Features

Showing features for chain.

TypeIDPosition(s)Description
ChainPRO_00002868021-225Insulin-induced gene 2 protein

Proteomic databases

Expression

Gene expression databases

Interaction

Subunit

Interacts with SCAP; interaction is direct and only takes place in the presence of sterols; it prevents interaction between SCAP and the coat protein complex II (COPII). Associates with the SCAP-SREBP complex; association is mediated via its interaction with SCAP and only takes place in the presence of sterols.

Protein-protein interaction databases

Structure

Family & Domains

Features

Showing features for motif.

TypeIDPosition(s)Description
Motif219-225KxHxx

Domain

Binds oxysterols in a pocket within their transmembrane domains and interacts with SCAP via transmembrane domains 3 and 4.
The KxHxx motif mediates association with the coatomer complex.

Sequence similarities

Belongs to the INSIG family.

Keywords

Phylogenomic databases

Family and domain databases

Sequence & Isoform

Align isoforms (2)
  • Sequence status
    Complete

This entry describes 2 isoforms produced by Alternative splicing.

Q5F3W2-1

This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

  • Length
    225
  • Mass (Da)
    24,828
  • Last updated
    2020-08-12 v2
  • Checksum
    527D8FC990190236
MAENDAKPTLPKKSGPYISSVTSHGMNLVIRGIVLFFIGVFLALVLNLLQIQRNVTLFPPDVITSIFSSAWWVPPCCGTASAVIGLLYPCMDRHLGEPHKFKREWSSVMRCVAVFVGINHASAKVDFANNIQLSLTLAALSIGLWWTFDRSRSGFGLGVGIAFLATLVSQLLVYNGVYQYTSPDFLYVRSWLPCIFFAGGITMGNIGRQLAMYECKVIAEKSHED

Q5F3W2-2

  • Name
    2
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical
    • 50-116: QIQRNVTLFPPDVITSIFSSAWWVPPCCGTASAVIGLLYPCMDRHLGEPHKFKREWSSVMRCVAVFV → NAVCSGLCQ

Features

Showing features for sequence conflict, alternative sequence.

TypeIDPosition(s)Description
Sequence conflict24in Ref. 1; CAH65172
Alternative sequenceVSP_06067250-116in isoform 2
Sequence conflict186in Ref. 1; CAH65172

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AJ851538
EMBL· GenBank· DDBJ
CAH65172.1
EMBL· GenBank· DDBJ
mRNA
AC161466
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.

Genome annotation databases

Similar Proteins

Disclaimer

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