Q5F3W2 · INSI2_CHICK
- ProteinInsulin-induced gene 2 protein
- GeneINSIG2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids225 (go to sequence)
- Protein existenceEvidence at transcript level
- Annotation score3/5
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.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Site | 115 | Required for the recognition of 25-hydroxycholesterol | ||||
Sequence: F |
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Aspect | Term | |
---|---|---|
Cellular Component | endoplasmic reticulum | |
Cellular Component | SREBP-SCAP-Insig complex | |
Molecular Function | oxysterol binding | |
Biological Process | cellular response to insulin stimulus | |
Biological Process | cholesterol biosynthetic process | |
Biological Process | SREBP signaling pathway | |
Biological Process | SREBP-SCAP complex retention in endoplasmic reticulum |
Keywords
- Biological process
- Ligand
Names & Taxonomy
Protein names
- Recommended nameInsulin-induced gene 2 protein
- Short namesINSIG-2
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Archelosauria > Archosauria > Dinosauria > Saurischia > Theropoda > Coelurosauria > Aves > Neognathae > Galloanserae > Galliformes > Phasianidae > Phasianinae > Gallus
Accessions
- Primary accessionQ5F3W2
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Endoplasmic reticulum membrane ; Multi-pass membrane protein
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-28 | Cytoplasmic | ||||
Sequence: MAENDAKPTLPKKSGPYISSVTSHGMNL | ||||||
Transmembrane | 29-51 | Helical; Name=1 | ||||
Sequence: VIRGIVLFFIGVFLALVLNLLQI | ||||||
Topological domain | 52-70 | Lumenal | ||||
Sequence: QRNVTLFPPDVITSIFSSA | ||||||
Transmembrane | 71-88 | Helical; Name=2 | ||||
Sequence: WWVPPCCGTASAVIGLLY | ||||||
Topological domain | 89-103 | Cytoplasmic | ||||
Sequence: PCMDRHLGEPHKFKR | ||||||
Transmembrane | 104-126 | Helical; Name=3 | ||||
Sequence: EWSSVMRCVAVFVGINHASAKVD | ||||||
Topological domain | 127-129 | Lumenal | ||||
Sequence: FAN | ||||||
Transmembrane | 130-148 | Helical; Name=4 | ||||
Sequence: NIQLSLTLAALSIGLWWTF | ||||||
Topological domain | 149-153 | Cytoplasmic | ||||
Sequence: DRSRS | ||||||
Transmembrane | 154-175 | Helical; Name=5 | ||||
Sequence: GFGLGVGIAFLATLVSQLLVYN | ||||||
Topological domain | 176-189 | Lumenal | ||||
Sequence: GVYQYTSPDFLYVR | ||||||
Transmembrane | 190-207 | Helical; Name=6 | ||||
Sequence: SWLPCIFFAGGITMGNIG | ||||||
Topological domain | 208-225 | Cytoplasmic | ||||
Sequence: RQLAMYECKVIAEKSHED |
Keywords
- Cellular component
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000286802 | 1-225 | Insulin-induced gene 2 protein | |||
Sequence: MAENDAKPTLPKKSGPYISSVTSHGMNLVIRGIVLFFIGVFLALVLNLLQIQRNVTLFPPDVITSIFSSAWWVPPCCGTASAVIGLLYPCMDRHLGEPHKFKREWSSVMRCVAVFVGINHASAKVDFANNIQLSLTLAALSIGLWWTFDRSRSGFGLGVGIAFLATLVSQLLVYNGVYQYTSPDFLYVRSWLPCIFFAGGITMGNIGRQLAMYECKVIAEKSHED |
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.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Motif | 219-225 | KxHxx | ||||
Sequence: AEKSHED |
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
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
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.
- Name1
- Length225
- Mass (Da)24,828
- Last updated2020-08-12 v2
- Checksum527D8FC990190236
Q5F3W2-2
- Name2
- Differences from canonical
- 50-116: QIQRNVTLFPPDVITSIFSSAWWVPPCCGTASAVIGLLYPCMDRHLGEPHKFKREWSSVMRCVAVFV → NAVCSGLCQ
Features
Showing features for sequence conflict, alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 24 | in Ref. 1; CAH65172 | ||||
Sequence: H → R | ||||||
Alternative sequence | VSP_060672 | 50-116 | in isoform 2 | |||
Sequence: QIQRNVTLFPPDVITSIFSSAWWVPPCCGTASAVIGLLYPCMDRHLGEPHKFKREWSSVMRCVAVFV → NAVCSGLCQ | ||||||
Sequence conflict | 186 | in Ref. 1; CAH65172 | ||||
Sequence: L → I |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AJ851538 EMBL· GenBank· DDBJ | CAH65172.1 EMBL· GenBank· DDBJ | mRNA | ||
AC161466 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. |