INSIG1
Insulin-induced gene 1 protein
Also known as: CL-6, INSI1_HUMAN, MGC1405
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- O15503
- Gene
- INSIG1
- Ensembl
- ENSG00000186480
- Chromosome
- 7
- Canonical length
- 277 aa
- Protein class
- Plasma proteins, Predicted membrane proteins, Transporters
- Subcellular location
- Vesicles
OverviewNCBI 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]
Canonical amino-acid sequenceUniProt
277 residues, UniProt reviewed canonical sequence.
>O15503|INSIG1
1 MPRLHDHFWS CSCAHSARRR GPPRASAAGL AAKVGEMINV SVSGPSLLAA HGAPDADPAP
61 RGRSAAMSGP EPGSPYPNTW HHRLLQRSLV LFSVGVVLAL VLNLLQIQRN VTLFPEEVIA
121 TIFSSAWWVP PCCGTAAAVV GLLYPCIDSH LGEPHKFKRE WASVMRCIAV FVGINHASAK
181 LDFANNVQLS LTLAALSLGL WWTFDRSRSG LGLGITIAFL ATLITQFLVY NGVYQYTSPD
241 FLYIRSWLPC IFFSGGVTVG NIGRQLAMGV PEKPHSDLocalizationUniProt · AlphaFold · HPA
Whether an antibody against INSIG1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Other membrane
- Secreted
- No
- Transmembrane segments
- 6
- Mean surface accessibility (rSASA)
- 0.45
- Highest tissue expression
- 527 nTPM
Expression across tissuesHPA
Tissue
- liver: 527 nTPM
- pancreas: 105 nTPM
- choroid plexus: 99 nTPM
- adipose tissue: 74 nTPM
- salivary gland: 67 nTPM
- spinal cord: 63 nTPM
Single-cell type
- cdc: 1,591 nCPM
- hepatocytes: 687 nCPM
- epididymal principal cells: 536 nCPM
- parietal cells: 506 nCPM
- monocytes: 476 nCPM
- esophageal apical cells: 414 nCPM
Immune cell
- non-classical monocyte: 504 nTPM
- intermediate monocyte: 273 nTPM
- total PBMC: 85 nTPM
- myeloid DC: 79 nTPM
- T-reg: 77 nTPM
- neutrophil: 63 nTPM
Brain region
- white matter: 188 nTPM
- pons: 139 nTPM
- medulla oblongata: 138 nTPM
- choroid plexus: 133 nTPM
- midbrain: 119 nTPM
- cerebral cortex: 115 nTPM
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 1.12
- gnomAD pLI
- 0
- gnomAD missense Z
- 1.9
- DepMap mean gene effect
- 0.03
- DepMap dependency class
- selective
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 6% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- cellular response to insulin stimulus
- cellular response to sterol
- cholesterol biosynthetic process
- cholesterol homeostasis
- cranial suture morphogenesis
- inner ear morphogenesis
- middle ear morphogenesis
- negative regulation of cholesterol biosynthetic process
- negative regulation of fat cell differentiation
- negative regulation of fatty acid biosynthetic process
- roof of mouth development
- SREBP signaling pathway
- SREBP-SCAP complex retention in endoplasmic reticulum
- triglyceride metabolic process
- negative regulation of cargo loading into COPII-coated vesicle
- negative regulation of protein exit from endoplasmic reticulum
Molecular functions
Cellular components
Protein domainsUniProt · Pfam · InterPro
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of INSIG1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads INSIG1 as an antibody target. Whether an autoantibody or antibody against INSIG1 could matter depends on whether native INSIG1 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
INSIG1 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.
Annotation status
The present source text does not explicitly label INSIG1 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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