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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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CASTOR1
cytosolic arginine sensor for mTORC1 subunit 1
Chromosome 22 · 22q12.2
NCBI Gene: 652968Ensembl: ENSG00000239282.9HGNC: HGNC:34423UniProt: Q8WTX7
25PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
GATOR2 complexprotein bindingarginine bindingidentical protein bindingsarcoidosisneoplasmrheumatoid arthritisaortic aneurysm
✦AI Summary

CASTOR1 functions as a cytosolic arginine sensor that regulates mTORC1 signaling through the amino acid-sensing pathway 1. The protein forms homodimers or heterodimers with CASTOR2 and binds to the GATOR2 complex, inhibiting mTORC1 activity under arginine-depleted conditions 1. When arginine becomes available, it binds directly to CASTOR1 with a dissociation constant of ~30 μM, inducing conformational changes that disrupt the CASTOR1-GATOR2 interaction and allow mTORC1 activation 12. Structurally, CASTOR1 engages GATOR2 through interactions with MIOS WD40 β-propellers, with arginine binding causing conformational rearrangements at the ACT domain interface that trigger dissociation from GATOR2 34. CASTOR1 activity is also regulated post-translationally through AKT-mediated phosphorylation and RNF167-mediated ubiquitination, which promotes its degradation and constitutive mTORC1 activation in cancer cells 5. Clinically, CASTOR1 dysregulation contributes to breast cancer progression when degraded by RNF167, and its overexpression can modulate microglial polarization through mTOR pathway inhibition 56. CASTOR1 responds to low arginine levels, complementing CASTOR2's response to high arginine concentrations for fine-tuned mTORC1 regulation 4.

Sources cited
1
CASTOR1 functions as an arginine sensor, forms dimers, binds GATOR2, and has arginine dissociation constant of ~30 μM
PMID: 26972053
2
Arginine induces structural rearrangements in CASTOR1 that trigger dissociation from GATOR2
PMID: 40836086
3
CASTOR1 engages GATOR2 through MIOS WD40 β-propellers and arginine binding blocks this interaction
PMID: 40715445
4
CASTOR1 responds to low arginine levels and arginine binding causes conformational changes at ACT domain interface
PMID: 41506264
5
AKT phosphorylates CASTOR1 leading to RNF167-mediated ubiquitination and degradation, promoting cancer progression
PMID: 33594058
6
CASTOR1 overexpression modulates microglial polarization through mTOR pathway inhibition
PMID: 36454504
Disease Associationsⓘ20
sarcoidosisOpen Targets
0.19Weak
neoplasmOpen Targets
0.09Suggestive
rheumatoid arthritisOpen Targets
0.08Suggestive
aortic aneurysmOpen Targets
0.06Suggestive
immune system diseaseOpen Targets
0.05Suggestive
cancerOpen Targets
0.05Suggestive
breast cancerOpen Targets
0.04Suggestive
Abdominal Aortic AneurysmOpen Targets
0.04Suggestive
lung cancerOpen Targets
0.04Suggestive
coronary artery diseaseOpen Targets
0.04Suggestive
lung adenocarcinomaOpen Targets
0.03Suggestive
myocardial infarctionOpen Targets
0.03Suggestive
aneurysmOpen Targets
0.02Suggestive
atrial fibrillationOpen Targets
0.02Suggestive
non-small cell lung carcinomaOpen Targets
0.02Suggestive
Neoplasm of the lungOpen Targets
0.01Suggestive
cerebral palsyOpen Targets
0.01Suggestive
cardiovascular diseaseOpen Targets
0.00Suggestive
Miyoshi myopathyOpen Targets
0.00Suggestive
multiple myelomaOpen Targets
0.00Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
ZC2HC1AProtein interaction87%RHEBProtein interaction78%SEC13Protein interaction78%RRAGBProtein interaction77%RRAGAProtein interaction77%RRAGDProtein interaction77%
Tissue Expression6 tissues
Ovary
100%
Lung
67%
Liver
61%
Heart
34%
Brain
23%
Bone Marrow
13%
Gene Interaction Network
Click a node to explore
CASTOR1ZC2HC1ARHEBSEC13RRAGBRRAGARRAGD
PROTEIN STRUCTURE
Preparing viewer…
PDB5I2C · 1.80 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.91LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.60 [0.41–0.91]
RankingsWhere CASTOR1 stands among ~20K protein-coding genes
  • #12,952of 20,598
    Most Researched25
  • #8,226of 17,882
    Most Constrained (LOEUF)0.91
Genes detectedCASTOR1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Structure of the nutrient-sensing hub GATOR2.
PMID: 35831510
Nature · 2022
1.00
2
The CASTOR Proteins Are Arginine Sensors for the mTORC1 Pathway.
PMID: 26972053
Cell · 2016
0.90
3
RNF167 activates mTORC1 and promotes tumorigenesis by targeting CASTOR1 for ubiquitination and degradation.
PMID: 33594058
Nat Commun · 2021
0.80
4
Structural basis for the dynamic regulation of mTORC1 by amino acids.
PMID: 40836086
Nature · 2025
0.70
5
Structural basis for mTORC1 regulation by the CASTOR1-GATOR2 complex.
PMID: 40715445
Nat Struct Mol Biol · 2025
0.60