CASTOR1
entrez
652968
canonical
uniprot
Q8WTX7
canonical
ensembl
ENSG00000239282
resolver
ensp
ENSP00000384183
resolver
enst
ENST00000407689
resolver
genesymbol
CASTOR1
resolver
genesymbol_syn
GATSL3
resolver
hgnc
HGNC:34423
resolver
uniprot
O76052
resolver
uniprot
Q96ND9
resolver
uniprot
Q9UIE8
resolver
uniprot_entry
CAST1_HUMAN
resolver
uniprot_sec
O76052
resolver
uniprot_sec
Q96ND9
resolver
uniprot_sec
Q9UIE8
resolver
amino_acid_sequence
MELHILEHRVRVLSVARPGLWLYTHPLIKLLFLPRRSRCKFFSLTETPEDYTLMVDEEGFKELPPSEFLQVAEATWLVLNVSSHSGAAVQAAGVTKIARSVIAPLAEHHVSVLMLSTYQTDFILVREQDLSVVIHTLAQEFDIYREVGGEPVPVTRDDSSNGFPRTQHGPSPTVHPIQSPQNRFCVLTLDPETLPAIATTLIDVLFYSHSTPKEAASSSPEPSSITFFAFSLIEGYISIVMDAETQKKFPSDLLLTSSSGELWRMVRIGGQPLGFDECGIVAQIAGPLAAADISAYYISTFNFDHALVPEDGIGSVIEVLQRRQEGLAS
uniprot
proteins
function
FUNCTION: Functions as an intracellular arginine sensor within the amino acid-sensing branch of the TORC1 signaling pathway (PubMed:26972053, PubMed:27487210, PubMed:33594058). As a homodimer or a heterodimer with CASTOR2, binds and inhibits the GATOR subcomplex GATOR2 and thereby mTORC1 (PubMed:26972053, PubMed:27487210, PubMed:33594058). Binding of arginine to CASTOR1 allosterically disrupts the interaction of CASTOR1-containing dimers with GATOR2 which can in turn activate mTORC1 and the TORC1 signaling pathway (PubMed:26972053, PubMed:27487210, PubMed:33594058). {ECO:0000269|PubMed:26972053, ECO:0000269|PubMed:27487210, ECO:0000269|PubMed:33594058}.
uniprot
proteins
mass_dalton
36275
uniprot
proteins
mutagenesis
MUTAGEN 14; /note="S->A: Abolished phosphorylation by AKT1, leading to decreased interaction with RNF167 and subsequent ubiquitination."; /evidence="ECO:0000269|PubMed:33594058"; MUTAGEN 14; /note="S->D: Mimics phosphorylation, leading to promote interaction with RNF167 and subsequent ubiquitination."; /evidence="ECO:0000269|PubMed:33594058"; MUTAGEN 61; /note="K->R: In 3KR mutant; abolished ubiquitination by RNF167; when associated with R-96 and R-213."; /evidence="ECO:0000269|PubMed:33594058"; MUTAGEN 90; /note="Q->A: No effect on interaction with the GATOR2 complex."; /evidence="ECO:0000269|PubMed:27487210"; MUTAGEN 96; /note="K->A: No effect on interaction with the GATOR2 complex."; /evidence="ECO:0000269|PubMed:27487210"; MUTAGEN 96; /note="K->R: In 3KR mutant; abolished ubiquitination by RNF167; when associated with R-61 and R-213."; /evidence="ECO:0000269|PubMed:33594058"; MUTAGEN 99; /note="R->A: No effect on interaction with the GATOR2 complex."; /evidence="ECO:0000269|PubMed:27487210"; MUTAGEN 108..110; /note="HHV->QNI: Loss of arginine-binding. Constitutively interacts with the GATOR2 complex."; /evidence="ECO:0000269|PubMed:27487210"; MUTAGEN 111; /note="S->A: Loss of arginine-binding. Constitutively interacts with the GATOR2 complex. Constitutively inhibits the TORC1 signaling pathway."; /evidence="ECO:0000269|PubMed:27487210"; MUTAGEN 113; /note="L->F: No effect on interaction with the GATOR2 complex."; /evidence="ECO:0000269|PubMed:27487210"; MUTAGEN 118..119; /note="YQ->AA: No effect on arginine-binding. No effect on homodimerization. Loss of interaction with the GATOR2 complex which constitutively activates the TORC1 signaling pathway."; /evidence="ECO:0000269|PubMed:27487210"; MUTAGEN 121; /note="D->A: No effect on arginine-binding. No effect on homodimerization. Loss of interaction with the GATOR2 complex which constitutively activates the TORC1 signaling pathway."; /evidence="ECO:0000269|PubMed:27487210"; MUTAGEN 126; /note="R->A: Decreased arginine-binding. Constitutively interacts with the GATOR2 complex."; /evidence="ECO:0000269|PubMed:27487210"; MUTAGEN 175; /note="H->A: Decreased arginine-binding. Constitutively interacts with the GATOR2 complex."; /evidence="ECO:0000269|PubMed:27487210"; MUTAGEN 202; /note="I->E: No effect on arginine-binding. Loss of homodimerization. Decreased interaction with the GATOR2 complex which constitutively activates the TORC1 signaling pathway."; /evidence="ECO:0000269|PubMed:27487210"; MUTAGEN 207; /note="Y->S: No effect on arginine-binding. Loss of homodimerization. Decreased interaction with the GATOR2 complex which constitutively activates the TORC1 signaling pathway."; /evidence="ECO:0000269|PubMed:27487210"; MUTAGEN 213; /note="K->R: In 3KR mutant; abolished ubiquitination by RNF167; when associated with R-61 and R-96."; /evidence="ECO:0000269|PubMed:33594058"; MUTAGEN 261; /note="E->A: No effect on arginine-binding. No effect on homodimerization. Loss of interaction with the GATOR2 complex."; /evidence="ECO:0000269|PubMed:27487210"; MUTAGEN 264; /note="R->A: No effect on interaction with the GATOR2 complex."; /evidence="ECO:0000269|PubMed:27487210"; MUTAGEN 276; /note="D->A: Decreased arginine-binding. Constitutively interacts with the GATOR2 complex."; /evidence="ECO:0000269|PubMed:27487210"; MUTAGEN 277; /note="E->A: Decreased arginine-binding. Constitutively interacts with the GATOR2 complex."; /evidence="ECO:0000269|PubMed:27487210"; MUTAGEN 278; /note="C->A: Decreased arginine-binding. Constitutively interacts with the GATOR2 complex."; /evidence="ECO:0000269|PubMed:27487210"; MUTAGEN 280; /note="I->A: Loss of arginine-binding. Constitutively inhibits the TORC1 signaling pathway."; /evidence="ECO:0000269|PubMed:26972053"; MUTAGEN 292; /note="D->A: No effect on arginine-binding. No effect on homodimerization. Loss of interaction with the GATOR2 complex."; /evidence="ECO:0000269|PubMed:27487210"; MUTAGEN 302; /note="N->K: No effect on interaction with the GATOR2 complex."; /evidence="ECO:0000269|PubMed:27487210"; MUTAGEN 304; /note="D->A: Loss of arginine-binding. Constitutively interacts with the GATOR2 complex. Constitutively inhibits the TORC1 signaling pathway."; /evidence="ECO:0000269|PubMed:27487210
uniprot
proteins
post_translational_modification
PTM: Phosphorylation at Ser-14 by AKT1, promoting the interaction between CASTOR1 and RNF167. {ECO:0000269|PubMed:33594058}.; PTM: Ubiquitinated by RNF167 via 'Lys-29'-polyubiquitination, leading to its degradation, releasing the GATOR2 complex (PubMed:33594058). Ubiquitination by RNF167 is promoted by phosphorylation at Ser-14 by AKT1 (PubMed:33594058). {ECO:0000269|PubMed:33594058}.
uniprot
proteins
protein_family
GATS family
uniprot
proteins
pubmed
10591208
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15461802
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
26972053
uniprot
proteins
pubmed
27487210
uniprot
proteins
pubmed
30956113
uniprot
proteins
pubmed
33594058
uniprot
proteins
sequence_length
329
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:26972053}.
uniprot
proteins