CAST1_MOUSE
ID CAST1_MOUSE Reviewed; 331 AA.
AC Q9CWQ8; Q29R56;
DT 02-SEP-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 120.
DE RecName: Full=Cytosolic arginine sensor for mTORC1 subunit 1 {ECO:0000250|UniProtKB:Q8WTX7};
DE AltName: Full=GATS-like protein 3 {ECO:0000305};
GN Name=Castor1 {ECO:0000250|UniProtKB:Q8WTX7};
GN Synonyms=Gatsl3 {ECO:0000312|MGI:MGI:1919212};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Mammary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
CC -!- FUNCTION: Functions as an intracellular arginine sensor within the
CC amino acid-sensing branch of the TORC1 signaling pathway. As a
CC homodimer or a heterodimer with CASTOR2, binds and inhibits the GATOR
CC subcomplex GATOR2 and thereby mTORC1. Binding of arginine to CASTOR1
CC allosterically disrupts the interaction of CASTOR1-containing dimers
CC with GATOR2 which can in turn activate mTORC1 and the TORC1 signaling
CC pathway. {ECO:0000250|UniProtKB:Q8WTX7}.
CC -!- SUBUNIT: Forms homodimers and heterodimers with CASTOR2 (By
CC similarity). Interacts with the GATOR2 complex which is composed of
CC MIOS, SEC13, SEH1L, WDR24 and WDR59; the interaction is negatively
CC regulated by arginine (By similarity). Interacts with TM4SF5; the
CC interaction is positively regulated by leucine and is negatively
CC regulated by arginine (By similarity). {ECO:0000250|UniProtKB:Q8WTX7}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:Q8WTX7}.
CC -!- DOMAIN: Based on x-ray crystallography data, the protein would be
CC constituted of 4 tandem ACT domains instead of the 2 predicted from the
CC sequence. {ECO:0000250|UniProtKB:Q8WTX7}.
CC -!- PTM: Phosphorylation at Ser-14 by AKT1, promoting the interaction
CC between CASTOR1 and RNF167. {ECO:0000250|UniProtKB:Q8WTX7}.
CC -!- PTM: Ubiquitinated by RNF167 via 'Lys-29'-polyubiquitination, leading
CC to its degradation, releasing the GATOR2 complex. Ubiquitination by
CC RNF167 is promoted by phosphorylation at Ser-14 by AKT1.
CC {ECO:0000250|UniProtKB:Q8WTX7}.
CC -!- SIMILARITY: Belongs to the GATS family. {ECO:0000305}.
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DR EMBL; AK010455; BAB26953.1; -; mRNA.
DR EMBL; AL807825; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC039988; AAH39988.1; -; mRNA.
DR CCDS; CCDS24381.1; -.
DR RefSeq; NP_082298.1; NM_028022.1.
DR AlphaFoldDB; Q9CWQ8; -.
DR SMR; Q9CWQ8; -.
DR STRING; 10090.ENSMUSP00000020699; -.
DR PhosphoSitePlus; Q9CWQ8; -.
DR EPD; Q9CWQ8; -.
DR MaxQB; Q9CWQ8; -.
DR PaxDb; Q9CWQ8; -.
DR PeptideAtlas; Q9CWQ8; -.
DR PRIDE; Q9CWQ8; -.
DR ProteomicsDB; 265442; -.
DR Antibodypedia; 54095; 18 antibodies from 10 providers.
DR Ensembl; ENSMUST00000020699; ENSMUSP00000020699; ENSMUSG00000020424.
DR GeneID; 71962; -.
DR KEGG; mmu:71962; -.
DR UCSC; uc007hur.1; mouse.
DR CTD; 652968; -.
DR MGI; MGI:1919212; Castor1.
DR VEuPathDB; HostDB:ENSMUSG00000020424; -.
DR eggNOG; ENOG502QV83; Eukaryota.
DR GeneTree; ENSGT00390000006208; -.
DR HOGENOM; CLU_057799_0_0_1; -.
DR InParanoid; Q9CWQ8; -.
DR OMA; QGLWLYT; -.
DR OrthoDB; 1166424at2759; -.
DR PhylomeDB; Q9CWQ8; -.
DR TreeFam; TF331648; -.
DR Reactome; R-MMU-9639288; Amino acids regulate mTORC1.
DR BioGRID-ORCS; 71962; 4 hits in 73 CRISPR screens.
DR PRO; PR:Q9CWQ8; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q9CWQ8; protein.
DR Bgee; ENSMUSG00000020424; Expressed in ectoplacental cone and 191 other tissues.
DR Genevisible; Q9CWQ8; MM.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0061700; C:GATOR2 complex; ISO:MGI.
DR GO; GO:0034618; F:arginine binding; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0140311; F:protein sequestering activity; ISS:UniProtKB.
DR GO; GO:1903577; P:cellular response to L-arginine; ISS:UniProtKB.
DR GO; GO:1904262; P:negative regulation of TORC1 signaling; ISS:UniProtKB.
DR GO; GO:1902531; P:regulation of intracellular signal transduction; IBA:GO_Central.
DR InterPro; IPR045865; ACT-like_dom_sf.
DR InterPro; IPR030415; CASTOR1.
DR InterPro; IPR040778; CASTOR1_N.
DR InterPro; IPR027795; CASTOR_ACT_dom.
DR InterPro; IPR026249; CASTOR_fam.
DR PANTHER; PTHR31131:SF3; PTHR31131:SF3; 1.
DR Pfam; PF13840; ACT_7; 2.
DR Pfam; PF18700; Castor1_N; 1.
DR PRINTS; PR02078; GATSLIKEFMLY.
DR SUPFAM; SSF55021; SSF55021; 2.
PE 2: Evidence at transcript level;
KW Cytoplasm; Phosphoprotein; Reference proteome; Ubl conjugation.
FT CHAIN 1..331
FT /note="Cytosolic arginine sensor for mTORC1 subunit 1"
FT /id="PRO_0000348591"
FT DOMAIN 72..137
FT /note="ACT 1"
FT DOMAIN 259..320
FT /note="ACT 2"
FT BINDING 110..111
FT /ligand="L-arginine"
FT /ligand_id="ChEBI:CHEBI:32682"
FT /evidence="ECO:0000250|UniProtKB:Q8WTX7"
FT BINDING 273
FT /ligand="L-arginine"
FT /ligand_id="ChEBI:CHEBI:32682"
FT /evidence="ECO:0000250|UniProtKB:Q8WTX7"
FT BINDING 279..280
FT /ligand="L-arginine"
FT /ligand_id="ChEBI:CHEBI:32682"
FT /evidence="ECO:0000250|UniProtKB:Q8WTX7"
FT BINDING 299..303
FT /ligand="L-arginine"
FT /ligand_id="ChEBI:CHEBI:32682"
FT /evidence="ECO:0000250|UniProtKB:Q8WTX7"
FT MOD_RES 14
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8WTX7"
SQ SEQUENCE 331 AA; 36575 MW; FFD5008E87C545EE CRC64;
MELHILEHRV RVLSIARPGL WLYTHPLIKL LFLPCRSRCK FFSLTETPED YTLMVDEEGF
KELPPSEFLQ VAEATWLVMN VSHSGSVVQA AGVTKIARSV IAPLAEHHVS VLMLSTYQTD
FILVREQDLS VVIHTLAQEF QIYREVGGEP VPVTGDDSSN GFPQIQHGPS PTVHPIQSPQ
NRFCVLTLDP ETLPAVATTL IDVLFYSHSV PKEAASGGPE STSIPFFAFS LIEGYISIVM
DAEIQRKFPS DLLLTSSSGE LWRMVRIGGQ PLGFDECGIV AQIAGPLAAV DISAYYISTF
NFDHALVPED EIGCVIDILQ RRQESQASKD P
