CAST2_HUMAN
ID CAST2_HUMAN Reviewed; 329 AA.
AC A6NHX0; A6NNH0; B9EJH9;
DT 10-JUN-2008, integrated into UniProtKB/Swiss-Prot.
DT 10-JUN-2008, sequence version 3.
DT 03-AUG-2022, entry version 102.
DE RecName: Full=Cytosolic arginine sensor for mTORC1 subunit 2 {ECO:0000312|HGNC:HGNC:37073};
DE AltName: Full=Cellular arginine sensor for mTORC1 protein 2 {ECO:0000305|PubMed:26972053};
DE AltName: Full=GATS-like protein 2 {ECO:0000305};
GN Name=CASTOR2 {ECO:0000303|PubMed:26972053, ECO:0000312|HGNC:HGNC:37073};
GN Synonyms=GATSL1 {ECO:0000312|HGNC:HGNC:37073},
GN GATSL2 {ECO:0000312|HGNC:HGNC:37073};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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).
RN [3]
RP FUNCTION, INTERACTION WITH GATOR2 COMPLEX, OLIGOMERIZATION, SUBCELLULAR
RP LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=26972053; DOI=10.1016/j.cell.2016.02.035;
RA Chantranupong L., Scaria S.M., Saxton R.A., Gygi M.P., Shen K., Wyant G.A.,
RA Wang T., Harper J.W., Gygi S.P., Sabatini D.M.;
RT "The CASTOR proteins are arginine sensors for the mTORC1 pathway.";
RL Cell 165:153-164(2016).
CC -!- FUNCTION: Functions as a negative regulator of the TORC1 signaling
CC pathway through the GATOR complex. As part of homodimers or
CC heterodimers with CASTOR1, directly binds and inhibits the GATOR
CC subcomplex GATOR2 and thereby mTORC1. Does not directly bind arginine,
CC but binding of arginine to CASTOR1 disrupts the interaction of CASTOR2-
CC containing heterodimers with GATOR2 which can in turn activate mTORC1
CC and the TORC1 signaling pathway. {ECO:0000269|PubMed:26972053}.
CC -!- SUBUNIT: Forms homodimers and heterodimers with CASTOR1
CC (PubMed:26972053). Interacts with the GATOR2 complex which is composed
CC of MIOS, SEC13, SEH1L, WDR24 and WDR59; the interaction is not
CC regulated by arginine (PubMed:26972053). {ECO:0000269|PubMed:26972053}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:26972053}.
CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000303|PubMed:26972053}.
CC -!- SIMILARITY: Belongs to the GATS family. {ECO:0000305}.
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DR EMBL; AC245150; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC147030; AAI47031.1; -; mRNA.
DR EMBL; BC147031; AAI47032.1; -; mRNA.
DR EMBL; BC150658; AAI50659.1; -; mRNA.
DR CCDS; CCDS75620.1; -.
DR RefSeq; NP_001138536.1; NM_001145064.2.
DR AlphaFoldDB; A6NHX0; -.
DR SMR; A6NHX0; -.
DR BioGRID; 609839; 12.
DR DIP; DIP-62097N; -.
DR IntAct; A6NHX0; 2.
DR STRING; 9606.ENSP00000484732; -.
DR iPTMnet; A6NHX0; -.
DR PhosphoSitePlus; A6NHX0; -.
DR BioMuta; CASTOR2; -.
DR EPD; A6NHX0; -.
DR jPOST; A6NHX0; -.
DR MassIVE; A6NHX0; -.
DR MaxQB; A6NHX0; -.
DR PaxDb; A6NHX0; -.
DR PeptideAtlas; A6NHX0; -.
DR PRIDE; A6NHX0; -.
DR ProteomicsDB; 1231; -.
DR Antibodypedia; 74738; 32 antibodies from 7 providers.
DR DNASU; 729438; -.
DR Ensembl; ENST00000616305.2; ENSP00000484732.1; ENSG00000274070.2.
DR GeneID; 729438; -.
DR KEGG; hsa:729438; -.
DR MANE-Select; ENST00000616305.2; ENSP00000484732.1; NM_001145064.3; NP_001138536.1.
DR UCSC; uc003ucg.4; human.
DR CTD; 729438; -.
DR DisGeNET; 729438; -.
DR GeneCards; CASTOR2; -.
DR HGNC; HGNC:37073; CASTOR2.
DR HPA; ENSG00000274070; Group enriched (brain, skeletal muscle, tongue).
DR MIM; 617033; gene.
DR neXtProt; NX_A6NHX0; -.
DR OpenTargets; ENSG00000274070; -.
DR PharmGKB; PA164720237; -.
DR VEuPathDB; HostDB:ENSG00000274070; -.
DR eggNOG; ENOG502QV83; Eukaryota.
DR GeneTree; ENSGT00390000006208; -.
DR HOGENOM; CLU_057799_0_0_1; -.
DR InParanoid; A6NHX0; -.
DR OMA; STHIRFF; -.
DR OrthoDB; 1166424at2759; -.
DR PhylomeDB; A6NHX0; -.
DR TreeFam; TF331648; -.
DR PathwayCommons; A6NHX0; -.
DR Reactome; R-HSA-9639288; Amino acids regulate mTORC1.
DR BioGRID-ORCS; 729438; 17 hits in 982 CRISPR screens.
DR ChiTaRS; GATSL2; human.
DR GenomeRNAi; 729438; -.
DR Pharos; A6NHX0; Tbio.
DR PRO; PR:A6NHX0; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; A6NHX0; protein.
DR Bgee; ENSG00000274070; Expressed in tibialis anterior and 189 other tissues.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IDA:UniProtKB.
DR GO; GO:1903577; P:cellular response to L-arginine; IBA:GO_Central.
DR GO; GO:1904262; P:negative regulation of TORC1 signaling; IMP:UniProtKB.
DR GO; GO:1902531; P:regulation of intracellular signal transduction; IBA:GO_Central.
DR InterPro; IPR045865; ACT-like_dom_sf.
DR InterPro; IPR040778; CASTOR1_N.
DR InterPro; IPR027795; CASTOR_ACT_dom.
DR InterPro; IPR026249; CASTOR_fam.
DR Pfam; PF13840; ACT_7; 2.
DR Pfam; PF18700; Castor1_N; 1.
DR PRINTS; PR02078; GATSLIKEFMLY.
DR SUPFAM; SSF55021; SSF55021; 2.
PE 1: Evidence at protein level;
KW Cytoplasm; Reference proteome.
FT CHAIN 1..329
FT /note="Cytosolic arginine sensor for mTORC1 subunit 2"
FT /id="PRO_0000341304"
FT DOMAIN 72..140
FT /note="ACT 1"
FT DOMAIN 262..322
FT /note="ACT 2"
SQ SEQUENCE 329 AA; 36056 MW; BC86CEFC0FBC21B2 CRC64;
MELHILEHRL QVASVAKESI PLFTYGLIKL AFLSSKTRCK FFSLTETPED YTIIVDEEGF
LELPSSEHLS VADATWLALN VVSGGGSFSS SQPIGVTKIA KSVIAPLADQ NISVFMLSTY
QTDFILVRER DLPFVTHTLS SEFTILRVVN GETVAAENLG ITNGFVKPKL VQRPVIHPLS
SPSNRFCVTS LDPDTLPAVA TLLMDVMFYS NGVKDPMATG DDCGHIRFFS FSLIEGYISL
VMDVQTQQRF PSNLLFTSAS GELWKMVRIG GQPLGFDECG IVAQISEPLA AADIPAYYIS
TFKFDHALVP EENINGVISA LKVSQAEKH
