CAST1_HUMAN
ID CAST1_HUMAN Reviewed; 329 AA.
AC Q8WTX7; O76052; Q96ND9; Q9UIE8;
DT 02-SEP-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 1.
DT 03-AUG-2022, entry version 128.
DE RecName: Full=Cytosolic arginine sensor for mTORC1 subunit 1 {ECO:0000303|PubMed:26972053};
DE AltName: Full=Cellular arginine sensor for mTORC1 protein 1 {ECO:0000305|PubMed:26972053};
DE AltName: Full=GATS-like protein 3 {ECO:0000305};
GN Name=CASTOR1 {ECO:0000303|PubMed:26972053, ECO:0000312|HGNC:HGNC:34423};
GN Synonyms=GATSL3 {ECO:0000312|HGNC:HGNC:34423};
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 MRNA].
RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84;
RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A.,
RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J.,
RA Beare D.M., Dunham I.;
RT "A genome annotation-driven approach to cloning the human ORFeome.";
RL Genome Biol. 5:R84.1-R84.11(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10591208; DOI=10.1038/990031;
RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M.,
RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C.,
RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E.,
RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C.,
RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G.,
RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V.,
RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M.,
RA Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E.,
RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F.,
RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M.,
RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A.,
RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D.,
RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y.,
RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S.,
RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E.,
RA Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A.,
RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L.,
RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P.,
RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P.,
RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q.,
RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J.,
RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J.,
RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D.,
RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T.,
RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P.,
RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K.,
RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L.,
RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J.,
RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E.,
RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P.,
RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y.,
RA Wright H.;
RT "The DNA sequence of human chromosome 22.";
RL Nature 402:489-495(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Uterus;
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 [6]
RP FUNCTION, INTERACTION WITH GATOR2 COMPLEX, SUBUNIT, SUBCELLULAR LOCATION,
RP TISSUE SPECIFICITY, AND MUTAGENESIS OF ILE-280.
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).
RN [7]
RP INTERACTION WITH TM4SF5.
RX PubMed=30956113; DOI=10.1016/j.cmet.2019.03.005;
RA Jung J.W., Macalino S.J.Y., Cui M., Kim J.E., Kim H.J., Song D.G.,
RA Nam S.H., Kim S., Choi S., Lee J.W.;
RT "Transmembrane 4 L six family member 5 senses arginine for mTORC1
RT signaling.";
RL Cell Metab. 29:1306-1319(2019).
RN [8]
RP FUNCTION, UBIQUITINATION, PHOSPHORYLATION AT SER-14, AND MUTAGENESIS OF
RP SER-14; LYS-61; LYS-96 AND LYS-213.
RX PubMed=33594058; DOI=10.1038/s41467-021-21206-3;
RA Li T., Wang X., Ju E., da Silva S.R., Chen L., Zhang X., Wei S., Gao S.J.;
RT "RNF167 activates mTORC1 and promotes tumorigenesis by targeting CASTOR1
RT for ubiquitination and degradation.";
RL Nat. Commun. 12:1055-1055(2021).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) IN COMPLEX WITH ARGININE, FUNCTION,
RP SUBUNIT, MUTAGENESIS OF GLN-90; LYS-96; ARG-99; 108-HIS--VAL-110; SER-111;
RP LEU-113; 118-TYR-GLN-119; ASP-121; ARG-126; HIS-175; ILE-202; TYR-207;
RP GLU-261; ARG-264; ASP-276; GLU-277; CYS-278; ASP-292; ASN-302 AND ASP-304,
RP AND DOMAIN.
RX PubMed=27487210; DOI=10.1038/nature19079;
RA Saxton R.A., Chantranupong L., Knockenhauer K.E., Schwartz T.U.,
RA Sabatini D.M.;
RT "Mechanism of arginine sensing by CASTOR1 upstream of mTORC1.";
RL Nature 536:229-233(2016).
CC -!- FUNCTION: Functions as an intracellular arginine sensor within the
CC amino acid-sensing branch of the TORC1 signaling pathway
CC (PubMed:26972053, PubMed:27487210, PubMed:33594058). As a homodimer or
CC a heterodimer with CASTOR2, binds and inhibits the GATOR subcomplex
CC GATOR2 and thereby mTORC1 (PubMed:26972053, PubMed:27487210,
CC PubMed:33594058). Binding of arginine to CASTOR1 allosterically
CC disrupts the interaction of CASTOR1-containing dimers with GATOR2 which
CC can in turn activate mTORC1 and the TORC1 signaling pathway
CC (PubMed:26972053, PubMed:27487210, PubMed:33594058).
CC {ECO:0000269|PubMed:26972053, ECO:0000269|PubMed:27487210,
CC ECO:0000269|PubMed:33594058}.
CC -!- SUBUNIT: Forms homodimers and heterodimers with CASTOR2
CC (PubMed:26972053, PubMed:27487210). Interacts with the GATOR2 complex
CC which is composed of MIOS, SEC13, SEH1L, WDR24 and WDR59; the
CC interaction is negatively regulated by arginine (PubMed:26972053,
CC PubMed:27487210, PubMed:33594058). Interacts with TM4SF5; the
CC interaction is positively regulated by leucine and is negatively
CC regulated by arginine (PubMed:30956113). {ECO:0000269|PubMed:26972053,
CC ECO:0000269|PubMed:27487210, ECO:0000269|PubMed:30956113,
CC ECO:0000269|PubMed:33594058}.
CC -!- INTERACTION:
CC Q8WTX7; Q8WTX7: CASTOR1; NbExp=4; IntAct=EBI-10276168, EBI-10276168;
CC Q8WTX7; Q16401: PSMD5; NbExp=3; IntAct=EBI-10276168, EBI-752143;
CC Q8WTX7; Q96EY4: TMA16; NbExp=3; IntAct=EBI-10276168, EBI-1045338;
CC Q8WTX7; Q96GY0: ZC2HC1A; NbExp=12; IntAct=EBI-10276168, EBI-5458880;
CC Q8WTX7; Q5TFG8: ZC2HC1B; NbExp=3; IntAct=EBI-10276168, EBI-12275374;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:26972053}.
CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000303|PubMed:26972053}.
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:0000303|PubMed:27487210}.
CC -!- PTM: Phosphorylation at Ser-14 by AKT1, promoting the interaction
CC between CASTOR1 and RNF167. {ECO:0000269|PubMed:33594058}.
CC -!- PTM: Ubiquitinated by RNF167 via 'Lys-29'-polyubiquitination, leading
CC to its degradation, releasing the GATOR2 complex (PubMed:33594058).
CC Ubiquitination by RNF167 is promoted by phosphorylation at Ser-14 by
CC AKT1 (PubMed:33594058). {ECO:0000269|PubMed:33594058}.
CC -!- SIMILARITY: Belongs to the GATS family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC23432.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=AAC23433.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=BAB70963.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305};
CC Sequence=EAW59868.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; CR456449; CAG30335.1; -; mRNA.
DR EMBL; AK055587; BAB70963.1; ALT_SEQ; mRNA.
DR EMBL; AC004997; AAC23432.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AC004997; AAC23433.1; ALT_SEQ; Genomic_DNA.
DR EMBL; CH471095; EAW59868.1; ALT_SEQ; Genomic_DNA.
DR EMBL; CH471095; EAW59870.1; -; Genomic_DNA.
DR EMBL; BC021927; AAH21927.1; -; mRNA.
DR CCDS; CCDS43001.1; -.
DR RefSeq; NP_001032755.1; NM_001037666.2.
DR PDB; 5GS9; X-ray; 2.50 A; A/B/C/D=1-329.
DR PDB; 5GT7; X-ray; 2.05 A; A/B/C/D=1-323.
DR PDB; 5GT8; X-ray; 2.80 A; A/B/C/D=1-329.
DR PDB; 5GV2; X-ray; 2.06 A; A/C=1-329.
DR PDB; 5I2C; X-ray; 1.80 A; A/B/C/D=1-329.
DR PDBsum; 5GS9; -.
DR PDBsum; 5GT7; -.
DR PDBsum; 5GT8; -.
DR PDBsum; 5GV2; -.
DR PDBsum; 5I2C; -.
DR AlphaFoldDB; Q8WTX7; -.
DR SMR; Q8WTX7; -.
DR BioGRID; 535021; 19.
DR DIP; DIP-62096N; -.
DR IntAct; Q8WTX7; 8.
DR STRING; 9606.ENSP00000384183; -.
DR BindingDB; Q8WTX7; -.
DR iPTMnet; Q8WTX7; -.
DR PhosphoSitePlus; Q8WTX7; -.
DR BioMuta; CASTOR1; -.
DR DMDM; 74730646; -.
DR EPD; Q8WTX7; -.
DR jPOST; Q8WTX7; -.
DR MassIVE; Q8WTX7; -.
DR MaxQB; Q8WTX7; -.
DR PaxDb; Q8WTX7; -.
DR PeptideAtlas; Q8WTX7; -.
DR PRIDE; Q8WTX7; -.
DR ProteomicsDB; 74612; -.
DR TopDownProteomics; Q8WTX7; -.
DR Antibodypedia; 54095; 18 antibodies from 10 providers.
DR DNASU; 652968; -.
DR Ensembl; ENST00000407689.8; ENSP00000384183.4; ENSG00000239282.8.
DR GeneID; 652968; -.
DR KEGG; hsa:652968; -.
DR MANE-Select; ENST00000407689.8; ENSP00000384183.4; NM_001037666.3; NP_001032755.1.
DR UCSC; uc003ahd.4; human.
DR CTD; 652968; -.
DR DisGeNET; 652968; -.
DR GeneCards; CASTOR1; -.
DR HGNC; HGNC:34423; CASTOR1.
DR HPA; ENSG00000239282; Tissue enhanced (esophagus).
DR MIM; 617034; gene.
DR neXtProt; NX_Q8WTX7; -.
DR OpenTargets; ENSG00000239282; -.
DR PharmGKB; PA164720260; -.
DR VEuPathDB; HostDB:ENSG00000239282; -.
DR eggNOG; ENOG502QV83; Eukaryota.
DR GeneTree; ENSGT00390000006208; -.
DR InParanoid; Q8WTX7; -.
DR OMA; QGLWLYT; -.
DR OrthoDB; 1166424at2759; -.
DR PhylomeDB; Q8WTX7; -.
DR TreeFam; TF331648; -.
DR PathwayCommons; Q8WTX7; -.
DR Reactome; R-HSA-9639288; Amino acids regulate mTORC1.
DR SignaLink; Q8WTX7; -.
DR BioGRID-ORCS; 652968; 16 hits in 1072 CRISPR screens.
DR ChiTaRS; GATSL3; human.
DR GenomeRNAi; 652968; -.
DR Pharos; Q8WTX7; Tbio.
DR PRO; PR:Q8WTX7; -.
DR Proteomes; UP000005640; Chromosome 22.
DR RNAct; Q8WTX7; protein.
DR Bgee; ENSG00000239282; Expressed in lower esophagus mucosa and 93 other tissues.
DR ExpressionAtlas; Q8WTX7; baseline and differential.
DR Genevisible; Q8WTX7; HS.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0034618; F:arginine binding; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IDA:UniProtKB.
DR GO; GO:0140311; F:protein sequestering activity; IDA:UniProtKB.
DR GO; GO:1903577; P:cellular response to L-arginine; IDA:UniProtKB.
DR GO; GO:1904262; P:negative regulation of TORC1 signaling; IDA: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 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Phosphoprotein; Reference proteome;
KW Ubl conjugation.
FT CHAIN 1..329
FT /note="Cytosolic arginine sensor for mTORC1 subunit 1"
FT /id="PRO_0000348590"
FT DOMAIN 72..138
FT /note="ACT 1"
FT DOMAIN 260..321
FT /note="ACT 2"
FT BINDING 111..112
FT /ligand="L-arginine"
FT /ligand_id="ChEBI:CHEBI:32682"
FT /evidence="ECO:0000269|PubMed:27487210,
FT ECO:0007744|PDB:5I2C"
FT BINDING 274
FT /ligand="L-arginine"
FT /ligand_id="ChEBI:CHEBI:32682"
FT /evidence="ECO:0000269|PubMed:27487210,
FT ECO:0007744|PDB:5I2C"
FT BINDING 280..281
FT /ligand="L-arginine"
FT /ligand_id="ChEBI:CHEBI:32682"
FT /evidence="ECO:0000269|PubMed:27487210,
FT ECO:0007744|PDB:5I2C"
FT BINDING 300..304
FT /ligand="L-arginine"
FT /ligand_id="ChEBI:CHEBI:32682"
FT /evidence="ECO:0000269|PubMed:27487210,
FT ECO:0007744|PDB:5I2C"
FT MOD_RES 14
FT /note="Phosphoserine; by PKB/AKT1"
FT /evidence="ECO:0000269|PubMed:33594058"
FT MUTAGEN 14
FT /note="S->A: Abolished phosphorylation by AKT1, leading to
FT decreased interaction with RNF167 and subsequent
FT ubiquitination."
FT /evidence="ECO:0000269|PubMed:33594058"
FT MUTAGEN 14
FT /note="S->D: Mimics phosphorylation, leading to promote
FT interaction with RNF167 and subsequent ubiquitination."
FT /evidence="ECO:0000269|PubMed:33594058"
FT MUTAGEN 61
FT /note="K->R: In 3KR mutant; abolished ubiquitination by
FT RNF167; when associated with R-96 and R-213."
FT /evidence="ECO:0000269|PubMed:33594058"
FT MUTAGEN 90
FT /note="Q->A: No effect on interaction with the GATOR2
FT complex."
FT /evidence="ECO:0000269|PubMed:27487210"
FT MUTAGEN 96
FT /note="K->A: No effect on interaction with the GATOR2
FT complex."
FT /evidence="ECO:0000269|PubMed:27487210"
FT MUTAGEN 96
FT /note="K->R: In 3KR mutant; abolished ubiquitination by
FT RNF167; when associated with R-61 and R-213."
FT /evidence="ECO:0000269|PubMed:33594058"
FT MUTAGEN 99
FT /note="R->A: No effect on interaction with the GATOR2
FT complex."
FT /evidence="ECO:0000269|PubMed:27487210"
FT MUTAGEN 108..110
FT /note="HHV->QNI: Loss of arginine-binding. Constitutively
FT interacts with the GATOR2 complex."
FT /evidence="ECO:0000269|PubMed:27487210"
FT MUTAGEN 111
FT /note="S->A: Loss of arginine-binding. Constitutively
FT interacts with the GATOR2 complex. Constitutively inhibits
FT the TORC1 signaling pathway."
FT /evidence="ECO:0000269|PubMed:27487210"
FT MUTAGEN 113
FT /note="L->F: No effect on interaction with the GATOR2
FT complex."
FT /evidence="ECO:0000269|PubMed:27487210"
FT MUTAGEN 118..119
FT /note="YQ->AA: No effect on arginine-binding. No effect on
FT homodimerization. Loss of interaction with the GATOR2
FT complex which constitutively activates the TORC1 signaling
FT pathway."
FT /evidence="ECO:0000269|PubMed:27487210"
FT MUTAGEN 121
FT /note="D->A: No effect on arginine-binding. No effect on
FT homodimerization. Loss of interaction with the GATOR2
FT complex which constitutively activates the TORC1 signaling
FT pathway."
FT /evidence="ECO:0000269|PubMed:27487210"
FT MUTAGEN 126
FT /note="R->A: Decreased arginine-binding. Constitutively
FT interacts with the GATOR2 complex."
FT /evidence="ECO:0000269|PubMed:27487210"
FT MUTAGEN 175
FT /note="H->A: Decreased arginine-binding. Constitutively
FT interacts with the GATOR2 complex."
FT /evidence="ECO:0000269|PubMed:27487210"
FT MUTAGEN 202
FT /note="I->E: No effect on arginine-binding. Loss of
FT homodimerization. Decreased interaction with the GATOR2
FT complex which constitutively activates the TORC1 signaling
FT pathway."
FT /evidence="ECO:0000269|PubMed:27487210"
FT MUTAGEN 207
FT /note="Y->S: No effect on arginine-binding. Loss of
FT homodimerization. Decreased interaction with the GATOR2
FT complex which constitutively activates the TORC1 signaling
FT pathway."
FT /evidence="ECO:0000269|PubMed:27487210"
FT MUTAGEN 213
FT /note="K->R: In 3KR mutant; abolished ubiquitination by
FT RNF167; when associated with R-61 and R-96."
FT /evidence="ECO:0000269|PubMed:33594058"
FT MUTAGEN 261
FT /note="E->A: No effect on arginine-binding. No effect on
FT homodimerization. Loss of interaction with the GATOR2
FT complex."
FT /evidence="ECO:0000269|PubMed:27487210"
FT MUTAGEN 264
FT /note="R->A: No effect on interaction with the GATOR2
FT complex."
FT /evidence="ECO:0000269|PubMed:27487210"
FT MUTAGEN 276
FT /note="D->A: Decreased arginine-binding. Constitutively
FT interacts with the GATOR2 complex."
FT /evidence="ECO:0000269|PubMed:27487210"
FT MUTAGEN 277
FT /note="E->A: Decreased arginine-binding. Constitutively
FT interacts with the GATOR2 complex."
FT /evidence="ECO:0000269|PubMed:27487210"
FT MUTAGEN 278
FT /note="C->A: Decreased arginine-binding. Constitutively
FT interacts with the GATOR2 complex."
FT /evidence="ECO:0000269|PubMed:27487210"
FT MUTAGEN 280
FT /note="I->A: Loss of arginine-binding. Constitutively
FT inhibits the TORC1 signaling pathway."
FT /evidence="ECO:0000269|PubMed:26972053"
FT MUTAGEN 292
FT /note="D->A: No effect on arginine-binding. No effect on
FT homodimerization. Loss of interaction with the GATOR2
FT complex."
FT /evidence="ECO:0000269|PubMed:27487210"
FT MUTAGEN 302
FT /note="N->K: No effect on interaction with the GATOR2
FT complex."
FT /evidence="ECO:0000269|PubMed:27487210"
FT MUTAGEN 304
FT /note="D->A: Loss of arginine-binding. Constitutively
FT interacts with the GATOR2 complex. Constitutively inhibits
FT the TORC1 signaling pathway."
FT /evidence="ECO:0000269|PubMed:27487210"
FT CONFLICT 4
FT /note="H -> R (in Ref. 2; BAB70963)"
FT /evidence="ECO:0000305"
FT STRAND 2..16
FT /evidence="ECO:0007829|PDB:5I2C"
FT HELIX 17..19
FT /evidence="ECO:0007829|PDB:5I2C"
FT HELIX 20..32
FT /evidence="ECO:0007829|PDB:5I2C"
FT HELIX 34..36
FT /evidence="ECO:0007829|PDB:5I2C"
FT STRAND 41..46
FT /evidence="ECO:0007829|PDB:5I2C"
FT STRAND 48..56
FT /evidence="ECO:0007829|PDB:5I2C"
FT HELIX 57..60
FT /evidence="ECO:0007829|PDB:5I2C"
FT STRAND 69..71
FT /evidence="ECO:0007829|PDB:5I2C"
FT STRAND 76..81
FT /evidence="ECO:0007829|PDB:5I2C"
FT HELIX 84..86
FT /evidence="ECO:0007829|PDB:5GT7"
FT STRAND 91..93
FT /evidence="ECO:0007829|PDB:5GT7"
FT HELIX 94..97
FT /evidence="ECO:0007829|PDB:5I2C"
FT TURN 98..101
FT /evidence="ECO:0007829|PDB:5I2C"
FT HELIX 102..107
FT /evidence="ECO:0007829|PDB:5I2C"
FT STRAND 112..116
FT /evidence="ECO:0007829|PDB:5I2C"
FT STRAND 121..126
FT /evidence="ECO:0007829|PDB:5I2C"
FT HELIX 127..129
FT /evidence="ECO:0007829|PDB:5I2C"
FT HELIX 130..137
FT /evidence="ECO:0007829|PDB:5I2C"
FT TURN 138..140
FT /evidence="ECO:0007829|PDB:5I2C"
FT STRAND 141..147
FT /evidence="ECO:0007829|PDB:5I2C"
FT STRAND 150..153
FT /evidence="ECO:0007829|PDB:5I2C"
FT STRAND 184..188
FT /evidence="ECO:0007829|PDB:5I2C"
FT HELIX 191..193
FT /evidence="ECO:0007829|PDB:5I2C"
FT HELIX 195..197
FT /evidence="ECO:0007829|PDB:5I2C"
FT HELIX 198..206
FT /evidence="ECO:0007829|PDB:5I2C"
FT TURN 216..218
FT /evidence="ECO:0007829|PDB:5I2C"
FT STRAND 228..233
FT /evidence="ECO:0007829|PDB:5I2C"
FT STRAND 236..242
FT /evidence="ECO:0007829|PDB:5I2C"
FT HELIX 243..248
FT /evidence="ECO:0007829|PDB:5I2C"
FT TURN 251..253
FT /evidence="ECO:0007829|PDB:5I2C"
FT STRAND 254..258
FT /evidence="ECO:0007829|PDB:5GT8"
FT STRAND 263..268
FT /evidence="ECO:0007829|PDB:5I2C"
FT TURN 274..276
FT /evidence="ECO:0007829|PDB:5I2C"
FT HELIX 280..290
FT /evidence="ECO:0007829|PDB:5I2C"
FT STRAND 295..299
FT /evidence="ECO:0007829|PDB:5I2C"
FT STRAND 304..309
FT /evidence="ECO:0007829|PDB:5I2C"
FT HELIX 310..312
FT /evidence="ECO:0007829|PDB:5I2C"
FT HELIX 313..320
FT /evidence="ECO:0007829|PDB:5I2C"
SQ SEQUENCE 329 AA; 36275 MW; C6AE6FE6038C5D3A CRC64;
MELHILEHRV RVLSVARPGL WLYTHPLIKL LFLPRRSRCK FFSLTETPED YTLMVDEEGF
KELPPSEFLQ VAEATWLVLN VSSHSGAAVQ AAGVTKIARS VIAPLAEHHV SVLMLSTYQT
DFILVREQDL SVVIHTLAQE FDIYREVGGE PVPVTRDDSS NGFPRTQHGP SPTVHPIQSP
QNRFCVLTLD PETLPAIATT LIDVLFYSHS TPKEAASSSP EPSSITFFAF SLIEGYISIV
MDAETQKKFP SDLLLTSSSG ELWRMVRIGG QPLGFDECGI VAQIAGPLAA ADISAYYIST
FNFDHALVPE DGIGSVIEVL QRRQEGLAS
