ID REBL1_HUMAN Reviewed; 183 AA. AC Q8TAI7; Q56VH8; DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-2002, sequence version 1. DT 24-JAN-2024, entry version 185. DE RecName: Full=GTPase RhebL1; DE AltName: Full=Ras homolog enriched in brain like-1 c; DE Short=RhebL1c; DE AltName: Full=Ras homolog enriched in brain-like protein 1; DE Short=Rheb-like protein 1; DE AltName: Full=Rheb2; DE Flags: Precursor; GN Name=RHEBL1; 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 [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, RP TISSUE SPECIFICITY, AND MUTAGENESIS OF ASP-60 AND GLN-64. RC TISSUE=Brain; RX PubMed=16328882; DOI=10.1007/s11033-005-0984-x; RA Yuan J., Shan Y., Chen X., Tang W., Luo K., Ni J., Wan B., Yu L.; RT "Identification and characterization of RHEBL1, a novel member of Ras RT family, which activates transcriptional activities of NF-kappa B."; RL Mol. Biol. Rep. 32:205-214(2005). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RA Wu M., Mao Y., Xie Y.; RT "Ras homolog enriched in brain like 1 c."; RL Submitted (DEC-2003) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Testis; 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 [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] (ISOFORM 1). RC TISSUE=Duodenum; 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. RX PubMed=12869548; DOI=10.1074/jbc.m306553200; RA Tabancay A.P. Jr., Gau C.L., Machado I.M., Uhlmann E.J., Gutmann D.H., RA Guo L., Tamanoi F.; RT "Identification of dominant negative mutants of Rheb GTPase and their use RT to implicate the involvement of human Rheb in the activation of p70S6K."; RL J. Biol. Chem. 278:39921-39930(2003). RN [7] RP FUNCTION, INTERACTION WITH MTOR, AND MUTAGENESIS OF ASN-41; PHE-54 AND RP LEU-56. RX PubMed=16098514; DOI=10.1016/j.febslet.2005.07.054; RA Tee A.R., Blenis J., Proud C.G.; RT "Analysis of mTOR signaling by the small G-proteins, Rheb and RhebL1."; RL FEBS Lett. 579:4763-4768(2005). RN [8] RP TISSUE SPECIFICITY, AND ISOPRENYLATION AT CYS-180. RX PubMed=16006564; DOI=10.1074/jbc.m503763200; RA Basso A.D., Mirza A., Liu G., Long B.J., Bishop W.R., Kirschmeier P.; RT "The farnesyl transferase inhibitor (FTI) SCH66336 (lonafarnib) inhibits RT Rheb farnesylation and mTOR signaling. Role in FTI enhancement of taxane RT and tamoxifen anti-tumor activity."; RL J. Biol. Chem. 280:31101-31108(2005). RN [9] RP FUNCTION. RX PubMed=17162089; DOI=10.1016/j.juro.2006.08.076; RA Robb V.A., Karbowniczek M., Klein-Szanto A.J., Henske E.P.; RT "Activation of the mTOR signaling pathway in renal clear cell carcinoma."; RL J. Urol. 177:346-352(2007). RN [10] RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) IN COMPLEX WITH GTP. RG RG Structural genomics consortium (SGC); RT "Crystal structure of the small GTPase RhebL1."; RL Submitted (AUG-2010) to the PDB data bank. CC -!- FUNCTION: Binds GTP and exhibits intrinsic GTPase activity. May CC activate NF-kappa-B-mediated gene transcription. Promotes signal CC transduction through MTOR, activates RPS6KB1, and is a downstream CC target of the small GTPase-activating proteins TSC1 and TSC2. CC {ECO:0000269|PubMed:12869548, ECO:0000269|PubMed:16098514, CC ECO:0000269|PubMed:16328882, ECO:0000269|PubMed:17162089}. CC -!- SUBUNIT: Interacts with MTOR. {ECO:0000269|PubMed:16098514}. CC -!- INTERACTION: CC Q8TAI7; Q9UKG1: APPL1; NbExp=3; IntAct=EBI-746555, EBI-741243; CC Q8TAI7; P54253: ATXN1; NbExp=3; IntAct=EBI-746555, EBI-930964; CC Q8TAI7; Q13643: FHL3; NbExp=3; IntAct=EBI-746555, EBI-741101; CC Q8TAI7; O43741: PRKAB2; NbExp=7; IntAct=EBI-746555, EBI-1053424; CC Q8TAI7; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-746555, EBI-5235340; CC Q8TAI7; P09936: UCHL1; NbExp=3; IntAct=EBI-746555, EBI-714860; CC -!- SUBCELLULAR LOCATION: Endomembrane system CC {ECO:0000305|PubMed:16328882}; Lipid-anchor CC {ECO:0000305|PubMed:16006564}; Cytoplasmic side {ECO:0000305}. CC Cytoplasm {ECO:0000269|PubMed:16328882}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q8TAI7-1; Sequence=Displayed; CC Name=2; CC IsoId=Q8TAI7-2; Sequence=VSP_040851, VSP_040852; CC -!- TISSUE SPECIFICITY: Ubiquitously expressed. Expression increased at CC least 2-fold in several tumor cell lines. {ECO:0000269|PubMed:16006564, CC ECO:0000269|PubMed:16328882}. CC -!- MISCELLANEOUS: [Isoform 2]: May be produced at very low levels due to a CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA CC decay. {ECO:0000305}. CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Rheb family. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAS80166.1; Type=Erroneous translation; Note=Wrong choice of CDS.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AY327412; AAP92804.1; -; mRNA. DR EMBL; AY509932; AAS80166.1; ALT_SEQ; mRNA. DR EMBL; AK098663; BAC05370.1; -; mRNA. DR EMBL; CH471111; EAW58038.1; -; Genomic_DNA. DR EMBL; BC027482; AAH27482.1; -; mRNA. DR CCDS; CCDS8778.1; -. [Q8TAI7-1] DR RefSeq; NP_001290055.1; NM_001303126.1. DR RefSeq; NP_653194.1; NM_144593.2. [Q8TAI7-1] DR PDB; 3OES; X-ray; 2.30 A; A=1-183. DR PDBsum; 3OES; -. DR AlphaFoldDB; Q8TAI7; -. DR SMR; Q8TAI7; -. DR BioGRID; 125715; 9. DR IntAct; Q8TAI7; 11. DR MINT; Q8TAI7; -. DR STRING; 9606.ENSP00000301068; -. DR iPTMnet; Q8TAI7; -. DR PhosphoSitePlus; Q8TAI7; -. DR BioMuta; RHEBL1; -. DR DMDM; 74730357; -. DR jPOST; Q8TAI7; -. DR MassIVE; Q8TAI7; -. DR PaxDb; 9606-ENSP00000301068; -. DR PeptideAtlas; Q8TAI7; -. DR Antibodypedia; 25823; 151 antibodies from 23 providers. DR DNASU; 121268; -. DR Ensembl; ENST00000301068.11; ENSP00000301068.6; ENSG00000167550.11. [Q8TAI7-1] DR Ensembl; ENST00000550797.1; ENSP00000446726.1; ENSG00000167550.11. [Q8TAI7-2] DR GeneID; 121268; -. DR KEGG; hsa:121268; -. DR MANE-Select; ENST00000301068.11; ENSP00000301068.6; NM_144593.3; NP_653194.1. DR UCSC; uc001rtc.2; human. [Q8TAI7-1] DR AGR; HGNC:21166; -. DR CTD; 121268; -. DR DisGeNET; 121268; -. DR GeneCards; RHEBL1; -. DR HGNC; HGNC:21166; RHEBL1. DR HPA; ENSG00000167550; Tissue enhanced (brain). DR MIM; 618956; gene. DR neXtProt; NX_Q8TAI7; -. DR OpenTargets; ENSG00000167550; -. DR PharmGKB; PA134984759; -. DR VEuPathDB; HostDB:ENSG00000167550; -. DR eggNOG; KOG0395; Eukaryota. DR GeneTree; ENSGT00940000161665; -. DR HOGENOM; CLU_041217_9_8_1; -. DR InParanoid; Q8TAI7; -. DR OMA; HQGHGKT; -. DR OrthoDB; 8685at2759; -. DR PhylomeDB; Q8TAI7; -. DR TreeFam; TF314986; -. DR BRENDA; 3.6.5.2; 2681. DR PathwayCommons; Q8TAI7; -. DR SignaLink; Q8TAI7; -. DR BioGRID-ORCS; 121268; 22 hits in 1160 CRISPR screens. DR EvolutionaryTrace; Q8TAI7; -. DR GenomeRNAi; 121268; -. DR Pharos; Q8TAI7; Tbio. DR PRO; PR:Q8TAI7; -. DR Proteomes; UP000005640; Chromosome 12. DR RNAct; Q8TAI7; Protein. DR Bgee; ENSG00000167550; Expressed in oocyte and 119 other cell types or tissues. DR ExpressionAtlas; Q8TAI7; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0012505; C:endomembrane system; IEA:UniProtKB-SubCell. DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central. DR GO; GO:0019003; F:GDP binding; IBA:GO_Central. DR GO; GO:0005525; F:GTP binding; IDA:UniProtKB. DR GO; GO:0003924; F:GTPase activity; IBA:GO_Central. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IDA:UniProtKB. DR GO; GO:0007264; P:small GTPase mediated signal transduction; IBA:GO_Central. DR GO; GO:0031929; P:TOR signaling; IMP:UniProtKB. DR CDD; cd04137; RheB; 1. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1. DR InterPro; IPR027417; P-loop_NTPase. DR InterPro; IPR005225; Small_GTP-bd_dom. DR InterPro; IPR001806; Small_GTPase. DR InterPro; IPR020849; Small_GTPase_Ras-type. DR NCBIfam; TIGR00231; small_GTP; 1. DR PANTHER; PTHR24070:SF253; GTPASE RHEBL1; 1. DR PANTHER; PTHR24070; RAS, DI-RAS, AND RHEB FAMILY MEMBERS OF SMALL GTPASE SUPERFAMILY; 1. DR Pfam; PF00071; Ras; 1. DR PRINTS; PR00449; RASTRNSFRMNG. DR SMART; SM00175; RAB; 1. DR SMART; SM00173; RAS; 1. DR SMART; SM00174; RHO; 1. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1. DR PROSITE; PS51421; RAS; 1. DR Genevisible; Q8TAI7; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cytoplasm; GTP-binding; Lipoprotein; KW Magnesium; Membrane; Metal-binding; Methylation; Nucleotide-binding; KW Prenylation; Reference proteome. FT CHAIN 1..180 FT /note="GTPase RhebL1" FT /id="PRO_0000324292" FT PROPEP 181..183 FT /note="Removed in mature form" FT /evidence="ECO:0000250" FT /id="PRO_0000324293" FT MOTIF 35..43 FT /note="Effector region" FT BINDING 16..21 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000269|Ref.10" FT BINDING 32..38 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000269|Ref.10" FT BINDING 38 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250|UniProtKB:Q15382" FT BINDING 63 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000269|Ref.10" FT BINDING 119..122 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000269|Ref.10" FT BINDING 149..150 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000269|Ref.10" FT MOD_RES 180 FT /note="Cysteine methyl ester" FT /evidence="ECO:0000250" FT LIPID 180 FT /note="S-farnesyl cysteine" FT /evidence="ECO:0000269|PubMed:16006564" FT VAR_SEQ 18..68 FT /note="GKTSLAHQFVEGEFSEGYDPTVENTYSKIVTLGKDEFHLHLVDTAGQDEYS FT -> VRKDRGCECGWMIWIQLSHCSPQGRHLWHINLWKASSRKATILQWRILTAR (in FT isoform 2)" FT /evidence="ECO:0000303|Ref.2" FT /id="VSP_040851" FT VAR_SEQ 69..183 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|Ref.2" FT /id="VSP_040852" FT MUTAGEN 41 FT /note="N->A: Partially impaired in RPS6K1 activation." FT /evidence="ECO:0000269|PubMed:16098514" FT MUTAGEN 54 FT /note="F->A: Partially deficient in guanine nucleotide FT binding." FT /evidence="ECO:0000269|PubMed:16098514" FT MUTAGEN 56 FT /note="L->A: Partially deficient in guanine nucleotide FT binding." FT /evidence="ECO:0000269|PubMed:16098514" FT MUTAGEN 60 FT /note="D->K: Significant decrease in NF-kappa B FT activation." FT /evidence="ECO:0000269|PubMed:16328882" FT MUTAGEN 64 FT /note="Q->L: Constitutively active." FT /evidence="ECO:0000269|PubMed:16328882" FT STRAND 6..14 FT /evidence="ECO:0007829|PDB:3OES" FT HELIX 19..28 FT /evidence="ECO:0007829|PDB:3OES" FT STRAND 39..47 FT /evidence="ECO:0007829|PDB:3OES" FT STRAND 54..61 FT /evidence="ECO:0007829|PDB:3OES" FT HELIX 72..74 FT /evidence="ECO:0007829|PDB:3OES" FT TURN 75..77 FT /evidence="ECO:0007829|PDB:3OES" FT STRAND 80..86 FT /evidence="ECO:0007829|PDB:3OES" FT HELIX 90..104 FT /evidence="ECO:0007829|PDB:3OES" FT STRAND 114..119 FT /evidence="ECO:0007829|PDB:3OES" FT HELIX 124..126 FT /evidence="ECO:0007829|PDB:3OES" FT HELIX 131..141 FT /evidence="ECO:0007829|PDB:3OES" FT STRAND 144..147 FT /evidence="ECO:0007829|PDB:3OES" FT HELIX 153..169 FT /evidence="ECO:0007829|PDB:3OES" SQ SEQUENCE 183 AA; 20682 MW; 0C5408800B61DD62 CRC64; MPLVRYRKVV ILGYRCVGKT SLAHQFVEGE FSEGYDPTVE NTYSKIVTLG KDEFHLHLVD TAGQDEYSIL PYSFIIGVHG YVLVYSVTSL HSFQVIESLY QKLHEGHGKT RVPVVLVGNK ADLSPEREVQ AVEGKKLAES WGATFMESSA RENQLTQGIF TKVIQEIARV ENSYGQERRC HLM //