REBL1_HUMAN
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 03-AUG-2022, entry version 178.
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};
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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 PaxDb; Q8TAI7; -.
DR PeptideAtlas; Q8TAI7; -.
DR PRIDE; Q8TAI7; -.
DR Antibodypedia; 25823; 142 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 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; 1320427at2759; -.
DR PhylomeDB; Q8TAI7; -.
DR TreeFam; TF314986; -.
DR BRENDA; 3.6.5.2; 2681.
DR PathwayCommons; Q8TAI7; -.
DR SignaLink; Q8TAI7; -.
DR BioGRID-ORCS; 121268; 21 hits in 1082 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 117 other tissues.
DR ExpressionAtlas; Q8TAI7; baseline and differential.
DR Genevisible; Q8TAI7; HS.
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 Gene3D; 3.40.50.300; -; 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 PANTHER; PTHR24070; PTHR24070; 1.
DR Pfam; PF00071; Ras; 1.
DR SMART; SM00174; RHO; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR00231; small_GTP; 1.
DR PROSITE; PS51421; RAS; 1.
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
