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Protein

GTPase RhebL1

Gene

RHEBL1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Binds GTP and exhibits intrinsic GTPase activity. May activate NF-kappa-B-mediated gene transcription. Promotes signal transduction through MTOR, activates RPS6KB1, and is a downstream target of the small GTPase-activating proteins TSC1 and TSC2.4 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi38 – 381MagnesiumBy similarity
Binding sitei63 – 631GTP; via amide nitrogen1 Publication

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi16 – 216GTP1 Publication
Nucleotide bindingi32 – 387GTP1 Publication
Nucleotide bindingi119 – 1224GTP1 Publication
Nucleotide bindingi149 – 1502GTP1 Publication

GO - Molecular functioni

  1. GTP binding Source: UniProtKB
  2. metal ion binding Source: UniProtKB-KW

GO - Biological processi

  1. GTP catabolic process Source: InterPro
  2. positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
  3. small GTPase mediated signal transduction Source: InterPro
  4. TOR signaling Source: UniProtKB
Complete GO annotation...

Keywords - Ligandi

GTP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi3.6.5.2. 2681.

Names & Taxonomyi

Protein namesi
Recommended name:
GTPase RhebL1
Alternative name(s):
Ras homolog enriched in brain like-1 c
Short name:
RhebL1c
Ras homolog enriched in brain-like protein 1
Short name:
Rheb-like protein 1
Rheb2
Gene namesi
Name:RHEBL1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 12

Organism-specific databases

HGNCiHGNC:21166. RHEBL1.

Subcellular locationi

Endomembrane system 1 Publication; Lipid-anchor 1 Publication; Cytoplasmic side Curated. Cytoplasm 1 Publication

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. endomembrane system Source: UniProtKB-SubCell
  3. membrane Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi41 – 411N → A: Partially impaired in RPS6K1 activation. 1 Publication
Mutagenesisi54 – 541F → A: Partially deficient in guanine nucleotide binding. 1 Publication
Mutagenesisi56 – 561L → A: Partially deficient in guanine nucleotide binding. 1 Publication
Mutagenesisi60 – 601D → K: Significant decrease in NF-kappa B activation. 1 Publication
Mutagenesisi64 – 641Q → L: Constitutively active. 1 Publication

Organism-specific databases

PharmGKBiPA134984759.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 180180GTPase RhebL1PRO_0000324292Add
BLAST
Propeptidei181 – 1833Removed in mature formBy similarityPRO_0000324293

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei180 – 1801Cysteine methyl esterBy similarity
Lipidationi180 – 1801S-farnesyl cysteine1 Publication

Keywords - PTMi

Lipoprotein, Methylation, Prenylation

Proteomic databases

PaxDbiQ8TAI7.
PRIDEiQ8TAI7.

PTM databases

PhosphoSiteiQ8TAI7.

Expressioni

Tissue specificityi

Ubiquitously expressed. Expression increased at least 2-fold in several tumor cell lines.2 Publications

Gene expression databases

BgeeiQ8TAI7.
CleanExiHS_RHEBL1.
ExpressionAtlasiQ8TAI7. baseline and differential.
GenevestigatoriQ8TAI7.

Organism-specific databases

HPAiHPA053111.
HPA061001.

Interactioni

Subunit structurei

Interacts with MTOR.1 Publication

Protein-protein interaction databases

BioGridi125715. 9 interactions.
IntActiQ8TAI7. 5 interactions.
MINTiMINT-1365371.
STRINGi9606.ENSP00000301068.

Structurei

Secondary structure

1
183
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi6 – 149Combined sources
Helixi19 – 2810Combined sources
Beta strandi39 – 479Combined sources
Beta strandi54 – 618Combined sources
Helixi72 – 743Combined sources
Turni75 – 773Combined sources
Beta strandi80 – 867Combined sources
Helixi90 – 10415Combined sources
Beta strandi114 – 1196Combined sources
Helixi124 – 1263Combined sources
Helixi131 – 14111Combined sources
Beta strandi144 – 1474Combined sources
Helixi153 – 16917Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3OESX-ray2.30A1-183[»]
ProteinModelPortaliQ8TAI7.
SMRiQ8TAI7. Positions 5-170.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ8TAI7.

Family & Domainsi

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi35 – 439Effector region

Sequence similaritiesi

Belongs to the small GTPase superfamily. Rheb family.Curated

Phylogenomic databases

eggNOGiCOG1100.
GeneTreeiENSGT00780000121877.
HOGENOMiHOG000233973.
HOVERGENiHBG009351.
InParanoidiQ8TAI7.
KOiK07849.
OMAiRYRKVAI.
OrthoDBiEOG7Q2N6K.
PhylomeDBiQ8TAI7.
TreeFamiTF314986.

Family and domain databases

Gene3Di3.40.50.300. 1 hit.
InterProiIPR027417. P-loop_NTPase.
IPR005225. Small_GTP-bd_dom.
IPR001806. Small_GTPase.
IPR020849. Small_GTPase_Ras.
[Graphical view]
PANTHERiPTHR24070. PTHR24070. 1 hit.
PfamiPF00071. Ras. 1 hit.
[Graphical view]
PRINTSiPR00449. RASTRNSFRMNG.
SMARTiSM00173. RAS. 1 hit.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 1 hit.
TIGRFAMsiTIGR00231. small_GTP. 1 hit.
PROSITEiPS51421. RAS. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8TAI7-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MPLVRYRKVV ILGYRCVGKT SLAHQFVEGE FSEGYDPTVE NTYSKIVTLG
60 70 80 90 100
KDEFHLHLVD TAGQDEYSIL PYSFIIGVHG YVLVYSVTSL HSFQVIESLY
110 120 130 140 150
QKLHEGHGKT RVPVVLVGNK ADLSPEREVQ AVEGKKLAES WGATFMESSA
160 170 180
RENQLTQGIF TKVIQEIARV ENSYGQERRC HLM
Length:183
Mass (Da):20,682
Last modified:June 1, 2002 - v1
Checksum:i0C5408800B61DD62
GO
Isoform 2 (identifier: Q8TAI7-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     18-68: GKTSLAHQFV...VDTAGQDEYS → VRKDRGCECG...ILQWRILTAR
     69-183: Missing.

Note: No experimental confirmation available. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Show »
Length:68
Mass (Da):8,176
Checksum:i5412A25D63C02FB8
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei18 – 6851GKTSL…QDEYS → VRKDRGCECGWMIWIQLSHC SPQGRHLWHINLWKASSRKA TILQWRILTAR in isoform 2. 1 PublicationVSP_040851Add
BLAST
Alternative sequencei69 – 183115Missing in isoform 2. 1 PublicationVSP_040852Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY327412 mRNA. Translation: AAP92804.1.
AY509932 mRNA. Translation: AAS80166.1. Sequence problems.
AK098663 mRNA. Translation: BAC05370.1.
CH471111 Genomic DNA. Translation: EAW58038.1.
BC027482 mRNA. Translation: AAH27482.1.
CCDSiCCDS8778.1. [Q8TAI7-1]
RefSeqiNP_001290055.1. NM_001303126.1.
NP_653194.1. NM_144593.2. [Q8TAI7-1]
UniGeneiHs.159013.

Genome annotation databases

EnsembliENST00000301068; ENSP00000301068; ENSG00000167550. [Q8TAI7-1]
ENST00000550797; ENSP00000446726; ENSG00000167550. [Q8TAI7-2]
GeneIDi121268.
KEGGihsa:121268.
UCSCiuc001rtc.1. human. [Q8TAI7-1]

Polymorphism databases

DMDMi74730357.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY327412 mRNA. Translation: AAP92804.1.
AY509932 mRNA. Translation: AAS80166.1. Sequence problems.
AK098663 mRNA. Translation: BAC05370.1.
CH471111 Genomic DNA. Translation: EAW58038.1.
BC027482 mRNA. Translation: AAH27482.1.
CCDSiCCDS8778.1. [Q8TAI7-1]
RefSeqiNP_001290055.1. NM_001303126.1.
NP_653194.1. NM_144593.2. [Q8TAI7-1]
UniGeneiHs.159013.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3OESX-ray2.30A1-183[»]
ProteinModelPortaliQ8TAI7.
SMRiQ8TAI7. Positions 5-170.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi125715. 9 interactions.
IntActiQ8TAI7. 5 interactions.
MINTiMINT-1365371.
STRINGi9606.ENSP00000301068.

PTM databases

PhosphoSiteiQ8TAI7.

Polymorphism databases

DMDMi74730357.

Proteomic databases

PaxDbiQ8TAI7.
PRIDEiQ8TAI7.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000301068; ENSP00000301068; ENSG00000167550. [Q8TAI7-1]
ENST00000550797; ENSP00000446726; ENSG00000167550. [Q8TAI7-2]
GeneIDi121268.
KEGGihsa:121268.
UCSCiuc001rtc.1. human. [Q8TAI7-1]

Organism-specific databases

CTDi121268.
GeneCardsiGC12M049458.
HGNCiHGNC:21166. RHEBL1.
HPAiHPA053111.
HPA061001.
neXtProtiNX_Q8TAI7.
PharmGKBiPA134984759.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG1100.
GeneTreeiENSGT00780000121877.
HOGENOMiHOG000233973.
HOVERGENiHBG009351.
InParanoidiQ8TAI7.
KOiK07849.
OMAiRYRKVAI.
OrthoDBiEOG7Q2N6K.
PhylomeDBiQ8TAI7.
TreeFamiTF314986.

Enzyme and pathway databases

BRENDAi3.6.5.2. 2681.

Miscellaneous databases

EvolutionaryTraceiQ8TAI7.
GenomeRNAii121268.
NextBioi80692.
PROiQ8TAI7.

Gene expression databases

BgeeiQ8TAI7.
CleanExiHS_RHEBL1.
ExpressionAtlasiQ8TAI7. baseline and differential.
GenevestigatoriQ8TAI7.

Family and domain databases

Gene3Di3.40.50.300. 1 hit.
InterProiIPR027417. P-loop_NTPase.
IPR005225. Small_GTP-bd_dom.
IPR001806. Small_GTPase.
IPR020849. Small_GTPase_Ras.
[Graphical view]
PANTHERiPTHR24070. PTHR24070. 1 hit.
PfamiPF00071. Ras. 1 hit.
[Graphical view]
PRINTSiPR00449. RASTRNSFRMNG.
SMARTiSM00173. RAS. 1 hit.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 1 hit.
TIGRFAMsiTIGR00231. small_GTP. 1 hit.
PROSITEiPS51421. RAS. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Identification and characterization of RHEBL1, a novel member of Ras family, which activates transcriptional activities of NF-kappa B."
    Yuan J., Shan Y., Chen X., Tang W., Luo K., Ni J., Wan B., Yu L.
    Mol. Biol. Rep. 32:205-214(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, MUTAGENESIS OF ASP-60 AND GLN-64.
    Tissue: Brain.
  2. "Ras homolog enriched in brain like 1 c."
    Wu M., Mao Y., Xie Y.
    Submitted (DEC-2003) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
  3. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Testis.
  4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Duodenum.
  6. "Identification of dominant negative mutants of Rheb GTPase and their use to implicate the involvement of human Rheb in the activation of p70S6K."
    Tabancay A.P. Jr., Gau C.L., Machado I.M., Uhlmann E.J., Gutmann D.H., Guo L., Tamanoi F.
    J. Biol. Chem. 278:39921-39930(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  7. "Analysis of mTOR signaling by the small G-proteins, Rheb and RhebL1."
    Tee A.R., Blenis J., Proud C.G.
    FEBS Lett. 579:4763-4768(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH MTOR, MUTAGENESIS OF ASN-41; PHE-54 AND LEU-56.
  8. "The farnesyl transferase inhibitor (FTI) SCH66336 (lonafarnib) inhibits Rheb farnesylation and mTOR signaling. Role in FTI enhancement of taxane and tamoxifen anti-tumor activity."
    Basso A.D., Mirza A., Liu G., Long B.J., Bishop W.R., Kirschmeier P.
    J. Biol. Chem. 280:31101-31108(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY, ISOPRENYLATION AT CYS-180.
  9. "Activation of the mTOR signaling pathway in renal clear cell carcinoma."
    Robb V.A., Karbowniczek M., Klein-Szanto A.J., Henske E.P.
    J. Urol. 177:346-352(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  10. "Crystal structure of the small GTPase RhebL1."
    RG Structural genomics consortium (SGC)
    Submitted (AUG-2010) to the PDB data bank
    Cited for: X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) IN COMPLEX WITH GTP.

Entry informationi

Entry nameiREBL1_HUMAN
AccessioniPrimary (citable) accession number: Q8TAI7
Secondary accession number(s): Q56VH8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 18, 2008
Last sequence update: June 1, 2002
Last modified: March 4, 2015
This is version 125 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.