Q8TAI7 (REBL1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:

RHEBL1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	183 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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. Ref.1 Ref.6 Ref.7 Ref.9
Subunit structure	Interacts with MTOR. Ref.7
Subcellular location	Cell membrane; Lipid-anchor; Cytoplasmic side By similarity. Cytoplasm Ref.1.
Tissue specificity	Ubiquitously expressed. Expression increased at least 2-fold in several tumor cell lines. Ref.1 Ref.8
Sequence similarities	Belongs to the small GTPase superfamily. Rheb family.
Sequence caution	The sequence AAS80166.1 differs from that shown. Reason: Erroneous translation. Wrong choice of CDS.

Ontologies

Keywords
Cellular component	Cell membrane Cytoplasm Membrane
Coding sequence diversity	Alternative splicing
Ligand	GTP-binding Nucleotide-binding
PTM	Lipoprotein Methylation Prenylation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	TOR signaling cascade Inferred from mutant phenotype Ref.6. Source: UniProtKB positive regulation of NF-kappaB transcription factor activity Inferred from direct assay Ref.1. Source: UniProtKB small GTPase mediated signal transduction Inferred from electronic annotation. Source: InterPro
Cellular_component	cytoplasm Inferred from direct assay Ref.1. Source: UniProtKB plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	GTP binding Inferred from direct assay Ref.6. Source: UniProtKB GTPase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q8TAI7-1)

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.

Isoform 2 (identifier: Q8TAI7-2)

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.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 180

180

GTPase RhebL1

PRO_0000324292

Propeptide

181 – 183

3

Removed in mature form By similarity

PRO_0000324293

Regions

Nucleotide binding

13 – 20

8

GTP By similarity

Nucleotide binding

60 – 64

5

GTP By similarity

Nucleotide binding

119 – 122

4

GTP By similarity

Motif

35 – 43

9

Effector region By similarity

Amino acid modifications

Modified residue

180

1

Cysteine methyl ester By similarity

Lipidation

180

1

S-farnesyl cysteine Ref.8

Natural variations

Alternative sequence

18 – 68

51

GKTSL…QDEYS → VRKDRGCECGWMIWIQLSHC SPQGRHLWHINLWKASSRKA TILQWRILTAR in isoform 2.

VSP_040851

Alternative sequence

69 – 183

115

Missing in isoform 2.

VSP_040852

Experimental info

Mutagenesis

41

1

N → A: Partially impaired in RPS6K1 activation. Ref.7

Mutagenesis

54

1

F → A: Partially deficient in guanine nucleotide binding. Ref.7

Mutagenesis

56

1

L → A: Partially deficient in guanine nucleotide binding. Ref.7

Mutagenesis

60

1

D → K: Significant decrease in NF-kappa B activation. Ref.1

Mutagenesis

64

1

Q → L: Constitutively active. Ref.1

Secondary structure

1

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183

Helix Strand Turn

Details...

Beta strand

6 – 14

9

Helix

19 – 28

10

Beta strand

39 – 47

9

Beta strand

54 – 61

8

Helix

72 – 74

3

Turn

75 – 77

3

Beta strand

80 – 86

7

Helix

90 – 104

15

Beta strand

114 – 119

6

Helix

124 – 126

3

Helix

131 – 141

11

Beta strand

144 – 147

4

Helix

153 – 169

17

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 1, 2002. Version 1. Checksum: 0C5408800B61DD62	FASTA	183	20,682
	10 20 30 40 50 60 MPLVRYRKVV ILGYRCVGKT SLAHQFVEGE FSEGYDPTVE NTYSKIVTLG KDEFHLHLVD 70 80 90 100 110 120 TAGQDEYSIL PYSFIIGVHG YVLVYSVTSL HSFQVIESLY QKLHEGHGKT RVPVVLVGNK 130 140 150 160 170 180 ADLSPEREVQ AVEGKKLAES WGATFMESSA RENQLTQGIF TKVIQEIARV ENSYGQERRC HLM
	Isoform 2 [UniParc]. Checksum: 5412A25D63C02FB8	FASTA	68	8,176
	10 20 30 40 50 60 MPLVRYRKVV ILGYRCVVRK DRGCECGWMI WIQLSHCSPQ GRHLWHINLW KASSRKATIL QWRILTAR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases 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.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.

IPI

IPI00152059.
IPI00556561.

RefSeq

NP_653194.1. NM_144593.1.

UniGene

Hs.159013.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3OES	X-ray	2.30	A	1-183	[»]

ProteinModelPortal

Q8TAI7.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q8TAI7. 5 interactions.

MINT

MINT-1365371.

STRING

9606.ENSP00000301068.

PTM databases

PhosphoSite

Q8TAI7.

Polymorphism databases

DMDM

74730357.

Proteomic databases

PaxDb

Q8TAI7.

PRIDE

Q8TAI7.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000301068; ENSP00000301068; ENSG00000167550.
ENST00000550797; ENSP00000446726; ENSG00000167550.

GeneID

121268.

KEGG

hsa:121268.

UCSC

uc001rtc.1. human.

Organism-specific databases

CTD

121268.

GeneCards

GC12M049458.

HGNC

HGNC:21166. RHEBL1.

neXtProt

NX_Q8TAI7.

PharmGKB

PA134984759.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG1100.

HOGENOM

HOG000233973.

HOVERGEN

HBG009351.

InParanoid

Q8TAI7.

KO

K07849.

OMA

ERRCRLM.

OrthoDB

EOG4VMFGG.

PhylomeDB

Q8TAI7.

Enzyme and pathway databases

BRENDA

3.6.5.2. 2681.

Gene expression databases

ArrayExpress

Q8TAI7.

Bgee

Q8TAI7.

CleanEx

HS_RHEBL1.

Genevestigator

Q8TAI7.

Family and domain databases

InterPro

IPR005225. Small_GTP-bd_dom.
IPR001806. Small_GTPase.
IPR020849. Small_GTPase_Ras.
[Graphical view]

PANTHER

PTHR24070. PTHR24070. 1 hit.

Pfam

PF00071. Ras. 1 hit.
[Graphical view]

PRINTS

PR00449. RASTRNSFRMNG.

SMART

SM00173. RAS. 1 hit.
[Graphical view]

TIGRFAMs

TIGR00231. small_GTP. 1 hit.

PROSITE

PS51421. RAS. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q8TAI7.

GenomeRNAi

121268.

NextBio

80692.

Entry information

Entry name

REBL1_HUMAN

Accession

Primary (citable) accession number: Q8TAI7
Secondary accession number(s): Q56VH8

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 18, 2008
Last sequence update:	June 1, 2002
Last modified:	May 1, 2013
This is version 109 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.