Reviewed, UniProtKB/Swiss-Prot P62070 (RRAS2_HUMAN)

Names and origin

Protein names

Recommended name:
    Ras-related protein R-Ras2
Alternative name(s):
    Ras-like protein TC21
    Teratocarcinoma oncogene

Gene names

Name:	RRAS2
Synonyms:	TC21

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	204 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	It is a plasma membrane-associated GTP-binding protein with GTPase activity. Might transduce growth inhibitory signals across the cell membrane, exerting its effect through an effector shared with the Ras proteins but in an antagonistic fashion.
Subcellular location	Cell membrane; Lipid-anchor; Cytoplasmic side By similarity. Note: Inner surface of plasma membrane possibly with attachment requiring acylation of the C-terminal cysteine (By similarity with RAS).
Tissue specificity	Ubiquitously present in all tissues examined, with the highest levels in heart, placenta, and skeletal muscle. Moderate levels in lung and liver; low levels in brain, kidney, and pancreas. Ref.2
Post-translational modification	May be post-translationally modified by both palmitoylation and polyisoprenylation.
Involvement in disease	Defects in RRAS2 are associated with ovarian cancer [MIM:167000]. Ovarian cancer is the leading cause of death from gynecologic malignancy. It is characterized by advanced presentation with loco-regional dissemination in the peritoneal cavity and the rare incidence of visceral metastases. These typical features relate to the biology of the disease, which is a principal determinant of outcome.
Sequence similarities	Belongs to the small GTPase superfamily. Ras family.
Sequence caution	The sequence AAA36545.1 differs from that shown. Reason: Frameshift at positions 4, 8 and 12. The sequence AAM12638.1 differs from that shown. Reason: Frameshift at positions 4, 8 and 12.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Disease	Disease mutation Proto-oncogene
Ligand	GTP-binding Nucleotide-binding
PTM	Lipoprotein Methylation Phosphoprotein Prenylation
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Cellular component	endoplasmic reticulum Non-traceable author statement. Source: ProtInc plasma membrane Non-traceable author statement. Source: ProtInc
Molecular function	GTP binding Inferred from electronic annotation. Source: UniProtKB-KW GTPase activity Traceable author statement. Source: ProtInc protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ARAF	P10398	3	EBI-491037,EBI-365961

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 201

201

Ras-related protein R-Ras2

PRO_0000082652

Propeptide

202 – 204

3

Removed in mature form By similarity

PRO_0000281302

Regions

Nucleotide binding

21 – 28

8

GTP By similarity

Nucleotide binding

68 – 72

5

GTP By similarity

Nucleotide binding

127 – 130

4

GTP By similarity

Motif

43 – 51

9

Effector region By similarity

Amino acid modifications

Modified residue

186

1

Phosphoserine Ref.6 Ref.7 Ref.8

Modified residue

201

1

Cysteine methyl ester Probable

Lipidation

201

1

S-farnesyl cysteine

Natural variations

Natural variant

72

1

Q → L in ovarian cancer; somatic mutation.

VAR_006848

Secondary structure

1

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204

Helix Strand Turn

Details...

Beta strand

14 – 21

8

Helix

27 – 36

10

Beta strand

49 – 57

9

Beta strand

60 – 68

9

Helix

77 – 85

9

Beta strand

87 – 94

8

Helix

98 – 102

5

Helix

104 – 115

12

Beta strand

121 – 127

7

Helix

139 – 148

10

Beta strand

152 – 155

4

Turn

158 – 161

4

Helix

164 – 178

15

Sequences

	Sequence		Length	Mass (Da)
	P62070-1 [UniParc]. Last modified June 21, 2004. Version 1. Checksum: BA7D4759DC49446F	FASTA	204	23,400
	10 20 30 40 50 60 MAAAGWRDGS GQEKYRLVVV GGGGVGKSAL TIQFIQSYFV TDYDPTIEDS YTKQCVIDDR 70 80 90 100 110 120 AARLDILDTA GQEEFGAMRE QYMRTGEGFL LVFSVTDRGS FEEIYKFQRQ ILRVKDRDEF 130 140 150 160 170 180 PMILIGNKAD LDHQRQVTQE EGQQLARQLK VTYMEASAKI RMNVDQAFHE LVRVIRKFQE 190 200 QECPPSPEPT RKEKDKKGCH CVIF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Characterization of four novel ras-like genes expressed in a human teratocarcinoma cell line." Drivas G.T., Shih A., Coutavas E., Rush M.G., D'Eustachio P. Mol. Cell. Biol. 10:1793-1798(1990) [PubMed: 2108320] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"A human oncogene of the RAS superfamily unmasked by expression cDNA cloning." Chan A.M.-L., Miki T., Meyers K.A., Aaronson S.A. Proc. Natl. Acad. Sci. U.S.A. 91:7558-7562(1994) [PubMed: 8052619] [Abstract] Cited for: SEQUENCE REVISION TO 5-11, TISSUE SPECIFICITY, VARIANT OVARIAN CANCER LEU-72.
[3]	"cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org)." Puhl H.L. III, Ikeda S.R., Aronstam R.S. Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Heart.
[4]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Bone.
[5]	"A tagging-via-substrate technology for detection and proteomics of farnesylated proteins." Kho Y., Kim S.C., Jiang C., Barma D., Kwon S.W., Cheng J., Jaunbergs J., Weinbaum C., Tamanoi F., Falck J., Zhao Y. Proc. Natl. Acad. Sci. U.S.A. 101:12479-12484(2004) [PubMed: 15308774] [Abstract] Cited for: ISOPRENYLATION AT CYS-201.
[6]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-186, MASS SPECTROMETRY. Tissue: Epithelium.
[7]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-186, MASS SPECTROMETRY.
[8]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-186, MASS SPECTROMETRY.
[9]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

M31468 mRNA. Translation: AAA36545.1. Frameshift.
AF493924 mRNA. Translation: AAM12638.1. Frameshift.
BC013106 mRNA. Translation: AAH13106.1.

IPI

IPI00012512.

PIR

TVHUC2. B34788.

RefSeq

NP_001096139.1.
NP_036382.2.

UniGene

Hs.502004

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2ERY	X-ray	1.70	A/B	12-181	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P62070. 8 interactions.

PTM databases

PhosphoSite

P62070.

Proteomic databases

PeptideAtlas

P62070.

PRIDE

P62070.

Genome annotation databases

Ensembl

ENSG00000133818. Homo sapiens. [Contig view]

GeneID

22800.

KEGG

hsa:22800.

UCSC

uc001mlf.2. human.

Organism-specific databases

GeneCards

GC11M014256.

H-InvDB

HIX0009465.

HGNC

HGNC:17271. RRAS2.

HPA

CAB010420.

MIM

167000. phenotype.
600098. gene.

PharmGKB

PA34862.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P62070.

HOVERGEN

P62070.

OMA

P62070. AITIQFI.

Gene expression databases

ArrayExpress

P62070.

Bgee

P62070.

CleanEx

HS_RRAS2.

GermOnline

ENSG00000133818. Homo sapiens.

Family and domain databases

InterPro

IPR003577. GTPase_Ras.
IPR013753. Ras.
IPR001806. Ras_GTPase.
IPR005225. Small_GTP_bd.
[Graphical view]

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 Resources

NextBio

43146.

SOURCE

Search...

Entry information

Entry name

RRAS2_HUMAN

Accession

Primary (citable) accession number: P62070
Secondary accession number(s): P17082

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 21, 2004
Last sequence update:	June 21, 2004
Last modified:	July 7, 2009
This is version 68 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)