P62070 (RRAS2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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)

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 a cause of susceptibility to ovarian cancer (OC) [MIM:167000]. The term ovarian cancer defines common malignancies originating from ovarian tissue. Although many histologic types of ovarian tumors have been described, epithelial ovarian carcinoma is the most common form. Ovarian cancers are often asymptomatic and the recognized signs and symptoms, even of late-stage disease, are vague. Consequently, most patients are diagnosed with advanced disease.
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	Acetylation Lipoprotein Methylation Palmitate Phosphoprotein Prenylation
Technical term	3D-structure Complete proteome Reference 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

Initiator methionine

1

1

Removed

Chain

2 – 201

200

Ras-related protein R-Ras2

PRO_0000082652

Propeptide

202 – 204

3

Removed in mature form By similarity

PRO_0000281302

Regions

Nucleotide binding

21 – 29

9

GTP

Nucleotide binding

68 – 72

5

GTP By similarity

Nucleotide binding

127 – 130

4

GTP

Nucleotide binding

157 – 159

3

GTP

Motif

43 – 51

9

Effector region By similarity

Amino acid modifications

Modified residue

2

1

N-acetylalanine Ref.11

Modified residue

186

1

Phosphoserine Ref.8 Ref.9 Ref.10 Ref.11 Ref.12

Modified residue

190

1

Phosphothreonine Ref.11

Modified residue

201

1

Cysteine methyl ester Probable

Lipidation

199

1

S-palmitoyl cysteine Potential

Lipidation

201

1

S-farnesyl cysteine Ref.7

Natural variations

Natural variant

72

1

Q → L in an ovarian cancer sample; somatic mutation. Ref.2

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 [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]	"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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Uterus.
[5]	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 (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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.
[7]	"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.
[8]	"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: Cervix carcinoma.
[9]	"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. Tissue: Cervix carcinoma.
[10]	"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. Tissue: Cervix carcinoma.
[11]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-186 AND THR-190, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[12]	"Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed: 19369195] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-186, MASS SPECTROMETRY.
[13]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[14]	"The crystal structure of the Ras related protein RRAS2 in the GDP bound state." Structural genomics consortium (SGC) Submitted (FEB-2009) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 10-181 IN COMPLEX WITH GDP.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M31468 mRNA. Translation: AAA36545.1. Frameshift.
AF493924 mRNA. Translation: AAM12638.1. Frameshift.
AK313976 mRNA. Translation: BAG36690.1.
CH471064 Genomic DNA. Translation: EAW68487.1.
BC013106 mRNA. Translation: AAH13106.1.

IPI

IPI01011983.

PIR

TVHUC2. B34788.

RefSeq

NP_036382.2. NM_012250.5.

UniGene

Hs.502004.
Hs.712835.

3D structure databases

PDBe
RCSB PDB
PDBj

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

ProteinModelPortal

P62070.

SMR

P62070. Positions 13-181.

ModBase

Search...

Protein-protein interaction databases

IntAct

P62070. 14 interactions.

MINT

MINT-5001153.

STRING

P62070.

PTM databases

PhosphoSite

P62070.

Polymorphism databases

DMDM

49065833.

Proteomic databases

PeptideAtlas

P62070.

PRIDE

P62070.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000256196; ENSP00000256196; ENSG00000133818.

GeneID

22800.

KEGG

hsa:22800.

UCSC

uc001mlf.2. human.

Organism-specific databases

CTD

22800.

GeneCards

GC11M014299.

H-InvDB

HIX0009465.

HGNC

HGNC:17271. RRAS2.

HPA

CAB010420.

MIM

167000. phenotype.
600098. gene.

neXtProt

NX_P62070.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG07554.

GeneTree

ENSGT00600000084306.

HOVERGEN

HBG009351.

InParanoid

P62070.

OMA

AITIQFI.

OrthoDB

EOG4P5KB6.

PhylomeDB

P62070.

Gene expression databases

ArrayExpress

P62070.

Bgee

P62070.

CleanEx

HS_RRAS2.

Genevestigator

P62070.

GermOnline

ENSG00000133818. Homo sapiens.

Family and domain databases

InterPro

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

KO

K07830.

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

NextBio

43146.

SOURCE

Search...

Entry information

Entry name

RRAS2_HUMAN

Accession

Primary (citable) accession number: P62070
Secondary accession number(s): B2R9Z3, P17082

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 21, 2004
Last sequence update:	June 21, 2004
Last modified:	January 25, 2012
This is version 95 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.