Reviewed, UniProtKB/Swiss-Prot P10114 (RAP2A_HUMAN)

Names and origin

Protein names

Recommended name:
    Ras-related protein Rap-2a
Alternative name(s):
    RbBP-30

Gene names

Name:

RAP2A

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	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)

Enzyme regulation	Activated by guanine nucleotide-exchange factors (GEF) EPAC and EPAC2 in a cAMP-dependent manner, and GFR.
Subunit structure	Interacts with PLCE1. Interacts with SGSM1, SGSM2, SGSM3 and ARHGAP29. The GTP-bound form of RAP2A interacts with RUNDC3A By similarity.
Subcellular location	Cell membrane; Lipid-anchor; Cytoplasmic side Potential.
Domain	The effector domain mediates the interaction with RUNDC3A By similarity.
Sequence similarities	Belongs to the small GTPase superfamily. Ras family.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Ligand	GTP-binding Nucleotide-binding
PTM	Lipoprotein Methylation Prenylation
Technical term	3D-structure
Gene Ontology (GO)
Biological process	small GTPase mediated signal transduction Inferred from electronic annotation. Source: InterPro
Cellular component	intracellular Inferred from electronic annotation. Source: InterPro plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	GTP binding Inferred from electronic annotation. Source: UniProtKB-KW GTPase activity Ref.6 Traceable author statement. Source: ProtInc protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
MINK1	Q8N4C8	2	EBI-602366,EBI-2133481

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 180

180

Ras-related protein Rap-2a

PRO_0000082687

Propeptide

181 – 183

3

Removed in mature form By similarity

PRO_0000281336

Regions

Nucleotide binding

10 – 17

8

GTP By similarity

Nucleotide binding

57 – 61

5

GTP By similarity

Nucleotide binding

116 – 119

4

GTP By similarity

Motif

32 – 40

9

Effector region Probable

Amino acid modifications

Modified residue

180

1

Cysteine methyl ester Probable

Lipidation

180

1

S-farnesyl cysteine

Experimental info

Mutagenesis

12

1

G → V: 2-fold decrease in GDP dissociation rate constant and GTPase activity.

Mutagenesis

17

1

S → N: Severely impairs GTP-binding.

Mutagenesis

35

1

T → A: Decreases affinity for GTP and 3-fold reduction of GTPase activity.

Mutagenesis

145

1

T → I: Imperfect binding of guanyl nucleotides.

Secondary structure

1

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183

Helix Strand Turn

Details...

Beta strand

3 – 9

7

Helix

16 – 25

10

Beta strand

38 – 46

9

Beta strand

49 – 57

9

Helix

65 – 74

10

Beta strand

76 – 83

8

Helix

87 – 103

17

Turn

104 – 106

3

Beta strand

111 – 116

6

Helix

118 – 123

6

Helix

128 – 138

11

Beta strand

142 – 145

4

Helix

150 – 166

17

Sequences

	Sequence		Length	Mass (Da)
	P10114-1 [UniParc]. Last modified July 1, 1989. Version 1. Checksum: 047D49762765F0B7	FASTA	183	20,615
	10 20 30 40 50 60 MREYKVVVLG SGGVGKSALT VQFVTGTFIE KYDPTIEDFY RKEIEVDSSP SVLEILDTAG 70 80 90 100 110 120 TEQFASMRDL YIKNGQGFIL VYSLVNQQSF QDIKPMRDQI IRVKRYEKVP VILVGNKVDL 130 140 150 160 170 180 ESEREVSSSE GRALAEEWGC PFMETSAKSK TMVDELFAEI VRQMNYAAQP DKDDPCCSAC NIQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human cDNAs rap1 and rap2 homologous to the Drosophila gene Dras3 encode proteins closely related to ras in the 'effector' region." Pizon V., Chardin P., Lerosey I., Olofsson B., Tavitian A. Oncogene 3:201-204(1988) [PubMed: 3045729] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"A novel new gene associated with pRb." Fan Z.S., Ao S.Z. Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Lymph node.
[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].
[4]	"The DNA sequence and analysis of human chromosome 13." Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L., Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S., Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P., Ambrose K.D., Andrews D.T. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P., Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C., Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P., Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L., Frankish A.G., Frankland J., French L., Garner P., Garnett J., Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M., Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D., Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D., Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S., Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S., Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R., Rogers J., Ross M.T. Nature 428:522-528(2004) [PubMed: 15057823] [Abstract] 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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[6]	"The product of the rap2 gene, member of the ras superfamily. Biochemical characterization and site-directed mutagenesis." Lerosey I., Chardin P., de Gunzburg J., Tavitian A. J. Biol. Chem. 266:4315-4321(1991) [PubMed: 1900290] [Abstract] Cited for: GTP-BINDING, MUTAGENESIS.
[7]	"Prenyl group identification of rap2 proteins: a ras superfamily member other than ras that is farnesylated." Farrell F.X., Yamamoto K., Lapetina E.G. Biochem. J. 289:349-355(1993) [PubMed: 8424780] [Abstract] Cited for: ISOPRENYLATION AT CYS-180.
[8]	"Differential roles of Ras and Rap1 in growth factor-dependent activation of phospholipase C epsilon." Song C., Satoh T., Edamatsu H., Wu D., Tadano M., Gao X., Kataoka T. Oncogene 21:8105-8113(2002) [PubMed: 12444546] [Abstract] Cited for: INTERACTION WITH PLCE1.
[9]	"PARG1, a protein-tyrosine phosphatase-associated RhoGAP, as a putative Rap2 effector." Myagmar B.-E., Umikawa M., Asato T., Taira K., Oshiro M., Hino A., Takei K., Uezato H., Kariya K. Biochem. Biophys. Res. Commun. 329:1046-1052(2005) [PubMed: 15752761] [Abstract] Cited for: INTERACTION WITH ARHGAP29.
[10]	"Identification of three novel proteins (SGSM1, 2, 3) which modulate small G protein (RAP and RAB)-mediated signaling pathway." Yang H., Sasaki T., Minoshima S., Shimizu N. Genomics 90:249-260(2007) [PubMed: 17509819] [Abstract] Cited for: INTERACTION WITH SGSM1; SGSM2 AND SGSM3.
[11]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[12]	"Crystal structures of the small G protein Rap2A in complex with its substrate GTP, with GDP and with GTPgammaS." Cherfils J., Menetrey J., Le Bras G., Janoueix-Lerosey I., de Gunzburg J., Garel J.-R., Auzat I. EMBO J. 16:5582-5591(1997) [PubMed: 9312017] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS).
[13]	"Structure of the small G protein Rap2 in a non-catalytic complex with GTP." Menetrey J., Cherfils J. Proteins 37:465-473(1999) [PubMed: 10591105] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBLGenBankDDBJ

X12534 mRNA. Translation: CAA31052.1.
AF205602 mRNA. Translation: AAN71845.1.
AF493914 mRNA. Translation: AAM12628.1.
AL442067 Genomic DNA. Translation: CAI39499.1.
BC041333 mRNA. Translation: AAH41333.1.
BC070031 mRNA. Translation: AAH70031.1.

IPI

IPI00019346.

PIR

S03180.

RefSeq

NP_066361.1.

UniGene

Hs.508480

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1KAO	X-ray	1.70	A	1-167	[»]
2RAP	X-ray	2.60	A	1-167	[»]
3RAP	X-ray	2.20	R/S	1-167	[»]

DisProt

DP00167.

ModBase

Search...

Protein-protein interaction databases

IntAct

P10114. 13 interactions.

Proteomic databases

PRIDE

P10114.

Genome annotation databases

Ensembl

ENSG00000125249. Homo sapiens. [Contig view]

GeneID

5911.

KEGG

hsa:5911.

Organism-specific databases

GeneCards

GC13P096884.

H-InvDB

HIX0037306.

HGNC

HGNC:9861. RAP2A.

MIM

179540. gene.

PharmGKB

PA34222.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P10114.

HOVERGEN

P10114.

OMA

P10114. CCSSCNI.

Gene expression databases

ArrayExpress

P10114.

Bgee

P10114.

CleanEx

HS_RAP2A.

GermOnline

ENSG00000125249. 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

23004.

SOURCE

Search...

Entry information

Entry name

RAP2A_HUMAN

Accession

Primary (citable) accession number: P10114
Secondary accession number(s): Q5JSC1, Q5JSC2

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1989
Last sequence update:	July 1, 1989
Last modified:	June 16, 2009
This is version 108 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)