Reviewed, UniProtKB/Swiss-Prot P62834 (RAP1A_HUMAN)

Names and origin

Protein names

Recommended name:
    Ras-related protein Rap-1A
Alternative name(s):
    GTP-binding protein smg-p21A
    Ras-related protein Krev-1
    C21KG
    G-22K

Gene names

Name:	RAP1A
Synonyms:	KREV1

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	184 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	Induces morphological reversion of a cell line transformed by a Ras oncogene. Counteracts the mitogenic function of Ras, at least partly because it can interact with Ras GAPs and RAF in a competitive manner.
Enzyme regulation	Activated by guanine nucleotide-exchange factors (GEF) EPAC and EPAC2 in a cAMP-dependent manner, and GFR.
Subunit structure	In its GTP-bound form interacts with PLCE1 and RADIL. Interacts with SGSM1, SGSM2 and SGSM3. Ref.10 Ref.11 Ref.12 Ref.13
Subcellular location	Cell membrane; Lipid-anchor.
Sequence similarities	Belongs to the small GTPase superfamily. Ras family.
Sequence caution	The sequence CAB55685.2 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Biological process	Cell cycle
Cellular component	Cell membrane Membrane
Ligand	GTP-binding Nucleotide-binding
Molecular function	Anti-oncogene
PTM	Lipoprotein Methylation Prenylation
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	cell cycle Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of cell cycle Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytosol Inferred from Experiment. Source: Reactome plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	GTP binding Inferred from electronic annotation. Source: UniProtKB-KW GTPase activity Traceable author statement. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Rabac1	Q9Z0S9	1	EBI-491414,EBI-476965	From a different organism.
RAF1	P04049	2	EBI-491414,EBI-365996
RASSF5	Q8WWW0	1	EBI-491414,EBI-367390
RASSF5	Q8WWW0-2	2	EBI-491414,EBI-960502
Rassf5	Q5EBH1	1	EBI-491414,EBI-960530	From a different organism.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 181

181

Ras-related protein Rap-1A

PRO_0000030199

Propeptide

182 – 184

3

Removed in mature form

PRO_0000030200

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

181

1

Cysteine methyl ester Ref.9

Lipidation

181

1

S-geranylgeranyl cysteine

Secondary structure

1

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184

Helix Strand Turn

Details...

Beta strand

3 – 9

7

Helix

16 – 25

10

Beta strand

36 – 48

13

Beta strand

50 – 58

9

Helix

67 – 74

8

Beta strand

76 – 83

8

Helix

87 – 91

5

Helix

93 – 104

12

Beta strand

111 – 116

6

Helix

121 – 123

3

Helix

128 – 137

10

Beta strand

142 – 145

4

Turn

148 – 151

4

Helix

154 – 165

12

Sequences

	Sequence		Length	Mass (Da)
	P62834-1 [UniParc]. Last modified August 16, 2004. Version 1. Checksum: 42C39290C98E0A92	FASTA	184	20,987
	10 20 30 40 50 60 MREYKLVVLG SGGVGKSALT VQFVQGIFVE KYDPTIEDSY RKQVEVDCQQ CMLEILDTAG 70 80 90 100 110 120 TEQFTAMRDL YMKNGQGFAL VYSITAQSTF NDLQDLREQI LRVKDTEDVP MILVGNKCDL 130 140 150 160 170 180 EDERVVGKEQ GQNLARQWCN CAFLESSAKS KINVNEIFYD LVRQINRKTP VEKKKPKKKS CLLL

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]	Pizon V. Submitted (FEB-1989) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION TO 3.
[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: Brain.
[4]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed: 16710414] [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: Skin.
[6]	"Purification, identification, and characterization of two GTP-binding proteins with molecular weights of 25,000 and 21,000 in human platelet cytosol. One is the rap1/smg21/Krev-1 protein and the other is a novel GTP-binding protein." Nagata K., Itoh H., Katada T., Takenaka K., Ui M., Kaziro Y., Nozawa Y. J. Biol. Chem. 264:17000-17005(1989) [PubMed: 2507536] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE. Tissue: Platelet.
[7]	"Purification and characterization of the 22,000-dalton GTP-binding protein substrate for ADP-ribosylation by botulinum toxin, G22K." Bokoch G.M., Parkos C.A., Mumby S.M. J. Biol. Chem. 263:16744-16749(1988) [PubMed: 3141412] [Abstract] Cited for: PROTEIN SEQUENCE OF 1-35.
[8]	"Identification of a platelet Mr 22,000 GTP-binding protein as the novel smg-21 gene product having the same putative effector domain as the ras gene products." Ohmori T., Kikuchi A., Yamamoto K., Kawata M., Kondo J., Takai Y. Biochem. Biophys. Res. Commun. 157:670-676(1988) [PubMed: 3144274] [Abstract] Cited for: PROTEIN SEQUENCE OF 1-5; 17-24; 32-42 AND 152-168.
[9]	"The COOH-terminal domain of the Rap1A (Krev-1) protein is isoprenylated and supports transformation by an H-Ras:Rap1A chimeric protein." Buss J.E., Quilliam L.A., Kato K., Casey P.J., Solski P.A., Wong G., Clark R., McCormick F., Bokoch G.M., Der C.J. Mol. Cell. Biol. 11:1523-1530(1991) [PubMed: 1899909] [Abstract] Cited for: ISOPRENYLATION AT CYS-181, METHYLATION AT CYS-181.
[10]	"Regulation of a novel human phospholipase C, PLCepsilon, through membrane targeting by Ras." Song C., Hu C.-D., Masago M., Kariya K., Yamawaki-Kataoka Y., Shibatohge M., Wu D., Satoh T., Kataoka T. J. Biol. Chem. 276:2752-2757(2001) [PubMed: 11022048] [Abstract] Cited for: INTERACTION WITH PLCE1.
[11]	"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.
[12]	"A Rap GTPase interactor, RADIL, mediates migration of neural crest precursors." Smolen G.A., Schott B.J., Stewart R.A., Diederichs S., Muir B., Provencher H.L., Look A.T., Sgroi D.C., Peterson R.T., Haber D.A. Genes Dev. 21:2131-2136(2007) [PubMed: 17704304] [Abstract] Cited for: INTERACTION WITH RADIL.
[13]	"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.
[14]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[15]	"The 2.2 A crystal structure of the Ras-binding domain of the serine/threonine kinase c-Raf1 in complex with Rap1A and a GTP analogue." Nassar N., Horn G., Herrmann C., Scherer A., McCormick F., Wittinghofer A. Nature 375:554-560(1995) [PubMed: 7791872] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 1-167.
[16]	"Ras/Rap effector specificity determined by charge reversal." Nassar N., Horn G., Herrmann C., Block C., Janknecht R., Wittinghofer A. Nat. Struct. Biol. 3:723-729(1996) [PubMed: 8756332] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 1-167.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBLGenBankDDBJ

X12533 mRNA. Translation: CAA31051.1.
M22995 mRNA. Translation: AAA36150.1.
AF493912 mRNA. Translation: AAM12626.1.
AL049557 Genomic DNA. Translation: CAB55685.2. Sequence problems.
BC014086 mRNA. Translation: AAH14086.1.

IPI

IPI00019345.

PIR

A32342.

RefSeq

NP_001010935.1.
NP_002875.1.

UniGene

Hs.190334

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1C1Y	X-ray	1.90	A	1-167	[»]
1GUA	X-ray	2.00	A	1-167	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:29106N.

IntAct

P62834. 7 interactions.

PTM databases

PhosphoSite

P62834.

2-D gel databases

OGP

P62834.

Proteomic databases

PRIDE

P62834.

Genome annotation databases

Ensembl

ENSG00000116473. Homo sapiens. [Contig view]

GeneID

5906.

KEGG

hsa:5906.

Organism-specific databases

GeneCards

GC01P111886.

H-InvDB

HIX0000882.

HGNC

HGNC:9855. RAP1A.

HPA

CAB018335.

MIM

179520. gene.

PharmGKB

PA34217.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P62834.

HOVERGEN

P62834.

OMA

P62834. DSIGTHE.

Enzyme and pathway databases

Pathway_Interaction_DB

amb2_neutrophils_pathway. amb2 Integrin signaling.
pi3kcipathway. Class I PI3K signaling events.
ephbfwdpathway. EPHB forward signaling.
epopathway. EPO signaling pathway.
ifngpathway. IFN-gamma pathway.
trkrpathway. Neurotrophic factor-mediated Trk receptor signaling.
reelinpathway. Reelin signaling pathway.
met_pathway. Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met).
ret_pathway. Signaling events regulated by Ret tyrosine kinase.
tcrpathway. TCR signaling in naive CD4+ T cells.
cd8tcrpathway. TCR signaling in naive CD8+ T cells.
mapktrkpathway. Trk receptor signaling mediated by the MAPK pathway.

Reactome

REACT_11061. Signalling by NGF.

Gene expression databases

ArrayExpress

P62834.

Bgee

P62834.

CleanEx

HS_RAP1A.

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

22972.

SOURCE

Search...

Entry information

Entry name

RAP1A_HUMAN

Accession

Primary (citable) accession number: P62834
Secondary accession number(s): P10113

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 16, 2004
Last sequence update:	August 16, 2004
Last modified:	June 16, 2009
This is version 66 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)