P62834 (RAP1A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ras-related protein Rap-1A

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

Gene names

Name:	RAP1A
Synonyms:	KREV1

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	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
Cellular component	Cell membrane Membrane
Disease	Tumor suppressor
Ligand	GTP-binding Nucleotide-binding
PTM	Lipoprotein Methylation Prenylation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	activation of MAPKK activity Traceable author statement. Source: Reactome energy reserve metabolic process Traceable author statement. Source: Reactome nerve growth factor receptor signaling pathway Traceable author statement. Source: Reactome platelet activation Traceable author statement. Source: Reactome regulation of insulin secretion Traceable author statement. Source: Reactome small GTPase mediated signal transduction Inferred from electronic annotation. Source: Compara
Cellular_component	cytosol Traceable author statement. Source: Reactome guanyl-nucleotide exchange factor complex Inferred from electronic annotation. Source: Compara plasma membrane Traceable author statement. Source: Reactome
Molecular_function	GTP binding Inferred from electronic annotation. Source: UniProtKB-KW GTPase activity Traceable author statement PubMed 10777492. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
RAF1	P04049	2	EBI-491414,EBI-365996
RASSF5	Q8WWW0-2	3	EBI-491414,EBI-960502
Rassf5	Q5EBH1	2	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 Ref.9

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

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

Turn

138 – 140

3

Beta strand

142 – 145

4

Turn

148 – 151

4

Helix

154 – 165

12

Sequences

	Sequence		Length	Mass (Da)
	P62834 [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SGSM1; SGSM2 AND SGSM3.
[14]	"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] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[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] [Europe PMC] [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] [Europe PMC] [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

EMBL
GenBank
DDBJ

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. NM_001010935.1.
NP_002875.1. NM_002884.2.

UniGene

Hs.190334.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1C1Y	X-ray	1.90	A	1-167	[»]
1GUA	X-ray	2.00	A	1-167	[»]
3KUC	X-ray	1.92	A	1-167	[»]

ProteinModelPortal

P62834.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29106N.

IntAct

P62834. 7 interactions.

STRING

9606.ENSP00000348786.

PTM databases

PhosphoSite

P62834.

Polymorphism databases

DMDM

51338607.

2D gel databases

OGP

P62834.

Proteomic databases

PaxDb

P62834.

PRIDE

P62834.

Protocols and materials databases

DNASU

5906.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000356415; ENSP00000348786; ENSG00000116473.
ENST00000369709; ENSP00000358723; ENSG00000116473.
ENST00000433097; ENSP00000396741; ENSG00000116473.
ENST00000436150; ENSP00000394318; ENSG00000116473.
ENST00000545460; ENSP00000443009; ENSG00000116473.

GeneID

5906.

KEGG

hsa:5906.

UCSC

uc001ebi.3. human.

Organism-specific databases

CTD

5906.

GeneCards

GC01P112084.

HGNC

HGNC:9855. RAP1A.

HPA

CAB018335.

MIM

179520. gene.

neXtProt

NX_P62834.

PharmGKB

PA34217.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG1100.

HOGENOM

HOG000233973.

HOVERGEN

HBG009351.

InParanoid

P62834.

KO

K04353.

OMA

DSIGTHE.

OrthoDB

EOG45MN6H.

PhylomeDB

P62834.

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_111102. Signal Transduction.
REACT_111217. Metabolism.
REACT_604. Hemostasis.
REACT_6900. Immune System.

Gene expression databases

ArrayExpress

P62834.

Bgee

P62834.

CleanEx

HS_RAP1A.

Genevestigator

P62834.

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

BindingDB

P62834.

ChEMBL

CHEMBL1255139.

ChiTaRS

RAP1A. human.

EvolutionaryTrace

P62834.

GenomeRNAi

5906.

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:	May 1, 2013
This is version 108 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.