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P62834 (RAP1A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 122. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length184 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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. Together with ITGB1BP1, regulates KRIT1 localization to microtubules and membranes. Plays a role in nerve growth factor (NGF)-induced neurite outgrowth. Plays a role in the regulation of embryonic blood vessel formation. Involved in the establishment of basal endothelial barrier function. May be involved in the regulation of the vascular endothelial growth factor receptor KDR expression at endothelial cell-cell junctions. Ref.14 Ref.18

Enzyme regulation

Activated by guanine nucleotide-exchange factors (GEF) EPAC and EPAC2 in a cAMP-dependent manner, and GFR.

Subunit structure

Found in a complex, at least composed of ITGB1BP1, KRIT1 and RAP1A. Interacts (active GTP-bound form preferentially) with KRIT1 (via C-terminus FERM domain); the interaction does not induce the opening conformation of KRIT1. In its GTP-bound form interacts with PLCE1 and RADIL. Interacts with SGSM1, SGSM2 and SGSM3. Interacts (via GTP-bound active form) with RAPGEF2 (via Ras-associating domain). Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16

Subcellular location

Cell membrane; Lipid-anchor. Cytoplasm. Cytoplasmperinuclear region. Cell junction By similarity. Early endosome By similarity. Note: Recruited from early endosome to late endosome compartment after nerve growth factor (NGF) stimulation. Localized with RAPGEF2 at cell-cell junctions By similarity. Colocalized with RAPGEF2 in the perinuclear region. Ref.12

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 processNeurogenesis
   Cellular componentCell junction
Cell membrane
Cytoplasm
Endosome
Membrane
   DiseaseTumor suppressor
   LigandGTP-binding
Nucleotide-binding
   PTMLipoprotein
Methylation
Prenylation
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processRap protein signal transduction

Inferred from mutant phenotype Ref.18. Source: UniProtKB

activation of MAPKK activity

Traceable author statement. Source: Reactome

blood coagulation

Traceable author statement. Source: Reactome

cellular response to cAMP

Inferred from direct assay Ref.18. Source: UniProtKB

cellular response to nerve growth factor stimulus

Inferred from sequence or structural similarity. Source: UniProtKB

energy reserve metabolic process

Traceable author statement. Source: Reactome

establishment of endothelial barrier

Inferred from mutant phenotype Ref.18. Source: UniProtKB

nerve growth factor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

neurotrophin TRK receptor signaling pathway

Traceable author statement. Source: Reactome

platelet activation

Traceable author statement. Source: Reactome

positive regulation of ERK1 and ERK2 cascade

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of Rap GTPase activity

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of neuron projection development

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of protein kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of vasculogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

protein transport

Inferred from direct assay Ref.14. Source: UniProtKB

regulation of cell junction assembly

Inferred from mutant phenotype Ref.18. Source: UniProtKB

regulation of insulin secretion

Traceable author statement. Source: Reactome

signal transduction

Traceable author statement PubMed 2642744. Source: ProtInc

small molecule metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentcell junction

Inferred from sequence or structural similarity. Source: UniProtKB

cytoplasm

Inferred from direct assay Ref.12. Source: UniProtKB

cytosol

Traceable author statement. Source: Reactome

early endosome

Inferred from sequence or structural similarity. Source: UniProtKB

extracellular vesicular exosome

Inferred from direct assay PubMed 20458337PubMed 23376485. Source: UniProt

guanyl-nucleotide exchange factor complex

Inferred from electronic annotation. Source: Ensembl

late endosome

Inferred from sequence or structural similarity. Source: UniProtKB

perinuclear region of cytoplasm

Inferred from direct assay Ref.12. Source: UniProtKB

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functionGTP binding

Inferred from electronic annotation. Source: UniProtKB-KW

GTPase activity

Traceable author statement PubMed 10777492. Source: ProtInc

Rap guanyl-nucleotide exchange factor activity

Inferred from sequence or structural similarity. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.10Ref.11Ref.12Ref.14. Source: UniProtKB

protein complex binding

Inferred from direct assay Ref.14. Source: UniProtKB

protein transporter activity

Inferred from direct assay Ref.14. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

RAF1P040492EBI-491414,EBI-365996
RASSF5Q8WWW0-23EBI-491414,EBI-960502
Rassf5Q5EBH12EBI-491414,EBI-960530From a different organism.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 181181Ras-related protein Rap-1A
PRO_0000030199
Propeptide182 – 1843Removed in mature form
PRO_0000030200

Regions

Nucleotide binding10 – 178GTP By similarity
Nucleotide binding57 – 615GTP By similarity
Nucleotide binding116 – 1194GTP By similarity
Motif32 – 409Effector region Probable

Amino acid modifications

Modified residue1811Cysteine methyl ester Ref.9
Lipidation1811S-geranylgeranyl cysteine Ref.9

Secondary structure

.............................. 184
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P62834 [UniParc].

Last modified August 16, 2004. Version 1.
Checksum: 42C39290C98E0A92

FASTA18420,987
        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 

« Hide

References

« Hide '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. expand/collapse author list , 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]"RA-GEF, a novel Rap1A guanine nucleotide exchange factor containing a Ras/Rap1A-associating domain, is conserved between nematode and humans."
Liao Y., Kariya K., Hu C.-D., Shibatohge M., Goshima M., Okada T., Watari Y., Gao X., Jin T.-G., Yamawaki-Kataoka Y., Kataoka T.
J. Biol. Chem. 274:37815-37820(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RAPGEF2.
[11]"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.
[12]"RA-GEF-1, a guanine nucleotide exchange factor for Rap1, is activated by translocation induced by association with Rap1*GTP and enhances Rap1-dependent B-Raf activation."
Liao Y., Satoh T., Gao X., Jin T.G., Hu C.D., Kataoka T.
J. Biol. Chem. 276:28478-28483(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RAPGEF2, SUBCELLULAR LOCATION.
[13]"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.
[14]"Krit 1 interactions with microtubules and membranes are regulated by Rap1 and integrin cytoplasmic domain associated protein-1."
Beraud-Dufour S., Gautier R., Albiges-Rizo C., Chardin P., Faurobert E.
FEBS J. 274:5518-5532(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, IDENTIFICATION IN A COMPLEX WITH ITGB1BP1 AND KRIT1, INTERACTION WITH KRIT1.
[15]"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.
[16]"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.
[17]"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].
[18]"Epac1 and PDZ-GEF cooperate in Rap1 mediated endothelial junction control."
Pannekoek W.J., van Dijk J.J., Chan O.Y., Huveneers S., Linnemann J.R., Spanjaard E., Brouwer P.M., van der Meer A.J., Zwartkruis F.J., Rehmann H., de Rooij J., Bos J.L.
Cell. Signal. 23:2056-2064(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[19]"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.
[20]"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.

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.
CCDSCCDS840.1.
PIRA32342.
RefSeqNP_001010935.1. NM_001010935.2.
NP_001278825.1. NM_001291896.1.
NP_002875.1. NM_002884.3.
UniGeneHs.190334.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1C1YX-ray1.90A1-167[»]
1GUAX-ray2.00A1-167[»]
3KUCX-ray1.92A1-167[»]
4KVGX-ray1.65A/C1-167[»]
ProteinModelPortalP62834.
SMRP62834. Positions 1-167.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111841. 42 interactions.
DIPDIP-29106N.
IntActP62834. 9 interactions.
MINTMINT-1509313.
STRING9606.ENSP00000348786.

Chemistry

BindingDBP62834.
ChEMBLCHEMBL1255139.

PTM databases

PhosphoSiteP62834.

Polymorphism databases

DMDM51338607.

2D gel databases

OGPP62834.

Proteomic databases

MaxQBP62834.
PaxDbP62834.
PRIDEP62834.

Protocols and materials databases

DNASU5906.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000356415; ENSP00000348786; ENSG00000116473.
ENST00000369709; ENSP00000358723; ENSG00000116473.
ENST00000436150; ENSP00000394318; ENSG00000116473.
ENST00000545460; ENSP00000443009; ENSG00000116473.
GeneID5906.
KEGGhsa:5906.
UCSCuc001ebi.3. human.

Organism-specific databases

CTD5906.
GeneCardsGC01P112084.
HGNCHGNC:9855. RAP1A.
HPACAB018335.
MIM179520. gene.
neXtProtNX_P62834.
PharmGKBPA34217.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1100.
HOGENOMHOG000233973.
HOVERGENHBG009351.
InParanoidP62834.
KOK04353.
OMAKPKKSLC.
OrthoDBEOG7QVM41.
PhylomeDBP62834.
TreeFamTF313014.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_111217. Metabolism.
REACT_604. Hemostasis.
REACT_6900. Immune System.
SignaLinkP62834.

Gene expression databases

ArrayExpressP62834.
BgeeP62834.
CleanExHS_RAP1A.
GenevestigatorP62834.

Family and domain databases

Gene3D3.40.50.300. 1 hit.
InterProIPR027417. P-loop_NTPase.
IPR005225. Small_GTP-bd_dom.
IPR001806. Small_GTPase.
IPR020849. Small_GTPase_Ras.
[Graphical view]
PANTHERPTHR24070. PTHR24070. 1 hit.
PfamPF00071. Ras. 1 hit.
[Graphical view]
PRINTSPR00449. RASTRNSFRMNG.
SMARTSM00173. RAS. 1 hit.
[Graphical view]
SUPFAMSSF52540. SSF52540. 1 hit.
TIGRFAMsTIGR00231. small_GTP. 1 hit.
PROSITEPS51421. RAS. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSRAP1A. human.
EvolutionaryTraceP62834.
GeneWikiRAP1A.
GenomeRNAi5906.
NextBio22972.
PROP62834.
SOURCESearch...

Entry information

Entry nameRAP1A_HUMAN
AccessionPrimary (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: July 9, 2014
This is version 122 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM