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Protein

Ras-related protein Rap-1A

Gene

RAP1A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.2 Publications

Enzyme regulationi

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei60GTP; via amide nitrogen2 Publications1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi10 – 18GTP2 Publications9
Nucleotide bindingi29 – 35GTP2 Publications7
Nucleotide bindingi116 – 119GTP2 Publications4

GO - Molecular functioni

  • GTPase activity Source: ProtInc
  • GTP binding Source: UniProtKB-KW
  • protein complex binding Source: UniProtKB
  • protein transporter activity Source: UniProtKB
  • Rap guanyl-nucleotide exchange factor activity Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Neurogenesis

Keywords - Ligandi

GTP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000116473-MONOMER.
ReactomeiR-HSA-170968. Frs2-mediated activation.
R-HSA-170984. ARMS-mediated activation.
R-HSA-354192. Integrin alphaIIb beta3 signaling.
R-HSA-354194. GRB2:SOS provides linkage to MAPK signaling for Integrins.
R-HSA-372708. p130Cas linkage to MAPK signaling for integrins.
R-HSA-381676. Glucagon-like Peptide-1 (GLP1) regulates insulin secretion.
R-HSA-392517. Rap1 signalling.
R-HSA-5674135. MAP2K and MAPK activation.
R-HSA-6798695. Neutrophil degranulation.
R-HSA-6802946. Signaling by moderate kinase activity BRAF mutants.
R-HSA-6802948. Signaling by high-kinase activity BRAF mutants.
R-HSA-6802949. Signaling by RAS mutants.
R-HSA-6802952. Signaling by BRAF and RAF fusions.
R-HSA-6802955. Paradoxical activation of RAF signaling by kinase inactive BRAF.
R-HSA-8875555. MET activates RAP1 and RAC1.
SignaLinkiP62834.
SIGNORiP62834.

Names & Taxonomyi

Protein namesi
Recommended name:
Ras-related protein Rap-1A
Alternative name(s):
C21KG
G-22K
GTP-binding protein smg p21A
Ras-related protein Krev-1
Gene namesi
Name:RAP1A
Synonyms:KREV1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:9855. RAP1A.

Subcellular locationi

  • Cell membrane 1 Publication; Lipid-anchor 1 Publication
  • Cytoplasm 1 Publication
  • Cytoplasmperinuclear region 1 Publication
  • 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.By similarity

GO - Cellular componenti

  • cell junction Source: UniProtKB
  • cytoplasm Source: UniProtKB
  • cytosol Source: Reactome
  • early endosome Source: UniProtKB
  • extracellular exosome Source: UniProtKB
  • guanyl-nucleotide exchange factor complex Source: Ensembl
  • late endosome Source: UniProtKB
  • myelin sheath Source: Ensembl
  • neuron projection Source: Ensembl
  • perinuclear region of cytoplasm Source: UniProtKB
  • plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Cytoplasm, Endosome, Membrane

Pathology & Biotechi

Keywords - Diseasei

Tumor suppressor

Organism-specific databases

DisGeNETi5906.
OpenTargetsiENSG00000116473.
PharmGKBiPA34217.

Chemistry databases

ChEMBLiCHEMBL1255139.

Polymorphism and mutation databases

BioMutaiRAP1A.
DMDMi51338607.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000301991 – 181Ras-related protein Rap-1AAdd BLAST181
PropeptideiPRO_0000030200182 – 184Removed in mature form3

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei181Cysteine methyl ester1 Publication1
Lipidationi181S-geranylgeranyl cysteine1 Publication1

Keywords - PTMi

Lipoprotein, Methylation, Prenylation

Proteomic databases

EPDiP62834.
MaxQBiP62834.
PaxDbiP62834.
PeptideAtlasiP62834.
PRIDEiP62834.
TopDownProteomicsiP62834.

2D gel databases

OGPiP62834.

PTM databases

iPTMnetiP62834.
PhosphoSitePlusiP62834.
SwissPalmiP62834.

Expressioni

Gene expression databases

BgeeiENSG00000116473.
CleanExiHS_RAP1A.
ExpressionAtlasiP62834. baseline and differential.
GenevisibleiP62834. HS.

Organism-specific databases

HPAiCAB018335.

Interactioni

Subunit structurei

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).7 Publications

Binary interactionsi

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

GO - Molecular functioni

  • protein complex binding Source: UniProtKB

Protein-protein interaction databases

BioGridi111841. 71 interactors.
DIPiDIP-29106N.
IntActiP62834. 23 interactors.
MINTiMINT-1509313.
STRINGi9606.ENSP00000348786.

Chemistry databases

BindingDBiP62834.

Structurei

Secondary structure

1184
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi2 – 9Combined sources8
Helixi16 – 25Combined sources10
Beta strandi36 – 46Combined sources11
Beta strandi49 – 58Combined sources10
Helixi66 – 74Combined sources9
Beta strandi76 – 83Combined sources8
Helixi87 – 91Combined sources5
Helixi93 – 104Combined sources12
Beta strandi111 – 116Combined sources6
Helixi121 – 123Combined sources3
Helixi128 – 137Combined sources10
Turni138 – 140Combined sources3
Beta strandi142 – 145Combined sources4
Turni148 – 150Combined sources3
Helixi154 – 166Combined sources13

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1C1YX-ray1.90A1-167[»]
1GUAX-ray2.00A1-167[»]
3KUCX-ray1.92A1-167[»]
4KVGX-ray1.65A/C1-167[»]
ProteinModelPortaliP62834.
SMRiP62834.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP62834.

Family & Domainsi

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi32 – 40Effector regionCurated9

Sequence similaritiesi

Belongs to the small GTPase superfamily. Ras family.Curated

Phylogenomic databases

eggNOGiKOG0395. Eukaryota.
COG1100. LUCA.
GeneTreeiENSGT00860000133678.
HOGENOMiHOG000233973.
HOVERGENiHBG009351.
InParanoidiP62834.
KOiK04353.
OMAiARSFNSA.
OrthoDBiEOG091G0OOG.
PhylomeDBiP62834.
TreeFamiTF313014.

Family and domain databases

Gene3Di3.40.50.300. 1 hit.
InterProiIPR027417. P-loop_NTPase.
IPR005225. Small_GTP-bd_dom.
IPR001806. Small_GTPase.
IPR020849. Small_GTPase_Ras.
[Graphical view]
PANTHERiPTHR24070. PTHR24070. 1 hit.
PfamiPF00071. Ras. 1 hit.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 1 hit.
TIGRFAMsiTIGR00231. small_GTP. 1 hit.
PROSITEiPS51421. RAS. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P62834-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MREYKLVVLG SGGVGKSALT VQFVQGIFVE KYDPTIEDSY RKQVEVDCQQ
60 70 80 90 100
CMLEILDTAG TEQFTAMRDL YMKNGQGFAL VYSITAQSTF NDLQDLREQI
110 120 130 140 150
LRVKDTEDVP MILVGNKCDL EDERVVGKEQ GQNLARQWCN CAFLESSAKS
160 170 180
KINVNEIFYD LVRQINRKTP VEKKKPKKKS CLLL
Length:184
Mass (Da):20,987
Last modified:August 16, 2004 - v1
Checksum:i42C39290C98E0A92
GO

Sequence cautioni

The sequence CAB55685 differs from that shown. Reason: Erroneous gene model prediction.Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS840.1.
PIRiA32342.
RefSeqiNP_001010935.1. NM_001010935.2.
NP_001278825.1. NM_001291896.1.
NP_002875.1. NM_002884.3.
XP_016857451.1. XM_017001962.1.
XP_016857452.1. XM_017001963.1.
XP_016857453.1. XM_017001964.1.
UniGeneiHs.190334.
Hs.586618.

Genome annotation databases

EnsembliENST00000356415; ENSP00000348786; ENSG00000116473.
ENST00000369709; ENSP00000358723; ENSG00000116473.
GeneIDi5906.
KEGGihsa:5906.
UCSCiuc001ebi.4. human.

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS840.1.
PIRiA32342.
RefSeqiNP_001010935.1. NM_001010935.2.
NP_001278825.1. NM_001291896.1.
NP_002875.1. NM_002884.3.
XP_016857451.1. XM_017001962.1.
XP_016857452.1. XM_017001963.1.
XP_016857453.1. XM_017001964.1.
UniGeneiHs.190334.
Hs.586618.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1C1YX-ray1.90A1-167[»]
1GUAX-ray2.00A1-167[»]
3KUCX-ray1.92A1-167[»]
4KVGX-ray1.65A/C1-167[»]
ProteinModelPortaliP62834.
SMRiP62834.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111841. 71 interactors.
DIPiDIP-29106N.
IntActiP62834. 23 interactors.
MINTiMINT-1509313.
STRINGi9606.ENSP00000348786.

Chemistry databases

BindingDBiP62834.
ChEMBLiCHEMBL1255139.

PTM databases

iPTMnetiP62834.
PhosphoSitePlusiP62834.
SwissPalmiP62834.

Polymorphism and mutation databases

BioMutaiRAP1A.
DMDMi51338607.

2D gel databases

OGPiP62834.

Proteomic databases

EPDiP62834.
MaxQBiP62834.
PaxDbiP62834.
PeptideAtlasiP62834.
PRIDEiP62834.
TopDownProteomicsiP62834.

Protocols and materials databases

DNASUi5906.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000356415; ENSP00000348786; ENSG00000116473.
ENST00000369709; ENSP00000358723; ENSG00000116473.
GeneIDi5906.
KEGGihsa:5906.
UCSCiuc001ebi.4. human.

Organism-specific databases

CTDi5906.
DisGeNETi5906.
GeneCardsiRAP1A.
HGNCiHGNC:9855. RAP1A.
HPAiCAB018335.
MIMi179520. gene.
neXtProtiNX_P62834.
OpenTargetsiENSG00000116473.
PharmGKBiPA34217.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0395. Eukaryota.
COG1100. LUCA.
GeneTreeiENSGT00860000133678.
HOGENOMiHOG000233973.
HOVERGENiHBG009351.
InParanoidiP62834.
KOiK04353.
OMAiARSFNSA.
OrthoDBiEOG091G0OOG.
PhylomeDBiP62834.
TreeFamiTF313014.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000116473-MONOMER.
ReactomeiR-HSA-170968. Frs2-mediated activation.
R-HSA-170984. ARMS-mediated activation.
R-HSA-354192. Integrin alphaIIb beta3 signaling.
R-HSA-354194. GRB2:SOS provides linkage to MAPK signaling for Integrins.
R-HSA-372708. p130Cas linkage to MAPK signaling for integrins.
R-HSA-381676. Glucagon-like Peptide-1 (GLP1) regulates insulin secretion.
R-HSA-392517. Rap1 signalling.
R-HSA-5674135. MAP2K and MAPK activation.
R-HSA-6798695. Neutrophil degranulation.
R-HSA-6802946. Signaling by moderate kinase activity BRAF mutants.
R-HSA-6802948. Signaling by high-kinase activity BRAF mutants.
R-HSA-6802949. Signaling by RAS mutants.
R-HSA-6802952. Signaling by BRAF and RAF fusions.
R-HSA-6802955. Paradoxical activation of RAF signaling by kinase inactive BRAF.
R-HSA-8875555. MET activates RAP1 and RAC1.
SignaLinkiP62834.
SIGNORiP62834.

Miscellaneous databases

ChiTaRSiRAP1A. human.
EvolutionaryTraceiP62834.
GeneWikiiRAP1A.
GenomeRNAii5906.
PROiP62834.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000116473.
CleanExiHS_RAP1A.
ExpressionAtlasiP62834. baseline and differential.
GenevisibleiP62834. HS.

Family and domain databases

Gene3Di3.40.50.300. 1 hit.
InterProiIPR027417. P-loop_NTPase.
IPR005225. Small_GTP-bd_dom.
IPR001806. Small_GTPase.
IPR020849. Small_GTPase_Ras.
[Graphical view]
PANTHERiPTHR24070. PTHR24070. 1 hit.
PfamiPF00071. Ras. 1 hit.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 1 hit.
TIGRFAMsiTIGR00231. small_GTP. 1 hit.
PROSITEiPS51421. RAS. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiRAP1A_HUMAN
AccessioniPrimary (citable) accession number: P62834
Secondary accession number(s): P10113
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 16, 2004
Last sequence update: August 16, 2004
Last modified: November 30, 2016
This is version 149 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.