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Protein

Ras-related protein Rap-2a

Gene

RAP2A

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

Functioni

Small GTP-binding protein which cycles between a GDP-bound inactive and a GTP-bound active form. In its active form interacts with and regulates several effectors including MAP4K4, MINK1 and TNIK. Part of a signaling complex composed of NEDD4, RAP2A and TNIK which regulates neuronal dendrite extension and arborization during development. More generally, it is part of several signaling cascades and may regulate cytoskeletal rearrangements, cell migration, cell adhesion and cell spreading.6 Publications

Enzyme regulationi

Activated by the guanine nucleotide-exchange factors RAPGEF3 and RAPGEF4 in a cAMP-dependent manner. Nucleotide exchange is also specifically stimulated by RAPGEF5, RASGEF1A and RASGEF1B.1 Publication

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi10 – 17GTPBy similarity8
Nucleotide bindingi57 – 61GTPBy similarity5
Nucleotide bindingi116 – 119GTPBy similarity4

GO - Molecular functioni

  • GTPase activity Source: UniProtKB
  • GTP binding Source: UniProtKB

GO - Biological processi

  • actin cytoskeleton reorganization Source: UniProtKB
  • cellular protein localization Source: UniProtKB
  • cellular response to drug Source: UniProtKB
  • establishment of protein localization Source: MGI
  • microvillus assembly Source: UniProtKB
  • negative regulation of cell migration Source: Ensembl
  • positive regulation of protein autophosphorylation Source: UniProtKB
  • positive regulation of protein phosphorylation Source: UniProtKB
  • protein localization to plasma membrane Source: UniProtKB
  • Rap protein signal transduction Source: UniProtKB
  • regulation of dendrite morphogenesis Source: UniProtKB
  • regulation of JNK cascade Source: UniProtKB
Complete GO annotation...

Keywords - Ligandi

GTP-binding, Nucleotide-binding

Enzyme and pathway databases

SignaLinkiP10114.

Names & Taxonomyi

Protein namesi
Recommended name:
Ras-related protein Rap-2a
Alternative name(s):
RbBP-30
Gene namesi
Name:RAP2A
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 13

Organism-specific databases

HGNCiHGNC:9861. RAP2A.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: Ensembl
  • extracellular exosome Source: UniProtKB
  • midbody Source: UniProtKB-SubCell
  • plasma membrane Source: UniProtKB
  • recycling endosome Source: UniProtKB
  • recycling endosome membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Endosome, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi5K → R: Reduced NEDD4-dependent ubiquitination; when associated with R-94; R-148 and R-150. 1 Publication1
Mutagenesisi12G → V: Dominant active. 2-fold decrease in GDP dissociation rate constant and GTPase activity. No change in interaction with TNIK. 2 Publications1
Mutagenesisi17S → N: Dominant negative. Severely impairs GTP-binding and partial loss of interaction with MAP4K4, MINK1 and TNIK. 2 Publications1
Mutagenesisi35T → A: Decreases affinity for GTP and 3-fold reduction of GTPase activity. 1 Publication1
Mutagenesisi39F → S: Loss of RASGEF1A- and RASGEF1B-mediated GDP to GTP exchange. Complete loss of interaction with MAP4K4, MINK1 and TNIK, and loss of ubiquitination by NEDD4. 3 Publications1
Mutagenesisi94K → R: Reduced NEDD4-dependent ubiquitination; when associated with R-5; R-148 and R-150. 1 Publication1
Mutagenesisi145T → I: Imperfect binding of guanyl nucleotides. 1 Publication1
Mutagenesisi148K → R: Reduced NEDD4-dependent ubiquitination; when associated with R-5; R-94 and R-150. 1 Publication1
Mutagenesisi150K → R: Reduced NEDD4-dependent ubiquitination; when associated with R-5; R-94 and R-148. 1 Publication1

Organism-specific databases

DisGeNETi5911.
OpenTargetsiENSG00000125249.
PharmGKBiPA34222.

Polymorphism and mutation databases

BioMutaiRAP2A.
DMDMi131852.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000826871 – 180Ras-related protein Rap-2aAdd BLAST180
PropeptideiPRO_0000281336181 – 183Removed in mature form1 Publication3

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi176S-palmitoyl cysteineBy similarity1
Lipidationi177S-palmitoyl cysteineBy similarity1
Modified residuei180Cysteine methyl ester1 Publication1
Lipidationi180S-farnesyl cysteine1 Publication1

Post-translational modificationi

Ubiquitinated; undergoes 'Lys-63' monoubiquitination and diubiquitination by NEDD4. Multiple lysine residues are probably modified. Ubiquitination requires TNIK, prevents interaction with effectors and inactivates RAP2A.1 Publication
Palmitoylated. Palmitoylation is required for association with recycling endosome membranes and activation of TNIK.By similarity

Keywords - PTMi

Lipoprotein, Methylation, Palmitate, Prenylation, Ubl conjugation

Proteomic databases

EPDiP10114.
MaxQBiP10114.
PaxDbiP10114.
PeptideAtlasiP10114.
PRIDEiP10114.

PTM databases

iPTMnetiP10114.
PhosphoSitePlusiP10114.
SwissPalmiP10114.

Expressioni

Gene expression databases

BgeeiENSG00000125249.
CleanExiHS_RAP2A.
ExpressionAtlasiP10114. baseline and differential.
GenevisibleiP10114. HS.

Organism-specific databases

HPAiCAB018552.

Interactioni

Subunit structurei

Interacts (GTP-bound form) with RUNDC3A. Interacts with RGS14; the interaction is GTP-dependent (By similarity). Interacts with PLCE1. Interacts with ARHGAP29, SGSM1, SGSM2 and SGSM3. Interacts (GTP-bound form preferentially) with TNIK (via the CNH domain); the interaction is direct and recruits RAP2A to the E3 ubiquitin ligase NEDD4. Interacts with MINK1. Interacts (GTP-bound form preferentially) with MAP4K4. Interacts with cytoskeletal actin.By similarity8 Publications

Protein-protein interaction databases

BioGridi111846. 41 interactors.
IntActiP10114. 14 interactors.
MINTiMINT-1172095.
STRINGi9606.ENSP00000245304.

Structurei

Secondary structure

1183
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi3 – 9Combined sources7
Helixi16 – 25Combined sources10
Beta strandi38 – 46Combined sources9
Beta strandi49 – 57Combined sources9
Helixi65 – 74Combined sources10
Beta strandi76 – 83Combined sources8
Helixi87 – 103Combined sources17
Turni104 – 106Combined sources3
Beta strandi111 – 116Combined sources6
Helixi118 – 123Combined sources6
Helixi128 – 138Combined sources11
Beta strandi142 – 145Combined sources4
Helixi150 – 166Combined sources17

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1KAOX-ray1.70A1-167[»]
2RAPX-ray2.60A1-167[»]
3RAPX-ray2.20R/S1-167[»]
DisProtiDP00167.
ProteinModelPortaliP10114.
SMRiP10114.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP10114.

Family & Domainsi

Motif

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

Domaini

The effector domain mediates the interaction with RUNDC3A.By similarity

Sequence similaritiesi

Belongs to the small GTPase superfamily. Ras family.Curated

Phylogenomic databases

eggNOGiKOG0395. Eukaryota.
COG1100. LUCA.
GeneTreeiENSGT00860000133678.
HOGENOMiHOG000233973.
HOVERGENiHBG009351.
InParanoidiP10114.
KOiK07837.
OMAiEINGASW.
OrthoDBiEOG091G0OOG.
PhylomeDBiP10114.
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.

P10114-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MREYKVVVLG SGGVGKSALT VQFVTGTFIE KYDPTIEDFY RKEIEVDSSP
60 70 80 90 100
SVLEILDTAG TEQFASMRDL YIKNGQGFIL VYSLVNQQSF QDIKPMRDQI
110 120 130 140 150
IRVKRYEKVP VILVGNKVDL ESEREVSSSE GRALAEEWGC PFMETSAKSK
160 170 180
TMVDELFAEI VRQMNYAAQP DKDDPCCSAC NIQ
Length:183
Mass (Da):20,615
Last modified:July 1, 1989 - v1
Checksum:i047D49762765F0B7
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X12534 mRNA. Translation: CAA31052.1.
AF205602 mRNA. Translation: AAN71845.1.
AF493914 mRNA. Translation: AAM12628.1.
AK315139 mRNA. Translation: BAG37588.1.
AL442067 Genomic DNA. Translation: CAI39499.1.
CH471085 Genomic DNA. Translation: EAX08974.1.
BC041333 mRNA. Translation: AAH41333.1.
BC070031 mRNA. Translation: AAH70031.1.
CCDSiCCDS9485.1.
PIRiS03180.
RefSeqiNP_066361.1. NM_021033.6.
UniGeneiHs.508480.

Genome annotation databases

EnsembliENST00000245304; ENSP00000245304; ENSG00000125249.
GeneIDi5911.
KEGGihsa:5911.
UCSCiuc001vnd.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
X12534 mRNA. Translation: CAA31052.1.
AF205602 mRNA. Translation: AAN71845.1.
AF493914 mRNA. Translation: AAM12628.1.
AK315139 mRNA. Translation: BAG37588.1.
AL442067 Genomic DNA. Translation: CAI39499.1.
CH471085 Genomic DNA. Translation: EAX08974.1.
BC041333 mRNA. Translation: AAH41333.1.
BC070031 mRNA. Translation: AAH70031.1.
CCDSiCCDS9485.1.
PIRiS03180.
RefSeqiNP_066361.1. NM_021033.6.
UniGeneiHs.508480.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1KAOX-ray1.70A1-167[»]
2RAPX-ray2.60A1-167[»]
3RAPX-ray2.20R/S1-167[»]
DisProtiDP00167.
ProteinModelPortaliP10114.
SMRiP10114.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111846. 41 interactors.
IntActiP10114. 14 interactors.
MINTiMINT-1172095.
STRINGi9606.ENSP00000245304.

PTM databases

iPTMnetiP10114.
PhosphoSitePlusiP10114.
SwissPalmiP10114.

Polymorphism and mutation databases

BioMutaiRAP2A.
DMDMi131852.

Proteomic databases

EPDiP10114.
MaxQBiP10114.
PaxDbiP10114.
PeptideAtlasiP10114.
PRIDEiP10114.

Protocols and materials databases

DNASUi5911.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000245304; ENSP00000245304; ENSG00000125249.
GeneIDi5911.
KEGGihsa:5911.
UCSCiuc001vnd.4. human.

Organism-specific databases

CTDi5911.
DisGeNETi5911.
GeneCardsiRAP2A.
HGNCiHGNC:9861. RAP2A.
HPAiCAB018552.
MIMi179540. gene.
neXtProtiNX_P10114.
OpenTargetsiENSG00000125249.
PharmGKBiPA34222.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0395. Eukaryota.
COG1100. LUCA.
GeneTreeiENSGT00860000133678.
HOGENOMiHOG000233973.
HOVERGENiHBG009351.
InParanoidiP10114.
KOiK07837.
OMAiEINGASW.
OrthoDBiEOG091G0OOG.
PhylomeDBiP10114.
TreeFamiTF313014.

Enzyme and pathway databases

SignaLinkiP10114.

Miscellaneous databases

ChiTaRSiRAP2A. human.
EvolutionaryTraceiP10114.
GeneWikiiRAP2A.
GenomeRNAii5911.
PROiP10114.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000125249.
CleanExiHS_RAP2A.
ExpressionAtlasiP10114. baseline and differential.
GenevisibleiP10114. 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 nameiRAP2A_HUMAN
AccessioniPrimary (citable) accession number: P10114
Secondary accession number(s): B2RCJ1, Q5JSC1, Q5JSC2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: July 1, 1989
Last modified: November 30, 2016
This is version 184 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, Reference proteome

Documents

  1. Human chromosome 13
    Human chromosome 13: 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.