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Protein

Ras-related protein Rap-2a

Gene

RAP2A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Activity 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

  • GDP binding Source: CAFA
  • GTPase activity Source: UniProtKB
  • GTP binding Source: UniProtKB
  • magnesium ion binding Source: CAFA

GO - Biological processi

Keywordsi

LigandGTP-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

EuPathDBiHostDB:ENSG00000125249.6
HGNCiHGNC:9861 RAP2A
MIMi179540 gene
neXtProtiNX_P10114

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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

Chemistry databases

DrugBankiDB04315 Guanosine-5'-Diphosphate
DB04137 Guanosine-5'-Triphosphate

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
ProteomicsDBi52567

PTM databases

iPTMnetiP10114
PhosphoSitePlusiP10114
SwissPalmiP10114

Expressioni

Gene expression databases

BgeeiENSG00000125249 Expressed in 247 organ(s), highest expression level in frontal cortex
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
STRINGi9606.ENSP00000245304

Structurei

Secondary structure

1183
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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
OMAiENLLYWK
OrthoDBiEOG091G0OOG
PhylomeDBiP10114
TreeFamiTF313014

Family and domain databases

InterProiView protein in InterPro
IPR027417 P-loop_NTPase
IPR005225 Small_GTP-bd_dom
IPR001806 Small_GTPase
IPR020849 Small_GTPase_Ras-type
PANTHERiPTHR24070 PTHR24070, 1 hit
PfamiView protein in Pfam
PF00071 Ras, 1 hit
SUPFAMiSSF52540 SSF52540, 1 hit
TIGRFAMsiTIGR00231 small_GTP, 1 hit
PROSITEiView protein in PROSITE
PS51421 RAS, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

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

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F6U784F6U784_HUMAN
Ras-related protein Rap-2a
RAP2A
108Annotation score:

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 No translation available.
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

Similar proteinsi

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 No translation available.
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
STRINGi9606.ENSP00000245304

Chemistry databases

DrugBankiDB04315 Guanosine-5'-Diphosphate
DB04137 Guanosine-5'-Triphosphate

PTM databases

iPTMnetiP10114
PhosphoSitePlusiP10114
SwissPalmiP10114

Polymorphism and mutation databases

BioMutaiRAP2A
DMDMi131852

Proteomic databases

EPDiP10114
MaxQBiP10114
PaxDbiP10114
PeptideAtlasiP10114
PRIDEiP10114
ProteomicsDBi52567

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
EuPathDBiHostDB:ENSG00000125249.6
GeneCardsiRAP2A
HGNCiHGNC:9861 RAP2A
HPAiCAB018552
MIMi179540 gene
neXtProtiNX_P10114
OpenTargetsiENSG00000125249
PharmGKBiPA34222
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

SignaLinkiP10114

Miscellaneous databases

ChiTaRSiRAP2A human
EvolutionaryTraceiP10114
GeneWikiiRAP2A
GenomeRNAii5911
PROiPR:P10114
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000125249 Expressed in 247 organ(s), highest expression level in frontal cortex
CleanExiHS_RAP2A
ExpressionAtlasiP10114 baseline and differential
GenevisibleiP10114 HS

Family and domain databases

InterProiView protein in InterPro
IPR027417 P-loop_NTPase
IPR005225 Small_GTP-bd_dom
IPR001806 Small_GTPase
IPR020849 Small_GTPase_Ras-type
PANTHERiPTHR24070 PTHR24070, 1 hit
PfamiView protein in Pfam
PF00071 Ras, 1 hit
SUPFAMiSSF52540 SSF52540, 1 hit
TIGRFAMsiTIGR00231 small_GTP, 1 hit
PROSITEiView protein in PROSITE
PS51421 RAS, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiRAP2A_HUMAN
AccessioniPrimary (citable) accession number: P10114
Secondary accession number(s): B2RCJ1, Q5JSC1, Q5JSC2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: July 1, 1989
Last modified: November 7, 2018
This is version 196 of the entry and version 1 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  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. Human chromosome 13
    Human chromosome 13: entries, gene names and cross-references to MIM
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