P10114 · RAP2A_HUMAN
- ProteinRas-related protein Rap-2a
- GeneRAP2A
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids183 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
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.
Catalytic activity
- GTP + H2O = GDP + H+ + phosphate
Activity regulation
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.
Features
Showing features for binding site.
GO annotations
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameRas-related protein Rap-2a
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP10114
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Recycling endosome membrane ; Lipid-anchor
Keywords
- Cellular component
Disease & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 5 | Reduced NEDD4-dependent ubiquitination; when associated with R-94; R-148 and R-150. | ||||
Sequence: K → R | ||||||
Mutagenesis | 12 | Dominant active. 2-fold decrease in GDP dissociation rate constant and GTPase activity. No change in interaction with TNIK. | ||||
Sequence: G → V | ||||||
Mutagenesis | 17 | Dominant negative. Severely impairs GTP-binding and partial loss of interaction with MAP4K4, MINK1 and TNIK. | ||||
Sequence: S → N | ||||||
Mutagenesis | 35 | Decreases affinity for GTP and 3-fold reduction of GTPase activity. | ||||
Sequence: T → A | ||||||
Mutagenesis | 39 | 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. | ||||
Sequence: F → S | ||||||
Mutagenesis | 94 | Reduced NEDD4-dependent ubiquitination; when associated with R-5; R-148 and R-150. | ||||
Sequence: K → R | ||||||
Mutagenesis | 145 | Imperfect binding of guanyl nucleotides. | ||||
Sequence: T → I | ||||||
Mutagenesis | 148 | Reduced NEDD4-dependent ubiquitination; when associated with R-5; R-94 and R-150. | ||||
Sequence: K → R | ||||||
Mutagenesis | 150 | Reduced NEDD4-dependent ubiquitination; when associated with R-5; R-94 and R-148. | ||||
Sequence: K → R |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 97 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, glycosylation, modified residue (large scale data), lipidation, modified residue, propeptide.
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000082687 | 1-180 | UniProt | Ras-related protein Rap-2a | |||
Sequence: MREYKVVVLGSGGVGKSALTVQFVTGTFIEKYDPTIEDFYRKEIEVDSSPSVLEILDTAGTEQFASMRDLYIKNGQGFILVYSLVNQQSFQDIKPMRDQIIRVKRYEKVPVILVGNKVDLESEREVSSSEGRALAEEWGCPFMETSAKSKTMVDELFAEIVRQMNYAAQPDKDDPCCSAC | |||||||
Glycosylation | 35 | UniProt | (Microbial infection) O-linked (Glc) threonine; by C.difficile toxin TcdA, and by P.sordellii toxin TcsL | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 66 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 129 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Lipidation | 176 | UniProt | S-palmitoyl cysteine | ||||
Sequence: C | |||||||
Lipidation | 177 | UniProt | S-palmitoyl cysteine | ||||
Sequence: C | |||||||
Modified residue | 180 | UniProt | Cysteine methyl ester | ||||
Sequence: C | |||||||
Lipidation | 180 | UniProt | S-farnesyl cysteine | ||||
Sequence: C | |||||||
Propeptide | PRO_0000281336 | 181-183 | UniProt | Removed in mature form | |||
Sequence: NIQ |
Post-translational modification
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.
Palmitoylated. Palmitoylation is required for association with recycling endosome membranes and activation of TNIK.
(Microbial infection) Glucosylated at Thr-35 by C.difficile toxin TcdA in the colonic epithelium, and by P.sordellii toxin TcsL in the vascular endothelium.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Interaction
Subunit
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
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
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P10114 | EMP3 P54852 | 3 | EBI-602366, EBI-3907816 | |
BINARY | P10114 | MINK1 Q8N4C8 | 3 | EBI-602366, EBI-2133481 | |
BINARY | P10114 | RGL1 Q9NZL6-2 | 3 | EBI-602366, EBI-23868346 | |
BINARY | P10114 | RUNDC3A Q59EK9-3 | 3 | EBI-602366, EBI-11957366 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Motif | 32-40 | Effector region | ||||
Sequence: YDPTIEDFY |
Domain
The effector domain mediates the interaction with RUNDC3A.
Sequence similarities
Belongs to the small GTPase superfamily. Ras family.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length183
- Mass (Da)20,615
- Last updated1989-07-01 v1
- Checksum047D49762765F0B7
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
F6U784 | F6U784_HUMAN | RAP2A | 108 |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
X12534 EMBL· GenBank· DDBJ | CAA31052.1 EMBL· GenBank· DDBJ | mRNA | ||
AF205602 EMBL· GenBank· DDBJ | AAN71845.1 EMBL· GenBank· DDBJ | mRNA | ||
AF493914 EMBL· GenBank· DDBJ | AAM12628.1 EMBL· GenBank· DDBJ | mRNA | ||
AK315139 EMBL· GenBank· DDBJ | BAG37588.1 EMBL· GenBank· DDBJ | mRNA | ||
AL442067 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH471085 EMBL· GenBank· DDBJ | EAX08974.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC041333 EMBL· GenBank· DDBJ | AAH41333.1 EMBL· GenBank· DDBJ | mRNA | ||
BC070031 EMBL· GenBank· DDBJ | AAH70031.1 EMBL· GenBank· DDBJ | mRNA |