RAP2A
entrez
5911
canonical
uniprot
P10114
canonical
ensembl
ENSG00000125249
resolver
ensp
ENSP00000245304
resolver
enst
ENST00000245304
resolver
genesymbol
RAP2A
resolver
hgnc
HGNC:9861
resolver
uniprot
B2RCJ1
resolver
uniprot
Q5JSC1
resolver
uniprot
Q5JSC2
resolver
uniprot_entry
RAP2A_HUMAN
resolver
uniprot_sec
B2RCJ1
resolver
uniprot_sec
Q5JSC1
resolver
uniprot_sec
Q5JSC2
resolver
activity_regulation
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. {ECO:0000269|PubMed:23894443}.
uniprot
proteins
amino_acid_sequence
MREYKVVVLGSGGVGKSALTVQFVTGTFIEKYDPTIEDFYRKEIEVDSSPSVLEILDTAGTEQFASMRDLYIKNGQGFILVYSLVNQQSFQDIKPMRDQIIRVKRYEKVPVILVGNKVDLESEREVSSSEGRALAEEWGCPFMETSAKSKTMVDELFAEIVRQMNYAAQPDKDDPCCSACNIQ
uniprot
proteins
ec_number
3.6.5.2
uniprot
proteins
function
FUNCTION: Small GTP-binding protein which cycles between a GDP-bound inactive and a GTP-bound active form (PubMed:14966141, PubMed:15342639, PubMed:16246175, PubMed:16540189, PubMed:18930710, PubMed:20159449, PubMed:35293963). In its active form interacts with and regulates several effectors including MAP4K4, MINK1 and TNIK (PubMed:14966141, PubMed:15342639, PubMed:18930710, PubMed:20159449). Part of a signaling complex composed of NEDD4, RAP2A and TNIK which regulates neuronal dendrite extension and arborization during development (PubMed:20159449). More generally, it is part of several signaling cascades and regulates cytoskeletal rearrangements, cell migration, cell adhesion and cell spreading (PubMed:14966141, PubMed:15342639, PubMed:16246175, PubMed:16540189, PubMed:18930710, PubMed:20159449, PubMed:35293963). {ECO:0000269|PubMed:14966141, ECO:0000269|PubMed:15342639, ECO:0000269|PubMed:16246175, ECO:0000269|PubMed:16540189, ECO:0000269|PubMed:18930710, ECO:0000269|PubMed:20159449, ECO:0000269|PubMed:35293963}.
uniprot
proteins
mass_dalton
20615
uniprot
proteins
mutagenesis
MUTAGEN 5; /note="K->R: Reduced NEDD4-dependent ubiquitination; when associated with R-94; R-148 and R-150."; /evidence="ECO:0000269|PubMed:20159449"; MUTAGEN 12; /note="G->V: Dominant active (GTP-bound mutant). 2-fold decrease in GDP dissociation rate constant and GTPase activity. No change in interaction with TNIK. No change in endosomal trafficking."; /evidence="ECO:0000269|PubMed:15342639, ECO:0000269|PubMed:1900290, ECO:0000269|PubMed:35293963"; MUTAGEN 17; /note="S->N: Dominant negative (GDP-bound mutant). Severely impairs GTP-binding and partial loss of interaction with MAP4K4, MINK1 and TNIK. Decreased localization to the plasma membrane; increaded localization to lysosomes and late endosomes."; /evidence="ECO:0000269|PubMed:15342639, ECO:0000269|PubMed:1900290, ECO:0000269|PubMed:35293963"; MUTAGEN 35; /note="T->A: Decreases affinity for GTP and 3-fold reduction of GTPase activity."; /evidence="ECO:0000269|PubMed:1900290"; MUTAGEN 39; /note="F->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."; /evidence="ECO:0000269|PubMed:15342639, ECO:0000269|PubMed:19645719, ECO:0000269|PubMed:20159449"; MUTAGEN 94; /note="K->R: Reduced NEDD4-dependent ubiquitination; when associated with R-5; R-148 and R-150."; /evidence="ECO:0000269|PubMed:20159449"; MUTAGEN 117; /note="K->R: Increased binding to RAB40C; when associated with R-148 and R-150. Increased localization within endolysosomes; when associated with R-148 and R-150. Decreased cell invasion; when associated with R-148 and R-150."; /evidence="ECO:0000269|PubMed:35293963"; MUTAGEN 145; /note="T->I: Imperfect binding of guanyl nucleotides."; /evidence="ECO:0000269|PubMed:1900290"; MUTAGEN 148; /note="K->R: Reduced NEDD4-dependent ubiquitination; when associated with R-5; R-94 and R-150. Increased binding to RAB40C; when associated with R-117 and R-150. Increased localization within endolysosomes; when associated with R-117 and R-150. Decreased cell invasion; when associated with R-117 and R-150."; /evidence="ECO:0000269|PubMed:20159449, ECO:0000269|PubMed:35293963"; MUTAGEN 150; /note="K->R: Reduced NEDD4-dependent ubiquitination; when associated with R-5; R-94 and R-148. Increased binding to RAB40C; when associated with R-117 and R-148. Increased localization within endolysosomes; when associated with R-117 and R-148. Decreased cell invasion; when associated with R-117 and R-148."; /evidence="ECO:0000269|PubMed:20159449, ECO:0000269|PubMed:35293963
uniprot
proteins
post_translational_modification
PTM: 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 (PubMed:20159449). Ubiquitination by the ECS(RAB40B) complex leads to RAP2A localization to lamellipodia plasma membrane, activation, and regulation of sorting at early endosomes for recycling to the lamellipodia plasma membrane (PubMed:35293963). {ECO:0000269|PubMed:20159449, ECO:0000269|PubMed:35293963}.; PTM: Palmitoylated. Palmitoylation is required for association with recycling endosome membranes and activation of TNIK. {ECO:0000250|UniProtKB:Q80ZJ1}.; PTM: (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. {ECO:0000269|PubMed:22267739, ECO:0000269|PubMed:8626586}.
uniprot
proteins
protein_family
Ras family
uniprot
proteins
protein_family
Small GTPase superfamily
uniprot
proteins
pubmed
10572250
uniprot
proteins
pubmed
10591105
uniprot
proteins
pubmed
10777494
uniprot
proteins
pubmed
12444546
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
14966141
uniprot
proteins
pubmed
15057823
uniprot
proteins
pubmed
15342639
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15752761
uniprot
proteins
pubmed
16246175
uniprot
proteins
pubmed
16540189
uniprot
proteins
pubmed
17509819
uniprot
proteins
pubmed
18930710
uniprot
proteins
pubmed
1900290
uniprot
proteins
pubmed
19061864
uniprot
proteins
pubmed
19645719
uniprot
proteins
pubmed
20159449
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
22267739
uniprot
proteins
pubmed
23894443
uniprot
proteins
pubmed
3045729
uniprot
proteins
pubmed
35293963
uniprot
proteins
pubmed
7962206
uniprot
proteins
pubmed
8391995
uniprot
proteins
pubmed
8424780
uniprot
proteins
pubmed
8626586
uniprot
proteins
pubmed
9312017
uniprot
proteins
sequence_length
183
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Midbody {ECO:0000269|PubMed:23894443}. Cell projection, lamellipodium membrane {ECO:0000269|PubMed:35293963}. Golgi apparatus {ECO:0000269|PubMed:35293963}. Recycling endosome membrane; Lipid-anchor; Cytoplasmic side {ECO:0000269|PubMed:35293963}. Lysosome {ECO:0000269|PubMed:35293963}. Note=Localized to the Golgi (PubMed:35293963, PubMed:7962206). May also localize to the gelatinase-containing granules of neutrophils (PubMed:8391995). Colocalized with RASGEF1B to midbody at telophase (PubMed:23894443). Localized predominantly to the plasma membrane, where it is enriched at lamellipodia ruffles (PubMed:35293963). Cycles between the lamellipodia plasma membrane and endosomes when ubiquitinated by the ECS(RAB40B) complex (PubMed:35293963). Without the ubiquitin signal, sorted to lysosomes for degradation (PubMed:35293963). {ECO:0000269|PubMed:23894443, ECO:0000269|PubMed:35293963, ECO:0000269|PubMed:7962206, ECO:0000269|PubMed:8391995}.
uniprot
proteins