RAP1A_RAT
ID RAP1A_RAT Reviewed; 184 AA.
AC P62836; P10113;
DT 16-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT 16-AUG-2004, sequence version 1.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=Ras-related protein Rap-1A;
DE EC=3.6.5.2 {ECO:0000250|UniProtKB:P61224};
DE AltName: Full=Ras-related protein Krev-1;
DE Flags: Precursor;
GN Name=Rap1a; Synonyms=Krev1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2642744; DOI=10.1016/0092-8674(89)90985-9;
RA Kitayama H., Sugimoto Y., Matsuzaki T., Ikawa Y., Noda M.;
RT "A ras-related gene with transformation suppressor activity.";
RL Cell 56:77-84(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP INTERACTION WITH PLCE1.
RX PubMed=11179219; DOI=10.1093/emboj/20.4.743;
RA Kelley G.G., Reks S.E., Ondrako J.M., Smrcka A.V.;
RT "Phospholipase C(epsilon): a novel Ras effector.";
RL EMBO J. 20:743-754(2001).
RN [4]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=17724123; DOI=10.1083/jcb.200610073;
RA Hisata S., Sakisaka T., Baba T., Yamada T., Aoki K., Matsuda M., Takai Y.;
RT "Rap1-PDZ-GEF1 interacts with a neurotrophin receptor at late endosomes,
RT leading to sustained activation of Rap1 and ERK and neurite outgrowth.";
RL J. Cell Biol. 178:843-860(2007).
CC -!- FUNCTION: Induces morphological reversion of a cell line transformed by
CC a Ras oncogene. Counteracts the mitogenic function of Ras, at least
CC partly because it can interact with Ras GAPs and RAF in a competitive
CC manner. Together with ITGB1BP1, regulates KRIT1 localization to
CC microtubules and membranes (By similarity). Plays a role in nerve
CC growth factor (NGF)-induced neurite outgrowth. Plays a role in the
CC regulation of embryonic blood vessel formation. Involved in the
CC establishment of basal endothelial barrier function. May be involved in
CC the regulation of the vascular endothelial growth factor receptor KDR
CC expression at endothelial cell-cell junctions. {ECO:0000250,
CC ECO:0000269|PubMed:17724123}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=GTP + H2O = GDP + H(+) + phosphate; Xref=Rhea:RHEA:19669,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:37565,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:58189; EC=3.6.5.2;
CC Evidence={ECO:0000250|UniProtKB:P61224};
CC -!- ACTIVITY REGULATION: Activated by guanine nucleotide-exchange factors
CC (GEF) EPAC and EPAC2 in a cAMP-dependent manner, and GFR.
CC {ECO:0000250}.
CC -!- SUBUNIT: Found in a complex, at least composed of ITGB1BP1, KRIT1 and
CC RAP1A. Interacts (active GTP-bound form preferentially) with KRIT1 (via
CC C-terminus FERM domain); the interaction does not induce the opening
CC conformation of KRIT1. In its GTP-bound form interacts with PLCE1 and
CC RADIL. Interacts with SGSM1, SGSM2 and SGSM3. Interacts (via GTP-bound
CC active form) with RAPGEF2 (via Ras-associating domain) (By similarity).
CC Interacts with TBC1D21 (By similarity). Interacts with RAP1GDS1 (By
CC similarity). {ECO:0000250|UniProtKB:P62834,
CC ECO:0000250|UniProtKB:P62835}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Lipid-anchor
CC {ECO:0000250}. Cytoplasm, perinuclear region
CC {ECO:0000269|PubMed:17724123}. Early endosome
CC {ECO:0000269|PubMed:17724123}. Late endosome
CC {ECO:0000269|PubMed:17724123}. Cytoplasm {ECO:0000250}. Cell junction
CC {ECO:0000250}. Note=Localized with RAPGEF2 at cell-cell junctions.
CC Colocalized with RAPGEF2 in the perinuclear region (By similarity).
CC Recruited from early endosome to late endosome compartment after nerve
CC growth factor (NGF) stimulation. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Ras family.
CC {ECO:0000305}.
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DR EMBL; BC083813; AAH83813.1; -; mRNA.
DR PIR; A61216; A61216.
DR RefSeq; NP_001005765.1; NM_001005765.1.
DR AlphaFoldDB; P62836; -.
DR SMR; P62836; -.
DR BioGRID; 254977; 4.
DR IntAct; P62836; 1.
DR STRING; 10116.ENSRNOP00000040409; -.
DR iPTMnet; P62836; -.
DR PhosphoSitePlus; P62836; -.
DR jPOST; P62836; -.
DR PaxDb; P62836; -.
DR PRIDE; P62836; -.
DR Ensembl; ENSRNOT00000047836; ENSRNOP00000040409; ENSRNOG00000032463.
DR GeneID; 295347; -.
DR KEGG; rno:295347; -.
DR UCSC; RGD:1359694; rat.
DR CTD; 5906; -.
DR RGD; 1359694; Rap1a.
DR eggNOG; KOG0395; Eukaryota.
DR GeneTree; ENSGT00940000160251; -.
DR HOGENOM; CLU_041217_9_8_1; -.
DR InParanoid; P62836; -.
DR OMA; NVPMVIV; -.
DR OrthoDB; 1353024at2759; -.
DR PhylomeDB; P62836; -.
DR TreeFam; TF313014; -.
DR Reactome; R-RNO-170968; Frs2-mediated activation.
DR Reactome; R-RNO-170984; ARMS-mediated activation.
DR Reactome; R-RNO-354192; Integrin signaling.
DR Reactome; R-RNO-354194; GRB2:SOS provides linkage to MAPK signaling for Integrins.
DR Reactome; R-RNO-372708; p130Cas linkage to MAPK signaling for integrins.
DR Reactome; R-RNO-381676; Glucagon-like Peptide-1 (GLP1) regulates insulin secretion.
DR Reactome; R-RNO-392517; Rap1 signalling.
DR Reactome; R-RNO-5674135; MAP2K and MAPK activation.
DR Reactome; R-RNO-6798695; Neutrophil degranulation.
DR Reactome; R-RNO-8875555; MET activates RAP1 and RAC1.
DR PRO; PR:P62836; -.
DR Proteomes; UP000002494; Chromosome 2.
DR Bgee; ENSRNOG00000032463; Expressed in thymus and 20 other tissues.
DR Genevisible; P62836; RN.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-SubCell.
DR GO; GO:0030054; C:cell junction; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005769; C:early endosome; IDA:UniProtKB.
DR GO; GO:0098978; C:glutamatergic synapse; ISO:RGD.
DR GO; GO:0032045; C:guanyl-nucleotide exchange factor complex; ISO:RGD.
DR GO; GO:0005770; C:late endosome; IDA:UniProtKB.
DR GO; GO:0043005; C:neuron projection; ISO:RGD.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0045335; C:phagocytic vesicle; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR GO; GO:0097225; C:sperm midpiece; ISS:UniProtKB.
DR GO; GO:0003925; F:G protein activity; IEA:UniProtKB-EC.
DR GO; GO:0019003; F:GDP binding; IBA:GO_Central.
DR GO; GO:0005525; F:GTP binding; IDA:RGD.
DR GO; GO:0003924; F:GTPase activity; ISO:RGD.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IMP:UniProtKB.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:RGD.
DR GO; GO:0031267; F:small GTPase binding; ISO:RGD.
DR GO; GO:0071320; P:cellular response to cAMP; IEP:RGD.
DR GO; GO:1990090; P:cellular response to nerve growth factor stimulus; IDA:UniProtKB.
DR GO; GO:0071407; P:cellular response to organic cyclic compound; IDA:RGD.
DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; IDA:RGD.
DR GO; GO:0061028; P:establishment of endothelial barrier; ISS:UniProtKB.
DR GO; GO:0097421; P:liver regeneration; IEP:RGD.
DR GO; GO:0032966; P:negative regulation of collagen biosynthetic process; IMP:RGD.
DR GO; GO:2000301; P:negative regulation of synaptic vesicle exocytosis; ISO:RGD.
DR GO; GO:0038180; P:nerve growth factor signaling pathway; IDA:UniProtKB.
DR GO; GO:0007399; P:nervous system development; IEA:UniProtKB-KW.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IMP:UniProtKB.
DR GO; GO:1905451; P:positive regulation of Fc-gamma receptor signaling pathway involved in phagocytosis; IMP:RGD.
DR GO; GO:0046326; P:positive regulation of glucose import; IMP:RGD.
DR GO; GO:0043547; P:positive regulation of GTPase activity; IMP:UniProtKB.
DR GO; GO:0010976; P:positive regulation of neuron projection development; IMP:UniProtKB.
DR GO; GO:0045860; P:positive regulation of protein kinase activity; IMP:UniProtKB.
DR GO; GO:2001214; P:positive regulation of vasculogenesis; ISS:UniProtKB.
DR GO; GO:0072659; P:protein localization to plasma membrane; ISS:UniProtKB.
DR GO; GO:0032486; P:Rap protein signal transduction; ISS:UniProtKB.
DR GO; GO:1901888; P:regulation of cell junction assembly; ISS:UniProtKB.
DR GO; GO:0098696; P:regulation of neurotransmitter receptor localization to postsynaptic specialization membrane; ISO:RGD.
DR GO; GO:0097327; P:response to antineoplastic agent; IDA:RGD.
DR GO; GO:0009743; P:response to carbohydrate; IEP:RGD.
DR GO; GO:0007264; P:small GTPase mediated signal transduction; ISO:RGD.
DR CDD; cd04175; Rap1; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR038851; Rap1.
DR InterPro; IPR005225; Small_GTP-bd_dom.
DR InterPro; IPR001806; Small_GTPase.
DR InterPro; IPR020849; Small_GTPase_Ras-type.
DR PANTHER; PTHR24070; PTHR24070; 1.
DR Pfam; PF00071; Ras; 1.
DR SMART; SM00174; RHO; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR00231; small_GTP; 1.
DR PROSITE; PS51421; RAS; 1.
PE 1: Evidence at protein level;
KW Cell junction; Cell membrane; Cytoplasm; Endosome; GTP-binding; Hydrolase;
KW Lipoprotein; Membrane; Methylation; Neurogenesis; Nucleotide-binding;
KW Prenylation; Reference proteome; Tumor suppressor.
FT CHAIN 1..181
FT /note="Ras-related protein Rap-1A"
FT /id="PRO_0000030203"
FT PROPEP 182..184
FT /note="Removed in mature form"
FT /evidence="ECO:0000250"
FT /id="PRO_0000030204"
FT MOTIF 32..40
FT /note="Effector region"
FT /evidence="ECO:0000305"
FT BINDING 10..18
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P62834"
FT BINDING 29..35
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P62834"
FT BINDING 60
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P62834"
FT BINDING 116..119
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P62834"
FT MOD_RES 181
FT /note="Cysteine methyl ester"
FT /evidence="ECO:0000250|UniProtKB:P62834"
FT LIPID 181
FT /note="S-geranylgeranyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:P62834"
SQ SEQUENCE 184 AA; 20987 MW; 42C39290C98E0A92 CRC64;
MREYKLVVLG SGGVGKSALT VQFVQGIFVE KYDPTIEDSY RKQVEVDCQQ CMLEILDTAG
TEQFTAMRDL YMKNGQGFAL VYSITAQSTF NDLQDLREQI LRVKDTEDVP MILVGNKCDL
EDERVVGKEQ GQNLARQWCN CAFLESSAKS KINVNEIFYD LVRQINRKTP VEKKKPKKKS
CLLL
