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FLASH GENE
Symbol RAP1A contributors: mct - updated : 24-08-2016
HGNC name RAP1A, member of RAS oncogene family
HGNC id 9855
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Endocrinethyroid   highly
Lymphoid/Immunelymph node   highly
Respiratorylung   highly
 respiratory tractlarynx  highly
Urinarykidney   highly
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a domain spanning amino acids 85-89 with a pivotal role in perinuclear localization
  • HOMOLOGY
    interspecies ortholog to murine Rap1a
    ortholog to rattus rap-1a
    Homologene
    FAMILY
  • small GTPase superfamily
  • Ras family
  • CATEGORY signaling
    SUBCELLULAR LOCALIZATION     plasma membrane,junction
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,organelle,endosome
    intracellular,cytoplasm,cytosolic
    text
  • attached to the membrane by a lipid anchor
  • localized in the perinuclear region including the Golgi apparatus and endosomes
  • basic FUNCTION
  • inducing morphological reversion of a cell line transformed by a ras oncogene
  • increases KRIT1 targeting to endothelial cell-cell junctions where it suppresses stress fibers and stabilizes junctional integrity
  • role for RAP1A and its exchange factor RAPGEF1 in mediating Fc gammaR-dependent phagocytosis
  • responsible of the direct regulation of adhesion processes during mitosis
  • inhibits non-homologous end joining at telomeres and identify RAP1A as a mediator of genome stability
  • inhibits non-homologous end joining at mammalian telomeres and identify RAP1A as a mediator of genome stability
  • several critical steps of RAP1A, which are RASSF5-dependent and -independent, are implicated in lymphocyte trafficking
  • activated RAP1A promotes glucose-stimulated insulin secretion, islet cell hypertrophy, and islet cell proliferation, suggesting that it is an important regulator of beta-cell function
  • has a critical role in regulating cell-matrix and cell-cell adhesion
  • involved in the generation of peripheral Treg and this effect is mediated via ITGB2-dependent and ITGB2-independent mechanisms
  • member of small GTPase family involved in control of cell-cell interactions
  • plays a key role in T-cell receptor (TCR)-signaling
  • TLN1 and RAP1A are critical for bone resorptive function, and their selective inhibition in mature osteoclasts retards pathological bone loss
  • endothelial barrier resistance is determined by the combined antagonistic actions of RAP1A and RAP2A
  • RAP1A and its effector RASIP1 as critical mediators of endothelial junction stabilization, and the relationship between RAP1A effectors and modulation of different subsets of endothelial junctions
  • promotes integrin- and cadherin-mediated signaling and is a critical regulator of NO production and endothelial function
  • controls the actin cytoskeleton by regulating Rho GTPase signaling
  • likely requirement for RAP1A in maintenance of lens epithelial phenotype and morphogenesis
  • regulates osteoblast differentiation through modulating the ERK/MAPK14 signaling
  • implicated in the control of multiple stem cell, leukocyte and vascular cell functions, and in maintaining epithelial and endothelial cell junction integrity
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
  • critical roles for a PI3K3CG-RAP1A-dependent pathway in integrin activation during tumor inflammation
  • RASIP1-ARHGAP29 pathway also functions in RAP1A-mediated regulation of endothelial junctions, which controls endothelial barrier function
  • a component
  • component of a complex (RAP1A-RADIL) required downstream of receptor stimulation for the activation of integrins and the positive modulation of cell-matrix adhesiveness
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding partners of MLLT4
  • RASGRP3 activates RAP1A, which in some cases can antagonize the function of RAS (RAP1A can antagonize the function of RAS, and DGKI regulates RASGRP3 with a predominant effect on RAP1A activity)
  • binds to KRIT1, a guanosine triphosphatase that maintains the integrity of endothelial junctions (RAP1A activity regulated the junctional localization of KRIT1 and its physical association with junction proteins)
  • interacting with RAPGEF3 (interaction of RAPGEF3 with RAN is necessary for the efficient activation of RAP1A by RAPGEF3)
  • binding of MLLT4 to RAP1A regulated the activity of RAP1A in a positive-feedback manner
  • interacting with HRAS and acting dominantly over C-terminal lipid modification of HRAS (essential and sufficient for the plasma membrane localization)
  • interaction of RASSF1 with RAP1A is shown to influence the effect of RASSF1 on microtubule behavior
  • SDC1 restrains migration in lung epithelium by activating RAP1A to slow focal adhesion disassembly
  • RADIL, a novel RAP1A effector, regulates ITGB1, ITGB2 activation and controls neutrophil chemotaxis
  • RADIL is emerging as an important RAP1A effector implicated in cell spreading and migration
  • RAP1A signaling enables plasticity and fear learning by regulating CACNA1D at cortico-amygdala synapses
  • RASIP1 is a RAP1A-effector involved in cell spreading and endothelial barrier function
  • induces integrin activation via an inside-out signaling pathway mediated by APBB1IP
  • MEX3B regulate the cortical level of activated RAP1A, a small G protein controlling phagocytosis and cell-cell interaction, through the activation and transport of RAP1GAP
  • ZSCAN4 functions as a mediator of telomere length through its direct interaction with RAP1A, possibly regulating shelterin complex-controlled telomere elongation in both telomerase positive and alternative lengthening of telomere pathways
  • RAPGEF2 acts on the multipolar-bipolar transition during neuronal migration via a RAP1A/N-cadherin pathway
  • RAP1A effectors RADIL and RASIP1, together with the RHO GTPase activating protein ARHGAP29, mediate RAP1A-induced inhibition of RHO signaling in the processes of epithelial cell spreading and endothelial barrier function
  • two effectors of RAP1A regulate integrins, RASSF5 and APBB1IP
  • RASIP1 can act as a RAP1A and RAS effector and RASIP1 defines a subgroup of dimeric RA domains that could mediate cooperative binding to membrane-associated RAS superfamily members
  • novel roles for PODXL as an important modulator of neutrophil and monocyte formation and of RAP1A activation during stress hematopoiesis
  • UBE2I acts as a functional binding partner of FYB1 and plays a selective role in integrin-mediated T cell adhesion via modulation of RAP1A-RASSF5 membrane recruitment and RAC1 activation
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    ANIMAL & CELL MODELS