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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
DNA
TYPE functioning gene
STRUCTURE 22.15 kb     8 Exon(s)
Genomic sequence alignment details
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status confirmed
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
9 - 5122 21 184 - 2009 19763083
8 - 5028 - 184 - 2009 19763083
8 - 5077 - 184 - -
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