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FLASH GENE
Symbol RACGAP1 contributors: mct/npt/pgu - updated : 10-01-2017
HGNC name Rac GTPase activating protein 1
HGNC id 9804
Location 12q13.12      Physical location : 50.382.944 - 50.419.307
Synonym name
  • centralspindlin
  • male germ cell RacGap
  • protein CYK4 homolog
  • Synonym symbol(s) ID-GAP, MGCRACGAP, HsCYK-4, MgcRacGAP, KIAA1478, CYK-4
    DNA
    TYPE functioning gene
    STRUCTURE 36.36 kb     19 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    19 - 3326 - 632 - 2008 18201571
    19 - 3315 - 632 - 2008 18201571
    17 - 3206 - 632 - 2008 18201571
    16 - 2979 - 558 - 2008 18201571
    16 - 3093 - 574 - 2008 18201571
    17 - 3178 - 632 - 2008 18201571
    17 - 3248 - 632 - 2008 18201571
    18 - 3252 - 644 - 2008 18201571
    17 - 3129 - 632 - 2008 18201571
    17 - 3182 - 632 - 2008 18201571
    17 - 3207 - 632 - 2008 18201571
    19 - 3256 - 632 - 2008 18201571
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Reproductivemale systemtestis    Homo sapiensAdult
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
    HOMOLOGY
    Homologene
    FAMILY
    CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule,mitotic spindle
    intracellular,nucleus,nucleoplasm
    text
  • at anaphase, RACGAP1 localizes to a narrow region of antiparallel microtubule overlap and initiates central spindle assembly
  • basic FUNCTION
  • Rho GAP essential to cytokinesis, working both as a Rho GTPase regulator and as a scaffolding protein (PMID :
  • chromosomal passenger complex (CPC) and centralspindlin are conserved cytokinesis regulators that localize to the spindle midzone, which forms between the separating chromosomes
  • centralspindlin and the CPC make independent contributions to control transformation of the sheet-like equatorial band into a ribbon-like contractile ring at the furrow tip
  • negatively regulated RAC1 activity at the cell equator in anaphase
  • RACGAP1 GAP activity is required during anaphase to inhibit RAC1-dependent effector pathways associated with control of cell spreading and adhesion
  • links the mitotic spindle to the plasma membrane during cytokinesis
  • centralspindlin links likely the mitotic spindle to the plasma membrane to secure the final cut during cytokinesis in cells
  • is a critical regulator of cytokinesis in animal cells
  • plays a critical role in the cytokinesis of somatic cells
  • endothelial RACGAP1 may play critical roles in pathogenic processes of cancer by regulating endothelial permeability
  • both KIF23 and RACGAP1 are required for efficient microtubule bundling
  • is not a passive cargo of the KIF23 motor, but an integrated component of a microtubule-organizing machinery
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with ECT2 and regulating the activation and function of CDC42 in mitosis
  • linking CEP55 through a cellular mechanism which, in turn, controls the midbody structure and membrane fusion at the terminal stage of cytokinesis
  • interacting with HIF1A (HIF-1alpha function is negatively affected by its interaction with RACGAP1)
  • interacts with KIF23 to form the centralspindlin complex and associates with the RhoGEF ECT2 (PMID :
  • expression of ECT2, RACGAP1, and KIF23 is tightly regulated during cell cycle progression
  • CUX1 and E2F1 regulate coordinated expression of the mitotic complex genes ECT2, RACGAP1, and KIF23 in S phase
  • at anaphase, binding to RACGAP1 at the spindle midzone repositions ECT2 to induce local actomyosin ring formation
  • is a crucial regulator of RAC1 in adherent cells and that inhibition of RAC1-dependent effector pathways in anaphase is needed for cytokinesis
  • is a GAP for RAC1 and CDC42 but not RHOA
  • negatively controls the activity of RAC1 and CDC42, which are key molecular switches acting on the microtubule and actin cytoskeleton and controlling various cell processes such as proliferation, adhesion and motility
  • RACGAP1 promoted the activations of RHOA, PTK2, PXN and triggered focal adhesion formation and cytoskeletal rearrangement
  • ECT2 binds to RACGAP1 via its N-terminal BRCT domain (BRCA1 C-terminal), which docks at specific phosphorylated residues
  • cell & other
    REGULATION
    Phosphorylated by PLK1 and phosphorylation of RACGAP1 major site, S157, is necessary but not sufficient to bind the ECT2 BRCT domain, and an additional site at S164 is also required to elicit efficient binding
    Other RACGAP1 GAP activity is regulated by AURKB phosphorylation
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional germinal mutation     loss of function
    inherited homozygous loss of function mutations in RACGAP1 would be lethal and, de novo mutations in the testis might account for some cases of non-obstructive oligo- and/or azoo-spermia syndromes
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • may be used as a potential predictor for tumor proliferative and patient prognosis in meningiomas
  • Therapy target
    ANIMAL & CELL MODELS