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FLASH GENE
Symbol ASAP1 contributors: mct - updated : 19-09-2017
HGNC name ArfGAP with SH3 domain, ankyrin repeat and PH domain 1
HGNC id 2720
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Endocrinethyroid   highly
Hearing/Equilibriumear   highly
Nervousbrain    
Reproductivefemale systembreastmammary gland highly
Respiratoryrespiratory tractlarynx  highly
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • from the N terminus, a pleckstrin homology domain PH, having two anionic phospholipid binding sites proposed to work in concert to regulate ASAP1 GAP activity , and BAR domain required for the assembly of podosomes , and functioning as a protein binding site
  • a GAP domain that includes a zinc finger motif
  • three ankyrin repeats, a proline-rich region with alternative splicing and SH3 binding domains, responsible for binding of ASAP1 to the src homology 3 (SH3) domain of cortactin
  • eight repeats of the sequence E/DLPPKP
  • a C terminal SH3 domain
  • HOMOLOGY
    interspecies homolog to rattus Asap1 (96.7pc)
    homolog to murine Asap1 (96.4pc)
    Homologene
    FAMILY
  • beta family
  • CATEGORY protooncogene
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    text
  • localizing to focal adhesions
  • colocalized with IKBKG in the pericentrosomal endocytic recycling compartment
  • colocalized with ARHGEF2 in podosomes
  • basic FUNCTION
  • ADP ribosylation factor (ARF) GTPase activating protein,phosphatidyl 4,5 biphosphate (PIP2)-dependent
  • regulator and coordinator of cell growth, actin cytoskeletal organization and ARF nucleotide cycle
  • cycling with FA proteins when cells are stimulated to move
  • plays a crucial role in the invasive activities, such as matrix degradation activity
  • monoubiquitination, but not poly-ubiquitination, is necessary to be involved in invasive activities
  • like IKBKG, functions as a component of the endocytic recycling compartment
  • plays a role in prostate cancer metastasis
  • mediates GTP hydrolysis on ARF4 and functions as an ARF4 effector that regulates budding of post-TGN carriers, along with IKBKG and RAB11A
  • critical target of tyrosine kinase signaling involved in the regulation of podosomes and invadopodia and potentially may function as a coincidence detector of simultaneous protein association through the ASAP1 SH3 domain and phosphorylation by Src
  • present in cell structures required for cell migration and invasion, such as focal adhesions, invadopodias, and podosomes, and are involved in endocytosis and cytoskeletal remodeling
  • involvement in carcinogenesis and metastasis highlights the importance of the presented structure in general and the Ca2+-binding pocket in particular as it may give clues for designing inhibitors for therapeutic applications
  • plays an important role in the progression and metastasis of ovarian cancer
  • RAB11FIP3 acts synergistically with ASAP1 to direct RAB3IP in ciliary receptor targeting
  • is involved in actin and membrane remodeling and has been associated with podosomes
  • regulates F-actin-based structures and functions, including focal adhesions (FAs) and circular dorsal ruffles (CDRs), cell spreading and migration
  • may directly link signaling and the mechanical machinery of cell migration
  • CELLULAR PROCESS cell life, proliferation/growth
    cell organization/biogenesis
    PHYSIOLOGICAL PROCESS development
    PATHWAY
    metabolism
    signaling
  • IQSEC1-ARF6-ASAP1-cortactin pathway is essential for angiogenesis activities, including cell migration and tubular formation
  • a component
  • associated with and phosphorylated by SRC
  • interacting with REPS2 through its proline-rich motif, thereby regulating cell migration
  • forming a trimeric protein complex with cortactin and paxillin
  • INTERACTION
    DNA binding
    RNA
    small molecule
    protein
  • GTPase activating protein for ARF1
  • ASAP2
  • binds to the src homology 3 (SH3) domain of cortactin via its proline-rich peptide, SKKRPPPPPPGHKRT
  • binding to SH3KBP1 (important for the invasive activities of several different breast cancer cells)
  • IKBKG, which is a putative ARF6- and RAB11A-effector, is a candidate ASAP1 BAR domain-binding proteinv
  • interacts with PTK2 (residues 676-840) and DLGAP3
  • substrate of SRC that controls invadopodia
  • ARHGEF2 is a binding partner of the BAR domain of ASAP1
  • GTP-RAB5C bound to ASAP1, and activation of RAB5C by EGFR signaling was necessary to promote the intracellular association of ASAP1 and PRKD2
  • ASAP1 serves as a scaffold that brings together the proteins necessary for transport to the cilia including the GTP-binding protein ARF4 and the two G proteins of the Rab family--RAB11A and RAB8A--linked by the RAB8A guanine nucleotide exchange factor RAB3IP
  • activation of NFKB1 induced translocation of ASAP1 to cytoplasm from cell membrane and nucleus, which resulted in augmented interaction of ASAP1 and IKBKB
  • KDELR1, KDELR2 induces SRC activation at the invadopodia and leads to phosphorylation of the SRC substrates cortactin and ASAP1, which are required for basal and KDELR-stimulated ECM (extracellular matrix) degradation
  • RAB11FIP3 coordinates the interactions of ASAP1 and RAB11A with RAB3IP
  • ASAP1 is a positive regulator of MYH9
  • cell & other
  • inhibiting the formation of PDGF-induced dorsal membrane ruffles in NIH 3T3 fibroblasts, when overexpressed
  • REGULATION
    Other targeted by PYK2
    phosphorylated by SRC
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --other  
    aberrantly expressed in invasive phenotypes of primary tumors of the breast
    tumoral     --over  
    in invasive breast cancer and in other types of invasive and malignant tumors, such as uveal melanomas
    tumoral     --over  
    in epithelial ovarian cancer (EOC)
    Susceptibility to tuberculosis (tB)
    Variant & Polymorphism other
  • association between TB and variants located in introns of the ASAP1 gene
  • Candidate gene strongly upregulated in a variety of tumors, expression correlating with poor metastasis-free survival and prognosis in colorectal cancer patients
    Marker
  • may be used as a biomarker in predicting patient outcome in epithelial ovarian cancer (EOC) patients
  • Therapy target
    SystemTypeDisorderPubmed
    cancermetastases 
    therapeutic target and/or biomarker for metastatic disease
    ANIMAL & CELL MODELS