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Symbol ASAP1 contributors: mct - updated : 19-09-2017
HGNC name ArfGAP with SH3 domain, ankyrin repeat and PH domain 1
HGNC id 2720
Location 8q24.21      Physical location : 131.064.352 - 131.414.217
Synonym name
  • paxillin-associated protein 2 with ADP-ribosylation factor GTPase-activating protein activity
  • development and differentiation enhancing factor 1
  • cattle differentiation enhancing factor 1 homolog
  • centaurin, beta 4
  • ADP-ribosylation factor-directed GTPase-activating protein
  • 1
  • PIP2-dependent ARF1 GAP
  • 130 kDa phosphatidylinositol 4,5-biphosphate-dependent ARF1
  • GTPase-activating protein
    Synonym symbol(s) PAP, PYK2, KIAA1249, PAG2, ZG14P, AMAP1, DDEF1, CENTB4, DEF-1
    TYPE functioning gene
    STRUCTURE 391.74 kb     30 Exon(s)
    MAPPING cloned Y linked N status provisional
    Map cen - D2S1801 - [D2S1921 - D2S1945 ] - D2S478 - D2S557 - D2S1835 - qter
    Authors Gene Map (99)
    Text [DDEF1 ]
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    30 - 6042 124.4 1129 - 2008 18685082
  • ASAP1A
  • associated with invadopodia and podosomes
  • 31 - 6361 - 1122 - 2008 18685082
    Type widely
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrinethyroid   highly
    Hearing/Equilibriumear   highly
    Reproductivefemale systembreastmammary gland highly
    Respiratoryrespiratory tractlarynx  highly
    cell lineage
    cell lines
    at STAGE
  • 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
    interspecies homolog to rattus Asap1 (96.7pc)
    homolog to murine Asap1 (96.4pc)
  • beta family
  • CATEGORY protooncogene
    SUBCELLULAR LOCALIZATION     plasma membrane
  • 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
  • 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
    DNA binding
    small molecule
  • 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
    Other targeted by PYK2
    phosphorylated by SRC
    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
  • may be used as a biomarker in predicting patient outcome in epithelial ovarian cancer (EOC) patients
  • Therapy target
    therapeutic target and/or biomarker for metastatic disease