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FLASH GENE
Symbol SH3PXD2A contributors: mct/npt - updated : 14-11-2016
HGNC name SH3 and PX domains 2A
HGNC id 23664
Location 10q24.33      Physical location : 105.353.783 - 105.615.164
Synonym name
  • likely ortholog of mouse five SH3 domains (but see YMEL1)
  • related to neutrophil cytosolic factor 2, >100kDa
  • tyrosine kinase substrate 5/five SH3 domains
  • Synonym symbol(s) FISH, KIAA0418, SH3MD1, Tks5
    DNA
    TYPE functioning gene
    STRUCTURE 261.44 kb     14 Exon(s)
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    14 - 11264 - 1105 - 2014 25259869
  • tipping the TKS5 isoform balance to a high TKS5long to TKS5short ratio promotes invadopodia-mediated invasion and metastasis
  • - - - - - - 2013 23873940
  • decreased invadopodia stability and proteolysis, acting as a natural dominant-negative inhibitor to TKS5long
  • tipping the TKS5 isoform balance to a high TKS5long to TKS5short ratio promotes invadopodia-mediated invasion and metastasis
  • EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • an N-terminal PX domain
  • five SH3 domains (SH3A-E)(tandem SH3A and SH3B domains constitute a versatile module for the implementation of isoform-specific protein-protein interactions)(Rufer 2009), and the fifth SH3 domain binds to the N-terminus of AFAP1L2, which contains polyproline-rich motifs
  • C-terminal fragment containing the ADAMs binding region is found to be sufficient for induction of neuronal death (Malinin 2005)
  • HOMOLOGY
    intraspecies homolog to neutrophil cytosolic factor 2
    Homologene
    FAMILY
    CATEGORY adaptor
    SUBCELLULAR LOCALIZATION     plasma membrane,junction
        intracellular
    intracellular,cytoplasm
    text
  • appears to localize exclusively to invadopodia in cancer cells
  • basic FUNCTION
  • adapter protein involved in tyrosine phosphorylation of APP (Malinin 2005)
  • required for podosome formation, for degradation of the extracellular matrix, and for invasion of some cancer cells (Seals 2005)
  • scaffold protein that may serve as a specific recruiting adapter for various components during podosome formation (Crimaldi 2009)
  • plays a central role in the recruitment of AFAP1, GRLF1, and cortactin to drive podosome formation (Crimaldi 2009)
  • co-localizes to podosomes/invadopodia in different cancer cells and contribute to tumor progression (role of podosomes as mediators of tumor angiogenesis)(Blouw 2008)
  • important and novel role for the SRC-SH3PXD2A pathway in neural crest cell migration during embryonic development
  • SH3PXD2B, and SH3PXD2A are also required for proper embryonic development, probably because of their roles in cell migration
  • is crucial for osteoclast fusion downstream of phosphoinositide 3-kinase and SRC
  • may take part in the pathogenesis of pre-eclampsia (PE) through its role in the regulation of trophoblast cell invasion in the period of placenta formation
  • adaptor protein that is a major actor of the invadosome degradation function
  • is a scaffold protein and SRC substrate involved in cell migration and matrix degradation through its essential role in invadosome formation and function
  • is important for the integrity and permeability of the tumor vasculature
  • similar to AFAP1L2, plays a role in cell proliferation and cell survival and the interaction between AFAP1L2 and SH3PXD2A appears to be critical for regulation of SRC-mediated cellular homeostasis
  • importance of adaptor proteins SH3PXD2B, and SH3PXD2A in melanoma growth and metastasis, likely via functional invadopodia formation
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component crucial component of a protein network that controls the invasiveness of cancer cells and progression of Alzheimer disease (Rufer 2009)
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binds to and potentially regulates certain ADAM family members (with ADAM12 mediate the neurotoxic effect of APP) (Malinin 2005)
  • SOS1 binding partner (Rufer 2009)
  • bind a range of SOS1 and dynamin peptides including conventional proline-rich motifs and atypical recognition sequences (Rufer 2009)
  • SH3PXD2B, SH3PXD2A directly bind to NOXA1, and the integrity of the N-terminal PRR of NOXA1 is essential for this direct interaction with the Tks proteins
  • SH3PXD2A and AFAP1L2 interact endogenously and form a complex with SRC tyrosine kinase
  • interaction between AFAP1L2 and another scaffold protein, SH3PXD2A, regulates cell proliferation and survival in human bronchial epithelial cell
  • cell & other
    REGULATION
    Other induced during osteoclastogenesis, and prevention of this induction impaired both the formation of circumferential podosomes and osteoclast fusion without affecting cell differentiation
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in approximately 50p100 of primary invasive breast cancers
    Susceptibility
  • to late-onset Alzheimer disease
  • Variant & Polymorphism other interaction between the ADAM12 and SH3PXD2A genes may confer susceptibility to late-onset Alzheimer disease (Harold 2007)
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS