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FLASH GENE
Symbol PXN contributors: mct/pgu - updated : 17-06-2015
HGNC name paxillin
HGNC id 9718
Location 12q24.31      Physical location : 120.648.249 - 120.703.563
Synonym symbol(s) FAP68, EVI66, FLJ16691
DNA
TYPE functioning gene
STRUCTURE 55.31 kb     12 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status provisional
Physical map
LOC387890 12 similar to hypothetical protein C130069F04 PRKAB1 12q24.1-q24.3 protein kinase, AMP-activated, beta 1 non-catalytic subunit CIT 12q24.2 citron (rho-interacting, serine/threonine kinase 21) LOC92558 12q24.31 hypothetical protein LOC92558 RAB35 12q24.31 RAB35, member RAS oncogene family GCN1L1 12q24.3 GCN1 general control of amino-acid synthesis 1-like 1 (yeast) RPLP0 12q24.2 ribosomal protein, large, P0 PXN 12q24 paxillin FLJ23042 12q24.31 hypothetical protein FLJ23042 LOC283458 12q24.31 nucleoside diphosphate kinase B-like pseudogene SIRT4 12q sirtuin (silent mating type information regulation 2 homolog) 4 (S. cerevisiae) PLA2G1B 12q23-q24.32 phospholipase A2, group IB (pancreas) MSI1 12q24.1-q24.31 musashi homolog 1 (Drosophila) COX6A1 12q24.2 cytochrome c oxidase subunit VIa polypeptide 1 HSPC132 12q24.31 hypothetical protein HSPC132 LOC387891 12 LOC387891 SFRS9 12q24.31 splicing factor, arginine/serine-rich 9 DNCL1 12q24.23 dynein, cytoplasmic, light polypeptide 1 MGC4767 12q24.31 hypothetical protein MGC4767 RNF10 12q24.2-q24.3 ring finger protein 10 POP5 12q24.31 RNase MRP/RNase P protein-like LOC390362 12 similar to 60S ribosomal protein L11 CABP1 12q24.2-q24.3 calcium binding protein 1 (calbrain) KIAA0152 12q24.31 calcium binding protein 1 (calbrain) ACADS 12q24.31-q24.32 acyl-Coenzyme A dehydrogenase, C-2 to C-3 short chain LOC387892 12 LOC387892 MGC5139 12q24.31 hypothetical protein MGC5139 SPPL3 12q24.31 SPPL3 protein LOC390363 12 similar to 60S ribosomal protein L12
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
11 - 3691 60 557 - 2007 17574549
  • isoform 2
  • 11 - 3834 - 424 - 1995 7534286
  • isoform 3
  • 12 - 3788 - 591 - 1995 7534286
  • isoform 1
  • EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Hearing/EquilibriumearinnercochleaCorti  Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Lymphoid/ImmuneT cell Homo sapiens
    Skeletonosteoblast
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • four LIM domains (double-zinc finger, binding two zinc ions), involved in targeting CTNNB1 in a RAC-dependent manner, which may play a role in RAC-dependent control of focal adhesions (FA) and adherens junctions (AJ) interactions and monolayer integrity
  • a proline-rich domain
  • a SH3-binding site
  • leucine-aspartic acid domains (LD)
  • three SH2-binding sites
  • HOMOLOGY
    interspecies homolog to murine Pxn (93.6pc)
    homolog to rattus Pxn (94.6pc)
    Homologene
    FAMILY
  • paxillin family
  • subfamily of LIM domains proteins
  • CATEGORY adaptor , adhesion , structural protein , protooncogene
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytoskeleton,microtubule
    intracellular,nucleus
    text
  • localised to the poles of elongated osteocyte cell bodies
  • localised to the ‘polar’ regions of elongated osteocyte cell bodies in fibula, whereas paxillin proteins are distributed more evenly across the relatively round osteocyte cell bodies in calvaria
  • cytoskeleton, cell junction, focal adhesion
  • shuttles between cytoplasm and nucleus, nuclear localization stimulating DNA synthesis and cell proliferation
  • localizes to the microtubule organizing center (MTOC) in T cells
  • LIM domain protein localized at integrin-mediated focal adhesions
  • basic FUNCTION
  • cytoskeletal protein involved in actin-membrane attachment at sites of cell adhesion to the extracellular matrix (focal adhesion)
  • in addition to its well established role at focal adhesions, could also be associated with the lymphocyte microtubule network
  • adaptor/scaffold protein involved in the dissemination of signals from extracellular cell adhesion proteins such as integrins and growth factor receptors
  • playing an essential role for PTPN12 inhibition of cell spreading and membrane protrusion as well as inhibition of adhesion-induced Rac activation
  • functioning as an elongated adaptor protein that links actin filaments with integrin
  • having a dual role in the HGF- and VEGF-mediated encdothelial barrier regulation
  • having a role in the modulation of Rac-Rho crosstalk
  • plays a previously unknown role as a scaffold protein of Arf guanine-nucleotide exchange factor
  • role of paxillin in facilitating attachment-independent signal transduction implicated in cancer
  • is recruited, through its LD (leucine-aspartic acid) domains, to sites of integrin engagement and may contribute to microtubule organizing center (MTOC) reorientation required for directional degranulation
  • is required for the early phase of endothelial cells (ECs) orientation in response to cyclic stretching by scaffolding for accumulation of focal adhesions (FAs) proteins
  • KCNA10, ODF2, PXN specific expression patterns imply potential functional significance in the inner ear
  • roles for PXN and TGFB1I1 in RAC1 and RHOA-dependent cell adhesion formation and maturation, processes essential for productive cell migration
  • new regulator protein of pulmonary arterial smooth muscle cells (PASMC) growth
  • focal adhesion (FA) scaffold protein that mediates integrin anchorage to the cytoskeleton, and has been implicated in regulation of FA assembly and cell migration
  • PXN variants play a prominent role in mitochondrial dynamics with direct implications on lung cancer progression
  • critical role of LIM-domain proteins PXN and zyxin in responding to mechanical stress in the actin cytoskeleton
  • negatively regulates several common platelet signaling pathways
  • controls endothelial cell migration and tumor angiogenesis by altering NRP2 expression
  • CELLULAR PROCESS cell migration & motility
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • protein constituent of cytoskeleton
  • integral component of focal adhesion complexes and widely used as a parameter to study the distribution of focal adhesions
  • forms a complex with PXN
  • INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • ions Zn2+
  • protein
  • NF2 (through PBD1) to regulate Schwann cells morphology growth and differentiation
  • phosphorylation by JNK seems essential for maintaining the labile adhesions required for rapid cell migration
  • interacting with RACK1 (modulation of paxillin phosphorylation at early adhesions)
  • being one of the major binding partners of GIT proteins in focal adhesions (elongated adaptor protein that links actin filaments with integrin)
  • interacting with ITGA4, RNF5
  • binding to ASAP2
  • interacting directly with PTPRT (PTPRT is a key regulator of paxillin Y88 phosphorylation)
  • dynamic interaction between PXN and GIT2 is regulated by SRC/PTK2-dependent phosphorylation of GIT2 and this interaction is necessary for the coordination of Rho family GTPase signaling controlling front-rear cell polarity and thus directional migration
  • Erk activity is governed by GPLD1 activity and regulates the tyrosine phosphorylation of PXN, potentially explaining its role in cell motility
  • MAPK8 binds and phosphorylates paxillin to regulate Schwann cell migration
  • dual phosphorylation of PXN by JNK and MAPK14 is essential for T-cell activation, suggesting that NFATC1 is a functional target of the JNK/MAPK14 phosphorylated paxillin
  • SLK phosphorylation of PXN on serine 250 is required for PTK2-dependent FA dynamics
  • PTPN12 control phosphorylation of PTK2B and PXN, thereby regulating cell polarization, migration, and spreading
  • RACGAP1 promoted the activations of RHOA, PTK2, PXN and triggered focal adhesion formation and cytoskeletal rearrangement
  • GIT2 bind to PXN to control cell polarization and directional migration
  • cell & other
    REGULATION
    repressed by overexpression of RPS27 in head and neck squamous cell carcinoma
    Other LPXN suppresses phosphorylation of PXN during integrin signaling
    fibronectin promotes tyr-phosphorylation of PXN and cell invasiveness in the gastric cancer cell line AGS
    IL8 stimulation leads to PXN phosphorylation
    phosphorylation of its LD4 motif blocks its nuclear export
    phosphorylated by JNK1
    phosphorylated during integrin-mediated cell adhesion, embryonic development, fibroblast transformation and following stimulation of cells by mitogens
    regulated by LPXN (functions as a paxillin counterpart that potently suppresses the tyrosine phosphorylation of paxillin during integrin signaling)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral somatic mutation amplification    
    mutated and amplified in roughly 20 p100 of lung cancers
    tumoral     --over  
    in colorectal cancer
    Susceptibility
    Variant & Polymorphism
    Candidate gene integral component of focal adhesion complexes and is widely used as a parameter to study the distribution of focal adhesions
    Marker
    Therapy target
    ANIMAL & CELL MODELS