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FLASH GENE
Symbol CTTN contributors: shn/mct - updated : 10-09-2015
HGNC name cortactin
HGNC id 3338
DNA
TYPE functioning gene
STRUCTURE 38.08 kb     19 Exon(s)
MAPPING cloned Y linked   status provisional
Map cen - D11S4095 - D11S4136 - CTTN - D11S4139 - D11S4196 - qter
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
18 - 3319 - 550 - 2005 15579908
17 - 3208 - 513 - 2005 15579908
19 - 2325 - 634 - 2005 15579908
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestivemouth   highly
 pharynx   highly
Reproductivemale systemprostate  highly
Respiratoryrespiratory tractlarynx  highly
Urinarybladder   highly
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a F-actin binding domain
  • contains a Src homology 3 (SH3) domain at the distal C terminus
  • a N-terminal acidic domain (NTA), six and a half tandem repeats of a
  • unique 37-amino acid sequence
  • a proline-rich region
  • conjugated PhosphoP , Other
    HOMOLOGY
    interspecies ortholog to Cttn, Rattus norvegicus
    ortholog to CTTN, Pan troglodytes
    ortholog to cttn, danio rerio
    ortholog to Cttn, Mus musculus
    Homologene
    FAMILY
    CATEGORY protooncogene
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton
    text translocation from the cytosol to lamellipodia after growth factor stimulation
    basic FUNCTION
  • regulates the interactions between components of adherens-type junctions and organizes the cytoskeleton and cell adhesion structures of epithelia and carcinoma cells
  • involved in the restructuring of the cortical actin cytoskeleton
  • a key regulator of cell migration
  • filamentous actin binding protein, modulating F-actin polymerization and cell migration through overexpression and/or tyrosine phosphorylation
  • can contribute to cell polarity by controlling the extent of ARPCs activation by WASP family members and the stability of the F-actin network
  • cortactin-mediated actin remodeling in excitable cells is not only important for cell structure, but may directly impact membrane excitability
  • contributes to KCNA2 endocytosis by complexing with dynamin
  • major target for tyrosine phosphorylation
  • its role would switch from a scaffold linking KCNA2 to the cortical actin cytoskeleton to a proximal protein capable of facilitating channel endocytosis through actin remodeling
  • playing an important role in CXCR4 signaling and trafficking as well in the receptor-mediated cell migration
  • involved in keratinocyte migration promoted by both FGF7 and FGF10)
  • critical mediator of tumor cell invasion
  • cortactin involvement in the keratinocyte growth factor and fibroblast growth factor 10 promotion of migration and cortical actin assembly in human keratinocytes
  • synergize with N-WASP for ARCTs-dependent actin polymerization
  • actin-binding protein enriched in lamellipodia of motile cells and at dynamic actin structures such as membrane ruffles
  • plays important roles in vesicular transport, receptor
  • downregulation, post-Golgi transport and endocytosis
  • involved in tumor metastasis
  • with DNM2, functions as a dynamic actin filament remodeling complex that influences the global organization of the actomyosin cytoskeleton
  • multifunctional regulator of cellular invasiveness
  • controls cell motility and lamellipodial dynamics by regulating extracellular matrix (ECM) secretion
  • phosphorylation regulates cell invasion through a pH-dependent pathway
  • DBNL and cortactin (CTTN) play distinct roles in podosome regulation
  • actin-binding protein, is essential for cell growth and motility
  • branched actin regulator and tumor-overexpressed protein that promotes vesicular trafficking at a variety of cellular sites, including endosomes and the trans-Golgi network
  • involved in regulation of late endosomal/lysosomal maturation and trafficking that affects Golgi morphology
  • role for CTTN acetylation in the regulation of DLG4 dendritic clustering, which may work in concert with cortactin role in spine development
  • is a key scaffold for actin regulation at the zonula adherens (ZA), which localizes to the ZA through influences from both CDH1 and WASL
  • phosphorylated CTTN may facilitate the recruitment of PFN1 to the cell edge, which promotes localized actin polymerization, leading edge formation, and cell movement
  • actin-interacting protein, implicated in cytoskeletal architecture and often amplified in several types of cancer
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component CTTN and RCC2/TD60 complex may play a functional role in cells undergoing mitosis
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • Rho GTPase activating protein 8 (ARHGAP8, BPGAP1)
  • cadherin associated protein delta 1 (CTNND1)
  • dynamin 2
  • fer (fps/fes related) tyrosine kinase (FER)
  • faciogenital dysplasia protein (FGD1)
  • hepatocyte growth factor/scatter factor (GRB2)
  • potassium voltage-gated channel, shaker-related subfamily, member 2 (TKCNA2, Kv1.2)
  • myosin light chain kinase (MYLK)
  • N-syndecan (syndecan-3, SDC3)
  • cortactin-binding protein 1 (CortBP1)
  • tyrosine kinase Syk
  • F-actin and the Arp2/3 complex
  • Wiskott-Aldrich syndrome protein (N-WASP)
  • WASp-Interacting Protein (WIP)
  • cortactin-binding protein 90 KDa (CBP90)
  • histone deacetylase 6 (HDAC6) (modulates cell motility by altering the acetylation level of cortactin)
  • association between NAA15 and CTTN, and NAA15 is involved in the regulation of retinal-endothelial-cell permeability to albumin
  • sirtuin 1 (SIRT1)
  • mechanistic link among the cell adhesion molecule, CDH2, the actin-binding scaffold protein, CTTN, and KCNA5 remodeling in the heart
  • SH3PXD2B is a scaffold protein that plays a key role in regulating the actin cytoskeleton via SRC and CTTN
  • cell spreading promotes the association of cortactin and PTK2 and tyrosine phosphorylation of CTTN disrupts this interaction, which may explain how it inhibits cell spreading
  • E3 ligase subunit BTRC interacts with CTTN, and its overexpression reduced cortactin protein levels, an effect attenuated by MAPK1 inhibition
  • efficient colocalization of capping protein (CP) and CTTN at the cell periphery required CD2AP
  • recruits WASF2 to the cell membrane and SKAP2 inhibits their interaction
  • tyrosine phosphorylation of SDC1 triggers the robust recruitment of CTTN, which we found to be an essential mediator of efficient actin-dependent endocytosis
  • can directly bind WASF2, as well as Arp2/3, and both these interactions are necessary for actin assembly at the zonula adherens (ZA)
  • interaction of CTTN with PFN1 plays a pivotal role in regulating actin dynamics, smooth muscle contraction, and airway hyperresponsiveness in asthma (the association of CTTN with PFN1 is regulated by ABL1-mediated CTTN phosphorylation)
  • FBXL5 interacts with and targets CTTN for ubiquitylation and subsequent proteasomal degradation (negative regulation of CTTN by FBXL5 in gastric cancer cells migration)
  • NAA15, a subunit of the N-terminal acetyltransferase NatA, complexes with the SRC substrate CTTN and supports adult retinal homeostasis through regulation of vascular permeability
  • cell & other
    REGULATION
    Other cortactin acetylation is catalysed by EP300
    cortactin is a specific target for SIRT1 deacetylase activity
    regulated by PRKD, an upstream regulator of cortactin and the Arp actin polymerization machinery
    regulated by reversible phosphorylation
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in breast cancer with poor prognosis, in cell lines from breast and squamous carcinomas of head and neck
    tumoral   amplification    
    coamplified with CCND1 in oral squamous cell carcinoma
    tumoral     --over  
    is closely associated with hepatocellular carcinoma poor prognosis that caused by cancer embolus and metastasis
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    tumor  
    EGFR-independent role of cortactin in HNSCC (squamous carcinomas of head and neck) may have important implications regarding the design of targeted therapies to combat tumor spread
    ANIMAL & CELL MODELS