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Symbol NCK1 contributors: mct - updated : 13-04-2017
HGNC name NCK adaptor protein 1
HGNC id 7664
  • three SH3 domains
  • a unique SH2 domain that recognizes a specific phosphotyrosine residue on RTKS or on substrates of RTKS like IRS1, lacking a catalytic domain
  • a previously unrecognized activation motif in a linker between the first two SH3 domains, and this linker sequence, reminiscent of bacterial virulence factors, di26554011)rectly engages the WASL GTPase binding domain (GBD) and competes with verprolin-homology, connector-helix, acidic motif (VCA) binding
    CATEGORY protooncogene , signaling
    SUBCELLULAR LOCALIZATION     plasma membrane
    basic FUNCTION
  • adaptor protein involved in transducing signals from receptor tyrosine kinases to downstream signal recipients such as RAS
  • intracellular adaptor protein that is involved in actin polymerization
  • independent roles and mechanisms of action of NCK1 and NCK2 in dermal fibroblast migration, which is critical for wound healing
  • endogenous regulator of PKR and NCK1-PKR interaction could be a way to limit PKR activation
  • NCK1 is the regulator of RASA1 activity
  • proteasomal regulation is a key factor in the distinct and non-redundant effects of NCK1 on RHOA-mediated actin dynamics
  • NCK1 and NCK2 have non-redundant roles in human T cell activation
  • role for NCK1 in regulating gene expression through its role as the scaffold for assembly of the cytoplasmic capping complex
  • crucial role for NCK1 as a master regulator within the endothelium to control actin cytoskeleton organization, vascular network remodeling, and endothelial-to-mesenchymal transition (EnMT) during cardiovascular development
  • regulates preosteoblastic/osteoblastic migration and bone mass
    signaling signal transduction
    LCP2/GRAP2/NCK1 adaptor protein pathway, implicated in regulation of the actin cytoskeleton by BCR-ABL kinase
    a component
  • FYB/NCK1 complex might provide a means to link integrin activation with the actin cytoskeleton
    small molecule
  • associates with BLNK, PCLG1, VAV1 and NCK1 in a B-cell antigen receptor-dependent fashion
  • strong binding of CD3epsilon to EPS8L1 and NCK1 SH3 domains
  • connection between septins, SOCS7, NCK1/NCK2 signaling, and the DNA damage response
  • in podocytes, links the slit-diaphragm protein nephrin to the actin cytoskeleton (interaction essential for nephrin-dependent reorganization of actin in podocyte injury)
  • connect PDGF-BB signaling to the actin cytoskeleton and cell motility
  • interaction with SORBS1 (implications for a role in cytoskeletal remodelling during differentiation of skeletal muscle cells)
  • functional cooperation between NCK1 and FYB mediates LCP2/WAS interactions and actin rearrangement
  • directly binds and activates the GTPase-activating protein of RAS (RASA1), which is responsible for the down-regulation of RAS
  • NCK1 interacts with PTPN1 and the NCK1/PTPN1 complex inducibly associates with the IR for the attenuation of IR activation in mammalian cells
  • LRFN4 complexed with SFN and NCK1 to mediate elongation in monocytic cells via RAC-1-mediated actin cytoskeleton reorganization
  • NCK1 directly modulates NPHS1 phosphorylation through formation of a signaling complex with the Src family kinase FYN
  • NCK1 recruitment to the TCR required for ZAP70 activation during thymic development
  • WIPF1 acts as an essential link between NCK1 and WASL
  • adaptor function for NCK1 in recruiting PK3AP1 to sites of BCR signaling
  • ITSN1 is an important general regulator of CDC42-, NCK1- and WASL-dependent actin polymerisation
  • NCK1 recruitment to the TCR is fundamental to mount an efficient T cell response, and the NCK1-CD3E interaction may represent a target for pharmacological modulation of the immune response
  • NCK1-ELMO1 interaction promoting RAC1 activation and cell motility
  • interacts with PTPN1 and also regulates PTPN1 expression, playing a role in regulating the PI3K/AKT1 pathway
  • NCK1 was the most potent activator of WASL-driven actin assembly
  • NCK1 integrates NPHS1 with the Hippo kinase cascade through association with the adaptor protein WTIP
  • cell & other
    Other phosphorylated on ser and tyr residues
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    NCK1 silencing in pancreatic beta cells promotes EIF2AK3 activation and signaling to protect beta cells against pathological stresses
    Susceptibility to diabetic nephropathy (DN) in type 1 diabetes mellitus
    Variant & Polymorphism other variant increasing the risk of diabetic nephropathy (DN) in type 1 diabetes mellitus
    Candidate gene
    Therapy target