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FLASH GENE
Symbol MARCKS contributors: mct/npt/pgu - updated : 20-12-2016
HGNC name myristoylated alanine-rich protein kinase C substrate
HGNC id 6759
Location 6q22.1      Physical location : 114.178.526 - 114.184.650
Synonym name
  • kinase C substrate 80 kD light chan
  • myristoylated alanine-rich protein kinase C substrate (MARCKS, 80K-L)
  • 80K-L protein
  • phosphomyristin
  • protein kinase C substrate, 80 kDa protein, light chain
  • Synonym symbol(s) MACS, PKCSL, 80K-L, FLJ14368, FLJ90045, PRKCSL
    DNA
    TYPE functioning gene
    STRUCTURE 6.13 kb     2 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Physical map
    LOC51212 6q22.1 diferentiation-related protein dif13 C6orf4 6q21 chromosome 6 open reading frame 4 FYN 6q21 FYN oncogene related to SRC, FGR, YES WISP3 6q22-q23 WNT1 inducible signaling pathway protein 3 TUBE1 6q12 tubulin, epsilon 1 LAMA4 6q21 laminin, alpha 4 LOC345882 6q22.1 similar to Pin2-interacting protein X1 (TRF1-interacting protein 1) (Liver-related putative tumor suppressor) (67-11-3 protein) LOC221278 6q22.1 similar to ret finger protein-like 1 LOC391960 6 similar to 40S ribosomal protein SA (P40) (34/67 kDa laminin receptor) (Colon carcinoma laminin-binding protein) (NEM/1CHD4) (Multidrug resistance-associated protein MGr1-Ag) LOC345884 6q22.1 similar to Keratin, type I cytoskeletal 18 (Cytokeratin 18) (K18) (CK 18) LOC391961 6 similar to fem-1 homolog a (C.elegans) LOC389424 6 similar to Proliferation-associated protein 2G4 (Cell cycle protein p38-2G4 homolog) (hG4-1) LOC391962 6 similar to Cytokine inducible SH2-containing protein 5 (Suppressor of cytokine signaling 5) (SOCS-5) (Cytokine-inducible SH2 protein 6) (CIS-6) LOC389425 6 similar to ribosomal protein S27a LOC221286 6q22.1 similar to ribosomal protein L30 MARCKS 6q21-q22.2 myristoylated alanine-rich protein kinase C substrate FLJ34503 6q22.2 hypothetical protein FLJ34503 HDAC2 6q21 histone deacetylase 2 HS3ST5 6q22.31 heparan sulfate (glucosamine) 3-O-sulfotransferase 5 LOC391963 6 similar to DnaJ homolog subfamily A member 1 (Heat shock 40 kDa protein 4) (DnaJ protein homolog 2) (HSJ-2) (HSDJ) FRK 6q21-q22.3 fyn-related kinase NT5C2L1 6q22.31 5'-nucleotidase, cytosolic II-like 1 COL10A1 6q21-q22.3 collagen, type X, alpha 1(Schmid metaphyseal chondrodysplasia)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    2 - 4304 31.4 332 - 2009 19475567
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Nervousbrain   highly Homo sapiens
     gangliasensory gangliadorsal root   Homo sapiensFetal
    Reproductivemale systemtestis    Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoietic    
    Nervouscentral  highly Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticneutrophil
    Lymphoid/Immunemacrophage
    Nervousneuron Homo sapiens
    Reproductivespermatozoa Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal
    Text cochlea
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N terminal site of myristoylation
  • a PSD effector domain
  • conjugated PhosphoP
    HOMOLOGY
    Homologene
    FAMILY
  • MARCKS family of phospholipid binding proteins
  • CATEGORY structural protein
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    intracellular,cytoplasm,cytoskeleton,microfilament
    text
  • binding actin filaments when not phosphorylated
  • presence of MARCKS in plasmalemmal caveolae and/or lipid rafts
  • localized to the nucleus
  • basic FUNCTION
  • actin filament crosslinking protein regulator of actin cytoskeleton
  • MARCKS and MARCKSL1 are membrane-binding proteins implicated in cell spreading, integrin activation and exocytosis
  • play a major key role in PDGF-BB-induced chemotaxis in activated hepatic stellate cells
  • directly involved in dendrite branching during neurogenesis and mediates the regulation of the actin cytoskeleton at particular cortical cell regions where filopodia are being formed
  • participate in formation of F-actin-based lamellipodia, which represents the first stage of neurite formation
  • may be having a novel role in lamellipodia formation induced by IGF1 via the translocation of MARCKS, and accumulation of beta-actin in the membrane microdomains
  • plays a key role in insulin-dependent endothelial signaling to PIP2 and is a critical determinant of actin assembly and directed cell movement in the vascular endothelium
  • critical determinant of insulin-modulated PIP2 responses in endothelial cells, and having a key role in WASL/Arp2/3 signaling in endothelial cells
  • may potentially play a role in vascular disease states characterized by deficient endothelium-dependent signaling responses
  • distinct role for MARCKS in the regulation of H2O2-induced permeability change in endothelial cells
  • is a mediator of the H2O2-induced endothelial permeability change, but does not modulate changes in basal permeability
  • regulates endothelial permeability and cytoskeleton organization
  • important functional role for the interaction between MARCKS and PSA in the developing and adult nervous system
  • actin-binding protein, with special functions in the development of the central nervous system
  • might also be important for the differentiation of of PNS cells and precursors
  • is a negative modulator of the acrosomal exocytosis, probably by sequestering PIP2, and it is phosphorylated during acrosomal exocytosis
  • novel function of MARCKS in mediating membrane targeting of plasmalemmal precursor vesicles (PPVs) during axon development
  • is postulated to regulate the passage of secretory granules through cortical actin in the early phase of exocytosis
  • appears to be a nonessential regulatory protein in mast cell exocytosis but exerts a negative modulation
  • PRKCD-mediated MARCKS phosphorylation as a key step in the inflammatory response of neutrophils
  • is a novel translational target with beneficial cell type-specific effects on both endothelial cell (EC) and vascular smooth muscle cell (VSMC)
  • acts as a "molecular switch," binding to and regulating PIP2 signaling to regulate processes like proplatelet extension (microtubule-driven) vs proplatelet branching (Arp2/3 and actin polymerization-driven)
  • is enriched in the developing brain and plays an important, phosphorylation-dependent role in the modulation of axonal growth cone adhesion
  • CELLULAR PROCESS cell cycle
    cell life, proliferation/growth
    cell communication
    PHYSIOLOGICAL PROCESS development , nervous system , cellular trafficking transport
    PATHWAY
    metabolism
    signaling
    trafficking
    a component
  • DNAJC5 appeared to form a trimeric complex with MARCKS and HSP70 associated with mucin granule membranes within airway epithelial cells
  • INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • Ca2+
  • protein
  • FRKCA in skeletal muscle
  • interacting with DNAJC5 (HSP70, DNAJC5, and their interactions with MARCKS, are involved in mucin secretion)
  • binds directly to Hsp70, and Hsp70 binds directly to DNAJC5, but MARCKS binding to DNAJC5 appears to require the presence of Hsp70
  • functional interaction between actin filaments and MARCKS in cells, and particularly of an action in maintaining a phosphorylation in a region of the N-terminal moiety of MARCKS
  • major cellular substrate of PKC (protein kinase C) which phosphorylates MARCKS at serine residues located at the effector domain (ED) or phosphorylation site domain (PSD) but can also be phosphorylated by other kinases like MAPK and Cdks at serine/threonine residues located either at the C- or N-moieties
  • target for phosphorylation by PRKC
  • cleavage of MARCKS by Calpain may have an important role in regulation of the PKC/MARCKS pathway regulating airway mucin secretion
  • cathepsin K exocytosis is controlled by PRKCD through modulation of the actin bundling protein myristoylated alanine-rich C-kinase substrate (MARCKS)
  • RAC1 is an early component of the H2O2-initiated signaling cascade leading to MARCKS phosphorylation
  • MARCKS mediates membrane targeting of RAB10-positive plasmalemmal precursor vesicles (PPVs), and this regulation is critical for axon development
  • CALM1 and CAMK2A modulate SCNN1A activity by destabilizing the association between the actin cytoskeleton, SCNN1A, and MARCKS, or MARCKSL1 at the apical membrane
  • its upregulation increases VSMC motility by activation of RAC1 and CDC42
  • PIN1 is present in the growth cone, interacts with MARCKS-Phosphorylated, and regulates its dephosphorylation
  • CALM1 does stimulate PI3K lipid kinase activity by binding MARCKS and displacing it from PIP2 headgroups
  • cell & other
    REGULATION
    inhibited by protein kinase C and Ca2+/calmodulin
    Other phosphorylation at S25 does not modify the overall distribution of MARCKS clusters in the different cell regions of developing neuroblasts
    its phosphorylation also promotes its interactions with actin and actin-binding proteins
    phosphorylation regulates MARCKS function in acrosomal exocytosis
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    associated with poor patient survival in epithelial ovarian cancer (EOC)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerreproductiveovary
    the potential of MARCKS inhibition as a novel stroma-oriented therapy in epithelial ovarian cancer (EOC)
    ANIMAL & CELL MODELS
    MARCKS-null mouse is embryonic lethal because of severe neural defects