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FLASH GENE
Symbol MACF1 contributors: mct/npt - updated : 30-08-2018
HGNC name microtubule-actin crosslinking factor 1
HGNC id 13664
Corresponding disease
LDHCC lissencephaly with dysplastic hippocampus, and corpus callosum
Location 1p34.3      Physical location : 39.547.117 - 39.952.789
Synonym name
  • macrophin, actin crosslinking protein, superfamily member 7
  • trabeculin-alpha
  • 620 kDa actin binding protein
  • spectraplakin
  • macrophin 1
  • Synonym symbol(s) KIAA0465, ACF7, ABP620, KIAA1251, FLJ45612, FLJ46776, OFC4, MACF
    DNA
    TYPE functioning gene
    STRUCTURE 405.67 kb     98 Exon(s)
    Genomic sequence alignment details
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Map see OXCT2 OXCT2
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    98 - 17821 620.3 5430 - 1999 10559237
    - splicing 1400 - 258 - 1999 10559237
    only seven exons (near the 3' end of variant 1)
    - splicing 8000 - 2350 - 1999 10559237
    utilizing an alternative splice site at exon 45
    64 - 19271 670.1 5938 - 1999 10559237
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart     Homo sapiens
    Digestiveintestine     Homo sapiens
    Endocrineneuroendocrinepituitary  highly
    Nervousbrain   predominantly Homo sapiens
    Visualeyeretina    Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumcardiac  
    Nervouscentral  predominantly Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Digestiveepithelial cell Homo sapiens
    Skin/Tegumenthair follicle cell Homo sapiens
    Visualganglion cell Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a N terminal actin-binding domain, N terminus containing two calponin-homology (CH) domains that bind actin, a plakin domain, and a long spectrin-repeat rod domain that confers flexibility
  • a central rod region with 37 spectrin-like repeats
  • an intrinsic actin-regulated ATPase domain
  • a SH3 domain
  • ATPase domain that is required for microtubule tracking along actin fibers toward focal adhesions
  • C terminus functions as a Micotubule binding domain and contains two calcium-binding EF-hand domains, a zinc-binding GAR (growth-arrest specific 2 or Gas2-related) domain, a positively charged Gly-Ser-Arg (GSR) region, and an EB1-binding SxIP domain
  • HOMOLOGY
    interspecies ortholog to Drosophila kakapo
    homolog to murine Aclp7
    intraspecies homolog to plectin and dystrophin
    Homologene
    FAMILY
  • actin crosslinking protein superfamily
  • plakin family of cytoskeletal linker protein (spectraplakin family)
  • CATEGORY structural protein
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,cytoskeleton,microtubule
    text
  • targeting to the plasma membrane is both required and sufficient for microtubule capture downstream of ERBB2
  • basic FUNCTION
  • forming bridges between different cytoskeletal elements through specialized modular domains
  • stabilizing actin at sites where microtubules and microfilaments meet, and essential integrator of microtubule dynamics
  • multidomain protein that can associate with microfilaments and microtubules
  • may be playing a role in the Wnt signaling pathway
  • can function as an ATPase, and, importantly, it behaves as an actin-regulated rather than microtubules- or calcium-regulated ATPase
  • having particular functions in establishing and maintaining proper cytoskeletal coordination during cell movement
  • MACF1 and SHOX2 regulate the organisation of neuronal microtubules, a role dependent on both the F-actin- and microtubule-binding domains
  • having functions in regulating dynamic interactions between microtubules and F-actin to sustain directional cell movement
  • MACF1 and SHOX2 regulate the organisation of neuronal microtubules, a role dependent on both the F-actin- and microtubule-binding domains
  • required and sufficient for MT capture, probably via its ability to interact with ANKS1B at MT ends
  • seems to use two different modes of action associated with distinct functions: displacement along actin might require motor-like activity, whereas MT capture might not
  • integrates signaling, cytoskeletal dynamics, and polarized locomotion of somatic stem cells
  • regulates MT growth as well as the dynamics of focal adhesions associated with F-actin
  • critical in CNS development
  • ELMO1 and MACF1 cooperate to promote the formation of membrane protrusions
  • role for MACF1 in cardiomyocyte microtubule distribution and in adaptation to hemodynamic overload
  • novel role for MACF1 in neurite differentiation that is critical to the creation of neuronal connectivity in the developing brain
  • plays a role in the coordination of microtubules and actin in multiple cellular processes
  • is an important regulator of apico-basal polarity in mammalian intestinal cells and that a radial centrosome-centered microtubule organization can act as an inhibitor of epithelial polarity
  • play critical roles in many cytoskeleton-related processes
  • may play a part in neuromuscular disorders and have a neuroprotective role in the optic nerve
  • plays an essential function in various cellular processes, including cell proliferation, migration, signaling transduction and embryo development
  • large spectraplakin protein known to have crucial roles in regulating cytoskeletal dynamics, cell migration, growth, and differentiation
  • control of MACF1 levels by HECTD1 modulates likely epithelial-to-mesenchymal transition (EMT) and the efficiency of metastasis
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    Wnt signaling pathway
    a component
    INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • Ca2+
  • protein
  • interacting with ANKS1B
  • role for ELMO2 in the recruitment of MACF1 to the membrane to promote microtubule capture and stability
  • DOCK1 is required for signaling by ELMO1-MACF1
  • MACF1 interacts with and mediates GSK3B signaling in developing neurons
  • regulates dendritic arborization and axon outgrowth of developing pyramidal neurons by arranging cytoskeleton components and mediating GSK3B signaling
  • MACF1 also interacts with the ciliary proteins MKKS and KIAA0586
  • specifically binds to CAMSAP3 and is required for the apical localization of CAMSAP3-decorated microtubule minus ends
  • promotes osteoblast differentiation by promoting CTNNB1/HNF1A/RUNX2 signaling axis
  • MACF1 was found to enhance CTNNB1 expression and activity, and mechanical unloading decreased CTNNB1 expression through MACF1
  • cell & other
  • microfilament and actin filament cross-linker
  • REGULATION
    Phosphorylated by GSK3B, a kinase inhibited by Wnt signaling, that directly phosphorylates MACF1
    Other upregulated upon differentiation of myoblasts into myotubes
    ASSOCIATED DISORDERS
    corresponding disease(s) LDHCC
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional germinal mutation      
    causes a novel myopathy genetic disease
    constitutional       loss of function
    abolishes ciliogenesis and disrupts apicobasal polarity establishment in the retina
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    potential target to enhance the efficacy of therapeutic treatment modalities in cancers
    cancerbrainglioma/neuroblstoma
    potential as a unique biomarker that can be targeted synergistically with TMZ as part of a combinatorial therapeutic approach for the treatment of genetically multifarious glioblastomas
    ANIMAL & CELL MODELS