Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol TPPP contributors: mct/pgu - updated : 29-06-2017
HGNC name tubulin polymerization promoting protein
HGNC id 24164
Location 5p15.33      Physical location : 659.977 - 693.510
Synonym name
  • brain-specific protein p25 alpha
  • tubulin polymerization-promoting protein
  • Synonym symbol(s) p24, p25, TPPP1, TPPP/p25, p25alpha
    DNA
    TYPE functioning gene
    STRUCTURE 33.53 kb     4 Exon(s)
    MAPPING cloned Y linked N status confirmed
    Map pter - D5S392 - TPPP - D5S1981 - D5S2005 - cen
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    4 - 6039 23.6 219 - 2007 17105200
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrineparathyroid   highly
    Lymphoid/Immunespleen   moderately
    Nervousbrain   specific Homo sapiens
     nervecranial nerve  moderately
    Respiratoryrespiratory tractlarynx  highly
    Visualeye   moderately
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose  highly
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Nervousoligodendrocyte Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • two microtubule binding sites, both located in intrinsically disordered domains, one at the N-terminal and the other in the C-terminal domain
  • a central folded domain following binding to microtubules can drives homotypic protein-protein interactions leading to bundled microtubules
  • conjugated GlycoP , PhosphoP
    mono polymer dimer
    HOMOLOGY
    interspecies homolog to murine Tppp (93.1 pc)
    homolog to drosophila Ringer
    homolog to rattus Tppp (93.1 pc)
    intraspecies paralog to TPPP2, TPPP3
    Homologene
    FAMILY
  • TPPP family
  • CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule
    intracellular,nucleus
    intracellular,nuclear envelope
    text
  • perinuclear region of cytoplasm
  • colocalizes specifically with the microtubules
  • basic FUNCTION
  • promoting in vitro the polymerization of tubulin into double-walled tubules and polymorphic aggregates or bundled stabilized microtubules blocks
  • inhibiting mitotic spindle assembly and nuclear enveloppe breakdown, when overexpressed, apparently without affecting other cellular events
  • associated with a basic function of cilia
  • multiple effector of the microtubule organization, having microtubule bundling activity able to protect the microtubules from depolymerization
  • influences the microtubule dynamics by decreasing the growth velocity of the microtubule plus ends and also affects cell motility
  • may be controling the differentiation of oligodendrocytes via microtubule acetylation by inhibition of tubulin deacetylation
  • its physiological function in oligodendrocytes could be the reorganization and stabilization of the microtubular ultrastructures in the course of ensheathment of axons
  • regulates microtubule (MT) dynamics via promoting MT polymerization and inhibiting histone deacetylase 6 (HDAC6) activity to increase MT acetylation
  • TPPP inhibits cell proliferation by delaying the G1/S-phase and the mitosis to G1-phase transitions
  • plays a crucial role in the differentiation of the zinc-rich oligodendrocytes, the major constituent of myelin sheath
  • microtubule-associated protein, detected in protein inclusions associated with various neurodegenerative disease
  • TPPP and SNCA have two key features: they are disordered and co-enriched/co-localized in brain inclusions
  • TPPP and TPPP3 are intrinsically unstructured proteins (IUPs) that bind and polymerize tubulin and stabilize microtubules, but TPPP2 does not
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • may form dimers
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • tubulin (binding is inhibited by GTP)
  • GSK3B
  • GAPDH
  • binds to HDAC6 (histone deacetylase 6), an enzyme responsible for tubulin deacetylation, inhibits HDCA6 activity and promotes acetylation of the microtubule network
  • interacting partner of MBP
  • LIMK2 acts through TPPP in the regulation of astral microtubule organization, whereas both LIMK1 and LIMK2 affect centrosome focusing
  • TPPP lowered the mobility of autophagosomes and hindered the final maturation of autophagosomes by preventing their fusion with lysosomes for the final degradation of SNCA
  • link between TPPP and BACE1 in AD (Alzheimer disease) brains, suggesting that upregulated CDK5 activation by TPPP accelerates AD pathogenesis by enhancing BACE1 activity via phosphorylation
  • cell & other
    REGULATION
    repressed by phosphorylated by TPK II
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   amplification    
    in early stages of non-small cell lung cancer
    tumoral   amplification    
    in high-grade bladder cancers
    constitutional     --over  
    in the cerebrospinal fluid (CSF) of MS patients, and its level is significantly higher than in the case of non-MS patients
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • loss of TPPP-positive oligodendrocytes in demyelinated lesions in the brain of Multiple sclerosis (MS) patients could be a biomarker for MS
  • TPPP in human CSF can become diagnostic marker for MS
  • Therapy target
    ANIMAL & CELL MODELS
  • ringer-null mutants show cell misplacement, and errors in axonal extension and targeting