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FLASH GENE
Symbol HACE1 contributors: mct - updated : 08-11-2017
HGNC name HECT domain and ankyrin repeat containing, E3 ubiquitin protein ligase 1
HGNC id 21033
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • six N-terminal ankyrin protein–protein interaction repeats with sequence similarity to those of INKA
  • a middle (MID) domain, with a role in conferring the specificity of association of HACE1 to the active form of RAC1
  • a C- terminus homologous to E6-associating protein carboxy terminus ubiquitin-protein ligase domain and HECT domain (Slade 2010)
    • HOMOLOGY
    interspecies ortholog to murine Hace1
    Homologene
    FAMILY
  • HECT family of E3 ubiqutin protein ligase
    • CATEGORY enzyme , regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,organelle,Golgi
    intracellular,nucleus
    basic FUNCTION
  • involved in protein modification, ubiquitin cycle
  • possessing intrinsic ubiquitin ligase activity
  • having tumor-suppressor function dependent on its E3 ligase activity and controling adhesion-dependent growth and cell cycle progression during cell stress through degradation of cyclin D1
  • involved in repression of RAR-regulated transcription which is due to its ability to inhibit the RA-dependent degradation of RARs (Zhao 2010)
  • play a role in the regulation of cell cycle progression during cellular stress by influencing cyclin D1 degradation (Slade 2010)
  • role of the HACE1 E3 ubiquitin-ligase in controlling RAC1 ubiquitylation and activity
  • is an antagonist of cell migration through its ability to degrade active RAC1
  • protects the heart under pressure stress by controlling protein degradation
  • has a protective function in the heart in response to haemodynamic stress, suggesting that HACE1 may be a potential diagnostic and therapeutic target for heart disease
  • critical role for HACE1 in breast cancer progression
  • can act as a haploinsufficient tumor suppressor gene in most B-cell lymphomas
  • HACE1 controls TNF-elicited cell fate decisions and exerts tumor suppressor and anti-inflammatory activities via a TNFRSF1A-RIPK3 kinase-necroptosis pathway
  • E3 ubiquitin ligase HACE1 is a potent tumor suppressor that controls cell proliferation and ubiquitylates the small GTPase RAC1 to target it to proteasomal degradation
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component HACE1-OPTN axis synergistically suppresses growth and tumorigenicity of lung cancer cells
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with UBCH7
  • HACE1 plays a role in the NFE2L2 antioxidative stress response pathway and in neurodegeneration
  • ubiquitylates OPTN and promotes its interaction with p62/SQSTM1 to form the autophagy receptor complex, thus accelerating autophagic flux
  • HACE1 is a specific E3 ligase that polyubiquitinates YBX1 through non-canonical K27 linked ubiquitin chains
  • HACE1 is a central gatekeeper of TNFRSF1A-induced cell fate
  • is essential for the ubiquitylation of the adaptor protein TRAF2 and formation of the apoptotic CASP8 effector complex
  • STX5 is monoubiquitinated by the ubiquitin ligase HACE1 in early mitosis and deubiquitinated by the deubiquitinase VCPIP1 in late mitosis
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) SPPRS
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    in sporadic Wilms tumor (by hypermethylation)
    tumoral     --low  
    in multiple human tumor type
    tumoral     --low  
    by hyper methylation in gastric carcinoma (Sakata 2009)
    constitutional     --low  
    associated with a significant decrease in apoptosis and an accumulation of cells in the S and G2/M phases
    constitutional     --over  
    in the serum of patients with heart failure
    constitutional     --low  
    reduction of HACE1 levels in the striatum of Huntington disease patients, implicating HACE1 in the pathology of Huntington disease
    tumoral     --low  
    by hypermethylation in hepatocellular carcinoma
    Susceptibility to neuroblastoma
    Variant & Polymorphism other
  • common variants in HACE1 and LIN28B influence neuroblastoma susceptibility
    • Candidate gene
    Marker
  • may be a valuable prognostic biomarker for hepatocellular carcinoma
    • Therapy target
    SystemTypeDisorderPubmed
    cancerdigestiveliver
    potential therapeutic target for hepatocellular carcinoma treatment
    ANIMAL & CELL MODELS