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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
Corresponding disease
SPPRS spastic paraplegia and psychomotor retardation with or without seizures
Location 6q16.3      Physical location : 105.175.967 - 105.307.794
Synonym name E3 ubiquitin-protein ligase HACE1
Synonym symbol(s) KIAA1320, SPPRS
EC.number 2.3.2.26
DNA
TYPE functioning gene
STRUCTURE 177.25 kb     24 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status provisional
Map cen - D6S1121E - D6S2097 -HACE1 - D6S2180 - qter
Authors Anglesio (04)
Physical map
GRIK2 6q16.3-q21 glutamate receptor, ionotropic, kainate 2 LOC389419 6 similar to hypothetical protein (L1H 3 region) - human LOC391956 6 similar to Hypothetical protein KIAA1002 HACE1 6q21 HECT domain and ankyrin repeat containing, E3 ubiquitin protein ligase 1 LOC389420 6 LOC389420 LOC389421 6 similar to LOC373796 protein BVES 6q21 blood vessel epicardial substance POPDC3 6q21 popeye domain containing 3 PREP 6q16.3-q21 prolyl endopeptidase LOC391957 6 similar to Chromatin assembly factor 1 subunit B (CAF-1 subunit B) (Chromatin assembly factor I p60 subunit) (CAF-I 60 kDa subunit) (CAF-Ip60) PRDM1 6q21-q22.1 PR domain containing 1, with ZNF domain APG5L 6q21 APG5 autophagy 5-like (S. cerevisiae) AIM1 6q21 absent in melanoma 1 RTN4IP1 6q21 reticulon 4 interacting protein 1 QRSL1 6q21 glutaminyl-tRNA synthase (glutamine-hydrolyzing)-like 1 C6orf203 6q21 chromosome 6 open reading frame 203 KIAA1553 6q21 KIAA1553 C6orf210 6q21 chromosome 6 open reading frame 210 FLJ10159 6q21 hypothetical protein FLJ10159 SCML4 6q21 sex comb on midleg-like 4 (Drosophila) SEC63 6q21 SEC63-like (S. cerevisiae) LOC285752 6q21 similar to ribosomal protein L3; 60S ribosomal protein L3; HIV-1 TAR RNA-binding protein B OSTM1 6q21 osteopetrosis associated transmembrane protein 1 NR2E1 6q21 nuclear receptor subfamily 2, group E, member 1 SNX3 6q13-q22.3 sorting nexin 3 LACE1 6q22.1 lactation elevated 1
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
24 - 4576 102.2 909 - 2007 17694067
23 - 4459 - 865 - 2007 17694067
24 - 4323 - 741 - 2007 17694067
24 - 4406 - 875 - 2007 17694067
- - 4502 - 831 - 2007 17694067
- - 4285 - 812 - 2007 17694067
- - 4500 - 747 - 2007 17694067
- - 4417 - 741 - 2007 17694067
- - 4493 - 741 - 2007 17694067
- - 4361 - 715 - 2007 17694067
- - 4368 - 648 - 2007 17694067
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Endocrineneuroendocrinepituitary  highly
Lymphoid/Immunethymus   highly
Reproductivemale systemtestis   
Respiratoryrespiratory tracttrachea  highly
Urinarykidney   moderately
cell lineage
cell lines
fluid/secretion
at STAGE
physiological period fetal
Text brain, kidney
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