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FLASH GENE
Symbol HERPUD1 contributors: mct/npt - updated : 27-10-2017
HGNC name homocysteine-inducible, endoplasmic reticulum stress-inducible, ubiquitin-like domain member 1
HGNC id 13744
Location 16q13      Physical location : 56.965.747 - 56.977.793
Synonym name
  • MMS-inducible gene
  • methyl methanesulfonate (MMF)-inducible fragment protein 1
  • Synonym symbol(s) SUP, HERP, MIF1, KIAA0025
    DNA
    TYPE functioning gene
    STRUCTURE 11.79 kb     8 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    8 - 1787 - 275 - 2000 10922362
    8 - 1944 - 391 - 2000 10922362
    8 - 1941 - 390 - 2000 10922362
    7 - 2123 - 366 - 2000 10922362
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Lymphoid/Immunelymph node   highly
    Nervousbrain   highly Homo sapiens
    Urinarykidney   highly
    Visualeye   highly
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Nervousastrocyte Homo sapiens
    Nervousglia Homo sapiens
    Nervousneuron Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • an ubiquitin-like domain (ULD)
  • HOMOLOGY
    Homologene
    FAMILY
    CATEGORY chaperone/stress
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    basic FUNCTION
  • may play a role in both unfolded protein response (UPR), and the destruction of misfolded proteins by the ER-associated protein degradation (ERAD)
  • ER membrane protein upregulated by ER stress, is implicated in regulation of ERAD
  • HERPUD1 binding to ubiquilin proteins plays an important role in the ERAD pathway
  • suggested to improve ER-folding, decrease ER protein load, and participate in ER-associated degradation (ERAD) of proteins
  • may potentially delay the degradation of cytosolic proteins at the ubiquitination step
  • ubiquitin domain protein, which is strongly induced by the unfolded protein response
  • regulates SYVN1-mediated ubiquitylation in a ubiquitin-like domain-dependent manner
  • likely involved in degradation of immature nicastrin by facilitating VCP-dependent nicastrin retranslocation and ubiquitination
  • could play a role in the elimination of the excess unassembled components of a multimeric complex
  • functionally, HERPUD1 plays a role in maintaining ER homeostasis by facilitating proteasome-mediated degradation of ER-resident Ca(2+) release channels
  • is likely essential for the resolution of ER stress through maintenance of ER Ca(2+) homeostasis
  • operates as a relevant factor in the defense against glucose starvation by modulating autophagy levels
  • playslikely a dual role in cellular stress adaptation
  • endoplasmic reticulum- (ER-) resident membrane protein that plays a role in ER-associated degradation
  • is involved in endoplasmic reticulum stress response
  • role of HERPUD1 in the regulation of host innate immunity in response to viral infection
  • HERPUD1 is a novel negative regulator of pathological cardiac hypertrophy
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component component of the endoplasmic reticulum-associated degradation (ERAD) complex
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with both PSEN1 and PSEN2
  • interacts with PKD2 and promotes its degradation through the ERAD pathway
  • target of CREB3
  • interacts with members of the ubiquilin family, which function as a shuttle factor to deliver ubiquitinated substrates to the proteasome for degradation
  • interacts directly with the ubiquitin ligase SYVN1, which is found in high molecular mass complexes of the ER membrane
  • interaction with NCSTN (is likely involved in degradation of immature nicastrin by facilitating VCP-dependent nicastrin retranslocation and ubiquitination)
  • HERPUD1 regulates insulin secretion via control of NNT expression
  • HERPUD1 is a direct NRF1 target gene and NRF1 is a transcriptional activator of HERPUD1 expression during ER stress
  • HERPUD1 is a modulator of the ER stress response which is dependent on the participation of MAVS
  • through interacting with TBK1, HERPUD1 amplifies the MAVS signaling and facilitates the phosphorylation and nuclear translocation of IRF3 and NFKB1 to enhance the expression of IFNs, which leads to a broad inhibition of the replication of RNA viruses
  • cell & other
    REGULATION
    induced by endoplasmic reticulum (ER) stress
    Other ubiquitin-proteasome-mediated degradation of HERPUD1 is a novel mechanism that fine-tunes the stress tolerance capacity of the cell
    strongly induced by ER stress but rapidly degraded by proteasome
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    in glia could help to explain the inflammation-like changes observed in Parkinson disease
    constitutional       loss of function
    likely suppressed the development of atherosclerosis by attenuating the ER stress-induced inflammatory reactions
    constitutional     --low  
    protects from protein aggregation by up-regulating autophagy
    Susceptibility to polypoidal choroidal vasculopathy (PCV)
    Variant & Polymorphism SNP
  • HERPUD1 rs2217332 is significant associated with Chinese PCV
  • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    neurologyneurodegenerativeParkinson/dementia Parkinsonism
    therapeutic potential in PD for agents that increase HERPUD1 levels or its ER Ca(2+)-stabilizing action
    ANIMAL & CELL MODELS
  • Herpud1-knockout mice exhibit cardiac hypertrophy and dysfunction and decreased Herpud1 protein levels lead to elevated levels of hypertrophic markers in cultured rat cardiomyocytes