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FLASH GENE
Symbol LONP1 contributors: mct - updated : 26-01-2016
HGNC name lon peptidase 1, mitochondrial
HGNC id 9479
Corresponding disease
CODAS cerebral, ocular, dental, auricular, and skeletal anomalies syndrome
Location 19p13.2      Physical location : 5.691.845 - 5.720.176
Synonym name
  • LON protease like protein
  • protease, serine, 15
  • mitochondrial ATP-dependent protease Lon
  • Synonym symbol(s) LONP, LONHS, HLON, LON, PRSS15, PIM1, MGC1498
    EC.number 3.4.21.-
    DNA
    TYPE functioning gene
    STRUCTURE 28.33 kb     18 Exon(s)
    MAPPING cloned Y linked N status inconsistent : contradictory evidence
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    18 - 3111 106 959 - 2017 26852705
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinesmall intestineduodenum  
     liver    
     salivary gland   highly
    Endocrineadrenal gland   highly
     thyroid   highly
    Respiratorylung    
    Skin/Tegumentskin   highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • three characteristic domains of the Lon A family:
  • a substrate-recognition N region,
  • an ATP-binding and hydrolysis region,
  • a serine-proteolytic site
  • a NB-ARC domain, a mitochondrial targeting sequence
  • a LON domain
  • HOMOLOGY
    interspecies homolog to bacterial Lon protease
    homolog to yeast PIM1
    Homologene
    FAMILY
  • PRS protease subfamily S
  • peptidase S16 family
  • CATEGORY enzyme , regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria,matrix
    text
  • is a nuclear-encoded gene from chromosome 19 that is transported into mitochondria via a mitochondrial targeting sequence located at the N-terminus
  • basic FUNCTION
  • regulator of mitochondrial DNA replication and for gene expression
  • participates directly in the metabolism of mtDNA
  • required for normal survival and proliferation
  • degrades folded proteins and initiates substrate cleavage non-processively
  • recognizes specific surface determinants or folds, initiates proteolysis at solvent-accessible sites, and generates unfolded polypeptides that are then processively degraded
  • potential roles for LONP1 in linking protein and mtDNA quality control
  • seems to play a major role in the elimination of oxidatively modified proteins in the mitochondrial matrix
  • ATP-powered protease that binds DNA
  • LONP1 and CLPP have been shown to degrade unfolded and damaged proteins in the matrix of mitochondria
  • regulates mitochondrial transcription by stabilizing the mitochondrial TFAM/mtDNA ratio via selective degradation of TFAM
  • modulates mtDNA biogenesis by the selective degradation of TFAM
  • nuclear-encoded mitochondrial enzyme, degrades oxidized proteins of the mitochondrial (mt) matrix, and participates in the replication of mtDNA
  • can be considered a stress responsive protein
  • ATP-dependent protease that controls the selective turnover of mitochondrial matrix proteins
  • nuclearly encoded and mitochondrially located stress-responsive protease, that is involved in heme-mediated ALAS1 turnover
  • has a wide variety of targets and is likely to play different roles depending of the cell type
  • plays a key role in metabolic reprogramming by remodeling OXPHOS complexes and protecting against senescence
  • independent of its proteolytic activity, LONP1 influences function of the mitochondrial genome and respiratory chain
  • importance of mitochondrial Lon (LONP1) in relation to oxidative stress and aging
  • may also contribute, albeit indirectly, to transcriptional regulation within the mitochondria
  • plays an important role in maintaining mitochondrial integrity during aging and aging-related diseases
  • LONP1, LONP2 are in high concentration and close proximity to proteins that are at risk of oxidative damage and have the need for rapid degradation
  • CELLULAR PROCESS protein, degradation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA binds a specific sequence in the light and heavy chain promoters of the mitochondrial genome which are involved in regulation of DNA replication and transcription
    RNA
    small molecule nucleotide,
  • ATP dependent
  • protein
  • binds G-quartets through rigid-body binding
  • binds specifically to a single-stranded GT-rich DNA sequence overlapping the light strand promoter of human mitochondrial DNA (mtDNA)
  • in cells with normal mtDNA levels, HMG1-phosphorylated TFAM is degraded by LONP1, but in cells with severe mtDNA deficits, nonphosphorylated TFAM is also degraded, as it is DNA free
  • LONP1 is a target of SIRT3, likely at K917
  • MT-CO2 is a LONP1 substrate
  • cell & other
  • associates with sites distributed primarily within one-half of the genome and preferentially with the control region for mtDNA replication and transcription
  • REGULATION
    Other mitochondrial ATP-dependent
    ASSOCIATED DISORDERS
    corresponding disease(s) CODAS
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    is a poor prognosis marker in human colorectal cancer and melanoma
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS