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FLASH GENE

Symbol

LONP1

contributors: mct - updated : 26-01-2017

HGNC name	lon peptidase 1, mitochondrial
HGNC id	9479

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

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

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_004793 18 - 3111 106 959 - 2017 26852705

EXPRESSION

Type	ubiquitous

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive intestine small intestine duodenum       liver           salivary gland       highly Endocrine adrenal gland       highly   thyroid       highly Respiratory lung         Skin/Tegument skin       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
	is a nuclear-encoded mitochondrial protease

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)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   is a poor prognosis marker in human colorectal cancer and melanoma

Susceptibility

to Congenital diaphragmatic hernia (CDH)

Variant & Polymorphism other	CDH probands with LONP1 variants had higher mortality in the neonatal period compared with other children with CDH

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

inactivation of Lonp1 in mouse embryonic lung epithelium leads to disrupted lung development and full lethality at birth