LONP1

Protein identityUniProt · HPA

UniProt accession

P36776

Gene

LONP1

Ensembl

ENSG00000196365

Chromosome

19

Canonical length

959 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Potential drug targets, Predicted intracellular proteins

Subcellular location

Nucleoplasm,Mitochondria

Quaternary structure

Homohexamer

OverviewNCBI Gene

This gene encodes a mitochondrial matrix protein that belongs to the Lon family of ATP-dependent proteases. This protein mediates the selective degradation of misfolded, unassembled or oxidatively damaged polypeptides in the mitochondrial matrix. It may also have a chaperone function in the assembly of inner membrane protein complexes, and participate in the regulation of mitochondrial gene expression and maintenance of the integrity of the mitochondrial genome. Decreased expression of this gene has been noted in a patient with hereditary spastic paraplegia (PMID:18378094). Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Feb 2013]

Canonical amino-acid sequenceUniProt

959 residues, UniProt reviewed canonical sequence.

>P36776|LONP1
     1  MAASTGYVRL WGAARCWVLR RPMLAAAGGR VPTAAGAWLL RGQRTCDASP PWALWGRGPA
    61  IGGQWRGFWE ASSRGGGAFS GGEDASEGGA EEGAGGAGGS AGAGEGPVIT ALTPMTIPDV
   121  FPHLPLIAIT RNPVFPRFIK IIEVKNKKLV ELLRRKVRLA QPYVGVFLKR DDSNESDVVE
   181  SLDEIYHTGT FAQIHEMQDL GDKLRMIVMG HRRVHISRQL EVEPEEPEAE NKHKPRRKSK
   241  RGKKEAEDEL SARHPAELAM EPTPELPAEV LMVEVENVVH EDFQVTEEVK ALTAEIVKTI
   301  RDIIALNPLY RESVLQMMQA GQRVVDNPIY LSDMGAALTG AESHELQDVL EETNIPKRLY
   361  KALSLLKKEF ELSKLQQRLG REVEEKIKQT HRKYLLQEQL KIIKKELGLE KDDKDAIEEK
   421  FRERLKELVV PKHVMDVVDE ELSKLGLLDN HSSEFNVTRN YLDWLTSIPW GKYSNENLDL
   481  ARAQAVLEED HYGMEDVKKR ILEFIAVSQL RGSTQGKILC FYGPPGVGKT SIARSIARAL
   541  NREYFRFSVG GMTDVAEIKG HRRTYVGAMP GKIIQCLKKT KTENPLILID EVDKIGRGYQ
   601  GDPSSALLEL LDPEQNANFL DHYLDVPVDL SKVLFICTAN VTDTIPEPLR DRMEMINVSG
   661  YVAQEKLAIA ERYLVPQARA LCGLDESKAK LSSDVLTLLI KQYCRESGVR NLQKQVEKVL
   721  RKSAYKIVSG EAESVEVTPE NLQDFVGKPV FTVERMYDVT PPGVVMGLAW TAMGGSTLFV
   781  ETSLRRPQDK DAKGDKDGSL EVTGQLGEVM KESARIAYTF ARAFLMQHAP ANDYLVTSHI
   841  HLHVPEGATP KDGPSAGCTI VTALLSLAMG RPVRQNLAMT GEVSLTGKIL PVGGIKEKTI
   901  AAKRAGVTCI VLPAENKKDF YDLAAFITEG LEVHFVEHYR EIFDIAFPDE QAEALAVER

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against LONP1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.35

Highest tissue expression

190 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about LONP1.

Disease | AllUniProt

Conditions LONP1 is implicated in, by any mechanism.

• CODAS syndrome (CODASS) MIM:600373

Disease | GeneticClinVar

25 pathogenic / likely-pathogenic of 1,169 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• CODAS syndrome
• LONP1-related disorder
• Epilepsy of infancy with migrating focal seizures
• See cases
• Inborn genetic diseases

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.24

gnomAD pLI

1

gnomAD missense Z

0.43

DepMap mean gene effect

-1.38

DepMap dependency class

common

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cellular response to oxidative stress
• chaperone-mediated protein complex assembly
• mitochondrial protein catabolic process
• mitochondrion organization
• negative regulation of insulin receptor signaling pathway
• protein quality control for misfolded or incompletely synthesized proteins
• proteolysis involved in protein catabolic process
• response to aluminum ion
• response to hormone
• response to hypoxia
• oxidation-dependent protein catabolic process

Molecular functions

• ADP binding
• ATP binding
• ATP hydrolysis activity
• ATP-dependent peptidase activity
• DNA polymerase binding
• G-quadruplex DNA binding
• identical protein binding
• insulin receptor substrate binding
• PH domain binding
• sequence-specific DNA binding
• serine-type endopeptidase activity
• single-stranded DNA binding
• single-stranded RNA binding

Cellular components

• cytosol
• membrane
• mitochondrial matrix
• mitochondrial nucleoid
• mitochondrion
• nucleoplasm

Protein domainsUniProt · Pfam · InterPro

• Lon protease, N-terminal domain
• AAA+ ATPase domain
• ATPase, AAA-type, core
• Lon protease, bacterial/eukaryotic-type
• Peptidase S16, active site
• Peptidase S16, Lon proteolytic domain
• Small ribosomal subunit protein uS5 domain 2-type fold, subgroup
• PUA-like superfamily
• Ribosomal protein uS5 domain 2-type superfamily
• Lon protease
• P-loop containing nucleoside triphosphate hydrolase
• Lon protease, N-terminal domain superfamily
• Lon protease, AAA+ ATPase lid domain
• ATPase family associated with various cellular activities (AAA)
• ATP-dependent protease La (LON) substrate-binding domain
• Lon protease (S16) C-terminal proteolytic domain
• Lon protease AAA+ ATPase lid domain
• Lon protease homologue, chloroplastic/mitochondrial

KeywordsUniProt

• ATP-binding
• Cataract
• Deafness
• DNA-binding
• Dwarfism
• Hydrolase
• Mitochondrion
• Nucleotide-binding
• Protease
• Serine protease
• Transit peptide

InteractionsUniProt · HPA

Protein binding partners of LONP1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• TWNK
• AURKAIP1
• ECHS1
• MRPS2
• MRPS24
• MRPS26
• NDUFS7