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P36776 · LONM_HUMAN

  • Protein
    Lon protease homolog, mitochondrial
  • Gene
    LONP1
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

ATP-dependent serine protease that mediates the selective degradation of misfolded, unassembled or oxidatively damaged polypeptides as well as certain short-lived regulatory proteins in the mitochondrial matrix (PubMed:12198491, PubMed:15870080, PubMed:17579211, PubMed:37327776, PubMed:8248235).
Endogenous substrates include mitochondrial steroidogenic acute regulatory (StAR) protein, DELE1, helicase Twinkle (TWNK) and the large ribosomal subunit protein MRPL32/bL32m (PubMed:17579211, PubMed:28377575, PubMed:37327776).
MRPL32/bL32m is protected from degradation by LONP1 when it is bound to a nucleic acid (RNA), but TWNK is not (PubMed:17579211, PubMed:28377575).
May also have a chaperone function in the assembly of inner membrane protein complexes (By similarity).
Participates in the regulation of mitochondrial gene expression and in the maintenance of the integrity of the mitochondrial genome (PubMed:17420247).
Binds to mitochondrial promoters and RNA in a single-stranded, site-specific, and strand-specific manner (PubMed:17420247).
May regulate mitochondrial DNA replication and/or gene expression using site-specific, single-stranded DNA binding to target the degradation of regulatory proteins binding to adjacent sites in mitochondrial promoters (PubMed:14739292, PubMed:17420247).

Catalytic activity

  • Hydrolysis of proteins in presence of ATP.
    EC:3.4.21.53 (UniProtKB | ENZYME | Rhea)

Activity regulation

Peptidase activity is subject to substrate inhibition by ATP.

Features

Showing features for binding site, active site.

Type
IDPosition(s)Description
Binding site523-530ATP (UniProtKB | ChEBI)
Active site855
Active site898

GO annotations

AspectTerm
Cellular Componentcytosol
Cellular Componentmembrane
Cellular Componentmitochondrial matrix
Cellular Componentmitochondrial nucleoid
Cellular Componentmitochondrion
Cellular Componentnucleoplasm
Molecular FunctionADP binding
Molecular FunctionATP binding
Molecular FunctionATP hydrolysis activity
Molecular FunctionATP-dependent peptidase activity
Molecular FunctionDNA polymerase binding
Molecular FunctionG-quadruplex DNA binding
Molecular Functionidentical protein binding
Molecular Functioninsulin receptor substrate binding
Molecular FunctionPH domain binding
Molecular Functionsequence-specific DNA binding
Molecular Functionserine-type endopeptidase activity
Molecular Functionsingle-stranded DNA binding
Molecular Functionsingle-stranded RNA binding
Biological Processcellular response to oxidative stress
Biological Processchaperone-mediated protein complex assembly
Biological Processmitochondrial DNA metabolic process
Biological Processmitochondrial genome maintenance
Biological Processmitochondrial protein catabolic process
Biological Processmitochondrion organization
Biological Processnegative regulation of insulin receptor signaling pathway
Biological Processoxidation-dependent protein catabolic process
Biological Processprotein catabolic process
Biological Processprotein quality control for misfolded or incompletely synthesized proteins
Biological Processproteolysis involved in protein catabolic process
Biological Processresponse to hypoxia

Keywords

Enzyme and pathway databases

Protein family/group databases

Names & Taxonomy

Protein names

  • Recommended name
    Lon protease homolog, mitochondrial
  • EC number
  • Alternative names
    • LONHs
    • Lon protease-like protein
      (LONP
      )
    • Mitochondrial ATP-dependent protease Lon
    • Serine protease 15

Gene names

    • Name
      LONP1
    • Synonyms
      PRSS15

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo

Accessions

  • Primary accession
    P36776
  • Secondary accessions
    • B3KPH8
    • D6W635
    • E5KMH8
    • F5GZ27
    • P36777

Proteomes

Organism-specific databases

Subcellular Location

Disease & Variants

Involvement in disease

CODAS syndrome (CODASS)

  • Note
    • The disease is caused by variants affecting the gene represented in this entry
  • Description
    A rare syndrome characterized by the combination of cerebral, ocular, dental, auricular, and skeletal features. These include developmental delay, craniofacial anomalies, cataracts, ptosis, median nasal groove, delayed tooth eruption, hearing loss, short stature, delayed epiphyseal ossification, metaphyseal hip dysplasia, and vertebral coronal clefts.
  • See also
    MIM:600373
Natural variants in CODASS
Variant IDPosition(s)ChangeDescription
VAR_073338476E>Ain CODASS
VAR_073339631S>Yin CODASS; dbSNP:rs879255248
VAR_073340670A>Vin CODASS; dbSNP:rs770036526
VAR_073341672R>Cin CODASS; dbSNP:rs777009012
VAR_073342676P>Sin CODASS; dbSNP:rs879255247
VAR_073343679R>Hin CODASS; dbSNP:rs549574673
VAR_073344721R>Gin CODASS; dbSNP:rs147588238
VAR_073345724A>Vin CODASS; dbSNP:rs879255249
VAR_073346749P>Sin CODASS; dbSNP:rs2145578983
VAR_073347767G>Ein CODASS; dbSNP:rs562553348
VAR_073348927missingin CODASS

Features

Showing features for natural variant, mutagenesis.

Type
IDPosition(s)Description
Natural variantVAR_05156487in dbSNP:rs34413649
Natural variantVAR_051565241in dbSNP:rs11085147
Natural variantVAR_073338476in CODASS
Mutagenesis529Abolishes ATPase activity, and presumably ATP-driven protein unfolding, but does not block access to the proteolytic active site or prevent a substrate from binding to it.
Natural variantVAR_073339631in CODASS; dbSNP:rs879255248
Natural variantVAR_073340670in CODASS; dbSNP:rs770036526
Natural variantVAR_073341672in CODASS; dbSNP:rs777009012
Natural variantVAR_073342676in CODASS; dbSNP:rs879255247
Natural variantVAR_073343679in CODASS; dbSNP:rs549574673
Natural variantVAR_073344721in CODASS; dbSNP:rs147588238
Natural variantVAR_073345724in CODASS; dbSNP:rs879255249
Natural variantVAR_073346749in CODASS; dbSNP:rs2145578983
Natural variantVAR_073347767in CODASS; dbSNP:rs562553348
Mutagenesis770Has low basal, but normal stimulated ATPase activity, and retains peptidase activity.
Mutagenesis770Has normal basal, but low stimulated ATPase activity, and abolishes peptidase activity.
Natural variantVAR_067708829in dbSNP:rs35804229
Mutagenesis855Lacks both ATPase and protease activity, but retains DNA binding activity.
Mutagenesis880Enhances the basal, but not the stimulated ATPase activity.
Mutagenesis893Has low basal, but normal stimulated ATPase activity, and retains peptidase activity.
Mutagenesis893Has normal basal, but low stimulated ATPase activity, and abolishes peptidase activity.
Mutagenesis894Enhances the basal, but not the stimulated ATPase activity, and retains peptidase activity.
Mutagenesis894Enhances the basal, but not the stimulated ATPase activity, and abolishes peptidase activity.
Natural variantVAR_067709911in dbSNP:rs1062373
Natural variantVAR_073348927in CODASS

Variants

We now provide the "Disease & Variants" viewer in its own tab.

The viewer provides 1,233 variants from UniProt as well as other sources including ClinVar and dbSNP.

Go to variant viewer

Keywords

Organism-specific databases

Miscellaneous

Chemistry

Genetic variation databases

PTM/Processing

Features

Showing features for transit peptide, chain, modified residue (large scale data).

Type
IDPosition(s)Source
Description
Transit peptide1-67UniProtMitochondrion
ChainPRO_000002673468-959UniProtLon protease homolog, mitochondrial
Modified residue (large scale data)176PRIDEPhosphoserine
Modified residue (large scale data)548PRIDEPhosphoserine

Proteomic databases

PTM databases

Expression

Tissue specificity

Duodenum, heart, lung and liver, but not thymus.

Gene expression databases

Organism-specific databases

Interaction

Subunit

Homohexamer (PubMed:14739292, PubMed:20222013, PubMed:25369343).
Organized in a ring with a central cavity (PubMed:20222013, PubMed:25369343).
The ATP-binding and proteolytic domains (AP-domain) form a hexameric chamber, while the N-terminal domain is arranged as a trimer of dimers (PubMed:27632940).
DNA and RNA binding is stimulated by substrate and inhibited by ATP binding. Interacts with TWNK and mitochondrial DNA polymerase subunit POLG (PubMed:14739292).

Binary interactions

Type
Entry 1
Entry 2Number of experimentsIntAct
XENO P36776CSN2 P026666EBI-357448, EBI-5260183
BINARY P36776-1LONP1 P36776-13EBI-25473602, EBI-25473602

Protein-protein interaction databases

Chemistry

Miscellaneous

Family & Domains

Features

Showing features for region, domain, compositional bias.

Type
IDPosition(s)Description
Region77-102Disordered
Domain124-370Lon N-terminal
Compositional bias218-233Basic and acidic residues
Region218-257Disordered
Compositional bias241-255Basic and acidic residues
Domain759-949Lon proteolytic

Domain

The Lon N-terminal domains are crucial for the overall structure of the protein, maintaining it in a conformation allowing its proper functioning.
The AP-domain (ATP-binding and proteolytic domains) has a closed-ring conformation in the presence of AMP-PNP and its N-terminal entry gate appears closed. Upon ADP binding, it switches to a lock-washer conformation and its N-terminal gate opens.
The proteolytic site is connected to the ATP binding site through the GG loop (Gly-893 and Gly-894) and the loop containing Trp-770. Binding of a protein substrate such as beta-casein appears to trigger movement of both these loops as part of the conformational changes which lead to enhanced ATPase and peptidase activities.

Sequence similarities

Belongs to the peptidase S16 family.

Keywords

Phylogenomic databases

Family and domain databases

Sequence & Isoforms

Align isoforms (3)
  • Sequence status
    Complete
  • Sequence processing
    The displayed sequence is further processed into a mature form.

This entry describes 3 isoforms produced by Alternative splicing.

P36776-1

This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

  • Length
    959
  • Mass (Da)
    106,489
  • Last updated
    2000-12-01 v2
  • MD5 Checksum
    23BBC933C5C6A85B52600D3C16957113
MAASTGYVRLWGAARCWVLRRPMLAAAGGRVPTAAGAWLLRGQRTCDASPPWALWGRGPAIGGQWRGFWEASSRGGGAFSGGEDASEGGAEEGAGGAGGSAGAGEGPVITALTPMTIPDVFPHLPLIAITRNPVFPRFIKIIEVKNKKLVELLRRKVRLAQPYVGVFLKRDDSNESDVVESLDEIYHTGTFAQIHEMQDLGDKLRMIVMGHRRVHISRQLEVEPEEPEAENKHKPRRKSKRGKKEAEDELSARHPAELAMEPTPELPAEVLMVEVENVVHEDFQVTEEVKALTAEIVKTIRDIIALNPLYRESVLQMMQAGQRVVDNPIYLSDMGAALTGAESHELQDVLEETNIPKRLYKALSLLKKEFELSKLQQRLGREVEEKIKQTHRKYLLQEQLKIIKKELGLEKDDKDAIEEKFRERLKELVVPKHVMDVVDEELSKLGLLDNHSSEFNVTRNYLDWLTSIPWGKYSNENLDLARAQAVLEEDHYGMEDVKKRILEFIAVSQLRGSTQGKILCFYGPPGVGKTSIARSIARALNREYFRFSVGGMTDVAEIKGHRRTYVGAMPGKIIQCLKKTKTENPLILIDEVDKIGRGYQGDPSSALLELLDPEQNANFLDHYLDVPVDLSKVLFICTANVTDTIPEPLRDRMEMINVSGYVAQEKLAIAERYLVPQARALCGLDESKAKLSSDVLTLLIKQYCRESGVRNLQKQVEKVLRKSAYKIVSGEAESVEVTPENLQDFVGKPVFTVERMYDVTPPGVVMGLAWTAMGGSTLFVETSLRRPQDKDAKGDKDGSLEVTGQLGEVMKESARIAYTFARAFLMQHAPANDYLVTSHIHLHVPEGATPKDGPSAGCTIVTALLSLAMGRPVRQNLAMTGEVSLTGKILPVGGIKEKTIAAKRAGVTCIVLPAENKKDFYDLAAFITEGLEVHFVEHYREIFDIAFPDEQAEALAVER

P36776-2

  • Name
    2
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical

P36776-3

  • Name
    3
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical

Computationally mapped potential isoform sequences

There are 7 potential isoforms mapped to this entry

View all
EntryEntry nameGene nameLength
K7EJE8K7EJE8_HUMANLONP1829
K7EKE6K7EKE6_HUMANLONP1845
K7ER56K7ER56_HUMANLONP1210
K7ER27K7ER27_HUMANLONP1242
K7EQF8K7EQF8_HUMANLONP1185
K7ERR6K7ERR6_HUMANLONP1264
K7ERS1K7ERS1_HUMANLONP186

Sequence caution

The sequence CAA52291.1 differs from that shown. Reason: Erroneous initiation Truncated N-terminus.

Features

Showing features for sequence conflict, alternative sequence, compositional bias.

Type
IDPosition(s)Description
Sequence conflict1-55in Ref. 1; AAA61616
Alternative sequenceVSP_0553101-196in isoform 3
Alternative sequenceVSP_05461742-105in isoform 2
Sequence conflict65-66in Ref. 1; AAA61616
Compositional bias218-233Basic and acidic residues
Compositional bias241-255Basic and acidic residues
Sequence conflict257-258in Ref. 1; AAA61616
Sequence conflict423in Ref. 4; BAG51690
Sequence conflict456in Ref. 1; AAA61616
Sequence conflict501in Ref. 4; BAG51690
Sequence conflict556in Ref. 1; AAA61616
Sequence conflict842in Ref. 1; AAA61616
Sequence conflict859in Ref. 1; AAA61616

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
U02389
EMBL· GenBank· DDBJ
AAA61616.1
EMBL· GenBank· DDBJ
mRNA
HQ204946
EMBL· GenBank· DDBJ
ADP90374.1
EMBL· GenBank· DDBJ
Genomic DNA
HQ204947
EMBL· GenBank· DDBJ
ADP90375.1
EMBL· GenBank· DDBJ
Genomic DNA
HQ204948
EMBL· GenBank· DDBJ
ADP90376.1
EMBL· GenBank· DDBJ
Genomic DNA
HQ204949
EMBL· GenBank· DDBJ
ADP90377.1
EMBL· GenBank· DDBJ
Genomic DNA
HQ204950
EMBL· GenBank· DDBJ
ADP90378.1
EMBL· GenBank· DDBJ
Genomic DNA
HQ204951
EMBL· GenBank· DDBJ
ADP90379.1
EMBL· GenBank· DDBJ
Genomic DNA
HQ204952
EMBL· GenBank· DDBJ
ADP90380.1
EMBL· GenBank· DDBJ
Genomic DNA
HQ204953
EMBL· GenBank· DDBJ
ADP90381.1
EMBL· GenBank· DDBJ
Genomic DNA
HQ204954
EMBL· GenBank· DDBJ
ADP90382.1
EMBL· GenBank· DDBJ
Genomic DNA
HQ204955
EMBL· GenBank· DDBJ
ADP90383.1
EMBL· GenBank· DDBJ
Genomic DNA
HQ204956
EMBL· GenBank· DDBJ
ADP90384.1
EMBL· GenBank· DDBJ
Genomic DNA
HQ204957
EMBL· GenBank· DDBJ
ADP90385.1
EMBL· GenBank· DDBJ
Genomic DNA
HQ204958
EMBL· GenBank· DDBJ
ADP90386.1
EMBL· GenBank· DDBJ
Genomic DNA
HQ204959
EMBL· GenBank· DDBJ
ADP90387.1
EMBL· GenBank· DDBJ
Genomic DNA
HQ204960
EMBL· GenBank· DDBJ
ADP90388.1
EMBL· GenBank· DDBJ
Genomic DNA
HQ204961
EMBL· GenBank· DDBJ
ADP90389.1
EMBL· GenBank· DDBJ
Genomic DNA
HQ204962
EMBL· GenBank· DDBJ
ADP90390.1
EMBL· GenBank· DDBJ
Genomic DNA
HQ204963
EMBL· GenBank· DDBJ
ADP90391.1
EMBL· GenBank· DDBJ
Genomic DNA
HQ204964
EMBL· GenBank· DDBJ
ADP90392.1
EMBL· GenBank· DDBJ
Genomic DNA
HQ204965
EMBL· GenBank· DDBJ
ADP90393.1
EMBL· GenBank· DDBJ
Genomic DNA
HQ204966
EMBL· GenBank· DDBJ
ADP90394.1
EMBL· GenBank· DDBJ
Genomic DNA
HQ204968
EMBL· GenBank· DDBJ
ADP90396.1
EMBL· GenBank· DDBJ
Genomic DNA
HQ204969
EMBL· GenBank· DDBJ
ADP90397.1
EMBL· GenBank· DDBJ
Genomic DNA
HQ204970
EMBL· GenBank· DDBJ
ADP90398.1
EMBL· GenBank· DDBJ
Genomic DNA
HQ204971
EMBL· GenBank· DDBJ
ADP90399.1
EMBL· GenBank· DDBJ
Genomic DNA
HQ204972
EMBL· GenBank· DDBJ
ADP90400.1
EMBL· GenBank· DDBJ
Genomic DNA
HQ204973
EMBL· GenBank· DDBJ
ADP90401.1
EMBL· GenBank· DDBJ
Genomic DNA
HQ204974
EMBL· GenBank· DDBJ
ADP90402.1
EMBL· GenBank· DDBJ
Genomic DNA
HQ204975
EMBL· GenBank· DDBJ
ADP90403.1
EMBL· GenBank· DDBJ
Genomic DNA
HQ204976
EMBL· GenBank· DDBJ
ADP90404.1
EMBL· GenBank· DDBJ
Genomic DNA
HQ204977
EMBL· GenBank· DDBJ
ADP90405.1
EMBL· GenBank· DDBJ
Genomic DNA
HQ204978
EMBL· GenBank· DDBJ
ADP90406.1
EMBL· GenBank· DDBJ
Genomic DNA
HQ204979
EMBL· GenBank· DDBJ
ADP90407.1
EMBL· GenBank· DDBJ
Genomic DNA
HQ204980
EMBL· GenBank· DDBJ
ADP90408.1
EMBL· GenBank· DDBJ
Genomic DNA
HQ204981
EMBL· GenBank· DDBJ
ADP90409.1
EMBL· GenBank· DDBJ
Genomic DNA
HQ204982
EMBL· GenBank· DDBJ
ADP90410.1
EMBL· GenBank· DDBJ
Genomic DNA
HQ204983
EMBL· GenBank· DDBJ
ADP90411.1
EMBL· GenBank· DDBJ
Genomic DNA
HQ204984
EMBL· GenBank· DDBJ
ADP90412.1
EMBL· GenBank· DDBJ
Genomic DNA
HQ204985
EMBL· GenBank· DDBJ
ADP90413.1
EMBL· GenBank· DDBJ
Genomic DNA
AF059309
EMBL· GenBank· DDBJ
AAD24414.1
EMBL· GenBank· DDBJ
Genomic DNA
AF059296
EMBL· GenBank· DDBJ
AAD24414.1
EMBL· GenBank· DDBJ
Genomic DNA
AF059297
EMBL· GenBank· DDBJ
AAD24414.1
EMBL· GenBank· DDBJ
Genomic DNA
AF059298
EMBL· GenBank· DDBJ
AAD24414.1
EMBL· GenBank· DDBJ
Genomic DNA
AF059299
EMBL· GenBank· DDBJ
AAD24414.1
EMBL· GenBank· DDBJ
Genomic DNA
AF059300
EMBL· GenBank· DDBJ
AAD24414.1
EMBL· GenBank· DDBJ
Genomic DNA
AF059301
EMBL· GenBank· DDBJ
AAD24414.1
EMBL· GenBank· DDBJ
Genomic DNA
AF059302
EMBL· GenBank· DDBJ
AAD24414.1
EMBL· GenBank· DDBJ
Genomic DNA
AF059303
EMBL· GenBank· DDBJ
AAD24414.1
EMBL· GenBank· DDBJ
Genomic DNA
AF059304
EMBL· GenBank· DDBJ
AAD24414.1
EMBL· GenBank· DDBJ
Genomic DNA
AF059305
EMBL· GenBank· DDBJ
AAD24414.1
EMBL· GenBank· DDBJ
Genomic DNA
AF059306
EMBL· GenBank· DDBJ
AAD24414.1
EMBL· GenBank· DDBJ
Genomic DNA
AF059307
EMBL· GenBank· DDBJ
AAD24414.1
EMBL· GenBank· DDBJ
Genomic DNA
AF059308
EMBL· GenBank· DDBJ
AAD24414.1
EMBL· GenBank· DDBJ
Genomic DNA
AK056366
EMBL· GenBank· DDBJ
BAG51690.1
EMBL· GenBank· DDBJ
mRNA
AK096626
EMBL· GenBank· DDBJ
BAC04829.1
EMBL· GenBank· DDBJ
mRNA
AC011499
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
CH471139
EMBL· GenBank· DDBJ
EAW69151.1
EMBL· GenBank· DDBJ
Genomic DNA
CH471139
EMBL· GenBank· DDBJ
EAW69154.1
EMBL· GenBank· DDBJ
Genomic DNA
BC000235
EMBL· GenBank· DDBJ
AAH00235.1
EMBL· GenBank· DDBJ
mRNA
X74215
EMBL· GenBank· DDBJ
CAA52291.1
EMBL· GenBank· DDBJ
mRNA Different initiation
X76040
EMBL· GenBank· DDBJ
CAA53625.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. Our staff consists of biologists and biochemists that are not trained to give medical advice.
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