Protein: P36776

UniprotKB AC UniprotKB ID Gene name Full name Species Curated set
P36776 (Uniprot) LONM_HUMAN LONP1 Lon protease homolog, mitochondrial human Yes
Uniprot: 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. May also have a chaperone function in the assembly of inner membrane protein complexes. Participates in the regulation of mitochondrial gene expression and in the maintenance of the integrity of the mitochondrial genome. Binds to mitochondrial promoters and RNA in a single-stranded, site-specific, and strand-specific manner. 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:12198491, PubMed:15870080, PubMed:17420247, PubMed:8248235). Endogenous substrates include mitochondrial steroidogenic acute regulatory (StAR) protein, helicase Twinkle (TWNK) and the large ribosomal subunit protein bL32m. bL32m is protected from degradation by LONP1 when it is bound to a nucleic acid (RNA), but TWNK is not (PubMed:17579211, PubMed:28377575). more..
Dissimilar Functions Manual Curation

Function 1: Mitochondrial protease (ATP-dependant mitochondrial protease).

Function 2: Chaperone function in the assembly of inner membrane protein complexes. Participates in the regulation of mitochondrial gene expression and in the maintenance of the integrity of the mitochondrial genome. Binds to mitochondrial promoters and RNA in a single-stranded, site-specific, and strand-specific manner.

Publications (PMID): 9149530, 17420247

Biological Processes
Module ID (MoonGO) GO ID (BP) GO Name
129 GO:0044267 cellular protein metabolic process
129 GO:0007165 signal transduction
Cellular Components
Module ID (MoonGO) GO ID (CC) GO Name
129 GO:0005829 cytosol
129 GO:0070013 intracellular organelle lumen
293 GO:0005634 nucleus
600 GO:0005634 nucleus
717 GO:0005829 cytosol
717 GO:0043232 intracellular non-membrane-bounded organelle
717 GO:0005634 nucleus
GO ID (BP) GO Name Evidence Code (GO EC)
GO:0000002 mitochondrial genome maintenance NAS
GO:0001666 response to hypoxia IEP
GO:0006515 protein quality control for misfolded or incompletely synthesized proteins IBA
GO:0007005 mitochondrion organization IMP
GO:0007568 aging IEA
GO:0009725 response to hormone IEA
GO:0010044 response to aluminum ion IEA
GO:0032042 mitochondrial DNA metabolic process NAS
GO:0034599 cellular response to oxidative stress IDA
GO:0043623 cellular protein complex assembly IEA
GO:0051260 protein homooligomerization IDA
GO:0051603 proteolysis involved in cellular protein catabolic process IDA
GO:0070407 oxidation-dependent protein catabolic process IMP
GO ID (CC) GO Name Evidence Code (GO EC)
GO:0005634 nucleus IDA
GO:0005654 nucleoplasm IDA
GO:0005739 mitochondrion IDA
GO:0005759 mitochondrial matrix IMP
GO:0005829 cytosol IDA
GO:0016020 membrane IDA
GO:0042645 mitochondrial nucleoid IDA
GO ID 1 Component 1 GO ID 2 Component 2 Association Probability (PrOnto) Interaction Probability (PrOnto)
GO:0005634 nucleus GO:0016020 membrane 0.00e+00 4.39e-236
GO:0005654 nucleoplasm GO:0016020 membrane 5.76e-255 1.32e-206
PMID Article Title
7961901 Synthesis, processing, and localization of human Lon protease.
8119403 Cloning and sequence analysis of cDNA for a human homolog of eubacterial ATP-dependent Lon proteases.
8248235 A human mitochondrial ATP-dependent protease that is highly homologous to bacterial Lon protease.
9485316 The human LON protease binds to mitochondrial promoters in a single-stranded, site-specific, strand-specific manner.
12198491 Lon protease preferentially degrades oxidized mitochondrial aconitase by an ATP-stimulated mechanism.
14702039 Complete sequencing and characterization of 21,243 full-length human cDNAs.
14739292 DNA and RNA binding by the mitochondrial lon protease is regulated by nucleotide and protein substrate.
15057824 The DNA sequence and biology of human chromosome 19.
15489334 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15870080 Cleavage site selection within a folded substrate by the ATP-dependent lon protease.
17420247 Roles for the human ATP-dependent Lon protease in mitochondrial DNA maintenance.
17579211 Turnover of mitochondrial steroidogenic acute regulatory (StAR) protein by Lon protease: the unexpected effect of proteasome inhibitors.
20222013 Structure of the catalytic domain of the human mitochondrial Lon protease: proposed relation of oligomer formation and activity.
20843780 Identification of rare DNA variants in mitochondrial disorders with improved array-based sequencing.
21269460 Initial characterization of the human central proteome.
23186163 Toward a comprehensive characterization of a human cancer cell phosphoproteome.
24275569 An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.
24520911 Mutations to a glycine loop in the catalytic site of human Lon changes its protease, peptidase and ATPase activities.
25369343 Three-dimensional reconstruction of the S885A mutant of human mitochondrial Lon protease.
25574826 CODAS syndrome is associated with mutations of LONP1, encoding mitochondrial AAA+ Lon protease.
25808063 Mutations in LONP1, a mitochondrial matrix protease, cause CODAS syndrome.
25944712 N-terminome analysis of the human mitochondrial proteome.
27632940 The N-terminal domain plays a crucial role in the structure of a full-length human mitochondrial Lon protease.
28377575 The role of Lon-mediated proteolysis in the dynamics of mitochondrial nucleic acid-protein complexes.
OMIM ID Disease Name
600373 CODAS syndrome
Domain Name Domain ID Source
Lon_substr-bd IPR003111 InterPro
AAA+_ATPase IPR003593 InterPro
ATPase_AAA_core IPR003959 InterPro
Lon_bac/euk-typ IPR004815 InterPro
Peptidase_S16_AS IPR008268 InterPro
Lon_proteolytic IPR008269 InterPro
Ribosomal_S5_D2-typ_fold_subgr IPR014721 InterPro
PUA-like_sf IPR015947 InterPro
Ribosomal_S5_D2-typ_fold IPR020568 InterPro
Lon_Prtase IPR027065 InterPro
P-loop_NTPase IPR027417 InterPro
Lonm_euk IPR027503 InterPro
lonm_euk MF_03120 HAMAP
AAA PF00004 Pfam
LON_substr_bdg PF02190 Pfam
Lon_C PF05362 Pfam
LON_SER PS01046 PROSITE
LON_PROTEOLYTIC PS51786 PROSITE
LON_N PS51787 PROSITE
PTHR43718 PTHR43718 PANTHER
S42366 S42366 PIR
S57342 S57342 PIR
AAA SM00382 SMART
LON SM00464 SMART
SSF52540 SSF52540 SUPFAM
SSF54211 SSF54211 SUPFAM
SSF88697 SSF88697 SUPFAM
lon TIGR00763 TIGRFAMs