LONP1
entrez
9361
canonical
uniprot
P36776
canonical
ensembl
ENSG00000196365
resolver
ensp
ENSP00000353826
resolver
ensp
ENSP00000441523
resolver
ensp
ENSP00000468541
resolver
ensp
ENSP00000654687
resolver
genesymbol
LONP1
resolver
genesymbol_syn
Lon
resolver
genesymbol_syn
PRSS15
resolver
hgnc
HGNC:9479
resolver
uniprot
B3KPH8
resolver
uniprot
D6W635
resolver
uniprot
E5KMH8
resolver
uniprot
F5GZ27
resolver
uniprot
P36777
resolver
uniprot
Q8N8K8
resolver
uniprot
Q9UQ95
resolver
uniprot_entry
LONM_HUMAN
resolver
uniprot_sec
B3KPH8
resolver
uniprot_sec
D6W635
resolver
uniprot_sec
E5KMH8
resolver
uniprot_sec
F5GZ27
resolver
uniprot_sec
P36777
resolver
uniprot_sec
Q8N8K8
resolver
uniprot_sec
Q9UQ95
resolver
activity_regulation
ACTIVITY REGULATION: Peptidase activity is subject to substrate inhibition by ATP (PubMed:24520911). Inorganic polyphosphate (polyP) acts as a potent inhibitor (PubMed:38688959). {ECO:0000269|PubMed:24520911, ECO:0000269|PubMed:38688959}.
uniprot
proteins
amino_acid_sequence
MAASTGYVRLWGAARCWVLRRPMLAAAGGRVPTAAGAWLLRGQRTCDASPPWALWGRGPAIGGQWRGFWEASSRGGGAFSGGEDASEGGAEEGAGGAGGSAGAGEGPVITALTPMTIPDVFPHLPLIAITRNPVFPRFIKIIEVKNKKLVELLRRKVRLAQPYVGVFLKRDDSNESDVVESLDEIYHTGTFAQIHEMQDLGDKLRMIVMGHRRVHISRQLEVEPEEPEAENKHKPRRKSKRGKKEAEDELSARHPAELAMEPTPELPAEVLMVEVENVVHEDFQVTEEVKALTAEIVKTIRDIIALNPLYRESVLQMMQAGQRVVDNPIYLSDMGAALTGAESHELQDVLEETNIPKRLYKALSLLKKEFELSKLQQRLGREVEEKIKQTHRKYLLQEQLKIIKKELGLEKDDKDAIEEKFRERLKELVVPKHVMDVVDEELSKLGLLDNHSSEFNVTRNYLDWLTSIPWGKYSNENLDLARAQAVLEEDHYGMEDVKKRILEFIAVSQLRGSTQGKILCFYGPPGVGKTSIARSIARALNREYFRFSVGGMTDVAEIKGHRRTYVGAMPGKIIQCLKKTKTENPLILIDEVDKIGRGYQGDPSSALLELLDPEQNANFLDHYLDVPVDLSKVLFICTANVTDTIPEPLRDRMEMINVSGYVAQEKLAIAERYLVPQARALCGLDESKAKLSSDVLTLLIKQYCRESGVRNLQKQVEKVLRKSAYKIVSGEAESVEVTPENLQDFVGKPVFTVERMYDVTPPGVVMGLAWTAMGGSTLFVETSLRRPQDKDAKGDKDGSLEVTGQLGEVMKESARIAYTFARAFLMQHAPANDYLVTSHIHLHVPEGATPKDGPSAGCTIVTALLSLAMGRPVRQNLAMTGEVSLTGKILPVGGIKEKTIAAKRAGVTCIVLPAENKKDFYDLAAFITEGLEVHFVEHYREIFDIAFPDEQAEALAVER
uniprot
proteins
disease_involvement
DISEASE: CODAS syndrome (CODASS) [MIM:600373]: 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. {ECO:0000269|PubMed:25574826, ECO:0000269|PubMed:25808063, ECO:0000269|PubMed:33431889}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
3.4.21.53
uniprot
proteins
ec_number
3.6.4.10
uniprot
proteins
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, PubMed:35870450, PubMed:38688959). 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). In addtion to its protease activity, has also an ATP-dependent protein folding chaperone activity and functions in mitochondrial protein folding (PubMed:33431889). 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). {ECO:0000255|HAMAP-Rule:MF_03120, ECO:0000269|PubMed:12198491, ECO:0000269|PubMed:14739292, ECO:0000269|PubMed:15870080, ECO:0000269|PubMed:17420247, ECO:0000269|PubMed:17579211, ECO:0000269|PubMed:28377575, ECO:0000269|PubMed:33431889, ECO:0000269|PubMed:37327776, ECO:0000269|PubMed:8248235}.
uniprot
proteins
mass_dalton
106489
uniprot
proteins
mutagenesis
MUTAGEN 186; /note="Y->E: Decreased protease activity. Decreased ATPase activity."; /evidence="ECO:0000269|PubMed:38688959"; MUTAGEN 394; /note="Y->E: Decreased protease activity. Decreased ATPase activity."; /evidence="ECO:0000269|PubMed:38688959"; MUTAGEN 520; /note="C->S: No effect on protease activity. No effect on ATPase activity. Decrease protease activity and ATPase activity; when associated with S-637."; /evidence="ECO:0000269|PubMed:35870450"; MUTAGEN 529; /note="K->R: Loss of ATP-dependent protein folding chaperone activity. Dominant negative that induces protein aggregation in the mitochondria. Does not block access to the proteolytic active site or prevent a substrate from binding to it. Loss of ATPase activity."; /evidence="ECO:0000269|PubMed:24520911, ECO:0000269|PubMed:33431889, ECO:0000269|PubMed:35870450"; MUTAGEN 591; /note="E->Q: Loss of protease activity. Loss of ATPase activity."; /evidence="ECO:0000269|PubMed:35870450"; MUTAGEN 637; /note="C->S: Decreased protease activity and ATPase activity; when associated with S-520."; /evidence="ECO:0000269|PubMed:35870450"; MUTAGEN 770; /note="W->A: Has low basal, but normal stimulated ATPase activity, and retains peptidase activity."; /evidence="ECO:0000269|PubMed:24520911"; MUTAGEN 770; /note="W->P: Has normal basal, but low stimulated ATPase activity, and abolishes peptidase activity."; /evidence="ECO:0000269|PubMed:24520911"; MUTAGEN 801; /note="E->A: Loss of protease activity. Decreased ATPase activity."; /evidence="ECO:0000269|PubMed:35870450"; MUTAGEN 803; /note="T->V: Loss of protease activity. Decreased ATPase activity."; /evidence="ECO:0000269|PubMed:35870450"; MUTAGEN 812; /note="E->A: Loss of protease activity. Decreased ATPase activity."; /evidence="ECO:0000269|PubMed:35870450"; MUTAGEN 841; /note="H->F: Loss of protease activity. Decreased ATPase activity."; /evidence="ECO:0000269|PubMed:35870450"; MUTAGEN 843; /note="H->F: Loss of protease activity. Decreased ATPase activity."; /evidence="ECO:0000269|PubMed:35870450"; MUTAGEN 855; /note="S->A: Loss of protease activity. No effect on DNA binding activity. Decreased chaperone activity. Decreased ATPase activity."; /evidence="ECO:0000269|PubMed:14739292, ECO:0000269|PubMed:24520911, ECO:0000269|PubMed:33431889, ECO:0000269|PubMed:35870450"; MUTAGEN 880; /note="T->V: Enhances the basal, but not the stimulated ATPase activity."; /evidence="ECO:0000269|PubMed:24520911"; MUTAGEN 893; /note="G->A: Has low basal, but normal stimulated ATPase activity, and retains peptidase activity."; /evidence="ECO:0000269|PubMed:24520911"; MUTAGEN 893; /note="G->P: Has normal basal, but low stimulated ATPase activity, and abolishes peptidase activity."; /evidence="ECO:0000269|PubMed:24520911"; MUTAGEN 894; /note="G->A,S: Enhances the basal, but not the stimulated ATPase activity, and retains peptidase activity."; /evidence="ECO:0000269|PubMed:24520911"; MUTAGEN 894; /note="G->P: Enhances the basal, but not the stimulated ATPase activity, and abolishes peptidase activity."; /evidence="ECO:0000269|PubMed:24520911
uniprot
proteins
post_translational_modification
PTM: Phosphorylated. Phosphorylation at Tyr-186 and Tyr-394 inhibits the ATP-dependent protease activity. {ECO:0000269|PubMed:38688959}.
uniprot
proteins
protein_family
Peptidase S16 family
uniprot
proteins
pubmed
12198491
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
14739292
uniprot
proteins
pubmed
15057824
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15870080
uniprot
proteins
pubmed
17420247
uniprot
proteins
pubmed
17579211
uniprot
proteins
pubmed
20222013
uniprot
proteins
pubmed
20843780
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
24520911
uniprot
proteins
pubmed
25369343
uniprot
proteins
pubmed
25574826
uniprot
proteins
pubmed
25808063
uniprot
proteins
pubmed
25944712
uniprot
proteins
pubmed
27632940
uniprot
proteins
pubmed
28377575
uniprot
proteins
pubmed
33431889
uniprot
proteins
pubmed
35870450
uniprot
proteins
pubmed
37327776
uniprot
proteins
pubmed
38688959
uniprot
proteins
pubmed
7961901
uniprot
proteins
pubmed
8119403
uniprot
proteins
pubmed
8248235
uniprot
proteins
pubmed
9485316
uniprot
proteins
sequence_length
959
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Mitochondrion matrix {ECO:0000255|HAMAP-Rule:MF_03120, ECO:0000269|PubMed:7961901}.
uniprot
proteins