P36776 (LONM_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Lon protease homolog, mitochondrial
EC=3.4.21.-

Alternative name(s):
LONHs
Lon protease-like protein
Short name=LONP
Mitochondrial ATP-dependent protease Lon
Serine protease 15

Gene names

Name:	LONP1
Synonyms:	PRSS15

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	959 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

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. 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. Endogenous substrates include mitochondrial steroidogenic acute regulatory (StAR) protein. Ref.1 Ref.9 Ref.11 Ref.12
Subunit structure	Homohexamer or homoheptamer. Organized in a ring with a central cavity. DNA and RNA binding is stimulated by substrate and inhibited by ATP binding. Interacts with PEO1 and mitochondrial DNA polymerase subunit POLG. Ref.10 Ref.15
Subcellular location	Mitochondrion matrix Ref.7.
Tissue specificity	Duodenum, heart, lung and liver, but not thymus.
Sequence similarities	Belongs to the peptidase S16 family. Contains 1 Lon domain.
Sequence caution	The sequence CAA52291.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Cellular component	Mitochondrion
Coding sequence diversity	Polymorphism
Domain	Transit peptide
Ligand	ATP-binding DNA-binding Nucleotide-binding
Molecular function	Hydrolase Protease Serine protease
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	aging Inferred from electronic annotation. Source: Compara cellular protein complex assembly Inferred from electronic annotation. Source: Compara cellular response to oxidative stress Inferred from direct assay Ref.12. Source: UniProtKB misfolded or incompletely synthesized protein catabolic process Inferred from Biological aspect of Ancestor. Source: RefGenome mitochondrial DNA metabolic process Non-traceable author statement Ref.10. Source: UniProtKB oxidation-dependent protein catabolic process Inferred from mutant phenotype Ref.9. Source: UniProtKB protein homooligomerization Inferred from direct assay Ref.10. Source: UniProtKB response to aluminum ion Inferred from electronic annotation. Source: Compara response to hormone stimulus Inferred from electronic annotation. Source: Compara response to hypoxia Inferred from expression pattern PubMed 17418790. Source: UniProtKB
Cellular_component	mitochondrial nucleoid Inferred from direct assay PubMed 18063578. Source: BHF-UCL
Molecular_function	ADP binding Inferred from direct assay Ref.10. Source: UniProtKB ATP binding Inferred from direct assay Ref.10. Source: UniProtKB ATP-dependent peptidase activity Inferred from direct assay Ref.12Ref.1. Source: UniProtKB G-quadruplex DNA binding Inferred from direct assay PubMed 18174225. Source: UniProtKB mitochondrial heavy strand promoter anti-sense binding Inferred from direct assay Ref.8. Source: UniProtKB mitochondrial light strand promoter anti-sense binding Inferred from direct assay Ref.8. Source: UniProtKB sequence-specific DNA binding Inferred from direct assay Ref.10. Source: UniProtKB serine-type endopeptidase activity Inferred from Biological aspect of Ancestor. Source: RefGenome single-stranded DNA binding Inferred from Biological aspect of Ancestor. Source: RefGenome single-stranded RNA binding Inferred from direct assay Ref.10. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Transit peptide

1 – 67

67

Mitochondrion By similarity

Chain

68 – 959

892

Lon protease homolog, mitochondrial HAMAP-Rule MF_03120

PRO_0000026734

Regions

Domain

124 – 368

245

Lon

Nucleotide binding

523 – 530

8

ATP By similarity

Sites

Active site

855

1

By similarity

Active site

898

1

By similarity

Natural variations

Natural variant

87

1

E → D.
Corresponds to variant rs34413649 [ dbSNP | Ensembl ].

VAR_051564

Natural variant

241

1

R → Q.
Corresponds to variant rs11085147 [ dbSNP | Ensembl ].

VAR_051565

Natural variant

829

1

A → T.
Corresponds to variant rs35804229 [ dbSNP | Ensembl ].

VAR_067708

Natural variant

911

1

V → I. Ref.2 Ref.6
Corresponds to variant rs1062373 [ dbSNP | Ensembl ].

VAR_067709

Experimental info

Mutagenesis

855

1

S → A: Lacks both ATPase and protease activity, but retains DNA binding activity. Ref.10

Sequence conflict

1 – 55

55

MAAST…PWALW → MAGLWRRALATCDCGERRGA GCCGGRCWPRRGAGSHCSRS VVAPRPADLRRLSSLGTV in AAA61616. Ref.1

Sequence conflict

65 – 66

2

WR → CG in AAA61616. Ref.1

Sequence conflict

257 – 258

2

EL → DV in AAA61616. Ref.1

Sequence conflict

456

1

N → D in AAA61616. Ref.1

Sequence conflict

556

1

A → T in AAA61616. Ref.1

Sequence conflict

842

1

L → P in AAA61616. Ref.1

Sequence conflict

859

1

T → A in AAA61616. Ref.1

Secondary structure

1

.

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959

Helix Strand Turn

Details...

Beta strand

764 – 786

23

Beta strand

799 – 804

6

Helix

808 – 828

21

Helix

834 – 837

4

Beta strand

839 – 843

5

Turn

850 – 852

3

Helix

853 – 856

4

Helix

857 – 869

13

Beta strand

877 – 879

3

Beta strand

887 – 890

4

Helix

895 – 904

10

Beta strand

909 – 913

5

Helix

914 – 916

3

Helix

917 – 921

5

Helix

925 – 928

4

Beta strand

932 – 938

7

Helix

939 – 946

8

Sequences

	Sequence		Length	Mass (Da)
	P36776 [UniParc]. Last modified December 1, 2000. Version 2. Checksum: B5E03D9C27C220FF	FASTA	959	106,489
	10 20 30 40 50 60 MAASTGYVRL WGAARCWVLR RPMLAAAGGR VPTAAGAWLL RGQRTCDASP PWALWGRGPA 70 80 90 100 110 120 IGGQWRGFWE ASSRGGGAFS GGEDASEGGA EEGAGGAGGS AGAGEGPVIT ALTPMTIPDV 130 140 150 160 170 180 FPHLPLIAIT RNPVFPRFIK IIEVKNKKLV ELLRRKVRLA QPYVGVFLKR DDSNESDVVE 190 200 210 220 230 240 SLDEIYHTGT FAQIHEMQDL GDKLRMIVMG HRRVHISRQL EVEPEEPEAE NKHKPRRKSK 250 260 270 280 290 300 RGKKEAEDEL SARHPAELAM EPTPELPAEV LMVEVENVVH EDFQVTEEVK ALTAEIVKTI 310 320 330 340 350 360 RDIIALNPLY RESVLQMMQA GQRVVDNPIY LSDMGAALTG AESHELQDVL EETNIPKRLY 370 380 390 400 410 420 KALSLLKKEF ELSKLQQRLG REVEEKIKQT HRKYLLQEQL KIIKKELGLE KDDKDAIEEK 430 440 450 460 470 480 FRERLKELVV PKHVMDVVDE ELSKLGLLDN HSSEFNVTRN YLDWLTSIPW GKYSNENLDL 490 500 510 520 530 540 ARAQAVLEED HYGMEDVKKR ILEFIAVSQL RGSTQGKILC FYGPPGVGKT SIARSIARAL 550 560 570 580 590 600 NREYFRFSVG GMTDVAEIKG HRRTYVGAMP GKIIQCLKKT KTENPLILID EVDKIGRGYQ 610 620 630 640 650 660 GDPSSALLEL LDPEQNANFL DHYLDVPVDL SKVLFICTAN VTDTIPEPLR DRMEMINVSG 670 680 690 700 710 720 YVAQEKLAIA ERYLVPQARA LCGLDESKAK LSSDVLTLLI KQYCRESGVR NLQKQVEKVL 730 740 750 760 770 780 RKSAYKIVSG EAESVEVTPE NLQDFVGKPV FTVERMYDVT PPGVVMGLAW TAMGGSTLFV 790 800 810 820 830 840 ETSLRRPQDK DAKGDKDGSL EVTGQLGEVM KESARIAYTF ARAFLMQHAP ANDYLVTSHI 850 860 870 880 890 900 HLHVPEGATP KDGPSAGCTI VTALLSLAMG RPVRQNLAMT GEVSLTGKIL PVGGIKEKTI 910 920 930 940 950 AAKRAGVTCI VLPAENKKDF YDLAAFITEG LEVHFVEHYR EIFDIAFPDE QAEALAVER

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A human mitochondrial ATP-dependent protease that is highly homologous to bacterial Lon protease." Wang N., Gottesman S., Willingham M.C., Gottesman M.M., Maurizi M.R. Proc. Natl. Acad. Sci. U.S.A. 90:11247-11251(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION. Tissue: Brain.
[2]	"Identification of rare DNA variants in mitochondrial disorders with improved array-based sequencing." Wang W., Shen P., Thiyagarajan S., Lin S., Palm C., Horvath R., Klopstock T., Cutler D., Pique L., Schrijver I., Davis R.W., Mindrinos M., Speed T.P., Scharfe C. Nucleic Acids Res. 39:44-58(2011) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ILE-911.
[3]	"Chromosomal mapping and genomic organization of the ATP-dependent human LON protease gene." Huang N.N., Maurizi M.R., Torres R.R., Polymeropoulos M.H., Lennon G.G., Gottesman M.M. Submitted (APR-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Eye.
[6]	"Cloning and sequence analysis of cDNA for a human homolog of eubacterial ATP-dependent Lon proteases." Amerik A.Y., Petukhova G.V., Grigorenko V.G., Lykov I.P., Yarovoi S.V., Lipkin V.M., Gorbalenya A.E. FEBS Lett. 340:25-28(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 3-959, VARIANT ILE-911. Tissue: Brain.
[7]	"Synthesis, processing, and localization of human Lon protease." Wang N., Maurizi M.R., Emmert-Buck L., Gottesman M.M. J. Biol. Chem. 269:29308-29313(1994) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[8]	"The human LON protease binds to mitochondrial promoters in a single-stranded, site-specific, strand-specific manner." Fu G.K., Markovitz D.M. Biochemistry 37:1905-1909(1998) [PubMed] [Europe PMC] [Abstract] Cited for: DNA-BINDING.
[9]	"Lon protease preferentially degrades oxidized mitochondrial aconitase by an ATP-stimulated mechanism." Bota D.A., Davies K.J. Nat. Cell Biol. 4:674-680(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[10]	"DNA and RNA binding by the mitochondrial lon protease is regulated by nucleotide and protein substrate." Liu T., Lu B., Lee I., Ondrovicova G., Kutejova E., Suzuki C.K. J. Biol. Chem. 279:13902-13910(2004) [PubMed] [Europe PMC] [Abstract] Cited for: DNA-BINDING, MUTAGENESIS OF SER-855, SUBUNIT, INTERACTION WITH PEO1 AND POLG.
[11]	"Cleavage site selection within a folded substrate by the ATP-dependent lon protease." Ondrovicova G., Liu T., Singh K., Tian B., Li H., Gakh O., Perecko D., Janata J., Granot Z., Orly J., Kutejova E., Suzuki C.K. J. Biol. Chem. 280:25103-25110(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[12]	"Roles for the human ATP-dependent Lon protease in mitochondrial DNA maintenance." Lu B., Yadav S., Shah P.G., Liu T., Tian B., Pukszta S., Villaluna N., Kutejova E., Newlon C.S., Santos J.H., Suzuki C.K. J. Biol. Chem. 282:17363-17374(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, DNA-BINDING.
[13]	"Turnover of mitochondrial steroidogenic acute regulatory (StAR) protein by Lon protease: the unexpected effect of proteasome inhibitors." Granot Z., Kobiler O., Melamed-Book N., Eimerl S., Bahat A., Lu B., Braun S., Maurizi M.R., Suzuki C.K., Oppenheim A.B., Orly J. Mol. Endocrinol. 21:2164-2177(2007) [PubMed] [Europe PMC] [Abstract] Cited for: SUBSTRATE.
[14]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[15]	"Structure of the catalytic domain of the human mitochondrial Lon protease: proposed relation of oligomer formation and activity." Garcia-Nafria J., Ondrovicova G., Blagova E., Levdikov V.M., Bauer J.A., Suzuki C.K., Kutejova E., Wilkinson A.J., Wilson K.S. Protein Sci. 19:987-999(2010) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 753-959, SUBUNIT.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U02389 mRNA. Translation: AAA61616.1.
HQ204946 Genomic DNA. Translation: ADP90374.1.
HQ204947 Genomic DNA. Translation: ADP90375.1.
HQ204948 Genomic DNA. Translation: ADP90376.1.
HQ204949 Genomic DNA. Translation: ADP90377.1.
HQ204950 Genomic DNA. Translation: ADP90378.1.
HQ204951 Genomic DNA. Translation: ADP90379.1.
HQ204952 Genomic DNA. Translation: ADP90380.1.
HQ204953 Genomic DNA. Translation: ADP90381.1.
HQ204954 Genomic DNA. Translation: ADP90382.1.
HQ204955 Genomic DNA. Translation: ADP90383.1.
HQ204956 Genomic DNA. Translation: ADP90384.1.
HQ204957 Genomic DNA. Translation: ADP90385.1.
HQ204958 Genomic DNA. Translation: ADP90386.1.
HQ204959 Genomic DNA. Translation: ADP90387.1.
HQ204960 Genomic DNA. Translation: ADP90388.1.
HQ204961 Genomic DNA. Translation: ADP90389.1.
HQ204962 Genomic DNA. Translation: ADP90390.1.
HQ204963 Genomic DNA. Translation: ADP90391.1.
HQ204964 Genomic DNA. Translation: ADP90392.1.
HQ204965 Genomic DNA. Translation: ADP90393.1.
HQ204966 Genomic DNA. Translation: ADP90394.1.
HQ204968 Genomic DNA. Translation: ADP90396.1.
HQ204969 Genomic DNA. Translation: ADP90397.1.
HQ204970 Genomic DNA. Translation: ADP90398.1.
HQ204971 Genomic DNA. Translation: ADP90399.1.
HQ204972 Genomic DNA. Translation: ADP90400.1.
HQ204973 Genomic DNA. Translation: ADP90401.1.
HQ204974 Genomic DNA. Translation: ADP90402.1.
HQ204975 Genomic DNA. Translation: ADP90403.1.
HQ204976 Genomic DNA. Translation: ADP90404.1.
HQ204977 Genomic DNA. Translation: ADP90405.1.
HQ204978 Genomic DNA. Translation: ADP90406.1.
HQ204979 Genomic DNA. Translation: ADP90407.1.
HQ204980 Genomic DNA. Translation: ADP90408.1.
HQ204981 Genomic DNA. Translation: ADP90409.1.
HQ204982 Genomic DNA. Translation: ADP90410.1.
HQ204983 Genomic DNA. Translation: ADP90411.1.
HQ204984 Genomic DNA. Translation: ADP90412.1.
HQ204985 Genomic DNA. Translation: ADP90413.1.
AF059309 , AF059296, AF059297, AF059298, AF059299, AF059300, AF059301, AF059302, AF059303, AF059304, AF059305, AF059306, AF059307, AF059308 Genomic DNA. Translation: AAD24414.1.
CH471139 Genomic DNA. Translation: EAW69151.1.
CH471139 Genomic DNA. Translation: EAW69154.1.
BC000235 mRNA. Translation: AAH00235.1.
X74215 mRNA. Translation: CAA52291.1. Different initiation.
X76040 mRNA. Translation: CAA53625.1.

IPI

IPI00005158.

PIR

S42366.
S57342.

RefSeq

NP_004784.2. NM_004793.3.

UniGene

Hs.350265.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2X36	X-ray	2.00	A/B/C/D/E/F	753-959	[»]

ProteinModelPortal

P36776.

ModBase

Search...

Protein-protein interaction databases

IntAct

P36776. 17 interactions.

STRING

9606.ENSP00000353826.

Protein family/group databases

MEROPS

S16.002.

PTM databases

PhosphoSite

P36776.

Polymorphism databases

DMDM

12644239.

Proteomic databases

PaxDb

P36776.

PRIDE

P36776.

Protocols and materials databases

DNASU

9361.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000360614; ENSP00000353826; ENSG00000196365.

GeneID

9361.

KEGG

hsa:9361.

UCSC

uc002mcx.3. human.

Organism-specific databases

CTD

9361.

GeneCards

GC19M005691.

HGNC

HGNC:9479. LONP1.

HPA

HPA002192.

MIM

605490. gene.

neXtProt

NX_P36776.

PharmGKB

PA162394145.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0466.

HOGENOM

HOG000261409.

HOVERGEN

HBG000798.

InParanoid

P36776.

KO

K08675.

OMA

TGSPEYA.

OrthoDB

EOG4PK273.

PhylomeDB

P36776.

Enzyme and pathway databases

BRENDA

3.4.21.53. 2681.

Gene expression databases

ArrayExpress

P36776.

Bgee

P36776.

CleanEx

HS_LONP1.

Genevestigator

P36776.

GermOnline

ENSG00000196365. Homo sapiens.

Family and domain databases

Gene3D

3.30.230.10. 1 hit.

HAMAP

MF_03120. lonm_euk.

InterPro

IPR003593. AAA+_ATPase.
IPR003959. ATPase_AAA_core.
IPR027065. Lon_Prtase.
IPR008269. Pept_S16_C.
IPR004815. Pept_S16_lon.
IPR003111. Pept_S16_N.
IPR008268. Peptidase_S16_AS.
IPR015947. PUA-like_domain.
IPR020568. Ribosomal_S5_D2-typ_fold.
IPR014721. Ribosomal_S5_D2-typ_fold_subgr.
[Graphical view]

PANTHER

PTHR10046. PTHR10046. 1 hit.

Pfam

PF00004. AAA. 1 hit.
PF02190. LON. 1 hit.
PF05362. Lon_C. 1 hit.
[Graphical view]

PIRSF

PIRSF001174. Lon_proteas. 1 hit.

SMART

SM00382. AAA. 1 hit.
SM00464. LON. 1 hit.
[Graphical view]

SUPFAM

SSF88697. PUA-like. 1 hit.
SSF54211. Ribosomal_S5_D2-typ_fold. 1 hit.

TIGRFAMs

TIGR00763. lon. 1 hit.

PROSITE

PS01046. LON_SER. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

LONP1. human.

EvolutionaryTrace

P36776.

GenomeRNAi

9361.

NextBio

35055.

SOURCE

Search...

Entry information

Entry name

LONM_HUMAN

Accession

Primary (citable) accession number: P36776
Secondary accession number(s): D6W635 , E5KMH8, P36777, Q9UQ95

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 1, 1994
Last sequence update:	December 1, 2000
Last modified:	May 1, 2013
This is version 130 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.