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Q5JRX3 (PREP_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 95. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Presequence protease, mitochondrial

Short name=hPreP
EC=3.4.24.-
Alternative name(s):
Pitrilysin metalloproteinase 1
Short name=Metalloprotease 1
Short name=hMP1
Gene names
Name:PITRM1
Synonyms:KIAA1104, MP1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1037 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

ATP-independent protease that degrades mitochondrial transit peptides after their cleavage. Also degrades other unstructured peptides. Specific for peptides in the range of 10 to 65 residues. Able to degrade amyloid beta A4 (APP) protein when it accumulates in mitochondrion, suggesting a link with Alzheimer disease. Shows a preference for cleavage after small polar residues and before basic residues, but without any positional preference. Ref.6

Cofactor

Binds 1 zinc ion per subunit By similarity.

Enzyme regulation

Inhibited by nickel and zinc excess, and slightly activated by manganese. Ref.7

Subunit structure

Homodimer By similarity.

Subcellular location

Mitochondrion matrix Ref.6.

Tissue specificity

Widely expressed. Expressed at higher level in muscle and heart compared to brain, pancreas, liver, lung and placenta. Ref.1

Post-translational modification

The disulfide bond may lock the enzyme in a closed conformation under oxidized conditions, suggesting that it may participate in redox regulation of the enzyme.

Sequence similarities

Belongs to the peptidase M16 family. PreP subfamily.

Sequence caution

The sequence AAH01150.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

The sequence CAI39997.1 differs from that shown. Reason: Erroneous gene model prediction.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q5JRX3-1)

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.
Isoform 2 (identifier: Q5JRX3-2)

The sequence of this isoform differs from the canonical sequence as follows:
     664-664: Q → QV
Note: No experimental confirmation available.
Isoform 3 (identifier: Q5JRX3-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-53: MWRCGGRQGLCVLRRLSGGHAHHRAWRWNSNRACERALQYKLGDKIHGFTVNQ → MRNVALRRAAGPVCAEAAERR
     624-689: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 1515Mitochondrion
Chain16 – 10371022Presequence protease, mitochondrial
PRO_0000249931

Sites

Active site1071Proton acceptor
Metal binding1041Zinc; catalytic By similarity
Metal binding1081Zinc; catalytic By similarity
Metal binding2051Zinc; catalytic By similarity

Amino acid modifications

Modified residue7591N6-acetyllysine By similarity
Modified residue7701N6-acetyllysine; alternate By similarity
Modified residue7701N6-succinyllysine; alternate By similarity
Modified residue8491N6-succinyllysine By similarity
Modified residue8841N6-acetyllysine By similarity
Modified residue9461N6-succinyllysine By similarity
Disulfide bond119 ↔ 556 Probable

Natural variations

Alternative sequence1 – 5353MWRCG…FTVNQ → MRNVALRRAAGPVCAEAAER R in isoform 3.
VSP_046494
Alternative sequence624 – 68966Missing in isoform 3.
VSP_046495
Alternative sequence6641Q → QV in isoform 2.
VSP_020597
Natural variant81Q → R. Ref.4
Corresponds to variant rs11818724 [ dbSNP | Ensembl ].
VAR_027517
Natural variant1451L → V. Ref.4
Corresponds to variant rs9423502 [ dbSNP | Ensembl ].
VAR_027518
Natural variant1691F → S. Ref.1
Corresponds to variant rs3814596 [ dbSNP | Ensembl ].
VAR_027519
Natural variant3281I → V. Ref.1 Ref.2 Ref.4
Corresponds to variant rs4242746 [ dbSNP | Ensembl ].
VAR_027520
Natural variant3971A → V. Ref.1 Ref.2 Ref.4
Corresponds to variant rs3182535 [ dbSNP | Ensembl ].
VAR_027521
Natural variant5161Q → H.
Corresponds to variant rs3765101 [ dbSNP | Ensembl ].
VAR_027522
Natural variant5541A → D.
Corresponds to variant rs12248937 [ dbSNP | Ensembl ].
VAR_057059
Natural variant6211V → I. Ref.1
Corresponds to variant rs2388556 [ dbSNP | Ensembl ].
VAR_027523
Natural variant8051R → Q.
Corresponds to variant rs34837384 [ dbSNP | Ensembl ].
VAR_057060
Natural variant9521I → M.
Corresponds to variant rs2279219 [ dbSNP | Ensembl ].
VAR_027524
Natural variant9631V → I. Ref.4
Corresponds to variant rs17849904 [ dbSNP | Ensembl ].
VAR_027525
Natural variant9691P → L.
Corresponds to variant rs2279218 [ dbSNP | Ensembl ].
VAR_027526
Natural variant10371Q → R. Ref.1 Ref.2 Ref.4 Ref.5
Corresponds to variant rs6901 [ dbSNP | Ensembl ].
VAR_027527

Experimental info

Mutagenesis1071E → Q: Loss of function. Ref.6
Mutagenesis1191C → S: Still active under oxidizing conditions. Ref.6
Sequence conflict1211D → N in AAC67244. Ref.1
Sequence conflict2111T → V in CAI40001. Ref.3
Sequence conflict2121D → N in CAI40001. Ref.3
Sequence conflict3731D → E in AAC67244. Ref.1
Sequence conflict418 – 4203KGF → TRI in AAC67244. Ref.1
Sequence conflict883 – 8842LK → FE in AAH95422. Ref.4

Secondary structure

................................................................................................................................................................... 1037
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified May 1, 2013. Version 3.
Checksum: F488389F0E219718

FASTA1,037117,413
        10         20         30         40         50         60 
MWRCGGRQGL CVLRRLSGGH AHHRAWRWNS NRACERALQY KLGDKIHGFT VNQVTSVPEL 

        70         80         90        100        110        120 
FLTAVKLTHD DTGARYLHLA REDTNNLFSV QFRTTPMDST GVPHILEHTV LCGSQKYPCR 

       130        140        150        160        170        180 
DPFFKMLNRS LSTFMNAFTA SDYTLYPFST QNPKDFQNLL SVYLDATFFP CLRELDFWQE 

       190        200        210        220        230        240 
GWRLEHENPS DPQTPLVFKG VVFNEMKGAF TDNERIFSQH LQNRLLPDHT YSVVSGGDPL 

       250        260        270        280        290        300 
CIPELTWEQL KQFHATHYHP SNARFFTYGN FPLEQHLKQI HEEALSKFQK IEPSTVVPAQ 

       310        320        330        340        350        360 
TPWDKPREFQ ITCGPDSFAT DPSKQTTISV SFLLPDITDT FEAFTLSLLS SLLTSGPNSP 

       370        380        390        400        410        420 
FYKALIESGL GTDFSPDVGY NGYTREAYFS VGLQGIAEKD IETVRSLIDR TIDEVVEKGF 

       430        440        450        460        470        480 
EDDRIEALLH KIEIQMKHQS TSFGLMLTSY IASCWNHDGD PVELLKLGNQ LAKFRQCLQE 

       490        500        510        520        530        540 
NPKFLQEKVK QYFKNNQHKL TLSMRPDDKY HEKQAQVEAT KLKQKVEALS PGDRQQIYEK 

       550        560        570        580        590        600 
GLELRSQQSK PQDASCLPAL KVSDIEPTIP VTELDVVLTA GDIPVQYCAQ PTNGMVYFRA 

       610        620        630        640        650        660 
FSSLNTLPEE LRPYVPLFCS VLTKLGCGLL DYREQAQQIE LKTGGMSASP HVLPDDSHMD 

       670        680        690        700        710        720 
TYEQGVLFSS LCLDRNLPDM MQLWSEIFNN PCFEEEEHFK VLVKMTAQEL ANGIPDSGHL 

       730        740        750        760        770        780 
YASIRAGRTL TPAGDLQETF SGMDQVRLMK RIAEMTDIKP ILRKLPRIKK HLLNGDNMRC 

       790        800        810        820        830        840 
SVNATPQQMP QTEKAVEDFL RSIGRSKKER RPVRPHTVEK PVPSSSGGDA HVPHGSQVIR 

       850        860        870        880        890        900 
KLVMEPTFKP WQMKTHFLMP FPVNYVGECI RTVPYTDPDH ASLKILARLM TAKFLHTEIR 

       910        920        930        940        950        960 
EKGGAYGGGA KLSHNGIFTL YSYRDPNTIE TLQSFGKAVD WAKSGKFTQQ DIDEAKLSVF 

       970        980        990       1000       1010       1020 
STVDAPVAPS DKGMDHFLYG LSDEMKQAHR EQLFAVSHDK LLAVSDRYLG TGKSTHGLAI 

      1030 
LGPENPKIAK DPSWIIQ 

« Hide

Isoform 2 [UniParc].

Checksum: 8A55B3A43B434A4E
Show »

FASTA1,038117,512
Isoform 3 [UniParc].

Checksum: 21E09CEE32236867
Show »

FASTA939106,065

References

« Hide 'large scale' references
[1]"Cloning, expression, and characterization of human metalloprotease 1: a novel member of the pitrilysin family of metalloendoproteases."
Mzhavia N., Berman Y.L., Qian Y., Yan L., Devi L.A.
DNA Cell Biol. 18:369-380(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY, VARIANTS SER-169; VAL-328; VAL-397; ILE-621 AND ARG-1037.
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3), VARIANTS VAL-328; VAL-397 AND ARG-1037.
Tissue: Placenta and Thymus.
[3]"The DNA sequence and comparative analysis of human chromosome 10."
Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. expand/collapse author list , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.
Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"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] (ISOFORM 1), VARIANTS ARG-8; VAL-145; VAL-328; VAL-397; ILE-963 AND ARG-1037.
Tissue: Brain, Lung and Testis.
[5]"Prediction of the coding sequences of unidentified human genes. XIV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro."
Kikuno R., Nagase T., Ishikawa K., Hirosawa M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.
DNA Res. 6:197-205(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 402-1037 (ISOFORM 1), VARIANT ARG-1037.
Tissue: Brain.
[6]"Degradation of the amyloid beta-protein by the novel mitochondrial peptidasome, PreP."
Falkevall A., Alikhani N., Bhushan S., Pavlov P.F., Busch K., Johnson K.A., Eneqvist T., Tjernberg L., Ankarcrona M., Glaser E.
J. Biol. Chem. 281:29096-29104(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, DISULFIDE BOND, MUTAGENESIS OF GLU-107 AND CYS-119.
[7]"Mammalian pitrilysin: substrate specificity and mitochondrial targeting."
Chow K.M., Gakh O., Payne I.C., Juliano M.A., Juliano L., Isaya G., Hersh L.B.
Biochemistry 48:2868-2877(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: TRANSIT PEPTIDE CLEAVAGE SITE, ENZYME REGULATION, SUBSTRATE SPECIFICITY.
[8]"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].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF061243 mRNA. Translation: AAC67244.1.
AK002061 mRNA. Translation: BAG51008.1.
AK303406 mRNA. Translation: BAG64460.1.
AL451164 Genomic DNA. Translation: CAI40001.1.
AL451164 Genomic DNA. Translation: CAI39997.1. Sequence problems.
BC001150 mRNA. Translation: AAH01150.1. Different initiation.
BC005025 mRNA. Translation: AAH05025.1.
BC095422 mRNA. Translation: AAH95422.1.
BC111987 mRNA. Translation: AAI11988.1.
BC113369 mRNA. Translation: AAI13370.1.
AB029027 mRNA. Translation: BAA83056.2.
CCDSCCDS55699.1. [Q5JRX3-2]
CCDS55700.1. [Q5JRX3-3]
CCDS59208.1. [Q5JRX3-1]
RefSeqNP_001229236.1. NM_001242307.1. [Q5JRX3-2]
NP_001229238.1. NM_001242309.1. [Q5JRX3-3]
NP_055704.2. NM_014889.3. [Q5JRX3-1]
UniGeneHs.528300.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4L3TX-ray2.03A/B33-1037[»]
4NGEX-ray2.70A/D33-1037[»]
ProteinModelPortalQ5JRX3.
SMRQ5JRX3. Positions 33-1037.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid115786. 8 interactions.
IntActQ5JRX3. 2 interactions.

Protein family/group databases

MEROPSM16.009.

PTM databases

PhosphoSiteQ5JRX3.

Polymorphism databases

DMDM485956568.

Proteomic databases

MaxQBQ5JRX3.
PaxDbQ5JRX3.
PRIDEQ5JRX3.

Protocols and materials databases

DNASU10531.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000224949; ENSP00000224949; ENSG00000107959. [Q5JRX3-1]
ENST00000380989; ENSP00000370377; ENSG00000107959. [Q5JRX3-2]
ENST00000451104; ENSP00000401201; ENSG00000107959. [Q5JRX3-3]
GeneID10531.
KEGGhsa:10531.

Organism-specific databases

CTD10531.
GeneCardsGC10M003179.
H-InvDBHIX0008597.
HGNCHGNC:17663. PITRM1.
HPAHPA006753.
HPA006754.
neXtProtNX_Q5JRX3.
PharmGKBPA134902269.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1026.
HOVERGENHBG082167.
KOK06972.
OMALHKIEIQ.
OrthoDBEOG7KH9HZ.
TreeFamTF300333.

Enzyme and pathway databases

SignaLinkQ5JRX3.

Gene expression databases

ArrayExpressQ5JRX3.
BgeeQ5JRX3.
CleanExHS_PITRM1.
GenevestigatorQ5JRX3.

Family and domain databases

Gene3D3.30.830.10. 3 hits.
InterProIPR011249. Metalloenz_LuxS/M16.
IPR011237. Pept_M16_dom.
IPR011765. Pept_M16_N.
IPR007863. Peptidase_M16_C.
IPR013578. Peptidase_M16C_assoc.
[Graphical view]
PfamPF08367. M16C_assoc. 1 hit.
PF00675. Peptidase_M16. 1 hit.
PF05193. Peptidase_M16_C. 2 hits.
[Graphical view]
SUPFAMSSF63411. SSF63411. 4 hits.
ProtoNetSearch...

Other

ChiTaRSPITRM1. human.
GeneWikiPITRM1.
GenomeRNAi10531.
NextBio39957.
PROQ5JRX3.

Entry information

Entry namePREP_HUMAN
AccessionPrimary (citable) accession number: Q5JRX3
Secondary accession number(s): B3KMJ6 expand/collapse secondary AC list , B4E0J8, C9JSL2, E7ES23, O95204, Q2M2G6, Q4VBR1, Q5JRW7, Q7L5Z7, Q9BSI6, Q9BVJ5, Q9UPP8
Entry history
Integrated into UniProtKB/Swiss-Prot: September 19, 2006
Last sequence update: May 1, 2013
Last modified: July 9, 2014
This is version 95 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 10

Human chromosome 10: entries, gene names and cross-references to MIM