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Reviewed, UniProtKB/Swiss-Prot Q5JRX3 (PREP_HUMAN)

Last modified February 9, 2010. Version 53. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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) [Complete 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.

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

Ontologies

Keywords
   Cellular componentMitochondrion
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainTransit peptide
   LigandMetal-binding
Zinc
   Molecular functionHydrolase
Metalloprotease
Protease
   PTMDisulfide bond
   Technical termComplete proteome
Gene Ontology (GO)
   Biological processproteolysis Ref.6

Inferred from mutant phenotype. Source: UniProtKB

   Cellular componentmitochondrial matrix Ref.6

Inferred from direct assay. Source: UniProtKB

nucleus

Inferred from direct assay. Source: HPA

   Molecular functionenzyme activator activity

Traceable author statement. Source: ProtInc

metalloendopeptidase activity Ref.6

Inferred from mutant phenotype. Source: UniProtKB

zinc ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Alternative products

This entry describes 2 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.

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

Disulfide bond119 ↔ 556 Probable

Natural variations

Alternative sequence6641Q → QV in isoform 2.
VSP_020597
Natural variant81Q → R: dbSNP rs11818724. Ref.4
VAR_027517
Natural variant1451L → V: dbSNP rs9423502. Ref.4
VAR_027518
Natural variant1691F → S: dbSNP rs3814596. Ref.1
VAR_027519
Natural variant3281V → I: dbSNP rs4242746. Ref.1 Ref.3
VAR_027520
Natural variant3971V → A: dbSNP rs3182535. Ref.1 Ref.3
VAR_027521
Natural variant5161Q → H: dbSNP rs3765101.
VAR_027522
Natural variant5541A → D: dbSNP rs12248937.
VAR_057059
Natural variant6211V → I: dbSNP rs2388556. Ref.1
VAR_027523
Natural variant8051R → Q: dbSNP rs34837384.
VAR_057060
Natural variant9521I → M: dbSNP rs2279219.
VAR_027524
Natural variant9631V → I: dbSNP rs17849904. Ref.4
VAR_027525
Natural variant9691P → L: dbSNP rs2279218.
VAR_027526
Natural variant10371R → Q: dbSNP rs6901. Ref.1 Ref.3
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

Sequences

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

Last modified September 19, 2006. Version 2.
Checksum: 7FD1A4AA2BBEF9F5

FASTA1,037117,455
        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 DPSKQTTVSV SFLLPDITDT FEAFTLSLLS SLLTSGPNSP 

       370        380        390        400        410        420 
FYKALIESGL GTDFSPDVGY NGYTREAYFS VGLQGIVEKD 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 DPSWIIR 

« Hide

Isoform 2.

Checksum: 00FC3A380E66D520
Show »

FASTA1,038117,554

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: 10360838] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY, VARIANTS SER-169; ILE-328; ALA-397; ILE-621 AND GLN-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: 14702039] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Placenta.
[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: 15164054] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANTS ILE-328; ALA-397 AND GLN-1037.
[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: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANTS ARG-8; VAL-145 AND ILE-963.
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: 10470851] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 402-1037 (ISOFORM 1).
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: 16849325] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, DISULFIDE BOND, MUTAGENESIS OF GLU-107 AND CYS-119.
[7]Colinge J., Superti-Furga G., Bennett K.L.
Submitted (OCT-2008) to UniProtKB
Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[8]"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: 19196155] [Abstract]
Cited for: TRANSIT PEPTIDE, ENZYME REGULATION, SUBSTRATE SPECIFICITY.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF061243 mRNA. Translation: AAC67244.1.
AK002061 mRNA. Translation: BAG51008.1.
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.
IPIIPI00787827.
IPI00952680.
RefSeqNP_055704.2.
UniGeneHs.528300

3D structure databases

HSSPHSSP built from PDB template 2FGE based on UniProtKB Q9LJL3.
ModBaseSearch...

Protein-protein interaction databases

STRINGQ5JRX3.

Protein family/group databases

MEROPSM16.009.

Proteomic databases

PRIDEQ5JRX3.

Genome annotation databases

EnsemblENST00000224949; ENSP00000224949; ENSG00000107959; Homo sapiens. [Genome view]
GeneID10531.
KEGGhsa:10531.
UCSCuc001igt.1. human.

Organism-specific databases

CTD10531.
GeneCardsGC10M003169.
HGNCHGNC:17663. PITRM1.
HPAHPA006753.
HPA006754.
PharmGKBPA134902269.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG13299.
HOVERGENQ5JRX3.
PhylomeDBQ5JRX3.

Gene expression databases

ArrayExpressQ5JRX3.
BgeeQ5JRX3.
CleanExHS_PITRM1.
GenevestigatorQ5JRX3.
GermOnlineENSG00000107959. Homo sapiens.

Family and domain databases

InterProIPR011249. Metalloenz_metal-bd.
IPR011237. Pept_M16_core.
IPR011765. Pept_M16_N.
IPR007863. Peptidase_M16_C.
IPR013578. Peptidase_M16C_assoc.
[Graphical view]
Gene3DG3DSA:3.30.830.10. Pept_M16_core. 1 hit.
PfamPF08367. M16C_assoc. 1 hit.
PF00675. Peptidase_M16. 1 hit.
PF05193. Peptidase_M16_C. 2 hits.
[Graphical view]
PROSITEPS00143. INSULINASE. False negative.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio39957.

Entry information

Entry namePREP_HUMAN
AccessionPrimary (citable) accession number: Q5JRX3
Secondary accession number(s): B3KMJ6 expand/collapse secondary AC list , O95204, Q2M2G6, Q4VBR1, Q5JRW7, Q7L5Z7, Q9BSI6, Q9BVJ5, Q9UPP8
Entry history
Integrated into UniProtKB/Swiss-Prot: September 19, 2006
Last sequence update: September 19, 2006
Last modified: February 9, 2010
This is version 53 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)
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

Human chromosome 10

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

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Peptidase families

Classification of peptidase families and list of entries

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents