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UniProtKB/Swiss-Prot entry Q5JRX3


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name PREP_HUMAN
Primary accession number Q5JRX3
Secondary accession numbers O95204 Q2M2G6 Q4VBR1 Q5JRW7 Q7L5Z7 Q9BSI6 Q9BVJ5 Q9UPP8
Integrated into Swiss-Prot on September 19, 2006
Sequence was last modified on September 19, 2006 (Sequence version 2)
Annotations were last modified on    September 2, 2008 (Entry version 35)
Name and origin of the protein
Protein name Presequence protease, mitochondrial [Precursor]
Synonyms hPreP
EC 3.4.24.-
Pitrilysin metalloproteinase 1
Metalloprotease 1
hMP1
Gene name
Name: PITRM1
Synonyms: KIAA1104, MP1
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY, AND VARIANTS SER-169; ILE-328; ALA-397; ILE-621 AND GLN-1037.
DOI=10.1089/104454999315268; PubMed=10360838 [NCBI, ExPASy, EBI, Israel, Japan]
Mzhavia N., Berman Y.L., Qian Y., Yan L., Devi L.A.;
"Cloning, expression, and characterization of human metalloprotease 1: a novel member of the pitrilysin family of metalloendoproteases.";
DNA Cell Biol. 18:369-380(1999).
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANTS ILE-328; ALA-397 AND GLN-1037.
DOI=10.1038/nature02462; PubMed=15164054 [NCBI, ExPASy, EBI, Israel, Japan]
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., 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.;
"The DNA sequence and comparative analysis of human chromosome 10.";
Nature 429:375-381(2004).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS ARG-8; VAL-145 AND ILE-963.
TISSUE=Brain, Lung, and Testis;
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 402-1037 (ISOFORM 1).
TISSUE=Brain;
DOI=10.1093/dnares/6.3.197; PubMed=10470851 [NCBI, ExPASy, EBI, Israel, Japan]
Kikuno R., Nagase T., Ishikawa K., Hirosawa M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.;
"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.";
DNA Res. 6:197-205(1999).
[5]
FUNCTION, SUBCELLULAR LOCATION, DISULFIDE BOND, AND MUTAGENESIS OF GLU-107 AND CYS-119.
DOI=10.1074/jbc.M602532200; PubMed=16849325 [NCBI, ExPASy, EBI, Israel, Japan]
Falkevall A., Alikhani N., Bhushan S., Pavlov P.F., Busch K., Johnson K.A., Eneqvist T., Tjernberg L., Ankarcrona M., Glaser E.;
"Degradation of the amyloid beta-protein by the novel mitochondrial peptidasome, PreP.";
J. Biol. Chem. 281:29096-29104(2006).
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.
  • COFACTOR: Binds 1 zinc ion per subunit (By similarity).
  • SUBUNIT: Homodimer (By similarity).
  • SUBCELLULAR LOCATION: Mitochondrion matrix.
  • ALTERNATIVE PRODUCTS: 2 named isoforms [FASTA] produced by alternative splicing.
    Name1
    Isoform IDQ5JRX3-1
    This is the isoform sequence displayed in this entry.
    Name2
    Isoform IDQ5JRX3-2
    Note: No experimental confirmation available.
    Features which should be applied to build the isoform sequence: VSP_020597.
  • TISSUE SPECIFICITY: Widely expressed. Expressed at higher level in muscle and heart compared to brain, pancreas, liver, lung and placenta.
  • PTM: 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.
  • SIMILARITY: Belongs to the peptidase M16 family. PreP subfamily [view classification].
  • SEQUENCE CAUTION:
    • Sequence=CAI39997.1; Type=Erroneous gene model prediction;
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
AF061243; AAC67244.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AL451164; CAI40001.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AL451164; CAI39997.1; ALT_SEQ; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC001150; AAH01150.1; ALT_INIT; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC005025; AAH05025.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC095422; AAH95422.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC111987; AAI11988.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC113369; AAI13370.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AB029027; BAA83056.2; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
RefSeq NP_055704.2; -.
UniGene Hs.528300
3D structure databases
ModBase Q5JRX3.
Protein family/group databases
MEROPS M16.009; -.
Organism-specific databases
HGNC HGNC:17663; PITRM1.
GenAtlas PITRM1.
HPA HPA006753; -.
HPA006754; -.
PharmGKB PA134902269; -.
GeneCards Q5JRX3.
HUGE KIAA1104.
Gene expression databases
ArrayExpress Q5JRX3; -.
CleanEx HS_PITRM1; -.
GermOnline ENSG00000107959; Homo sapiens.
Ontologies
GO
GO:0005759; Cellular component: mitochondrial matrix (inferred from direct assay from UniProtKB).
GO:0008047; Molecular function: enzyme activator activity (traceable author statement from ProtInc).
GO:0004222; Molecular function: metalloendopeptidase activity (inferred from mutant phenotype from UniProtKB).
GO:0006508; Biological process: proteolysis (inferred from mutant phenotype from UniProtKB).
QuickGo view.
Family and domain databases
InterPro IPR011237; Pept_M16_core.
IPR001431; Pept_M16_Zn_BS.
IPR007863; Peptidase_M16_C.
IPR013578; Peptidase_M16C_assoc.
Graphical view of domain structure.
Gene3D G3DSA:3.30.830.10; Pept_M16_core; 1.
Pfam PF08367; M16C_assoc; 1.
PF05193; Peptidase_M16_C; 2.
Pfam graphical view of domain structure.
PROSITE PS00143; INSULINASE; FALSE_NEG.
BLOCKS Q5JRX3.
Genome annotation databases
Ensembl ENSG00000107959; Homo sapiens. [Contig view]
GeneID 10531; -.
KEGG hsa:10531; -.
Phylogenomic databases
HOVERGEN Q5JRX3; -.
Other
ProtoNet Q5JRX3.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
Alternative splicing; Hydrolase; Metal-binding; Metalloprotease; Mitochondrion; Polymorphism; Protease; Transit peptide; Zinc.
Features
SEVIEWER logo Feature table viewer
KeyFrom    To Length Description FTId
TRANSIT   1     84  84     Mitochondrion (Potential). 
CHAIN   85   1037  953     Presequence protease, mitochondrial. PRO_0000249931
ACT_SITE   107    107        Proton acceptor. 
METAL   104    104        Zinc; catalytic (By similarity). 
METAL   108    108        Zinc; catalytic (By similarity). 
METAL   205    205        Zinc; catalytic (By similarity). 
DISULFID   119    556        Probable. 
VAR_SEQ   664    664        Q -> QV (in isoform 2). VSP_020597
VARIANT   8      8  1     Q -> R (in dbSNP:rs11818724 [NCBI]). VAR_027517 
VARIANT   145    145  1     L -> V (in dbSNP:rs9423502 [NCBI]). VAR_027518 
VARIANT   169    169  1     F -> S (in dbSNP:rs3814596 [NCBI]). VAR_027519 
VARIANT   328    328  1     V -> I (in dbSNP:rs4242746 [NCBI]). VAR_027520 
VARIANT   397    397  1     V -> A (in dbSNP:rs3182535 [NCBI]). VAR_027521 
VARIANT   516    516  1     Q -> H (in dbSNP:rs3765101 [NCBI]). VAR_027522 
VARIANT   621    621  1     V -> I (in dbSNP:rs2388556 [NCBI]). VAR_027523 
VARIANT   952    952  1     I -> M (in dbSNP:rs2279219 [NCBI]). VAR_027524 
VARIANT   963    963  1     V -> I (in dbSNP:rs17849904 [NCBI]). VAR_027525 
VARIANT   969    969  1     P -> L (in dbSNP:rs2279218 [NCBI]). VAR_027526 
VARIANT   1037   1037  1     R -> Q (in dbSNP:rs6901 [NCBI]). VAR_027527 
MUTAGEN   107    107        E->Q: Loss of function. 
MUTAGEN   119    119        C->S: Still active under oxidizing conditions. 
CONFLICT   121    121        D -> N (in Ref. 1; AAC67244). 
CONFLICT   211    211        T -> V (in Ref. 2; CAI40001). 
CONFLICT   212    212        D -> N (in Ref. 2; CAI40001). 
CONFLICT   373    373        D -> E (in Ref. 1; AAC67244). 
CONFLICT   418    420        KGF -> TRI (in Ref. 1; AAC67244). 
CONFLICT   883    884        LK -> FE (in Ref. 3; AAH95422). 
Sequence information
Length: 1037 AA [This is the length of the unprocessed precursor] Molecular weight: 117455 Da [This is the MW of the unprocessed precursor] CRC64: 7FD1A4AA2BBEF9F5 [This is a checksum on the sequence]
        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 

Q5JRX3 in FASTA format

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View entry in raw text format (no links)
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BLAST logo BLAST submission on ExPASy/SIB
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Tools Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
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