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Q9JIY5

- HTRA2_MOUSE

UniProt

Q9JIY5 - HTRA2_MOUSE

Protein

Serine protease HTRA2, mitochondrial

Gene

Htra2

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 130 (01 Oct 2014)
      Sequence version 2 (27 Mar 2002)
      Previous versions | rss
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    Functioni

    Serine protease that shows proteolytic activity against a non-specific substrate beta-casein. Promotes or induces cell death either by direct binding to and inhibition of BIRC proteins (also called inhibitor of apoptosis proteins, IAPs), leading to an increase in caspase activity, or by a BIRC inhibition-independent, caspase-independent and serine protease activity-dependent mechanism. Cleaves THAP5 and promotes its degradation during apoptosis By similarity.By similarity

    Catalytic activityi

    Cleavage of non-polar aliphatic amino acids at the P1 position, with a preference for Val, Ile and Met. At the P2 and P3 positions, Arg is selected most strongly with a secondary preference for other hydrophilic residues.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei198 – 1981Charge relay systemSequence Analysis
    Active sitei228 – 2281Charge relay systemSequence Analysis
    Active sitei306 – 3061Charge relay systemSequence Analysis

    GO - Molecular functioni

    1. protein binding Source: IntAct
    2. serine-type endopeptidase activity Source: InterPro

    GO - Biological processi

    1. adult locomotory behavior Source: MGI
    2. adult walking behavior Source: MGI
    3. cellular response to growth factor stimulus Source: Ensembl
    4. cellular response to heat Source: Ensembl
    5. ceramide metabolic process Source: Ensembl
    6. forebrain development Source: MGI
    7. intrinsic apoptotic signaling pathway Source: MGI
    8. mitochondrion organization Source: MGI
    9. negative regulation of cell death Source: Ensembl
    10. neuron development Source: MGI
    11. pentacyclic triterpenoid metabolic process Source: Ensembl
    12. positive regulation of apoptotic process Source: UniProtKB
    13. positive regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: Ensembl
    14. positive regulation of extrinsic apoptotic signaling pathway in absence of ligand Source: Ensembl
    15. regulation of multicellular organism growth Source: MGI
    16. response to herbicide Source: Ensembl

    Keywords - Molecular functioni

    Hydrolase, Protease, Serine protease

    Keywords - Biological processi

    Apoptosis

    Enzyme and pathway databases

    BRENDAi3.4.21.108. 3474.

    Protein family/group databases

    MEROPSiS01.278.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Serine protease HTRA2, mitochondrial (EC:3.4.21.108)
    Alternative name(s):
    High temperature requirement protein A2
    Short name:
    HtrA2
    Omi stress-regulated endoprotease
    Serine protease 25
    Serine proteinase OMI
    Gene namesi
    Name:Htra2
    Synonyms:Omi, Prss25
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 6

    Organism-specific databases

    MGIiMGI:1928676. Htra2.

    Subcellular locationi

    Mitochondrion intermembrane space. Mitochondrion membrane Curated; Single-pass membrane protein Curated
    Note: Predominantly present in the intermembrane space. Released into the cytosol following apoptotic stimuli, such as UV treatment, and stimulation of mitochondria with BID.

    GO - Cellular componenti

    1. CD40 receptor complex Source: BHF-UCL
    2. cytoplasmic side of plasma membrane Source: BHF-UCL
    3. cytosol Source: Ensembl
    4. mitochondrial intermembrane space Source: MGI
    5. mitochondrial membrane Source: UniProtKB-SubCell
    6. mitochondrion Source: ParkinsonsUK-UCL
    7. nucleus Source: Ensembl

    Keywords - Cellular componenti

    Membrane, Mitochondrion

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi134 – 1341A → G: Loss of interaction with XIAP. 1 Publication
    Mutagenesisi137 – 1371A → I: Stronger interaction with XIAP third BIR domain. 1 Publication
    Mutagenesisi306 – 3061S → A: Loss of protease activity. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transit peptidei1 – 3131MitochondrionAdd
    BLAST
    Propeptidei32 – 133102Sequence AnalysisPRO_0000026947Add
    BLAST
    Chaini134 – 458325Serine protease HTRA2, mitochondrialPRO_0000026948Add
    BLAST

    Post-translational modificationi

    Autoproteolytically activated.By similarity

    Keywords - PTMi

    Zymogen

    Proteomic databases

    MaxQBiQ9JIY5.
    PaxDbiQ9JIY5.
    PRIDEiQ9JIY5.

    2D gel databases

    REPRODUCTION-2DPAGEQ9JIY5.

    PTM databases

    PhosphoSiteiQ9JIY5.

    Expressioni

    Gene expression databases

    ArrayExpressiQ9JIY5.
    BgeeiQ9JIY5.
    CleanExiMM_HTRA2.
    GenevestigatoriQ9JIY5.

    Interactioni

    Subunit structurei

    Homotrimer. Interacts with MXI2. Interacts with THAP5 under apoptotic conditions By similarity. The mature protein, but not the precursor, binds to BIRC2/c-IAP1, BIRC3/c-IAP2 and XIAP/BIRC4 By similarity. Interacts with BIRC6/bruce By similarity.By similarity

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    XIAPP981704EBI-2365838,EBI-517127From a different organism.
    XiapQ609892EBI-2365838,EBI-517478

    Protein-protein interaction databases

    BioGridi211100. 8 interactions.
    DIPiDIP-41272N.
    IntActiQ9JIY5. 5 interactions.
    MINTiMINT-219738.

    Structurei

    3D structure databases

    ProteinModelPortaliQ9JIY5.
    SMRiQ9JIY5. Positions 139-458.
    ModBaseiSearch...
    MobiDBiSearch...

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei105 – 12521HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini364 – 44683PDZPROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni166 – 342177Serine proteaseAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi134 – 1374IAP-binding motifBy similarity

    Domaini

    The mature N-terminus is involved in the interaction with XIAP.
    The PDZ domain mediates interaction with MXI2.

    Sequence similaritiesi

    Belongs to the peptidase S1B family.Curated
    Contains 1 PDZ (DHR) domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Transit peptide, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiCOG0265.
    GeneTreeiENSGT00510000046315.
    HOGENOMiHOG000223641.
    HOVERGENiHBG052044.
    InParanoidiQ9JIY5.
    KOiK08669.
    OMAiLIHRVIM.
    PhylomeDBiQ9JIY5.
    TreeFamiTF323480.

    Family and domain databases

    Gene3Di2.30.42.10. 1 hit.
    InterProiIPR001478. PDZ.
    IPR001940. Peptidase_S1C.
    IPR009003. Trypsin-like_Pept_dom.
    [Graphical view]
    PfamiPF13180. PDZ_2. 1 hit.
    [Graphical view]
    PRINTSiPR00834. PROTEASES2C.
    SMARTiSM00228. PDZ. 1 hit.
    [Graphical view]
    SUPFAMiSSF50156. SSF50156. 1 hit.
    SSF50494. SSF50494. 1 hit.
    PROSITEiPS50106. PDZ. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    Q9JIY5-1 [UniParc]FASTAAdd to Basket

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    MAALKAGRGA NWSLRAWRAL GGIFWRKPPL LAPDLRALLT SGTPDSQIWM    50
    TYGTPSLPAQ VPEGFLASRA DLTSRTPDLW ARLNVGTSGS SDQEARRSPG 100
    SRRREWLAVA VGAGGAVVLL LWGWGRGLST VLAAVPAPPP TSPRSQYNFI 150
    ADVVEKTAPA VVYIEILDRH PFSGREVPIS NGSGFVVASD GLIVTNAHVV 200
    ADRRRVRVRL PSGDTYEAMV TAVDPVADIA TLRIQTKEPL PTLPLGRSAD 250
    VRQGEFVVAM GSPFALQNTI TSGIVSSAQR PARDLGLPQN NVEYIQTDAA 300
    IDFGNSGGPL VNLDGEVIGV NTMKVTAGIS FAIPSDRLRE FLHRGEKKNS 350
    WFGTSGSQRR YIGVMMLTLT PSILIELQLR EPSFPDVQHG VLIHKVILGS 400
    PAHRAGLRPG DVILAIGEKL AQNAEDVYEA VRTQSQLAVR IRRGSETLTL 450
    YVTPEVTE 458
    Length:458
    Mass (Da):49,348
    Last modified:March 27, 2002 - v2
    Checksum:iC1E77346FB8D75BD
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti449 – 4491T → I in AAF89534. (PubMed:10971580)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF164513 mRNA. Translation: AAF89534.1.
    AF175324 mRNA. Translation: AAD50499.1.
    CCDSiCCDS20267.1.
    RefSeqiNP_062726.3. NM_019752.3.
    UniGeneiMm.21880.

    Genome annotation databases

    EnsembliENSMUST00000089645; ENSMUSP00000087073; ENSMUSG00000068329.
    GeneIDi64704.
    KEGGimmu:64704.
    UCSCiuc009clu.3. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF164513 mRNA. Translation: AAF89534.1 .
    AF175324 mRNA. Translation: AAD50499.1 .
    CCDSi CCDS20267.1.
    RefSeqi NP_062726.3. NM_019752.3.
    UniGenei Mm.21880.

    3D structure databases

    ProteinModelPortali Q9JIY5.
    SMRi Q9JIY5. Positions 139-458.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 211100. 8 interactions.
    DIPi DIP-41272N.
    IntActi Q9JIY5. 5 interactions.
    MINTi MINT-219738.

    Protein family/group databases

    MEROPSi S01.278.

    PTM databases

    PhosphoSitei Q9JIY5.

    2D gel databases

    REPRODUCTION-2DPAGE Q9JIY5.

    Proteomic databases

    MaxQBi Q9JIY5.
    PaxDbi Q9JIY5.
    PRIDEi Q9JIY5.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000089645 ; ENSMUSP00000087073 ; ENSMUSG00000068329 .
    GeneIDi 64704.
    KEGGi mmu:64704.
    UCSCi uc009clu.3. mouse.

    Organism-specific databases

    CTDi 27429.
    MGIi MGI:1928676. Htra2.

    Phylogenomic databases

    eggNOGi COG0265.
    GeneTreei ENSGT00510000046315.
    HOGENOMi HOG000223641.
    HOVERGENi HBG052044.
    InParanoidi Q9JIY5.
    KOi K08669.
    OMAi LIHRVIM.
    PhylomeDBi Q9JIY5.
    TreeFami TF323480.

    Enzyme and pathway databases

    BRENDAi 3.4.21.108. 3474.

    Miscellaneous databases

    ChiTaRSi HTRA2. mouse.
    NextBioi 320171.
    PROi Q9JIY5.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q9JIY5.
    Bgeei Q9JIY5.
    CleanExi MM_HTRA2.
    Genevestigatori Q9JIY5.

    Family and domain databases

    Gene3Di 2.30.42.10. 1 hit.
    InterProi IPR001478. PDZ.
    IPR001940. Peptidase_S1C.
    IPR009003. Trypsin-like_Pept_dom.
    [Graphical view ]
    Pfami PF13180. PDZ_2. 1 hit.
    [Graphical view ]
    PRINTSi PR00834. PROTEASES2C.
    SMARTi SM00228. PDZ. 1 hit.
    [Graphical view ]
    SUPFAMi SSF50156. SSF50156. 1 hit.
    SSF50494. SSF50494. 1 hit.
    PROSITEi PS50106. PDZ. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Strain: BALB/c.
      Tissue: Brain.
    2. "Characterization of the mouse homolog of Omi serine protease."
      Faccio L., Fusco C., Zervos A.S.
      Submitted (AUG-1999) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Strain: C57BL/6J.
      Tissue: Embryo.
    3. "HtrA2 promotes cell death through its serine protease activity and its ability to antagonize inhibitor of apoptosis proteins."
      Verhagen A.M., Silke J., Ekert P.G., Pakusch M., Kaufmann H., Connolly L.M., Day C.L., Tikoo A., Burke R., Wrobel C., Moritz R.L., Simpson R.J., Vaux D.L.
      J. Biol. Chem. 277:445-454(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN APOPTOSIS, MUTAGENESIS OF ALA-134; ALA-137 AND SER-306.

    Entry informationi

    Entry nameiHTRA2_MOUSE
    AccessioniPrimary (citable) accession number: Q9JIY5
    Secondary accession number(s): Q9R108
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: September 26, 2001
    Last sequence update: March 27, 2002
    Last modified: October 1, 2014
    This is version 130 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. Peptidase families
      Classification of peptidase families and list of entries
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3