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O43464

- HTRA2_HUMAN

UniProt

O43464 - HTRA2_HUMAN

Protein

Serine protease HTRA2, mitochondrial

Gene

HTRA2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 161 (01 Oct 2014)
      Sequence version 2 (01 May 2000)
      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. Isoform 2 seems to be proteolytically inactive.2 Publications

    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 system
    Active sitei228 – 2281Charge relay system
    Active sitei306 – 3061Charge relay system

    GO - Molecular functioni

    1. peptidase activity Source: UniProtKB
    2. protein binding Source: UniProtKB
    3. serine-type endopeptidase activity Source: UniProtKB
    4. serine-type peptidase activity Source: UniProtKB
    5. unfolded protein binding Source: UniProtKB

    GO - Biological processi

    1. adult walking behavior Source: Ensembl
    2. cellular protein catabolic process Source: ParkinsonsUK-UCL
    3. cellular response to growth factor stimulus Source: UniProtKB
    4. cellular response to heat Source: UniProtKB
    5. cellular response to interferon-beta Source: ParkinsonsUK-UCL
    6. cellular response to retinoic acid Source: ParkinsonsUK-UCL
    7. ceramide metabolic process Source: Ensembl
    8. execution phase of apoptosis Source: UniProtKB
    9. forebrain development Source: Ensembl
    10. intrinsic apoptotic signaling pathway in response to DNA damage Source: ParkinsonsUK-UCL
    11. mitochondrion organization Source: Ensembl
    12. negative regulation of cell cycle Source: UniProtKB
    13. negative regulation of cell death Source: Ensembl
    14. neuron development Source: Ensembl
    15. pentacyclic triterpenoid metabolic process Source: Ensembl
    16. positive regulation of apoptotic process Source: UniProtKB
    17. positive regulation of cell death Source: UniProtKB
    18. positive regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
    19. positive regulation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway Source: ParkinsonsUK-UCL
    20. positive regulation of extrinsic apoptotic signaling pathway in absence of ligand Source: UniProtKB
    21. protein autoprocessing Source: ParkinsonsUK-UCL
    22. proteolysis Source: UniProtKB
    23. regulation of multicellular organism growth Source: Ensembl
    24. response to herbicide Source: Ensembl

    Keywords - Molecular functioni

    Hydrolase, Protease, Serine protease

    Keywords - Biological processi

    Apoptosis

    Enzyme and pathway databases

    BRENDAi3.4.21.108. 2681.

    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
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 2

    Organism-specific databases

    HGNCiHGNC:14348. 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 caspase-8 truncated BID/tBID.

    GO - Cellular componenti

    1. CD40 receptor complex Source: BHF-UCL
    2. chromatin Source: ParkinsonsUK-UCL
    3. cytoplasmic side of plasma membrane Source: BHF-UCL
    4. cytoskeleton Source: ParkinsonsUK-UCL
    5. cytosol Source: ParkinsonsUK-UCL
    6. endoplasmic reticulum Source: UniProtKB
    7. endoplasmic reticulum membrane Source: UniProtKB
    8. membrane Source: ParkinsonsUK-UCL
    9. mitochondrial intermembrane space Source: MGI
    10. mitochondrial membrane Source: UniProtKB-SubCell
    11. mitochondrion Source: UniProtKB
    12. nucleus Source: UniProtKB

    Keywords - Cellular componenti

    Membrane, Mitochondrion

    Pathology & Biotechi

    Involvement in diseasei

    Parkinson disease 13 (PARK13) [MIM:610297]: A complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability, as well as by a clinically significant response to treatment with levodopa. The pathology involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti399 – 3991G → S in PARK13; reduced protease activity. 1 Publication
    Corresponds to variant rs72470545 [ dbSNP | Ensembl ].
    VAR_027350

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi134 – 1341A → M: Loss of interaction with XIAP. Loss of inhibition of XIAP activity. 1 Publication
    Mutagenesisi306 – 3061S → A: Loss of protease activity. 1 Publication

    Keywords - Diseasei

    Disease mutation, Neurodegeneration, Parkinson disease, Parkinsonism

    Organism-specific databases

    MIMi168600. phenotype.
    610297. phenotype.
    Orphaneti2828. Young adult-onset Parkinsonism.
    PharmGKBiPA33836.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transit peptidei1 – 3131MitochondrionAdd
    BLAST
    Propeptidei32 – 1331021 PublicationPRO_0000026945Add
    BLAST
    Chaini134 – 458325Serine protease HTRA2, mitochondrialPRO_0000026946Add
    BLAST

    Post-translational modificationi

    Autoproteolytically activated.

    Keywords - PTMi

    Zymogen

    Proteomic databases

    MaxQBiO43464.
    PaxDbiO43464.
    PRIDEiO43464.

    2D gel databases

    OGPiO43464.

    PTM databases

    PhosphoSiteiO43464.

    Miscellaneous databases

    PMAP-CutDBO43464.

    Expressioni

    Tissue specificityi

    Isoform 1 is ubiquitous. Isoform 2 is expressed predominantly in the kidney, colon and thyroid.

    Gene expression databases

    BgeeiO43464.
    CleanExiHS_HTRA2.
    GenevestigatoriO43464.

    Organism-specific databases

    HPAiCAB004004.
    HPA027366.

    Interactioni

    Subunit structurei

    Homotrimer. Interacts with MXI2. Interacts with THAP5 under apoptotic conditions. The mature protein, but not the precursor, binds to BIRC2/c-IAP1, BIRC3/c-IAP2 and XIAP/BIRC4. Interacts with BIRC6/bruce.4 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    BIRC7Q96CA52EBI-517086,EBI-517623
    CSN2P026665EBI-517086,EBI-5260183From a different organism.
    NDUFA13Q9P0J06EBI-517086,EBI-372742
    Ripk1Q608552EBI-517086,EBI-529119From a different organism.
    XIAPP9817018EBI-517086,EBI-517127

    Protein-protein interaction databases

    BioGridi118165. 47 interactions.
    IntActiO43464. 37 interactions.
    MINTiMINT-216075.
    STRINGi9606.ENSP00000258080.

    Structurei

    Secondary structure

    1
    458
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi143 – 1464
    Helixi149 – 1579
    Helixi158 – 1603
    Beta strandi161 – 17010
    Turni171 – 1744
    Beta strandi175 – 18814
    Turni189 – 1913
    Beta strandi192 – 1954
    Helixi197 – 2004
    Beta strandi204 – 2096
    Beta strandi215 – 22410
    Turni225 – 2284
    Beta strandi229 – 2335
    Helixi248 – 2503
    Beta strandi256 – 2594
    Beta strandi265 – 2684
    Beta strandi271 – 2755
    Beta strandi295 – 2995
    Turni303 – 3075
    Beta strandi308 – 3125
    Beta strandi317 – 32610
    Beta strandi329 – 3346
    Helixi335 – 3417
    Beta strandi364 – 3685
    Helixi371 – 3777
    Beta strandi391 – 3966
    Helixi401 – 4055
    Beta strandi412 – 4165
    Helixi424 – 4318
    Beta strandi435 – 4439
    Beta strandi446 – 4527

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1LCYX-ray2.00A134-458[»]
    2PZDX-ray2.75A/B359-458[»]
    DisProtiDP00315.
    ProteinModelPortaliO43464.
    SMRiO43464. Positions 139-458.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiO43464.

    Transmembrane

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

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini364 – 44582PDZPROSITE-ProRule annotationAdd
    BLAST

    Region

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

    Motif

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

    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.
    HOGENOMiHOG000223641.
    HOVERGENiHBG052044.
    InParanoidiO43464.
    KOiK08669.
    OMAiFKEECTE.
    OrthoDBiEOG7V1FR7.
    PhylomeDBiO43464.
    TreeFamiTF323480.

    Family and domain databases

    Gene3Di2.30.42.10. 1 hit.
    InterProiIPR001478. PDZ.
    IPR001254. Peptidase_S1.
    IPR001940. Peptidase_S1C.
    IPR009003. Trypsin-like_Pept_dom.
    [Graphical view]
    PfamiPF13180. PDZ_2. 1 hit.
    [Graphical view]
    PRINTSiPR00834. PROTEASES2C.
    SMARTiSM00228. PDZ. 1 hit.
    SM00020. Tryp_SPc. 1 hit.
    [Graphical view]
    SUPFAMiSSF50156. SSF50156. 1 hit.
    SSF50494. SSF50494. 1 hit.
    PROSITEiPS50106. PDZ. 1 hit.
    [Graphical view]

    Sequences (4)i

    Sequence statusi: Complete.

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

    This entry describes 4 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: O43464-1) [UniParc]FASTAAdd to Basket

    Also known as: 13B

    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.

    « Hide

    MAAPRAGRGA GWSLRAWRAL GGIRWGRRPR LTPDLRALLT SGTSDPRARV    50
    TYGTPSLWAR LSVGVTEPRA CLTSGTPGPR AQLTAVTPDT RTREASENSG 100
    TRSRAWLAVA LGAGGAVLLL LWGGGRGPPA VLAAVPSPPP ASPRSQYNFI 150
    ADVVEKTAPA VVYIEILDRH PFLGREVPIS NGSGFVVAAD GLIVTNAHVV 200
    ADRRRVRVRL LSGDTYEAVV TAVDPVADIA TLRIQTKEPL PTLPLGRSAD 250
    VRQGEFVVAM GSPFALQNTI TSGIVSSAQR PARDLGLPQT NVEYIQTDAA 300
    IDFGNSGGPL VNLDGEVIGV NTMKVTAGIS FAIPSDRLRE FLHRGEKKNS 350
    SSGISGSQRR YIGVMMLTLS PSILAELQLR EPSFPDVQHG VLIHKVILGS 400
    PAHRAGLRPG DVILAIGEQM VQNAEDVYEA VRTQSQLAVQ IRRGRETLTL 450
    YVTPEVTE 458
    Length:458
    Mass (Da):48,841
    Last modified:May 1, 2000 - v2
    Checksum:iCEA955A7D0DD8C0D
    GO
    Isoform 2 (identifier: O43464-2) [UniParc]FASTAAdd to Basket

    Also known as: D-Omi

    The sequence of this isoform differs from the canonical sequence as follows:
         238-302: Missing.
         372-403: Missing.

    Show »
    Length:361
    Mass (Da):38,493
    Checksum:iBD0824D4308140D7
    GO
    Isoform 3 (identifier: O43464-3) [UniParc]FASTAAdd to Basket

    Also known as: p7

    The sequence of this isoform differs from the canonical sequence as follows:
         313-313: L → LARELGAVSLQ
         372-403: Missing.

    Show »
    Length:436
    Mass (Da):46,382
    Checksum:iB48266A8EB7E4EE8
    GO
    Isoform 4 (identifier: O43464-4) [UniParc]FASTAAdd to Basket

    Also known as: p4

    The sequence of this isoform differs from the canonical sequence as follows:
         314-458: DGEVIGVNTM...TLYVTPEVTE → VSETSFLPRI...FGCPHPLLFV

    Show »
    Length:377
    Mass (Da):39,914
    Checksum:i14D0982E08A58FB2
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti72 – 721L → P.1 Publication
    Corresponds to variant rs150047108 [ dbSNP | Ensembl ].
    VAR_046134
    Natural varianti141 – 1411A → S Polymorphism; associated with a 2.15-fold increased risk of PD; reduced protease activity. 2 Publications
    Corresponds to variant rs72470544 [ dbSNP | Ensembl ].
    VAR_027349
    Natural varianti399 – 3991G → S in PARK13; reduced protease activity. 1 Publication
    Corresponds to variant rs72470545 [ dbSNP | Ensembl ].
    VAR_027350
    Natural varianti404 – 4041R → W Could be associated with an increased risk of developing PD. 1 Publication
    VAR_046135

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei238 – 30265Missing in isoform 2. 1 PublicationVSP_005359Add
    BLAST
    Alternative sequencei313 – 3131L → LARELGAVSLQ in isoform 3. 1 PublicationVSP_005360
    Alternative sequencei314 – 458145DGEVI…PEVTE → VSETSFLPRIPAPGQCGKGR FPLIQGCLVKFLSSSLLAIS QYPTRSPQHLLVLLFGCPHP LLFV in isoform 4. 1 PublicationVSP_005362Add
    BLAST
    Alternative sequencei372 – 40332Missing in isoform 2 and isoform 3. 2 PublicationsVSP_005361Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF020760 mRNA. Translation: AAB94569.2.
    AF141305 mRNA. Translation: AAF66596.1.
    AF141306 mRNA. Translation: AAF66597.1.
    AF141307 mRNA. Translation: AAF66598.1.
    AF184911 mRNA. Translation: AAG13126.1.
    AC006544 Genomic DNA. No translation available.
    BC000096 mRNA. Translation: AAH00096.1.
    CCDSiCCDS1951.1. [O43464-1]
    CCDS1952.1. [O43464-2]
    RefSeqiNP_037379.1. NM_013247.4. [O43464-1]
    NP_659540.1. NM_145074.2. [O43464-2]
    UniGeneiHs.469045.
    Hs.744841.

    Genome annotation databases

    EnsembliENST00000258080; ENSP00000258080; ENSG00000115317. [O43464-1]
    ENST00000352222; ENSP00000312893; ENSG00000115317. [O43464-2]
    ENST00000437202; ENSP00000399166; ENSG00000115317.
    GeneIDi27429.
    KEGGihsa:27429.
    UCSCiuc002smi.1. human. [O43464-1]
    uc002smj.1. human. [O43464-2]
    uc002smk.1. human. [O43464-3]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    Atlas of Genetics and Cytogenetics in Oncology and Haematology

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF020760 mRNA. Translation: AAB94569.2 .
    AF141305 mRNA. Translation: AAF66596.1 .
    AF141306 mRNA. Translation: AAF66597.1 .
    AF141307 mRNA. Translation: AAF66598.1 .
    AF184911 mRNA. Translation: AAG13126.1 .
    AC006544 Genomic DNA. No translation available.
    BC000096 mRNA. Translation: AAH00096.1 .
    CCDSi CCDS1951.1. [O43464-1 ]
    CCDS1952.1. [O43464-2 ]
    RefSeqi NP_037379.1. NM_013247.4. [O43464-1 ]
    NP_659540.1. NM_145074.2. [O43464-2 ]
    UniGenei Hs.469045.
    Hs.744841.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1LCY X-ray 2.00 A 134-458 [» ]
    2PZD X-ray 2.75 A/B 359-458 [» ]
    DisProti DP00315.
    ProteinModelPortali O43464.
    SMRi O43464. Positions 139-458.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 118165. 47 interactions.
    IntActi O43464. 37 interactions.
    MINTi MINT-216075.
    STRINGi 9606.ENSP00000258080.

    Protein family/group databases

    MEROPSi S01.278.

    PTM databases

    PhosphoSitei O43464.

    2D gel databases

    OGPi O43464.

    Proteomic databases

    MaxQBi O43464.
    PaxDbi O43464.
    PRIDEi O43464.

    Protocols and materials databases

    DNASUi 27429.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000258080 ; ENSP00000258080 ; ENSG00000115317 . [O43464-1 ]
    ENST00000352222 ; ENSP00000312893 ; ENSG00000115317 . [O43464-2 ]
    ENST00000437202 ; ENSP00000399166 ; ENSG00000115317 .
    GeneIDi 27429.
    KEGGi hsa:27429.
    UCSCi uc002smi.1. human. [O43464-1 ]
    uc002smj.1. human. [O43464-2 ]
    uc002smk.1. human. [O43464-3 ]

    Organism-specific databases

    CTDi 27429.
    GeneCardsi GC02P074757.
    GeneReviewsi HTRA2.
    HGNCi HGNC:14348. HTRA2.
    HPAi CAB004004.
    HPA027366.
    MIMi 168600. phenotype.
    606441. gene.
    610297. phenotype.
    neXtProti NX_O43464.
    Orphaneti 2828. Young adult-onset Parkinsonism.
    PharmGKBi PA33836.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0265.
    HOGENOMi HOG000223641.
    HOVERGENi HBG052044.
    InParanoidi O43464.
    KOi K08669.
    OMAi FKEECTE.
    OrthoDBi EOG7V1FR7.
    PhylomeDBi O43464.
    TreeFami TF323480.

    Enzyme and pathway databases

    BRENDAi 3.4.21.108. 2681.

    Miscellaneous databases

    ChiTaRSi HTRA2. human.
    EvolutionaryTracei O43464.
    GeneWikii HtrA_serine_peptidase_2.
    GenomeRNAii 27429.
    NextBioi 50463.
    PMAP-CutDB O43464.
    PROi O43464.
    SOURCEi Search...

    Gene expression databases

    Bgeei O43464.
    CleanExi HS_HTRA2.
    Genevestigatori O43464.

    Family and domain databases

    Gene3Di 2.30.42.10. 1 hit.
    InterProi IPR001478. PDZ.
    IPR001254. Peptidase_S1.
    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.
    SM00020. Tryp_SPc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF50156. SSF50156. 1 hit.
    SSF50494. SSF50494. 1 hit.
    PROSITEi PS50106. PDZ. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Characterization of a novel human serine protease that has extensive homology to bacterial heat shock endoprotease HtrA and is regulated by kidney ischemia."
      Faccio L., Fusco C., Chen A., Martinotti S., Bonventre J.V., Zervos A.S.
      J. Biol. Chem. 275:2581-2588(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), MUTAGENESIS OF SER-306.
    2. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 3 AND 4), CHARACTERIZATION.
      Tissue: Brain.
    3. "Tissue-specific splicing of Omi stress-regulated endoprotease leads to an inactive protease with a modified PDZ motif."
      Faccio L., Fusco C., Viel A., Zervos A.S.
      Genomics 68:343-347(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
      Tissue: Kidney.
    4. "Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
      Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H.
      , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
      Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
      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] (ISOFORM 1).
      Tissue: Brain.
    6. "A serine protease, HtrA2, is released from the mitochondria and interacts with XIAP, inducing cell death."
      Suzuki Y., Imai Y., Nakayama H., Takahashi K., Takio K., Takahashi R.
      Mol. Cell 8:613-621(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 134-458, INTERACTION WITH XIAP, MUTAGENESIS OF ALA-134.
    7. "Expression, purification, and functional analysis of the human serine protease HtrA2."
      Savopoulos J.W., Carter P.S., Turconi S., Pettman G.R., Karran E.H., Gray C.W., Ward R.V., Jenkins O., Creasy C.L.
      Protein Expr. Purif. 19:227-234(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: CHARACTERIZATION.
    8. "Dual role of BRUCE as an antiapoptotic IAP and a chimeric E2/E3 ubiquitin ligase."
      Bartke T., Pohl C., Pyrowolakis G., Jentsch S.
      Mol. Cell 14:801-811(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH BIRC6/BRUCE.
    9. "THAP5 is a human cardiac-specific inhibitor of cell cycle that is cleaved by the proapoptotic Omi/HtrA2 protease during cell death."
      Balakrishnan M.P., Cilenti L., Mashak Z., Popat P., Alnemri E.S., Zervos A.S.
      Am. J. Physiol. 297:H643-H653(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH THAP5.
    10. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    11. "Structural insights into the pro-apoptotic function of mitochondrial serine protease HtrA2/Omi."
      Li W., Srinivasula S.M., Chai J., Li P., Wu J.W., Zhang Z., Alnemri E.S., Shi Y.
      Nat. Struct. Biol. 9:436-441(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 134-458, SUBUNIT.
    12. Cited for: VARIANT PARK13 SER-399, VARIANT SER-141, CHARACTERIZATION OF VARIANTS SER-141 AND SER-399.
    13. "Genetic variability in the mitochondrial serine protease HTRA2 contributes to risk for Parkinson disease."
      Bogaerts V., Nuytemans K., Reumers J., Pals P., Engelborghs S., Pickut B., Corsmit E., Peeters K., Schymkowitz J., De Deyn P.P., Cras P., Rousseau F., Theuns J., Van Broeckhoven C.
      Hum. Mutat. 29:832-840(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS PRO-72; SER-141 AND TRP-404, ASSOCIATION WITH INCREASED RISK OF PARKINSON DISEASE.

    Entry informationi

    Entry nameiHTRA2_HUMAN
    AccessioniPrimary (citable) accession number: O43464
    Secondary accession number(s): Q9HBZ4, Q9P0Y3, Q9P0Y4
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: September 26, 2001
    Last sequence update: May 1, 2000
    Last modified: October 1, 2014
    This is version 161 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (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.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Human chromosome 2
      Human chromosome 2: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. Peptidase families
      Classification of peptidase families and list of entries
    7. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3