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Q9JIY5

- HTRA2_MOUSE

UniProt

Q9JIY5 - HTRA2_MOUSE

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Protein

Serine protease HTRA2, mitochondrial

Gene

Htra2

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

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. 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. intrinsic apoptotic signaling pathway in response to DNA damage Source: Ensembl
  9. mitochondrion organization Source: MGI
  10. negative regulation of cell death Source: Ensembl
  11. neuron development Source: MGI
  12. pentacyclic triterpenoid metabolic process Source: Ensembl
  13. positive regulation of apoptotic process Source: UniProtKB
  14. positive regulation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway Source: Ensembl
  15. positive regulation of extrinsic apoptotic signaling pathway in absence of ligand Source: Ensembl
  16. regulation of multicellular organism growth Source: MGI
  17. response to herbicide Source: Ensembl
Complete GO annotation...

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. mitochondrion Source: ParkinsonsUK-UCL
  6. nucleus Source: Ensembl
Complete GO annotation...

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

BgeeiQ9JIY5.
CleanExiMM_HTRA2.
ExpressionAtlasiQ9JIY5. baseline and differential.
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 S1C 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

« Hide

        10         20         30         40         50
MAALKAGRGA NWSLRAWRAL GGIFWRKPPL LAPDLRALLT SGTPDSQIWM
60 70 80 90 100
TYGTPSLPAQ VPEGFLASRA DLTSRTPDLW ARLNVGTSGS SDQEARRSPG
110 120 130 140 150
SRRREWLAVA VGAGGAVVLL LWGWGRGLST VLAAVPAPPP TSPRSQYNFI
160 170 180 190 200
ADVVEKTAPA VVYIEILDRH PFSGREVPIS NGSGFVVASD GLIVTNAHVV
210 220 230 240 250
ADRRRVRVRL PSGDTYEAMV TAVDPVADIA TLRIQTKEPL PTLPLGRSAD
260 270 280 290 300
VRQGEFVVAM GSPFALQNTI TSGIVSSAQR PARDLGLPQN NVEYIQTDAA
310 320 330 340 350
IDFGNSGGPL VNLDGEVIGV NTMKVTAGIS FAIPSDRLRE FLHRGEKKNS
360 370 380 390 400
WFGTSGSQRR YIGVMMLTLT PSILIELQLR EPSFPDVQHG VLIHKVILGS
410 420 430 440 450
PAHRAGLRPG DVILAIGEKL AQNAEDVYEA VRTQSQLAVR IRRGSETLTL

YVTPEVTE
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

Bgeei Q9JIY5.
CleanExi MM_HTRA2.
ExpressionAtlasi Q9JIY5. baseline and differential.
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 29, 2014
This is version 131 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