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Protein

Serine protease HTRA2, mitochondrial

Gene

Htra2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: 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 similarity1 Publication

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)DescriptionActionsGraphical viewLength
Active sitei198Charge relay systemBy similarity1
Active sitei228Charge relay systemBy similarity1
Active sitei306Charge relay systemBy similarity1

GO - Molecular functioni

  • identical protein binding Source: MGI
  • peptidase activity Source: ParkinsonsUK-UCL
  • serine-type endopeptidase activity Source: MGI
  • serine-type peptidase activity Source: MGI

GO - Biological processi

  • adult locomotory behavior Source: MGI
  • adult walking behavior Source: MGI
  • aging Source: Ensembl
  • cellular protein catabolic process Source: MGI
  • cellular response to growth factor stimulus Source: MGI
  • cellular response to heat Source: MGI
  • cellular response to interferon-beta Source: MGI
  • cellular response to oxidative stress Source: ParkinsonsUK-UCL
  • cellular response to retinoic acid Source: MGI
  • ceramide metabolic process Source: Ensembl
  • forebrain development Source: MGI
  • intrinsic apoptotic signaling pathway Source: MGI
  • intrinsic apoptotic signaling pathway in response to DNA damage Source: MGI
  • mitochondrion organization Source: MGI
  • negative regulation of cell death Source: Ensembl
  • negative regulation of mitophagy in response to mitochondrial depolarization Source: ParkinsonsUK-UCL
  • neuron development Source: MGI
  • pentacyclic triterpenoid metabolic process Source: Ensembl
  • positive regulation of apoptotic process Source: UniProtKB
  • positive regulation of cell death Source: MGI
  • positive regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: MGI
  • positive regulation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway Source: MGI
  • positive regulation of extrinsic apoptotic signaling pathway in absence of ligand Source: MGI
  • positive regulation of mitochondrion organization Source: MGI
  • positive regulation of protein targeting to mitochondrion Source: MGI
  • protein homotrimerization Source: MGI
  • proteolysis Source: ParkinsonsUK-UCL
  • regulation of multicellular organism growth Source: MGI
  • response to herbicide Source: Ensembl

Keywordsi

Molecular functionHydrolase, Protease, Serine protease
Biological processApoptosis

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 6

Organism-specific databases

MGIiMGI:1928676. Htra2.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transmembranei105 – 125HelicalSequence analysisAdd BLAST21

GO - Cellular componenti

  • CD40 receptor complex Source: BHF-UCL
  • chromatin Source: MGI
  • cytoplasmic side of plasma membrane Source: BHF-UCL
  • cytoskeleton Source: MGI
  • cytosol Source: MGI
  • membrane Source: MGI
  • mitochondrial intermembrane space Source: MGI
  • mitochondrial membrane Source: UniProtKB-SubCell
  • mitochondrion Source: ParkinsonsUK-UCL
  • nucleus Source: MGI
  • serine-type endopeptidase complex Source: MGI

Keywords - Cellular componenti

Membrane, Mitochondrion

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi134A → G: Loss of interaction with XIAP. 1 Publication1
Mutagenesisi137A → I: Stronger interaction with XIAP third BIR domain. 1 Publication1
Mutagenesisi306S → A: Loss of protease activity. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL3259508.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 31MitochondrionAdd BLAST31
PropeptideiPRO_000002694732 – 133Sequence analysisAdd BLAST102
ChainiPRO_0000026948134 – 458Serine protease HTRA2, mitochondrialAdd BLAST325

Post-translational modificationi

Autoproteolytically activated.By similarity

Keywords - PTMi

Zymogen

Proteomic databases

EPDiQ9JIY5.
MaxQBiQ9JIY5.
PaxDbiQ9JIY5.
PeptideAtlasiQ9JIY5.
PRIDEiQ9JIY5.

2D gel databases

REPRODUCTION-2DPAGEiQ9JIY5.

PTM databases

iPTMnetiQ9JIY5.
PhosphoSitePlusiQ9JIY5.

Expressioni

Gene expression databases

BgeeiENSMUSG00000068329.
CleanExiMM_HTRA2.
ExpressionAtlasiQ9JIY5. baseline and differential.
GenevisibleiQ9JIY5. MM.

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

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi211100. 8 interactors.
DIPiDIP-41272N.
IntActiQ9JIY5. 5 interactors.
MINTiMINT-219738.
STRINGi10090.ENSMUSP00000087073.

Structurei

3D structure databases

ProteinModelPortaliQ9JIY5.
SMRiQ9JIY5.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini364 – 446PDZPROSITE-ProRule annotationAdd BLAST83

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni166 – 342Serine proteaseAdd BLAST177

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi134 – 137IAP-binding motifBy similarity4

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

Keywords - Domaini

Transit peptide, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1320. Eukaryota.
COG0265. LUCA.
GeneTreeiENSGT00510000046315.
HOGENOMiHOG000223641.
HOVERGENiHBG052044.
InParanoidiQ9JIY5.
KOiK08669.
OMAiAHVVINK.
OrthoDBiEOG091G0LXR.
PhylomeDBiQ9JIY5.
TreeFamiTF323480.

Family and domain databases

InterProiView protein in InterPro
IPR001478. PDZ.
IPR009003. Peptidase_S1_PA.
IPR001940. Peptidase_S1C.
PfamiView protein in Pfam
PF13180. PDZ_2. 1 hit.
PRINTSiPR00834. PROTEASES2C.
SMARTiView protein in SMART
SM00228. PDZ. 1 hit.
SUPFAMiSSF50156. SSF50156. 1 hit.
SSF50494. SSF50494. 1 hit.
PROSITEiView protein in PROSITE
PS50106. PDZ. 1 hit.

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)DescriptionActionsGraphical viewLength
Sequence conflicti449T → I in AAF89534 (PubMed:10971580).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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.

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.

Entry informationi

Entry nameiHTRA2_MOUSE
AccessioniPrimary (citable) accession number: Q9JIY5
Secondary accession number(s): Q9R108
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 26, 2001
Last sequence update: March 27, 2002
Last modified: June 7, 2017
This is version 152 of the entry and version 2 of the sequence. See 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