HTRA2_DROSI
ID HTRA2_DROSI Reviewed; 422 AA.
AC B4QZU6;
DT 01-SEP-2009, integrated into UniProtKB/Swiss-Prot.
DT 23-SEP-2008, sequence version 1.
DT 03-AUG-2022, entry version 67.
DE RecName: Full=Serine protease HTRA2, mitochondrial {ECO:0000250|UniProtKB:Q9VFJ3};
DE EC=3.4.21.108;
DE AltName: Full=High temperature requirement protein A2 {ECO:0000250|UniProtKB:Q9VFJ3};
DE Flags: Precursor;
GN Name=HtrA2 {ECO:0000250|UniProtKB:Q9VFJ3}; ORFNames=GD20417;
OS Drosophila simulans (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7240;
RN [1] {ECO:0000312|EMBL:EDX12944.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=17994087; DOI=10.1038/nature06341;
RG Drosophila 12 genomes consortium;
RT "Evolution of genes and genomes on the Drosophila phylogeny.";
RL Nature 450:203-218(2007).
CC -!- FUNCTION: Serine protease that shows proteolytic activity against a
CC non-specific substrate beta-casein. Promotes or induces cell death
CC either by direct binding to and inhibition of BIRC proteins (also
CC called inhibitor of apoptosis proteins, IAPs), leading to an increase
CC in caspase activity, or by a BIRC inhibition-independent, caspase-
CC independent and serine protease activity-dependent mechanism. Can
CC antagonize antiapoptotic activity of th by directly inducing the
CC degradation of th (By similarity). {ECO:0000250|UniProtKB:Q9VFJ3}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Cleavage of non-polar aliphatic amino-acids at the P1
CC position, with a preference for Val, Ile and Met. At the P2 and P3
CC positions, Arg is selected most strongly with a secondary preference
CC for other hydrophilic residues.; EC=3.4.21.108;
CC -!- SUBUNIT: Interacts with th/DIAP1 (via BIR 2 domain).
CC {ECO:0000250|UniProtKB:Q9VFJ3}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion intermembrane space
CC {ECO:0000250|UniProtKB:Q9VFJ3}; Single-pass membrane protein
CC {ECO:0000255}. Mitochondrion membrane {ECO:0000250|UniProtKB:Q9VFJ3};
CC Single-pass membrane protein {ECO:0000255}. Note=Predominantly present
CC in the intermembrane space. Released into the cytosol following
CC apoptotic stimuli, such as UV treatment. The extramitochondrial protein
CC does not diffuse throughout the cytosol but stays near the
CC mitochondria. {ECO:0000250|UniProtKB:Q9VFJ3}.
CC -!- SIMILARITY: Belongs to the peptidase S1C family. {ECO:0000255}.
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DR EMBL; CM000364; EDX12944.1; -; Genomic_DNA.
DR RefSeq; XP_002103441.1; XM_002103405.2.
DR AlphaFoldDB; B4QZU6; -.
DR SMR; B4QZU6; -.
DR STRING; 7240.B4QZU6; -.
DR EnsemblMetazoa; FBtr0220327; FBpp0218819; FBgn0191889.
DR GeneID; 6728089; -.
DR HOGENOM; CLU_020120_6_0_1; -.
DR OMA; DTRHFDY; -.
DR PhylomeDB; B4QZU6; -.
DR Proteomes; UP000000304; Chromosome 3r.
DR Bgee; FBgn0191889; Expressed in male reproductive system and 3 other tissues.
DR GO; GO:0005829; C:cytosol; IEA:EnsemblMetazoa.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005758; C:mitochondrial intermembrane space; IEA:UniProtKB-SubCell.
DR GO; GO:0031966; C:mitochondrial membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016006; C:Nebenkern; IEA:EnsemblMetazoa.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IEA:EnsemblMetazoa.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0035234; P:ectopic germ cell programmed cell death; IEA:EnsemblMetazoa.
DR GO; GO:0007005; P:mitochondrion organization; IEA:EnsemblMetazoa.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IEA:EnsemblMetazoa.
DR GO; GO:2001056; P:positive regulation of cysteine-type endopeptidase activity; IEA:EnsemblMetazoa.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR GO; GO:0007283; P:spermatogenesis; IEA:EnsemblMetazoa.
DR Gene3D; 2.30.42.10; -; 1.
DR InterPro; IPR001478; PDZ.
DR InterPro; IPR041489; PDZ_6.
DR InterPro; IPR036034; PDZ_sf.
DR InterPro; IPR009003; Peptidase_S1_PA.
DR InterPro; IPR001940; Peptidase_S1C.
DR Pfam; PF17820; PDZ_6; 1.
DR PRINTS; PR00834; PROTEASES2C.
DR SMART; SM00228; PDZ; 1.
DR SUPFAM; SSF50156; SSF50156; 1.
DR SUPFAM; SSF50494; SSF50494; 1.
DR PROSITE; PS50106; PDZ; 1.
PE 3: Inferred from homology;
KW Apoptosis; Hydrolase; Membrane; Mitochondrion; Protease;
KW Reference proteome; Serine protease; Transit peptide; Transmembrane;
KW Transmembrane helix; Zymogen.
FT TRANSIT 1..17
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT PROPEP 18..74
FT /evidence="ECO:0000255"
FT /id="PRO_0000382195"
FT CHAIN 75..422
FT /note="Serine protease HTRA2, mitochondrial"
FT /evidence="ECO:0000250|UniProtKB:Q9VFJ3"
FT /id="PRO_0000382196"
FT TRANSMEM 64..82
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 325..410
FT /note="PDZ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT REGION 33..55
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 139..302
FT /note="Serine protease"
FT /evidence="ECO:0000255"
FT MOTIF 75..78
FT /note="IAP-binding"
FT /evidence="ECO:0000255"
FT MOTIF 94..97
FT /note="IAP-binding"
FT /evidence="ECO:0000255"
FT COMPBIAS 33..54
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 157
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:O43464"
FT ACT_SITE 189
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:O43464"
FT ACT_SITE 266
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:Q9VFJ3"
SQ SEQUENCE 422 AA; 46005 MW; C42FBBB27F980241 CRC64;
MALRGCHRLE VIFKRCIASP VLHSQAGNRR SSQLAIKGVD PNSNGNSGQY QQNGEHKEKG
WRRLVRFFVP FSLGAAVSAA IIQREDFTPT IAASKMTGRR RDFNFIADVV AGCADSVVYI
EIKDTRHFDY FSGQPITASN GSGFIIEQNG LILTNAHVVI NKPHTMVQVR LSDGRTFPAT
IEDVDQTSDL ATLRIQVNNL SVMRLGKSST LRSGEWVVAL GSPLALSNTV TAGVISSTQR
ASQELGLRNR DINYLQTDAA ITFGNSGGPL VNLDGEAIGV NSMKVTAGIS FAIPIDYVKV
FLERAAEKRK KGSAYKTGYP VKRYMGITML TLTPDILFEL KSRSQNMPNN LTHGVLVWKV
IVGSPAHSGG LQPGDIVTHI NKKEIKNSSD VYDALADNSK TLDIVILRGV KQMHVTITPE
DP