HTRA2_DROPS
ID HTRA2_DROPS Reviewed; 427 AA.
AC Q297U2;
DT 01-SEP-2009, integrated into UniProtKB/Swiss-Prot.
DT 04-APR-2006, sequence version 1.
DT 03-AUG-2022, entry version 87.
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=GA21097;
OS Drosophila pseudoobscura pseudoobscura (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=46245;
RN [1] {ECO:0000312|EMBL:EAL28113.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=MV2-25 / Tucson 14011-0121.94;
RX PubMed=15632085; DOI=10.1101/gr.3059305;
RA Richards S., Liu Y., Bettencourt B.R., Hradecky P., Letovsky S.,
RA Nielsen R., Thornton K., Hubisz M.J., Chen R., Meisel R.P., Couronne O.,
RA Hua S., Smith M.A., Zhang P., Liu J., Bussemaker H.J., van Batenburg M.F.,
RA Howells S.L., Scherer S.E., Sodergren E., Matthews B.B., Crosby M.A.,
RA Schroeder A.J., Ortiz-Barrientos D., Rives C.M., Metzker M.L., Muzny D.M.,
RA Scott G., Steffen D., Wheeler D.A., Worley K.C., Havlak P., Durbin K.J.,
RA Egan A., Gill R., Hume J., Morgan M.B., Miner G., Hamilton C., Huang Y.,
RA Waldron L., Verduzco D., Clerc-Blankenburg K.P., Dubchak I., Noor M.A.F.,
RA Anderson W., White K.P., Clark A.G., Schaeffer S.W., Gelbart W.M.,
RA Weinstock G.M., Gibbs R.A.;
RT "Comparative genome sequencing of Drosophila pseudoobscura: chromosomal,
RT gene, and cis-element evolution.";
RL Genome Res. 15:1-18(2005).
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; CM000070; EAL28113.1; -; Genomic_DNA.
DR RefSeq; XP_001358970.1; XM_001358933.3.
DR AlphaFoldDB; Q297U2; -.
DR SMR; Q297U2; -.
DR STRING; 7237.FBpp0281879; -.
DR EnsemblMetazoa; FBtr0283441; FBpp0281879; FBgn0081085.
DR GeneID; 4801955; -.
DR KEGG; dpo:Dpse_GA21097; -.
DR eggNOG; KOG1320; Eukaryota.
DR HOGENOM; CLU_020120_6_0_1; -.
DR InParanoid; Q297U2; -.
DR OMA; DTRHFDY; -.
DR PhylomeDB; Q297U2; -.
DR Proteomes; UP000001819; Chromosome 2.
DR Bgee; FBgn0081085; 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..?
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT PROPEP ?..77
FT /evidence="ECO:0000255"
FT /id="PRO_0000382191"
FT CHAIN 78..427
FT /note="Serine protease HTRA2, mitochondrial"
FT /evidence="ECO:0000250|UniProtKB:Q9VFJ3"
FT /id="PRO_0000382192"
FT TRANSMEM 66..86
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 330..415
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 144..307
FT /note="Serine protease"
FT /evidence="ECO:0000255"
FT MOTIF 78..81
FT /note="IAP-binding"
FT /evidence="ECO:0000255"
FT ACT_SITE 162
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:O43464"
FT ACT_SITE 194
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:O43464"
FT ACT_SITE 271
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:Q9VFJ3"
SQ SEQUENCE 427 AA; 46423 MW; 3D49E33F237B48FD CRC64;
MALRCINNLE IFLRRCTAPT LHRCCVASSR TAHTASSSKG SGGDNSKDKE NNGQNKSGYR
SFGWRSAFQF CVPFSLGALV SAVLIERHRD ELTPTISARS LKGRRNEFNF IADVVAGCGD
SVVYIEIKDT RHFDYFSGQP ITASNGSGFV IEQNGLILTN AHVVINKPHT MVQVRLSDGR
TFPATIEDVD QTSDLATLRI QVSGLPVMKL GKSSTLRSGE WVVALGSPLA LSNTVTAGVI
SATQRASQEL GLRNRDINYL QTDAAITFGN SGGPLVNLDG EAIGVNSMKV TAGISFAIPI
DYVKVFLERA AERRKKGSAH KTGYPVKRYM GITMLTLTPD ILFELKSRSQ NMPNNLMHGV
LVWKVIVGSP AHSGGLQPGD IVTHINKKEI KNSSDVYDAL AEGRKDLEIV ILRGVKQMHV
KITPEDP
