HTRA2_BOVIN
ID HTRA2_BOVIN Reviewed; 458 AA.
AC A0JNK3;
DT 15-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 12-DEC-2006, sequence version 1.
DT 03-AUG-2022, entry version 103.
DE RecName: Full=Serine protease HTRA2, mitochondrial;
DE EC=3.4.21.108;
DE Flags: Precursor;
GN Name=HTRA2;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Basal ganglia;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases.
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. Cleaves
CC THAP5 and promotes its degradation during apoptosis (By similarity).
CC {ECO:0000250}.
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: Homotrimer. Interacts with MXI2. Interacts with THAP5 under
CC apoptotic conditions (By similarity). The mature protein, but not the
CC precursor, binds to BIRC2/c-IAP1, BIRC3/c-IAP2 and XIAP/BIRC4 (By
CC similarity). Interacts with BIRC6/bruce (By similarity). Interacts with
CC AREL1 (via HECT domain); in the cytoplasm following induction of
CC apoptosis (By similarity). {ECO:0000250, ECO:0000250|UniProtKB:O43464}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion intermembrane space. Mitochondrion
CC membrane {ECO:0000305}; Single-pass membrane protein {ECO:0000305}.
CC Note=Predominantly present in the intermembrane space. Released into
CC the cytosol following apoptotic stimuli, such as UV treatment, and
CC stimulation of mitochondria with caspase-8 truncated BID/tBID (By
CC similarity). {ECO:0000250}.
CC -!- DOMAIN: The mature N-terminus is involved in the interaction with XIAP.
CC {ECO:0000250}.
CC -!- DOMAIN: The PDZ domain mediates interaction with MXI2. {ECO:0000250}.
CC -!- PTM: Autoproteolytically activated. {ECO:0000250|UniProtKB:O43464}.
CC -!- SIMILARITY: Belongs to the peptidase S1C family. {ECO:0000305}.
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DR EMBL; BC126737; AAI26738.1; -; mRNA.
DR RefSeq; NP_001071424.1; NM_001077956.1.
DR AlphaFoldDB; A0JNK3; -.
DR SMR; A0JNK3; -.
DR STRING; 9913.ENSBTAP00000026804; -.
DR MEROPS; S01.278; -.
DR PaxDb; A0JNK3; -.
DR PRIDE; A0JNK3; -.
DR Ensembl; ENSBTAT00000026804; ENSBTAP00000026804; ENSBTAG00000020124.
DR GeneID; 523039; -.
DR KEGG; bta:523039; -.
DR CTD; 27429; -.
DR VEuPathDB; HostDB:ENSBTAG00000020124; -.
DR VGNC; VGNC:30005; HTRA2.
DR eggNOG; KOG1320; Eukaryota.
DR GeneTree; ENSGT00940000155108; -.
DR HOGENOM; CLU_020120_6_0_1; -.
DR InParanoid; A0JNK3; -.
DR OMA; WRYATEQ; -.
DR OrthoDB; 630723at2759; -.
DR TreeFam; TF323480; -.
DR Proteomes; UP000009136; Chromosome 11.
DR Bgee; ENSBTAG00000020124; Expressed in retina and 105 other tissues.
DR GO; GO:0035631; C:CD40 receptor complex; IEA:Ensembl.
DR GO; GO:0000785; C:chromatin; IEA:Ensembl.
DR GO; GO:0009898; C:cytoplasmic side of plasma membrane; IEA:Ensembl.
DR GO; GO:0005856; C:cytoskeleton; IEA:Ensembl.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005758; C:mitochondrial intermembrane space; IEA:UniProtKB-SubCell.
DR GO; GO:0031966; C:mitochondrial membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IEA:Ensembl.
DR GO; GO:1905370; C:serine-type endopeptidase complex; IEA:Ensembl.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IBA:GO_Central.
DR GO; GO:0007628; P:adult walking behavior; IEA:Ensembl.
DR GO; GO:0071363; P:cellular response to growth factor stimulus; IEA:Ensembl.
DR GO; GO:0034605; P:cellular response to heat; IEA:Ensembl.
DR GO; GO:0035458; P:cellular response to interferon-beta; IEA:Ensembl.
DR GO; GO:0034599; P:cellular response to oxidative stress; IEA:Ensembl.
DR GO; GO:0071300; P:cellular response to retinoic acid; IEA:Ensembl.
DR GO; GO:0030900; P:forebrain development; IEA:Ensembl.
DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IEA:Ensembl.
DR GO; GO:0007005; P:mitochondrion organization; IEA:Ensembl.
DR GO; GO:1904924; P:negative regulation of mitophagy in response to mitochondrial depolarization; IEA:Ensembl.
DR GO; GO:0048666; P:neuron development; IEA:Ensembl.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IBA:GO_Central.
DR GO; GO:2001269; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway; IEA:Ensembl.
DR GO; GO:2001241; P:positive regulation of extrinsic apoptotic signaling pathway in absence of ligand; IEA:Ensembl.
DR GO; GO:0010822; P:positive regulation of mitochondrion organization; IEA:Ensembl.
DR GO; GO:0012501; P:programmed cell death; IBA:GO_Central.
DR GO; GO:0030163; P:protein catabolic process; IEA:Ensembl.
DR GO; GO:0006508; P:proteolysis; IBA:GO_Central.
DR GO; GO:0040014; P:regulation of multicellular organism growth; IEA:Ensembl.
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.
PE 2: Evidence at transcript level;
KW Apoptosis; Hydrolase; Membrane; Mitochondrion; Protease;
KW Reference proteome; Serine protease; Transit peptide; Transmembrane;
KW Transmembrane helix; Zymogen.
FT TRANSIT 1..31
FT /note="Mitochondrion"
FT /evidence="ECO:0000250"
FT PROPEP 32..133
FT /evidence="ECO:0000250"
FT /id="PRO_0000287725"
FT CHAIN 134..458
FT /note="Serine protease HTRA2, mitochondrial"
FT /id="PRO_0000287726"
FT TRANSMEM 105..125
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 364..445
FT /note="PDZ"
FT REGION 166..342
FT /note="Serine protease"
FT MOTIF 134..137
FT /note="IAP-binding motif"
FT ACT_SITE 198
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:O43464"
FT ACT_SITE 228
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:O43464"
FT ACT_SITE 306
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:O43464"
SQ SEQUENCE 458 AA; 49163 MW; 9BFC45475D18D334 CRC64;
MAALRAGRGA GWSLRGWRAL WGGRWGKGPL LTPDLRALLT SGTPDPRTRV TYGTPSFRAR
LSVGVPEPRT CLRSRTSDLR ARLIAGTPDP RTPEDSGTPG TRLRVWLAVA LGAGGAVLLL
FWGGGRGPPA VLASVLGSPP TSPRSQYNFI ADVVEKTAPA VVYIEILGRH PFSGREVPIS
NGSGFVVAAD GLIVTNAHVV ADRRRVRVRL PSGDTYEAVV TAVDPVADIA TLRIQTKEPL
PTLPLGRSAD VRQGEFVVAM GSPFALQNTI TSGIVSSAQR PAKDLGLPQT NVEYIQTDAA
IDFGNSGGPL VNLDGEVIGV NTMKVTSGIS FAIPSDRLRE FLHRGEKKNS WFGISGSQRR
YIGVMMLTLT PSILAELQLR EPSFPDVQHG VLIHKVILDS PAHRAGLRPG DVILAIGEQL
VQNAEDIYEA VRTQSQLAVR IRRGQETLTL YVTPEVTE
