HTRA2 (Drosophila melanogaster)
Description [+]
- Synonyms: HTRA2, OMI, SERINE PROTEASE HTRA2
- Species: Metazoa;Bilateria;Ecdysozoa;Arthropoda;Hexapoda; Drosophila melanogaster
- Short gene description: NA
- Family: other
- Process: apoptosis,
- Pathways:
- Criteria: manually curated
- Curator comment:
- Human ortholog(s): HTRA1 HTRA3 HTRA4 HTRA2
- WIKI: HTRA2-D_melanogaster
References [+]
- Drosophila Omi, a mitochondrial-localized IAP antagonist and proapoptotic serine protease.
- Challa M, Malladi S, Pellock BJ, Dresnek D, Varadarajan S, Yin YW, White K, Bratton SB
- Although essential in mammals, in flies the importance of mitochondrial outer membrane permeabilization for apoptosis remains highly controversial. Herein, we demonstrate that Drosophila Omi (dOmi), a fly homologue of the serine protease Omi/HtrA2, is a developmentally regulated mitochondrial intermembrane space protein that undergoes processive cleavage, in situ, to generate two distinct inhibitor of apoptosis (IAP) binding motifs. Depending upon the proapoptotic stimulus, mature dOmi is then differentially released into the cytosol, where it binds selectively to the baculovirus IAP repeat 2 (BIR2) domain in Drosophila IAP1 (DIAP1) and displaces the initiator caspase DRONC. This interaction alone, however, is insufficient to promote apoptosis, as dOmi fails to displace the effector caspase DrICE from the BIR1 domain in DIAP1. Rather, dOmi alleviates DIAP1 inhibition of all caspases by proteolytically degrading DIAP1 and induces apoptosis both in cultured cells and in the developing fly eye. In summary, we demonstrate for the first time in flies that mitochondrial permeabilization not only occurs during apoptosis but also results in the release of a bona fide proapoptotic protein. EMBO J. 2007 Jul 11;26(13):3144-56. Epub 2007 Jun 7.
- Evolution of mitochondrial cell death pathway: Proapoptotic role of HtrA2/Omi in Drosophila.
- Igaki T, Suzuki Y, Tokushige N, Aonuma H, Takahashi R, Miura M
- Despite the essential role of mitochondria in a variety of mammalian cell death processes, the involvement of mitochondrial pathway in Drosophila cell death has remained unclear. To address this, we cloned and characterized DmHtrA2, a Drosophila homolog of a mitochondrial serine protease HtrA2/Omi. We show that DmHtrA2 normally resides in mitochondria and is up-regulated by UV-irradiation. Upon receipt of apoptotic stimuli, DmHtrA2 is translocated to extramitochondrial compartment; however, unlike its mammalian counterpart, the extramitochondrial DmHtrA2 does not diffuse throughout the cytosol but stays near the mitochondria. RNAi-mediated knock-down of DmHtrA2 in larvae or adult flies results in a resistance to stress stimuli. DmHtrA2 specifically cleaves Drosophila inhibitor-of-apoptosis protein 1 (DIAP1), a cellular caspase inhibitor, and induces cell death both in vitro and in vivo as potent as other fly cell death proteins. Our observations suggest that DmHtrA2 promotes cell death through a cleavage of DIAP1 in the vicinity of mitochondria, which may represent a prototype of mitochondrial cell death pathway in evolution. Biochem Biophys Res Commun. 2007 May 18;356(4):993-7. Epub 2007 Mar 26.
- References from Human ortholog(s):
- A serine protease, HtrA2, is released from the mitochondria and interacts with XIAP, inducing cell death.
- Suzuki Y, Imai Y, Nakayama H, Takahashi K, Takio K, Takahashi R
- X chromosome-linked inhibitor of apoptosis (XIAP) is an endogenous inhibitor of caspase-3, -7, and -9. Smac/DIABLO, an inhibitor of XIAP, is released from mitochondria upon receiving apoptotic stimuli and binds to the BIR2 and BIR3 domains of XIAP, thereby inhibiting its caspase-inhibitory activity. Here we report that a serine protease called HtrA2/Omi is released from mitochondria and inhibits the function of XIAP by direct binding in a similar way to Smac. Moreover, when overexpressed extramitochondrially, HtrA2 induces atypical cell death, which is neither accompanied by a significant increase in caspase activity nor inhibited by caspase inhibitors, including XIAP. A catalytically inactive mutant of HtrA2, however, does not induce cell death. In short, HtrA2 is a Smac-like inhibitor of IAP activity with a serine protease-dependent cell death-inducing activity. Mol Cell. 2001 Sep;8(3):613-21.
Structure & Sequence [+]
Pfam domains:
(Pfam is a large collection of protein families.)
Source | Domain Name | Start | End |
---|---|---|---|
PFAM A | Trypsin | 130 | 302 |
Protein sequence [+]
HtrA2 | Drosophila melanogaster | 7227 | length:422
MALRGSHRLEVIFKRCIASPVLHSHAANRRSSQLAIKEGDPNSNGNSGQYQQNGEQKEKG
WRRLVRFFVPFSLGAVVSAAIIQREDLTPTIAASKMTGRRRDFNFIADVVAGCADSVVYI
EIKDTRHFDYFSGQPITASNGSGFIIEQNGLILTNAHVVINKPHTMVQVRLSDGRTFPAT
IEDVDQTSDLATLRIQVNNLSVMRLGKSSTLRSGEWVVALGSPLALSNTVTAGVISSTQR
ASQELGLRNRDINYLQTDAAITFGNSGGPLVNLDGEAIGVNSMKVTAGISFAIPIDYVKV
FLERAAEKRKKGSAYKTGYPVKRYMGITMLTLTPDILFELKSRSQNMPSNLTHGVLVWKV
IVGSPAHSGGLQPGDIVTHINKKEIKNSSDVYDALADNSKTLDIVILRGVKQMHVTITPE
DP
WRRLVRFFVPFSLGAVVSAAIIQREDLTPTIAASKMTGRRRDFNFIADVVAGCADSVVYI
EIKDTRHFDYFSGQPITASNGSGFIIEQNGLILTNAHVVINKPHTMVQVRLSDGRTFPAT
IEDVDQTSDLATLRIQVNNLSVMRLGKSSTLRSGEWVVALGSPLALSNTVTAGVISSTQR
ASQELGLRNRDINYLQTDAAITFGNSGGPLVNLDGEAIGVNSMKVTAGISFAIPIDYVKV
FLERAAEKRKKGSAYKTGYPVKRYMGITMLTLTPDILFELKSRSQNMPSNLTHGVLVWKV
IVGSPAHSGGLQPGDIVTHINKKEIKNSSDVYDALADNSKTLDIVILRGVKQMHVTITPE
DP
Structure links:
- Smartdomain prediction information: SM00228
Evolution [+]
View protein alignment and tree with Jalview:  
Explore tree at phylomeDB:   Click here.
Homologs list [+]
Name | Relationship | Species |
---|---|---|
A_aegypti_AAEL006373-PB | orthology | Aedes |
A_gambiae_AGAP000240-PA | orthology | Anopheles |
HTRA2 | orthology | Chicken |
HTRA3 | orthology | Chicken |
HTRA1 | orthology | Chicken |
HTRA4 | orthology | Chimpanzee |
HTRA1 | orthology | Chimpanzee |
XR_023548.1 | orthology | Chimpanzee |
HTRA3 | orthology | Chimpanzee |
C_intestinalis_ENSCINP00000020849 | orthology | Ciona |
HTRA2_BOVIN | orthology | Cow |
O97658_BOVIN | orthology | Cow |
IPI00705915.2 | orthology | Cow |
Q45FF7_CANFA | orthology | Dog |
HTRA1 | orthology | Dog |
HTRA3 | orthology | Dog |
HTRA4 | orthology | Dog |
HTRA3 | orthology | Fugu |
HTRA1 (1 of 2) | orthology | Fugu |
HTRA2 | orthology | Fugu |
HTRA1 (2 of 2) | orthology | Fugu |
HTRA2 | orthology | Gasterosteus |
G_aculeatus_ENSGACP00000024294 | orthology | Gasterosteus |
HTRA1 (1 of 2) | orthology | Gasterosteus |
HTRA3 | orthology | Gasterosteus |
HTRA1 (2 of 2) | orthology | Gasterosteus |
HTRA3 | orthology | Gorilla |
HTRA4 | orthology | Gorilla |
HTRA1 | orthology | Gorilla |
HTRA2 | orthology | Gorilla |
HTRA3 | orthology | Horse |
HTRA1 | orthology | Horse |
HTRA4 | orthology | Horse |
HTRA2 | orthology | Horse |
HTRA2 | orthology | Human |
HTRA1 | orthology | Human |
HTRA3 | orthology | Human |
HTRA4 | orthology | Human |
HTRA2 | orthology | Lyzard |
HTRA4 | orthology | Lyzard |
HTRA1 | orthology | Lyzard |
HTRA3 | orthology | Lyzard |
HTRA4 | orthology | Macaca |
HTRA3 | orthology | Macaca |
HTRA2 | orthology | Macaca |
HTRA1 | orthology | Macaca |
HTRA1 | orthology | Medaka |
HTRA3 | orthology | Medaka |
HTRA2 | orthology | Medaka |
HTRA4 | orthology | Monodelphis |
HTRA3 | orthology | Monodelphis |
HTRA2 | orthology | Monodelphis |
HTRA1 | orthology | Monodelphis |
M_musculus_ENSMUSP00000087073 | orthology | Mouse |
Htra3 | orthology | Mouse |
Htra1 | orthology | Mouse |
Htra4 | orthology | Mouse |
HTRA3 | orthology | Orangutan |
HTRA2 | orthology | Orangutan |
HTRA1 | orthology | Orangutan |
HTRA1 | orthology | Ornithorhynchus |
HTRA1 | orthology | Rabbit |
HTRA4 | orthology | Rabbit |
HTRA2 | orthology | Rabbit |
Htra3_predicted | orthology | Rat |
Htra1 | orthology | Rat |
NP_001100791.1 | orthology | Rat |
NP_001100069.1 | orthology | Rat |
HTRA1 (2 of 2) | orthology | Tetraodon |
HTRA1 (1 of 2) | orthology | Tetraodon |
HTRA2 | orthology | Tetraodon |
HTRA3 | orthology | Tetraodon |
HTRA1 | orthology | Xenopus |
HTRA4 | orthology | Xenopus |
NMA111 | orthology | Yeast |
HTRA2 | orthology | Zebra finch |
T_guttata_ENSTGUP00000010582 | orthology | Zebra finch |
T_guttata_ENSTGUP00000011678 | orthology | Zebra finch |
T_guttata_ENSTGUP00000015538 | orthology | Zebra finch |
D_rerio_ENSDARP00000090164 | orthology | Zebrafish |
HTRA2 (13 of 24) | orthology | Zebrafish |
NM_001089447.1 | orthology | Zebrafish |
zgc:91963 | orthology | Zebrafish |
LOC560031 | orthology | Zebrafish |
HTRA2 (18 of 24) | orthology | Zebrafish |
HTRA2 (14 of 24) | orthology | Zebrafish |
NP_001082916.1 | orthology | Zebrafish |
D_rerio_ENSDARP00000072673 | orthology | Zebrafish |
htra1 | orthology | Zebrafish |
HTRA2 (3 of 24) | orthology | Zebrafish |
HTRA2 (4 of 24) | orthology | Zebrafish |
HTRA2 (10 of 24) | orthology | Zebrafish |
XR_029734.1 | orthology | Zebrafish |
HTRA2 (12 of 24) | orthology | Zebrafish |
HTRA2 (9 of 24) | orthology | Zebrafish |
HTRA2 (17 of 24) | orthology | Zebrafish |
HTRA2 (22 of 24) | orthology | Zebrafish |
HTRA2 (23 of 24) | orthology | Zebrafish |
HTRA2 (6 of 24) | orthology | Zebrafish |
HTRA2 (21 of 24) | orthology | Zebrafish |
NP_001082916.1 | orthology | Zebrafish |
LOC100003255 | orthology | Zebrafish |
si:busm1-sl7.7 | orthology | Zebrafish |
HTRA3 | orthology | Zebrafish |
LOC565082 | orthology | Zebrafish |
HTRA2 (19 of 24) | orthology | Zebrafish |
A2BIG4_DANRE | orthology | Zebrafish |
XR_029000.1 | orthology | Zebrafish |
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Gene Ontology [+]
GO id | Name | Ontology type | Evidence |
---|---|---|---|
GO:0007155 | cell adhesion | biological_proccess | IEA |
GO:0005198 | structural molecule activity | mollecular_function | NAS |
GO:0005515 | protein binding | mollecular_function | IEA |
GO:0016020 | membrane | cell_component | IEA |
GO:0016600 | flotillin complex | cell_component | NAS |
Check GO Evidence Codes here
Information from other databases [+]
- Gene info from FyBase [?] FBgn0038233
- Ensembl genome browser [?] : FBgn0038233
- Expression info from Arrayexpress [?] : FBgn0038233
- Protein expression from Protein Atlas: [?] FBgn0038233
Click on [?] for more information.