HTRA2 (Homo sapiens)
Description [+]
- Synonyms: HTRA2, OMI, PARK13
- Species: Metazoa;Bilateria;Deuterostoma;Chordata;Vertebrata;Mammalia;Primates;Hominidae; Homo sapiens
- Short gene description: Serine protease HTRA2, mitochondrial Precursor (EC 3.4.21.108)(High temperature requirement protein A2)(HtrA2)(Omi stress-regulated endoprotease)(Serine proteinase OMI)(Serine protease 25) [Source:UniProtKB/Swiss-Prot;Acc:O43464]
- Family: other
- Process: cell death (other),
- Pathways:
- Criteria: manually curated
- Curator comment:
- Mouse ortholog(s):
- WIKI: HTRA2-H_sapiens
References [+]
- 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 | 166 | 342 |
Protein sequence [+]
HTRA2 | Homo sapiens | 9606 | length:458
MAAPRAGRGAGWSLRAWRALGGIRWGRRPRLTPDLRALLTSGTSDPRARVTYGTPSLWAR
LSVGVTEPRACLTSGTPGPRAQLTAVTPDTRTREASENSGTRSRAWLAVALGAGGAVLLL
LWGGGRGPPAVLAAVPSPPPASPRSQYNFIADVVEKTAPAVVYIEILDRHPFLGREVPIS
NGSGFVVAADGLIVTNAHVVADRRRVRVRLLSGDTYEAVVTAVDPVADIATLRIQTKEPL
PTLPLGRSADVRQGEFVVAMGSPFALQNTITSGIVSSAQRPARDLGLPQTNVEYIQTDAA
IDFGNSGGPLVNLDGEVIGVNTMKVTAGISFAIPSDRLREFLHRGEKKNSSSGISGSQRR
YIGVMMLTLSPSILAELQLREPSFPDVQHGVLIHKVILGSPAHRAGLRPGDVILAIGEQM
VQNAEDVYEAVRTQSQLAVQIRRGRETLTLYVTPEVTE
LSVGVTEPRACLTSGTPGPRAQLTAVTPDTRTREASENSGTRSRAWLAVALGAGGAVLLL
LWGGGRGPPAVLAAVPSPPPASPRSQYNFIADVVEKTAPAVVYIEILDRHPFLGREVPIS
NGSGFVVAADGLIVTNAHVVADRRRVRVRLLSGDTYEAVVTAVDPVADIATLRIQTKEPL
PTLPLGRSADVRQGEFVVAMGSPFALQNTITSGIVSSAQRPARDLGLPQTNVEYIQTDAA
IDFGNSGGPLVNLDGEVIGVNTMKVTAGISFAIPSDRLREFLHRGEKKNSSSGISGSQRR
YIGVMMLTLSPSILAELQLREPSFPDVQHGVLIHKVILGSPAHRAGLRPGDVILAIGEQM
VQNAEDVYEAVRTQSQLAVQIRRGRETLTLYVTPEVTE
Structure links:
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 |
| XR_023548.1 | orthology | Chimpanzee |
| HTRA2_BOVIN | orthology | Cow |
| Q45FF7_CANFA | orthology | Dog |
| HtrA2 | orthology | Fly |
| HTRA2 | orthology | Gorilla |
| HTRA2 | orthology | Horse |
| HTRA2 | orthology | Lyzard |
| HTRA2 | orthology | Macaca |
| HTRA2 | orthology | Monodelphis |
| M_musculus_ENSMUSP00000087073 | orthology | Mouse |
| HTRA2 | orthology | Orangutan |
| HTRA2 | orthology | Rabbit |
| NP_001100069.1 | orthology | Rat |
| HTRA2 | orthology | Zebra finch |
| HTRA1 | paralogy | Chicken |
| HTRA3 | paralogy | Chicken |
| HTRA4 | paralogy | Chimpanzee |
| HTRA1 | paralogy | Chimpanzee |
| HTRA3 | paralogy | Chimpanzee |
| C_intestinalis_ENSCINP00000023237 | paralogy | Ciona |
| C_intestinalis_ENSCINP00000020849 | paralogy | Ciona |
| IPI00705915.2 | paralogy | Cow |
| O97658_BOVIN | paralogy | Cow |
| HTRA1 | paralogy | Dog |
| HTRA3 | paralogy | Dog |
| HTRA4 | paralogy | Dog |
| HTRA1 (1 of 2) | paralogy | Fugu |
| HTRA1 (2 of 2) | paralogy | Fugu |
| HTRA2 | paralogy | Fugu |
| HTRA3 | paralogy | Fugu |
| HTRA3 | paralogy | Gasterosteus |
| G_aculeatus_ENSGACP00000024294 | paralogy | Gasterosteus |
| HTRA1 (2 of 2) | paralogy | Gasterosteus |
| HTRA2 | paralogy | Gasterosteus |
| HTRA1 (1 of 2) | paralogy | Gasterosteus |
| HTRA1 | paralogy | Gorilla |
| HTRA3 | paralogy | Gorilla |
| HTRA4 | paralogy | Gorilla |
| HTRA3 | paralogy | Horse |
| HTRA1 | paralogy | Horse |
| HTRA4 | paralogy | Horse |
| HTRA3 | paralogy | Human |
| HTRA4 | paralogy | Human |
| HTRA1 | paralogy | Human |
| HTRA1 | paralogy | Lyzard |
| HTRA4 | paralogy | Lyzard |
| HTRA3 | paralogy | Lyzard |
| HTRA3 | paralogy | Macaca |
| HTRA4 | paralogy | Macaca |
| HTRA1 | paralogy | Macaca |
| HTRA1 | paralogy | Medaka |
| HTRA3 | paralogy | Medaka |
| HTRA2 | paralogy | Medaka |
| HTRA1 | paralogy | Monodelphis |
| HTRA4 | paralogy | Monodelphis |
| HTRA3 | paralogy | Monodelphis |
| Htra1 | paralogy | Mouse |
| Htra3 | paralogy | Mouse |
| Htra4 | paralogy | Mouse |
| HTRA3 | paralogy | Orangutan |
| HTRA1 | paralogy | Orangutan |
| HTRA1 | paralogy | Ornithorhynchus |
| HTRA1 | paralogy | Rabbit |
| HTRA4 | paralogy | Rabbit |
| Htra1 | paralogy | Rat |
| Htra3_predicted | paralogy | Rat |
| NP_001100791.1 | paralogy | Rat |
| HTRA1 (2 of 2) | paralogy | Tetraodon |
| HTRA1 (1 of 2) | paralogy | Tetraodon |
| HTRA2 | paralogy | Tetraodon |
| HTRA3 | paralogy | Tetraodon |
| HTRA1 | paralogy | Xenopus |
| HTRA4 | paralogy | Xenopus |
| NMA111 | paralogy | Yeast |
| T_guttata_ENSTGUP00000011678 | paralogy | Zebra finch |
| T_guttata_ENSTGUP00000010582 | paralogy | Zebra finch |
| T_guttata_ENSTGUP00000015538 | paralogy | Zebra finch |
| LOC100003255 | paralogy | Zebrafish |
| XR_029000.1 | paralogy | Zebrafish |
| LOC560031 | paralogy | Zebrafish |
| HTRA3 | paralogy | Zebrafish |
| HTRA2 (6 of 24) | paralogy | Zebrafish |
| HTRA2 (19 of 24) | paralogy | Zebrafish |
| A2BIG4_DANRE | paralogy | Zebrafish |
| D_rerio_ENSDARP00000072673 | paralogy | Zebrafish |
| si:busm1-sl7.7 | paralogy | Zebrafish |
| NM_001089447.1 | paralogy | Zebrafish |
| HTRA2 (4 of 24) | paralogy | Zebrafish |
| zgc:91963 | paralogy | Zebrafish |
| HTRA2 (18 of 24) | paralogy | Zebrafish |
| HTRA2 (14 of 24) | paralogy | Zebrafish |
| HTRA2 (12 of 24) | paralogy | Zebrafish |
| HTRA2 (13 of 24) | paralogy | Zebrafish |
| HTRA2 (17 of 24) | paralogy | Zebrafish |
| NP_001082916.1 | paralogy | Zebrafish |
| htra1 | paralogy | Zebrafish |
| HTRA2 (23 of 24) | paralogy | Zebrafish |
| HTRA2 (3 of 24) | paralogy | Zebrafish |
| HTRA2 (10 of 24) | paralogy | Zebrafish |
| NP_001082916.1 | paralogy | Zebrafish |
| XR_029734.1 | paralogy | Zebrafish |
| LOC565082 | paralogy | Zebrafish |
| HTRA2 (9 of 24) | paralogy | Zebrafish |
| HTRA2 (21 of 24) | paralogy | Zebrafish |
| HTRA2 (22 of 24) | paralogy | Zebrafish |
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Gene Ontology [+]
| GO id | Name | Ontology type | Evidence |
|---|---|---|---|
| GO:0007628 | adult walking behavior | biological_proccess | IEA |
| GO:0030900 | forebrain development | biological_proccess | IEA |
| GO:0040014 | regulation of multicellular organism growth | biological_proccess | IEA |
| GO:0007005 | mitochondrion organization | biological_proccess | IEA |
| GO:0048666 | neuron development | biological_proccess | IEA |
| GO:0008629 | induction of apoptosis by intracellular signals | biological_proccess | IEA |
| GO:0006915 | apoptosis | biological_proccess | IEA |
| GO:0006950 | response to stress | biological_proccess | TAS |
| GO:0006508 | proteolysis | biological_proccess | TAS |
| GO:0008344 | adult locomotory behavior | biological_proccess | IEA |
| GO:0006508 | proteolysis | biological_proccess | IEA |
| GO:0008233 | peptidase activity | mollecular_function | IEA |
| GO:0051082 | unfolded protein binding | mollecular_function | NAS |
| GO:0004252 | serine-type endopeptidase activity | mollecular_function | TAS |
| GO:0005515 | protein binding | mollecular_function | IEA |
| GO:0008236 | serine-type peptidase activity | mollecular_function | IEA |
| GO:0003824 | catalytic activity | mollecular_function | IEA |
| GO:0004252 | serine-type endopeptidase activity | mollecular_function | IEA |
| GO:0005758 | mitochondrial intermembrane space | cell_component | IDA |
| GO:0005739 | mitochondrion | cell_component | IEA |
| GO:0016020 | membrane | cell_component | IEA |
| GO:0005789 | endoplasmic reticulum membrane | cell_component | TAS |
| GO:0005634 | nucleus | cell_component | TAS |
| GO:0005783 | endoplasmic reticulum | cell_component | NAS |
| GO:0016021 | integral to membrane | cell_component | IEA |
Check GO Evidence Codes here
Curated Isoforms [+]
Info from The Vertebrate Genome Annotation (VEGA) database.
(*) Canonical transcript and translation forms.
Information from other databases [+]
- Gene info from HGNC [?] :14348
- Gene related info from GeneCards [?] : HTRA2
- Ensembl genome browser [?] : ENSG00000115317
- Expression info from Arrayexpress [?] : ENSG00000115317
- Protein expression from Protein Atlas: [?] ENSG00000115317
- Community gene edition from Wikigenes: [?] 27429
Click on [?] for more information.
