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Protein Page:
HTRA2 (human)
p Phosphorylation
a Acetylation
m Methylation
m1 Mono-methylation
m2 Di-methylation
m3 Tri-methylation
u Ubiquitination
s Sumoylation
n Neddylation
gl O-GlcNAc
ga O-GalNAc
h Palmitoylation
ad Adenylylation
sn S-Nitrosylation
ca Caspase cleavage

Overview
HTRA2 a serine proteinase that normally resides in mitochondrial membranes. It exists in two populations in mitochondria: as an unprocessed form probably attached to the inner mitochondrial membrane through a N-terminal transmembrane domain, and as a processed form containing a reaper motif at its N-terminus. Following apoptotic stimuli it is autoproteolytically activated and released into the cytosol, where it promotes programmed cell death in caspase-dependent and -independent manners. The amino-terminal reaper motif binds to the IAP (inhibitor of apoptosis) proteins cIAP1, cIAP2, and and XIAP, disrupting IAP-caspase complexes in a manner similar to Smac/DIABLO. Phosphorylation by the protein kinase Akt attenuates its serine protease and pro-apoptotic activities. The PDZ domain mediates interaction with Mxi2, an alternatively spliced form of the p38 stress-activated kinase. In contrast to its pro-apoptotic effects, targeted deletion in mice indicates that it is involved in protection against cell stress in striatial neurons. Defects in HTRA2 are the cause of Parkinson disease 13 (PARK13). Four alternatively spliced human isoforms have been described. Note: This description may include information from UniProtKB.
Protein type: Protease; Mitochondrial; Membrane protein, integral; EC 3.4.21.108
Cellular Component: endoplasmic reticulum membrane; internal side of plasma membrane; mitochondrion; endoplasmic reticulum; mitochondrial membrane; mitochondrial intermembrane space; cytosol; nucleus
Molecular Function: peptidase activity; protein binding; serine-type peptidase activity; serine-type endopeptidase activity; unfolded protein binding
Biological Process: mitochondrion organization and biogenesis; positive regulation of apoptosis; regulation of multicellular organism growth; positive regulation of caspase activity; response to herbicide; proteolysis; adult walking behavior; negative regulation of cell cycle; protein autoprocessing; DNA damage response, signal transduction resulting in induction of apoptosis; pentacyclic triterpenoid metabolic process; forebrain development; neuron development; ceramide metabolic process
Reference #:  O43464 (UniProtKB)
Alt. Names/Synonyms: High temperature requirement protein A2; HtrA serine peptidase 2; HtrA-like serine protease; HTRA2; OMI; Omi stress-regulated endoprotease; PARK13; protease, serine, 25; PRSS25; Serine protease 25; Serine protease HTRA2, mitochondrial; Serine proteinase OMI
Gene Symbols: HTRA2
Molecular weight: 48,841 Da
Basal Isoelectric point: 10.07  Predict pI for various phosphorylation states
CST Pathways:  Apoptosis Regulation  |  Death Receptor Signaling  |  Mitochondrial Control of Apoptosis
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
Select Structure to View Below

HTRA2

Protein Structure Not Found.


STRING  |  Scansite  |  Phospho.ELM  |  NetworKIN  |  Pfam  |  RCSB PDB  |  ENZYME  |  Phospho3D  |  UniProtKB  |  Entrez-Gene  |  Ensembl Gene


Sites Implicated In
apoptosis, induced: S212‑p
enzymatic activity, induced: S142‑p
enzymatic activity, inhibited: S212‑p
intracellular localization: S212‑p

Modification Sites and Domains Show Modification Legend
Click here to view phosphorylation modifications only

Modification Sites in Parent Protein, Orthologs, and Isoforms Show Modification Legend
 

Show Multiple Sequence Alignment


 SS 

SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.


 MS 

MS: The number of records in which this modification site was assigned using ONLY proteomic discovery-mode mass spectrometry.


       human

► Hide Isoforms
 
0 1 R8-m1 MAAPRAGrGAGWSLR
0 1 T51-p SDPRARVtYGtPSLW
0 1 T54-p RARVtYGtPSLWARL
0 2 S96-p DTRTREAsENSGTRS
3 1 S142-p VPSPPPAsPRSQYNF
1 2 S212-p RVRVRLLsGDTYEAV
0 3 T215 VRLLsGDTYEAVVTA
0 10 K237-u ATLRIQTkEPLPTLP
0 2 Y361 ISGSQRRYIGVMMLT
0 1 K395-u QHGVLIHkVILGsPA
2 0 S400-p IHkVILGsPAHRAGL
  HTRA2 iso2  
R8 MAAPRAGRGAGWSLR
T51 SDPRARVTYGTPSLW
T54 RARVTYGTPSLWARL
S96 DTRTREASENSGTRS
S142 VPSPPPASPRSQYNF
S212 RVRVRLLSGDTYEAV
T215 VRLLSGDTYEAVVTA
K237 ATLRIQTKFGNSGGP
Y296-p ISGSQRRyIGVMMLT
- gap
- gap
  mouse

 
R8 MAALKAGRGANWSLR
T51 PDSQIWMTYGTPSLP
T54 QIWMTYGTPSLPAQV
R96 GSSDQEARRSPGSRR
S142-p VPAPPPTsPRSQYNF
S212-p RVRVRLPsGDtYEAM
T215-p VRLPsGDtYEAMVTA
K237 ATLRIQTKEPLPTLP
Y361 TSGSQRRYIGVMMLT
K395 QHGVLIHKVILGsPA
S400-p IHKVILGsPAHRAGL
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