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Protein Page:
HTRA2 (human)
p Phosphorylation
ac Acetylation
me Methylation
m1 Mono-methylation
m2 Di-methylation
m3 Tri-methylation
ub Ubiquitination
sm Sumoylation
ne Neddylation
gl O-GlcNAc
ga O-GalNAc
pa Palmitoylation
ad Adenylylation
sn S-Nitrosylation
ca Caspase cleavage
sc Succinylation

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: Membrane protein, integral; Mitochondrial; Protease; EC 3.4.21.108
Cellular Component: endoplasmic reticulum membrane; internal side of plasma membrane; cytoskeleton; mitochondrion; membrane; endoplasmic reticulum; mitochondrial membrane; mitochondrial intermembrane space; chromatin; nucleus; cytosol
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; positive regulation of caspase activity; regulation of multicellular organism growth; 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.


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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 R5-m1 ___MAAPrAGrGAGW
0 1 R8-m1 MAAPrAGrGAGWSLR
0 1 T51-p SDPRARVtYGtPSLW
0 1 T54-p RARVtYGtPSLWARL
0 2 S96-p DTRTREAsENSGTRS
0 1 P129 WGGGRGPPAVLAAVP
0 1 A130 GGGRGPPAVLAAVPS
0 1 A141 AVPSPPPAsPRSQYN
4 1 S142-p VPSPPPAsPRSQYNF
0 1 T157-p IADVVEKtAPAVVYI
1 2 S212-p RVRVRLLsGDTYEAV
0 3 T215 VRLLsGDTYEAVVTA
0 1 Y216 RLLsGDTYEAVVTAV
0 10 K237-ub ATLRIQTkEPLPtLP
0 1 T242-p QTkEPLPtLPLGRSA
0 1 T326-p GVNTMKVtAGIsFAI
0 1 S330-p MKVtAGIsFAIPSDR
0 1 S352-p GEKKNSSsGISGSQR
0 2 Y361 ISGSQRRYIGVMMLT
0 1 K395-ub QHGVLIHkVILGsPA
2 0 S400-p IHkVILGsPAHRAGL
0 1 T453-p ETLTLYVtPEVTE__
  HTRA2 iso2  
R5 ___MAAPRAGRGAGW
R8 MAAPRAGRGAGWSLR
T51 SDPRARVTYGTPSLW
T54 RARVTYGTPSLWARL
S96 DTRTREASENSGTRS
P129 WGGGRGPPAVLAAVP
A130 GGGRGPPAVLAAVPS
A141 AVPSPPPASPRSQYN
S142 VPSPPPASPRSQYNF
T157 IADVVEKTAPAVVYI
S212 RVRVRLLSGDTYEAV
T215 VRLLSGDTYEAVVTA
Y216 RLLSGDTYEAVVTAV
K237 ATLRIQTKFGNSGGP
- gap
T261 GVNTMKVTAGISFAI
S265 MKVTAGISFAIPSDR
S287 GEKKNSSSGISGSQR
Y296-p ISGSQRRyIGVMMLT
- gap
- gap
T356 ETLTLYVTPEVTE__
  mouse

 
K5 ___MAALKAGRGANW
R8 MAALKAGRGANWSLR
T51 PDSQIWMTYGTPSLP
T54 QIWMTYGTPSLPAQV
R96 GSSDQEARRSPGSRR
S129-p WGWGRGLstVLAAVP
T130-p GWGRGLstVLAAVPA
T141-p AVPAPPPtsPRSQYN
S142-p VPAPPPtsPRSQYNF
T157 IADVVEKTAPAVVYI
S212-p RVRVRLPsGDtyEAM
T215-p VRLPsGDtyEAMVTA
Y216-p RLPsGDtyEAMVTAV
K237 ATLRIQTKEPLPTLP
T242 QTKEPLPTLPLGRSA
T326 GVNTMKVTAGISFAI
S330 MKVTAGISFAIPSDR
F352 GEKKNSWFGTSGSQR
Y361 TSGSQRRYIGVMMLT
K395 QHGVLIHKVILGsPA
S400-p IHKVILGsPAHRAGL
T453 ETLTLYVTPEVTE__
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