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HTRA2 (human)

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; EC 3.4.21.108; Mitochondrial; Membrane protein, integral 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; cleavage of cytoskeletal proteins during apoptosis; positive regulation of apoptosis; forebrain development; neuron development; response to stress; regulation of multicellular organism growth; positive regulation of caspase activity; proteolysis; cell cycle arrest; adult walking behavior 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  |  Death Receptor Signaling  |  Mitochondrial Control of Apoptosis Protein-Specific Antibodies or siRNAs from Cell Signaling Technology®

Select Structure to View Below HTRA2 1LCY - A=134-458 (human) 2PZD - A/B=359-458 (human)

STRING  |  Scansite  |  Phospho.ELM  |  NetworKIN  |  Pfam  |  RCSB PDB 1LCY 2PZD  |  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

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		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
3	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-u	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-u	QHGVLIHkVILGsPA
2	0		S400-p	IHkVILGsPAHRAGL
0	1		T453-p	ETLTLYVtPEVTE__

	HTRA2 iso2
R5	___MAAPRAGRGAGW
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
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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