CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-000715
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Serine protease HTRA2, mitochondrial 
Protein Synonyms/Alias
 High temperature requirement protein A2; HtrA2; Omi stress-regulated endoprotease; Serine protease 25; Serine proteinase OMI 
Gene Name
 HTRA2 
Gene Synonyms/Alias
 OMI; PRSS25 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
237ATLRIQTKEPLPTLPubiquitination[1, 2, 3, 4, 5, 6, 7]
395QHGVLIHKVILGSPAubiquitination[2, 6]
Reference
 [1] Global analysis of lysine ubiquitination by ubiquitin remnant immunoaffinity profiling.
 Xu G, Paige JS, Jaffrey SR.
 Nat Biotechnol. 2010 Aug;28(8):868-73. [PMID: 20639865]
 [2] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [3] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [4] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
 [5] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [6] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [7] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302] 
Functional Description
 Serine protease that shows proteolytic activity against a non-specific substrate beta-casein. Promotes or induces cell death either by direct binding to and inhibition of BIRC proteins (also called inhibitor of apoptosis proteins, IAPs), leading to an increase in caspase activity, or by a BIRC inhibition-independent, caspase-independent and serine protease activity-dependent mechanism. Cleaves THAP5 and promotes its degradation during apoptosis. Isoform 2 seems to be proteolytically inactive. 
Sequence Annotation
 DOMAIN 364 445 PDZ.
 REGION 166 342 Serine protease.
 MOTIF 134 137 IAP-binding motif.
 ACT_SITE 198 198 Charge relay system.
 ACT_SITE 228 228 Charge relay system.
 ACT_SITE 306 306 Charge relay system.  
Keyword
 3D-structure; Alternative splicing; Apoptosis; Complete proteome; Direct protein sequencing; Disease mutation; Hydrolase; Membrane; Mitochondrion; Neurodegeneration; Parkinson disease; Parkinsonism; Polymorphism; Protease; Reference proteome; Serine protease; Transit peptide; Transmembrane; Transmembrane helix; Zymogen. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 458 AA 
Protein Sequence
MAAPRAGRGA GWSLRAWRAL GGIRWGRRPR LTPDLRALLT SGTSDPRARV TYGTPSLWAR 60
LSVGVTEPRA CLTSGTPGPR AQLTAVTPDT RTREASENSG TRSRAWLAVA LGAGGAVLLL 120
LWGGGRGPPA VLAAVPSPPP ASPRSQYNFI ADVVEKTAPA VVYIEILDRH PFLGREVPIS 180
NGSGFVVAAD GLIVTNAHVV ADRRRVRVRL LSGDTYEAVV TAVDPVADIA TLRIQTKEPL 240
PTLPLGRSAD VRQGEFVVAM GSPFALQNTI TSGIVSSAQR PARDLGLPQT NVEYIQTDAA 300
IDFGNSGGPL VNLDGEVIGV NTMKVTAGIS FAIPSDRLRE FLHRGEKKNS SSGISGSQRR 360
YIGVMMLTLS PSILAELQLR EPSFPDVQHG VLIHKVILGS PAHRAGLRPG DVILAIGEQM 420
VQNAEDVYEA VRTQSQLAVQ IRRGRETLTL YVTPEVTE 458 
Gene Ontology
 GO:0035631; C:CD40 receptor complex; ISS:BHF-UCL.
 GO:0005829; C:cytosol; IDA:UniProtKB.
 GO:0005789; C:endoplasmic reticulum membrane; TAS:UniProtKB.
 GO:0009898; C:internal side of plasma membrane; ISS:BHF-UCL.
 GO:0005758; C:mitochondrial intermembrane space; IDA:MGI.
 GO:0031966; C:mitochondrial membrane; IEA:UniProtKB-SubCell.
 GO:0005634; C:nucleus; TAS:UniProtKB.
 GO:0004252; F:serine-type endopeptidase activity; TAS:UniProtKB.
 GO:0051082; F:unfolded protein binding; NAS:UniProtKB.
 GO:0007628; P:adult walking behavior; IEA:Compara.
 GO:0007050; P:cell cycle arrest; TAS:UniProtKB.
 GO:0071363; P:cellular response to growth factor stimulus; IMP:UniProtKB.
 GO:0006672; P:ceramide metabolic process; IEA:Compara.
 GO:0006923; P:cleavage of cytoskeletal proteins involved in execution phase of apoptosis; TAS:UniProtKB.
 GO:0030900; P:forebrain development; IEA:Compara.
 GO:0097193; P:intrinsic apoptotic signaling pathway; IEA:Compara.
 GO:0007005; P:mitochondrion organization; IEA:Compara.
 GO:0060548; P:negative regulation of cell death; IEA:Compara.
 GO:0048666; P:neuron development; IEA:Compara.
 GO:0019742; P:pentacyclic triterpenoid metabolic process; IEA:Compara.
 GO:0043065; P:positive regulation of apoptotic process; IMP:UniProtKB.
 GO:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:UniProtKB.
 GO:2001244; P:positive regulation of intrinsic apoptotic signaling pathway; IMP:UniProtKB.
 GO:0040014; P:regulation of multicellular organism growth; IEA:Compara.
 GO:0009635; P:response to herbicide; IEA:Compara.
 GO:0006950; P:response to stress; TAS:UniProtKB. 
Interpro
 IPR001478; PDZ.
 IPR001254; Peptidase_S1.
 IPR001940; Peptidase_S1C.
 IPR009003; Trypsin-like_Pept_dom. 
Pfam
 PF13180; PDZ_2 
SMART
 SM00228; PDZ
 SM00020; Tryp_SPc 
PROSITE
 PS50106; PDZ 
PRINTS
 PR00834; PROTEASES2C.