ID HTRA2_HUMAN Reviewed; 458 AA. AC O43464; Q9HBZ4; Q9P0Y3; Q9P0Y4; DT 26-SEP-2001, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-2000, sequence version 2. DT 28-JAN-2026, entry version 241. DE RecName: Full=Serine protease HTRA2, mitochondrial; DE EC=3.4.21.108; DE AltName: Full=High temperature requirement protein A2; DE Short=HtrA2; DE AltName: Full=Omi stress-regulated endoprotease; DE AltName: Full=Serine protease 25; DE AltName: Full=Serine proteinase OMI; DE Flags: Precursor; GN Name=HTRA2; Synonyms=OMI, PRSS25; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, TISSUE RP SPECIFICITY, AND MUTAGENESIS OF SER-306. RX PubMed=10644717; DOI=10.1074/jbc.275.4.2581; RA Faccio L., Fusco C., Chen A., Martinotti S., Bonventre J.V., Zervos A.S.; RT "Characterization of a novel human serine protease that has extensive RT homology to bacterial heat shock endoprotease HtrA and is regulated by RT kidney ischemia."; RL J. Biol. Chem. 275:2581-2588(2000). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 3 AND 4), AND CHARACTERIZATION. RC TISSUE=Brain; RX PubMed=10971580; DOI=10.1046/j.1432-1327.2000.01589.x; RA Gray C.W., Ward R.V., Karran E.H., Turconi S., Rowles A., Viglienghi D., RA Southan C., Barton A., Fantom K.G., West A., Savopoulos J.W., Hassan N.J., RA Clinkenbeard H., Hanning C., Amegadzie B., Davis J.B., Dingwall C., RA Livi G.P., Creasy C.L.; RT "Characterization of human HtrA2, a novel serine protease involved in the RT mammalian cellular stress response."; RL Eur. J. Biochem. 267:5699-5710(2000). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RC TISSUE=Kidney; RX PubMed=10995577; DOI=10.1006/geno.2000.6263; RA Faccio L., Fusco C., Viel A., Zervos A.S.; RT "Tissue-specific splicing of Omi stress-regulated endoprotease leads to an RT inactive protease with a modified PDZ motif."; RL Genomics 68:343-347(2000). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP PROTEIN SEQUENCE OF 134-458, INTERACTION WITH XIAP, AND MUTAGENESIS OF RP ALA-134. RX PubMed=11583623; DOI=10.1016/s1097-2765(01)00341-0; RA Suzuki Y., Imai Y., Nakayama H., Takahashi K., Takio K., Takahashi R.; RT "A serine protease, HtrA2, is released from the mitochondria and interacts RT with XIAP, inducing cell death."; RL Mol. Cell 8:613-621(2001). RN [7] RP CHARACTERIZATION, AND PHOSPHORYLATION. RX PubMed=10873535; DOI=10.1006/prep.2000.1240; RA Savopoulos J.W., Carter P.S., Turconi S., Pettman G.R., Karran E.H., RA Gray C.W., Ward R.V., Jenkins O., Creasy C.L.; RT "Expression, purification, and functional analysis of the human serine RT protease HtrA2."; RL Protein Expr. Purif. 19:227-234(2000). RN [8] RP FUNCTION, AND INTERACTION WITH BIRC6/BRUCE. RX PubMed=15200957; DOI=10.1016/j.molcel.2004.05.018; RA Bartke T., Pohl C., Pyrowolakis G., Jentsch S.; RT "Dual role of BRUCE as an antiapoptotic IAP and a chimeric E2/E3 ubiquitin RT ligase."; RL Mol. Cell 14:801-811(2004). RN [9] RP FUNCTION, AND INTERACTION WITH THAP5. RX PubMed=19502560; DOI=10.1152/ajpheart.00234.2009; RA Balakrishnan M.P., Cilenti L., Mashak Z., Popat P., Alnemri E.S., RA Zervos A.S.; RT "THAP5 is a human cardiac-specific inhibitor of cell cycle that is cleaved RT by the proapoptotic Omi/HtrA2 protease during cell death."; RL Am. J. Physiol. 297:H643-H653(2009). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [11] RP INTERACTION WITH AREL1. RX PubMed=23479728; DOI=10.1074/jbc.m112.436113; RA Kim J.B., Kim S.Y., Kim B.M., Lee H., Kim I., Yun J., Jo Y., Oh T., Jo Y., RA Chae H.D., Shin D.Y.; RT "Identification of a novel anti-apoptotic E3 ubiquitin ligase that RT ubiquitinates antagonists of inhibitor of apoptosis proteins SMAC, HtrA2, RT and ARTS."; RL J. Biol. Chem. 288:12014-12021(2013). RN [12] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [13] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [14] {ECO:0007744|PDB:1LCY} RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 134-458, SUBUNIT, AND ACTIVE SITE. RX PubMed=11967569; DOI=10.1038/nsb795; RA Li W., Srinivasula S.M., Chai J., Li P., Wu J.W., Zhang Z., Alnemri E.S., RA Shi Y.; RT "Structural insights into the pro-apoptotic function of mitochondrial RT serine protease HtrA2/Omi."; RL Nat. Struct. Biol. 9:436-441(2002). RN [15] {ECO:0007744|PDB:8E2K} RP STRUCTURE BY ELECTRON MICROSCOPY (3.21 ANGSTROMS) OF 134-458 IN COMPLEX RP WITH BIRC6, FUNCTION, ACTIVITY REGULATION, SUBUNIT, AND UBIQUITINATION BY RP BIRC6. RX PubMed=36758104; DOI=10.1126/science.ade5750; RA Hunkeler M., Jin C.Y., Fischer E.S.; RT "Structures of BIRC6-client complexes provide a mechanism of SMAC-mediated RT release of caspases."; RL Science 379:1105-1111(2023). RN [16] {ECO:0007744|PDB:8AUK} RP STRUCTURE BY ELECTRON MICROSCOPY (6.20 ANGSTROMS) OF 134-458 IN COMPLEX RP WITH BIRC6, FUNCTION, ACTIVITY REGULATION, SUBUNIT, AND UBIQUITINATION BY RP BIRC6. RX PubMed=36758105; DOI=10.1126/science.ade8873; RA Ehrmann J.F., Grabarczyk D.B., Heinke M., Deszcz L., Kurzbauer R., RA Hudecz O., Shulkina A., Gogova R., Meinhart A., Versteeg G.A., Clausen T.; RT "Structural basis for regulation of apoptosis and autophagy by the RT BIRC6/SMAC complex."; RL Science 379:1117-1123(2023). RN [17] RP INVOLVEMENT IN PARK13, VARIANTS SER-141 AND SER-399, AND CHARACTERIZATION RP OF VARIANTS SER-141 AND SER-399. RX PubMed=15961413; DOI=10.1093/hmg/ddi215; RA Strauss K.M., Martins L.M., Plun-Favreau H., Marx F.P., Kautzmann S., RA Berg D., Gasser T., Wszolek Z., Mueller T., Bornemann A., Wolburg H., RA Downward J., Riess O., Schulz J.B., Krueger R.; RT "Loss of function mutations in the gene encoding Omi/HtrA2 in Parkinson's RT disease."; RL Hum. Mol. Genet. 14:2099-2111(2005). RN [18] RP INVOLVEMENT IN PARK13, VARIANTS PRO-72 AND SER-141, AND VARIANT PARK13 RP TRP-404. RX PubMed=18401856; DOI=10.1002/humu.20713; RA Bogaerts V., Nuytemans K., Reumers J., Pals P., Engelborghs S., Pickut B., RA Corsmit E., Peeters K., Schymkowitz J., De Deyn P.P., Cras P., Rousseau F., RA Theuns J., Van Broeckhoven C.; RT "Genetic variability in the mitochondrial serine protease HTRA2 contributes RT to risk for Parkinson disease."; RL Hum. Mutat. 29:832-840(2008). RN [19] RP VARIANTS CYS-12; LEU-128; SER-141; SER-227 AND SER-399. RX PubMed=18364387; DOI=10.1093/hmg/ddn096; RA Simon-Sanchez J., Singleton A.B.; RT "Sequencing analysis of OMI/HTRA2 shows previously reported pathogenic RT mutations in neurologically normal controls."; RL Hum. Mol. Genet. 17:1988-1993(2008). RN [20] RP VARIANT SER-399. RX PubMed=25422467; DOI=10.1073/pnas.1419581111; RA Unal Gulsuner H., Gulsuner S., Mercan F.N., Onat O.E., Walsh T., Shahin H., RA Lee M.K., Dogu O., Kansu T., Topaloglu H., Elibol B., Akbostanci C., RA King M.C., Ozcelik T., Tekinay A.B.; RT "Mitochondrial serine protease HTRA2 p.G399S in a kindred with essential RT tremor and Parkinson disease."; RL Proc. Natl. Acad. Sci. U.S.A. 111:18285-18290(2014). RN [21] RP INVOLVEMENT IN MGCA8, VARIANT MGCA8 GLN-404, AND CHARACTERIZATION OF RP VARIANT MGCA8 GLN-404. RX PubMed=27208207; DOI=10.1136/jmedgenet-2016-103922; RA Mandel H., Saita S., Edvardson S., Jalas C., Shaag A., Goldsher D., RA Vlodavsky E., Langer T., Elpeleg O.; RT "Deficiency of HTRA2/Omi is associated with infantile neurodegeneration and RT 3-methylglutaconic aciduria."; RL J. Med. Genet. 53:690-696(2016). RN [22] RP VARIANT SER-399. RX PubMed=27535533; DOI=10.1038/nature19057; RG Exome Aggregation Consortium; RA Lek M., Karczewski K.J., Minikel E.V., Samocha K.E., Banks E., Fennell T., RA O'Donnell-Luria A.H., Ware J.S., Hill A.J., Cummings B.B., Tukiainen T., RA Birnbaum D.P., Kosmicki J.A., Duncan L.E., Estrada K., Zhao F., Zou J., RA Pierce-Hoffman E., Berghout J., Cooper D.N., Deflaux N., DePristo M., RA Do R., Flannick J., Fromer M., Gauthier L., Goldstein J., Gupta N., RA Howrigan D., Kiezun A., Kurki M.I., Moonshine A.L., Natarajan P., RA Orozco L., Peloso G.M., Poplin R., Rivas M.A., Ruano-Rubio V., Rose S.A., RA Ruderfer D.M., Shakir K., Stenson P.D., Stevens C., Thomas B.P., Tiao G., RA Tusie-Luna M.T., Weisburd B., Won H.H., Yu D., Altshuler D.M., RA Ardissino D., Boehnke M., Danesh J., Donnelly S., Elosua R., Florez J.C., RA Gabriel S.B., Getz G., Glatt S.J., Hultman C.M., Kathiresan S., Laakso M., RA McCarroll S., McCarthy M.I., McGovern D., McPherson R., Neale B.M., RA Palotie A., Purcell S.M., Saleheen D., Scharf J.M., Sklar P., RA Sullivan P.F., Tuomilehto J., Tsuang M.T., Watkins H.C., Wilson J.G., RA Daly M.J., MacArthur D.G.; RT "Analysis of protein-coding genetic variation in 60,706 humans."; RL Nature 536:285-291(2016). RN [23] RP VARIANT MGCA8 243-LEU-PRO-244 DELINS PRO-SER, AND CHARACTERIZATION OF RP VARIANT MGCA8 243-LEU-PRO-244 DELINS PRO-SER. RX PubMed=27696117; DOI=10.1007/s10545-016-9977-2; RA Olahova M., Thompson K., Hardy S.A., Barbosa I.A., Besse A., RA Anagnostou M.E., White K., Davey T., Simpson M.A., Champion M., Enns G., RA Schelley S., Lightowlers R.N., Chrzanowska-Lightowlers Z.M., McFarland R., RA Deshpande C., Bonnen P.E., Taylor R.W.; RT "Pathogenic variants in HTRA2 cause an early-onset mitochondrial syndrome RT associated with 3-methylglutaconic aciduria."; RL J. Inherit. Metab. Dis. 40:121-130(2017). CC -!- FUNCTION: [Isoform 1]: Serine protease that shows proteolytic activity CC against a non-specific substrate beta-casein (PubMed:10873535). CC Promotes apoptosis by either relieving the inhibition of BIRC proteins CC on caspases, leading to an increase in caspase activity; or by a BIRC CC inhibition-independent, caspase-independent and serine protease CC activity-dependent mechanism (PubMed:15200957). Cleaves BIRC6 and CC relieves its inhibition on CASP3, CASP7 and CASP9, but it is also prone CC to inhibition by BIRC6 (PubMed:36758104, PubMed:36758105). Cleaves CC THAP5 and promotes its degradation during apoptosis (PubMed:19502560). CC {ECO:0000269|PubMed:10873535, ECO:0000269|PubMed:15200957, CC ECO:0000269|PubMed:19502560, ECO:0000269|PubMed:36758104, CC ECO:0000269|PubMed:36758105}. CC -!- FUNCTION: [Isoform 2]: Seems to be proteolytically inactive. CC {ECO:0000269|PubMed:10995577}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Cleavage of non-polar aliphatic amino-acids at the P1 CC position, with a preference for Val, Ile and Met. At the P2 and P3 CC positions, Arg is selected most strongly with a secondary preference CC for other hydrophilic residues.; EC=3.4.21.108; CC -!- ACTIVITY REGULATION: Inhibited by BIRC6. {ECO:0000269|PubMed:36758104, CC ECO:0000269|PubMed:36758105}. CC -!- SUBUNIT: Homotrimer (PubMed:36758104, PubMed:36758105). Interacts with CC MXI2. Interacts with THAP5 under apoptotic conditions. The mature CC protein, but not the precursor, binds to BIRC2/c-IAP1, BIRC3/c-IAP2 and CC XIAP/BIRC4. Interacts with AREL1 (via HECT domain); in the cytoplasm CC following induction of apoptosis (PubMed:23479728). CC {ECO:0000269|PubMed:11583623, ECO:0000269|PubMed:11967569, CC ECO:0000269|PubMed:15200957, ECO:0000269|PubMed:19502560, CC ECO:0000269|PubMed:23479728}. CC -!- INTERACTION: CC O43464; Q6ZTN6-2: ANKRD13D; NbExp=3; IntAct=EBI-517086, EBI-25840993; CC O43464; Q8IUR7: ARMC8; NbExp=6; IntAct=EBI-517086, EBI-1049469; CC O43464; Q86TN1: ARNT2; NbExp=3; IntAct=EBI-517086, EBI-25844820; CC O43464; Q9Y575-3: ASB3; NbExp=3; IntAct=EBI-517086, EBI-14199987; CC O43464; Q96DX5-3: ASB9; NbExp=3; IntAct=EBI-517086, EBI-25843552; CC O43464; Q96FT7-4: ASIC4; NbExp=3; IntAct=EBI-517086, EBI-9089489; CC O43464; Q13490: BIRC2; NbExp=4; IntAct=EBI-517086, EBI-514538; CC O43464; Q96CA5: BIRC7; NbExp=5; IntAct=EBI-517086, EBI-517623; CC O43464; Q7Z7K6: CENPV; NbExp=3; IntAct=EBI-517086, EBI-1210604; CC O43464; P02489: CRYAA; NbExp=3; IntAct=EBI-517086, EBI-6875961; CC O43464; Q5TAQ9-2: DCAF8; NbExp=3; IntAct=EBI-517086, EBI-25842815; CC O43464; O00303: EIF3F; NbExp=3; IntAct=EBI-517086, EBI-711990; CC O43464; Q8TC29: ENKUR; NbExp=3; IntAct=EBI-517086, EBI-9246952; CC O43464; Q13216-2: ERCC8; NbExp=3; IntAct=EBI-517086, EBI-16466949; CC O43464; Q99871: HAUS7; NbExp=3; IntAct=EBI-517086, EBI-395719; CC O43464; Q02363: ID2; NbExp=3; IntAct=EBI-517086, EBI-713450; CC O43464; Q8IY31-2: IFT20; NbExp=3; IntAct=EBI-517086, EBI-11742277; CC O43464; Q8N5Z5: KCTD17; NbExp=3; IntAct=EBI-517086, EBI-743960; CC O43464; Q6P597: KLC3; NbExp=3; IntAct=EBI-517086, EBI-1643885; CC O43464; P57682: KLF3; NbExp=3; IntAct=EBI-517086, EBI-8472267; CC O43464; Q9Y2M5: KLHL20; NbExp=3; IntAct=EBI-517086, EBI-714379; CC O43464; P08727: KRT19; NbExp=3; IntAct=EBI-517086, EBI-742756; CC O43464; Q14525: KRT33B; NbExp=3; IntAct=EBI-517086, EBI-1049638; CC O43464; Q1L5Z9: LONRF2; NbExp=3; IntAct=EBI-517086, EBI-2510853; CC O43464; Q99683: MAP3K5; NbExp=3; IntAct=EBI-517086, EBI-476263; CC O43464; Q8NA82: MARCHF10; NbExp=3; IntAct=EBI-517086, EBI-2341554; CC O43464; Q8N594: MPND; NbExp=3; IntAct=EBI-517086, EBI-2512452; CC O43464; Q8WY64: MYLIP; NbExp=3; IntAct=EBI-517086, EBI-6952711; CC O43464; Q9P0J0: NDUFA13; NbExp=8; IntAct=EBI-517086, EBI-372742; CC O43464; Q13562: NEUROD1; NbExp=3; IntAct=EBI-517086, EBI-3908303; CC O43464; O15381-5: NVL; NbExp=3; IntAct=EBI-517086, EBI-18577082; CC O43464; Q96FW1: OTUB1; NbExp=3; IntAct=EBI-517086, EBI-1058491; CC O43464; Q6GQQ9-2: OTUD7B; NbExp=3; IntAct=EBI-517086, EBI-25830200; CC O43464; Q9NUU6: OTULINL; NbExp=3; IntAct=EBI-517086, EBI-6916492; CC O43464; Q9HBE1-4: PATZ1; NbExp=3; IntAct=EBI-517086, EBI-11022007; CC O43464; Q9NV79: PCMTD2; NbExp=3; IntAct=EBI-517086, EBI-6309018; CC O43464; O14813: PHOX2A; NbExp=3; IntAct=EBI-517086, EBI-25844430; CC O43464; O75925: PIAS1; NbExp=3; IntAct=EBI-517086, EBI-629434; CC O43464; Q8WWB5: PIH1D2; NbExp=3; IntAct=EBI-517086, EBI-10232538; CC O43464; Q96T49: PPP1R16B; NbExp=3; IntAct=EBI-517086, EBI-10293968; CC O43464; Q6ZMI0-5: PPP1R21; NbExp=3; IntAct=EBI-517086, EBI-25835994; CC O43464; P17980: PSMC3; NbExp=3; IntAct=EBI-517086, EBI-359720; CC O43464; P57052: RBM11; NbExp=3; IntAct=EBI-517086, EBI-741332; CC O43464; Q8WVD3: RNF138; NbExp=3; IntAct=EBI-517086, EBI-749039; CC O43464; Q96D59: RNF183; NbExp=3; IntAct=EBI-517086, EBI-743938; CC O43464; Q15287: RNPS1; NbExp=2; IntAct=EBI-517086, EBI-395959; CC O43464; Q96GQ5: RUSF1; NbExp=3; IntAct=EBI-517086, EBI-8636004; CC O43464; Q8N488: RYBP; NbExp=3; IntAct=EBI-517086, EBI-752324; CC O43464; Q8N6K7-2: SAMD3; NbExp=3; IntAct=EBI-517086, EBI-11528848; CC O43464; Q9NR46: SH3GLB2; NbExp=3; IntAct=EBI-517086, EBI-749607; CC O43464; Q96GM5: SMARCD1; NbExp=3; IntAct=EBI-517086, EBI-358489; CC O43464; Q16637-3: SMN2; NbExp=3; IntAct=EBI-517086, EBI-395447; CC O43464; Q8WXH5: SOCS4; NbExp=3; IntAct=EBI-517086, EBI-3942425; CC O43464; Q5VWN6: TASOR2; NbExp=3; IntAct=EBI-517086, EBI-745958; CC O43464; Q86WV5: TEN1; NbExp=3; IntAct=EBI-517086, EBI-2562799; CC O43464; O95150: TNFSF15; NbExp=3; IntAct=EBI-517086, EBI-16355546; CC O43464; Q6DKK2: TTC19; NbExp=4; IntAct=EBI-517086, EBI-948354; CC O43464; Q495M9: USH1G; NbExp=3; IntAct=EBI-517086, EBI-8601749; CC O43464; O75604-3: USP2; NbExp=3; IntAct=EBI-517086, EBI-10696113; CC O43464; Q8NEZ2: VPS37A; NbExp=3; IntAct=EBI-517086, EBI-2850578; CC O43464; Q15007-2: WTAP; NbExp=3; IntAct=EBI-517086, EBI-25840023; CC O43464; O00308: WWP2; NbExp=3; IntAct=EBI-517086, EBI-743923; CC O43464; P98170: XIAP; NbExp=23; IntAct=EBI-517086, EBI-517127; CC O43464; P24278: ZBTB25; NbExp=3; IntAct=EBI-517086, EBI-739899; CC O43464; Q9UNY5: ZNF232; NbExp=3; IntAct=EBI-517086, EBI-749023; CC O43464; Q8N0Y2-2: ZNF444; NbExp=3; IntAct=EBI-517086, EBI-12010736; CC O43464; O60304: ZNF500; NbExp=3; IntAct=EBI-517086, EBI-18234077; CC O43464; O15535: ZSCAN9; NbExp=3; IntAct=EBI-517086, EBI-751531; CC O43464; Q86V28; NbExp=3; IntAct=EBI-517086, EBI-10259496; CC O43464; P02666: CSN2; Xeno; NbExp=7; IntAct=EBI-517086, EBI-5260183; CC O43464; Q60855: Ripk1; Xeno; NbExp=2; IntAct=EBI-517086, EBI-529119; CC PRO_0000026946; P02666: CSN2; Xeno; NbExp=2; IntAct=EBI-5271862, EBI-5260183; CC -!- SUBCELLULAR LOCATION: Mitochondrion intermembrane space. Mitochondrion CC membrane {ECO:0000305}; Single-pass membrane protein {ECO:0000305}. CC Note=Predominantly present in the intermembrane space. Released into CC the cytosol following apoptotic stimuli, such as UV treatment, and CC stimulation of mitochondria with caspase-8 truncated BID/tBID. CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Endoplasmic reticulum CC {ECO:0000269|PubMed:10644717}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; Synonyms=13B; CC IsoId=O43464-1; Sequence=Displayed; CC Name=2; Synonyms=D-Omi; CC IsoId=O43464-2; Sequence=VSP_005359, VSP_005361; CC Name=3; Synonyms=p7; CC IsoId=O43464-3; Sequence=VSP_005360, VSP_005361; CC Name=4; Synonyms=p4; CC IsoId=O43464-4; Sequence=VSP_005362; CC -!- TISSUE SPECIFICITY: [Isoform 1]: Ubiquitously expressed. CC {ECO:0000269|PubMed:10644717}. CC -!- DOMAIN: The mature N-terminus is involved in the interaction with XIAP. CC -!- DOMAIN: The PDZ domain mediates interaction with MXI2. CC -!- PTM: Ubiquitinated by BIRC6; this activity is inhibited by DIABLO/SMAC. CC {ECO:0000269|PubMed:36758104, ECO:0000269|PubMed:36758105}. CC -!- PTM: Autoproteolytically activated. {ECO:0000269|PubMed:10873535}. CC -!- DISEASE: 3-methylglutaconic aciduria 8 (MGCA8) [MIM:617248]: An CC autosomal recessive inborn error of metabolism resulting in early CC death. Clinical features include extreme hypertonia observed at birth, CC alternating with hypotonia, subsequent appearance of extrapyramidal CC symptoms, lack of psychomotor development, microcephaly, and CC intractable seizures. Patients show lactic acidemia, 3-methylglutaconic CC aciduria, intermittent neutropenia, and progressive brain atrophy. CC {ECO:0000269|PubMed:27208207, ECO:0000269|PubMed:27696117}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Parkinson disease 13 (PARK13) [MIM:610297]: A complex CC neurodegenerative disorder characterized by bradykinesia, resting CC tremor, muscular rigidity and postural instability, as well as by a CC clinically significant response to treatment with levodopa. The CC pathology involves the loss of dopaminergic neurons in the substantia CC nigra and the presence of Lewy bodies (intraneuronal accumulations of CC aggregated proteins), in surviving neurons in various areas of the CC brain. {ECO:0000269|PubMed:15961413, ECO:0000269|PubMed:18401856}. CC Note=Disease susceptibility is associated with variants affecting the CC gene represented in this entry. CC -!- SIMILARITY: Belongs to the peptidase S1C family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/41879/HTRA2"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF020760; AAB94569.2; -; mRNA. DR EMBL; AF141305; AAF66596.1; -; mRNA. DR EMBL; AF141306; AAF66597.1; -; mRNA. DR EMBL; AF141307; AAF66598.1; -; mRNA. DR EMBL; AF184911; AAG13126.1; -; mRNA. DR EMBL; AC006544; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC000096; AAH00096.1; -; mRNA. DR CCDS; CCDS1951.1; -. [O43464-1] DR CCDS; CCDS1952.1; -. [O43464-2] DR CCDS; CCDS92785.1; -. [O43464-3] DR RefSeq; NP_001308656.1; NM_001321727.1. [O43464-3] DR RefSeq; NP_037379.1; NM_013247.5. [O43464-1] DR RefSeq; NP_659540.1; NM_145074.2. [O43464-2] DR PDB; 1LCY; X-ray; 2.00 A; A=134-458. DR PDB; 2PZD; X-ray; 2.75 A; A/B=359-458. DR PDB; 5FHT; X-ray; 1.95 A; A=134-458. DR PDB; 5M3N; X-ray; 1.65 A; A=134-458. DR PDB; 5M3O; X-ray; 1.70 A; A=134-458. DR PDB; 5TNY; X-ray; 1.70 A; A=134-458. DR PDB; 5TNZ; X-ray; 1.75 A; A=134-458. DR PDB; 5TO0; X-ray; 1.90 A; A=134-458. DR PDB; 5TO1; X-ray; 1.69 A; A=134-458. DR PDB; 5WYN; X-ray; 2.05 A; A=134-458. DR PDB; 7VGE; X-ray; 4.00 A; A/B/C=140-342, D/F=140-341, E=140-340. DR PDB; 8AUK; EM; 6.20 A; C/D/E=134-458. DR PDB; 8E2K; EM; 3.21 A; X/Y/Z=134-458. DR PDBsum; 1LCY; -. DR PDBsum; 2PZD; -. DR PDBsum; 5FHT; -. DR PDBsum; 5M3N; -. DR PDBsum; 5M3O; -. DR PDBsum; 5TNY; -. DR PDBsum; 5TNZ; -. DR PDBsum; 5TO0; -. DR PDBsum; 5TO1; -. DR PDBsum; 5WYN; -. DR PDBsum; 7VGE; -. DR PDBsum; 8AUK; -. DR PDBsum; 8E2K; -. DR AlphaFoldDB; O43464; -. DR EMDB; EMD-15672; -. DR EMDB; EMD-27841; -. DR SASBDB; O43464; -. DR SMR; O43464; -. DR BioGRID; 118165; 304. DR CORUM; O43464; -. DR ELM; O43464; -. DR FunCoup; O43464; 1709. DR IntAct; O43464; 313. DR MINT; O43464; -. DR STRING; 9606.ENSP00000258080; -. DR BindingDB; O43464; -. DR ChEMBL; CHEMBL4523137; -. DR MEROPS; S01.278; -. DR MoonDB; O43464; Predicted. DR TCDB; 8.A.217.1.1; the apoptosis cell death regulator (acdr) family. DR iPTMnet; O43464; -. DR PhosphoSitePlus; O43464; -. DR BioMuta; HTRA2; -. DR OGP; O43464; -. DR jPOST; O43464; -. DR MassIVE; O43464; -. DR PaxDb; 9606-ENSP00000258080; -. DR PeptideAtlas; O43464; -. DR ProteomicsDB; 48958; -. [O43464-1] DR ProteomicsDB; 48959; -. [O43464-2] DR ProteomicsDB; 48960; -. [O43464-3] DR ProteomicsDB; 48961; -. [O43464-4] DR Pumba; O43464; -. DR TopDownProteomics; O43464-2; -. [O43464-2] DR ABCD; O43464; 1 sequenced antibody. DR Antibodypedia; 3554; 772 antibodies from 43 providers. DR DNASU; 27429; -. DR Ensembl; ENST00000258080.8; ENSP00000258080.3; ENSG00000115317.14. [O43464-1] DR Ensembl; ENST00000352222.7; ENSP00000312893.3; ENSG00000115317.14. [O43464-2] DR Ensembl; ENST00000437202.2; ENSP00000399166.2; ENSG00000115317.14. [O43464-3] DR GeneID; 27429; -. DR KEGG; hsa:27429; -. DR MANE-Select; ENST00000258080.8; ENSP00000258080.3; NM_013247.5; NP_037379.1. DR UCSC; uc002smi.2; human. [O43464-1] DR AGR; HGNC:14348; -. DR ClinPGx; PA33836; -. DR CTD; 27429; -. DR DisGeNET; 27429; -. DR GeneCards; HTRA2; -. DR HGNC; HGNC:14348; HTRA2. DR HPA; ENSG00000115317; Low tissue specificity. DR MalaCards; HTRA2; -. DR MIM; 168600; phenotype. DR MIM; 606441; gene. DR MIM; 610297; phenotype. DR MIM; 617248; phenotype. DR OpenTargets; ENSG00000115317; -. DR Orphanet; 505208; 3-methylglutaconic aciduria type 8. DR Orphanet; 2828; Young-onset Parkinson disease. DR VEuPathDB; HostDB:ENSG00000115317; -. DR eggNOG; KOG1320; Eukaryota. DR GeneTree; ENSGT00940000155108; -. DR HOGENOM; CLU_020120_6_0_1; -. DR InParanoid; O43464; -. DR OMA; MDNYRDE; -. DR OrthoDB; 4217619at2759; -. DR PAN-GO; O43464; 5 GO annotations based on evolutionary models. DR PhylomeDB; O43464; -. DR BRENDA; 3.4.21.108; 2681. DR PathwayCommons; O43464; -. DR Reactome; R-HSA-9837999; Mitochondrial protein degradation. DR Reactome; R-HSA-9841251; Mitochondrial unfolded protein response (UPRmt). DR SignaLink; O43464; -. DR SIGNOR; O43464; -. DR Agora; ENSG00000115317; -. DR BioGRID-ORCS; 27429; 97 hits in 1167 CRISPR screens. DR ChiTaRS; HTRA2; human. DR EvolutionaryTrace; O43464; -. DR GeneWiki; HtrA_serine_peptidase_2; -. DR GenomeRNAi; 27429; -. DR Pharos; O43464; Tbio. DR PRO; PR:O43464; -. DR Proteomes; UP000005640; Chromosome 2. DR RNAct; O43464; protein. DR Bgee; ENSG00000115317; Expressed in cortical plate and 199 other cell types or tissues. DR ExpressionAtlas; O43464; baseline and differential. DR GO; GO:0035631; C:CD40 receptor complex; ISS:BHF-UCL. DR GO; GO:0000785; C:chromatin; IDA:ParkinsonsUK-UCL. DR GO; GO:0009898; C:cytoplasmic side of plasma membrane; ISS:BHF-UCL. DR GO; GO:0005856; C:cytoskeleton; IDA:ParkinsonsUK-UCL. DR GO; GO:0005829; C:cytosol; IDA:UniProtKB. DR GO; GO:0005783; C:endoplasmic reticulum; NAS:UniProtKB. DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:UniProtKB. DR GO; GO:0016020; C:membrane; IDA:ParkinsonsUK-UCL. DR GO; GO:0005758; C:mitochondrial intermembrane space; IDA:MGI. DR GO; GO:0031966; C:mitochondrial membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005739; C:mitochondrion; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:1905370; C:serine-type endopeptidase complex; IMP:CAFA. DR GO; GO:0042802; F:identical protein binding; IPI:CAFA. DR GO; GO:0008233; F:peptidase activity; IDA:UniProtKB. DR GO; GO:0030291; F:protein serine/threonine kinase inhibitor activity; IDA:ParkinsonsUK-UCL. DR GO; GO:0004252; F:serine-type endopeptidase activity; IDA:ParkinsonsUK-UCL. DR GO; GO:0008236; F:serine-type peptidase activity; IDA:UniProtKB. DR GO; GO:1990948; F:ubiquitin ligase inhibitor activity; IDA:ParkinsonsUK-UCL. DR GO; GO:0051082; F:unfolded protein binding; NAS:UniProtKB. DR GO; GO:0007628; P:adult walking behavior; IEA:Ensembl. DR GO; GO:0071363; P:cellular response to growth factor stimulus; IMP:UniProtKB. DR GO; GO:0034605; P:cellular response to heat; IDA:UniProtKB. DR GO; GO:0035458; P:cellular response to interferon-beta; IDA:ParkinsonsUK-UCL. DR GO; GO:0034599; P:cellular response to oxidative stress; IMP:ParkinsonsUK-UCL. DR GO; GO:0071300; P:cellular response to retinoic acid; IDA:ParkinsonsUK-UCL. DR GO; GO:0006672; P:ceramide metabolic process; IEA:Ensembl. DR GO; GO:0097194; P:execution phase of apoptosis; TAS:UniProtKB. DR GO; GO:0030900; P:forebrain development; IEA:Ensembl. DR GO; GO:0035556; P:intracellular signal transduction; IDA:ParkinsonsUK-UCL. DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IMP:ParkinsonsUK-UCL. DR GO; GO:0035694; P:mitochondrial protein catabolic process; TAS:Reactome. DR GO; GO:0007005; P:mitochondrion organization; IMP:ParkinsonsUK-UCL. DR GO; GO:0045786; P:negative regulation of cell cycle; TAS:UniProtKB. DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; TAS:ParkinsonsUK-UCL. DR GO; GO:1902176; P:negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway; NAS:ParkinsonsUK-UCL. DR GO; GO:1905090; P:negative regulation of type 2 mitophagy; IEA:Ensembl. DR GO; GO:0051402; P:neuron apoptotic process; IEA:Ensembl. DR GO; GO:0048666; P:neuron development; IEA:Ensembl. DR GO; GO:0019742; P:pentacyclic triterpenoid metabolic process; IEA:Ensembl. DR GO; GO:0043065; P:positive regulation of apoptotic process; IDA:UniProtKB. DR GO; GO:1900119; P:positive regulation of execution phase of apoptosis; IDA:ParkinsonsUK-UCL. DR GO; GO:2001241; P:positive regulation of extrinsic apoptotic signaling pathway in absence of ligand; IMP:UniProtKB. DR GO; GO:1903955; P:positive regulation of protein targeting to mitochondrion; HMP:ParkinsonsUK-UCL. DR GO; GO:0012501; P:programmed cell death; IBA:GO_Central. DR GO; GO:0016540; P:protein autoprocessing; TAS:ParkinsonsUK-UCL. DR GO; GO:0030163; P:protein catabolic process; IDA:ParkinsonsUK-UCL. DR GO; GO:0006508; P:proteolysis; IMP:UniProtKB. DR GO; GO:1903146; P:regulation of autophagy of mitochondrion; TAS:ParkinsonsUK-UCL. DR GO; GO:0040014; P:regulation of multicellular organism growth; IEA:Ensembl. DR GO; GO:0009635; P:response to herbicide; IEA:Ensembl. DR CDD; cd06785; cpPDZ_HtrA-like; 1. DR DisProt; DP00315; -. DR FunFam; 2.40.10.120:FF:000004; Serine protease HTRA2, mitochondrial; 1. DR FunFam; 2.30.42.10:FF:000145; serine protease HTRA2, mitochondrial; 1. DR Gene3D; 2.30.42.10; -; 1. DR Gene3D; 2.40.10.120; -; 1. DR InterPro; IPR001478; PDZ. DR InterPro; IPR041489; PDZ_6. DR InterPro; IPR036034; PDZ_sf. DR InterPro; IPR009003; Peptidase_S1_PA. DR InterPro; IPR001940; Peptidase_S1C. DR PANTHER; PTHR22939; SERINE PROTEASE FAMILY S1C HTRA-RELATED; 1. DR PANTHER; PTHR22939:SF127; SERINE PROTEASE HTRA2, MITOCHONDRIAL; 1. DR Pfam; PF17820; PDZ_6; 1. DR Pfam; PF13365; Trypsin_2; 1. DR PRINTS; PR00834; PROTEASES2C. DR SMART; SM00228; PDZ; 1. DR SUPFAM; SSF50156; PDZ domain-like; 1. DR SUPFAM; SSF50494; Trypsin-like serine proteases; 1. DR PROSITE; PS50106; PDZ; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Apoptosis; Autocatalytic cleavage; KW Direct protein sequencing; Disease variant; Endoplasmic reticulum; KW Epilepsy; Hydrolase; Membrane; Mitochondrion; Neurodegeneration; KW Parkinson disease; Parkinsonism; Protease; Proteomics identification; KW Reference proteome; Serine protease; Transit peptide; Transmembrane; KW Transmembrane helix; Ubl conjugation; Zymogen. FT TRANSIT 1..31 FT /note="Mitochondrion" FT PROPEP 32..133 FT /evidence="ECO:0000269|PubMed:11583623" FT /id="PRO_0000026945" FT CHAIN 134..458 FT /note="Serine protease HTRA2, mitochondrial" FT /id="PRO_0000026946" FT TRANSMEM 105..125 FT /note="Helical" FT /evidence="ECO:0000255" FT DOMAIN 364..445 FT /note="PDZ" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143" FT REGION 166..342 FT /note="Serine protease" FT MOTIF 134..137 FT /note="IAP-binding motif" FT ACT_SITE 198 FT /note="Charge relay system" FT /evidence="ECO:0000269|PubMed:11967569" FT ACT_SITE 228 FT /note="Charge relay system" FT /evidence="ECO:0000269|PubMed:11967569" FT ACT_SITE 306 FT /note="Charge relay system" FT /evidence="ECO:0000269|PubMed:11967569" FT VAR_SEQ 238..302 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:10995577" FT /id="VSP_005359" FT VAR_SEQ 313 FT /note="L -> LARELGAVSLQ (in isoform 3)" FT /evidence="ECO:0000303|PubMed:10971580" FT /id="VSP_005360" FT VAR_SEQ 314..458 FT /note="DGEVIGVNTMKVTAGISFAIPSDRLREFLHRGEKKNSSSGISGSQRRYIGVM FT MLTLSPSILAELQLREPSFPDVQHGVLIHKVILGSPAHRAGLRPGDVILAIGEQMVQNA FT EDVYEAVRTQSQLAVQIRRGRETLTLYVTPEVTE -> VSETSFLPRIPAPGQCGKGRF FT PLIQGCLVKFLSSSLLAISQYPTRSPQHLLVLLFGCPHPLLFV (in isoform 4)" FT /evidence="ECO:0000303|PubMed:10971580" FT /id="VSP_005362" FT VAR_SEQ 372..403 FT /note="Missing (in isoform 2 and isoform 3)" FT /evidence="ECO:0000303|PubMed:10971580, FT ECO:0000303|PubMed:10995577" FT /id="VSP_005361" FT VARIANT 12 FT /note="W -> C (in dbSNP:rs775840965)" FT /evidence="ECO:0000269|PubMed:18364387" FT /id="VAR_076967" FT VARIANT 72 FT /note="L -> P (in dbSNP:rs150047108)" FT /evidence="ECO:0000269|PubMed:18401856" FT /id="VAR_046134" FT VARIANT 128 FT /note="P -> L (in dbSNP:rs757704467)" FT /evidence="ECO:0000269|PubMed:18364387" FT /id="VAR_076968" FT VARIANT 141 FT /note="A -> S (may be a risk factor for Parkinson disease; FT reduced protease activity; dbSNP:rs72470544)" FT /evidence="ECO:0000269|PubMed:15961413, FT ECO:0000269|PubMed:18364387, ECO:0000269|PubMed:18401856" FT /id="VAR_027349" FT VARIANT 227 FT /note="A -> S (in dbSNP:rs375322953)" FT /evidence="ECO:0000269|PubMed:18364387" FT /id="VAR_076969" FT VARIANT 243..244 FT /note="LP -> PS (in MGCA8; loss of protein expression; FT dbSNP:rs1057519082)" FT /evidence="ECO:0000269|PubMed:27696117" FT /id="VAR_077960" FT VARIANT 399 FT /note="G -> S (may be a risk factor for Parkinson disease; FT reduced protease activity; dbSNP:rs72470545)" FT /evidence="ECO:0000269|PubMed:15961413, FT ECO:0000269|PubMed:18364387, ECO:0000269|PubMed:25422467, FT ECO:0000269|PubMed:27535533" FT /id="VAR_027350" FT VARIANT 404 FT /note="R -> Q (in MGCA8; may lead to skipping of exon 7 and FT the resultant protein may be truncated; loss of protein FT expression in patient cells homozygous for the mutation; FT dbSNP:rs767006508)" FT /evidence="ECO:0000269|PubMed:27208207" FT /id="VAR_077961" FT VARIANT 404 FT /note="R -> W (in PARK13; dbSNP:rs1380794702)" FT /evidence="ECO:0000269|PubMed:18401856" FT /id="VAR_046135" FT MUTAGEN 134 FT /note="A->M: Loss of interaction with XIAP. Loss of FT inhibition of XIAP activity." FT /evidence="ECO:0000269|PubMed:11583623" FT MUTAGEN 306 FT /note="S->A: Loss of protease activity." FT /evidence="ECO:0000269|PubMed:10644717" FT HELIX 143..147 FT /evidence="ECO:0007829|PDB:5M3N" FT HELIX 149..157 FT /evidence="ECO:0007829|PDB:5M3N" FT HELIX 158..160 FT /evidence="ECO:0007829|PDB:5M3N" FT STRAND 161..170 FT /evidence="ECO:0007829|PDB:5M3N" FT TURN 171..174 FT /evidence="ECO:0007829|PDB:5M3N" FT STRAND 175..188 FT /evidence="ECO:0007829|PDB:5M3N" FT TURN 189..191 FT /evidence="ECO:0007829|PDB:5M3N" FT STRAND 192..195 FT /evidence="ECO:0007829|PDB:5M3N" FT HELIX 198..200 FT /evidence="ECO:0007829|PDB:5M3N" FT STRAND 204..209 FT /evidence="ECO:0007829|PDB:5M3N" FT STRAND 211..213 FT /evidence="ECO:0007829|PDB:5TO0" FT STRAND 215..224 FT /evidence="ECO:0007829|PDB:5M3N" FT TURN 225..228 FT /evidence="ECO:0007829|PDB:5M3N" FT STRAND 229..233 FT /evidence="ECO:0007829|PDB:5M3N" FT HELIX 248..250 FT /evidence="ECO:0007829|PDB:5M3N" FT STRAND 256..259 FT /evidence="ECO:0007829|PDB:5M3N" FT STRAND 265..268 FT /evidence="ECO:0007829|PDB:5FHT" FT STRAND 271..275 FT /evidence="ECO:0007829|PDB:5M3N" FT STRAND 295..299 FT /evidence="ECO:0007829|PDB:5M3N" FT TURN 303..307 FT /evidence="ECO:0007829|PDB:5M3N" FT STRAND 308..311 FT /evidence="ECO:0007829|PDB:5M3N" FT STRAND 317..326 FT /evidence="ECO:0007829|PDB:5M3N" FT STRAND 329..334 FT /evidence="ECO:0007829|PDB:5M3N" FT HELIX 335..342 FT /evidence="ECO:0007829|PDB:5M3N" FT STRAND 359..361 FT /evidence="ECO:0007829|PDB:5M3N" FT STRAND 364..368 FT /evidence="ECO:0007829|PDB:5M3N" FT HELIX 371..380 FT /evidence="ECO:0007829|PDB:5M3N" FT STRAND 382..384 FT /evidence="ECO:0007829|PDB:5WYN" FT STRAND 391..396 FT /evidence="ECO:0007829|PDB:5M3N" FT HELIX 401..405 FT /evidence="ECO:0007829|PDB:5M3N" FT STRAND 412..416 FT /evidence="ECO:0007829|PDB:5M3N" FT HELIX 424..433 FT /evidence="ECO:0007829|PDB:5M3N" FT STRAND 435..443 FT /evidence="ECO:0007829|PDB:5M3N" FT STRAND 446..452 FT /evidence="ECO:0007829|PDB:5M3N" FT STRAND 455..457 FT /evidence="ECO:0007829|PDB:5M3N" SQ SEQUENCE 458 AA; 48841 MW; CEA955A7D0DD8C0D CRC64; MAAPRAGRGA GWSLRAWRAL GGIRWGRRPR LTPDLRALLT SGTSDPRARV TYGTPSLWAR LSVGVTEPRA CLTSGTPGPR AQLTAVTPDT RTREASENSG TRSRAWLAVA LGAGGAVLLL LWGGGRGPPA VLAAVPSPPP ASPRSQYNFI ADVVEKTAPA VVYIEILDRH PFLGREVPIS NGSGFVVAAD GLIVTNAHVV ADRRRVRVRL LSGDTYEAVV TAVDPVADIA TLRIQTKEPL PTLPLGRSAD VRQGEFVVAM GSPFALQNTI TSGIVSSAQR PARDLGLPQT NVEYIQTDAA IDFGNSGGPL VNLDGEVIGV NTMKVTAGIS FAIPSDRLRE FLHRGEKKNS SSGISGSQRR YIGVMMLTLS PSILAELQLR EPSFPDVQHG VLIHKVILGS PAHRAGLRPG DVILAIGEQM VQNAEDVYEA VRTQSQLAVQ IRRGRETLTL YVTPEVTE //