ID XIAP_HUMAN Reviewed; 497 AA. AC P98170; D3DTF2; Q9NQ14; DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot. DT 24-JAN-2001, sequence version 2. DT 27-MAR-2024, entry version 239. DE RecName: Full=E3 ubiquitin-protein ligase XIAP; DE EC=2.3.2.27 {ECO:0000269|PubMed:19473982, ECO:0000269|PubMed:20154138, ECO:0000269|PubMed:21931591, ECO:0000269|PubMed:22304967, ECO:0000269|PubMed:22607974, ECO:0000269|PubMed:29452636, ECO:0000269|PubMed:30026309}; DE AltName: Full=Baculoviral IAP repeat-containing protein 4; DE AltName: Full=IAP-like protein {ECO:0000303|PubMed:8654366}; DE Short=ILP {ECO:0000303|PubMed:8654366}; DE Short=hILP {ECO:0000303|PubMed:8654366}; DE AltName: Full=Inhibitor of apoptosis protein 3; DE Short=IAP-3; DE Short=hIAP-3; DE Short=hIAP3; DE AltName: Full=RING-type E3 ubiquitin transferase XIAP; DE AltName: Full=X-linked inhibitor of apoptosis protein; DE Short=X-linked IAP; GN Name=XIAP {ECO:0000303|PubMed:12121969, ECO:0000312|HGNC:HGNC:592}; GN Synonyms=API3, BIRC4, IAP3; 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], TISSUE SPECIFICITY, AND VARIANT PRO-423. RC TISSUE=Fetal heart; RX PubMed=8654366; DOI=10.1002/j.1460-2075.1996.tb00629.x; RA Duckett C.S., Nava V.E., Gedrich R.W., Clem R.J., van Dongen J.L., RA Gilfillan M.C., Shiels H., Hardwick J.M., Thompson C.B.; RT "A conserved family of cellular genes related to the baculovirus iap gene RT and encoding apoptosis inhibitors."; RL EMBO J. 15:2685-2694(1996). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Fetal brain; RX PubMed=8552191; DOI=10.1038/379349a0; RA Liston P., Roy N., Tamai K., Lefebvre C., Baird S., Cherton-Horvat G., RA Farahani R., McLean M., Ikeda J., Mackenzie A., Korneluk R.G.; RT "Suppression of apoptosis in mammalian cells by NAIP and a related family RT of IAP genes."; RL Nature 379:349-353(1996). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS SER-107; PHE-133; GLU-242 RP AND PRO-423. RG NIEHS SNPs program; RL Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15772651; DOI=10.1038/nature03440; RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C., RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., RA Rogers J., Bentley D.R.; RT "The DNA sequence of the human X chromosome."; RL Nature 434:325-337(2005). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Uterus; 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 [7] RP FUNCTION. RX PubMed=9230442; DOI=10.1038/40901; RA Deveraux Q.L., Takahashi R., Salvesen G.S., Reed J.C.; RT "X-linked IAP is a direct inhibitor of cell-death proteases."; RL Nature 388:300-304(1997). RN [8] RP FUNCTION, AND MUTAGENESIS OF CYS-450. RX PubMed=11447297; DOI=10.1073/pnas.161506698; RA Suzuki Y., Nakabayashi Y., Takahashi R.; RT "Ubiquitin-protein ligase activity of X-linked inhibitor of apoptosis RT protein promotes proteasomal degradation of caspase-3 and enhances its RT anti-apoptotic effect in Fas-induced cell death."; RL Proc. Natl. Acad. Sci. U.S.A. 98:8662-8667(2001). RN [9] RP MUTAGENESIS OF ASP-148; ASP-214; ASN-259; TRP-310 AND GLU-314. RX PubMed=11604410; DOI=10.1074/jbc.m109891200; RA Verhagen A.M., Silke J., Ekert P.G., Pakusch M., Kaufmann H., RA Connolly L.M., Day C.L., Tikoo A., Burke R., Wrobel C., Moritz R.L., RA Simpson R.J., Vaux D.L.; RT "HtrA2 promotes cell death through its serine protease activity and its RT ability to antagonize inhibitor of apoptosis proteins."; RL J. Biol. Chem. 277:445-454(2002). RN [10] RP FUNCTION. RX PubMed=12121969; DOI=10.1074/jbc.m200317200; RA MacFarlane M., Merrison W., Bratton S.B., Cohen G.M.; RT "Proteasome-mediated degradation of Smac during apoptosis: XIAP promotes RT Smac ubiquitination in vitro."; RL J. Biol. Chem. 277:36611-36616(2002). RN [11] RP AUTOUBIQUITINATION AT LYS-322 AND LYS-328. RX PubMed=12747801; DOI=10.1042/bj20030583; RA Shin H., Okada K., Wilkinson J.C., Solomon K.M., Duckett C.S., Reed J.C., RA Salvesen G.S.; RT "Identification of ubiquitination sites on the X-linked inhibitor of RT apoptosis protein."; RL Biochem. J. 373:965-971(2003). RN [12] RP INTERACTION WITH COMMD1, AND FUNCTION. RX PubMed=14685266; DOI=10.1038/sj.emboj.7600031; RA Burstein E., Ganesh L., Dick R.D., van De Sluis B., Wilkinson J.C., RA Klomp L.W., Wijmenga C., Brewer G.J., Nabel G.J., Duckett C.S.; RT "A novel role for XIAP in copper homeostasis through regulation of MURR1."; RL EMBO J. 23:244-254(2004). RN [13] RP INTERACTION WITH SEPTIN4. RX PubMed=15029247; DOI=10.1038/sj.emboj.7600155; RA Gottfried Y., Rotem A., Lotan R., Steller H., Larisch S.; RT "The mitochondrial ARTS protein promotes apoptosis through targeting RT XIAP."; RL EMBO J. 23:1627-1635(2004). RN [14] RP RETRACTED PAPER. RX PubMed=14645242; DOI=10.1074/jbc.m312044200; RA Dan H.C., Sun M., Kaneko S., Feldman R.I., Nicosia S.V., Wang H.-G., RA Tsang B.K., Cheng J.Q.; RT "Akt phosphorylation and stabilization of X-linked inhibitor of apoptosis RT protein (XIAP)."; RL J. Biol. Chem. 279:5405-5412(2004). RN [15] RP SUBCELLULAR LOCATION, AND UBIQUITINATION BY TRIM32. RX PubMed=21628460; DOI=10.1074/jbc.m111.241893; RA Ryu Y.S., Lee Y., Lee K.W., Hwang C.Y., Maeng J.S., Kim J.H., Seo Y.S., RA You K.H., Song B., Kwon K.S.; RT "TRIM32 protein sensitizes cells to tumor necrosis factor (TNFalpha)- RT induced apoptosis via its RING domain-dependent E3 ligase activity against RT X-linked inhibitor of apoptosis (XIAP)."; RL J. Biol. Chem. 286:25729-25738(2011). RN [16] RP RETRACTION NOTICE OF PUBMED:14645242. RX PubMed=27825084; DOI=10.1074/jbc.a116.312044; RA Dan H.C., Sun M., Kaneko S., Feldman R.I., Nicosia S.V., Wang H.G., RA Tsang B.K., Cheng J.Q.; RL J. Biol. Chem. 291:22846-22846(2016). RN [17] RP SUBCELLULAR LOCATION. RX PubMed=15665297; DOI=10.1158/0008-5472.210.65.1; RA Samuel T., Okada K., Hyer M., Welsh K., Zapata J.M., Reed J.C.; RT "cIAP1 Localizes to the nuclear compartment and modulates the cell cycle."; RL Cancer Res. 65:210-218(2005). RN [18] RP FUNCTION. RX PubMed=16352606; DOI=10.1074/jbc.m507393200; RA Twiddy D., Cohen G.M., Macfarlane M., Cain K.; RT "Caspase-7 is directly activated by the approximately 700-kDa apoptosome RT complex and is released as a stable XIAP-caspase-7 approximately 200-kDa RT complex."; RL J. Biol. Chem. 281:3876-3888(2006). RN [19] RP INVOLVEMENT IN XLP2. RX PubMed=17080092; DOI=10.1038/nature05257; RA Rigaud S., Fondaneche M.-C., Lambert N., Pasquier B., Mateo V., Soulas P., RA Galicier L., Le Deist F., Rieux-Laucat F., Revy P., Fischer A., RA de Saint Basile G., Latour S.; RT "XIAP deficiency in humans causes an X-linked lymphoproliferative RT syndrome."; RL Nature 444:110-114(2006). RN [20] RP FUNCTION. RX PubMed=16916640; DOI=10.1016/j.molcel.2006.06.020; RA Denault J.B., Bekes M., Scott F.L., Sexton K.M., Bogyo M., Salvesen G.S.; RT "Engineered hybrid dimers: tracking the activation pathway of caspase-7."; RL Mol. Cell 23:523-533(2006). RN [21] RP REVIEW ON FUNCTION. RX PubMed=17382285; DOI=10.1016/j.abb.2007.01.033; RA Mufti A.R., Burstein E., Duckett C.S.; RT "XIAP: cell death regulation meets copper homeostasis."; RL Arch. Biochem. Biophys. 463:168-174(2007). RN [22] RP INTERACTION WITH TCF25. RX PubMed=18068114; DOI=10.1016/j.bbrc.2007.11.146; RA Steen H., Lindholm D.; RT "Nuclear localized protein-1 (Nulp1) increases cell death of human RT osteosarcoma cells and binds the X-linked inhibitor of apoptosis protein."; RL Biochem. Biophys. Res. Commun. 366:432-437(2008). RN [23] RP REVIEW ON FUNCTION. RX PubMed=18414036; DOI=10.4161/cc.7.8.5783; RA Dubrez-Daloz L., Dupoux A., Cartier J.; RT "IAPs: more than just inhibitors of apoptosis proteins."; RL Cell Cycle 7:1036-1046(2008). RN [24] RP INTERACTION WITH PDCL3. RX PubMed=19012568; DOI=10.1111/j.1747-0285.2008.00719.x; RA Bisson W.H., Zhang Z., Welsh K., Huang J.W., Ryan J., Reed J.C., RA Pellecchia M.; RT "Binding properties of the C-terminal domain of VIAF."; RL Chem. Biol. Drug Des. 72:331-336(2008). RN [25] RP FUNCTION, MUTAGENESIS OF HIS-467, AND INTERACTION WITH AIFM1. RX PubMed=17967870; DOI=10.1128/mcb.01065-07; RA Wilkinson J.C., Wilkinson A.S., Galban S., Csomos R.A., Duckett C.S.; RT "Apoptosis-inducing factor is a target for ubiquitination through RT interaction with XIAP."; RL Mol. Cell. Biol. 28:237-247(2008). RN [26] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [27] RP FUNCTION IN THE UBIQUITINATION OF PTEN, CATALYTIC ACTIVITY, AND INTERACTION RP WITH PTEN. RX PubMed=19473982; DOI=10.1074/jbc.c109.009522; RA Van Themsche C., Leblanc V., Parent S., Asselin E.; RT "X-linked inhibitor of apoptosis protein (XIAP) regulates PTEN RT ubiquitination, content, and compartmentalization."; RL J. Biol. Chem. 284:20462-20466(2009). RN [28] RP FUNCTION. RX PubMed=19667203; DOI=10.1073/pnas.0907131106; RA Krieg A., Correa R.G., Garrison J.B., Le Negrate G., Welsh K., Huang Z., RA Knoefel W.T., Reed J.C.; RT "XIAP mediates NOD signaling via interaction with RIP2."; RL Proc. Natl. Acad. Sci. U.S.A. 106:14524-14529(2009). RN [29] RP INTERACTION WITH HAX1. RX PubMed=20171186; DOI=10.1016/j.bbrc.2010.02.084; RA Kang Y.J., Jang M., Park Y.K., Kang S., Bae K.H., Cho S., Lee C.K., RA Park B.C., Chi S.W., Park S.G.; RT "Molecular interaction between HAX-1 and XIAP inhibits apoptosis."; RL Biochem. Biophys. Res. Commun. 393:794-799(2010). RN [30] RP REVIEW ON FUNCTION. RX PubMed=20888210; DOI=10.1016/j.ceb.2010.08.025; RA Lopez J., Meier P.; RT "To fight or die - inhibitor of apoptosis proteins at the crossroad of RT innate immunity and death."; RL Curr. Opin. Cell Biol. 22:872-881(2010). RN [31] RP S-NITROSYLATION AT CYS-450. RX PubMed=20670888; DOI=10.1016/j.molcel.2010.07.002; RA Nakamura T., Wang L., Wong C.C., Scott F.L., Eckelman B.P., Han X., RA Tzitzilonis C., Meng F., Gu Z., Holland E.A., Clemente A.T., Okamoto S., RA Salvesen G.S., Riek R., Yates J.R. III, Lipton S.A.; RT "Transnitrosylation of XIAP regulates caspase-dependent neuronal cell RT death."; RL Mol. Cell 39:184-195(2010). RN [32] RP FUNCTION AS AN E3 UBIQUITIN-PROTEIN LIGASE OF THE NEDD8 CONJUGATION RP PATHWAY. RX PubMed=21145488; DOI=10.1016/j.molcel.2010.11.011; RA Broemer M., Tenev T., Rigbolt K.T., Hempel S., Blagoev B., Silke J., RA Ditzel M., Meier P.; RT "Systematic in vivo RNAi analysis identifies IAPs as NEDD8-E3 ligases."; RL Mol. Cell 40:810-822(2010). RN [33] RP FUNCTION IN THE UBIQUITINATION OF CCS, CATALYTIC ACTIVITY, AND INTERACTION RP WITH CCS. RX PubMed=20154138; DOI=10.1128/mcb.00900-09; RA Brady G.F., Galban S., Liu X., Basrur V., Gitlin J.D., RA Elenitoba-Johnson K.S., Wilson T.E., Duckett C.S.; RT "Regulation of the copper chaperone CCS by XIAP-mediated ubiquitination."; RL Mol. Cell. Biol. 30:1923-1936(2010). RN [34] RP REVIEW ON FUNCTION. RX PubMed=20651737; DOI=10.1038/nrc2889; RA Gyrd-Hansen M., Meier P.; RT "IAPs: from caspase inhibitors to modulators of NF-kappaB, inflammation and RT cancer."; RL Nat. Rev. Cancer 10:561-574(2010). RN [35] RP INTERACTION WITH SEPTIN4 ISOFORM ARTS AND DIABLO, AND MUTAGENESIS OF RP TRP-310; GLU-314 AND HIS-343. RX PubMed=21695558; DOI=10.1007/s10495-011-0622-0; RA Bornstein B., Gottfried Y., Edison N., Shekhtman A., Lev T., Glaser F., RA Larisch S.; RT "ARTS binds to a distinct domain in XIAP-BIR3 and promotes apoptosis by a RT mechanism that is different from other IAP-antagonists."; RL Apoptosis 16:869-881(2011). RN [36] 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 [37] RP FUNCTION IN THE UBIQUITINATION OF AIFM1. RX PubMed=22103349; DOI=10.1021/bi201483g; RA Lewis E.M., Wilkinson A.S., Davis N.Y., Horita D.A., Wilkinson J.C.; RT "Nondegradative ubiquitination of apoptosis inducing factor (AIF) by X- RT linked inhibitor of apoptosis at a residue critical for AIF-mediated RT chromatin degradation."; RL Biochemistry 50:11084-11096(2011). RN [38] RP REVIEW ON FUNCTION. RX PubMed=21447281; RA Damgaard R.B., Gyrd-Hansen M.; RT "Inhibitor of apoptosis (IAP) proteins in regulation of inflammation and RT innate immunity."; RL Discov. Med. 11:221-231(2011). RN [39] RP INTERACTION WITH BIRC5/SURVIVIN. RX PubMed=21536684; DOI=10.1074/jbc.m111.237586; RA Pavlyukov M.S., Antipova N.V., Balashova M.V., Vinogradova T.V., RA Kopantzev E.P., Shakhparonov M.I.; RT "Survivin monomer plays an essential role in apoptosis regulation."; RL J. Biol. Chem. 286:23296-23307(2011). RN [40] RP INTERACTION WITH USP19. RX PubMed=21849505; DOI=10.1074/jbc.m111.282020; RA Mei Y., Hahn A.A., Hu S., Yang X.; RT "The USP19 deubiquitinase regulates the stability of c-IAP1 and c-IAP2."; RL J. Biol. Chem. 286:35380-35387(2011). RN [41] RP CATALYTIC ACTIVITY, AND INTERACTION WITH RIPK1; RIPK2; RIPK3 AND RIPK4. RX PubMed=21931591; DOI=10.1371/journal.pone.0022356; RA Bertrand M.J., Lippens S., Staes A., Gilbert B., Roelandt R., De Medts J., RA Gevaert K., Declercq W., Vandenabeele P.; RT "cIAP1/2 are direct E3 ligases conjugating diverse types of ubiquitin RT chains to receptor interacting proteins kinases 1 to 4 (RIP1-4)."; RL PLoS ONE 6:E22356-E22356(2011). RN [42] RP REVIEW ON FUNCTION. RX PubMed=22095281; DOI=10.1038/cdd.2011.163; RA Darding M., Meier P.; RT "IAPs: guardians of RIPK1."; RL Cell Death Differ. 19:58-66(2012). RN [43] RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF PHE-495. RX PubMed=22607974; DOI=10.1016/j.molcel.2012.04.014; RA Damgaard R.B., Nachbur U., Yabal M., Wong W.W., Fiil B.K., Kastirr M., RA Rieser E., Rickard J.A., Bankovacki A., Peschel C., Ruland J., RA Bekker-Jensen S., Mailand N., Kaufmann T., Strasser A., Walczak H., RA Silke J., Jost P.J., Gyrd-Hansen M.; RT "The ubiquitin ligase XIAP recruits LUBAC for NOD2 signaling in RT inflammation and innate immunity."; RL Mol. Cell 46:746-758(2012). RN [44] RP TISSUE SPECIFICITY. RX PubMed=30389919; DOI=10.1038/s41467-018-06941-4; RA Koren E., Yosefzon Y., Ankawa R., Soteriou D., Jacob A., Nevelsky A., RA Ben-Yosef R., Bar-Sela G., Fuchs Y.; RT "ARTS mediates apoptosis and regeneration of the intestinal stem cell RT niche."; RL Nat. Commun. 9:4582-4582(2018). RN [45] RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND INTERACTION WITH RP TLE3 AND TCF7L2/TCF4. RX PubMed=22304967; DOI=10.1016/j.molcel.2011.12.032; RA Hanson A.J., Wallace H.A., Freeman T.J., Beauchamp R.D., Lee L.A., Lee E.; RT "XIAP monoubiquitylates Groucho/TLE to promote canonical Wnt signaling."; RL Mol. Cell 45:619-628(2012). RN [46] RP FUNCTION, IDENTIFICATION IN A COMPLEX WITH BCL2 AND SEPTIN4 ISOFORM ARTS, RP AND INTERACTION WITH BCL2 AND SEPTIN4 ISOFORM ARTS. RX PubMed=29020630; DOI=10.1016/j.celrep.2017.09.052; RA Edison N., Curtz Y., Paland N., Mamriev D., Chorubczyk N., RA Haviv-Reingewertz T., Kfir N., Morgenstern D., Kupervaser M., Kagan J., RA Kim H.T., Larisch S.; RT "Degradation of Bcl-2 by XIAP and ARTS Promotes Apoptosis."; RL Cell Rep. 21:442-454(2017). RN [47] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=30026309; DOI=10.15252/embj.201899372; RA Hrdinka M., Schlicher L., Dai B., Pinkas D.M., Bufton J.C., Picaud S., RA Ward J.A., Rogers C., Suebsuwong C., Nikhar S., Cuny G.D., Huber K.V., RA Filippakopoulos P., Bullock A.N., Degterev A., Gyrd-Hansen M.; RT "Small molecule inhibitors reveal an indispensable scaffolding role of RT RIPK2 in NOD2 signaling."; RL EMBO J. 37:0-0(2018). RN [48] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=29452636; DOI=10.1016/j.molcel.2018.01.016; RA Goncharov T., Hedayati S., Mulvihill M.M., Izrael-Tomasevic A., Zobel K., RA Jeet S., Fedorova A.V., Eidenschenk C., deVoss J., Yu K., Shaw A.S., RA Kirkpatrick D.S., Fairbrother W.J., Deshayes K., Vucic D.; RT "Disruption of XIAP-RIP2 association blocks NOD2-mediated inflammatory RT signaling."; RL Mol. Cell 69:551-565(2018). RN [49] RP STRUCTURE BY NMR OF 124-240, AND MUTAGENESIS OF LEU-141; VAL-147; ASP-148; RP ILE-149; ASP-151; LEU-167 AND ASP-196. RX PubMed=10548111; DOI=10.1038/44617; RA Sun C., Cai M., Gunasekera A.H., Meadows R.P., Wang H., Chen J., Zhang H., RA Wu W., Xu N., Ng S.-C., Fesik S.W.; RT "NMR structure and mutagenesis of the inhibitor-of-apoptosis protein RT XIAP."; RL Nature 401:818-822(1999). RN [50] RP STRUCTURE BY NMR OF 238-358 IN COMPLEX WITH DIABLO/SMAC. RX PubMed=11140637; DOI=10.1038/35050006; RA Liu Z., Sun C., Olejniczak E.T., Meadows R.P., Betz S.F., Oost T., RA Herrmann J., Wu J.C., Fesik S.W.; RT "Structural basis for binding of Smac/DIABLO to the XIAP BIR3 domain."; RL Nature 408:1004-1008(2000). RN [51] {ECO:0007744|PDB:1I51} RP X-RAY CRYSTALLOGRAPHY (2.45 ANGSTROMS) OF 124-240 IN COMPLEX WITH CASP7, RP FUNCTION, AND DOMAIN. RX PubMed=11257230; DOI=10.1016/s0092-8674(01)00272-0; RA Chai J., Shiozaki E., Srinivasula S.M., Wu Q., Datta P., Alnemri E.S., RA Shi Y., Dataa P.; RT "Structural basis of caspase-7 inhibition by XIAP."; RL Cell 104:769-780(2001). RN [52] RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 120-260 IN COMPLEX WITH CASP7, RP FUNCTION, DOMAIN, AND INTERACTION WITH DIABLO. RX PubMed=11257231; DOI=10.1016/s0092-8674(02)02075-5; RA Huang Y., Park Y.C., Rich R.L., Segal D., Myszka D.G., Wu H.; RT "Structural basis of caspase inhibition by XIAP: differential roles of the RT linker versus the BIR domain."; RL Cell 104:781-790(2001). RN [53] RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 253-350 IN COMPLEX WITH CASP9, RP DOMAIN, AND FUNCTION. RX PubMed=12620238; DOI=10.1016/s1097-2765(03)00054-6; RA Shiozaki E.N., Chai J., Rigotti D.J., Riedl S.J., Li P., Srinivasula S.M., RA Alnemri E.S., Fairman R., Shi Y.; RT "Mechanism of XIAP-mediated inhibition of caspase-9."; RL Mol. Cell 11:519-527(2003). RN [54] RP STRUCTURE BY NMR OF 241-356. RX PubMed=15317454; DOI=10.1021/jm040037k; RA Oost T.K., Sun C., Armstrong R.C., Al-Assaad A.-S., Betz S.F., RA Deckwerth T.L., Ding H., Elmore S.W., Meadows R.P., Olejniczak E.T., RA Oleksijew A., Oltersdorf T., Rosenberg S.H., Shoemaker A.R., RA Tomaselli K.J., Zou H., Fesik S.W.; RT "Discovery of potent antagonists of the antiapoptotic protein XIAP for the RT treatment of cancer."; RL J. Med. Chem. 47:4417-4426(2004). RN [55] RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 249-354. RX PubMed=17336535; DOI=10.1016/j.bmc.2007.02.010; RA Wist A.D., Gu L., Riedl S.J., Shi Y., McLendon G.L.; RT "Structure-activity based study of the Smac-binding pocket within the BIR3 RT domain of XIAP."; RL Bioorg. Med. Chem. 15:2935-2943(2007). RN [56] RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 10-99, MUTAGENESIS OF SER-87, AND RP SUBUNIT. RX PubMed=17698078; DOI=10.1016/j.jmb.2007.07.019; RA Lin S.-C., Huang Y., Lo Y.-C., Lu M., Wu H.; RT "Crystal structure of the BIR1 domain of XIAP in two crystal forms."; RL J. Mol. Biol. 372:847-854(2007). RN [57] RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 10-99 IN COMPLEX WITH TAB1, RP FUNCTION, AND MUTAGENESIS OF TYR-75; VAL-80; VAL-86 AND LEU-98. RX PubMed=17560374; DOI=10.1016/j.molcel.2007.05.006; RA Lu M., Lin S.-C., Huang Y., Kang Y.J., Rich R., Lo Y.-C., Myszka D., RA Han J., Wu H.; RT "XIAP induces NF-kappaB activation via the BIR1/TAB1 interaction and BIR1 RT dimerization."; RL Mol. Cell 26:689-702(2007). RN [58] RP STRUCTURE BY NMR OF 427-497. RG RIKEN structural genomics initiative (RSGI); RT "Solution structure of the RING domain of the baculoviral IAP repeat- RT containing protein 4 from Homo sapiens."; RL Submitted (MAR-2008) to the PDB data bank. RN [59] RP VARIANTS XLP2 104-GLN--SER-497 DEL; GLU-188; ASN-194; 333-GLN--SER-497 DEL RP AND ARG-482. RX PubMed=20489057; DOI=10.1182/blood-2010-01-256099; RA Marsh R.A., Madden L., Kitchen B.J., Mody R., McClimon B., Jordan M.B., RA Bleesing J.J., Zhang K., Filipovich A.H.; RT "XIAP deficiency: a unique primary immunodeficiency best classified as X- RT linked familial hemophagocytic lymphohistiocytosis and not as X-linked RT lymphoproliferative disease."; RL Blood 116:1079-1082(2010). RN [60] RP VARIANTS XLP2 118-GLU--SER-497 DEL; 238-ARG--SER-497 DEL; 381-ARG--SER-497 RP DEL AND 466-GLY--SER-497 DEL. RX PubMed=21119115; DOI=10.1182/blood-2010-07-298372; RA Pachlopnik Schmid J., Canioni D., Moshous D., Touzot F., Mahlaoui N., RA Hauck F., Kanegane H., Lopez-Granados E., Mejstrikova E., Pellier I., RA Galicier L., Galambrun C., Barlogis V., Bordigoni P., Fourmaintraux A., RA Hamidou M., Dabadie A., Le Deist F., Haerynck F., Ouachee-Chardin M., RA Rohrlich P., Stephan J.L., Lenoir C., Rigaud S., Lambert N., Milili M., RA Schiff C., Chapel H., Picard C., de Saint Basile G., Blanche S., RA Fischer A., Latour S.; RT "Clinical similarities and differences of patients with X-linked RT lymphoproliferative syndrome type 1 (XLP-1/SAP deficiency) versus type 2 RT (XLP-2/XIAP deficiency)."; RL Blood 117:1522-1529(2011). CC -!- FUNCTION: Multi-functional protein which regulates not only caspases CC and apoptosis, but also modulates inflammatory signaling and immunity, CC copper homeostasis, mitogenic kinase signaling, cell proliferation, as CC well as cell invasion and metastasis (PubMed:11447297, PubMed:12121969, CC PubMed:9230442, PubMed:11257230, PubMed:11257231, PubMed:12620238, CC PubMed:17967870, PubMed:19473982, PubMed:20154138, PubMed:22103349, CC PubMed:17560374). Acts as a direct caspase inhibitor (PubMed:11257230, CC PubMed:11257231, PubMed:12620238). Directly bind to the active site CC pocket of CASP3 and CASP7 and obstructs substrate entry CC (PubMed:11257230, PubMed:11257231, PubMed:16352606, PubMed:16916640). CC Inactivates CASP9 by keeping it in a monomeric, inactive state CC (PubMed:12620238). Acts as an E3 ubiquitin-protein ligase regulating CC NF-kappa-B signaling and the target proteins for its E3 ubiquitin- CC protein ligase activity include: RIPK1, RIPK2, MAP3K2/MEKK2, CC DIABLO/SMAC, AIFM1, CCS, PTEN and BIRC5/survivin (PubMed:17967870, CC PubMed:19473982, PubMed:20154138, PubMed:22103349, PubMed:22607974, CC PubMed:30026309, PubMed:29452636, PubMed:17560374). Acts as an CC important regulator of innate immunity by mediating 'Lys-63'-linked CC polyubiquitination of RIPK2 downstream of NOD1 and NOD2, thereby CC transforming RIPK2 into a scaffolding protein for downstream effectors, CC ultimately leading to activation of the NF-kappa-B and MAP kinases CC signaling (PubMed:19667203, PubMed:22607974, PubMed:30026309, CC PubMed:29452636). 'Lys-63'-linked polyubiquitination of RIPK2 also CC promotes recruitment of the LUBAC complex to RIPK2 (PubMed:22607974, CC PubMed:29452636). Regulates the BMP signaling pathway and the SMAD and CC MAP3K7/TAK1 dependent pathways leading to NF-kappa-B and JNK activation CC (PubMed:17560374). Ubiquitination of CCS leads to enhancement of its CC chaperone activity toward its physiologic target, SOD1, rather than CC proteasomal degradation (PubMed:20154138). Ubiquitination of CC MAP3K2/MEKK2 and AIFM1 does not lead to proteasomal degradation CC (PubMed:17967870, PubMed:22103349). Plays a role in copper homeostasis CC by ubiquitinating COMMD1 and promoting its proteasomal degradation CC (PubMed:14685266). Can also function as E3 ubiquitin-protein ligase of CC the NEDD8 conjugation pathway, targeting effector caspases for CC neddylation and inactivation (PubMed:21145488). Ubiquitinates and CC therefore mediates the proteasomal degradation of BCL2 in response to CC apoptosis (PubMed:29020630). Protects cells from spontaneous formation CC of the ripoptosome, a large multi-protein complex that has the CC capability to kill cancer cells in a caspase-dependent and caspase- CC independent manner (PubMed:22095281). Suppresses ripoptosome formation CC by ubiquitinating RIPK1 and CASP8 (PubMed:22095281). Acts as a positive CC regulator of Wnt signaling and ubiquitinates TLE1, TLE2, TLE3, TLE4 and CC AES (PubMed:22304967). Ubiquitination of TLE3 results in inhibition of CC its interaction with TCF7L2/TCF4 thereby allowing efficient recruitment CC and binding of the transcriptional coactivator beta-catenin to CC TCF7L2/TCF4 that is required to initiate a Wnt-specific transcriptional CC program (PubMed:22304967). {ECO:0000269|PubMed:11257230, CC ECO:0000269|PubMed:11257231, ECO:0000269|PubMed:11447297, CC ECO:0000269|PubMed:12121969, ECO:0000269|PubMed:12620238, CC ECO:0000269|PubMed:14685266, ECO:0000269|PubMed:16352606, CC ECO:0000269|PubMed:16916640, ECO:0000269|PubMed:17560374, CC ECO:0000269|PubMed:17967870, ECO:0000269|PubMed:19473982, CC ECO:0000269|PubMed:19667203, ECO:0000269|PubMed:20154138, CC ECO:0000269|PubMed:21145488, ECO:0000269|PubMed:22103349, CC ECO:0000269|PubMed:22304967, ECO:0000269|PubMed:22607974, CC ECO:0000269|PubMed:29020630, ECO:0000269|PubMed:29452636, CC ECO:0000269|PubMed:30026309, ECO:0000269|PubMed:9230442, CC ECO:0000303|PubMed:22095281}. CC -!- CATALYTIC ACTIVITY: CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L- CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.; CC EC=2.3.2.27; Evidence={ECO:0000269|PubMed:19473982, CC ECO:0000269|PubMed:20154138, ECO:0000269|PubMed:21931591, CC ECO:0000269|PubMed:22304967, ECO:0000269|PubMed:22607974, CC ECO:0000269|PubMed:30026309}; CC -!- SUBUNIT: Monomer, and homodimer. Part of a complex composed of SEPTIN4 CC isoform ARTS, XIAP and BCL2, within the complex interacts with SEPTIN4 CC isoform ARTS and BCL2, SEPTIN4 isoform ARTS acts as a scaffold protein CC and stabilizes the complex (PubMed:29020630). Interacts (via BIR3 CC domain) with DIABLO/SMAC; the interaction inhibits apoptotic suppressor CC activity (PubMed:21695558, PubMed:11140637, PubMed:11257230). Interacts CC with HTRA2/PRSS25; the interaction inhibits apoptotic suppressor CC activity (PubMed:11604410). Interacts with TAB1/MAP3K7IP1 and AIFM1. CC Interaction with DIABLO/SMAC hinders binding of TAB1/MAP3K7IP1 and CC AIFM1. Interacts with TCF25 and COMMD1. Interacts (via BIR3 domain) CC with SEPTIN4 isoform ARTS (PubMed:21695558, PubMed:15029247). Interacts CC (via BIR3 domain) with SEPTIN4 (By similarity). Interacts with RIP1, CC RIP2, RIP3, RIP4, CCS and USP19. Interacts (via BIR 2 domain and BIR 3 CC domain) with HAX1 (via C-terminus) and this interaction blocks CC ubiquitination of XIAP/BIRC4. Interacts with the monomeric form of CC BIRC5/survivin. Interacts with TLE3 and TCF7L2/TCF4. Interacts (via BIR CC 3 and RING domains) with PDCL3 (PubMed:19012568). CC {ECO:0000250|UniProtKB:Q60989, ECO:0000269|PubMed:11140637, CC ECO:0000269|PubMed:11257230, ECO:0000269|PubMed:11257231, CC ECO:0000269|PubMed:11604410, ECO:0000269|PubMed:12620238, CC ECO:0000269|PubMed:14685266, ECO:0000269|PubMed:15029247, CC ECO:0000269|PubMed:17560374, ECO:0000269|PubMed:17698078, CC ECO:0000269|PubMed:17967870, ECO:0000269|PubMed:18068114, CC ECO:0000269|PubMed:19012568, ECO:0000269|PubMed:19473982, CC ECO:0000269|PubMed:20154138, ECO:0000269|PubMed:20171186, CC ECO:0000269|PubMed:21536684, ECO:0000269|PubMed:21695558, CC ECO:0000269|PubMed:21849505, ECO:0000269|PubMed:21931591, CC ECO:0000269|PubMed:22304967, ECO:0000269|PubMed:29020630}. CC -!- INTERACTION: CC P98170; Q9Y3E2: BOLA1; NbExp=3; IntAct=EBI-517127, EBI-1049556; CC P98170; A0A087WZT3: BOLA2-SMG1P6; NbExp=3; IntAct=EBI-517127, EBI-12006120; CC P98170; Q92851: CASP10; NbExp=3; IntAct=EBI-517127, EBI-495095; CC P98170; Q92851-4: CASP10; NbExp=3; IntAct=EBI-517127, EBI-6621134; CC P98170; P42574: CASP3; NbExp=4; IntAct=EBI-517127, EBI-524064; CC P98170; P55210: CASP7; NbExp=3; IntAct=EBI-517127, EBI-523958; CC P98170; P55211: CASP9; NbExp=23; IntAct=EBI-517127, EBI-516799; CC P98170; O14618: CCS; NbExp=2; IntAct=EBI-517127, EBI-11668690; CC P98170; P61024: CKS1B; NbExp=7; IntAct=EBI-517127, EBI-456371; CC P98170; Q9NR28: DIABLO; NbExp=9; IntAct=EBI-517127, EBI-517508; CC P98170; Q9NR28-1: DIABLO; NbExp=4; IntAct=EBI-517127, EBI-15490322; CC P98170; Q96FJ2: DYNLL2; NbExp=3; IntAct=EBI-517127, EBI-742371; CC P98170; P19447: ERCC3; NbExp=4; IntAct=EBI-517127, EBI-1183307; CC P98170; Q96CN9: GCC1; NbExp=3; IntAct=EBI-517127, EBI-746252; CC P98170; P07686: HEXB; NbExp=3; IntAct=EBI-517127, EBI-7133736; CC P98170; O43464: HTRA2; NbExp=21; IntAct=EBI-517127, EBI-517086; CC P98170; P83110: HTRA3; NbExp=8; IntAct=EBI-517127, EBI-2867394; CC P98170; P83110-1: HTRA3; NbExp=7; IntAct=EBI-517127, EBI-25469082; CC P98170; P83110-2: HTRA3; NbExp=6; IntAct=EBI-517127, EBI-22017714; CC P98170; P83105: HTRA4; NbExp=11; IntAct=EBI-517127, EBI-21776319; CC P98170; Q17RB8: LONRF1; NbExp=7; IntAct=EBI-517127, EBI-2341787; CC P98170; Q96EZ8: MCRS1; NbExp=3; IntAct=EBI-517127, EBI-348259; CC P98170; Q9HC98: NEK6; NbExp=4; IntAct=EBI-517127, EBI-740364; CC P98170; P46531: NOTCH1; NbExp=4; IntAct=EBI-517127, EBI-636374; CC P98170; Q96HA8: NTAQ1; NbExp=4; IntAct=EBI-517127, EBI-741158; CC P98170; Q4G0R1: PIBF1; NbExp=3; IntAct=EBI-517127, EBI-14066006; CC P98170; O43447: PPIH; NbExp=5; IntAct=EBI-517127, EBI-1055615; CC P98170; Q8N3J5: PPM1K; NbExp=3; IntAct=EBI-517127, EBI-3923368; CC P98170; P47897: QARS1; NbExp=3; IntAct=EBI-517127, EBI-347462; CC P98170; P63000: RAC1; NbExp=3; IntAct=EBI-517127, EBI-413628; CC P98170; P40937: RFC5; NbExp=9; IntAct=EBI-517127, EBI-712376; CC P98170; O43353: RIPK2; NbExp=21; IntAct=EBI-517127, EBI-358522; CC P98170; P57078: RIPK4; NbExp=2; IntAct=EBI-517127, EBI-4422308; CC P98170; Q06455-2: RUNX1T1; NbExp=3; IntAct=EBI-517127, EBI-11984663; CC P98170; O43236-6: SEPTIN4; NbExp=4; IntAct=EBI-517127, EBI-4372019; CC P98170; Q8IUQ4: SIAH1; NbExp=3; IntAct=EBI-517127, EBI-747107; CC P98170; Q9Y2D8: SSX2IP; NbExp=4; IntAct=EBI-517127, EBI-2212028; CC P98170; Q15750: TAB1; NbExp=4; IntAct=EBI-517127, EBI-358643; CC P98170; Q5W5X9-3: TTC23; NbExp=3; IntAct=EBI-517127, EBI-9090990; CC P98170; P0CG48: UBC; NbExp=3; IntAct=EBI-517127, EBI-3390054; CC P98170; P51668: UBE2D1; NbExp=6; IntAct=EBI-517127, EBI-743540; CC P98170; P62837: UBE2D2; NbExp=2; IntAct=EBI-517127, EBI-347677; CC P98170; P61077: UBE2D3; NbExp=2; IntAct=EBI-517127, EBI-348268; CC P98170; P61088: UBE2N; NbExp=2; IntAct=EBI-517127, EBI-1052908; CC P98170; Q13404: UBE2V1; NbExp=3; IntAct=EBI-517127, EBI-1050671; CC P98170; A5D8V6: VPS37C; NbExp=7; IntAct=EBI-517127, EBI-2559305; CC P98170; P98170: XIAP; NbExp=5; IntAct=EBI-517127, EBI-517127; CC P98170; PRO_0000021073 [Q9JIQ3]: Diablo; Xeno; NbExp=3; IntAct=EBI-517127, EBI-25438230; CC P98170; Q9JIY5: Htra2; Xeno; NbExp=4; IntAct=EBI-517127, EBI-2365838; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:21628460, CC ECO:0000269|PubMed:22304967}. Nucleus {ECO:0000269|PubMed:15665297, CC ECO:0000269|PubMed:22304967}. Note=TLE3 promotes its nuclear CC localization. {ECO:0000269|PubMed:22304967}. CC -!- TISSUE SPECIFICITY: Expressed in colonic crypts (at protein level) CC (PubMed:30389919). Ubiquitous, except peripheral blood leukocytes CC (PubMed:8654366). {ECO:0000269|PubMed:30389919, CC ECO:0000269|PubMed:8654366}. CC -!- DOMAIN: The first BIR domain is involved in interaction with CC TAB1/MAP3K7IP1 and is important for dimerization (PubMed:17560374). The CC second BIR domain is sufficient to inhibit CASP3 and CASP7, while the CC third BIR is involved in CASP9 inhibition (PubMed:11257231, CC PubMed:12620238). The interactions with DIABLO/SMAC and HTRA2/PRSS25 CC are mediated by the second and third BIR domains. CC {ECO:0000269|PubMed:11257231, ECO:0000269|PubMed:12620238, CC ECO:0000269|PubMed:17560374}. CC -!- PTM: S-Nitrosylation down-regulates its E3 ubiquitin-protein ligase CC activity. {ECO:0000269|PubMed:20670888}. CC -!- PTM: Autoubiquitinated (PubMed:12747801). Ubiquitinated by TRIM32; CC leading to proteasomal degradation (PubMed:21628460). CC {ECO:0000269|PubMed:12747801, ECO:0000269|PubMed:21628460}. CC -!- DISEASE: Lymphoproliferative syndrome, X-linked, 2 (XLP2) [MIM:300635]: CC A rare immunodeficiency characterized by extreme susceptibility to CC infection with Epstein-Barr virus (EBV). Symptoms include severe or CC fatal mononucleosis, acquired hypogammaglobulinemia, pancytopenia and CC malignant lymphoma. {ECO:0000269|PubMed:17080092, CC ECO:0000269|PubMed:20489057, ECO:0000269|PubMed:21119115}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the IAP family. {ECO:0000305}. CC -!- CAUTION: Was originally shown to be phosphorylated at Ser-87 by PKB, CC protecting the protein from ubiquitination and proteasomal degradation CC (PubMed:14645242). However, this work was later retracted CC (PubMed:27825084). {ECO:0000305|PubMed:14645242, CC ECO:0000305|PubMed:27825084}. CC -!- WEB RESOURCE: Name=BIRC4base; Note=XIAP mutation db; CC URL="http://structure.bmc.lu.se/idbase/BIRC4base/"; CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/birc4/"; 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; U32974; AAC50518.1; -; mRNA. DR EMBL; U45880; AAC50373.1; -; mRNA. DR EMBL; AY886519; AAW62257.1; -; Genomic_DNA. DR EMBL; AL121601; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471107; EAX11858.1; -; Genomic_DNA. DR EMBL; CH471107; EAX11859.1; -; Genomic_DNA. DR EMBL; CH471107; EAX11860.1; -; Genomic_DNA. DR EMBL; CH471107; EAX11861.1; -; Genomic_DNA. DR EMBL; BC032729; AAH32729.1; -; mRNA. DR CCDS; CCDS14606.1; -. DR PIR; S69544; S69544. DR RefSeq; NP_001158.2; NM_001167.3. DR RefSeq; NP_001191330.1; NM_001204401.1. DR RefSeq; XP_006724817.1; XM_006724754.2. DR RefSeq; XP_011529631.1; XM_011531329.2. DR PDB; 1C9Q; NMR; -; A=124-240. DR PDB; 1F9X; NMR; -; A=241-356. DR PDB; 1G3F; NMR; -; A=241-356. DR PDB; 1G73; X-ray; 2.00 A; C/D=238-358. DR PDB; 1I3O; X-ray; 2.70 A; E/F=124-240. DR PDB; 1I4O; X-ray; 2.40 A; C/D=120-260. DR PDB; 1I51; X-ray; 2.45 A; E/F=124-240. DR PDB; 1KMC; X-ray; 2.90 A; C/D=124-242. DR PDB; 1NW9; X-ray; 2.40 A; A=253-350. DR PDB; 1TFQ; NMR; -; A=241-356. DR PDB; 1TFT; NMR; -; A=241-356. DR PDB; 2ECG; NMR; -; A=430-497. DR PDB; 2JK7; X-ray; 2.82 A; A=241-356. DR PDB; 2KNA; NMR; -; A=357-449. DR PDB; 2OPY; X-ray; 2.80 A; A=249-354. DR PDB; 2OPZ; X-ray; 3.00 A; A/B/C/D=249-357. DR PDB; 2POI; X-ray; 1.80 A; A=10-99. DR PDB; 2POP; X-ray; 3.10 A; B/D=10-100. DR PDB; 2QRA; X-ray; 2.50 A; A/B/C/D=10-99. DR PDB; 2VSL; X-ray; 2.10 A; A=250-345. DR PDB; 3CLX; X-ray; 2.70 A; A/B/C/D=241-356. DR PDB; 3CM2; X-ray; 2.50 A; A/B/C/D/E/F/G/H/I/J=241-356. DR PDB; 3CM7; X-ray; 3.10 A; A/B/C/D=241-356. DR PDB; 3EYL; X-ray; 3.00 A; A/B=241-356. DR PDB; 3G76; X-ray; 3.00 A; A/B/C/D/E/F/G/H=241-356. DR PDB; 3HL5; X-ray; 1.80 A; A/B=256-346. DR PDB; 3UW4; X-ray; 1.79 A; A=338-348. DR PDB; 3UW5; X-ray; 1.71 A; A/B=336-348. DR PDB; 4EC4; X-ray; 3.30 A; A/B/C/D/E/F/G/J/K/L=241-356. DR PDB; 4HY0; X-ray; 2.84 A; A/B/C/D/E/F/G/H=238-357. DR PDB; 4IC2; X-ray; 2.20 A; A/B=429-497. DR PDB; 4IC3; X-ray; 1.78 A; A/B=429-497. DR PDB; 4J3Y; X-ray; 1.45 A; A/C=152-236. DR PDB; 4J44; X-ray; 1.30 A; A/C=152-236. DR PDB; 4J45; X-ray; 1.48 A; A/C=152-236. DR PDB; 4J46; X-ray; 1.42 A; A/C=152-236. DR PDB; 4J47; X-ray; 1.35 A; A/C=152-236. DR PDB; 4J48; X-ray; 2.10 A; A/C=152-236. DR PDB; 4KJU; X-ray; 1.60 A; A/C=152-236. DR PDB; 4KJV; X-ray; 1.70 A; A/C=152-236. DR PDB; 4KMP; X-ray; 1.95 A; A/B=256-348. DR PDB; 4MTZ; X-ray; 2.10 A; A/B/C/D=10-99. DR PDB; 4OXC; X-ray; 2.90 A; A/B/C/D=10-99. DR PDB; 4WVS; X-ray; 2.09 A; A=156-231. DR PDB; 4WVT; X-ray; 1.96 A; A/B=156-231. DR PDB; 4WVU; X-ray; 2.02 A; A=156-231. DR PDB; 5C0K; X-ray; 2.20 A; A=249-354. DR PDB; 5C0L; X-ray; 2.60 A; A=246-354. DR PDB; 5C3H; X-ray; 2.65 A; A=249-354. DR PDB; 5C3K; X-ray; 2.02 A; A=249-354. DR PDB; 5C7A; X-ray; 2.36 A; A=249-354. DR PDB; 5C7B; X-ray; 2.68 A; A=249-354. DR PDB; 5C7C; X-ray; 2.32 A; A=249-354. DR PDB; 5C7D; X-ray; 2.25 A; A=249-354. DR PDB; 5C83; X-ray; 2.33 A; A=249-354. DR PDB; 5C84; X-ray; 2.36 A; A=249-354. DR PDB; 5M6E; X-ray; 2.32 A; A=249-354. DR PDB; 5M6F; X-ray; 2.39 A; A=249-354. DR PDB; 5M6H; X-ray; 2.50 A; A=249-354. DR PDB; 5M6L; X-ray; 2.61 A; A=249-354. DR PDB; 5M6M; X-ray; 2.37 A; A=249-354. DR PDB; 5O6T; X-ray; 1.57 A; A/B=434-497. DR PDB; 5OQW; X-ray; 2.31 A; A/B=249-354. DR PDB; 6EY2; X-ray; 2.70 A; A/B/C/D/E/F/G/H=241-356. DR PDB; 6GJW; X-ray; 1.90 A; A/B/C/D=10-99. DR PDB; 6QCI; X-ray; 2.30 A; A/B/C/D=10-99. DR PDB; 8AZA; EM; 3.15 A; C=154-240. DR PDB; 8GH7; X-ray; 1.75 A; A/B=253-347. DR PDB; 8W59; X-ray; 1.34 A; A/B=434-496. DR PDB; 8W5A; X-ray; 1.65 A; A/B=434-497. DR PDBsum; 1C9Q; -. DR PDBsum; 1F9X; -. DR PDBsum; 1G3F; -. DR PDBsum; 1G73; -. DR PDBsum; 1I3O; -. DR PDBsum; 1I4O; -. DR PDBsum; 1I51; -. DR PDBsum; 1KMC; -. DR PDBsum; 1NW9; -. DR PDBsum; 1TFQ; -. DR PDBsum; 1TFT; -. DR PDBsum; 2ECG; -. DR PDBsum; 2JK7; -. DR PDBsum; 2KNA; -. DR PDBsum; 2OPY; -. DR PDBsum; 2OPZ; -. DR PDBsum; 2POI; -. DR PDBsum; 2POP; -. DR PDBsum; 2QRA; -. DR PDBsum; 2VSL; -. DR PDBsum; 3CLX; -. DR PDBsum; 3CM2; -. DR PDBsum; 3CM7; -. DR PDBsum; 3EYL; -. DR PDBsum; 3G76; -. DR PDBsum; 3HL5; -. DR PDBsum; 3UW4; -. DR PDBsum; 3UW5; -. DR PDBsum; 4EC4; -. DR PDBsum; 4HY0; -. DR PDBsum; 4IC2; -. DR PDBsum; 4IC3; -. DR PDBsum; 4J3Y; -. DR PDBsum; 4J44; -. DR PDBsum; 4J45; -. DR PDBsum; 4J46; -. DR PDBsum; 4J47; -. DR PDBsum; 4J48; -. DR PDBsum; 4KJU; -. DR PDBsum; 4KJV; -. DR PDBsum; 4KMP; -. DR PDBsum; 4MTZ; -. DR PDBsum; 4OXC; -. DR PDBsum; 4WVS; -. DR PDBsum; 4WVT; -. DR PDBsum; 4WVU; -. DR PDBsum; 5C0K; -. DR PDBsum; 5C0L; -. DR PDBsum; 5C3H; -. DR PDBsum; 5C3K; -. DR PDBsum; 5C7A; -. DR PDBsum; 5C7B; -. DR PDBsum; 5C7C; -. DR PDBsum; 5C7D; -. DR PDBsum; 5C83; -. DR PDBsum; 5C84; -. DR PDBsum; 5M6E; -. DR PDBsum; 5M6F; -. DR PDBsum; 5M6H; -. DR PDBsum; 5M6L; -. DR PDBsum; 5M6M; -. DR PDBsum; 5O6T; -. DR PDBsum; 5OQW; -. DR PDBsum; 6EY2; -. DR PDBsum; 6GJW; -. DR PDBsum; 6QCI; -. DR PDBsum; 8AZA; -. DR PDBsum; 8GH7; -. DR PDBsum; 8W59; -. DR PDBsum; 8W5A; -. DR AlphaFoldDB; P98170; -. DR BMRB; P98170; -. DR EMDB; EMD-15757; -. DR SASBDB; P98170; -. DR SMR; P98170; -. DR BioGRID; 106828; 260. DR CORUM; P98170; -. DR DIP; DIP-27626N; -. DR IntAct; P98170; 109. DR MINT; P98170; -. DR STRING; 9606.ENSP00000360242; -. DR BindingDB; P98170; -. DR ChEMBL; CHEMBL4198; -. DR DrugBank; DB02628; 1-[3,3-Dimethyl-2-(2-Methylamino-Propionylamino)-Butyryl]-Pyrrolidine-2-Carboxylic Acid(1,2,3,4-Tetrahydro-Naphthalen-1-Yl)-Amide. DR DrugBank; DB06184; AEG35156. DR DrugBank; DB04209; Dequalinium. DR DrugBank; DB04612; N-METHYLALANYL-3-METHYLVALYL-4-PHENOXY-N-(1,2,3,4-TETRAHYDRONAPHTHALEN-1-YL)PROLINAMIDE. DR DrugBank; DB12816; Terpinen-4-ol. DR GuidetoPHARMACOLOGY; 2790; -. DR MEROPS; I32.004; -. DR MEROPS; I32.007; -. DR MoonDB; P98170; Predicted. DR GlyGen; P98170; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P98170; -. DR MetOSite; P98170; -. DR PhosphoSitePlus; P98170; -. DR BioMuta; XIAP; -. DR DMDM; 12643387; -. DR EPD; P98170; -. DR jPOST; P98170; -. DR MassIVE; P98170; -. DR MaxQB; P98170; -. DR PaxDb; 9606-ENSP00000360242; -. DR PeptideAtlas; P98170; -. DR ProteomicsDB; 57803; -. DR Pumba; P98170; -. DR Antibodypedia; 3975; 817 antibodies from 44 providers. DR DNASU; 331; -. DR Ensembl; ENST00000355640.3; ENSP00000347858.3; ENSG00000101966.14. DR Ensembl; ENST00000371199.8; ENSP00000360242.3; ENSG00000101966.14. DR Ensembl; ENST00000422098.6; ENSP00000405529.2; ENSG00000101966.14. DR GeneID; 331; -. DR KEGG; hsa:331; -. DR MANE-Select; ENST00000371199.8; ENSP00000360242.3; NM_001167.4; NP_001158.2. DR UCSC; uc004etx.4; human. DR AGR; HGNC:592; -. DR CTD; 331; -. DR DisGeNET; 331; -. DR GeneCards; XIAP; -. DR GeneReviews; XIAP; -. DR HGNC; HGNC:592; XIAP. DR HPA; ENSG00000101966; Low tissue specificity. DR MalaCards; XIAP; -. DR MIM; 300079; gene. DR MIM; 300635; phenotype. DR neXtProt; NX_P98170; -. DR OpenTargets; ENSG00000101966; -. DR Orphanet; 538934; X-linked lymphoproliferative disease due to XIAP deficiency. DR PharmGKB; PA25361; -. DR VEuPathDB; HostDB:ENSG00000101966; -. DR eggNOG; KOG1101; Eukaryota. DR GeneTree; ENSGT00940000158743; -. DR HOGENOM; CLU_016347_1_1_1; -. DR InParanoid; P98170; -. DR OMA; CMDENIA; -. DR OrthoDB; 383715at2759; -. DR PhylomeDB; P98170; -. DR TreeFam; TF105356; -. DR PathwayCommons; P98170; -. DR Reactome; R-HSA-111459; Activation of caspases through apoptosome-mediated cleavage. DR Reactome; R-HSA-111463; SMAC (DIABLO) binds to IAPs. DR Reactome; R-HSA-111464; SMAC(DIABLO)-mediated dissociation of IAP:caspase complexes. DR Reactome; R-HSA-111469; SMAC, XIAP-regulated apoptotic response. DR Reactome; R-HSA-3769402; Deactivation of the beta-catenin transactivating complex. DR Reactome; R-HSA-5213460; RIPK1-mediated regulated necrosis. DR Reactome; R-HSA-5357786; TNFR1-induced proapoptotic signaling. DR Reactome; R-HSA-5357905; Regulation of TNFR1 signaling. DR Reactome; R-HSA-5357956; TNFR1-induced NF-kappa-B signaling pathway. DR Reactome; R-HSA-5675482; Regulation of necroptotic cell death. DR Reactome; R-HSA-8948747; Regulation of PTEN localization. DR Reactome; R-HSA-8948751; Regulation of PTEN stability and activity. DR Reactome; R-HSA-9627069; Regulation of the apoptosome activity. DR SABIO-RK; P98170; -. DR SignaLink; P98170; -. DR SIGNOR; P98170; -. DR BioGRID-ORCS; 331; 19 hits in 829 CRISPR screens. DR ChiTaRS; XIAP; human. DR EvolutionaryTrace; P98170; -. DR GeneWiki; XIAP; -. DR GenomeRNAi; 331; -. DR Pharos; P98170; Tchem. DR PRO; PR:P98170; -. DR Proteomes; UP000005640; Chromosome X. DR RNAct; P98170; Protein. DR Bgee; ENSG00000101966; Expressed in kidney epithelium and 194 other cell types or tissues. DR ExpressionAtlas; P98170; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0004869; F:cysteine-type endopeptidase inhibitor activity; IEA:UniProtKB-KW. DR GO; GO:0043027; F:cysteine-type endopeptidase inhibitor activity involved in apoptotic process; IDA:UniProtKB. DR GO; GO:0061135; F:endopeptidase regulator activity; IDA:UniProt. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0120283; F:protein serine/threonine kinase binding; IPI:UniProtKB. DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:FlyBase. DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:UniProtKB. DR GO; GO:0055070; P:copper ion homeostasis; TAS:UniProtKB. DR GO; GO:0042742; P:defense response to bacterium; IDA:UniProt. DR GO; GO:0006974; P:DNA damage response; IEP:UniProtKB. DR GO; GO:0097340; P:inhibition of cysteine-type endopeptidase activity; IDA:UniProtKB. DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB. DR GO; GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:UniProtKB. DR GO; GO:0010804; P:negative regulation of tumor necrosis factor-mediated signaling pathway; IDA:UniProtKB. DR GO; GO:0051402; P:neuron apoptotic process; IEA:Ensembl. DR GO; GO:0070427; P:nucleotide-binding oligomerization domain containing 1 signaling pathway; IDA:UniProt. DR GO; GO:0070431; P:nucleotide-binding oligomerization domain containing 2 signaling pathway; IDA:UniProtKB. DR GO; GO:0043123; P:positive regulation of canonical NF-kappaB signal transduction; IDA:UniProtKB. DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IMP:UniProtKB. DR GO; GO:0046330; P:positive regulation of JNK cascade; IDA:UniProtKB. DR GO; GO:1902530; P:positive regulation of protein linear polyubiquitination; IDA:UniProtKB. DR GO; GO:0031398; P:positive regulation of protein ubiquitination; IDA:UniProtKB. DR GO; GO:0032481; P:positive regulation of type I interferon production; IDA:UniProt. DR GO; GO:0070534; P:protein K63-linked ubiquitination; IDA:UniProtKB. DR GO; GO:0060785; P:regulation of apoptosis involved in tissue homeostasis; IEA:Ensembl. DR GO; GO:0042981; P:regulation of apoptotic process; IDA:UniProtKB. DR GO; GO:0030510; P:regulation of BMP signaling pathway; TAS:UniProtKB. DR GO; GO:0051726; P:regulation of cell cycle; IBA:GO_Central. DR GO; GO:0042127; P:regulation of cell population proliferation; TAS:UniProtKB. DR GO; GO:0050727; P:regulation of inflammatory response; TAS:UniProtKB. DR GO; GO:0045088; P:regulation of innate immune response; TAS:UniProtKB. DR GO; GO:0070424; P:regulation of nucleotide-binding oligomerization domain containing signaling pathway; TAS:UniProtKB. DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW. DR CDD; cd00022; BIR; 3. DR CDD; cd16714; RING-HC_BIRC4_8; 1. DR CDD; cd14395; UBA_BIRC4_8; 1. DR DisProt; DP01773; -. DR Gene3D; 1.10.533.10; Death Domain, Fas; 1. DR Gene3D; 1.10.8.10; DNA helicase RuvA subunit, C-terminal domain; 1. DR InterPro; IPR001370; BIR_rpt. DR InterPro; IPR048875; BIRC2-3-like_UBA. DR InterPro; IPR011029; DEATH-like_dom_sf. DR InterPro; IPR042579; XIAP/BIRC8_UBA. DR InterPro; IPR001841; Znf_RING. DR PANTHER; PTHR10044:SF115; E3 UBIQUITIN-PROTEIN LIGASE XIAP; 1. DR PANTHER; PTHR10044; INHIBITOR OF APOPTOSIS; 1. DR Pfam; PF00653; BIR; 3. DR Pfam; PF21290; BIRC2-3-like_UBA; 1. DR Pfam; PF13920; zf-C3HC4_3; 1. DR SMART; SM00238; BIR; 3. DR SMART; SM00184; RING; 1. DR SUPFAM; SSF57924; Inhibitor of apoptosis (IAP) repeat; 3. DR PROSITE; PS01282; BIR_REPEAT_1; 3. DR PROSITE; PS50143; BIR_REPEAT_2; 3. DR PROSITE; PS50089; ZF_RING_2; 1. DR Genevisible; P98170; HS. PE 1: Evidence at protein level; KW 3D-structure; Apoptosis; Cytoplasm; Isopeptide bond; Metal-binding; KW Nucleus; Phosphoprotein; Protease inhibitor; Reference proteome; Repeat; KW S-nitrosylation; Thiol protease inhibitor; Transferase; Ubl conjugation; KW Ubl conjugation pathway; Wnt signaling pathway; Zinc; Zinc-finger. FT CHAIN 1..497 FT /note="E3 ubiquitin-protein ligase XIAP" FT /id="PRO_0000122352" FT REPEAT 26..93 FT /note="BIR 1" FT REPEAT 163..230 FT /note="BIR 2" FT REPEAT 265..330 FT /note="BIR 3" FT ZN_FING 450..485 FT /note="RING-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175" FT REGION 141..149 FT /note="Interaction with caspase-7" FT REGION 262..277 FT /note="Required for interaction with SEPTIN4 isoform ARTS" FT /evidence="ECO:0000269|PubMed:21695558" FT REGION 329..350 FT /note="Required for interaction with DIABLO" FT /evidence="ECO:0000269|PubMed:21695558" FT REGION 450..497 FT /note="Required for ubiquitination and subsequent FT degradation of BCL2 during apoptosis" FT /evidence="ECO:0000269|PubMed:29020630" FT BINDING 300 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00029" FT BINDING 303 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00029" FT BINDING 320 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00029" FT BINDING 327 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00029" FT MOD_RES 450 FT /note="S-nitrosocysteine" FT /evidence="ECO:0000269|PubMed:20670888" FT CROSSLNK 322 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:12747801" FT CROSSLNK 328 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:12747801" FT VARIANT 104..497 FT /note="Missing (in XLP2; uncertain significance)" FT /evidence="ECO:0000269|PubMed:20489057" FT /id="VAR_088127" FT VARIANT 107 FT /note="N -> S (in dbSNP:rs28382721)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_022282" FT VARIANT 118..497 FT /note="Missing (in XLP2; uncertain significance)" FT /evidence="ECO:0000269|PubMed:21119115" FT /id="VAR_088128" FT VARIANT 133 FT /note="S -> F (in dbSNP:rs28382722)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_022283" FT VARIANT 188 FT /note="G -> E (in XLP2; uncertain significance)" FT /evidence="ECO:0000269|PubMed:20489057" FT /id="VAR_088129" FT VARIANT 194 FT /note="I -> N (in XLP2; uncertain significance)" FT /evidence="ECO:0000269|PubMed:20489057" FT /id="VAR_088130" FT VARIANT 238..497 FT /note="Missing (in XLP2; uncertain significance)" FT /evidence="ECO:0000269|PubMed:21119115" FT /id="VAR_088131" FT VARIANT 242 FT /note="D -> E (in dbSNP:rs28382723)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_022284" FT VARIANT 333..497 FT /note="Missing (in XLP2; uncertain significance)" FT /evidence="ECO:0000269|PubMed:20489057" FT /id="VAR_088132" FT VARIANT 381..497 FT /note="Missing (in XLP2; uncertain significance)" FT /evidence="ECO:0000269|PubMed:21119115" FT /id="VAR_088133" FT VARIANT 423 FT /note="Q -> P (in dbSNP:rs5956583)" FT /evidence="ECO:0000269|PubMed:8654366, ECO:0000269|Ref.3" FT /id="VAR_022285" FT VARIANT 466..497 FT /note="Missing (in XLP2; uncertain significance)" FT /evidence="ECO:0000269|PubMed:21119115" FT /id="VAR_088134" FT VARIANT 482 FT /note="P -> R (in XLP2; uncertain significance)" FT /evidence="ECO:0000269|PubMed:20489057" FT /id="VAR_088135" FT MUTAGEN 75 FT /note="Y->G: Loss of interaction with TAB1/MAP3K7IP1; when FT associated with G-75." FT /evidence="ECO:0000269|PubMed:17560374" FT MUTAGEN 80 FT /note="V->A: Strongly reduced interaction with FT TAB1/MAP3K7IP1. Reduced activation of MAP3K7/TAK1. Reduced FT activation of NF-kappa-B." FT /evidence="ECO:0000269|PubMed:17560374" FT MUTAGEN 80 FT /note="V->D: Loss of interaction with TAB1/MAP3K7IP1. FT Reduced activation of MAP3K7/TAK1. Strongly reduced FT activation of NF-kappa-B." FT /evidence="ECO:0000269|PubMed:17560374" FT MUTAGEN 86 FT /note="V->E: Loss of dimerization. Reduces activation of FT NF-kappa-B." FT /evidence="ECO:0000269|PubMed:17560374" FT MUTAGEN 87 FT /note="S->A: No effect on dimerization." FT /evidence="ECO:0000269|PubMed:17698078" FT MUTAGEN 87 FT /note="S->D,E: Abolishes dimerization. Interferes with FT ubiquitination." FT /evidence="ECO:0000269|PubMed:17698078" FT MUTAGEN 98 FT /note="L->G: Loss of interaction with TAB1/MAP3K7IP1; when FT associated with G-75." FT /evidence="ECO:0000269|PubMed:17560374" FT MUTAGEN 141 FT /note="L->A: Reduced inhibition of caspase-3." FT /evidence="ECO:0000269|PubMed:10548111" FT MUTAGEN 147 FT /note="V->A: Reduced inhibition of caspase-3." FT /evidence="ECO:0000269|PubMed:10548111" FT MUTAGEN 148 FT /note="D->A: Abolishes inhibition of caspase-3. Reduced FT interaction with HTRA2; when associated with S-214." FT /evidence="ECO:0000269|PubMed:10548111, FT ECO:0000269|PubMed:11604410" FT MUTAGEN 149 FT /note="I->A: Reduced inhibition of caspase-3." FT /evidence="ECO:0000269|PubMed:10548111" FT MUTAGEN 151 FT /note="D->A: Reduced inhibition of caspase-3." FT /evidence="ECO:0000269|PubMed:10548111" FT MUTAGEN 167 FT /note="L->A: Reduced inhibition of caspase-3." FT /evidence="ECO:0000269|PubMed:10548111" FT MUTAGEN 196 FT /note="D->A: Reduced inhibition of caspase-3. May affect FT protein folding and stability." FT /evidence="ECO:0000269|PubMed:10548111" FT MUTAGEN 214 FT /note="D->S: Reduced interaction with HTRA2. Reduced FT interaction with HTRA2; when associated with A-148." FT /evidence="ECO:0000269|PubMed:11604410" FT MUTAGEN 259 FT /note="N->D: Reduced interaction with HTRA2; when FT associated with S-314." FT /evidence="ECO:0000269|PubMed:11604410" FT MUTAGEN 310 FT /note="W->A: No effect on interaction with SEPTIN4 isoform FT ARTS." FT /evidence="ECO:0000269|PubMed:21695558" FT MUTAGEN 310 FT /note="W->R: Reduced interaction with HTRA2; when FT associated with S-314." FT /evidence="ECO:0000269|PubMed:11604410" FT MUTAGEN 314 FT /note="E->S: Decreased interaction with DIABLO/SMAC and FT with HTRA2. Decreases interaction with HTRA2; when FT associated with D-259 or A-310. No effect on interaction FT with SEPTIN4 isoform ARTS." FT /evidence="ECO:0000269|PubMed:11604410, FT ECO:0000269|PubMed:21695558" FT MUTAGEN 343 FT /note="H->A: No effect on interaction with SEPTIN4 isoform FT ARTS." FT /evidence="ECO:0000269|PubMed:21695558" FT MUTAGEN 450 FT /note="C->A,S: Inhibits degradation of active caspase-3." FT /evidence="ECO:0000269|PubMed:11447297" FT MUTAGEN 467 FT /note="H->A: Loss of E3 ubiquitin-protein ligase activity." FT /evidence="ECO:0000269|PubMed:17967870" FT MUTAGEN 495 FT /note="F->A: Abolished E3 ubiquitin-protein ligase activity FT and ability to ubiquitinate RIPK2." FT /evidence="ECO:0000269|PubMed:22607974" FT CONFLICT 162 FT /note="S -> C (in Ref. 2; AAC50373)" FT /evidence="ECO:0000305" FT HELIX 22..24 FT /evidence="ECO:0007829|PDB:6GJW" FT HELIX 26..30 FT /evidence="ECO:0007829|PDB:2POI" FT HELIX 31..33 FT /evidence="ECO:0007829|PDB:2POI" FT STRAND 40..42 FT /evidence="ECO:0007829|PDB:2POI" FT HELIX 44..49 FT /evidence="ECO:0007829|PDB:2POI" FT STRAND 52..54 FT /evidence="ECO:0007829|PDB:2POI" FT STRAND 61..63 FT /evidence="ECO:0007829|PDB:2POI" FT TURN 64..66 FT /evidence="ECO:0007829|PDB:2POI" FT HELIX 79..86 FT /evidence="ECO:0007829|PDB:2POI" FT TURN 91..97 FT /evidence="ECO:0007829|PDB:2POI" FT TURN 128..130 FT /evidence="ECO:0007829|PDB:1I3O" FT HELIX 136..142 FT /evidence="ECO:0007829|PDB:1I4O" FT HELIX 150..152 FT /evidence="ECO:0007829|PDB:1I3O" FT HELIX 158..161 FT /evidence="ECO:0007829|PDB:4J44" FT HELIX 163..168 FT /evidence="ECO:0007829|PDB:4J44" FT TURN 169..172 FT /evidence="ECO:0007829|PDB:4J44" FT HELIX 175..177 FT /evidence="ECO:0007829|PDB:4WVT" FT HELIX 181..186 FT /evidence="ECO:0007829|PDB:4J44" FT STRAND 189..191 FT /evidence="ECO:0007829|PDB:4J44" FT STRAND 198..200 FT /evidence="ECO:0007829|PDB:4J44" FT TURN 201..203 FT /evidence="ECO:0007829|PDB:4J44" FT STRAND 206..208 FT /evidence="ECO:0007829|PDB:4J44" FT HELIX 216..223 FT /evidence="ECO:0007829|PDB:4J44" FT HELIX 228..232 FT /evidence="ECO:0007829|PDB:4J44" FT HELIX 244..246 FT /evidence="ECO:0007829|PDB:1F9X" FT STRAND 249..251 FT /evidence="ECO:0007829|PDB:1F9X" FT STRAND 254..256 FT /evidence="ECO:0007829|PDB:5C3K" FT HELIX 260..262 FT /evidence="ECO:0007829|PDB:8GH7" FT HELIX 265..271 FT /evidence="ECO:0007829|PDB:8GH7" FT TURN 272..274 FT /evidence="ECO:0007829|PDB:8GH7" FT STRAND 277..279 FT /evidence="ECO:0007829|PDB:8GH7" FT HELIX 281..286 FT /evidence="ECO:0007829|PDB:8GH7" FT STRAND 289..291 FT /evidence="ECO:0007829|PDB:8GH7" FT STRAND 293..296 FT /evidence="ECO:0007829|PDB:2OPZ" FT STRAND 298..300 FT /evidence="ECO:0007829|PDB:8GH7" FT TURN 301..303 FT /evidence="ECO:0007829|PDB:8GH7" FT STRAND 306..309 FT /evidence="ECO:0007829|PDB:8GH7" FT STRAND 311..313 FT /evidence="ECO:0007829|PDB:1F9X" FT HELIX 316..323 FT /evidence="ECO:0007829|PDB:8GH7" FT HELIX 328..333 FT /evidence="ECO:0007829|PDB:3HL5" FT HELIX 336..342 FT /evidence="ECO:0007829|PDB:3UW5" FT TURN 343..345 FT /evidence="ECO:0007829|PDB:3HL5" FT HELIX 346..353 FT /evidence="ECO:0007829|PDB:1G73" FT HELIX 354..356 FT /evidence="ECO:0007829|PDB:1G73" FT HELIX 368..372 FT /evidence="ECO:0007829|PDB:2KNA" FT HELIX 375..381 FT /evidence="ECO:0007829|PDB:2KNA" FT HELIX 386..400 FT /evidence="ECO:0007829|PDB:2KNA" FT HELIX 407..419 FT /evidence="ECO:0007829|PDB:2KNA" FT HELIX 437..447 FT /evidence="ECO:0007829|PDB:8W59" FT TURN 451..453 FT /evidence="ECO:0007829|PDB:8W59" FT STRAND 454..457 FT /evidence="ECO:0007829|PDB:8W59" FT STRAND 460..463 FT /evidence="ECO:0007829|PDB:8W59" FT HELIX 472..475 FT /evidence="ECO:0007829|PDB:8W59" FT TURN 482..484 FT /evidence="ECO:0007829|PDB:8W59" FT STRAND 489..493 FT /evidence="ECO:0007829|PDB:8W59" SQ SEQUENCE 497 AA; 56685 MW; 9D394C16D45EB635 CRC64; MTFNSFEGSK TCVPADINKE EEFVEEFNRL KTFANFPSGS PVSASTLARA GFLYTGEGDT VRCFSCHAAV DRWQYGDSAV GRHRKVSPNC RFINGFYLEN SATQSTNSGI QNGQYKVENY LGSRDHFALD RPSETHADYL LRTGQVVDIS DTIYPRNPAM YSEEARLKSF QNWPDYAHLT PRELASAGLY YTGIGDQVQC FCCGGKLKNW EPCDRAWSEH RRHFPNCFFV LGRNLNIRSE SDAVSSDRNF PNSTNLPRNP SMADYEARIF TFGTWIYSVN KEQLARAGFY ALGEGDKVKC FHCGGGLTDW KPSEDPWEQH AKWYPGCKYL LEQKGQEYIN NIHLTHSLEE CLVRTTEKTP SLTRRIDDTI FQNPMVQEAI RMGFSFKDIK KIMEEKIQIS GSNYKSLEVL VADLVNAQKD SMQDESSQTS LQKEISTEEQ LRRLQEEKLC KICMDRNIAI VFVPCGHLVT CKQCAEAVDK CPMCYTVITF KQKIFMS //