XIAP_HUMAN
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 03-AUG-2022, entry version 230.
DE RecName: Full=E3 ubiquitin-protein ligase XIAP;
DE EC=2.3.2.27;
DE AltName: Full=Baculoviral IAP repeat-containing protein 4;
DE AltName: Full=IAP-like protein;
DE Short=ILP;
DE Short=hILP;
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; 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 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 [16]
RP SUBCELLULAR LOCATION.
RX PubMed=15665297;
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 [17]
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 [18]
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 [19]
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 [20]
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 [21]
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 [22]
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 [23]
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 [24]
RP FUNCTION IN THE UBIQUITINATION OF PTEN, AND INTERACTION 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 [25]
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 [26]
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 [27]
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 [28]
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 [29]
RP FUNCTION IN THE UBIQUITINATION OF CCS, AND INTERACTION 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 [30]
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 [31]
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 [32]
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 [33]
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 [34]
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 [35]
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 [36]
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 [37]
RP 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 [38]
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 [39]
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 [40]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH 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 [41]
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 [42]
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 [43]
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 [44]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 120-260 IN COMPLEX WITH CASP7.
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 [45]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 253-350 IN COMPLEX WITH CASP9.
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 [46]
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 [47]
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 [48]
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 [49]
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 [50]
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.
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. Acts as a direct caspase
CC inhibitor. Directly bind to the active site pocket of CASP3 and CASP7
CC and obstructs substrate entry. Inactivates CASP9 by keeping it in a
CC monomeric, inactive state. Acts as an E3 ubiquitin-protein ligase
CC regulating NF-kappa-B signaling and the target proteins for its E3
CC ubiquitin-protein ligase activity include: RIPK1, CASP3, CASP7, CASP8,
CC CASP9, MAP3K2/MEKK2, DIABLO/SMAC, AIFM1, CCS and BIRC5/survivin.
CC Ubiquitinion of CCS leads to enhancement of its chaperone activity
CC toward its physiologic target, SOD1, rather than proteasomal
CC degradation. Ubiquitinion of MAP3K2/MEKK2 and AIFM1 does not lead to
CC proteasomal degradation. Plays a role in copper homeostasis by
CC ubiquitinating COMMD1 and promoting its proteasomal degradation. Can
CC also function as E3 ubiquitin-protein ligase of the NEDD8 conjugation
CC pathway, targeting effector caspases for neddylation and inactivation.
CC Ubiquitinates and therefore mediates the proteosomal degradation of
CC BCL2 in response to apoptosis (PubMed:29020630). Regulates the BMP
CC signaling pathway and the SMAD and MAP3K7/TAK1 dependent pathways
CC leading to NF-kappa-B and JNK activation. Acts as an important
CC regulator of innate immune signaling via regulation of Nodlike
CC receptors (NLRs). Protects cells from spontaneous formation of the
CC ripoptosome, a large multi-protein complex that has the capability to
CC kill cancer cells in a caspase-dependent and caspase-independent
CC manner. Suppresses ripoptosome formation by ubiquitinating RIPK1 and
CC CASP8. Acts as a positive regulator of Wnt signaling and ubiquitinates
CC TLE1, TLE2, TLE3, TLE4 and AES. Ubiquitination of TLE3 results in
CC inhibition of its interaction with TCF7L2/TCF4 thereby allowing
CC efficient recruitment and binding of the transcriptional coactivator
CC beta-catenin to TCF7L2/TCF4 that is required to initiate a Wnt-specific
CC transcriptional program. {ECO:0000269|PubMed:11447297,
CC ECO:0000269|PubMed:12121969, ECO:0000269|PubMed:14685266,
CC ECO:0000269|PubMed:17560374, ECO:0000269|PubMed:17967870,
CC ECO:0000269|PubMed:19473982, ECO:0000269|PubMed:20154138,
CC ECO:0000269|PubMed:21145488, ECO:0000269|PubMed:22103349,
CC ECO:0000269|PubMed:22304967, ECO:0000269|PubMed:29020630,
CC ECO:0000269|PubMed:9230442}.
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;
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). Interacts with
CC HTRA2/PRSS25; the interaction inhibits apoptotic suppressor activity
CC (PubMed:11604410). Interacts with TAB1/MAP3K7IP1 and AIFM1. Interaction
CC with DIABLO/SMAC hinders binding of TAB1/MAP3K7IP1 and AIFM1. Interacts
CC with TCF25 and COMMD1. Interacts (via BIR3 domain) with SEPTIN4 isoform
CC ARTS (PubMed:21695558, PubMed:15029247). Interacts (via BIR3 domain)
CC with SEPTIN4 (By similarity). Interacts with RIP1, RIP2, RIP3, RIP4,
CC CCS and USP19. Interacts (via BIR 2 domain and BIR 3 domain) with HAX1
CC (via C-terminus) and this interaction blocks ubiquitination of
CC XIAP/BIRC4. Interacts with the monomeric form of BIRC5/survivin.
CC Interacts with TLE3 and TCF7L2/TCF4. Interacts (via BIR 3 and RING
CC domains) with PDCL3 (PubMed:19012568). {ECO:0000250|UniProtKB:Q60989,
CC ECO:0000269|PubMed:11140637, 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: BOLA2B; 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. Nucleus. Note=TLE3 promotes its
CC nuclear localization.
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. The second BIR domain
CC is sufficient to inhibit CASP3 and CASP7, while the third BIR is
CC involved in CASP9 inhibition. The interactions with DIABLO/SMAC and
CC HTRA2/PRSS25 are mediated by the second and third BIR domains.
CC -!- PTM: S-Nitrosylation down-regulates its E3 ubiquitin-protein ligase
CC activity. {ECO:0000269|PubMed:20670888}.
CC -!- PTM: Autoubiquitinated. {ECO:0000269|PubMed:12747801}.
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}. Note=The disease is
CC caused by variants affecting the gene represented in this 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/";
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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 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 AlphaFoldDB; P98170; -.
DR BMRB; P98170; -.
DR SASBDB; P98170; -.
DR SMR; P98170; -.
DR BioGRID; 106828; 231.
DR CORUM; P98170; -.
DR DIP; DIP-27626N; -.
DR IntAct; P98170; 103.
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 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; P98170; -.
DR PeptideAtlas; P98170; -.
DR PRIDE; P98170; -.
DR ProteomicsDB; 57803; -.
DR Antibodypedia; 3975; 739 antibodies from 44 providers.
DR DNASU; 331; -.
DR Ensembl; ENST00000355640.3; ENSP00000347858.3; ENSG00000101966.13.
DR Ensembl; ENST00000371199.8; ENSP00000360242.3; ENSG00000101966.13.
DR Ensembl; ENST00000434753.7; ENSP00000395230.3; ENSG00000101966.13.
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 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; 1340284at2759; -.
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-5357905; Regulation of TNFR1 signaling.
DR Reactome; R-HSA-5357956; TNFR1-induced NFkappaB 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; 16 hits in 747 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 192 other tissues.
DR ExpressionAtlas; P98170; baseline and differential.
DR Genevisible; P98170; HS.
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:0005876; C:spindle microtubule; IBA:GO_Central.
DR GO; GO:0043027; F:cysteine-type endopeptidase inhibitor activity involved in apoptotic process; IDA:ProtInc.
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; EXP:Reactome.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:UniProtKB.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IEP:UniProtKB.
DR GO; GO:0055070; P:copper ion homeostasis; TAS:UniProtKB.
DR GO; GO:0097340; P:inhibition of cysteine-type endopeptidase activity; IDA:UniProtKB.
DR GO; GO:1990001; P:inhibition of cysteine-type endopeptidase activity involved in apoptotic process; IEA:Ensembl.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP: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: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: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; cd14395; UBA_BIRC4_8; 1.
DR DisProt; DP01773; -.
DR Gene3D; 1.10.533.10; -; 1.
DR InterPro; IPR001370; BIR_rpt.
DR InterPro; IPR011029; DEATH-like_dom_sf.
DR InterPro; IPR042579; XIAP/BIRC8_UBA.
DR InterPro; IPR001841; Znf_RING.
DR Pfam; PF00653; BIR; 3.
DR SMART; SM00238; BIR; 3.
DR SMART; SM00184; RING; 1.
DR PROSITE; PS01282; BIR_REPEAT_1; 3.
DR PROSITE; PS50143; BIR_REPEAT_2; 3.
DR PROSITE; PS50089; ZF_RING_2; 1.
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 107
FT /note="N -> S (in dbSNP:rs28382721)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_022282"
FT VARIANT 133
FT /note="S -> F (in dbSNP:rs28382722)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_022283"
FT VARIANT 242
FT /note="D -> E (in dbSNP:rs28382723)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_022284"
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 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 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:3HL5"
FT HELIX 265..270
FT /evidence="ECO:0007829|PDB:3HL5"
FT TURN 271..274
FT /evidence="ECO:0007829|PDB:3HL5"
FT STRAND 277..279
FT /evidence="ECO:0007829|PDB:3HL5"
FT HELIX 281..286
FT /evidence="ECO:0007829|PDB:3HL5"
FT STRAND 289..291
FT /evidence="ECO:0007829|PDB:3HL5"
FT STRAND 293..296
FT /evidence="ECO:0007829|PDB:2OPZ"
FT STRAND 298..300
FT /evidence="ECO:0007829|PDB:3HL5"
FT TURN 301..303
FT /evidence="ECO:0007829|PDB:3HL5"
FT STRAND 306..309
FT /evidence="ECO:0007829|PDB:1G73"
FT STRAND 311..313
FT /evidence="ECO:0007829|PDB:1F9X"
FT HELIX 316..323
FT /evidence="ECO:0007829|PDB:3HL5"
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:5O6T"
FT TURN 451..453
FT /evidence="ECO:0007829|PDB:5O6T"
FT STRAND 454..457
FT /evidence="ECO:0007829|PDB:5O6T"
FT STRAND 460..463
FT /evidence="ECO:0007829|PDB:5O6T"
FT HELIX 472..475
FT /evidence="ECO:0007829|PDB:5O6T"
FT TURN 482..484
FT /evidence="ECO:0007829|PDB:5O6T"
FT STRAND 489..493
FT /evidence="ECO:0007829|PDB:5O6T"
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
