ID BIRC5_HUMAN Reviewed; 142 AA. AC O15392; A2SUH6; B2R4R1; Q2I3N8; Q4VGX0; Q53F61; Q5MGC6; Q6FHL2; AC Q75SP2; Q9P2W8; DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot. DT 21-MAR-2012, sequence version 3. DT 13-NOV-2013, entry version 162. DE RecName: Full=Baculoviral IAP repeat-containing protein 5; DE AltName: Full=Apoptosis inhibitor 4; DE AltName: Full=Apoptosis inhibitor survivin; GN Name=BIRC5; Synonyms=API4, IAP4; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1). RX PubMed=9256286; DOI=10.1038/nm0897-917; RA Ambrosini G., Adida C., Altieri D.C.; RT "A novel anti-apoptosis gene, survivin, expressed in cancer and RT lymphoma."; RL Nat. Med. 3:917-921(1997). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3), FUNCTION, AND TISSUE RP SPECIFICITY. RX PubMed=10626797; RA Mahotka C., Wenzel M., Springer E., Gabbert H.E., Gerharz C.D.; RT "Survivin-deltaEx3 and survivin-2B: two novel splice variants of the RT apoptosis inhibitor survivin with different antiapoptotic RT properties."; RL Cancer Res. 59:6097-6102(1999). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND SUBCELLULAR LOCATION. RX PubMed=11084331; DOI=10.1016/S0960-9822(00)00769-7; RA Uren A.G., Wong L., Pakusch M., Fowler K.J., Burrows F.J., Vaux D.L., RA Choo K.H.; RT "Survivin and the inner centromere protein INCENP show similar cell- RT cycle localization and gene knockout phenotype."; RL Curr. Biol. 10:1319-1328(2000). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), AND TISSUE SPECIFICITY. RC TISSUE=Myeloid leukemia cell; RX PubMed=14741722; DOI=10.1016/j.bbrc.2003.12.178; RA Badran A., Yoshida A., Ishikawa K., Goi T., Yamaguchi A., Ueda T., RA Inuzuka M.; RT "Identification of a novel splice variant of the human anti-apoptosis RT gene survivin."; RL Biochem. Biophys. Res. Commun. 314:902-907(2004). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5), AND TISSUE SPECIFICITY. RC TISSUE=Mammary cancer; RX PubMed=16329164; DOI=10.1080/10425170500226490; RA Zheng W., Ma X., Wei D., Wang T., Ma Y., Yang S.; RT "Molecular cloning and bioinformatics analysis of a novel spliced RT variant of survivin from human breast cancer cells."; RL DNA Seq. 16:321-328(2005). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RC TISSUE=Neuroblastoma; RA Kageyama H., Islam A., Takayasu H., Nakagawara A.; RT "An isoform of survivin (survivin-beta) which has 23 amino acids RT insertion into the BIR domain."; RL Submitted (JUN-1999) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 7). RA Caldas H., Honsey L.E., Altura R.A.; RT "Survivin 2 alpha: a novel survivin splice variant expressed in human RT malignancies."; RL Submitted (FEB-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 6). RC TISSUE=Myeloid leukemia cell; RA Vietri M.T., Cioffi M., Sessa M., Sica V., Molinari A.M.; RT "Identification of a novel survivin splicing variant 3alpha in acute RT myeloid leukemia."; RL Submitted (NOV-2005) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [11] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.; RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases. RN [12] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RG NIEHS SNPs program; RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases. RN [13] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT GLU-129. RX PubMed=16625196; DOI=10.1038/nature04689; RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., RA Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., RA Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., RA Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., RA Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., RA Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., RA Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., RA Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.; RT "DNA sequence of human chromosome 17 and analysis of rearrangement in RT the human lineage."; RL Nature 440:1045-1049(2006). RN [14] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [15] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Lung, Mammary gland, and Muscle; 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [16] RP FUNCTION. RX PubMed=9859993; DOI=10.1038/25141; RA Li F., Ambrosini G., Chu E.Y., Plescia J., Tognin S., Marchisio P.C., RA Altieri D.C.; RT "Control of apoptosis and mitotic spindle checkpoint by survivin."; RL Nature 396:580-584(1998). RN [17] RP PHOSPHORYLATION AT THR-34. RX PubMed=11069302; DOI=10.1073/pnas.240390697; RA O'Connor D.S., Grossman D., Plescia J., Li F., Zhang H., Villa A., RA Tognin S., Marchisio P.C., Altieri D.C.; RT "Regulation of apoptosis at cell division by p34cdc2 phosphorylation RT of survivin."; RL Proc. Natl. Acad. Sci. U.S.A. 97:13103-13107(2000). RN [18] RP FUNCTION IN APOPTOSIS SUPPRESSION, INTERACTION WITH LAMTOR5/HBXIP, RP MUTAGENESIS OF THR-34, AND SUBCELLULAR LOCATION. RX PubMed=12773388; DOI=10.1093/emboj/cdg263; RA Marusawa H., Matsuzawa S., Welsh K., Zou H., Armstrong R., Tamm I., RA Reed J.C.; RT "HBXIP functions as a cofactor of survivin in apoptosis suppression."; RL EMBO J. 22:2729-2740(2003). RN [19] RP INTERACTION WITH INCENP, SUBCELLULAR LOCATION, PHOSPHORYLATION AT RP THR-117, AND MUTAGENESIS OF THR-117. RX PubMed=14610074; DOI=10.1074/jbc.M311299200; RA Wheatley S.P., Henzing A.J., Dodson H., Khaled W., Earnshaw W.C.; RT "Aurora-B phosphorylation in vitro identifies a residue of survivin RT that is essential for its localization and binding to inner centromere RT protein (INCENP) in vivo."; RL J. Biol. Chem. 279:5655-5660(2004). RN [20] RP INTERACTION WITH CDCA8. RX PubMed=15249581; DOI=10.1083/jcb.200404001; RA Gassmann R., Carvalho A., Henzing A.J., Ruchaud S., Hudson D.F., RA Honda R., Nigg E.A., Gerloff D.L., Earnshaw W.C.; RT "Borealin: a novel chromosomal passenger required for stability of the RT bipolar mitotic spindle."; RL J. Cell Biol. 166:179-191(2004). RN [21] RP SUBCELLULAR LOCATION, AND INTERACTION WITH BIRC2/C-IAP1. 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 RT cycle."; RL Cancer Res. 65:210-218(2005). RN [22] RP REVIEW ON FUNCTION. RX PubMed=16344111; DOI=10.1016/S0074-7696(05)47002-3; RA Wheatley S.P., McNeish I.A.; RT "Survivin: a protein with dual roles in mitosis and apoptosis."; RL Int. Rev. Cytol. 247:35-88(2005). RN [23] RP FUNCTION, INTERACTION WITH USP9X, SUBCELLULAR LOCATION, RP UBIQUITINATION, AND MUTAGENESIS OF LYS-23; LYS-62; LYS-78 AND LYS-79. RX PubMed=16322459; DOI=10.1126/science.1120160; RA Vong Q.P., Cao K., Li H.Y., Iglesias P.A., Zheng Y.; RT "Chromosome alignment and segregation regulated by ubiquitination of RT survivin."; RL Science 310:1499-1504(2005). RN [24] RP MUTAGENESIS OF ASP-70; ASP-71 AND 70-ASP--ASP-71. RX PubMed=16762323; DOI=10.1016/j.bbrc.2006.05.131; RA Cao L., Yan X., Wu Y., Hu H., Li Q., Zhou T., Jiang S., Yu L.; RT "Survivin mutant (Surv-DD70, 71AA) disrupts the interaction of RT Survivin with Aurora B and causes multinucleation in HeLa cells."; RL Biochem. Biophys. Res. Commun. 346:400-407(2006). RN [25] RP INTERACTION WITH CDCA8. RX PubMed=16239925; DOI=10.1038/sj.embor.7400562; RA Vader G., Kauw J.J.W., Medema R.H., Lens S.M.A.; RT "Survivin mediates targeting of the chromosomal passenger complex to RT the centromere and midbody."; RL EMBO Rep. 7:85-92(2006). RN [26] RP INTERACTION WITH CDCA8. RX PubMed=16427043; DOI=10.1016/j.yexcr.2005.12.015; RA Chang J.-L., Chen T.-H., Wang C.-F., Chiang Y.-H., Huang Y.-L., RA Wong F.-H., Chou C.-K., Chen C.-M.; RT "Borealin/Dasra B is a cell cycle-regulated chromosomal passenger RT protein and its nuclear accumulation is linked to poor prognosis for RT human gastric cancer."; RL Exp. Cell Res. 312:962-973(2006). RN [27] RP INTERACTION WITH EVI5. RX PubMed=16764853; DOI=10.1016/j.yexcr.2006.03.032; RA Faitar S.L., Sossey-Alaoui K., Ranalli T.A., Cowell J.K.; RT "EVI5 protein associates with the INCENP-aurora B kinase-survivin RT chromosomal passenger complex and is involved in the completion of RT cytokinesis."; RL Exp. Cell Res. 312:2325-2335(2006). RN [28] RP FUNCTION, AND INTERACTION WITH CDCA8. RX PubMed=16291752; DOI=10.1074/jbc.M508773200; RA Noton E.A., Colnaghi R., Tate S., Starck C., Carvalho A., RA Ko Ferrigno P., Wheatley S.P.; RT "Molecular analysis of survivin isoforms: evidence that alternatively RT spliced variants do not play a role in mitosis."; RL J. Biol. Chem. 281:1286-1295(2006). RN [29] RP INTERACTION WITH CDCA8. RX PubMed=16436504; DOI=10.1091/mbc.E05-08-0727; RA Lens S.M.A., Rodriguez J.A., Vader G., Span S.W., Giaccone G., RA Medema R.H.; RT "Uncoupling the central spindle-associated function of the chromosomal RT passenger complex from its role at centromeres."; RL Mol. Biol. Cell 17:1897-1909(2006). RN [30] RP INTERACTION WITH BIRC6/BRUCE. RX PubMed=18329369; DOI=10.1016/j.cell.2008.01.012; RA Pohl C., Jentsch S.; RT "Final stages of cytokinesis and midbody ring formation are controlled RT by BRUCE."; RL Cell 132:832-845(2008). RN [31] RP INDUCTION. RX PubMed=17993464; DOI=10.1074/jbc.M704035200; RA Gagarina V., Carlberg A.L., Pereira-Mouries L., Hall D.J.; RT "Cartilage oligomeric matrix protein protects cells against death by RT elevating members of the IAP family of survival proteins."; RL J. Biol. Chem. 283:648-659(2008). RN [32] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-34, AND MASS RP SPECTROMETRY. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of RT the kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [33] RP FUNCTION, INTERACTION WITH RAN; AURKB AND CDCA8, SUBCELLULAR LOCATION, RP DEVELOPMENTAL STAGE, AND MUTAGENESIS OF GLU-65. RX PubMed=18591255; DOI=10.1128/MCB.02039-07; RA Xia F., Canovas P.M., Guadagno T.M., Altieri D.C.; RT "A survivin-ran complex regulates spindle formation in tumor cells."; RL Mol. Cell. Biol. 28:5299-5311(2008). RN [34] RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH STAT3 AND XPO1/CRM1, RP ACETYLATION AT LYS-23; LYS-90; LYS-110; LYS-112; LYS-115; LYS-121 AND RP LYS-129, MUTAGENESIS OF LYS-129, AND CHARACTERIZATION OF VARIANT RP GLU-129. RX PubMed=20826784; DOI=10.1074/jbc.M110.152777; RA Wang H., Holloway M.P., Ma L., Cooper Z.A., Riolo M., Samkari A., RA Elenitoba-Johnson K.S., Chin Y.E., Altura R.A.; RT "Acetylation directs survivin nuclear localization to repress STAT3 RT oncogenic activity."; RL J. Biol. Chem. 285:36129-36137(2010). RN [35] RP PHOSPHORYLATION AT THR-48, AND MUTAGENESIS OF THR-48. RX PubMed=21252625; RA Barrett R.M., Colnaghi R., Wheatley S.P.; RT "Threonine 48 in the BIR domain of survivin is critical to its mitotic RT and anti-apoptotic activities and can be phosphorylated by CK2 in RT vitro."; RL Cell Cycle 10:538-548(2011). RN [36] RP INTERACTION WITH JTB. RX PubMed=21225229; DOI=10.3892/ijo.2011.900; RA Platica M., Ionescu A., Ivan E., Holland J.F., Mandeli J., Platica O.; RT "PAR, a protein involved in the cell cycle, is functionally related to RT chromosomal passenger proteins."; RL Int. J. Oncol. 38:777-785(2011). RN [37] RP FUNCTION, SUBUNIT, AND INTERACTION WITH XIAP/BIRC4 AND DIABLO/SMAC. 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 [38] RP X-RAY CRYSTALLOGRAPHY (2.71 ANGSTROMS) OF ISOFORM 1. RX PubMed=10949039; DOI=10.1016/S1097-2765(00)00019-8; RA Chantalat L., Skoufias D.A., Kleman J.P., Jung B., Dideberg O., RA Margolis R.L.; RT "Crystal structure of human survivin reveals a bow tie-shaped dimer RT with two unusual alpha-helical extensions."; RL Mol. Cell 6:183-189(2000). RN [39] RP X-RAY CRYSTALLOGRAPHY (2.58 ANGSTROMS) OF ISOFORM 1. RX PubMed=10876248; DOI=10.1038/76838; RA Verdecia M.A., Huang H., Dutil E., Kaiser D.A., Hunter T., Noel J.P.; RT "Structure of the human anti-apoptotic protein survivin reveals a RT dimeric arrangement."; RL Nat. Struct. Biol. 7:602-608(2000). RN [40] RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) IN COMPLEX WITH ZINC IONS, RP SUBUNIT, AND INTERACTION WITH CDCA8 AND INCENP. RX PubMed=17956729; DOI=10.1016/j.cell.2007.07.045; RA Jeyaprakash A.A., Klein U.R., Lindner D., Ebert J., Nigg E.A., RA Conti E.; RT "Structure of a Survivin-Borealin-INCENP core complex reveals how RT chromosomal passengers travel together."; RL Cell 131:271-285(2007). RN [41] RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS). RX PubMed=19530738; DOI=10.1021/bi900530v; RA Bourhis E., Lingel A., Phung Q., Fairbrother W.J., Cochran A.G.; RT "Phosphorylation of a borealin dimerization domain is required for RT proper chromosome segregation."; RL Biochemistry 48:6783-6793(2009). CC -!- FUNCTION: Multitasking protein that has dual roles in promoting CC cell proliferation and preventing apoptosis. Component of a CC chromosome passage protein complex (CPC) which is essential for CC chromosome alignment and segregation during mitosis and CC cytokinesis. Acts as an important regulator of the localization of CC this complex; directs CPC movement to different locations from the CC inner centromere during prometaphase to midbody during cytokinesis CC and participates in the organization of the center spindle by CC associating with polymerized microtubules. The complex with RAN CC plays a role in mitotic spindle formation by serving as a physical CC scaffold to help deliver the RAN effector molecule TPX2 to CC microtubules. May counteract a default induction of apoptosis in CC G2/M phase. The acetylated form represses STAT3 transactivation of CC target gene promoters. May play a role in neoplasia. Inhibitor of CC CASP3 and CASP7. Isoform 2 and isoform 3 do not appear to play CC vital roles in mitosis. Isoform 3 shows a marked reduction in its CC anti-apoptotic effects when compared with the displayed wild-type CC isoform. CC -!- SUBUNIT: Monomer or homodimer. Exists as a homodimer in the apo CC state and as a monomer in the CPC-bound state. The monomer CC protects cells against apoptosis more efficiently than the dimer. CC Only the dimeric form is capable of enhancing tubulin stability in CC cells. When phosphorylated, interacts with LAMTOR5/HBXIP; the CC resulting complex binds pro-CASP9, as well as active CASP9, but CC much less efficiently. Component of the chromosomal passenger CC complex (CPC) composed of at least BIRC5/survivin, CDCA8/borealin, CC INCENP, AURKB and AURKC. Interacts with JTB. Interacts with CDCA8 CC and INCENP; interaction is direct. Interacts with EVI5. Interacts CC with GTP-bound RAN in both the S and M phases of the cell cycle. CC Interacts with USP9X. Interacts with tubulin. Interacts with CC BIRC2/c-IAP1. The acetylated form at Lys-129 interacts with STAT3. CC The monomeric form deacetylated at Lys-129 interacts with CC XPO1/CRM1. The monomeric form interacts with XIAP/BIRC4. Both the CC dimeric and monomeric form can interact with DIABLO/SMAC. CC Interacts with BIRC6/bruce. CC -!- INTERACTION: CC Q96GD4:AURKB; NbExp=6; IntAct=EBI-518823, EBI-624291; CC Q14457:BECN1; NbExp=3; IntAct=EBI-518823, EBI-949378; CC Q53HL2:CDCA8; NbExp=14; IntAct=EBI-518823, EBI-979174; CC P06493:CDK1; NbExp=6; IntAct=EBI-518823, EBI-444308; CC Q9NQS7:INCENP; NbExp=10; IntAct=EBI-518823, EBI-307907; CC O14980:XPO1; NbExp=2; IntAct=EBI-518823, EBI-355867; CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Chromosome. Chromosome, CC centromere. Cytoplasm, cytoskeleton, spindle. Chromosome, CC centromere, kinetochore. Midbody. Note=Localizes on chromosome CC arms and inner centromeres from prophase through metaphase. CC Localizes to kinetochores in metaphase, distributes to the midzone CC microtubules in anaphase and at telophase, localizes exclusively CC to the midbody. Colocalizes with AURKB at mitotic chromosomes. CC Acetylation at Lys-129 directs its localization to the nucleus by CC enhancing homodimerization and thereby inhibiting XPO1/CRM1- CC mediated nuclear export. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=7; CC Name=1; Synonyms=Alpha; CC IsoId=O15392-1; Sequence=Displayed; CC Name=2; Synonyms=2B, Beta; CC IsoId=O15392-2; Sequence=VSP_002454; CC Name=3; Synonyms=DeltaEx3; CC IsoId=O15392-3; Sequence=VSP_020338; CC Name=4; Synonyms=3B; CC IsoId=O15392-4; Sequence=VSP_020342; CC Name=5; Synonyms=SI; CC IsoId=O15392-5; Sequence=VSP_020341; CC Name=6; Synonyms=3 alpha; CC IsoId=O15392-6; Sequence=VSP_020339; CC Name=7; Synonyms=2 alpha; CC IsoId=O15392-7; Sequence=VSP_020340; CC -!- TISSUE SPECIFICITY: Expressed only in fetal kidney and liver, and CC to lesser extent, lung and brain. Abundantly expressed in CC adenocarcinoma (lung, pancreas, colon, breast, and prostate) and CC in high-grade lymphomas. Also expressed in various renal cell CC carcinoma cell lines. CC -!- DEVELOPMENTAL STAGE: Expression is cell cycle-dependent and peaks CC at mitosis. CC -!- INDUCTION: Up-regulated by COMP. CC -!- DOMAIN: The BIR repeat is necessary and sufficient for LAMTOR5 CC binding. CC -!- PTM: Ubiquitination is required for centrosomal targeting. CC -!- PTM: In vitro phosphorylation at Thr-117 by AURKB prevents CC interaction with INCENP and localization to mitotic chromosomes. CC Phosphorylation at Thr-48 by CK2 is critical for its mitotic and CC anti-apoptotic activities. CC -!- PTM: Acetylation at Lys-129 by CBP results in its CC homodimerization, while deacetylation promotes the formation of CC monomers which heterodimerize with XPO1/CRM1 which facilitates its CC nuclear export. The acetylated form represses STAT3 CC transactivation. The dynamic equilibrium between its acetylation CC and deacetylation at Lys-129 determines its interaction with CC XPO1/CRM1, its subsequent subcellular localization, and its CC ability to inhibit STAT3 transactivation. CC -!- SIMILARITY: Belongs to the IAP family. CC -!- SIMILARITY: Contains 1 BIR repeat. CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/birc5/"; 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; U75285; AAC51660.1; -; Genomic_DNA. DR EMBL; AF077350; AAD34226.1; -; mRNA. DR EMBL; AB154416; BAD11155.1; -; mRNA. DR EMBL; AY830084; AAW22624.1; -; mRNA. DR EMBL; AB028869; BAA93676.1; -; mRNA. DR EMBL; AY927772; AAY15202.1; -; mRNA. DR EMBL; DQ227257; ABB76601.1; -; mRNA. DR EMBL; DQ310375; ABC42341.1; -; mRNA. DR EMBL; DQ310376; ABC42342.1; -; mRNA. DR EMBL; DQ310377; ABC42343.1; -; mRNA. DR EMBL; DQ310378; ABC42344.1; -; mRNA. DR EMBL; DQ310379; ABC42345.1; -; mRNA. DR EMBL; CR541740; CAG46540.1; -; mRNA. DR EMBL; AK223428; BAD97148.1; -; mRNA. DR EMBL; AK311917; BAG34858.1; -; mRNA. DR EMBL; AY795969; AAV40840.1; -; Genomic_DNA. DR EMBL; AC087645; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471099; EAW89514.1; -; Genomic_DNA. DR EMBL; BC008718; AAH08718.1; -; mRNA. DR EMBL; BC034148; AAH34148.1; -; mRNA. DR EMBL; BC065497; AAH65497.1; -; mRNA. DR IPI; IPI00006210; -. DR IPI; IPI00218095; -. DR IPI; IPI00735946; -. DR IPI; IPI00784873; -. DR IPI; IPI00784916; -. DR IPI; IPI00784964; -. DR IPI; IPI00785191; -. DR RefSeq; NP_001012270.1; NM_001012270.1. DR RefSeq; NP_001012271.1; NM_001012271.1. DR RefSeq; NP_001159.2; NM_001168.2. DR UniGene; Hs.744872; -. DR PDB; 1E31; X-ray; 2.71 A; A/B=1-142. DR PDB; 1F3H; X-ray; 2.58 A; A/B=1-142. DR PDB; 1XOX; NMR; -; A/B=1-117. DR PDB; 2QFA; X-ray; 1.40 A; A=1-142. DR PDB; 2RAW; X-ray; 2.40 A; A=1-142. DR PDB; 2RAX; X-ray; 3.30 A; A/E/X=1-120. DR PDB; 3UEC; X-ray; 2.18 A; A=1-142. DR PDB; 3UED; X-ray; 2.70 A; A/C=1-142. DR PDB; 3UEE; X-ray; 2.61 A; A/C=1-142. DR PDB; 3UEF; X-ray; 2.45 A; A/C=1-142. DR PDB; 3UEG; X-ray; 2.80 A; A/B=1-142. DR PDB; 3UEH; X-ray; 2.60 A; A/B=1-142. DR PDB; 3UEI; X-ray; 2.70 A; A/B=1-142. DR PDB; 3UIG; X-ray; 2.40 A; A/B=1-142. DR PDB; 3UIH; X-ray; 2.40 A; A/B=1-142. DR PDB; 3UII; X-ray; 2.60 A; A/B=1-142. DR PDB; 3UIJ; X-ray; 2.70 A; A/B=1-142. DR PDB; 3UIK; X-ray; 2.70 A; A/B=1-142. DR PDB; 4A0I; X-ray; 2.60 A; A/B=1-142. DR PDB; 4A0J; X-ray; 2.80 A; A/B=1-142. DR PDB; 4A0N; X-ray; 2.74 A; A=1-142. DR PDBsum; 1E31; -. DR PDBsum; 1F3H; -. DR PDBsum; 1XOX; -. DR PDBsum; 2QFA; -. DR PDBsum; 2RAW; -. DR PDBsum; 2RAX; -. DR PDBsum; 3UEC; -. DR PDBsum; 3UED; -. DR PDBsum; 3UEE; -. DR PDBsum; 3UEF; -. DR PDBsum; 3UEG; -. DR PDBsum; 3UEH; -. DR PDBsum; 3UEI; -. DR PDBsum; 3UIG; -. DR PDBsum; 3UIH; -. DR PDBsum; 3UII; -. DR PDBsum; 3UIJ; -. DR PDBsum; 3UIK; -. DR PDBsum; 4A0I; -. DR PDBsum; 4A0J; -. DR PDBsum; 4A0N; -. DR ProteinModelPortal; O15392; -. DR SMR; O15392; 5-142. DR DIP; DIP-34662N; -. DR IntAct; O15392; 12. DR MINT; MINT-147138; -. DR STRING; 9606.ENSP00000301633; -. DR MEROPS; I32.005; -. DR PhosphoSite; O15392; -. DR PaxDb; O15392; -. DR PRIDE; O15392; -. DR DNASU; 332; -. DR Ensembl; ENST00000374948; ENSP00000364086; ENSG00000089685. DR Ensembl; ENST00000590449; ENSP00000465868; ENSG00000089685. DR Ensembl; ENST00000590925; ENSP00000467336; ENSG00000089685. DR Ensembl; ENST00000592734; ENSP00000466617; ENSG00000089685. DR GeneID; 332; -. DR KEGG; hsa:332; -. DR UCSC; uc002jvg.3; human. DR CTD; 332; -. DR GeneCards; GC17P076210; -. DR HGNC; HGNC:593; BIRC5. DR HPA; CAB004270; -. DR HPA; HPA002830; -. DR MIM; 603352; gene. DR neXtProt; NX_O15392; -. DR PharmGKB; PA25362; -. DR eggNOG; NOG271140; -. DR HOVERGEN; HBG050690; -. DR KO; K08731; -. DR Reactome; REACT_115566; Cell Cycle. DR Reactome; REACT_21300; Mitotic M-M/G1 phases. DR SignaLink; O15392; -. DR BindingDB; O15392; -. DR ChEMBL; CHEMBL5989; -. DR ChiTaRS; BIRC5; human. DR EvolutionaryTrace; O15392; -. DR GeneWiki; Survivin; -. DR GenomeRNAi; 332; -. DR NextBio; 1369; -. DR PRO; PR:O15392; -. DR ArrayExpress; O15392; -. DR Bgee; O15392; -. DR CleanEx; HS_BIRC5; -. DR Genevestigator; O15392; -. DR GO; GO:0005814; C:centriole; IDA:UniProtKB. DR GO; GO:0032133; C:chromosome passenger complex; IPI:UniProtKB. DR GO; GO:0000775; C:chromosome, centromeric region; IDA:UniProtKB. DR GO; GO:0000777; C:condensed chromosome kinetochore; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005881; C:cytoplasmic microtubule; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:UniProtKB. DR GO; GO:0031021; C:interphase microtubule organizing center; IDA:UniProtKB. DR GO; GO:0005874; C:microtubule; IEA:UniProtKB-KW. DR GO; GO:0030496; C:midbody; IDA:UniProtKB. DR GO; GO:0000228; C:nuclear chromosome; IDA:UniProtKB. DR GO; GO:0005819; C:spindle; IEA:UniProtKB-SubCell. DR GO; GO:0005876; C:spindle microtubule; IDA:UniProtKB. DR GO; GO:0050897; F:cobalt ion binding; NAS:UniProtKB. DR GO; GO:0048037; F:cofactor binding; 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; IMP:UniProtKB. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0008017; F:microtubule binding; IDA:UniProtKB. DR GO; GO:0046982; F:protein heterodimerization activity; IDA:UniProtKB. DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB. DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB. DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW. DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW. DR GO; GO:0007059; P:chromosome segregation; IEA:UniProtKB-KW. DR GO; GO:0000910; P:cytokinesis; IMP:UniProtKB. DR GO; GO:0051303; P:establishment of chromosome localization; IMP:UniProtKB. DR GO; GO:0000086; P:G2/M transition of mitotic cell cycle; IDA:UniProtKB. DR GO; GO:0007067; P:mitosis; IEA:UniProtKB-KW. DR GO; GO:0000278; P:mitotic cell cycle; TAS:Reactome. DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB. DR GO; GO:0045892; P:negative regulation of transcription, DNA-dependent; IMP:UniProtKB. DR GO; GO:0008284; P:positive regulation of cell proliferation; TAS:UniProtKB. DR GO; GO:0031536; P:positive regulation of exit from mitosis; IMP:UniProtKB. DR GO; GO:0045931; P:positive regulation of mitotic cell cycle; IMP:UniProtKB. DR GO; GO:0031503; P:protein complex localization; IMP:UniProtKB. DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB. DR GO; GO:0031577; P:spindle checkpoint; IMP:UniProtKB. DR GO; GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW. DR Gene3D; 1.10.1170.10; -; 1. DR InterPro; IPR001370; BIR. DR Pfam; PF00653; BIR; 1. DR SMART; SM00238; BIR; 1. DR PROSITE; PS01282; BIR_REPEAT_1; FALSE_NEG. DR PROSITE; PS50143; BIR_REPEAT_2; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Apoptosis; KW Cell cycle; Cell division; Centromere; Chromosome; KW Chromosome partition; Complete proteome; Cytoplasm; Cytoskeleton; KW Kinetochore; Metal-binding; Microtubule; Mitosis; Nucleus; KW Phosphoprotein; Polymorphism; Protease inhibitor; Reference proteome; KW Repressor; Thiol protease inhibitor; Transcription; KW Transcription regulation; Ubl conjugation; Zinc. FT CHAIN 1 142 Baculoviral IAP repeat-containing protein FT 5. FT /FTId=PRO_0000122356. FT REPEAT 18 88 BIR. FT METAL 57 57 Zinc. FT METAL 60 60 Zinc. FT METAL 77 77 Zinc. FT METAL 84 84 Zinc. FT MOD_RES 23 23 N6-acetyllysine. FT MOD_RES 34 34 Phosphothreonine; by CDK1. FT MOD_RES 48 48 Phosphothreonine; by CK2; in vitro. FT MOD_RES 90 90 N6-acetyllysine. FT MOD_RES 110 110 N6-acetyllysine. FT MOD_RES 112 112 N6-acetyllysine. FT MOD_RES 115 115 N6-acetyllysine. FT MOD_RES 117 117 Phosphothreonine; by AURKB. FT MOD_RES 121 121 N6-acetyllysine. FT MOD_RES 129 129 N6-acetyllysine. FT VAR_SEQ 74 142 IEEHKKHSSGCAFLSVKKQFEELTLGEFLKLDRERAKNKIA FT KETNNKKKEFEETAKKVRRAIEQLAAMD -> MQRKPTIRR FT KNLRKLRRKCAVPSSSWLPWIEASGRSCLVPEWLHHFQGLF FT PGATSLPVGPLAMS (in isoform 3). FT /FTId=VSP_020338. FT VAR_SEQ 74 142 IEEHKKHSSGCAFLSVKKQFEELTLGEFLKLDRERAKNKIA FT KETNNKKKEFEETAKKVRRAIEQLAAMD -> MRELC (in FT isoform 6). FT /FTId=VSP_020339. FT VAR_SEQ 74 142 IEEHKKHSSGCAFLSVKKQFEELTLGEFLKLDRERAKNKIA FT KETNNKKKEFEETAKKVRRAIEQLAAMD -> M (in FT isoform 7). FT /FTId=VSP_020340. FT VAR_SEQ 74 74 I -> IGPGTVAYACNTSTLGGRGGRITR (in isoform FT 2). FT /FTId=VSP_002454. FT VAR_SEQ 105 142 DRERAKNKIAKETNNKKKEFEETAKKVRRAIEQLAAMD -> FT VRETLPPPRSFIR (in isoform 5). FT /FTId=VSP_020341. FT VAR_SEQ 114 142 AKETNNKKKEFEETAKKVRRAIEQLAAMD -> ERALLAE FT (in isoform 4). FT /FTId=VSP_020342. FT VARIANT 129 129 K -> E (loss of acetylation; localization FT primarily within the cytoplasm; increased FT likelihood of existing as monomer; FT stronger binding to XPO1/CRM1; FT dbSNP:rs2071214). FT /FTId=VAR_021071. FT MUTAGEN 23 23 K->R: Increases ubiquitination and blocks FT dissociation from centromeres; when FT associated with R-62; R-78 and R-79. FT MUTAGEN 34 34 T->A: Loss of LAMTOR5 binding. FT MUTAGEN 34 34 T->E: Higher affinity for LAMTOR5 FT binding. FT MUTAGEN 48 48 T->A,E: Localizes normally during mitosis FT but cannot support cell proliferation. FT Increased affinity for CDCA8/borealin. FT MUTAGEN 62 62 K->R: Increases ubiquitination and blocks FT dissociation from centromeres; when FT associated with R-23; R-78 and R-79. FT MUTAGEN 65 65 E->A: Almost abolishes RAN-binding. Does FT not disrupt binding to AURKB or CDCA8. FT Disrupts mitotic spindle assembly. Does FT not disrupt nuclear export. FT MUTAGEN 70 70 D->A: No change. Loss of interaction with FT AURKB; when associated with A-71. FT MUTAGEN 71 71 D->A: No change. Loss of interaction with FT AURKB; when associated with A-70. FT MUTAGEN 78 78 K->R: Increases ubiquitination and blocks FT dissociation from centromeres; when FT associated with R-23; R-62 and R-79. FT MUTAGEN 79 79 K->R: Increases ubiquitination and blocks FT dissociation from centromeres; when FT associated with R-23; R-62 and R-78. FT MUTAGEN 84 84 C->A: Loss of cytoprotection. FT MUTAGEN 117 117 T->A: Prevents phosphorylation by AURKB. FT Still able to localize correctly but FT prevents interaction with INCENP. FT MUTAGEN 117 117 T->E: Mimics phosphorylation. Disrupts FT subcellular localization during mitosis FT and prevents interaction with INCENP. FT MUTAGEN 129 129 K->A,Q: Mimics acetylation. Localization FT primarily within the nucleus. FT MUTAGEN 129 129 K->R: Loss of acetylation. Localization FT primarily within the cytoplasm. FT CONFLICT 57 58 CF -> WV (in Ref. 5; AAW22624). FT CONFLICT 58 58 F -> L (in Ref. 11; BAD97148). FT CONFLICT 128 128 A -> V (in Ref. 9; CAG46540). FT TURN 8 10 FT HELIX 11 13 FT HELIX 15 20 FT STRAND 31 33 FT HELIX 35 40 FT STRAND 43 45 FT STRAND 49 51 FT STRAND 55 57 FT TURN 58 60 FT STRAND 63 65 FT HELIX 73 80 FT TURN 81 83 FT HELIX 85 88 FT HELIX 93 95 FT HELIX 98 139 SQ SEQUENCE 142 AA; 16389 MW; 9E7CADCDF2822286 CRC64; MGAPTLPPAW QPFLKDHRIS TFKNWPFLEG CACTPERMAE AGFIHCPTEN EPDLAQCFFC FKELEGWEPD DDPIEEHKKH SSGCAFLSVK KQFEELTLGE FLKLDRERAK NKIAKETNNK KKEFEETAKK VRRAIEQLAA MD //