PDBsum entry 1m4m

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Apoptosis PDB id
Protein chain
112 a.a. *
_ZN ×2
* Residue conservation analysis
PDB id:
Name: Apoptosis
Title: Mouse survivin
Structure: Baculoviral iap repeat-containing protein 5. Chain: a. Synonym: apoptosis inhibitor survivin, apoptosis inhibitor engineered: yes
Source: Mus musculus. House mouse. Organism_taxid: 10090. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Dimer (from PQS)
2.80Å     R-factor:   0.243     R-free:   0.312
Authors: S.W.Muchmore,J.Chen,C.Jakob,D.Zakula,E.D.Matayoshi,W.Wu,H.Zh S.C.Ng,D.C.Altieri
Key ref: S.W.Muchmore et al. (2000). Crystal structure and mutagenic analysis of the inhibitor-of-apoptosis protein survivin. Mol Cell, 6, 173-182. PubMed id: 10949038
03-Jul-02     Release date:   25-Sep-02    
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Protein chain
Pfam   ArchSchema ?
O70201  (BIRC5_MOUSE) -  Baculoviral IAP repeat-containing protein 5
140 a.a.
112 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     midbody   16 terms 
  Biological process     regulation of insulin secretion involved in cellular response to glucose stimulus   28 terms 
  Biochemical function     protein binding     11 terms  


Mol Cell 6:173-182 (2000)
PubMed id: 10949038  
Crystal structure and mutagenic analysis of the inhibitor-of-apoptosis protein survivin.
S.W.Muchmore, J.Chen, C.Jakob, D.Zakula, E.D.Matayoshi, W.Wu, H.Zhang, F.Li, S.C.Ng, D.C.Altieri.
The coupling of apoptosis (programmed cell death) to the cell division cycle is essential for homeostasis and genomic integrity. Here, we report the crystal structure of survivin, an inhibitor of apoptosis, which has been implicated in both control of cell death and regulation of cell division. In addition to a conserved N-terminal Zn finger baculovirus IAP repeat, survivin forms a dimer through a symmetric interaction with an intermolecularly bound Zn atom located along the molecular dyad axis. The interaction of the dimer-related C-terminal alpha helices forms an extended surface of approximately 70 A in length. Mutagenesis analysis revealed that survivin dimerization and an extended negatively charged surface surrounding Asp-71 are required to counteract apoptosis and preserve ploidy. These findings may provide a structural basis for a dual role of survivin in inhibition of apoptosis and regulation of cell division.

Literature references that cite this PDB file's key reference

  PubMed id Reference
20920299 C.H.Cheung, X.Sun, J.R.Kanwar, J.Z.Bai, L.Cheng, and G.W.Krissansen (2010).
A cell-permeable dominant-negative survivin protein induces apoptosis and sensitizes prostate cancer cells to TNF-α therapy.
  Cancer Cell Int, 10, 36.  
20925597 S.Baratchi, R.K.Kanwar, and J.R.Kanwar (2010).
Survivin: a target from brain cancer to neurodegenerative disease.
  Crit Rev Biochem Mol Biol, 45, 535-554.  
20519042 Z.Shen, D.Ye, X.Zhang, Z.Jiang, B.Xiao, and J.Guo (2010).
Inhibitory effect of HuR gene small interfering RNA segment on laryngeal carcinoma Hep-2 cell growth.
  J Laryngol Otol, 124, 1183-1189.  
19146389 L.Zhou, J.Li, R.George, S.Ruchaud, H.G.Zhou, J.E.Ladbury, W.C.Earnshaw, and X.Yuan (2009).
Effects of full-length borealin on the composition and protein-protein interaction activity of a binary chromosomal passenger complex.
  Biochemistry, 48, 1156-1161.  
19602047 Z.H.Fang, C.L.Dong, Z.Chen, B.Zhou, N.Liu, H.F.Lan, L.Liang, W.B.Liao, L.Zhang, and Z.C.Han (2009).
Transcriptional regulation of survivin by c-Myc in BCR/ABL-transformed cells: implications in anti-leukaemic strategy.
  J Cell Mol Med, 13, 2039-2052.  
18539906 C.Li, Z.Wu, M.Liu, M.Pazgier, and W.Lu (2008).
Chemically synthesized human survivin does not inhibit caspase-3.
  Protein Sci, 17, 1624-1629.  
18348682 M.Pennati, M.Folini, and N.Zaffaroni (2008).
Targeting survivin in cancer therapy.
  Expert Opin Ther Targets, 12, 463-476.  
18936249 Z.Yue, A.Carvalho, Z.Xu, X.Yuan, S.Cardinale, S.Ribeiro, F.Lai, H.Ogawa, E.Gudmundsdottir, R.Gassmann, C.G.Morrison, S.Ruchaud, and W.C.Earnshaw (2008).
Deconstructing Survivin: comprehensive genetic analysis of Survivin function by conditional knockout in a vertebrate cell line.
  J Cell Biol, 183, 279-296.  
17714426 D.Engelsma, J.A.Rodriguez, A.Fish, G.Giaccone, and M.Fornerod (2007).
Homodimerization antagonizes nuclear export of survivin.
  Traffic, 8, 1495-1502.  
17881355 E.Bourhis, S.G.Hymowitz, and A.G.Cochran (2007).
The mitotic regulator Survivin binds as a monomer to its functional interactor Borealin.
  J Biol Chem, 282, 35018-35023.
PDB codes: 2raw 2rax
17241471 H.Kaur, A.C.Stiff, D.A.Date, and W.R.Taylor (2007).
Analysis of mitotic phosphorylation of borealin.
  BMC Cell Biol, 8, 5.  
17671639 H.Zhang, A.Berezov, Q.Wang, G.Zhang, J.Drebin, R.Murali, and M.I.Greene (2007).
ErbB receptors: from oncogenes to targeted cancer therapies.
  J Clin Invest, 117, 2051-2058.  
16888809 P.M.Canovas, and T.M.Guadagno (2007).
Functional analysis of Survivin in spindle assembly in Xenopus egg extracts.
  J Cell Biochem, 100, 217-229.  
17848966 S.Ruchaud, M.Carmena, and W.C.Earnshaw (2007).
Chromosomal passengers: conducting cell division.
  Nat Rev Mol Cell Biol, 8, 798-812.  
16446167 A.Lladser, M.Párraga, L.Quevedo, M.Carmen Molina, S.Silva, A.Ferreira, R.Billetta, and A.F.G Quest (2006).
Naked DNA immunization as an approach to target the generic tumor antigen survivin induces humoral and cellular immune responses in mice.
  Immunobiology, 211, 11-27.  
16769825 G.Vader, R.H.Medema, and S.M.Lens (2006).
The chromosomal passenger complex: guiding Aurora-B through mitosis.
  J Cell Biol, 173, 833-837.  
16331679 H.G.Nguyen, and K.Ravid (2006).
Tetraploidy/aneuploidy and stem cells in cancer promotion: The role of chromosome passenger proteins.
  J Cell Physiol, 208, 12-22.  
16702945 H.Yan, J.Thomas, T.Liu, D.Raj, N.London, T.Tandeski, S.A.Leachman, R.M.Lee, and D.Grossman (2006).
Induction of melanoma cell apoptosis and inhibition of tumor growth using a cell-permeable Survivin antagonist.
  Oncogene, 25, 6968-6974.  
16534789 J.R.Fangusaro, H.Caldas, Y.Jiang, and R.A.Altura (2006).
Survivin: an inhibitor of apoptosis in pediatric cancer.
  Pediatr Blood Cancer, 47, 4.  
16436504 S.M.Lens, J.A.Rodriguez, G.Vader, S.W.Span, G.Giaccone, and R.H.Medema (2006).
Uncoupling the central spindle-associated function of the chromosomal passenger complex from its role at centromeres.
  Mol Biol Cell, 17, 1897-1909.  
16571674 U.R.Klein, E.A.Nigg, and U.Gruneberg (2006).
Centromere targeting of the chromosomal passenger complex requires a ternary subcomplex of Borealin, Survivin, and the N-terminal domain of INCENP.
  Mol Biol Cell, 17, 2547-2558.  
15608672 F.Li, X.Ling, H.Huang, L.Brattain, P.Apontes, J.Wu, L.Binderup, and M.G.Brattain (2005).
Differential regulation of survivin expression and apoptosis by vitamin D3 compounds in two isogenic MCF-7 breast cancer cell sublines.
  Oncogene, 24, 1385-1395.  
15743529 H.Caldas, L.E.Honsey, and R.A.Altura (2005).
Survivin 2alpha: a novel Survivin splice variant expressed in human malignancies.
  Mol Cancer, 4, 11.  
16199877 H.K.Huang, J.M.Bailis, J.D.Leverson, E.B.Gómez, S.L.Forsburg, and T.Hunter (2005).
Suppressors of Bir1p (Survivin) identify roles for the chromosomal passenger protein Pic1p (INCENP) and the replication initiation factor Psf2p in chromosome segregation.
  Mol Cell Biol, 25, 9000-9015.  
15729715 H.Kawakami, M.Tomita, T.Matsuda, T.Ohta, Y.Tanaka, M.Fujii, M.Hatano, T.Tokuhisa, and N.Mori (2005).
Transcriptional activation of survivin through the NF-kappaB pathway by human T-cell leukemia virus type I tax.
  Int J Cancer, 115, 967-974.  
15670305 J.P.Lee, K.H.Chang, J.H.Han, and H.S.Ryu (2005).
Survivin, a novel anti-apoptosis inhibitor, expression in uterine cervical cancer and relationship with prognostic factors.
  Int J Gynecol Cancer, 15, 113-119.  
15894266 J.Plescia, W.Salz, F.Xia, M.Pennati, N.Zaffaroni, M.G.Daidone, M.Meli, T.Dohi, P.Fortugno, Y.Nefedova, D.I.Gabrilovich, G.Colombo, and D.C.Altieri (2005).
Rational design of shepherdin, a novel anticancer agent.
  Cancer Cell, 7, 457-468.  
15453988 E.A.Johnson, S.I.Svetlov, B.R.Pike, P.J.Tolentino, G.Shaw, K.K.Wang, R.L.Hayes, and J.A.Pineda (2004).
Cell-specific upregulation of survivin after experimental traumatic brain injury in rats.
  J Neurotrauma, 21, 1183-1195.  
15351889 P.Vagnarelli, and W.C.Earnshaw (2004).
Chromosomal passengers: the four-dimensional regulation of mitotic events.
  Chromosoma, 113, 211-222.  
14712209 T.Liu, B.Brouha, and D.Grossman (2004).
Rapid induction of mitochondrial events and caspase-independent apoptosis in Survivin-targeted melanoma cells.
  Oncogene, 23, 39-48.  
14699067 Z.Song, S.Liu, H.He, N.Hoti, Y.Wang, S.Feng, and M.Wu (2004).
A single amino acid change (Asp 53 --> Ala53) converts Survivin from anti-apoptotic to pro-apoptotic.
  Mol Biol Cell, 15, 1287-1296.  
12529428 A.Temme, M.Rieger, F.Reber, D.Lindemann, B.Weigle, P.Diestelkoetter-Bachert, G.Ehninger, M.Tatsuka, Y.Terada, and E.P.Rieber (2003).
Localization, dynamics, and function of survivin revealed by expression of functional survivinDsRed fusion proteins in the living cell.
  Mol Biol Cell, 14, 78-92.  
12509766 D.C.Altieri (2003).
Validating survivin as a cancer therapeutic target.
  Nat Rev Cancer, 3, 46-54.  
  12937134 E.M.Conway, F.Zwerts, V.Van Eygen, A.DeVriese, N.Nagai, W.Luo, and D.Collen (2003).
Survivin-dependent angiogenesis in ischemic brain: molecular mechanisms of hypoxia-induced up-regulation.
  Am J Pathol, 163, 935-946.  
12942537 F.Li (2003).
Survivin study: what is the next wave?
  J Cell Physiol, 197, 8.  
12032073 H.W.Wang, T.V.Sharp, A.Koumi, G.Koentges, and C.Boshoff (2002).
Characterization of an anti-apoptotic glycoprotein encoded by Kaposi's sarcoma-associated herpesvirus which resembles a spliced variant of human survivin.
  EMBO J, 21, 2602-2615.  
11950927 J.D.Leverson, H.K.Huang, S.L.Forsburg, and T.Hunter (2002).
The Schizosaccharomyces pombe aurora-related kinase Ark1 interacts with the inner centromere protein Pic1 and mediates chromosome segregation and cytokinesis.
  Mol Biol Cell, 13, 1132-1143.  
12427028 L.E.Luque, K.P.Grape, and M.Junker (2002).
A highly conserved arginine is critical for the functional folding of inhibitor of apoptosis (IAP) BIR domains.
  Biochemistry, 41, 13663-13671.  
11741952 Y.T.Zhou, U.J.Soh, X.Shang, G.R.Guy, and B.C.Low (2002).
The BNIP-2 and Cdc42GAP homology/Sec14p-like domain of BNIP-Salpha is a novel apoptosis-inducing sequence.
  J Biol Chem, 277, 7483-7492.  
12401491 Z.Huang (2002).
The chemical biology of apoptosis. Exploring protein-protein interactions and the life and death of cells with small molecules.
  Chem Biol, 9, 1059-1072.  
11149963 D.Grossman, P.J.Kim, J.S.Schechner, and D.C.Altieri (2001).
Inhibition of melanoma tumor growth in vivo by survivin targeting.
  Proc Natl Acad Sci U S A, 98, 635-640.  
11179890 J.H.Laity, B.M.Lee, and P.E.Wright (2001).
Zinc finger proteins: new insights into structural and functional diversity.
  Curr Opin Struct Biol, 11, 39-46.  
11604477 J.R.Kanwar, W.P.Shen, R.K.Kanwar, R.W.Berg, and G.W.Krissansen (2001).
Effects of survivin antagonists on growth of established tumors and B7-1 immunogene therapy.
  J Natl Cancer Inst, 93, 1541-1552.  
11511363 J.W.Wu, A.E.Cocina, J.Chai, B.A.Hay, and Y.Shi (2001).
Structural analysis of a functional DIAP1 fragment bound to grim and hid peptides.
  Mol Cell, 8, 95.
PDB codes: 1jd4 1jd5 1jd6
11257232 S.J.Riedl, M.Renatus, R.Schwarzenbacher, Q.Zhou, C.Sun, S.W.Fesik, R.C.Liddington, and G.S.Salvesen (2001).
Structural basis for the inhibition of caspase-3 by XIAP.
  Cell, 104, 791-800.
PDB code: 1i3o
  11257231 Y.Huang, Y.C.Park, R.L.Rich, D.Segal, D.G.Myszka, and H.Wu (2001).
Structural basis of caspase inhibition by XIAP: differential roles of the linker versus the BIR domain.
  Cell, 104, 781-790.
PDB code: 1i4o
11069302 D.S.O'Connor, D.Grossman, J.Plescia, F.Li, H.Zhang, A.Villa, S.Tognin, P.C.Marchisio, and D.C.Altieri (2000).
Regulation of apoptosis at cell division by p34cdc2 phosphorylation of survivin.
  Proc Natl Acad Sci U S A, 97, 13103-13107.  
11007472 J.C.Reed, and J.R.Bischoff (2000).
BIRinging chromosomes through cell division--and survivin' the experience.
  Cell, 102, 545-548.  
10949039 L.Chantalat, D.A.Skoufias, J.P.Kleman, B.Jung, O.Dideberg, and R.L.Margolis (2000).
Crystal structure of human survivin reveals a bow tie-shaped dimer with two unusual alpha-helical extensions.
  Mol Cell, 6, 183-189.
PDB code: 1e31
11057900 S.W.Fesik (2000).
Insights into programmed cell death through structural biology.
  Cell, 103, 273-282.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.