Apoptosis Database

Description [+]

Synonyms: BIRC5
Species: Metazoa;Bilateria;Deuterostoma;Chordata;Vertebrata;Mammalia;Primates;Hominidae; Homo sapiens
Short gene description: Baculoviral IAP repeat-containing protein 5 (Apoptosis inhibitor survivin)(Apoptosis inhibitor 4) [Source:UniProtKB/Swiss-Prot;Acc:O15392]
Family: BIR-containing protein : other
Process: cell death (other),
Pathways:
Criteria: manually curated
Curator comment: Survivin is a protein with homology to IAPs but whose main role is the regulation of mitosis, not cell death.
Mouse ortholog(s): Birc5
WIKI: BIRC5-H_sapiens

References [+]

A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma.
Ambrosini G, Adida C, Altieri DC
Inhibitors of programmed cell death (apoptosis) aberrantly prolonging cell viability may contribute to cancer by facilitating the insurgence of mutations and by promoting resistance to therapy. Despite the identification of several new apoptosis inhibitors related to bcl-2 or to the baculovirus IAP gene, it is not clear whether apoptosis inhibition plays a general role in neoplasia. Here, we describe a new human gene encoding a structurally unique IAP apoptosis inhibitor, designated survivin. Survivin contains a single baculovirus IAP repeat and lacks a carboxyl-terminal RING finger. Present during fetal development, survivin is undetectable in terminally differentiated adult tissues. However, survivin becomes prominently expressed in transformed cell lines and in all the most common human cancers of lung, colon, pancreas, prostate and breast, in vivo. Survivin is also found in approximately 50% of high-grade non-Hodgkin's lymphomas (centroblastic, immunoblastic), but not in low-grade lymphomas (lymphocytic). Recombinant expression of survivin counteracts apoptosis of B lymphocyte precursors deprived of interleukin 3 (IL-3). These findings suggest that apoptosis inhibition may be a general feature of neoplasia and identify survivin as a potential new target for apoptosis-based therapy in cancer and lymphoma. Nat Med. 1997 Aug;3(8):917-21.

Two kinds of BIR-containing protein - inhibitors of apoptosis, or required for mitosis.
Silke J, Vaux DL
The baculoviral IAP repeat (BIR) is a zinc-binding fold. Some BIR-containing proteins (BIRCs), including several from insect viruses, insects and vertebrates, are inhibitors of cell death and act by binding to active caspases. Their ability to do so can be antagonized by pro-apoptotic insect proteins such as Grim, HID and Reaper, or the mammalian protein Diablo/Smac. Members of one structurally distinct subgroup of BIR-containing proteins, which are present in yeasts and Caenorhabditis elegans as well as insects and vertebrates, do not act as caspase inhibitors; instead, they are required for chromosome segregation and cytokinesis, and act in concert with inner centromere protein (INCENP) homologues and aurora kinase homologues. J Cell Sci. 2001 May;114(Pt 10):1821-7.

The case for Survivin as mitotic regulator.
Lens SM, Vader G, Medema RH
Survivin has been proposed to inhibit apoptosis and to regulate cell division. However, controversy still exists as to whether Survivin can indeed execute these distinct functions and if Survivin somehow coordinates apoptosis and (abnormal) cell division. Recent evidence has demonstrated that Survivin acts as a subunit of the chromosomal passenger complex, which is essential for proper chromosome segregation and cytokinesis. Within this complex, the mitotic kinase Aurora B acts as the enzymatic core, whereas Survivin dictates chromosomal passenger complex localization. This function of Survivin appears to be conserved throughout evolution. Although these findings do not exclude a role for Survivin as apoptosis inhibitor, they make a very strong case for Survivin as mitotic regulator. Curr Opin Cell Biol. 2006 Dec;18(6):616-22. Epub 2006 Sep 7.

References from Mouse ortholog(s):

Deficiency of survivin in transgenic mice exacerbates Fas-induced apoptosis via mitochondrial pathways.
Conway EM, Pollefeyt S, Steiner-Mosonyi M, Luo W, Devriese A, Lupu F, Bono F, Leducq N, Dol F, Schaeffer P, Collen D, Herbert JM
BACKGROUND & AIMS: Survivin is an inhibitor of apoptosis protein (IAP), which also is crucial for mitosis and cell cycle progression. IAPs participate in regulating Fas ligand-induced hepatic apoptosis. The aim was to study the contribution of survivin to hepatic apoptosis by generating transgenic mice lacking survivin. METHODS: The survivin gene was inactivated in mice by homologous recombination in embryonic stem cells. Survivin+/- and survivin+/+ mice were generated and injected with the Fas agonistic antibody Jo2. RESULTS: In 3 genetic backgrounds, survivin-/- embryos died before 4.5 days post coitum. Survivin+/- mice appeared normal, but liver lysates revealed baseline low-level activation of procaspase-8, Bid, procaspase-9, and procaspase-3, with accumulation of Bax, and release of cytochrome c, indicating a proapoptotic state. Intraperitoneal injection of low-dose Jo2 had no effect on survivin+/+ mice at 2 hours. However, in survivin+/- mice, Jo2 caused hemorrhagic necrosis of the liver, associated with prominent activation of the apoptotic pathway via the mitochondria, and up-regulation of hepatocellular expression of survivin in the cytosol, nuclei, and mitochondria. Isolated mitochondria from survivin+/- livers had more defects in oxidative phosphorylation after C(2)-ceramide exposure. CONCLUSIONS: Absence of survivin is incompatible with life. Although Jo2 induces expression of survivin, diminished baseline levels render the liver more sensitive to Fas, possibly due to functional effects on the mitochondria. This is the first in vivo documentation that survivin modulates caspase activation and that Fas-mediated hepatic apoptosis is regulated by survivin via mitochondrial pathways. Gastroenterology. 2002 Aug;123(2):619-31.

Two kinds of BIR-containing protein - inhibitors of apoptosis, or required for mitosis.
Silke J, Vaux DL
The baculoviral IAP repeat (BIR) is a zinc-binding fold. Some BIR-containing proteins (BIRCs), including several from insect viruses, insects and vertebrates, are inhibitors of cell death and act by binding to active caspases. Their ability to do so can be antagonized by pro-apoptotic insect proteins such as Grim, HID and Reaper, or the mammalian protein Diablo/Smac. Members of one structurally distinct subgroup of BIR-containing proteins, which are present in yeasts and Caenorhabditis elegans as well as insects and vertebrates, do not act as caspase inhibitors; instead, they are required for chromosome segregation and cytokinesis, and act in concert with inner centromere protein (INCENP) homologues and aurora kinase homologues. J Cell Sci. 2001 May;114(Pt 10):1821-7.

Structure & Sequence [+]

Source	Domain Name	Start	End
PFAM A	BIR	18	88

Evolution [+]

Name	Relationship	Species
NP_001012318.1	orthology	Chicken
BIRC5	orthology	Chimpanzee
BIRC5_BOVIN	orthology	Cow
BIRC5_CANFA	orthology	Dog
BIRC5	orthology	Fugu
BIRC5	orthology	Gasterosteus
XP_001504809.1	orthology	Horse
XP_001915435.1	orthology	Horse
BIRC5	orthology	Lyzard
LOC709565	orthology	Macaca
BIRC5	orthology	Medaka
BIRC5	orthology	Monodelphis
Birc5	orthology	Mouse
BIRC5_PONPY	orthology	Orangutan
BIRC5	orthology	Ornithorhynchus
BIRC5	orthology	Tetraodon
birc5	orthology	Xenopus
BIRC5	orthology	Zebra finch
D_rerio_ENSDARP00000003986	orthology	Zebrafish
A_aegypti_AAEL012446-PA	paralogy	Aedes
A_aegypti_AAEL014251-PA	paralogy	Aedes
IAP6	paralogy	Anopheles
A_gambiae_AGAP008420-PA	paralogy	Anopheles
BIRC6	paralogy	Chicken
IPI00578886.3	paralogy	Chicken
IPI00819997.1	paralogy	Chicken
XR_024877.1	paralogy	Chimpanzee
P_troglodytes_ENSPTRP00000048273	paralogy	Chimpanzee
XM_001156604.1	paralogy	Chimpanzee
XR_024877.1	paralogy	Chimpanzee
IPI00689691.3	paralogy	Cow
IPI00689691.3	paralogy	Cow
XR_042763.1	paralogy	Cow
XR_042763.1	paralogy	Cow
BIRC6	paralogy	Dog
BIRC6	paralogy	Dog
Bruce	paralogy	Fly
Bruce	paralogy	Fly
D_melanogaster_FBpp0082849	paralogy	Fly
BIRC6	paralogy	Fugu
BIRC6	paralogy	Fugu
T_rubripes_ENSTRUP00000033609	paralogy	Fugu
G_aculeatus_ENSGACP00000011826	paralogy	Gasterosteus
BIRC6	paralogy	Gorilla
E_caballus_ENSECAP00000002314	paralogy	Horse
XP_001504091.2	paralogy	Horse
BIRC6	paralogy	Horse
BIRC6	paralogy	Horse
BIRC1	paralogy	Human
NAIP	paralogy	Human
BIRC6	paralogy	Human
BIRC6	paralogy	Human
BIRC6	paralogy	Lyzard
BIRC6	paralogy	Lyzard
A_carolinensis_ENSACAP00000012402	paralogy	Lyzard
M_mulatta_ENSMMUP00000016076	paralogy	Macaca
UBE2Z (2 of 2)	paralogy	Medaka
O_latipes_ENSORLP00000009367	paralogy	Medaka
BIRC6	paralogy	Monodelphis
BIRC6	paralogy	Monodelphis
Birc6	paralogy	Mouse
Birc6	paralogy	Mouse
BIRC6	paralogy	Orangutan
BIRC6	paralogy	Orangutan
P_pygmaeus_ENSPPYP00000017359	paralogy	Orangutan
P_pygmaeus_ENSPPYP00000017359	paralogy	Orangutan
O_anatinus_ENSOANP00000007529	paralogy	Ornithorhynchus
Birc6_predicted	paralogy	Rat
Birc6	paralogy	Rat
BIRC6 (1 of 2)	paralogy	Tetraodon
T_nigroviridis_ENSTNIP00000008212	paralogy	Tetraodon
T_nigroviridis_ENSTNIP00000018133	paralogy	Tetraodon
TEgg052f17.1	paralogy	Xenopus
BIRC6	paralogy	Xenopus
BIRC6	paralogy	Xenopus
BIRC6	paralogy	Zebra finch
BIRC6	paralogy	Zebra finch
XP_002191417.1	paralogy	Zebra finch
T_guttata_ENSTGUP00000014209	paralogy	Zebra finch
birc5b	paralogy	Zebrafish
BIRC7	paralogy	Zebrafish
zgc:165605	paralogy	Zebrafish

Gene Ontology [+]

GO id	Name	Ontology type	Evidence
GO:0009790	embryonic development	biological_proccess	IEA
GO:0043524	negative regulation of neuron apoptosis	biological_proccess	IEA
GO:0000226	microtubule cytoskeleton organization	biological_proccess	IEA
GO:0007049	cell cycle	biological_proccess	IEA
GO:0007067	mitosis	biological_proccess	IEA
GO:0000086	G2/M transition of mitotic cell cycle	biological_proccess	ISS
GO:0000910	cytokinesis	biological_proccess	ISS
GO:0006916	anti-apoptosis	biological_proccess	ISS
GO:0031503	protein complex localization	biological_proccess	ISS
GO:0031536	positive regulation of exit from mitosis	biological_proccess	ISS
GO:0031577	spindle checkpoint	biological_proccess	ISS
GO:0043154	negative regulation of caspase activity	biological_proccess	ISS
GO:0045931	positive regulation of mitotic cell cycle	biological_proccess	ISS
GO:0051303	establishment of chromosome localization	biological_proccess	ISS
GO:0006915	apoptosis	biological_proccess	IEA
GO:0030414	peptidase inhibitor activity	mollecular_function	IEA
GO:0046872	metal ion binding	mollecular_function	IEA
GO:0008017	microtubule binding	mollecular_function	ISS
GO:0008270	zinc ion binding	mollecular_function	ISS
GO:0042803	protein homodimerization activity	mollecular_function	ISS
GO:0048037	cofactor binding	mollecular_function	ISS
GO:0008536	Ran GTPase binding	mollecular_function	IPI
GO:0051087	chaperone binding	mollecular_function	IPI
GO:0019899	enzyme binding	mollecular_function	IPI
GO:0043027	caspase inhibitor activity	mollecular_function	ISS
GO:0005622	intracellular	cell_component	IEA
GO:0005634	nucleus	cell_component	IEA
GO:0000775	chromosome, centromeric region	cell_component	ISS
GO:0005737	cytoplasm	cell_component	ISS
GO:0005829	cytosol	cell_component	ISS
GO:0005876	spindle microtubule	cell_component	ISS
GO:0005881	cytoplasmic microtubule	cell_component	ISS
GO:0030496	midbody	cell_component	ISS
GO:0031021	interphase microtubule organizing center	cell_component	ISS
GO:0043234	protein complex	cell_component	ISS
GO:0032133	chromosome passenger complex	cell_component	IPI
GO:0005694	chromosome	cell_component	IDA
GO:0005814	centriole	cell_component	ISS

Check GO Evidence Codes here

Information from other databases [+]

BIRC5 (Homo sapiens)