BIRC5
This gene is a member of the inhibitor of apoptosis (IAP) gene family, which encode negative regulatory proteins that prevent apoptotic cell death. IAP family members usually contain multiple baculovirus IAP repeat (BIR) domains, but this gene encodes proteins with only a single BIR domain. The encoded proteins also lack a C-terminus RING finger domain. Gene expression is high during fetal development and in most tumors, yet low in adult tissues. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jun 2011]
Full Name
Baculoviral IAP Repeat Containing 5
Function
Multitasking protein that has dual roles in promoting cell proliferation and preventing apoptosis (PubMed:9859993, PubMed:21364656, PubMed:20627126, PubMed:25778398, PubMed:28218735).
Component of a chromosome passage protein complex (CPC) which is essential for chromosome alignment and segregation during mitosis and cytokinesis (PubMed:16322459).
Acts as an important regulator of the localization of this complex; directs CPC movement to different locations from the inner centromere during prometaphase to midbody during cytokinesis and participates in the organization of the center spindle by associating with polymerized microtubules (PubMed:20826784).
Involved in the recruitment of CPC to centromeres during early mitosis via association with histone H3 phosphorylated at 'Thr-3' (H3pT3) during mitosis (PubMed:20929775).
The complex with RAN plays a role in mitotic spindle formation by serving as a physical scaffold to help deliver the RAN effector molecule TPX2 to microtubules (PubMed:18591255).
May counteract a default induction of apoptosis in G2/M phase (PubMed:9859993).
The acetylated form represses STAT3 transactivation of target gene promoters (PubMed:20826784).
May play a role in neoplasia (PubMed:10626797).
Inhibitor of CASP3 and CASP7 (PubMed:21536684).
Essential for the maintenance of mitochondrial integrity and function (PubMed:25778398).
Isoform 2 and isoform 3 do not appear to play vital roles in mitosis (PubMed:12773388, PubMed:16291752).
Isoform 3 shows a marked reduction in its anti-apoptotic effects when compared with the displayed wild-type isoform (PubMed:10626797).
Biological Process
Cell division Source: UniProtKB
Chromosome segregation Source: UniProtKB-KW
Cytokine-mediated signaling pathway Source: Reactome
Establishment of chromosome localization Source: UniProtKB
G2/M transition of mitotic cell cycle Source: UniProtKB
Mitotic cell cycle Source: UniProtKB
Mitotic cytokinesis Source: UniProtKB
Mitotic spindle assembly checkpoint Source: UniProtKB
Mitotic spindle organization Source: Reactome
Negative regulation of apoptotic process Source: UniProtKB
Negative regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
Negative regulation of transcription, DNA-templated Source: UniProtKB
Positive regulation of cell population proliferation Source: UniProtKB
Positive regulation of exit from mitosis Source: UniProtKB
Positive regulation of mitotic cell cycle Source: UniProtKB
Protein-containing complex localization Source: UniProtKB
Protein phosphorylation Source: UniProtKB
Regulation of apoptotic process Source: Reactome
Regulation of cell cycle Source: GO_Central
Sensory perception of sound Source: UniProtKB
Cellular Location
Spindle; Cytoplasm; Nucleus; Chromosome; Centromere; Kinetochore; Midbody. Localizes at the centromeres from prophase to metaphase, at the spindle midzone during anaphase and a the midbody during telophase and cytokinesis. Accumulates in the nucleus upon treatment with leptomycin B (LMB), a XPO1/CRM1 nuclear export inhibitor (By similarity). Localizes on chromosome arms and inner centromeres from prophase through metaphase. Localizes to kinetochores in metaphase, distributes to the midzone microtubules in anaphase and at telophase, localizes exclusively to the midbody (PubMed:11084331). Colocalizes with AURKB at mitotic chromosomes (PubMed:14610074). Acetylation at Lys-129 directs its localization to the nucleus by enhancing homodimerization and thereby inhibiting XPO1/CRM1-mediated nuclear export (PubMed:20826784).
PTM
Ubiquitinated by the Cul9-RING ubiquitin-protein ligase complex, leading to its degradation. Ubiquitination is required for centrosomal targeting.
In vitro phosphorylation at Thr-117 by AURKB prevents interaction with INCENP and localization to mitotic chromosomes (PubMed:14610074). Phosphorylation at Thr-48 by CK2 is critical for its mitotic and anti-apoptotic activities (PubMed:21252625). Phosphorylation at Thr-34 by CDK15 is critical for its anti-apoptotic activity (PubMed:24866247). Phosphorylation at Ser-20 by AURKC is critical for regulation of proper chromosome alignment and segregation, and possibly cytokinesis.
Acetylation at Lys-129 by CBP results in its homodimerization, while deacetylation promotes the formation of monomers which heterodimerize with XPO1/CRM1 which facilitates its nuclear export. The acetylated form represses STAT3 transactivation. The dynamic equilibrium between its acetylation and deacetylation at Lys-129 determines its interaction with XPO1/CRM1, its subsequent subcellular localization, and its ability to inhibit STAT3 transactivation.
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