UniProt functional annotation for O15392



	UniProt functional annotation for O15392

UniProt code: O15392.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

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). {ECO:0000269|PubMed:10626797, ECO:0000269|PubMed:12773388, ECO:0000269|PubMed:16291752, ECO:0000269|PubMed:16322459, ECO:0000269|PubMed:18591255, ECO:0000269|PubMed:20627126, ECO:0000269|PubMed:20826784, ECO:0000269|PubMed:20929775, ECO:0000269|PubMed:21364656, ECO:0000269|PubMed:21536684, ECO:0000269|PubMed:25778398, ECO:0000269|PubMed:28218735, ECO:0000269|PubMed:9859993}.

Subunit: Monomer or homodimer. Exists as a homodimer in the apo state and as a monomer in the CPC-bound state. The monomer protects cells against apoptosis more efficiently than the dimer. Only the dimeric form is capable of enhancing tubulin stability in cells. When phosphorylated, interacts with LAMTOR5/HBXIP; the resulting complex binds pro-CASP9, as well as active CASP9, but much less efficiently. Component of the chromosomal passenger complex (CPC) composed of at least BIRC5/survivin, CDCA8/borealin, INCENP, AURKB or AURKC; in the complex forms a triple-helix bundle-based subcomplex with INCENP and CDCA8 (PubMed:17956729). Interacts with JTB. Interacts (via BIR domain) with histone H3 phosphorylated at 'Thr-3' (H3pT3). Interacts with EVI5. Interacts with GTP-bound RAN in both the S and M phases of the cell cycle. Interacts with USP9X. Interacts with tubulin. Interacts with BIRC2/c-IAP1. The acetylated form at Lys-129 interacts with STAT3. The monomeric form deacetylated at Lys-129 interacts with XPO1/CRM1. The monomeric form interacts with XIAP/BIRC4. Both the dimeric and monomeric form can interact with DIABLO/SMAC. Interacts with BIRC6/bruce. Interacts with FBXL7; this interaction facilitates the polyubiquitination and subsequent proteasomal degradation of BIRC5 by the SCF(FBXL7) E3 ubiquitin-protein ligase complex (PubMed:25778398, PubMed:28218735). {ECO:0000269|PubMed:12773388, ECO:0000269|PubMed:14610074, ECO:0000269|PubMed:15249581, ECO:0000269|PubMed:15665297, ECO:0000269|PubMed:16239925, ECO:0000269|PubMed:16291752, ECO:0000269|PubMed:16322459, ECO:0000269|PubMed:16427043, ECO:0000269|PubMed:16436504, ECO:0000269|PubMed:16764853, ECO:0000269|PubMed:17956729, ECO:0000269|PubMed:18329369, ECO:0000269|PubMed:18591255, ECO:0000269|PubMed:20826784, ECO:0000269|PubMed:21225229, ECO:0000269|PubMed:21536684, ECO:0000269|PubMed:25778398, ECO:0000269|PubMed:28218735}.

Subcellular location: Cytoplasm {ECO:0000269|PubMed:20627126, ECO:0000269|PubMed:20826784, ECO:0000269|PubMed:21364656}. Nucleus {ECO:0000269|PubMed:20627126, ECO:0000269|PubMed:20826784, ECO:0000269|PubMed:21364656}. Chromosome {ECO:0000269|PubMed:14610074}. Chromosome, centromere {ECO:0000269|PubMed:11084331, ECO:0000269|PubMed:14610074, ECO:0000269|PubMed:16322459}. Cytoplasm, cytoskeleton, spindle {ECO:0000269|PubMed:11084331}. Chromosome, centromere, kinetochore {ECO:0000269|PubMed:11084331}. Midbody {ECO:0000269|PubMed:15665297}. Note=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). {ECO:0000250|UniProtKB:E3SCZ8, ECO:0000269|PubMed:11084331, ECO:0000269|PubMed:14610074, ECO:0000269|PubMed:20826784}.

Tissue specificity: Expressed only in fetal kidney and liver, and to lesser extent, lung and brain (PubMed:10626797). Abundantly expressed in adenocarcinoma (lung, pancreas, colon, breast, and prostate) and in high-grade lymphomas (PubMed:14741722, PubMed:16329164). Also expressed in various renal cell carcinoma cell lines (PubMed:10626797). Expressed in cochlea including the organ of Corti, the lateral wall, the interdental cells of the Limbus as well as in Schwann cells and cells of the cochlear nerve and the spiral ganglions (at protein level). Not expressed in cells of the inner and outer sulcus or the Reissner's membrane (at protein level) (PubMed:21364656, PubMed:20627126). {ECO:0000269|PubMed:10626797, ECO:0000269|PubMed:14741722, ECO:0000269|PubMed:16329164, ECO:0000269|PubMed:20627126, ECO:0000269|PubMed:21364656}.

Developmental stage: Expression is cell cycle-dependent and peaks at mitosis. {ECO:0000269|PubMed:18591255}.

Induction: Up-regulated by COMP. {ECO:0000269|PubMed:17993464}.

Domain: The BIR repeat is necessary and sufficient for LAMTOR5 binding. {ECO:0000269|PubMed:12773388}.

Ptm: Ubiquitinated by the Cul9-RING ubiquitin-protein ligase complex, leading to its degradation. Ubiquitination is required for centrosomal targeting. {ECO:0000269|PubMed:16322459, ECO:0000269|PubMed:24793696}.

Ptm: 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. {ECO:0000269|PubMed:11069302, ECO:0000269|PubMed:14610074, ECO:0000269|PubMed:21252625, ECO:0000269|PubMed:24866247, ECO:0000269|PubMed:27332895}.

Ptm: 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. {ECO:0000269|PubMed:20826784}.

Similarity: Belongs to the IAP family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



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). {ECO:0000269\|PubMed:10626797, ECO:0000269\|PubMed:12773388, ECO:0000269\|PubMed:16291752, ECO:0000269\|PubMed:16322459, ECO:0000269\|PubMed:18591255, ECO:0000269\|PubMed:20627126, ECO:0000269\|PubMed:20826784, ECO:0000269\|PubMed:20929775, ECO:0000269\|PubMed:21364656, ECO:0000269\|PubMed:21536684, ECO:0000269\|PubMed:25778398, ECO:0000269\|PubMed:28218735, ECO:0000269\|PubMed:9859993}.


Subunit:		Monomer or homodimer. Exists as a homodimer in the apo state and as a monomer in the CPC-bound state. The monomer protects cells against apoptosis more efficiently than the dimer. Only the dimeric form is capable of enhancing tubulin stability in cells. When phosphorylated, interacts with LAMTOR5/HBXIP; the resulting complex binds pro-CASP9, as well as active CASP9, but much less efficiently. Component of the chromosomal passenger complex (CPC) composed of at least BIRC5/survivin, CDCA8/borealin, INCENP, AURKB or AURKC; in the complex forms a triple-helix bundle-based subcomplex with INCENP and CDCA8 (PubMed:17956729). Interacts with JTB. Interacts (via BIR domain) with histone H3 phosphorylated at 'Thr-3' (H3pT3). Interacts with EVI5. Interacts with GTP-bound RAN in both the S and M phases of the cell cycle. Interacts with USP9X. Interacts with tubulin. Interacts with BIRC2/c-IAP1. The acetylated form at Lys-129 interacts with STAT3. The monomeric form deacetylated at Lys-129 interacts with XPO1/CRM1. The monomeric form interacts with XIAP/BIRC4. Both the dimeric and monomeric form can interact with DIABLO/SMAC. Interacts with BIRC6/bruce. Interacts with FBXL7; this interaction facilitates the polyubiquitination and subsequent proteasomal degradation of BIRC5 by the SCF(FBXL7) E3 ubiquitin-protein ligase complex (PubMed:25778398, PubMed:28218735). {ECO:0000269\|PubMed:12773388, ECO:0000269\|PubMed:14610074, ECO:0000269\|PubMed:15249581, ECO:0000269\|PubMed:15665297, ECO:0000269\|PubMed:16239925, ECO:0000269\|PubMed:16291752, ECO:0000269\|PubMed:16322459, ECO:0000269\|PubMed:16427043, ECO:0000269\|PubMed:16436504, ECO:0000269\|PubMed:16764853, ECO:0000269\|PubMed:17956729, ECO:0000269\|PubMed:18329369, ECO:0000269\|PubMed:18591255, ECO:0000269\|PubMed:20826784, ECO:0000269\|PubMed:21225229, ECO:0000269\|PubMed:21536684, ECO:0000269\|PubMed:25778398, ECO:0000269\|PubMed:28218735}.
Subcellular location:		Cytoplasm {ECO:0000269\|PubMed:20627126, ECO:0000269\|PubMed:20826784, ECO:0000269\|PubMed:21364656}. Nucleus {ECO:0000269\|PubMed:20627126, ECO:0000269\|PubMed:20826784, ECO:0000269\|PubMed:21364656}. Chromosome {ECO:0000269\|PubMed:14610074}. Chromosome, centromere {ECO:0000269\|PubMed:11084331, ECO:0000269\|PubMed:14610074, ECO:0000269\|PubMed:16322459}. Cytoplasm, cytoskeleton, spindle {ECO:0000269\|PubMed:11084331}. Chromosome, centromere, kinetochore {ECO:0000269\|PubMed:11084331}. Midbody {ECO:0000269\|PubMed:15665297}. Note=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). {ECO:0000250\|UniProtKB:E3SCZ8, ECO:0000269\|PubMed:11084331, ECO:0000269\|PubMed:14610074, ECO:0000269\|PubMed:20826784}.
Tissue specificity:		Expressed only in fetal kidney and liver, and to lesser extent, lung and brain (PubMed:10626797). Abundantly expressed in adenocarcinoma (lung, pancreas, colon, breast, and prostate) and in high-grade lymphomas (PubMed:14741722, PubMed:16329164). Also expressed in various renal cell carcinoma cell lines (PubMed:10626797). Expressed in cochlea including the organ of Corti, the lateral wall, the interdental cells of the Limbus as well as in Schwann cells and cells of the cochlear nerve and the spiral ganglions (at protein level). Not expressed in cells of the inner and outer sulcus or the Reissner's membrane (at protein level) (PubMed:21364656, PubMed:20627126). {ECO:0000269\|PubMed:10626797, ECO:0000269\|PubMed:14741722, ECO:0000269\|PubMed:16329164, ECO:0000269\|PubMed:20627126, ECO:0000269\|PubMed:21364656}.
Developmental stage:		Expression is cell cycle-dependent and peaks at mitosis. {ECO:0000269\|PubMed:18591255}.
Induction:		Up-regulated by COMP. {ECO:0000269\|PubMed:17993464}.
Domain:		The BIR repeat is necessary and sufficient for LAMTOR5 binding. {ECO:0000269\|PubMed:12773388}.
Ptm:		Ubiquitinated by the Cul9-RING ubiquitin-protein ligase complex, leading to its degradation. Ubiquitination is required for centrosomal targeting. {ECO:0000269\|PubMed:16322459, ECO:0000269\|PubMed:24793696}.
Ptm:		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. {ECO:0000269\|PubMed:11069302, ECO:0000269\|PubMed:14610074, ECO:0000269\|PubMed:21252625, ECO:0000269\|PubMed:24866247, ECO:0000269\|PubMed:27332895}.
Ptm:		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. {ECO:0000269\|PubMed:20826784}.
Similarity:		Belongs to the IAP family. {ECO:0000305}.