BIRC5_MOUSE
ID BIRC5_MOUSE Reviewed; 140 AA.
AC O70201; Q923F7; Q9WU53; Q9WU54;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1998, sequence version 1.
DT 03-AUG-2022, entry version 192.
DE RecName: Full=Baculoviral IAP repeat-containing protein 5;
DE AltName: Full=Apoptosis inhibitor 4;
DE AltName: Full=Apoptosis inhibitor survivin;
DE AltName: Full=TIAP;
GN Name=Birc5; Synonyms=Api4, Iap4;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Uren A.G., Vaux D.L.;
RT "Mammalian inhibitor of apoptosis (IAP) homolog.";
RL Submitted (SEP-1997) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Embryo;
RA Kobayashi K., Otaki M., Ogasawara T., Tokuhisa T.;
RL Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1; 2 AND 3).
RX PubMed=10666222;
RA Conway E.M., Pollefeyt S., Cornelissen J., DeBaere I., Steiner-Mosonyi M.,
RA Ong K., Baens M., Collen D., Schuh A.C.;
RT "Three differentially expressed survivin cDNA variants encode proteins with
RT distinct antiapoptotic functions.";
RL Blood 95:1435-1442(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP FUNCTION.
RX PubMed=25778398; DOI=10.1074/jbc.m114.629931;
RA Liu Y., Lear T., Iannone O., Shiva S., Corey C., Rajbhandari S., Jerome J.,
RA Chen B.B., Mallampalli R.K.;
RT "The Proapoptotic F-box Protein Fbxl7 Regulates Mitochondrial Function by
RT Mediating the Ubiquitylation and Proteasomal Degradation of Survivin.";
RL J. Biol. Chem. 290:11843-11852(2015).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 7-118, AND PHOSPHORYLATION AT
RP THR-34.
RX PubMed=10949038; DOI=10.1016/s1097-2765(05)00019-5;
RA Muchmore S.W., Chen J., Jakob C., Zakula D., Matayoshi E.D., Wu W.,
RA Zhang H., Li F., Ng S.C., Altieri D.C.;
RT "Crystal structure and mutagenic analysis of the inhibitor-of-apoptosis
RT protein survivin.";
RL Mol. Cell 6:173-182(2000).
CC -!- FUNCTION: Multitasking protein that has dual roles in promoting cell
CC proliferation and preventing apoptosis (PubMed:25778398). Component of
CC a chromosome passage protein complex (CPC) which is essential for
CC chromosome alignment and segregation during mitosis and cytokinesis (By
CC similarity). Acts as an important regulator of the localization of this
CC complex; directs CPC movement to different locations from the inner
CC centromere during prometaphase to midbody during cytokinesis and
CC participates in the organization of the center spindle by associating
CC with polymerized microtubules (By similarity). Involved in the
CC recruitment of CPC to centromeres during early mitosis via association
CC with histone H3 phosphorylated at 'Thr-3' (H3pT3) during mitosis (By
CC similarity). The complex with RAN plays a role in mitotic spindle
CC formation by serving as a physical scaffold to help deliver the RAN
CC effector molecule TPX2 to microtubules (By similarity). May counteract
CC a default induction of apoptosis in G2/M phase (By similarity). The
CC acetylated form represses STAT3 transactivation of target gene
CC promoters (By similarity). May play a role in neoplasia. Inhibitor of
CC CASP3 and CASP7 (By similarity). Essential for the maintenance of
CC mitochondrial integrity and function (PubMed:25778398).
CC {ECO:0000250|UniProtKB:O15392, ECO:0000269|PubMed:25778398}.
CC -!- SUBUNIT: Monomer or homodimer. Exists as a homodimer in the apo state
CC and as a monomer in the CPC-bound state. The monomer protects cells
CC against apoptosis more efficiently than the dimer. Only the dimeric
CC form is capable of enhancing tubulin stability in cells. When
CC phosphorylated, interacts with LAMTOR5/HBXIP; the resulting complex
CC binds pro-CASP9, as well as active CASP9, but much less efficiently.
CC Component of the chromosomal passenger complex (CPC) composed of at
CC least BIRC5/survivin, CDCA8/borealin, INCENP, AURKB or AURKC; in the
CC complex forms a triple-helix bundle-based subcomplex with INCENP and
CC CDCA8. Interacts with JTB. Interacts (via BIR domain) with histone H3
CC phosphorylated at 'Thr-3' (H3pT3). Interacts with EVI5. Interacts with
CC GTP-bound RAN in both the S and M phases of the cell cycle. Interacts
CC with USP9X. Interacts with tubulin. Interacts with BIRC2/c-IAP1. The
CC acetylated form at Lys-129 interacts with STAT3. The monomeric form
CC deacetylated at Lys-129 interacts with XPO1/CRM1. The monomeric form
CC interacts with XIAP/BIRC4. Both the dimeric and monomeric form can
CC interact with DIABLO/SMAC. Interacts with BIRC6/bruce. Interacts with
CC FBXL7; this interaction facilitates the polyubiquitination and
CC subsequent proteasomal degradation of BIRC5 by the SCF(FBXL7) E3
CC ubiquitin-protein ligase complex (By similarity).
CC {ECO:0000250|UniProtKB:O15392}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:O15392}. Nucleus
CC {ECO:0000250|UniProtKB:O15392}. Chromosome
CC {ECO:0000250|UniProtKB:O15392}. Chromosome, centromere
CC {ECO:0000250|UniProtKB:O15392}. Cytoplasm, cytoskeleton, spindle
CC {ECO:0000250|UniProtKB:O15392}. Chromosome, centromere, kinetochore
CC {ECO:0000250|UniProtKB:O15392}. Midbody {ECO:0000250|UniProtKB:O15392}.
CC Note=Localizes at the centromeres from prophase to metaphase, at the
CC spindle midzone during anaphase and a the midbody during telophase and
CC cytokinesis. Accumulates in the nucleus upon treatment with leptomycin
CC B (LMB), a XPO1/CRM1 nuclear export inhibitor (By similarity).
CC Localizes on chromosome arms and inner centromeres from prophase
CC through metaphase. Localizes to kinetochores in metaphase, distributes
CC to the midzone microtubules in anaphase and at telophase, localizes
CC exclusively to the midbody. Colocalizes with AURKB at mitotic
CC chromosomes. Acetylation at Lys-129 directs its localization to the
CC nucleus by enhancing homodimerization and thereby inhibiting XPO1/CRM1-
CC mediated nuclear export (By similarity). {ECO:0000250|UniProtKB:E3SCZ8,
CC ECO:0000250|UniProtKB:O15392}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=Survivin 140;
CC IsoId=O70201-1; Sequence=Displayed;
CC Name=2; Synonyms=Survivin 121;
CC IsoId=O70201-2; Sequence=VSP_002457;
CC Name=3; Synonyms=Survivin 40;
CC IsoId=O70201-3; Sequence=VSP_002455, VSP_002456;
CC -!- DOMAIN: The BIR repeat is necessary and sufficient for LAMTOR5 binding.
CC {ECO:0000250|UniProtKB:O15392}.
CC -!- PTM: Ubiquitinated by the Cul9-RING ubiquitin-protein ligase complex,
CC leading to its degradation. Ubiquitination is required for centrosomal
CC targeting. {ECO:0000250|UniProtKB:O15392}.
CC -!- PTM: Acetylation at Lys-129 results in its homodimerization, while
CC deacetylation promotes the formation of monomers which heterodimerize
CC with XPO1/CRM1 which facilitates its nuclear export. The acetylated
CC form represses STAT3 transactivation. The dynamic equilibrium between
CC its acetylation and deacetylation at Lys-129 determines its interaction
CC with XPO1/CRM1, its subsequent subcellular localization, and its
CC ability to inhibit STAT3 transactivation.
CC {ECO:0000250|UniProtKB:O15392}.
CC -!- PTM: In vitro phosphorylation at Thr-117 by AURKB prevents interaction
CC with INCENP and localization to mitotic chromosomes. Phosphorylation at
CC Thr-48 by CK2 is critical for its mitotic and anti-apoptotic
CC activities. Phosphorylation at Thr-34 by CDK15 is critical for its
CC anti-apoptotic activity. {ECO:0000250|UniProtKB:O15392}.
CC -!- SIMILARITY: Belongs to the IAP family. {ECO:0000305}.
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; AF077349; AAD34225.1; -; mRNA.
DR EMBL; AB013819; BAA28266.1; -; mRNA.
DR EMBL; AF115517; AAD26199.1; -; Genomic_DNA.
DR EMBL; AF115517; AAD26200.1; -; Genomic_DNA.
DR EMBL; AF115517; AAD26201.1; -; Genomic_DNA.
DR EMBL; BC004702; AAH04702.1; -; mRNA.
DR CCDS; CCDS25694.1; -. [O70201-1]
DR CCDS; CCDS25695.1; -. [O70201-2]
DR RefSeq; NP_001012273.1; NM_001012273.1. [O70201-2]
DR RefSeq; NP_033819.1; NM_009689.2. [O70201-1]
DR PDB; 1M4M; X-ray; 2.80 A; A=1-140.
DR PDBsum; 1M4M; -.
DR AlphaFoldDB; O70201; -.
DR SMR; O70201; -.
DR BioGRID; 198150; 2.
DR ComplexPortal; CPX-113; Survivin homodimer complex.
DR ComplexPortal; CPX-119; Chromosomal passenger complex.
DR STRING; 10090.ENSMUSP00000079124; -.
DR MEROPS; I32.005; -.
DR iPTMnet; O70201; -.
DR PhosphoSitePlus; O70201; -.
DR EPD; O70201; -.
DR MaxQB; O70201; -.
DR PaxDb; O70201; -.
DR PeptideAtlas; O70201; -.
DR PRIDE; O70201; -.
DR ProteomicsDB; 273492; -. [O70201-1]
DR ProteomicsDB; 273493; -. [O70201-2]
DR ProteomicsDB; 273494; -. [O70201-3]
DR Antibodypedia; 1073; 1805 antibodies from 53 providers.
DR DNASU; 11799; -.
DR Ensembl; ENSMUST00000081387; ENSMUSP00000079124; ENSMUSG00000017716. [O70201-1]
DR Ensembl; ENSMUST00000093906; ENSMUSP00000091433; ENSMUSG00000017716. [O70201-2]
DR GeneID; 11799; -.
DR KEGG; mmu:11799; -.
DR UCSC; uc007mod.1; mouse. [O70201-1]
DR UCSC; uc007moe.1; mouse. [O70201-2]
DR CTD; 332; -.
DR MGI; MGI:1203517; Birc5.
DR VEuPathDB; HostDB:ENSMUSG00000017716; -.
DR eggNOG; KOG1101; Eukaryota.
DR GeneTree; ENSGT00510000047537; -.
DR HOGENOM; CLU_016347_0_1_1; -.
DR InParanoid; O70201; -.
DR OMA; FEGWPFD; -.
DR PhylomeDB; O70201; -.
DR TreeFam; TF342652; -.
DR Reactome; R-MMU-141444; Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal.
DR Reactome; R-MMU-2467813; Separation of Sister Chromatids.
DR Reactome; R-MMU-2500257; Resolution of Sister Chromatid Cohesion.
DR Reactome; R-MMU-4615885; SUMOylation of DNA replication proteins.
DR Reactome; R-MMU-5663220; RHO GTPases Activate Formins.
DR Reactome; R-MMU-68877; Mitotic Prometaphase.
DR Reactome; R-MMU-8951664; Neddylation.
DR Reactome; R-MMU-9648025; EML4 and NUDC in mitotic spindle formation.
DR BioGRID-ORCS; 11799; 23 hits in 71 CRISPR screens.
DR ChiTaRS; Birc5; mouse.
DR EvolutionaryTrace; O70201; -.
DR PRO; PR:O70201; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; O70201; protein.
DR Bgee; ENSMUSG00000017716; Expressed in fetal liver hematopoietic progenitor cell and 222 other tissues.
DR ExpressionAtlas; O70201; baseline and differential.
DR Genevisible; O70201; MM.
DR GO; GO:0016324; C:apical plasma membrane; ISO:MGI.
DR GO; GO:0005814; C:centriole; ISS:UniProtKB.
DR GO; GO:0032133; C:chromosome passenger complex; ISS:UniProtKB.
DR GO; GO:0000775; C:chromosome, centromeric region; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005881; C:cytoplasmic microtubule; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0031021; C:interphase microtubule organizing center; ISS:UniProtKB.
DR GO; GO:0000776; C:kinetochore; ISS:UniProtKB.
DR GO; GO:0015630; C:microtubule cytoskeleton; ISO:MGI.
DR GO; GO:0030496; C:midbody; ISS:UniProtKB.
DR GO; GO:0000228; C:nuclear chromosome; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0005876; C:spindle microtubule; ISS:UniProtKB.
DR GO; GO:1990713; C:survivin complex; ISO:MGI.
DR GO; GO:0051087; F:chaperone binding; ISO:MGI.
DR GO; GO:0043027; F:cysteine-type endopeptidase inhibitor activity involved in apoptotic process; ISS:UniProtKB.
DR GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0008017; F:microtubule binding; ISS:UniProtKB.
DR GO; GO:0046982; F:protein heterodimerization activity; ISO:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0031267; F:small GTPase binding; ISO:MGI.
DR GO; GO:0015631; F:tubulin binding; ISS:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR GO; GO:0051301; P:cell division; ISS:UniProtKB.
DR GO; GO:0051303; P:establishment of chromosome localization; ISS:UniProtKB.
DR GO; GO:0000086; P:G2/M transition of mitotic cell cycle; ISS:UniProtKB.
DR GO; GO:0007127; P:meiosis I; IDA:MGI.
DR GO; GO:0000226; P:microtubule cytoskeleton organization; IMP:MGI.
DR GO; GO:0000278; P:mitotic cell cycle; IC:ComplexPortal.
DR GO; GO:0000281; P:mitotic cytokinesis; ISS:UniProtKB.
DR GO; GO:0007094; P:mitotic spindle assembly checkpoint signaling; ISS:UniProtKB.
DR GO; GO:0051256; P:mitotic spindle midzone assembly; IC:ComplexPortal.
DR GO; GO:0007052; P:mitotic spindle organization; IC:ComplexPortal.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; ISS:UniProtKB.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IMP:MGI.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:1902425; P:positive regulation of attachment of mitotic spindle microtubules to kinetochore; IC:ComplexPortal.
DR GO; GO:0045787; P:positive regulation of cell cycle; ISO:MGI.
DR GO; GO:0031536; P:positive regulation of exit from mitosis; ISS:UniProtKB.
DR GO; GO:0045931; P:positive regulation of mitotic cell cycle; ISS:UniProtKB.
DR GO; GO:0090267; P:positive regulation of mitotic cell cycle spindle assembly checkpoint; IC:ComplexPortal.
DR GO; GO:1903490; P:positive regulation of mitotic cytokinesis; IC:ComplexPortal.
DR GO; GO:1901970; P:positive regulation of mitotic sister chromatid separation; IC:ComplexPortal.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IC:ComplexPortal.
DR GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0031503; P:protein-containing complex localization; ISS:UniProtKB.
DR GO; GO:0051726; P:regulation of cell cycle; IBA:GO_Central.
DR GO; GO:0061178; P:regulation of insulin secretion involved in cellular response to glucose stimulus; IMP:MGI.
DR GO; GO:0007346; P:regulation of mitotic cell cycle; IMP:MGI.
DR GO; GO:0061469; P:regulation of type B pancreatic cell proliferation; IMP:MGI.
DR CDD; cd00022; BIR; 1.
DR DisProt; DP02534; -.
DR InterPro; IPR001370; BIR_rpt.
DR Pfam; PF00653; BIR; 1.
DR SMART; SM00238; BIR; 1.
DR PROSITE; PS50143; BIR_REPEAT_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Apoptosis; Cell cycle;
KW Cell division; Centromere; Chromosome; Chromosome partition; Cytoplasm;
KW Cytoskeleton; Kinetochore; Metal-binding; Microtubule; Mitosis; Nucleus;
KW Phosphoprotein; Protease inhibitor; Reference proteome; Repressor;
KW Thiol protease inhibitor; Transcription; Transcription regulation;
KW Ubl conjugation; Zinc.
FT CHAIN 1..140
FT /note="Baculoviral IAP repeat-containing protein 5"
FT /id="PRO_0000122357"
FT REPEAT 18..88
FT /note="BIR"
FT REGION 113..140
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 113..130
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 57
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT BINDING 60
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT BINDING 76
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT BINDING 77
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT BINDING 80
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT BINDING 84
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT SITE 126
FT /note="Interaction with FBXL7"
FT /evidence="ECO:0000250|UniProtKB:O15392"
FT MOD_RES 23
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O15392"
FT MOD_RES 34
FT /note="Phosphothreonine; by CDK1 and CDK15"
FT /evidence="ECO:0000269|PubMed:10949038"
FT MOD_RES 48
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O15392"
FT MOD_RES 90
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O15392"
FT MOD_RES 110
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O15392"
FT MOD_RES 112
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O15392"
FT MOD_RES 115
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O15392"
FT MOD_RES 117
FT /note="Phosphothreonine; by AURKB"
FT /evidence="ECO:0000250|UniProtKB:O15392"
FT MOD_RES 129
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O15392"
FT VAR_SEQ 38..40
FT /note="MAE -> RGA (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_002455"
FT VAR_SEQ 41..140
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_002456"
FT VAR_SEQ 114..140
FT /note="AKETNNKQKEFEETAKTTRQSIEQLAA -> VCMIENKD (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_002457"
FT HELIX 11..13
FT /evidence="ECO:0007829|PDB:1M4M"
FT HELIX 15..20
FT /evidence="ECO:0007829|PDB:1M4M"
FT STRAND 29..31
FT /evidence="ECO:0007829|PDB:1M4M"
FT HELIX 35..40
FT /evidence="ECO:0007829|PDB:1M4M"
FT STRAND 43..45
FT /evidence="ECO:0007829|PDB:1M4M"
FT STRAND 55..57
FT /evidence="ECO:0007829|PDB:1M4M"
FT TURN 58..60
FT /evidence="ECO:0007829|PDB:1M4M"
FT HELIX 73..79
FT /evidence="ECO:0007829|PDB:1M4M"
FT HELIX 85..88
FT /evidence="ECO:0007829|PDB:1M4M"
FT HELIX 93..95
FT /evidence="ECO:0007829|PDB:1M4M"
FT HELIX 98..116
FT /evidence="ECO:0007829|PDB:1M4M"
SQ SEQUENCE 140 AA; 16298 MW; 26F5ABF501A6D83C CRC64;
MGAPALPQIW QLYLKNYRIA TFKNWPFLED CACTPERMAE AGFIHCPTEN EPDLAQCFFC
FKELEGWEPD DNPIEEHRKH SPGCAFLTVK KQMEELTVSE FLKLDRQRAK NKIAKETNNK
QKEFEETAKT TRQSIEQLAA
