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FLASH GENE
Symbol BIRC5 contributors: mct - updated : 23-11-2015
HGNC name baculoviral IAP repeat-containing 5
HGNC id 593
DNA
TYPE functioning gene
SPECIAL FEATURE head to head, opposite orientation
STRUCTURE 11.44 kb     5 Exon(s)
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Promoter
cytosine-phosphate-guanine/HTF
motif repetitive sequence
text structure
  • arranged head to head with EPR1/1bir repeat
  • a canonical CpG island that has been described as epigenetically regulated
  • YY1 is capable of directly binding to the survivin promoter
  • MAPPING cloned Y linked N status confirmed
    Physical map
    FLJ12190 17q25.3 hypothetical protein FLJ12190 FLJ23416 17q25.3 hypothetical protein FLJ23416 KIAA1582 17q25.3 KIAA1582 protein EVER1 17q25.3 epidermodysplasia verruciformis 1 EVER2 17q25.3 epidermodysplasia verruciformis 2 EIF5AP2 17q25 eukaryotic translation initiation factor 5A pseudogene 2 SYNGR2 17q25.3 synaptogyrin 2 TK1 17q25.1 thymidine kinase 1, soluble LOC125061 BIRC5 17q25 baculoviral IAP repeat-containing 5 (survivin) LOC283999 17q25.3 hypothetical protein LOC283999 LOC390816 17 similar to RIKEN cDNA 1300017K07 SOCS3 17q25.3 suppressor of cytokine signaling 3 LOC388421 17 LOC388421 PGS1 17q25.3 phosphatidylglycerophosphate synthase FLJ40457 17q25.3 hypothetical protein FLJ40457 LOC284120 17q25.3 hypothetical LOC284120 PSCD1 17q25-qter pleckstrin homology, Sec7 and coiled-coil domains 1(cytohesin 1) USP36 17q25.3 ubiquitin specific protease 36 TIMP2 17q25..3 tissue inhibitor of metalloproteinase 2 LGALS3BP 17q25.2-q25.3 lectin, galactoside-binding, soluble, 3 binding protein SHAPY 17q25.3 Ca2+-dependent endoplasmic reticulum nucleoside diphosphatase
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    4 - 2655 16.4 142 overexpressed in rhabdomyosarcoma, in colorectal tissues 2007 17656368
  • also called variant 1/isoform 1
  • membrane anchored
  • 5 splicing 2724 - 165 . decreased expression in gastric tumor high grade . overexpressed in rhabdomyosarcoma . expressed in colorectal tissues 2007 17656368
  • also called survivin-2B or variant 3/isoform 3
  • no antiapoptotic, antagonist of survivin
  • can interact with wild type survivin but have reduced affinity for the partner protein of survivin, borealin
  • do not play a role in mitosis
  • 3 splicing 2537 - 137 elevated in colorectal tissues, overexpressed in rhabdomyosarcoma, high expression rate of the survivin delta Ex3 splice variant characterized thyroid carcinomas 2007 17656368
  • also called survivin-deltaEx3 or variant 2/
  • lacking exon 3, antiapoptosis
  • do not play a role in mitosis
  • localized in the nucleoli, where it degrades rapidly through ubiquitin-proteosome pathway, nucleolar localization and degradation is required for its antiapoptotic function
  • can interact with wild type survivin but have reduced affinity for the partner protein of survivin, borealin
  • expression levels were positively associated with colorectal tumor aggression
  • - splicing 594 - 120 . colon and gastric adenocarcinoma cell lines as well as mononuclear cells from myelodysplastic syndrome . colorectal tissues 2004 14741722
  • also called survivin 3B
  • 5 exons including novel exon 3B derived from a 165-bp long portion of intron
  • a single baculovirus IAP repeat (BIR),critical for apoptosis inhibition, and lacking a carboxyl-terminal coiled-coil domain, suggesting that it may not be associated with G2/M phase
  • expression levels were positively associated with colorectal tumor aggression
    - - 476 - 74 - 2006 15908567
    also called survivin-2alpha
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivesalivary gland   highly
    Lymphoid/Immunethymus   highly
    Nervousbrain     Homo sapiens
    Reproductivefemale systemuteruscervix highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Lymphoid    
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Respiratoryepithelial cell
    cell lineage
    cell lines lung adenocarcinoma, hepatocellular carcinoma, strong prognostic indicator for advanced stage neuroblastomas, lymphoma
    fluid/secretion
    at STAGE
    physiological period embryo, fetal, pregnancy
    cell cycle     cell cycle, checkpoint, G2M
    Text
  • placenta, lung, liver, kidney, brain
  • expressed in periventricular neurogenic regions in the embryo
  • PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a C terminal RING finger
  • six potential phophorylation sites
  • a single baculovirus IAP repeat (BIR) domain combined with a C-terminal alpha-helix coiled-coil domain instead of the more common zinc-binding RING finger, containing the sites on BIRC5 that interact with GSPT1 (AAs 65-76), which forms a beta-strand structure with an overall negative charge
  • HOMOLOGY
    interspecies homolog to murine Birc5
    Homologene
    FAMILY
  • baculovirus IAP related family
  • CATEGORY regulatory , protooncogene
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule,mitotic spindle
    intracellular,nucleus,chromatin/chromosome,kinetochore
    text
  • nuclear shuttling associated with the microtubules of mitotic spindle at the beginning of mitosis
  • as mitosis progresses, with CDCA8, Aurora B, INCENP dynamically colocalize to mitotic structures
  • basic FUNCTION
  • counteracting a default induction of apoptosis
  • playing a role in neoplasia
  • involved in both prevention of cell death and control of mitosis and in regulation of smooth muscle cells apoptosis after acute vascular injury
  • short-lived protein that is degraded by the ubiquitin-proteasome pathway
  • determines cardiac function by controlling total cardiomyocyte number
  • inhibits apoptosis via caspase inhibition and promotes mitosis via aurora-B kinase activation
  • necessary for survival of megakaryocyte progenitors, but not required for polyploidization of committed megakaryocytes
  • critical role during neural development, and its deficiency dramatically impact on postnatal neural function
  • with PLK1, are important mediators of cell survival that are required for chromosome alignment, cytokinesis, and protection from apoptosis
  • implicated to have a physiological role in normal endometrial function
  • reads phosphorylated histone H3 threonine 3 to activate the mitotic kinase Aurora B
  • role for survivin in erythroblast enucleation through previously unknown protein partners
  • critical regulator of chromosome segregation and spindle assembly checkpoint (SAC) in meiosis
  • may play an important role in human oogenesis and embryogenesis
  • important role for BIRC5 as a dual regulator of lens epithelial cell proliferation and lens fiber cell differentiation
  • involved in cell-cycle progression, especially in the G2/M transition, and has anti-apoptotic activity, which correlates with its strong expression in cases with a poor cancer treatment response and poor outcomes
  • basal transcriptional requirements of survivin gene expression which are likely to play important roles in the development of cancer and resistance to its treatment
  • has a dual role in mitosis and in apoptosis
  • critically safeguards chromosomal stability independently from TP53
  • BIRC7, CASP3, BIRC5 are closely related to the occurrence and development of prostatic cancer
  • CELLULAR PROCESS cell cycle, division, mitosis
    cell life, antiapoptosis
    PHYSIOLOGICAL PROCESS
    text regulation of cell cycle; cytokinesis
    PATHWAY
    metabolism
    signaling
  • PI3K/AKT1/RPS6KB1 pathway is essential for regulating BIRC5 mRNA expression
  • a component
  • component of a complex with INCENP (that links centromere to microtubules) and CDCA8
  • interacts with CDCA8, AURKB and INCENP to form the chromosomal passenger complex (CPC), which is involved in the regulation of microtubule-kinetochore attachments and cytokinesis
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • tubulin
  • inhibition of caspase 3 and caspase 7, SMAC releasing the inhibition of caspase
  • XPO1 (CRM1) for nuclear export
  • binding the catalytic domain of aurora B (AURKB)
  • interaction between survivin and aurora-B kinase may be essential for survivin to increase TERT expression
  • binding of TP53, a repressor of survivin expression, and DNA methylation inhibits TP53-mediated survivin repression
  • BCL2L1 and BIRC5 can critically contribute in a cooperative, nonredundant manner to augment the accumulation and persistence of CD8(+) T cells following encounter with Antigen
  • interacting with PLK1 (interact during mitosis and PLK1 phosphorylates survivin at serine 20, which is essential for accurate chromosome alignment and cell proliferation but is dispensable for its anti-apoptotic activity in cancer cells)
  • physiological substrate for GZMM (GZMM hydrolyzes Survivin at Leu-138 to remove the last four C-terminal residues)
  • interaction between BECN1 and BIRC5 affects the sensitivity of human glioma cells to TNFSF10-induced apoptosis
  • AIP-TOMM20 recognition contributes to cell survival in development and cancer by mediating the mitochondrial import of BIRC5
  • in apoptosis, BIRC5 recognize the DIABLO protein
  • YAP1, CTNNB1 and TBX5 form a complex that regulates the expression of genes that promote survival, including BIRC5 and BCL2L1
  • SOX2 directly up-regulates the expression of BIRC5, which inhibits the mitochondria-dependent apoptotic pathway in NSCs (neural stem cells)
  • depletion of KRAS promotes proteasome degradation of BIRC5 (PMID
  • GSPT1 interact with BIRC5 through the N-terminal domain (NTD: residues 131-200)
  • cooperation between MYCN and BIRC5 may be important in the genesis of several cancers
  • BIRC5 partially regulates HSC function by modulating the MECOM transcription factor and its downstream targets and identify new genetic pathways in HSCs regulated by BIRC5
  • BIRC5 expression promotes VEGFA-induced tumor angiogenesis via PI3K/Akt enhanced CTNNB1/HNF4A-LEF1 dependent transcription
  • protects pancreatic beta-cells against ER stress-mediated apoptosis by up-regulating BIRC5 expression and down-regulating DDIT3 expression, which we termed as "positive and negative regulation
  • cell & other
    REGULATION
    activated by TCFB (enhancing cell proliferation with resistance to apoptosis in colorectal cancer)
    POU5F1, that can upregulate BIRC5 and CCND1 expression by increasing their promoter activity, and these factors collusively promotes hepatocellular carcinoma cell proliferation
    Other PI3K/AKT1/RPS6KB1 pathway is essential for regulating BIRC5 mRNA expression
  • BIRC5 gene expression is transcriptionally regulated by TFAM in the nucleus
  • YY1 regulates the transcriptional repression of BIRC5
    phosphorylation, acetylation and ubiquitination seem to regulate survivin anti-apoptotic and mitotic roles and also its nuclear localization
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --other  
    disturbed expression of BIRC5 and EPR1 in hematological malignancy (in acute myeloid leukemia with unfavourable prognostic factor)
    tumoral     --over  
    with TERT in soft tissue sarcoma with very poor outlook, and in stomach tumor cell nuclei (with favorable prognosis)
    constitutional     --over  
    in endometriosis
    tumoral     --over  
    in uterus cancer,panceas, colon, gastric, breast, prostate adenocarcinomas, in alveolar rhabdomyosarcoma
    tumoral       gain of function
    in esophageal cancer
    tumoral     --low  
    silencing promotes XIAP degradation and enhances GZMM-induced caspase activation as well as GZMM- and NK cell-induced cytolysis of target tumor cells
    tumoral     --over  
    in the majority of non-small cell lung carcinoma, together with the abundant or upregulated expression of HBXIP and XIAP suggest that tumours are endowed with resistance against a variety of apoptosis-inducing conditions
    tumoral     --over  
    overexpression of FOXM1, XIAP, and BIRC5 contributes to the development of drug-resistance and is associated with poor clinical outcome in breast cancer patients
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerdigestiveliver
    co-suppression of POU5F1 and BIRC5 is potentially beneficial for HCC treatment
    cancer  
    therapeutic use of Survivin-targeted RNA interference for tumours that express high levels of this molecule
    cancerdigestiveoesophagus
    promoter could be useful tools for developing esophageal cancer-specific gene therapy vectors
    cardiovascularatheroma 
    promising new target for myocardial regeneration
    cancer  
    potentially important interaction between BECN1 and BIRC5 having therapeutic implication in human tumor cells
    ANIMAL & CELL MODELS
  • survivin gene deletion in the kidneys results in a cystic phenotype
  • Surv(-/-) mice exhibit severe global conduction attenuations in atrial and ventricular myocardium as well as the specific conduction system (22976005)