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Symbol SIVA1 contributors: mct/pgu - updated : 29-03-2016
HGNC name SIVA1, apoptosis-inducing factor
HGNC id 17712
Location 14q32.33      Physical location : 105.219.469 - 105.225.995
Synonym name
  • CD27-binding (Siva) protein
  • apoptosis regulatory protein Siva
  • Synonym symbol(s) CD27BP, SIVA, Siva-1, Siva-2
    TYPE functioning gene
    STRUCTURE 6.53 kb     4 Exon(s)
    MAPPING cloned Y linked N status provisional
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    4 - 790 18 175 - 2001 11278261
  • isoform 1
  • containing the apoptotic properties
  • 3 - 595 - 110 - 2001 11278261
  • isoform 2
  • mediates apoptosis in T lymphocytes via a caspase-dependent mitochondrial pathway that likely involves both cytoplasmic and nuclear events
    Type ubiquitous
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinesmall intestine   
    Reproductivefemale systemovary   
     male systemtestis   
     male systemprostate   
    cell lineage
    cell lines
    at STAGE
  • N-terminal region participating in the translocation of both SIVA proteins into the nuclear compartment, and containing amphipathic helices with potential to interact with the PRYSPRY domain of pyrin
  • death domain in the central part
  • a B-box like domain
  • a zinc finger-like C-terminal domain that bind the cytoplasmic tail domain of TNFRSF18 protein , and C-terminus domain (AAs 84-175) was fused to glutathione Stransferase (GST)
    interspecies ortholog to rattus Siva
    CATEGORY signaling
    SUBCELLULAR LOCALIZATION     intracellular
    basic FUNCTION
  • important role in the apoptotic pathways induced by CD27 antigen
  • exhibit an apoptotic property and to play an important role in the CD27-mediated apoptosis
  • binding BCL-XL and inhibiting its antiapoptotic activity, and so sensitizing cells ti UV radiation induced apoptosis
  • involved in apoptosis via caspase-dependent mitochondrial pathway
  • death domain-containing proapoptotic protein identified as an intracellular ligand of CD27 and of the glucocorticoid-induced TNFR family-related gene
  • pro-apoptotic protein that interacts with the cytoplasmic tail of several TNF receptor family members, TNFRSF18 is the only ligand of SIVA1 expressed in cells also expressing pyrin
  • mediating apoptosis in T lymphocytes via a caspase-dependent mitochondrial pathway that likely involves both cytoplasmic and nuclear events
  • plays an instructive role in apoptosis, and is essential for TP53-dependent apoptosis in cerebellar granule neurons
  • may be part of the negative feedback loop that inhibits TP53 activity at the end of a non-lethal stress response
  • important adaptor promoting TP53 degradation through MDM2
  • has the potential to induce both extrinsic (receptor-mediated) and intrinsic (non-receptor-mediated) apoptosis
  • important negative regular of stathmin and its down-regulation may promote EMT and tumor cell dissemination
  • plays an important role in suppressing tumor metastasis
  • may be important for proper Treg cell function
  • SIVA1 regulates cell cycle progression and cell proliferation in an ARF/TP53-dependent manner
  • CELLULAR PROCESS cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS immunity/defense
    signaling signal transduction
  • important function of SIVA1 in the regulation of the ARF-MDM2-TP53 pathway
  • a component forms a functional complex with TYK2 and participates in the transduction of signals that inhibit B lymphocyte growth
    small molecule
  • binding to CD27 antigen cytoplasmic tail
  • interacting with ABL2 (functional significance of the ABL2-SIVA1 interaction is supported by the finding that ABL2 is activated by oxidative stress and that this response involves ABL2-mediated phosphorylation of SIVA1 on Tyr(48)
  • binding to TP53 and MDM2
  • interacting with MEFV (interaction involves the C-terminal B30.2/rfp/SRPY domain of pyrin and exon 1 of SIVA1)
  • bound to TYK2 via its N-terminal region, and TYK2 phosphorylated SIVA1 at tyrosines 53 and 162 (interaction between SIVA1 and TYK2 directly augments the apoptotic activity of SIVA1)
  • a pyrin-PRYSPRY domain interacting protein
  • inhibits STMN1 activity directly as well as indirectly, and via the inhibition of STMN1, SIVA1 enhances the formation of microtubules and impedes focal adhesion assembly, cell migration, and EMT
  • SIVA1 repressed IL2 induction by suppressing IL2 promoter activity during T cell activation
  • SIVA1 interacts with RAD18 and serves as a molecular bridge between RAD18 and PCNA, thus targeting the E3 ligase activity of RAD18 onto PCNA
  • interaction between ANKHD1 and SIVA1, and ANKHD1 binds to SIVA1 and has an important role in inducing leukemia cell proliferation and migration via the STMN1 pathway
  • interacts with tumor protein TP53 and with the member of the tumor necrosis factor receptor superfamily, stathmin, among others
  • cell & other
    induced by TP53, E2F1