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FLASH GENE
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
    DNA
    TYPE functioning gene
    STRUCTURE 6.53 kb     4 Exon(s)
    MAPPING cloned Y linked N status provisional
    RNA
    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
  • EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinesmall intestine   
    Lymphoid/Immunespleen    
     thymus    
    Reproductivefemale systemovary   
     male systemtestis   
     male systemprostate   
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • 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)
  • HOMOLOGY
    interspecies ortholog to rattus Siva
    Homologene
    FAMILY
    CATEGORY signaling
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,nucleus,nucleoplasm
    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
    PATHWAY
    metabolism
    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
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • 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
    REGULATION
    induced by TP53, E2F1
    ASSOCIATED DISORDERS
    ANIMAL & CELL MODELS