Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol XAF1 contributors: mct - updated : 28-03-2020
HGNC name XIAP associated factor 1
HGNC id 30932
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularheart    
Digestiveesophagus   highly
Lymphoid/Immunespleen   highly
Reproductivefemale systemuterus   
 male systemtestis   
Urinarykidney   highly Homo sapiens
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • six zinc finger motifs at its N-terminus, a highly compact N-terminal domain (XAF1(NTD)
  • a middle domain (XAF1(MD)
  • TRAF type zinc finger, required for self-association or interaction with other proteins
  • a 42-residue unstructured linker
  • C-terminal portion critical for its pro-apoptotic function, XAF1(CTD), C-terminal XAF1 fragment harboring XAF1(RBD) was found to be substantially ubiquitinated by XIAP(RING)
  • HOMOLOGY
    intraspecies homolog to FLN29,TRAF3
    Homologene
    FAMILY
    CATEGORY transcription factor , tumor suppressor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    basic FUNCTION
  • regulation of apoptosis (loss of XAF1 important for malignant cell survival)
  • antagonizing the anticaspase activity of XIAP and may be important in mediating apoptosis resistance in cancer cells
  • plays a critical role in interferon-induced sensitization to TNF-related apoptosis-inducing ligand
  • mediates apoptosis induced by the ERK1/2 pathway in colon cancer (Yu 2007)
  • role of XAF1 in promoting apoptosis in vascular endothelial cells after DENV2 infection
  • novel role for XAF1 in TP53 stress response, adding a new layer of complexity to the mechanisms by which TP53 determines cell-fate decisions
  • XAF1 forms a positive feedback loop with IRF1 to drive apoptotic stress response and suppress tumorigenesis
  • both YY1 and XAF1 have key roles in prostate cancer (PCa) progression and are associated with worse clinical outcomes
  • pro&
  • 8209;apoptotic tumor suppressor that frequently displays epigenetic inactivation in various types of human malignancies, including colorectal cancer
    CELLULAR PROCESS cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • complexing with XIAP to regulate motoneuron resistance to apoptotic cell death
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • inhibiting the function of CASP3, CASP7 and CASP9 key effector proteases of apoptosis
  • XAF1 binds directly to the N-terminal proline-rich domain of TP53 and thus interferes with E3 ubiquitin ligase MDM2 binding and ubiquitination of TP53
  • XAF1 is involved in BRD7-associated senescence and plays an important role in the regulation of endothelial senescence through a TP53-dependent pathway. 8)
  • binds to XIAP and blocks its anti-apoptotic activity
  • XAF1 is likely a downstream target of KIF1B beta
  • XAF1 interacts with TRAF2 and inhibits TRAF2-dependent NFKB1 activation, in part, by blocking TRAF2 polyubiquitination
  • XAF1 acts as a feedback regulator of the TNF receptor signaling pathway to suppress NFKB1 activation
  • macrophages activated by metabolic endotoxemia infiltrated into islets and produced IFNB1, which induced beta-cell apoptosis by increasing the expression of XAF1
  • functions as a transcriptional coactivator of IRF1 to suppress tumorigenesis
  • YY1 is able to mediate XAF1 silencing
  • SARM1 deficiency exacerbates the progression of prion pathogenesis, by up-regulating XAF1, which promotes neuronal apoptosis, and accelerates prion disease
  • TGFB1 protects colon tumor cells from apoptosis through XAF1 suppression
  • cell & other
    REGULATION
    activated by IFNA,IFNB
    repressed by TGFB1 (TGFB1 represses XAF1 transcription through Erk activation, thereby protecting tumor cells from apoptotic stresses)
    Other induced expression in cancer cell lines, with high levels of XIAP
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    low expressed by aberrant promoter methylation in gastric adenocarcinoma in progression
    tumoral        
    by hypermethylation in prostate, kidney and bladder carcinoma, in malignant progression
    tumoral     --over  
    significantly reduced invasion and migration of SKOV3 cells (ovarian cancer), and inhibited vascular endothelial growth factor protein expression
    tumoral     --over  
    impairs neuroblastoma tumor progression
    tumoral     --low  
    implicated in clear-cell renal cancer progression
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • prognostic marker in pancreatic cancer
  • Therapy target
    SystemTypeDisorderPubmed
    immunologyinfectious 
    XAF1 might constitute a therapeutic target in prion disease
    cancerbrainglioma/neuroblstoma
    XAF1 may be a candidate tumor suppressor in neuroblastoma
    cancerendocrinepancreas
    could be a potential candidate for pancreatic cancer gene therapy
    ANIMAL & CELL MODELS