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FLASH GENE
Symbol BIRC7 contributors: mct - updated : 02-04-2019
HGNC name baculoviral IAP repeat-containing 7
HGNC id 13702
Location 20q13.33      Physical location : 61.867.275 - 61.871.853
Synonym name
  • melanoma inhibitor of apoptosis protein
  • kidney inhibitor of apoptosis protein
  • livin
  • RING finger protein 50
  • Synonym symbol(s) KIAP, MLIAP, LIVIN, ML-IAP, RNF50
    EC.number 2.3.2.27
    DNA
    TYPE functioning gene
    STRUCTURE 4.58 kb     7 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site
    text structure
  • MYCN directly associated with its regulatory motif (E-box) within the putative BIRC7 promoter
  • MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    text cleaved by effector caspases to produce a truncated form with paradoxical pro-apoptotic activity (PMID: 17294084)
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    7 - 1268 - 280 detected in some fetal and adult tissues and in the majority of livin-expressing tumors 2007 17294084
  • also called variant 2/isoform beta or livin beta
  • lacking the coiled coil
  • protection from apoptosis initiated by etoposide
  • truncated Livin (tLivin) is found in a peri-nuclear distribution with marked localization to the Golgi apparatus
  • having an intact RING domain enabling its pro-apoptotic function
  • 7 splicing 1322 39 298 detected in some fetal and adult tissues and in the majority of livin-expressing tumors 2007 17294084
  • also called variant 1 or KIAP livin alpha
  • protection from apoptosis induced by staurosporin
  • promote cell proliferation by regulating G(1)-S cell cycle transition and possibly play an important part in initiation of prostate cancer (PMID: 20607788)
  • promotes tumor initiation in comparison with control (PMID: 19549891)
  • - - - - - subcellular localization of tLivin was mainly restricted to the cytoplasm 2009 19549891
  • BIRC7 specifically cleaved by caspases to produce a truncated protein with paradoxical proapoptotic activity (tLivin)
  • exerted a pro-apoptotic effect on cells
  • BIRC7 plays a major role in tumorigenicity and NK cells induce cleavage of BIRC7 to its proapoptotic truncated protein that in turn inhibits tumor growth
  • EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Lymphoid/Immunelymph node    
    Skin/Tegumentskin    
    Visualeye    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Lymphoid    
    cell lineage
    cell lines melanoma cell lines, several cancer cell lines
    fluid/secretion
    at STAGE
    physiological period embryo, fetal, pregnancy
    Text placenta, kidney, developmental tissues, liver, testis, thymus
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • one baculovirus IAP repeat (BIR domain), essential for inhibitory activity and interacting with caspases
  • a C-terminal RING zinc finger domain, enhancing antiapoptotic activity
  • HOMOLOGY
    Homologene
    FAMILY
  • baculovirus IAP family, inhibitors of apoptosis proteins family
  • CATEGORY regulatory , protooncogene
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microfilament
    intracellular,nucleus
    text
  • filamentous pattern through the cytoplasm
  • full-length BIRC7 shows diffuse cytoplasmic localization, truncated form is found in a peri-nuclear distribution with marked localization to the Golgi apparatus
  • basic FUNCTION
  • involved in the regulation of apoptosis
  • important determinant for the apoptotic resistance of non-small cell lung cancer cells
  • may exert anti-apoptotic action by activating JNK1 signaling pathway and inhibiting caspase-3 activation
  • may contribute to drug resistance in neuroblastoma, and may be essential for survival of some cancer cells
  • has a role in thrombopoiesis by regulating the apoptotic and antiapoptotic balance in megakaryocyte endoreplication and platelet production
  • BIRC7,CASP3, BIRC5 are closely related to the occurrence and development of prostatic cancer
  • CELLULAR PROCESS cell life, antiapoptosis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • inhibitor of downstream caspase, CASP9 (strong), CASP3 (weak) and CASP7
  • can act as an E3 ubiquitin ligase for targeting the degradation of Smac/DIABLO (exhibits E3 ubiquitin ligase activity to degrade the pivotal apoptotic regulator Smac/DIABLO through the ubiquitin-proteasome pathway)
  • new, BIRC7-dependent, apoptotic role for TEAD1
  • cell & other
    REGULATION
    activated by MYCN (MYCN protein may act as a transcriptional activator of BIRC7 expression supporting the notion that, in cells co-expressing these genes, the antiapoptotic effect of BIRC7 may counteract the apoptotic effects associated with MYCN amplification)
    induced by various stimuli
    repressed by Smac/DIABLO
    Other cleaved by effector caspases to produce a truncated form with paradoxical pro-apoptotic activity
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in a significant portion of non-small cell lung cancer
    tumoral     --over  
    in renal cell carcinoma
    tumoral     --over  
    protect tumor cells of neuroblastoma with amplified MYCN oncogene from genotoxic agents
    tumoral     --over  
    significantly higher in pancreatic ductal adenocarcinoma, than that in peritumoral tissue, benign pancreatic lesions, and normal pancreatic tissue
    tumoral     --over  
    is specifically over-expressed in adrenocortical carcinoma (ACC)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • BIRC7 upregulation might serve as a valuable biomarker of increased recurrence risk in advanced T stages and medium-grade prostate cancer
  • new molecular marker of adrenocortical carcinoma (ACC)
  • livin expression could be a novel prognostic marker in childhood ALL
  • Therapy target
    SystemTypeDisorderPubmed
    cancerbrain 
    therapeutic targeting of BIRC7 to block its antiapoptotic effect in neuroblastoma
    cancer  
    BIRC7 cleavage will become a highly potent proapoptotic agent, and a novel strategy for cancer therapy
    ANIMAL & CELL MODELS