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FLASH GENE
Symbol BAG6 contributors: mct/pgu - updated : 23-05-2016
HGNC name HLA-B associated transcript 3
HGNC id 13919
Location 6p21.33      Physical location : -
Synonym name
  • scythe
  • DNA segment, single copy, probe G3
  • protein G3
  • large proline-rich protein BAT3
    • Synonym symbol(s) D6S52E, D6S52, G3, BAT3
    DNA
    TYPE functioning gene
    SPECIAL FEATURE component of a cluster
    STRUCTURE 13.67 kb     28 Exon(s)
    MAPPING cloned Y linked N status confirmed
    regionally located . localized in the vicinity of TNF alpha and TNF beta genes
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    25 splicing 3832 119.3 1132 - 2008 18056262
  • also called variant 1/isoform a
    • 25 splicing 3790 118.6 1126 - 2008 18056262
  • also called variant 2/isoform b
  • lacking 24 bases in the 5' UTR and 18 bases in the coding region compared to variant 1
  • encoding the same isoform b than variant 3
    • 25 splicing 3814 118.6 1126 - 2008 18056262
  • also called variant 3/isoform b
  • utilizing an alternative splice site, which removes 18 bases in the coding region compared to variant 1 but the reading frame is maintained
  • encoding the same isoform b as variant 2
    • 25 - 3660 - 1126 - 2008 18056262
    also called variant 4/isoform b
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   moderately
    Digestiveintestinesmall intestine  moderately
    Lymphoid/Immunetonsils   predominantly
    Nervousnerve   highly
    Reproductivefemale systemuteruscervix highly
     female systemovary  highly
    Skin/Tegumentskin   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectivebone  moderately
    Lymphoid    
    cell lineage
    cell lines
    fluid/secretion lymph
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • an N terminal ubiquitin-like domain
  • rich in proline and including short tracts of polyproline, polyglycine, and charged amino acids
  • an UBL domains from UBL4A and BAG6 directly compete for binding to SGTA at the same site
  • a BAGS domain promoting the tail-anchored (TA) protein biogenesis pathway in mammals by the interaction with UBL4A
  • an active C-terminal nuclear localization signal (NLS)
    • conjugated PhosphoP
    HOMOLOGY
    interspecies ortholog to rattus Bat3 (94.1pc)
    ortholog to murine Bat3 (94.7pc)
    Homologene
    FAMILY BAG protein family
    CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus
    text
  • localized to the cytoplasm in normal tissue, it was localized to the nucleus in osteosarcoma tissue
  • colocalization of ZNF395 and BAG6 in the nucleus might be an important factor for survival of osteosarcoma cells
    • basic FUNCTION
  • implicated in the control of apoptosis
  • plays a role in ricin-induced apoptosis
  • regulating heat shock protein
  • regulator of TP53 transcriptional activity, suggesting a role in the response to genotoxic stress
  • implicated in apoptosis and the protein complexes with E1A-binding protein EP300, and required for acetylation of TP53 in response to DNA damage
  • regulator of AIFM1
  • cochaperone of the heat shock protein HSP70 that is involved in various developmental processes, cellular stress and viability
  • central regulator of the cellular content of HSP70
  • influences the membrane integration of tail-anchored proteins using the ASNA1 pathway
  • either modulates the ASNA1 pathway in higher eukaryotes or provides an alternative fate for newly synthesised tail-anchored proteins
  • BAG6, GET4 and UBL4A facilitates tail-anchored (TA) protein capture by ASNA1
  • ubiquitin-like protein that was originally reported to be the product of a novel gene located within the human major histocompatibility complex
  • is potentially necessary for ubiquitin-mediated degradation of newly synthesized defective polypeptides
  • BAG6 acts as an inhibitor of HAVCR2–dependent exhaustion and cell death
  • enhance the proteasomal degradation of mislocalized proteins by selectively promoting their ubiquitination
  • BAG6/SGTA cycle operates likely during protein maturation and quality control in the cytosol and that together these components dictate the fate of a specific subset of newly synthesized proteins
  • nuclear BAG6 complex is an effector in DNA damage response pathway and its phosphorylation and nuclear localization are important determinants for its function
  • plays a central role in cellular homeostasis in a diverse array of processes and is part of the heterotrimeric BAG6 complex
    • CELLULAR PROCESS cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • SGTA-BAG6 complexes could be directly or indirectly required for complete chromosome congression
  • heterotrimeric BAG6 complex, which also includes UBL4A and transmembrane domain recognition complex 35 (GET4)
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • MHC
  • interaction between Scythe (BAT3) and the apoptogenic mitochondrial intermembrane protein AIFM1 (physically interacts with AIFM1 and regulates its stability)
  • BAG6 is a critical regulator of HSPA2 in spermatogenesis, thereby providing a possible molecular target in idiopathic male infertility
  • is a ZNF395-associated molecule acting as a nucleus-cytoplasm shuttling protein
  • SGTA actively promotes the deubiquitination of mislocalized proteins that are already covalently modified, thus reversing the actions of BAG6 and inhibiting its capacity to promote substrate-specific degradation
  • SGTA can bind either BAG6, or UBL4A, but not both at the same time
  • instead of targeting UBL4A for degradation, polyubiquitination is associated with irreversible proteolytic processing and inactivation of BAG6
  • tight association of BAG6 and UBL4A resulted in modulation of UBL4A protein stability in cells
  • CTSD nuclear targeting is controlled by BAG6
  • BAG6 binds not only RAB8A but also a functionally distinct set of Rab family proteins, and is also required for the correct distribution of Golgi and endosomal markers
    • cell & other
    REGULATION
    activated by caspase-3 cleavage
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility to lung cancer
    Variant & Polymorphism other rs3117582 associated to lung cancer
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    reproductionfertilitymale
    possible molecular target in idiopathic male infertility
    immunologyautoimmune 
    may thus represent a viable therapeutic target in autoimmune disorders, chronic infections
    cancer  
    may thus represent a viable therapeutic target in cancers
    ANIMAL & CELL MODELS