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Symbol TMBIM6 contributors: mct - updated : 12-07-2016
HGNC name transmembrane BAX inhibitor motif containing 6
HGNC id 11723
Location 12q13.12      Physical location : 50.135.292 - 50.158.717
Synonym name
  • BAX inhibitor 1
  • testis enhanced gene transcript (BAX inhibitor 1)
  • Synonym symbol(s) BAXI1, BI-1, TEGT
    TYPE functioning gene
    STRUCTURE 23.42 kb     10 Exon(s)
    regulatory sequence alternative promoter
    text structure two promoters upregulating the expression in lung (BAXI1) and testis (TEGT) in the perinatal period
    MAPPING cloned Y linked N status provisional
    TRANSCRIPTS type messenger
    text two alternatively polyadenylated signals (Walter)
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    10 - 2885 - 237 - 1995 8530040
    10 - 3255 - 295 - 1995 8530040
    Type ubiquitous
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveliver     Homo sapiens
     mouthtongue  highly
    Endocrineadrenal gland   highly
    Lymphoid/Immunespleen   highly Homo sapiens
    Reproductivemale systemtestis  highly
    Urinarykidney   highly Homo sapiens
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal moderately Homo sapiens
    cell lineage
    cell lines
    at STAGE
    physiological period perinatal
    Text testis
  • four cysteine residues, a potential glycosylation site
  • a nuclear localization signal (NLS)
  • six membrane-spanning topology with cytosolic N and C termini and a C-terminal reentrant loop
  • possess the di-aspartyl pH sensor responsible for pH sensing identified in TMBIM6 8)
  • a common structure of at least seven transmembrane domains with the last domain being semi-hydrophobic
  • a Ca2+-permeable channel pore in the C terminus, peptide derived from the C-terminal end(CTP1), corresponding to AAs 198–217 inducing Ca2+ release from the ER
    interspecies ortholog to murine Tegt
    homolog to rattus Tegt
    homolog to Xenopus Xl.6708
    homolog to Drosophila CG7188
    homolog to C.elegans F40F9.2
    FAMILY TMBIM family of proteins
    CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     plasma membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
  • intracellular membranes
  • multitransmembrane domain-spanning endoplasmic reticulum (ER)-located protein
  • localized in the endoplasmic reticulum
  • basic FUNCTION
  • acting as a suppressor of apoptosis
  • increases Ca(2+) leak rates from the ER through a mechanism that is dependent on pH and on the C-terminal cytosolic region of the TMBIM6 protein
  • play a role in apoptosis
  • increased actin polymerization and cell adhesion through Ca2+ regulation and actin interaction
  • conserved endoplasmic reticulum protein that suppresses the apoptosis induced by BAX, a pro-apoptotic member of the BCL2 family
  • endoplasmic reticulum (ER)-resident transmembrane protein that can interact with multiple partners to alter intracellular Ca(2+) flux control and lipid dynamics
  • common cell death suppressor that has provided a potential portal to this cell death core
  • has Ca2+ channel properties likely relevant for its function in ER stress and apoptosis
  • like TMBIM4, TMBIM6 also protects cells against intrinsic pro-apoptotic stimuli and lowers resting Ca2+ concentrations in the ER, which reduces Ca2+ release from intracellular stores upon stimulation, thus dampening the apoptotic response
  • promotes autophagy in an inositol triphosphate receptors (IP&
  • 8323;Rs)-dependent manner
  • is a novel autophagy regulator that bridges CaČ&
  • 8314; signaling between ER and mitochondria, reducing cellular oxygen consumption and contributing to cellular resilience in the face of metabolic stress
  • conserved six-transmembrane domain endoplasmic reticulum (ER)-localized protein that protects against ER stress-induced apoptotic cell death
  • associated with calcium (Ca(2+)) levels, reactive oxygen species (ROS) production, cytosolic acidification, and autophagy as well as endoplasmic reticulum stress signaling pathways
  • plays a regulatory role in mitochondrial Ca(2+) levels
  • plays a key role in the synthesis, folding, and sorting of proteins, and disturbances of this delicate system can cause cell death
  • conserved multifunctional protein that mediates Ca(2+) efflux from the ER and protects against ER stress
  • evolutionarily conserved pH-dependent CaČ&
  • 8314; leak channel in the endoplasmic reticulum and the founding member of a family of six highly hydrophobic mammalian proteins named transmembrane BAX inhibitor motif containing (TMBIM)
  • reduce the CaČ&
  • 8314; content of the endoplasmic reticulum, and all but TMBIM5 also reduce the cytosolic resting CaČ&
    8314; concentration
    CELLULAR PROCESS cell life, antiapoptosis
    a component
    small molecule
  • binding to BCL2, BCLXL, BAX or BAK
  • interacts with IRE1 and directly inhibits IRE1 activity
  • interacting with BFAR (overexpression of BFAR reduced TMBIM6 protein levels in a RING-dependent manner
  • interacting with KLF10 (directly modulates the transcription of TMBIM1)
  • GRINA synergies with TMBIM6 in the modulation of ER calcium homeostasis and apoptosis, associated with physical interactions with inositol trisphosphate receptors
  • activity of the mitochondrial membrane potential-dependent mitochondrial Ca(2+) intake pore, the Ca(2+) uniporter, was reduced in the presence of TMBIM6
  • ERN1 signaling is quite context-specific on account of many adaptor and modulator proteins that directly interact with it, including heat shock proteins (HSPs), RNF13, PARP16, TMBIM6
  • cell & other
    Other post-translational regulation of the TMBIM6 protein by E3 ligase BFAR contributes to the dynamic control of IRE1 signaling during ER stress
    pH dependence due likely to two aspartic acid AAs critical for the function of the Ca(2+)-channel pore and located in the ER membrane-dipping domain, which facilitates the protonation of these AAs
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in NPM-ALK positive anaplastic large cells lymphoma
    constitutional     --over  
    high mRNAs levels observed in early liver disease may protect virus-infected cells against apoptosis
    tumoral     --over  
    associated with a number of cancers, including cancers of the prostate, breast, ovary, and uterus
    tumoral     --over  
    in non-small cell lung cancer and promotes its progression and metastasis
    Variant & Polymorphism
    Candidate gene
    Therapy target