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Symbol CREB3L2 contributors: mct - updated : 31-01-2018
HGNC name cAMP responsive element binding protein 3-like 2
HGNC id 23720
Location 7q33      Physical location : 137.559.726 - 137.686.846
Synonym name
  • B-ZIB transcription factor
  • basic transcription factor 2
  • BBF2 human homolog on chromosome 7
  • FUS/BBF2H7 protein
  • spinal cord injury and regeneration-related gene 69
  • Synonym symbol(s) BBF2H7, MGC71006, MGC131709, TCAG_1951439, SCIRR69
    TYPE functioning gene
    STRUCTURE 127.12 kb     12 Exon(s)
    regulatory sequence Promoter
    Binding site   transcription factor
    text structure
  • B-box element, ATF6 and CRE binding sites
  • a cRE binding site in the promoter region, suggesting an autoregulation and/or regulation via other members of the CREB3 family or bZip transcription factors (Panagopoulos 2009)
  • MAPPING cloned Y linked N status provisional
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    12 - 7455 - 520 - 2012 22495181
    4 - 1175 - 248 - 2012 22495181
    12 - 7054 - 457 - 2012 22495181
    Type ubiquitous
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinelarge intestinecolon  
     liver   highly
     stomach   predominantly
    Lymphoid/Immunespleen   highly
    Nervousbrain   highly Homo sapiens
    Reproductivefemale systemplacenta  highly
     female systemuteruscervix  
     male systemprostate   
    Respiratorylung   highly
     respiratory tractlarynx  highly
    Skin/Tegumentskin   highly
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Nervouscentral  highly Homo sapiens
    SystemCellPubmedSpeciesStageRna symbol
    not specificchondrocyte Homo sapiensFetal
    Respiratoryalveolar cell type II
    cell lineage highly expressed in chondrocytes (Saito 2009)
    cell lines
    at STAGE
    physiological period pregnancy
    Text placenta, highly
  • N terminus functioning as a transcription factor to promote the expression of ER-Golgi trafficking-related genes and playing crucial roles in chondrocyte differentiation
  • a basic DNA-binding and leucine-zipper dimerization (B-ZIP) motif
  • a predicted transmembrane domain
  • an adjacent cleavage site for the Golgi protease S1P, with conserved features which indicate that it represents a specific subclass of S1P sites
  • a hydrophobic region predicted to be an alpha-helical transmembrane domain
  • secreted luminal CREB3L2 C-terminus that is involved in Hedgehog ligand-dependent cancer cell proliferation through activation of Hedgehog signaling , and is secreted into the extracellular space as a signaling molecule for cell-to-cell communication
  • mono polymer homomer , dimer
    interspecies homolog to drosophila Bbs2
    homolog to murine Creb3l2 (91.0pc)
    homolog to rattus Creb3l2 (91.0pc)
    intraspecies homolog to CREB3L1
  • OASIS B-ZIP family of transcription factors
  • cyclic AMP-responsive element-binding protein (CREB)/activating transcription factor (ATF) family
  • CATEGORY transcription factor
    SUBCELLULAR LOCALIZATION     plasma membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
  • full-length CREB3L2 and FUS/CREB3L2 were localized to reticular structures of the cytoplasm
  • the corresponding, truncated proteins lacking the transmembrane domain and the carboxy-terminal part of CREB3L2 resided within the nucleus
  • localized in the ER and is cleaved in its transmembrane region in response to ER stress
  • ER-resident transmembrane transcription factor
  • basic FUNCTION
  • cyclin-dependent kinase inhibitor involved in regulation of transcription, DNA-dependent (transcriptional activation)
  • might contribute to only the late phase of unfolded protein response signaling (Kondo 2007)
  • ER stress transducer which could play important roles in preventing accumulation of unfolded proteins in damaged neurons (Kondo 2007)
  • activating transcription through B-Box and ATF6 elements
  • activating Sec23A transcription (Saito 2009)
  • CREB3L1 and CREB3L2, have the ability to up-regulate the secretory pathway in nonsecretory cell types
  • CREB3L2 and CREB3L1 are ER stress transducers with roles in chondrogenesis and osteogenesis
  • plays crucial roles as a bifunctional regulator to accelerate ECM protein secretion and suppress ER stress-induced apoptosis by activating the ATF5-MCL1 pathway during chondrogenesis
  • plays an essential role in the inhibition of apoptosis induced by ER stress during chondrocyte differentiation
  • is a novel regulator of the BDNF gene and may play an important role in the repair and/or regeneration of damaged neural tissues by specifically activating BDNF promoter II
  • is an endoplasmic reticulum (ER)-resident transmembrane basic leucine zipper (bZIP) transcription factor that is cleaved at the transmembrane domain by regulated intramembrane proteolysis in response to ER stress
  • UPR transducer CREB3L2 allows export of type II collagen in a cargo- and developmental stage-specific manner
  • CELLULAR PROCESS nucleotide, transcription, regulation
    a component
    DNA binding CRE DNA sequences
    small molecule
  • CREB3L2-mediated SEC23A pathway is involved in regulation of intracellular procollagen trafficking
  • CREB3L2-mediated SEC23A pathway was required for ER-to-Golgi procollagen trafficking to promote collagen synthesis
  • target of CREB3L2 is SEC23A, one of the coat protein complex II components
  • ATF5 was also found to be a target of CEB3L2 in chondrocytes
  • directly acts on the CRE sequence within the ATF5 promoter and facilitates its transcription in chondrocytes
  • involved in the regulation of BDNF expression in injured neurons
  • CREB3L1 and CREB3L2 are substrates of FBXW7 controling osteogenesis and chondrogenesis by targeting CREB3L1 and CREB3L2, respectively, for degradation
  • activated CREB3L2 accelerates cartilage matrix protein secretion through the up-regulation of SEC23A, which is responsible for protein transport from the ER to the Golgi apparatus and is a target of CREB3L2
  • novel regulatory mechanisms of SOX9 for controlling the secretion of cartilage matrix proteins through the activation of CREB3L2-SEC23A signaling during chondrogenesis
  • cell & other
    activated by ER stress, activated in response to ER stress during chondrogenesis
    Other regulated by SOX9, a critical factor for chondrocyte differentiation that facilitates the expression of one of the major cartilage matrix proteins Type II collagen (Col2), through binding to the SOX DNA-binding motif in the CREB3L2 promoter
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral fusion      
    with FUS in t(7;16) (q33;p11 in fibromyxoid sarcoma, low-grade
    tumoral fusion translocation    
    CREB3L2-PPAR gamma fusion mutation with a t(3;7)(p25;q34) in thyroid carcinoma, inhibiting transcription of EVX1 and thyroglobulin (Lui 2008)
    Variant & Polymorphism
    Candidate gene
    Therapy target
  • Bbf2h7(-/-) mice showed severe chondrodysplasia and died by suffocation shortly after birth because of an immature chest cavity (Saito 2009)
  • Bbf2h7-deficient mice exhibit severe chondrodysplasia, with expansion of the rough ER in proliferating chondrocytes caused by impaired secretion of extracellular matrix (ECM) proteins