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FLASH GENE
Symbol CREB3L2 contributors: mct - updated : 31-01-2018
HGNC name cAMP responsive element binding protein 3-like 2
HGNC id 23720
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
12 - 7455 - 520 - 2012 22495181
4 - 1175 - 248 - 2012 22495181
12 - 7054 - 457 - 2012 22495181
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularheart    
 vessel    
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
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Connectivebone   
Muscularstriatumskeletal  
Nervouscentral  highly Homo sapiens
cells
SystemCellPubmedSpeciesStageRna symbol
Blood/Hematopoieticleukocyte
Lymhoid/Immunelymphocyte
not specificchondrocyte Homo sapiensFetal
Respiratoryalveolar cell type II
cell lineage highly expressed in chondrocytes (Saito 2009)
cell lines
fluid/secretion
at STAGE
physiological period pregnancy
Text placenta, highly
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • 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
    HOMOLOGY
    interspecies homolog to drosophila Bbs2
    homolog to murine Creb3l2 (91.0pc)
    homolog to rattus Creb3l2 (91.0pc)
    intraspecies homolog to CREB3L1
    Homologene
    FAMILY
  • 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
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,nucleus,nucleoplasm
    text
  • 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
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA binding CRE DNA sequences
    RNA
    small molecule
    protein
  • 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
    REGULATION
    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
    ASSOCIATED DISORDERS
    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)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • 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