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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
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
    DNA
    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
    Physical map
    LOC346674 7q33 similar to Na+/L-ascorbic acid transporter 1; SVCT1 CNOT4 7q33 CCR4-NOT transcription complex, subunit 4 LOC392099 7 hypothetical gene supported by AK075360; NM_003002 NUP205 7q33 nucleoporin 205kDa LOC136321 7q33 similar to 60S ribosomal protein L15 SLC13A4 7q33 solute carrier family 13 (sodium/sulfate symporters), member 4 LOC389558 7 similar to HWKM1940 MTPN 7q33-q35 myotrophin LOC392100 7 similar to protease (prosome, macropain) 26S subunit, ATPase 1 LOC389559 7 LOC389559 CHRM2 7q31-q35 cholinergic receptor, muscarinic 2 LOC389560 7 LOC389560 PTN 7q33-q34 pleiotrophin (heparin binding growth factor 8, neurite growth-promoting factor 1) DGKI 7q32.3-q33 diacylglycerol kinase, iota CREB3L2 7q33-q34 cAMP responsive element binding protein 3-like 2 AKR1D1 7q32-q33 aldo-keto reductase family 1, member D1 (delta 4-3-ketosteroid-5-beta-reductase) LOC392101 7 similar to dJ753D5.2 (novel protein similar to RPS17 (40S ribosomal protein S17)) LOC392102 7 similar to prothymosin, alpha (gene sequence 28) LOC136307 7q34 similar to inosine monophosphate dehydrogenase 1 isoform b; sWSS2608 TIF1 7q32-q34 transcriptional intermediary factor 1 LOC136306 7q34 hypothetical protein LOC136306 LOC392103 7 similar to 60S ribosomal protein L17 (L23) LOC202789 7q34 similar to Ubiquinol-cytochrome C reductase iron-sulfur subunit, mitochondrial precursor (Rieske iron-sulfur protein) (RISP) ATP6V0A4 7q33-q34 ATPase, H+ transporting, lysosomal V0 subunit a isoform 4 KIAA1549 7q34 KIAA1549 protein MGC14289 7q34 similar to RIKEN cDNA 1200014N16 gene ZC3HAV1 7q34 zinc finger CCCH type, antiviral 1 FLJ12571 7q34 hypothetical protein FLJ12571 LOC389561 7 similar to 60S ribosomal protein L37a FLJ25778 7q34 hypothetical protein FLJ25778 HSPC268 7q34 hypothetical protein HSPC268 LUC7L2 7q34 LUC7-like 2 (S. cerevisiae) FLJ44186 7q34 FLJ44186 protein LOC392104 7 similar to heat shock 70kD protein binding protein; progesterone receptor-associated p48 protein; putative tumor suppressor ST13; Hsp70-interacting protein HIPK2 7q32-q34 homeodomain interacting protein kinase 2 LOC389562 7 LOC389562 TBXAS1 7q34-q35 thromboxane A synthase 1 (platelet, cytochrome P450, family 5, subfamily A) ZC3HDC1 7q34 zinc finger CCCH type domain containing 1 SLC37A3 7q34 solute carrier family 37 (glycerol-3-phosphate transporter), member 3
    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