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FLASH GENE
Symbol CEBPA contributors: mct/npt/pgu - updated : 23-09-2014
HGNC name CCAAT/enhancer binding protein (C/EBP), alpha
HGNC id 1833
Location 19q13.11      Physical location : 33.790.841 - 33.793.430
Synonym symbol(s) CEBP, CEBA, C/EBP-alpha
DNA
TYPE functioning gene
STRUCTURE 2.63 kb     1 Exon(s)
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Binding site
text structure DNA binding protein, intronless
MAPPING cloned Y linked N status confirmed
Physical map
LOC147941 19q13.12 hypothetical LOC147941 LOC147942 19q13.12 hypothetical LOC147942 LOC388530 19 LOC388530 ZNF507 19q13.12 zinc finger protein 507 LOC147991 19q13.12 hypothetical protein LOC147991 DKFZP434L0718 PDCD5 19q13.1 programmed cell death 5 LOC388531 19 similar to regulator of G protein signaling 9-binding protein; RGS9-1 anchor; RGS9 anchor protein LOC390916 19 similar to RP2 protein, testosterone-regulated - ricefield mouse (Mus caroli) FLJ13072 19q13.12 hypothetical gene FLJ13072 SLC7A9 19q13.1 solute carrier family 7 (cationic amino acid transporter, y+ system), member 9 FLJ14640 19q13.12 hypothetical protein FLJ14640 MGC32020 19q13.12 hypothetical protein MGC32020 RHPN2 19q13.12 rhophilin, Rho GTPase binding protein 2 ECGP 19q13.12 evolutionarily conserved G-patch domain containing LOC126248 19q13.12 hypothetical protein LOC126248 LRP3 19q12-q13.2 low density lipoprotein receptor-related protein 3 SLC7A10 19q12-q13.1 solute carrier family 7, (cationic amino acid transporter, y+ system) member 10 CEBPA 19q13.1 CCAAT/enhancer binding protein (C/EBP), alpha FLJ12355 19q13.12 hypothetical protein FLJ12355 LOC126242 19q13.12 similar to Aldose reductase (AR) (Aldehyde reductase) CEBPG 19q13.12 CCAAT/enhancer binding protein (C/EBP), gamma PEPD 19q13.1 peptidase D LOC388532 19 similar to 60S ribosomal protein L21 CHST8 19q13.1 carbohydrate (N-acetylgalactosamine 4-0) sulfotransferase 8 KCTD15 19q13.12 potassium channel tetramerisation domain containing 15 LOC390917 19 similar to ribosomal protein S4 LOC126235 19q13.12 similar to ribosomal protein S4, X-linked LOC390918 19 similar to chromosome 7 open reading frame 17 protein; 16.7kD protein DKFZP434D1335 KIAA0355 19q13.12 similar to chromosome 7 open reading frame 17 protein; 16.7kD protein GPI 19q13.1 glucose phosphate isomerase MGC13096 19q13.12 hypothetical protein MGC13096 UBA2 9q12 hypothetical protein MGC13096 LOC126374 19q13.12 similar to LIM domains containing 1 LOC390919 19 similar to ZNF140-like transcription factor LOC390920 19 similar to zinc finger protein 2 ZNF302 19q13.2 zinc finger protein 302 LOC390921 19 similar to Major allergen I polypeptide chain 1 major form precursor (Allergen Fel d 1-A) (Fel d I-A) (Allergen Cat-1) (Fel dI) (AG4) ZNF181 19q13.1-q13.3 zinc finger protein 181 (HHZ181) FLJ30663 19q13.13 hypothetical protein FLJ30663 LOC390922 19 similar to FLJ38451 protein LOC390923 19 similar to zinc finger protein 113 LOC342885 19q13.13 similar to ABO histo-blood group B transferase DKFZp686N19164 FLJ38451 19q13.13 FLJ38451 protein
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
1 initiation site 2591 - 358 - 1993 8367486
1 initiation site 2631 30 239 - -
  • also called C/EBP30
  • AUG 351 nt dowstream of the first
  • truncating mutations enhancing the production of a 30kDa C terminal form
  • 1 - 2631 - 393 - -
    1 - 2631 - 344 - -
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinelarge intestinecolon  
     liver    
     mouthtongue   
     stomach   highly
    Reproductivefemale systemplacenta   
    Respiratorylung    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectivebone   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticgranulocyte
    Lymphoid/Immunemacrophage Homo sapiens
    cell lineage only myelomonocytic cells lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period pregnancy
    Text at highest level in placenta
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • transactivation domains (TADs) at its N-terminus
  • a DNA-binding and dimerization bZIP structure at its C-terminus, with a functional importance which may mediate cooperative activation by CEBPA and GABPA of myeloid-specific genes involved in CEBPA-dependent granulopoiesis
  • mono polymer heteromer , dimer
    HOMOLOGY
    interspecies homolog to rattus Cebpa (95.20 pc)
    homolog to murine Cebpa (95.76 pc)
    intraspecies homolog to CEBPG
    Homologene
    FAMILY
  • bZIP family
  • C/EBP subfamily
  • CATEGORY DNA associated , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus
    basic FUNCTION
  • granulocytic differentiation factor downregulated c-Myc target gene
  • coexpressed with and cross-regulated by PPARG, jointly required for full adipocyte differentiation and for granulocytic differentiation
  • a key regulator of airway epithelial maturation
  • mediating lineage specification and differentiation of multipotent myeloid progenitors into mature granulocytes
  • having a necessary role for transcriptional control of granulocyte, adipocyte and hepatocyte differentiation, glucose metabolism and lung development
  • important regulator of cytokine expression in human neutrophils
  • is the key transcriptional regulator of osteoclast (OC) lineage commitment
  • key transcription factor involved in the adipocyte differentiation
  • acts to modulate the epigenetic states of genes belonging to molecular pathways important for hematopoietic stem cells (HSCs) function
  • is required for macrophage activation, which plays an important role in maintaining skeletal muscle energy metabolism
  • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism energetic
    signaling
  • energy pathway
  • molecular pathway PTEN-CEBPA-CTNNA1 which is evolutionarily conserved, and controls myeloid development and transformation
  • a component
    INTERACTION
    DNA
  • binding to sequence CCAAT enhancer
  • RNA
    small molecule
    protein
  • inhibiting SPI1 (PU1) and influencing cell fate and directing the development to the granulocyte lineage
  • binds KLF3 and both are implicated in controlling adipogenesis
  • functional interaction with CDX1 and PPARG
  • (CDX1 enhanced the expression of PPARG, a master transcriptional regulator of intestinal differentiation, at the transcriptional level, via functional interaction with CEBPA)
  • TCERG1 functions as an inhibitor of CEBPA rather than a transcriptional co-repressor, and inhibits CEBPA activity by keeping it retained in inactive, pericentromeric heterochromatin
  • substrate for FBXW7 (FBXW7 is a negative regulator of CEBPA function by targeting it to phosphorylation-dependent degradation)
  • interacting with HDAC9 (induction of adipogenic differentiation promotes HDAC9 down-regulation and replacement by EP300 at the E-box site of the CEBPA gene promoter, thus switching on adipogenic gene expression)
  • PTPN11 is required for induction of CEBPA expression and granulopoiesis in response to G-CSF or other cytokines independent of PTPN11-mediated ERK activation 8)
  • in committed macrophage progenitors, CEBPA-activated QKI negatively regulates macrophage differentiation by down-regulating CSF1R expression, forming a negative feedback loop during macrophage differentiation
  • ATF3 may contribute to the inhibition of adipocyte differentiation in hypoxia through downregulation of CEBPA expression
  • DICER1 might have important roles in the expression of adipogenic genes including PPARG and CEBPA via regulation of the expression of miRNAs at the early, but not the late, stage of adipocyte differentiation
  • UBE3A may negatively control adipogenesis by inhibiting CEBPA expression by targeting it to ubiquitin-proteasome pathway for degradation
  • RARA-ZBTB16 acts as a modifier oncogene that subverts differentiation in the granulocytic lineage by associating with CEBPA and inhibiting its activity
  • MBD2 colocalizes with the transcription factor CEBPA, and MBD2 binding at these positions is reduced upon CEBPA depletion
  • IKZF1 is a suppressor of basophil differentiation under steady-state conditions and that it acts by regulating permissive chromatin modifications of CEBPA
  • CEBPA interacts with the ETS domain of widely expressed GABPA, which leads to cooperative transcriptional activation of the myeloid-specific promoter for FCAR in part by facilitating recruitment of CEBPA to the promoter
  • plays a dual role as an activator and as a repressor of GNAI2 gene transcription
  • regulatory role of CEBPA on VCAM1 expression
  • cell & other
    REGULATION
    induced by CEBPB and CEBPD
    inhibited by leukemic fusion gene AME
    repressed by BCR-ABL (through inhibitory action of PCBP2)
    ZBTB16 (represses transcription factors involved in normal myeloid differentiation, including GFI1, C/EBPalpha)
    ATF3, that represses CEBPA, resulting in inhibition of adipocyte differentiation, and thus playing a role in hypoxia-mediated inhibition of adipocyte differentiation
    Other regulated by an ERK1/2-mediated change in the conformation of CEBPA that favors monocyte differentiation by blocking granulopoiesis
    regulated by CITED2-TFAP2C complex which controls lung maturation by regulating CEBPA expression
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   deletion    
    212delC associated with familial acute myeloblastic leukemia with good prognostic
    tumoral       loss of function
    or low expressed in acute myeloid leukemia
    tumoral somatic mutation      
    cause a myeloid differentiation block and were detected in acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), multiple myeloma and non-Hodgkin's lymphoma (NHL)
    tumoral     --low  
    contributes to MN1-modulated proliferation and impaired myeloid differentiation of hematopoietic cells
    tumoral       loss of function
    SOX4 overexpression resulting from its inactivation contributes to the development of leukemia with a distinct leukemia-initiating cells (LICs) phenotype
    Susceptibility
    Variant & Polymorphism 212delC associated with familial acute myeloblastic leukemia with good prognostic
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS