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FLASH GENE
Symbol CD274 contributors: mct/npt/pgu - updated : 04-05-2018
HGNC name CD274 molecule
HGNC id 17635
Location 9p24.1      Physical location : 5.450.502 - 5.470.566
Synonym name
  • CD274 antigen
  • programmed cell death 1 ligand 1
  • B7 homolog 1
    • Synonym symbol(s) B7-H, B7H1, PDL1, PD-L1, PDCD1L1, PDCD1LG1, MGC142294, MGC142296
    DNA
    TYPE functioning gene
    STRUCTURE 20.19 kb     7 Exon(s)
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    7 - 1553 - 290 - 2002 12244148
    6 - 3349 - 176 - -
    - - 907 - 245 - -
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
    Endocrineplacenta   highly
    Lymphoid/Immunethymus    
    Reproductivefemale systemuterus   
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal  
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticmonocyte
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period pregnancy
    Text placenta
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • an immunoglobulin V-like domain
  • an immunoglobulin C-like domain
    • HOMOLOGY
    Homologene
    FAMILY
  • immunoglobulin superfamily
  • B7 costimulatory/co-inhibitory ligands (BTN/MOG) family
  • CD28 family of co-stimulatory molecules
    • CATEGORY adhesion , receptor membrane
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
        intracellular
    intracellular,cytoplasm
    text transmembrane protein
    basic FUNCTION
  • costimulates T cell proliferation and IL10 secretion
  • supresses T cell cytokine synthesis
  • may have a negative immunoregulatory function in idiopathic inflammatory myopathies
  • play an important role in the negative regulation of immune reactions with its ligand PDCD1
  • negatively regulates cytokine synthesis in T cells activated by endothelial cells
  • implicated in the suppression of host immunity in T-cell lymphoproliferative disorders
  • plays a key role in the regulation of proatherogenic T cell immunity by intervening antigen presenting cell (APC)-dependent T cell activation
  • implicated in mechanisms of immune escape
  • cell-to-cell contact depend mechanism in the selective immunosuppression of Mesenchymal stem cells on mature Th17 cells through up-regulation of CD274
  • HLAG, CD274 and CD276, are secreted from early and term placenta, and have important implications in the mechanisms by which trophoblast immunomodulators modify the maternal immunological environment
  • role of the PDCD1/CD274 pathway in regulating lymphocyte activation, promotion of T regulatory cell development and function, breakdown of tolerance and development of autoimmunity
  • plays an essential role in the neuroprotection afforded by Tregs against cerebral ischemia by mediating the suppressive effect of Tregs on neutrophil-derived MMP9
  • has a novel function in the negative regulation of cancer stem cells (CSC)-related phenotypes in cholangiocarcinoma, which is distinct from its immunomodulatory actions
  • in aggregate, likely, CD274 expressed on activated target keratinocytes presenting autoantigens, regulates autoaggressive CD8 T cells, and inhibits the development of mucocutaneous autoimmune diseases
    • CELLULAR PROCESS cell life, proliferation/growth
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
  • signaling via CD274 and PDCD1LG2 is crucial for maintaining peripheral tolerance
  • Treg cells may through PDCD1/CD274 pathway play a role of immunosuppression regulation, and the impairment of Treg cells function in recurrent early abortion cases may be due to CD274 decrease in deciduas or trophoblast cells rather than PDCD1 change
    • a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • receptor of PDCD1
  • STAT3 binds to the CD274 gene promoter and is required for the its gene expression
  • differential molecular mechanisms of interaction of CD274 and PDCD1LG2 with PDCD1, suggesting possible new approach for the therapy of chronic infection, cancer and transplantation
  • PIK3CD mediates double-stranded (ds) RNA-induced upregulation of CD274 without affecting the activation of NFKB1
  • DOK3 is a nonredundant regulator of plasma cell (PC) differentiation by up-regulating CD274 expression through the attenuation of calcium signaling
  • PDCD1 is a potent inhibitory receptor of T cells which binds to two different ligands, namely CD274 and PDCD1LG2, and upon binding, it inhibits T cell activation, differentiation, and proliferation, leading to a state of immune tolerance
  • induces epithelial-to-mesenchymal transition via activating SREBF1 in renal cell carcinoma
  • NK cell activation and secretion of IFNG1 results in activation of JAK1, JAK2 and STAT1 in tumor cells, resulting in rapid up-regulation of CD274 expression
  • CD274-dependent regulatory circuitry that involves the induction of ARL4D for limiting IL2 production in T cells
  • VGLL4 is an important regulator of CD274 expression, suggesting a central role of VGLL4 and YAP1 in the regulation of tumor immunity
  • CD274 interacts with PDCD1 on T cells to trigger an inhibitory signal that suppresses anti-tumor T cell responses as an important mechanism of tumor escape from anti-tumor immune response
  • IFNB1 signal may up-regulate CD274 expression through IRF9-dependent and independent pathways in lung cancer cells
  • USP22 is a novel deubiquitinase of CD274, USP22 directly interacted with the C terminus of CD274, inducing its deubiquitination and stabilization
  • important role of USP22 in CD274 mediated immune evasion
    • cell & other
    REGULATION
    induced by IFN-gamma in endothelial cells
    Other up-regulated in HIV infection
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    on leukemia cells of acute monocyte leukemia, can significantly affect the immunotherapeutic efficacies of the patients and is a novel prognostic marker for acute monocyte leukemia
    tumoral     --over  
    overexpression in keratinocytes promotes the epithelial-mesenchymal transition and accelerates carcinogenesis
    tumoral     --over  
    of the immune modulatory molecule CD274 in anaplastic meningioma
    tumoral     --over  
    in leukemic lymphocytes, higher levels of CD274 than circulating B lymphocytes from normal donors
    constitutional     --over  
    in Multiple sclerosis (MS) lesions elevated CD274 expression by glial cells
    Susceptibility
  • to subacute sclerosing panencephalitis (SSPE)
  • to autoimmune Addison disease (AAD) and Graves disease (GD)
    • Variant & Polymorphism SNP , other
  • GCG(C) haplotype containing -606G allele significantly higher in SSPE patients than in controls
  • SNP showing modest association with both AAD and GD
    • Candidate gene
    Marker
  • CD274 expression is an independent negative prognostic factor in human breast cancer
    • Therapy target
    SystemTypeDisorderPubmed
    cancerhemopathy 
    targeting of Cd274 may represent a novel therapeutic approach
    ANIMAL & CELL MODELS