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FLASH GENE
Symbol CD74 contributors: mct/ - updated : 22-06-2016
HGNC name CD74 molecule, major histocompatibility complex, class II invariant chain
HGNC id 1697
Location 5q32      Physical location : 149.781.200 - 149.792.332
Synonym name
  • CD74 antigen (invariant polypeptide of major histocompatibility complex, class II antigen-associated)
  • cell differentiation antigen CD74, identified by monoclonal antibodies LN2, BU-43, BU-45, chain Ii
  • HLA-DR-gamma
  • MHC HLA-DR gamma chain
  • gamma chain of class II antigens
  • Synonym symbol(s) DHLAG, HLADG, Ia-GAMMA, p33, li, HLA-DR-gamma, CLIP
    DNA
    TYPE functioning gene
    STRUCTURE 11.13 kb     9 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter (CAAT box) (TATA box)
    MAPPING cloned Y linked N status confirmed
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    9 splicing 1519 - 296 - 2014 25304249
  • variant 1, containing exon 1b (shorter than 1a), exon 9b (shorter than 9a)
  • isoform a
  • 8 splicing 1327 - 232 - 2014 25304249
  • variant 2, containing exon 1b (shorter than 1a), exon 9b (shorter than 9a)
  • lacking exon 7
  • isoform b
  • 6 splicing 1155 - 160 - 2014 25304249
  • variant 3, containing exon 1a (longer than 1b), exon 9a (longer than 9b)
  • lacking exons 5, 6 & 7
  • isoform c
  • EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    blood / hematopoieticspleen   highly
     thymus   highly
    Cardiovascularheart   highly
    Digestiveintestinelarge intestinecolon highly Homo sapiens
    Endocrinepancreas   highly
    Hearing/Equilibriumear   highly Mus musculus
    Nervousbrain   highly
    Respiratorylung   highly
    Urinarykidney   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoieticbone marrow   
    Epithelialsecretoryglandularendocrine 
    Lymphoid    
    Muscularstriatumskeletal  
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Digestiveepithelial cell Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a thyroglobulin type-I domain
  • conjugated GlycoP
    mono polymer heteromer , trimer , polymer
    HOMOLOGY
    interspecies homolog to C.elegans T04H1.5
    homolog to rattus Cd74 (75.92 pc)
    homolog to murine Cd74 (75.26 pc)
    Homologene
    FAMILY
    CATEGORY chaperone/stress , antigen
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,organelle,lysosome
    text type II membrane protein
    basic FUNCTION
  • playing a critical role in MHC class II antigen processing by stabilizing peptide-free class II alpha/beta heterodimers in a complex soon after their synthesis
  • directing transport of the complex from the endoplasmic reticulum to compartments where peptide loading of class II takes place
  • forms functional complexes with CXCR4 that mediate MIF-specific signaling
  • is a survival receptor on colon epithelial cells
  • MIF and CD74 play roles in CCL2-induced macrophage adhesion and migration, and they indicate that MIF and CD74 mediate this effect via both common and independent mechanisms
  • MIF and its receptor, CD74, are involved in regulating the migration of human mesenchymal stem cells (MSCs
  • presence of CD74 on statoacoustic ganglion (SAG) neurons supports the existence of a signaling pathway by which MIF influences SAG survival and outgrowth
  • mediates targeting of the MHCII complex to endosomal compartments, where CD74 undergoes degradation allowing MHCII to acquire peptides
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS immunity/defense
    PATHWAY
    metabolism
    signaling
    a component
  • nonamer composed of three alpha/beta/gamma heterotrimers
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with CXCR4 and MIF (CD74 forms functional complexes with CXCR4 that mediate MIF-specific signaling)
  • MIF inhibits the migration of cartilage end plate-derived stem cells by reacting with CD74
  • MIF promotes the migration of B cells through a ZAP70-dependent pathway mediated by cooperative engagement of CXCR4 and CD74
  • role of SPPL2A in CD74 proteolysis is conserved in human B cells, providing support for modulation of SPPL2A activity as a therapeutic concept
  • transcription factor MEF2A and PLAGL1 mediate MIF-induced SLC2A4 expression through CD74-dependent AMPK activation in cardiomyocytes
  • SPPL2A-mediated processing of CD74 N-terminal fragment (NTF) is indispensable to maintain appropriate levels of tonic BCR signaling to promote B cell maturation
  • MIF mediates its actions through a cell surface class II major histocompatibility chaperone, CD74 and co-receptors such as CD44, CXCR2, CXCR4 or CXCR7
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --other  
  • overexpressed in ulcerative colitis
  • low expressed in gastric cancer
  • constitutional     --low  
    leads to altered macrophage activation towards a pro-inflammatory signature and a disturbed crosstalk with trophoblasts
    tumoral     --over  
    CD74, MIF and TLR4 were found to be expressed in gastric cancer and increased significantly in the advanced stage, and were also associated with lymph node metastasis
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS