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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
    Physical map
    KIAA0843 FLJ36748 5q33.1 hypothetical protein FLJ36748 GRPEL2 5q33.1 GrpE-like 2, mitochondrial (E. coli) MGC3265 5q33.1 hypothetical protein MGC3265 IL17B 5q32-34 interleukin 17B CSNK1A1 13q13 casein kinase 1, alpha 1 LOC389337 5 similar to hypothetical protein 4933429F08 PERC 5q33.1 similar to hypothetical protein 4933429F08 PDE6A 5q31.3 phosphodiesterase 6A, cGMP-specific, rod, alpha SLC26A2 5q31.3 solute carrier family 26 (sulfate transporter), member 2 TIGD6 5q32 tigger transposable element derived 6 RPS20P4 5q33-qter ribosomal protein S20 pseudogene 4 CSF1R 5q31.3 colony stimulating factor 1 receptor, formerly McDonough feline sarcoma viral (v-fms) oncogene homolog RPL7P 5q33.3 ribosomal protein L7 pseudogene PDGFRB 5q31.3 platelet-derived growth factor receptor, beta polypeptide CDX1 5q31.3 caudal type homeo box transcription factor 1 SLC6A7 5q31-q32 solute carrier family 6 (neurotransmitter transporter, L-proline), member 7 CAMK2A 5q33.2 calcium/calmodulin-dependent protein kinase (CaM kinase) II alpha LOC340075 5q33.1 similar to RIKEN cDNA 9330196J05 TCOF1 5q32-q33.1 Treacher Collins-Franceschetti syndrome 1 CD74 5q31.3 CD74 antigen (invariant polypeptide of major histocompatibility complex, class II antigen-associated) RPS14 5q32 ribosomal protein S14 NDST1 5q31.3-q32 N-deacetylase/N-sulfotransferase (heparan glucosaminyl) 1 SYNPO 5q33.1 synaptopodin MYOZ3 5q33.1 myozenin 3 FLJ10290 5q33.1 hypothetical protein FLJ10290 DCTN4 5q31-q32 dynactin 4 (p62) NID67 5q33.1 putative small membrane protein NID67 LRG47 5q33.1 LRG-47-like protein ZNF300 21 zinc finger protein 300 GPX3 5q23 glutathione peroxidase 3 (plasma) TNIP1 5q32-q33.1 TNFAIP3 interacting protein 1 ANXA6 5q32 annexin A6 DKFZP434C171 5q33.1 DKFZP434C171 protein GM2A 5q32 GM2 ganglioside activator protein SLC36A3 5q33.1 solute carrier family 36 (proton/amino acid symporter), member 3 SLC36A2 5q33.1 solute carrier family 36 (proton/amino acid symporter), member 2 LOC391840 5 similar to Thyroid hormone receptor-associated protein complex 240 kDa component (Trap240) (Activator-recruited cofactor 250 kDa component) (ARC250) LOC391841 5 similar to hypothetical protein DKFZp761H0421 SLC36A1 5q33.1 solute carrier family 36 (proton/amino acid symporter), member 1 FAT2 5q31-q32 FAT tumor suppressor homolog 2 (Drosophila) SPARC 5q32 secreted protein, acidic, cysteine-rich (osteonectin)
    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