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    CD74 CD74 molecule [ Homo sapiens (human) ]

    Gene ID: 972, updated on 5-Jan-2022

    Summary

    Official Symbol
    CD74provided by HGNC
    Official Full Name
    CD74 moleculeprovided by HGNC
    Primary source
    HGNC:HGNC:1697
    See related
    Ensembl:ENSG00000019582 MIM:142790
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    II; p33; CLIP; DHLAG; HLADG; Ia-GAMMA
    Summary
    The protein encoded by this gene associates with class II major histocompatibility complex (MHC) and is an important chaperone that regulates antigen presentation for immune response. It also serves as cell surface receptor for the cytokine macrophage migration inhibitory factor (MIF) which, when bound to the encoded protein, initiates survival pathways and cell proliferation. This protein also interacts with amyloid precursor protein (APP) and suppresses the production of amyloid beta (Abeta). Multiple alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Aug 2011]
    Expression
    Broad expression in spleen (RPKM 1835.3), lymph node (RPKM 1421.7) and 24 other tissues See more
    Orthologs
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    See CD74 in Genome Data Viewer
    Location:
    5q33.1
    Exon count:
    8
    Annotation release Status Assembly Chr Location
    109.20211119 current GRCh38.p13 (GCF_000001405.39) 5 NC_000005.10 (150401637..150412910, complement)
    105.20201022 previous assembly GRCh37.p13 (GCF_000001405.25) 5 NC_000005.9 (149779604..149792499, complement)

    Chromosome 5 - NC_000005.10Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105378226 Neighboring gene treacle ribosome biogenesis factor 1 Neighboring gene ribosomal protein S14 Neighboring gene NDST1 antisense RNA 1

    Genomic regions, transcripts, and products

    Expression

    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?

    HIV-1 interactions

    Protein interactions

    Protein Gene Interaction Pubs
    Envelope transmembrane glycoprotein gp41 env HIV-1 gp41 is able to activate the ERK/MAPK pathway by binding to CD74 PubMed
    env HIV-1 gp41 directly interacts with CD74 in HIV-1 infected cells. The loop region (residues 590-624) of gp41 is required to interact with CD74 extracellular domain (residues 72-232) PubMed
    Nef nef HIV-1 Nef cloned from subjects with early/acute progressive HIV infection upregulates CD74 (Ii) in 721.221 cells to a greater extent relative to HIV-1 Nef cloned from subjects with chronic progressive infection PubMed
    nef HIV-1 group N and group O Nef alleles upregulate surface expression of invariant chain (Ii) associated with immature major histocompatibility complex (MHC) class II PubMed
    nef Upregulation of Ii expression by Nef at the cell surface impairs mature MHC class II antigen presentation PubMed
    nef HIV-1 Nef clones, isolated from plasma of elite controllers (EC) and chronic progressors (CP), show significantly lower HLA class II invariant chain (CD74) upregulation activity in EC than that in CP PubMed
    nef Two primary Nef alleles from HIV-1 subtype C and F impair for the MHC-II-associated chaperone invariant chain (Ii) upregulation PubMed
    nef Nef-mediated Ii upregulation depends on the AP-2 mu2 expression pathway PubMed
    nef LL164 and DD174 motifs in HIV-1 Nef and the Ii cytoplasmic tail (amino acids 1-17) are required for the Nef-mediated upregulation of Ii by slowing the rate of Ii internalization PubMed
    nef Substitution of HIV-1 Nef acidic residue E160 with uncharged residues impairs the ability of Nef to upregulate the expression of DC-SIGN and the invariant chain of MHC class II at the cell surface PubMed
    nef HIV-1 Nef induces drastic and moderate downregulation of CD4 and MHC-I in resting CD4(+) T lymphocytes, respectively, but markedly upregulates cell surface levels of the MHC-II invariant chain CD74 PubMed
    Vpu vpu HIV-1 Vpu interacts with CD74 and modulates MHC II in HIV-1-infected cells. The N-terminal 30 amino acids of CD74 are required for the interaction of CD74 with Vpu PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Homology

    Clone Names

    • FLJ98970

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables CD4 receptor binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables MHC class II protein binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    enables MHC class II protein binding ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    enables MHC class II protein binding NAS
    Non-traceable Author Statement
    more info
    PubMed 
    enables MHC class II protein binding, via antigen binding groove IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables MHC class II protein complex binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables amyloid-beta binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables cytokine binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables cytokine receptor activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    enables cytokine receptor activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables identical protein binding TAS
    Traceable Author Statement
    more info
    PubMed 
    enables macrophage migration inhibitory factor binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    enables macrophage migration inhibitory factor binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables nitric-oxide synthase binding IEA
    Inferred from Electronic Annotation
    more info
     
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables protein folding chaperone IDA
    Inferred from Direct Assay
    more info
    PubMed 
    Process Evidence Code Pubs
    involved_in T cell activation involved in immune response IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    involved_in T cell selection NAS
    Non-traceable Author Statement
    more info
    PubMed 
    involved_in antigen processing and presentation IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    involved_in antigen processing and presentation of endogenous antigen NAS
    Non-traceable Author Statement
    more info
    PubMed 
    involved_in antigen processing and presentation of exogenous peptide antigen via MHC class II IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in cell population proliferation IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in chaperone cofactor-dependent protein refolding IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in immunoglobulin mediated immune response ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in intracellular protein transport ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in macrophage migration inhibitory factor signaling pathway IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in negative regulation of DNA damage response, signal transduction by p53 class mediator IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    involved_in negative regulation of DNA damage response, signal transduction by p53 class mediator IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in negative regulation of T cell differentiation IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in negative regulation of apoptotic process IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in negative regulation of cell migration IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    involved_in negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in negative regulation of mature B cell apoptotic process IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in negative regulation of peptide secretion IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in negative thymic T cell selection IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive regulation of B cell proliferation IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of ERK1 and ERK2 cascade IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    involved_in positive regulation of ERK1 and ERK2 cascade IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of ERK1 and ERK2 cascade IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of I-kappaB kinase/NF-kappaB signaling IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of MAPK cascade IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of T cell differentiation IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive regulation of chemokine (C-X-C motif) ligand 2 production ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in positive regulation of chemokine production IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of cytokine-mediated signaling pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    involved_in positive regulation of cytokine-mediated signaling pathway IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of dendritic cell antigen processing and presentation IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive regulation of fibroblast proliferation IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of gene expression IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of interleukin-6 production IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of interleukin-8 production IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of kinase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    involved_in positive regulation of kinase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of macrophage cytokine production IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    involved_in positive regulation of macrophage cytokine production ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in positive regulation of macrophage migration inhibitory factor signaling pathway IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of monocyte differentiation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of neutrophil chemotaxis ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in positive regulation of peptidyl-tyrosine phosphorylation IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    involved_in positive regulation of peptidyl-tyrosine phosphorylation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of prostaglandin biosynthetic process IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of protein phosphorylation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of transcription, DNA-templated IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of type 2 immune response IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    involved_in positive regulation of viral entry into host cell IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive thymic T cell selection IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in prostaglandin biosynthetic process IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in protein trimerization IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in protein-containing complex assembly ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in regulation of macrophage activation NAS
    Non-traceable Author Statement
    more info
    PubMed 
    involved_in response to interferon-gamma IDA
    Inferred from Direct Assay
    more info
    PubMed 
    Component Evidence Code Pubs
    located_in ER to Golgi transport vesicle membrane TAS
    Traceable Author Statement
    more info
     
    located_in Golgi membrane TAS
    Traceable Author Statement
    more info
     
    part_of MHC class II protein complex ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    part_of NOS2-CD74 complex IEA
    Inferred from Electronic Annotation
    more info
     
    is_active_in cell surface IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    located_in cell surface IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in clathrin-coated endocytic vesicle membrane TAS
    Traceable Author Statement
    more info
     
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in endocytic vesicle membrane TAS
    Traceable Author Statement
    more info
     
    located_in external side of plasma membrane IEA
    Inferred from Electronic Annotation
    more info
     
    located_in extracellular exosome HDA PubMed 
    located_in integral component of lumenal side of endoplasmic reticulum membrane TAS
    Traceable Author Statement
    more info
     
    located_in integral component of membrane IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in lysosomal lumen TAS
    Traceable Author Statement
    more info
     
    located_in lysosomal membrane TAS
    Traceable Author Statement
    more info
     
    part_of macrophage migration inhibitory factor receptor complex IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in membrane HDA PubMed 
    located_in multivesicular body IEA
    Inferred from Electronic Annotation
    more info
     
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
     
    part_of protein-containing complex IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in trans-Golgi network membrane TAS
    Traceable Author Statement
    more info
     
    located_in transport vesicle membrane TAS
    Traceable Author Statement
    more info
     
    located_in vacuole IDA
    Inferred from Direct Assay
    more info
    PubMed 

    General protein information

    Preferred Names
    HLA class II histocompatibility antigen gamma chain
    Names
    CD74 antigen (invariant polypeptide of major histocompatibility complex, class II antigen-associated)
    CD74 molecule, major histocompatibility complex, class II invariant chain
    HLA-DR antigens-associated invariant chain
    HLA-DR-gamma
    Ia-associated invariant chain
    MHC HLA-DR gamma chain
    class II MHC-associated invariant chain peptide
    gamma chain of class II antigens

    NCBI Reference Sequences (RefSeq)

    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_029730.1 RefSeqGene

      Range
      5001..16300
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001025158.3NP_001020329.1  HLA class II histocompatibility antigen gamma chain isoform c

      See identical proteins and their annotated locations for NP_001020329.1

      Status: REVIEWED

      Source sequence(s)
      AC011372, AC011388
      Consensus CDS
      CCDS34276.1
      UniProtKB/Swiss-Prot
      P04233
      Related
      ENSP00000367026.3, ENST00000377795.7
      Conserved Domains (1) summary
      pfam09307
      Location:17128
      MHC2-interact; CLIP, MHC2 interacting
    2. NM_001025159.3NP_001020330.1  HLA class II histocompatibility antigen gamma chain isoform a

      See identical proteins and their annotated locations for NP_001020330.1

      Status: REVIEWED

      Source sequence(s)
      AC011372, AC011388
      Consensus CDS
      CCDS47309.1
      UniProtKB/Swiss-Prot
      P04233
      Related
      ENSP00000009530.7, ENST00000009530.13
      Conserved Domains (3) summary
      cd00191
      Location:212271
      TY; Thyroglobulin type I repeats.; The N-terminal region of human thyroglobulin contains 11 type-1 repeats TY repeats are proposed to be inhibitors of cysteine proteases
      pfam08831
      Location:136204
      MHCassoc_trimer; Class II MHC-associated invariant chain trimerization domain
      pfam09307
      Location:17128
      MHC2-interact; CLIP, MHC2 interacting
    3. NM_001364083.3NP_001351012.1  HLA class II histocompatibility antigen gamma chain isoform d

      Status: REVIEWED

      Source sequence(s)
      AC011372, AC011388
      Conserved Domains (2) summary
      pfam08831
      Location:127183
      MHCassoc_trimer; Class II MHC-associated invariant chain trimerisation domain
      pfam09307
      Location:17126
      MHC2-interact; CLIP, MHC2 interacting
    4. NM_001364084.3NP_001351013.1  HLA class II histocompatibility antigen gamma chain isoform e

      Status: REVIEWED

      Source sequence(s)
      AC011372, AC011388
      Conserved Domains (2) summary
      pfam08831
      Location:136184
      MHCassoc_trimer; Class II MHC-associated invariant chain trimerisation domain
      pfam09307
      Location:17128
      MHC2-interact; CLIP, MHC2 interacting
    5. NM_004355.4NP_004346.1  HLA class II histocompatibility antigen gamma chain isoform b

      See identical proteins and their annotated locations for NP_004346.1

      Status: REVIEWED

      Source sequence(s)
      AC011372, AC011388
      Consensus CDS
      CCDS47308.1
      UniProtKB/Swiss-Prot
      P04233
      Related
      ENSP00000230685.6, ENST00000353334.11
      Conserved Domains (2) summary
      pfam08831
      Location:136204
      MHCassoc_trimer; Class II MHC-associated invariant chain trimerisation domain
      pfam09307
      Location:17128
      MHC2-interact; CLIP, MHC2 interacting

    RNA

    1. NR_157074.3 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC011372, AC011388

    RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20211119

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p13 Primary Assembly

    Genomic

    1. NC_000005.10 Reference GRCh38.p13 Primary Assembly

      Range
      150401637..150412910 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017010090.2XP_016865579.1  HLA class II histocompatibility antigen gamma chain isoform X2

    2. XM_017010089.2XP_016865578.1  HLA class II histocompatibility antigen gamma chain isoform X1

    RNA

    1. XR_002956198.1 RNA Sequence

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