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CD74 CD74 molecule [ Homo sapiens (human) ]

Gene ID: 972, updated on 11-Jun-2021

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; 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
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Genomic context

See CD74 in Genome Data Viewer
Location:
5q33.1
Exon count:
8
Annotation release Status Assembly Chr Location
109.20210514 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 activation of MAPK activity IEA
Inferred from Electronic Annotation
more info
 
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 TAS
Traceable Author Statement
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 leukocyte migration TAS
Traceable Author Statement
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 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
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, ENST00000009530.12
    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 109.20210514

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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