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CD74 CD74 molecule [ Homo sapiens (human) ]

Gene ID: 972, updated on 12-Aug-2018

Summary

Official Symbol
CD74provided by HGNC
Official Full Name
CD74 moleculeprovided by HGNC
Primary source
HGNC:HGNC:1697
See related
Ensembl:ENSG00000019582 MIM:142790; Vega:OTTHUMG00000163559
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

Genomic context

See CD74 in Genome Data Viewer
Location:
5q33.1
Exon count:
9
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) 5 NC_000005.10 (150401637..150412936, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 5 NC_000005.9 (149781200..149792543, 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 Neighboring gene N-deacetylase and N-sulfotransferase 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 Jun 15 11:32:44 2016

Bibliography

GeneRIFs: Gene References Into FunctionsWhat'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 BioSystems

  • Adaptive Immune System, organism-specific biosystem (from REACTOME)
    Adaptive Immune System, organism-specific biosystemAdaptive immunity refers to antigen-specific immune response efficiently involved in clearing the pathogens. The adaptive immune system is comprised of B and T lymphocytes that express receptors with...
  • Antigen processing and presentation, organism-specific biosystem (from KEGG)
    Antigen processing and presentation, organism-specific biosystem
    Antigen processing and presentation
  • Antigen processing and presentation, conserved biosystem (from KEGG)
    Antigen processing and presentation, conserved biosystem
    Antigen processing and presentation
  • Cell surface interactions at the vascular wall, organism-specific biosystem (from REACTOME)
    Cell surface interactions at the vascular wall, organism-specific biosystemLeukocyte extravasation is a rigorously controlled process that guides white cell movement from the vascular lumen to sites of tissue inflammation. The powerful adhesive interactions that are require...
  • Hemostasis, organism-specific biosystem (from REACTOME)
    Hemostasis, organism-specific biosystemHemostasis is a physiological response that culminates in the arrest of bleeding from an injured vessel. Under normal conditions the vascular endothelium supports vasodilation, inhibits platelet adhe...
  • Herpes simplex infection, organism-specific biosystem (from KEGG)
    Herpes simplex infection, organism-specific biosystemHerpes simplex virus (HSV) infections are very common worldwide, with the prevalence of HSV-1 reaching up to 80%-90%. Primary infection with HSV takes place in the mucosa, followed by the establishme...
  • Herpes simplex infection, conserved biosystem (from KEGG)
    Herpes simplex infection, conserved biosystemHerpes simplex virus (HSV) infections are very common worldwide, with the prevalence of HSV-1 reaching up to 80%-90%. Primary infection with HSV takes place in the mucosa, followed by the establishme...
  • Immune System, organism-specific biosystem (from REACTOME)
    Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
  • MHC class II antigen presentation, organism-specific biosystem (from REACTOME)
    MHC class II antigen presentation, organism-specific biosystemAntigen presenting cells (APCs) such as B cells, dendritic cells (DCs) and monocytes/macrophages express major histocompatibility complex class II molecules (MHC II) at their surface and present exog...
  • Tuberculosis, organism-specific biosystem (from KEGG)
    Tuberculosis, organism-specific biosystemTuberculosis, or TB, is an infectious disease caused by Mycobacterium tuberculosis. One third of the world's population is thought to be infected with TB. About 90% of those infected result in latent...
  • Tuberculosis, conserved biosystem (from KEGG)
    Tuberculosis, conserved biosystemTuberculosis, or TB, is an infectious disease caused by Mycobacterium tuberculosis. One third of the world's population is thought to be infected with TB. About 90% of those infected result in latent...

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

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_001025158.2NP_001020329.1  HLA class II histocompatibility antigen gamma chain isoform c

    See identical proteins and their annotated locations for NP_001020329.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) lacks three consecutive exons in the 3' coding region, which results in a frame-shift, compared to variant 1. The resulting isoform (c) has a shorter and distinct C-terminus, compared to isoform a.
    Source sequence(s)
    BC024272, DC354760
    Consensus CDS
    CCDS34276.1
    UniProtKB/Swiss-Prot
    P04233
    Related
    ENSP00000367026.3, OTTHUMP00000224284, ENST00000377795.7, OTTHUMT00000374177
    Conserved Domains (1) summary
    pfam09307
    Location:17128
    MHC2-interact; CLIP, MHC2 interacting
  2. NM_001025159.2NP_001020330.1  HLA class II histocompatibility antigen gamma chain isoform a

    See identical proteins and their annotated locations for NP_001020330.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the longest isoform (a).
    Source sequence(s)
    AK297889, BC024272, DC354760
    Consensus CDS
    CCDS47309.1
    UniProtKB/Swiss-Prot
    P04233
    Related
    ENSP00000009530.7, OTTHUMP00000224285, ENST00000009530.11, OTTHUMT00000374178
    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_001364083.1NP_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_001364084.1NP_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_004355.3NP_004346.1  HLA class II histocompatibility antigen gamma chain isoform b

    See identical proteins and their annotated locations for NP_004346.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks an in-frame exon in the 3' coding region, compared to variant 1. The resulting isoform (b) lacks an internal segment in the C-terminal region, compared to isoform a.
    Source sequence(s)
    BC018726, BC024272, DC354760
    Consensus CDS
    CCDS47308.1
    UniProtKB/Swiss-Prot
    P04233
    Related
    ENSP00000230685.6, OTTHUMP00000224283, ENST00000353334.10, OTTHUMT00000374176
    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_157074.1 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC011372, AC011388

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109 details...Open this link in a new tab

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

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000005.10 Reference GRCh38.p12 Primary Assembly

    Range
    150401637..150412936 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

    Related
    ENSP00000430614.1, OTTHUMP00000224286, ENST00000518797.5

RNA

  1. XR_002956198.1 RNA Sequence

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