CD74

Domain

Antiviral activity requires delivery of the thyroglobulin domain to the endosomal membrane.

Function

Plays 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 and directing transport of the complex from the endoplasmic reticulum to the endosomal/lysosomal system where the antigen processing and binding of antigenic peptides to MHC class II takes place. Serves as cell surface receptor for the cytokine MIF.

Class-II-associated invariant chain peptide

Binds to the peptide-binding site of MHC class II alpha/beta heterodimers forming an alpha-beta-CLIP complex, thereby preventing the loading of antigenic peptides to the MHC class II complex until its release by HLA-DM in the endosome.

Isoform p41

Stabilizes the conformation of mature CTSL by binding to its active site and serving as a chaperone to help maintain a pool of mature enzyme in endocytic compartments and extracellular space of antigen-presenting cells (APCs). Has antiviral activity by stymieing the endosomal entry of Ebola virus and coronaviruses, including SARS-CoV-2 (PubMed:32855215). Disrupts cathepsin-mediated Ebola virus glycoprotein processing, which prevents viral fusion and entry. This antiviral activity is specific to p41 isoform (PubMed:32855215).

Involvement in disease

A chromosomal aberration involving CD74 is found in a non-small cell lung tumor. Results in the formation of a CD74-ROS1 chimeric protein.

Post-translational modifications

O-glycosylated with core 1 or possibly core 8 glycans (PubMed:22171320, PubMed:23234360). Contains chondroitin sulfate (PubMed:25326458).

Tissue Specificity

Detected in urine (at protein level).

Isoform p41

In B cells, represents 10% of total CD74 expression.

Isoform p33

In B cells, represents 70% of total CD74 expression.

Cellular localization

• Cell membrane
• Single-pass type II membrane protein
• Endoplasmic reticulum membrane
• Golgi apparatus
• trans-Golgi network
• Endosome
• Lysosome
• Secreted
• Transits through a number of intracellular compartments in the endocytic pathway. It can either undergo proteolysis or reach the cell membrane.
• Isoform p41
• Late endosome
• Lysosome

Alternative names

CD74, DHLAG, HLA class II histocompatibility antigen gamma chain, HLA-DR antigens-associated invariant chain, Ia antigen-associated invariant chain, Ii

Database links

swissprot:P04233 entrezGene:972 omim:142790

Other research areas

• Immuno-oncology