CD74, also known as Invariant chain (Ii) and p33, is a type 2 transmembrane glycoprotein that plays an important role in adaptive immunity, inflammation, and cancer (1). Mature mouse CD74 consists of a 29 amino acid (aa) cytoplasmic domain, a 29 aa transmembrane segment, and a 224 aa extracellular domain (ECD) that contains one thyroglobulin type 1 domain (2). Alternative splicing generates a short isoform that lacks the thyroglobulin domain (2). Within the ECD, mouse CD74 shares 75% and 88% aa sequence identity with human and rat CD74, respectively. CD74 functions as a chaperone for MHC class II molecules on antigen presenting cells and undergoes progressive proteolysis during class II trafficking and antigenic peptide loading (3). Full length CD74 assembles into trimers which then associate with class II molecules in nonameric complexes on the cell surface (4, 5). CD74 also associates with CD44 and binds with high affinity to the cytokine MIF, leading to inflammatory leukocyte responses, protection from tissue fibrosis, B cell proliferative and survival signaling, and the up‑regulation of angiogenic factors in endometrial stromal cells (6‑11). MIF binding notably induces the proteolytic cleavage of the CD74 intracellular domain which then promotes B cell differentiation (10). CD74 is upregulated on non‑immune cells at sites of inflammation including amyloid beta plaques and atherosclerotic plaques (12, 13). It is also upregulated in a variety of cancers and enhances tumorigenicity, tumor angiogenesis, and metastasis (1, 14).

References

Beswick, E.J. and V.E. Reyes (2009) World J. Gastroenterol. 15:2855.
Koch, N. et al. (1987) EMBO J. 6:1677.
Riberdy, J.M. et al. (1992) Nature 360:474.
Koch, N. et al. (1991) J. Immunol. 147:2643.
Roche, P.A. et al. (1991) Nature 354:392.
Leng, L. et al. (2003) J. Exp. Med. 197:1467.
Takahashi, K. et al. (2009) Respir. Res. 10:33.
Heinrichs, D. et al. (2011) Proc. Natl. Acad. Sci. USA 104:17444.
Shi, X. et al. (2006) Immunity 25:595.
Gore, Y. et al. (2008) J. Biol. Chem. 283:2784.
Veillat, V. et al. (2010) J. Clin. Endocrinol. Metab. 95:E403.
Bryan, K.J. et al. (2008) Mol. Neurodegen. 3:13.
Martin-Ventura, J.L. et al. (2009) Cardiovasc. Res. 83:586.
Liu, Y.-H. et al. (2008) J. Immunol. 181:6584.

Alternate Names

CD74, CLIP, DHLAG, HLADG, Ia-gamma, INVG34

Entrez Gene IDs

972 (Human); 16149 (Mouse); 25599 (Rat)

Gene Symbol

CD74

UniProt

P04441

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Product Specific Notices for Mouse CD74 Alexa Fluor™ Plus 555-conjugated Antibody

This product is provided under an intellectual property license from Life Technologies Corporation. The transfer of this product is conditioned on the buyer using the purchased product solely in research conducted by the buyer, excluding contract research or any fee for service research, and the buyer must not (1) use this product or its components for (a) diagnostic, therapeutic or prophylactic purposes; (b) testing, analysis or screening services, or information in return for compensation on a per-test basis; or (c) manufacturing or quality assurance or quality control, and/or (2) sell or transfer this product or its components for resale, whether or not resold for use in research. For information on purchasing a license to this product for purposes other than as described above, contact Life Technologies Corporation, 5781 Van Allen Way, Carlsbad, CA 92008 USA or outlicensing@thermofisher.com.

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Mouse CD74 Alexa Fluor™ Plus 555-conjugated Antibody

R&D Systems, part of Bio-Techne | Catalog # FAB7478AFP555

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Background: CD74