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CD74

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Immunopharmacology Ligand target has curated data in GtoImmuPdb

Target id: 2840

Nomenclature: CD74

Family: CD molecules

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 296 5q33.1 CD74 CD74 molecule 2,5
Mouse 1 279 18 34.41 cM Cd74 CD74 antigen (invariant polypeptide of major histocompatibility complex, class II antigen-associated)
Rat 1 280 18q12.1 Cd74 CD74 molecule
Previous and Unofficial Names Click here for help
HLA-DR-gamma | Ia-associated invariant chain | invariant polypeptide of major histocompatibility complex, class II antigen-associated | CD74 molecule, major histocompatibility complex, class II invariant chain | Cd74 molecule, major histocompatibility complex, class II invariant chain | CD74 antigen (invariant polypeptide of major histocompatibility complex, class II antigen-associated) | CD74 antigen (invariant polypeptide of major histocompatibility complex
Database Links Click here for help
Alphafold
CATH/Gene3D
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia

Download all structure-activity data for this target as a CSV file go icon to follow link

Antibodies
Key to terms and symbols Click column headers to sort
Antibody Sp. Action Value Parameter Reference
milatuzumab Peptide Primary target of this compound Immunopharmacology Ligand Hs Binding 9.3 pKd 9
pKd 9.3 (Kd 5x10-10 M) [9]
Immunopharmacology Comments
CD74 is a type II transmembrane glycoprotein which associates with the MHC class II α and β chains and directs the transport of class II molecules to lysosomal and endosomal compartments [3], where the invariant chain is degraded. CD74 is also involved in B cell maturation [8] and acts as a receptor for macrophage migration inhibitory factor (MIF) [6]. Based on findings that CD74 is expressed with high frequency in lymphomas [10], anti-CD74 monoclonal antibodies are being developed as immuno-oncology therapeutics. For example, the anti-CD74 antibody-drug conjugate STRO-001 (SP7675) is being developed by Sutro Biopharma as a potential treatment for B cell malignancies [7] including multiple myeloma (MM). STRO-001 was granted FDA orphan drug designation for MM in October 2018 [4].
Cell Type Associations
Immuno Cell Type:  Macrophages & monocytes
Cell Ontology Term:   macrophage (CL:0000235)
monocyte (CL:0000576)
Immuno Cell Type:  Dendritic cells
Cell Ontology Term:   dendritic cell (CL:0000451)
Immuno Cell Type:  T cells
Cell Ontology Term:   T cell (CL:0000084)
References:  1
Immuno Process Associations
Immuno Process:  Barrier integrity
Immuno Process:  Inflammation
Immuno Process:  Antigen presentation
Immuno Process:  T cell (activation)
Immuno Process:  B cell (activation)
Immuno Process:  Immune regulation
Immuno Process:  Immune system development
Immuno Process:  Cytokine production & signalling
Immuno Process:  Chemotaxis & migration
Immuno Process:  Cellular signalling

References

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1. A-González N, Castrillo A. (2011) Liver X receptors as regulators of macrophage inflammatory and metabolic pathways. Biochim Biophys Acta, 1812 (8): 982-94. [PMID:21193033]

2. Claesson L, Larhammar D, Rask L, Peterson PA. (1983) cDNA clone for the human invariant gamma chain of class II histocompatibility antigens and its implications for the protein structure. Proc Natl Acad Sci USA, 80 (24): 7395-9. [PMID:6324166]

3. Cresswell P. (1994) Assembly, transport, and function of MHC class II molecules. Annu Rev Immunol, 12: 259-93. [PMID:8011283]

4. FDA. antibody-drug conjugate comprised of a human aglycosylated anti-CD74 IgG1 antibody (SP7219) and two non-cleavable maytansinoid linker warheads. Accessed on 13/11/2018. Modified on 13/11/2018. www.accessdata.fda.gov, https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=654118

5. Kudo J, Chao LY, Narni F, Saunders GF. (1985) Structure of the human gene encoding the invariant gamma-chain of class II histocompatibility antigens. Nucleic Acids Res, 13 (24): 8827-41. [PMID:3001652]

6. Leng L, Metz CN, Fang Y, Xu J, Donnelly S, Baugh J, Delohery T, Chen Y, Mitchell RA, Bucala R. (2003) MIF signal transduction initiated by binding to CD74. J Exp Med, 197 (11): 1467-76. [PMID:12782713]

7. Li X, Abrahams C, Embury M, Yu A, Kahana J, Brown M, Narla RK, Barnes L, Schwartz E, Boylan J et al.. (2016) Targeting CD74 with Novel Antibody Drug Conjugates (ADCs) for the Treatment of B-Cell Non-Hodgkin's Lymphoma (NHL). Blood, 128 (22): 464 Meeting poster. DOI: 10.1182/blood.V128.22.464.464

8. Matza D, Wolstein O, Dikstein R, Shachar I. (2001) Invariant chain induces B cell maturation by activating a TAF(II)105-NF-kappaB-dependent transcription program. J Biol Chem, 276 (29): 27203-6. [PMID:11371575]

9. Sapra P, Stein R, Pickett J, Qu Z, Govindan SV, Cardillo TM, Hansen HJ, Horak ID, Griffiths GL, Goldenberg DM. (2005) Anti-CD74 antibody-doxorubicin conjugate, IMMU-110, in a human multiple myeloma xenograft and in monkeys. Clin Cancer Res, 11 (14): 5257-64. [PMID:16033844]

10. Zhao S, Molina A, Yu A, Hanson J, Cheung H, Li X, Natkunam Y. (2019) High frequency of CD74 expression in lymphomas: implications for targeted therapy using a novel anti-CD74-drug conjugate. J Pathol Clin Res, 5 (1): 12-24. [PMID:30191677]

How to cite this page

CD molecules: CD74. Last modified on 13/11/2018. Accessed on 22/06/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2840.