CD74

Immunopharmacology Ligand Target has curated data in GtoImmuPdb

Target id: 2840

Nomenclature: CD74

Gene and Protein Information
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
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

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
Alphafold	P04233 (Hs), P04441 (Mm), P10247 (Rn)
CATH/Gene3D	1.10.870.10, 4.10.800.10
ChEMBL Target	CHEMBL4692 (Hs)
Ensembl Gene	ENSG00000019582 (Hs), ENSMUSG00000024610 (Mm), ENSRNOG00000018735 (Rn)
Entrez Gene	972 (Hs), 16149 (Mm), 25599 (Rn)
Human Protein Atlas	ENSG00000019582 (Hs)
KEGG Gene	hsa:972 (Hs), mmu:16149 (Mm), rno:25599 (Rn)
OMIM	142790 (Hs)
Pharos	P04233 (Hs)
RefSeq Nucleotide	NM_001025159 (Hs), NM_001042605 (Mm)
RefSeq Protein	NP_001020330 (Hs), NP_001036070 (Mm)
UniProtKB	P04233 (Hs), P04441 (Mm), P10247 (Rn)
Wikipedia	CD74 (Hs)

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Antibodies

Key to terms and symbols

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Antibody											Sp.	Action	Value	Parameter	Reference
milatuzumab											Hs	Binding	9.3	pK_d	9
⤷	pK_d 9.3 (K_d 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].

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

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Immune system development

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Cytokine production & signalling

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Chemotaxis & migration

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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]