CD74

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)

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											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

Immuno Process:

Barrier integrity

GO Annotations:

Associated to 2 GO processes

GO:0046597	negative regulation of viral entry into host cell	IDA
GO:0046598	positive regulation of viral entry into host cell	IDA

Immuno Process:

Inflammation

GO Annotations:

Associated to 4 GO processes

GO:0002286	T cell activation involved in immune response	IBA
GO:0034341	response to type II interferon	IDA
GO:0043030	regulation of macrophage activation	NAS
GO:0090023	positive regulation of neutrophil chemotaxis	ISS

Immuno Process:

Antigen presentation

GO Annotations:

Associated to 4 GO processes

GO:0019882	antigen processing and presentation	IBA
GO:0019883	antigen processing and presentation of endogenous antigen	NAS
	click arrow to show/hide IEA associations
GO:0002606	positive regulation of dendritic cell antigen processing and presentation	IEA
GO:0019886	antigen processing and presentation of exogenous peptide antigen via MHC class II	IEA

Immuno Process:

T cell (activation)

GO Annotations:

Associated to 7 GO processes

GO:0002286	T cell activation involved in immune response	IBA
GO:0016064	immunoglobulin mediated immune response	ISS
GO:0045058	T cell selection	NAS
	click arrow to show/hide IEA associations
GO:0045059	positive thymic T cell selection	IEA
GO:0045060	negative thymic T cell selection	IEA
GO:0045581	negative regulation of T cell differentiation	IEA
GO:0045582	positive regulation of T cell differentiation	IEA

Immuno Process:

B cell (activation)

GO Annotations:

Associated to 3 GO processes

GO:0016064	immunoglobulin mediated immune response	ISS
GO:0030890	positive regulation of B cell proliferation	IMP
	click arrow to show/hide IEA associations
GO:0002906	negative regulation of mature B cell apoptotic process	IEA

Immuno Process:

Immune regulation

GO Annotations:

Associated to 10 GO processes

GO:0002830	positive regulation of type 2 immune response	IBA
GO:0030890	positive regulation of B cell proliferation	IMP
GO:0043030	regulation of macrophage activation	NAS
GO:0045657	positive regulation of monocyte differentiation	IDA
GO:0060907	positive regulation of macrophage cytokine production	ISS
GO:0090023	positive regulation of neutrophil chemotaxis	ISS
	click arrow to show/hide IEA associations
GO:0002606	positive regulation of dendritic cell antigen processing and presentation	IEA
GO:0002906	negative regulation of mature B cell apoptotic process	IEA
GO:0045581	negative regulation of T cell differentiation	IEA
GO:0045582	positive regulation of T cell differentiation	IEA

Immuno Process:

Immune system development

GO Annotations:

Associated to 6 GO processes

GO:0045058	T cell selection	NAS
GO:0045657	positive regulation of monocyte differentiation	IDA
	click arrow to show/hide IEA associations
GO:0045059	positive thymic T cell selection	IEA
GO:0045060	negative thymic T cell selection	IEA
GO:0045581	negative regulation of T cell differentiation	IEA
GO:0045582	positive regulation of T cell differentiation	IEA

Immuno Process:

Cytokine production & signalling

GO Annotations:

Associated to 10 GO processes

GO:0001961	positive regulation of cytokine-mediated signaling pathway	IMP
GO:0004896	cytokine receptor activity	IDA
GO:0032722	positive regulation of chemokine production	IMP
GO:0032755	positive regulation of interleukin-6 production	IMP
GO:0032757	positive regulation of interleukin-8 production	IMP
GO:0034341	response to type II interferon	IDA
GO:0060907	positive regulation of macrophage cytokine production	ISS
GO:2000343	positive regulation of chemokine (C-X-C motif) ligand 2 production	ISS
GO:2000448	positive regulation of macrophage migration inhibitory factor signaling pathway	IMP
	click arrow to show/hide IEA associations
GO:0035691	macrophage migration inhibitory factor signaling pathway	IEA

Immuno Process:

Chemotaxis & migration

GO Annotations:

Associated to 5 GO processes

GO:0032722	positive regulation of chemokine production	IMP
GO:0090023	positive regulation of neutrophil chemotaxis	ISS
GO:2000343	positive regulation of chemokine (C-X-C motif) ligand 2 production	ISS
	click arrow to show/hide IEA associations
GO:0045581	negative regulation of T cell differentiation	IEA
GO:0045582	positive regulation of T cell differentiation	IEA

Immuno Process:

Cellular signalling

GO Annotations:

Associated to 8 GO processes

GO:0002286	T cell activation involved in immune response	IBA
GO:0030890	positive regulation of B cell proliferation	IMP
GO:0043030	regulation of macrophage activation	NAS
GO:0045058	T cell selection	NAS
	click arrow to show/hide IEA associations
GO:0045059	positive thymic T cell selection	IEA
GO:0045060	negative thymic T cell selection	IEA
GO:0045581	negative regulation of T cell differentiation	IEA
GO:0045582	positive regulation of T cell differentiation	IEA

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 10/06/2023. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=2840.

CD74

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References

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