CD74 CD74 molecule [Homo sapiens (human)] - Gene

Summary

Official Symbol: CD74provided by HGNC
Official Full Name: CD74 moleculeprovided by HGNC
Primary source: HGNC:HGNC:1697
See related: Ensembl:ENSG00000019582 MIM:142790; AllianceGenome:HGNC:1697
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: II; p33; CLIP; DHLAG; HLADG; Ia-GAMMA
Summary: The protein encoded by this gene associates with class II major histocompatibility complex (MHC) and is an important chaperone that regulates antigen presentation for immune response. It also serves as cell surface receptor for the cytokine macrophage migration inhibitory factor (MIF) which, when bound to the encoded protein, initiates survival pathways and cell proliferation. This protein also interacts with amyloid precursor protein (APP) and suppresses the production of amyloid beta (Abeta). Multiple alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Aug 2011]
Expression: Broad expression in spleen (RPKM 1835.3), lymph node (RPKM 1421.7) and 24 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 5q33.1

Exon count:: 9

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	5	NC_000005.10 (150401639..150412910, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	5	NC_060929.1 (150938180..150949451, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	5	NC_000005.9 (149781202..149792473, complement)

Chromosome 5 - NC_000005.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Potential protumor function of CD74 in clear cell renal cell carcinoma.
Title: Potential protumor function of CD74 in clear cell renal cell carcinoma.
Macrophage migration inhibitory factor mediates skin aging via CD74: Insights from single-cell and bulk RNA sequencing data.
Title: Macrophage migration inhibitory factor mediates skin aging via CD74: Insights from single-cell and bulk RNA sequencing data.
CD74 supports accumulation and function of regulatory T cells in tumors.
Title: CD74 supports accumulation and function of regulatory T cells in tumors.
CD74-ROS1 L2026M mutant enhances autophagy through the MEK/ERK pathway to promote invasion, metastasis and crizotinib resistance in non-small cell lung cancer cells.
Title: CD74-ROS1 L2026M mutant enhances autophagy through the MEK/ERK pathway to promote invasion, metastasis and crizotinib resistance in non-small cell lung cancer cells.
Increased Expression of CD74 in Atherosclerosis Associated with Inflammatory Responses of Endothelial Cells and Macrophages.
Title: Increased Expression of CD74 in Atherosclerosis Associated with Inflammatory Responses of Endothelial Cells and Macrophages.
CD74 is associated with inflamed tumor immune microenvironment and predicts responsiveness to PD-1/CTLA-4 bispecific antibody in patients with solid tumors.
Title: CD74 is associated with inflamed tumor immune microenvironment and predicts responsiveness to PD-1/CTLA-4 bispecific antibody in patients with solid tumors.
Macrophage migration inhibitory factor receptor CD74 expression is associated with expansion and differentiation of effector T cells in COVID-19 patients.
Title: Macrophage migration inhibitory factor receptor CD74 expression is associated with expansion and differentiation of effector T cells in COVID-19 patients.
CD74 deficiency reduces trophoblast invasion and proliferation mediated by SIRT1 in preeclampsia.
Title: CD74 deficiency reduces trophoblast invasion and proliferation mediated by SIRT1 in preeclampsia.
CD74 Promotes a Pro-Inflammatory Tumor Microenvironment by Inducing S100A8 and S100A9 Secretion in Pancreatic Cancer.
Title: CD74 Promotes a Pro-Inflammatory Tumor Microenvironment by Inducing S100A8 and S100A9 Secretion in Pancreatic Cancer.
The invariant chain CD74 protein is a cell surface binding partner of TIMP-1 in breast cancer cells.
Title: The invariant chain CD74 protein is a cell surface binding partner of TIMP-1 in breast cancer cells.

Submit: New GeneRIF Correction See all GeneRIFs (136)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope transmembrane glycoprotein gp41	env	HIV-1 gp41 is able to activate the ERK/MAPK pathway by binding to CD74	PubMed
	env	HIV-1 gp41 directly interacts with CD74 in HIV-1 infected cells. The loop region (residues 590-624) of gp41 is required to interact with CD74 extracellular domain (residues 72-232)	PubMed
Nef	nef	HIV-1 Nef cloned from subjects with early/acute progressive HIV infection upregulates CD74 (Ii) in 721.221 cells to a greater extent relative to HIV-1 Nef cloned from subjects with chronic progressive infection	PubMed
	nef	HIV-1 group N and group O Nef alleles upregulate surface expression of invariant chain (Ii) associated with immature major histocompatibility complex (MHC) class II	PubMed
	nef	Upregulation of Ii expression by Nef at the cell surface impairs mature MHC class II antigen presentation	PubMed
	nef	HIV-1 Nef clones, isolated from plasma of elite controllers (EC) and chronic progressors (CP), show significantly lower HLA class II invariant chain (CD74) upregulation activity in EC than that in CP	PubMed
	nef	Two primary Nef alleles from HIV-1 subtype C and F impair for the MHC-II-associated chaperone invariant chain (Ii) upregulation	PubMed
	nef	Nef-mediated Ii upregulation depends on the AP-2 mu2 expression pathway	PubMed
	nef	LL164 and DD174 motifs in HIV-1 Nef and the Ii cytoplasmic tail (amino acids 1-17) are required for the Nef-mediated upregulation of Ii by slowing the rate of Ii internalization	PubMed
	nef	Substitution of HIV-1 Nef acidic residue E160 with uncharged residues impairs the ability of Nef to upregulate the expression of DC-SIGN and the invariant chain of MHC class II at the cell surface	PubMed
	nef	HIV-1 Nef induces drastic and moderate downregulation of CD4 and MHC-I in resting CD4(+) T lymphocytes, respectively, but markedly upregulates cell surface levels of the MHC-II invariant chain CD74	PubMed
Vpu	vpu	HIV-1 Vpu interacts with CD74 and modulates MHC II in HIV-1-infected cells. The N-terminal 30 amino acids of CD74 are required for the interaction of CD74 with Vpu	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D5S2405 (e-PCR)
- UniSTS:30767

RH11594 (e-PCR)
- UniSTS:44115

RH11625 (e-PCR)
- UniSTS:65644

PMC316580P4 (e-PCR)
- UniSTS:273011

RH46360 (e-PCR)
- UniSTS:78565

RH93024 (e-PCR)
- UniSTS:86264

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables CD4 receptor binding	IPI Inferred from Physical Interaction more info	PubMed
enables MHC class II protein binding	IBA Inferred from Biological aspect of Ancestor more info
enables MHC class II protein binding	ISS Inferred from Sequence or Structural Similarity more info
enables MHC class II protein binding	NAS Non-traceable Author Statement more info	PubMed
enables MHC class II protein binding, via antigen binding groove	IDA Inferred from Direct Assay more info	PubMed
enables MHC class II protein complex binding	IDA Inferred from Direct Assay more info	PubMed
enables amyloid-beta binding	IPI Inferred from Physical Interaction more info	PubMed
enables cytokine binding	IPI Inferred from Physical Interaction more info	PubMed
enables cytokine receptor activity	IBA Inferred from Biological aspect of Ancestor more info
enables cytokine receptor activity	IDA Inferred from Direct Assay more info	PubMed
enables identical protein binding	TAS Traceable Author Statement more info	PubMed
enables macrophage migration inhibitory factor binding	IBA Inferred from Biological aspect of Ancestor more info
enables macrophage migration inhibitory factor binding	IPI Inferred from Physical Interaction more info	PubMed
enables nitric-oxide synthase binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein folding chaperone	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in T cell activation involved in immune response	IBA Inferred from Biological aspect of Ancestor more info
involved_in T cell selection	NAS Non-traceable Author Statement more info	PubMed
involved_in antigen processing and presentation	IBA Inferred from Biological aspect of Ancestor more info
involved_in antigen processing and presentation of endogenous antigen	NAS Non-traceable Author Statement more info	PubMed
involved_in antigen processing and presentation of exogenous peptide antigen via MHC class II	IEA Inferred from Electronic Annotation more info
involved_in chaperone cofactor-dependent protein refolding	IEA Inferred from Electronic Annotation more info
involved_in immunoglobulin mediated immune response	ISS Inferred from Sequence or Structural Similarity more info
involved_in intracellular protein transport	ISS Inferred from Sequence or Structural Similarity more info
involved_in macrophage migration inhibitory factor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of DNA damage response, signal transduction by p53 class mediator	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of DNA damage response, signal transduction by p53 class mediator	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of T cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of apoptotic process	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of cell migration	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of mature B cell apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of peptide secretion	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of viral entry into host cell	IDA Inferred from Direct Assay more info	PubMed
involved_in negative thymic T cell selection	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of B cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of DNA-templated transcription	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of ERK1 and ERK2 cascade	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of ERK1 and ERK2 cascade	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of ERK1 and ERK2 cascade	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of MAPK cascade	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of T cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of canonical NF-kappaB signal transduction	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of chemokine (C-X-C motif) ligand 2 production	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of chemokine production	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of cytokine-mediated signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of cytokine-mediated signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of dendritic cell antigen processing and presentation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of fibroblast proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of gene expression	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of interleukin-6 production	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of interleukin-8 production	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of kinase activity	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of macrophage cytokine production	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of macrophage cytokine production	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of macrophage migration inhibitory factor signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of monocyte differentiation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of neutrophil chemotaxis	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of prostaglandin biosynthetic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of protein phosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of type 2 immune response	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of viral entry into host cell	IDA Inferred from Direct Assay more info	PubMed
involved_in positive thymic T cell selection	IEA Inferred from Electronic Annotation more info
involved_in prostaglandin biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
involved_in protein stabilization	ISS Inferred from Sequence or Structural Similarity more info
involved_in protein trimerization	IEA Inferred from Electronic Annotation more info
involved_in protein-containing complex assembly	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of macrophage activation	NAS Non-traceable Author Statement more info	PubMed
involved_in response to type II interferon	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
located_in ER to Golgi transport vesicle membrane	TAS Traceable Author Statement more info
located_in Golgi membrane	TAS Traceable Author Statement more info
part_of MHC class II protein complex	ISS Inferred from Sequence or Structural Similarity more info
part_of NOS2-CD74 complex	IEA Inferred from Electronic Annotation more info
is_active_in cell surface	IBA Inferred from Biological aspect of Ancestor more info
located_in cell surface	IDA Inferred from Direct Assay more info	PubMed
located_in clathrin-coated endocytic vesicle membrane	TAS Traceable Author Statement more info
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in endocytic vesicle membrane	TAS Traceable Author Statement more info
located_in external side of plasma membrane	IEA Inferred from Electronic Annotation more info
located_in extracellular exosome	HDA more info	PubMed
located_in late endosome	ISS Inferred from Sequence or Structural Similarity more info
located_in lumenal side of endoplasmic reticulum membrane	TAS Traceable Author Statement more info
located_in lysosomal lumen	TAS Traceable Author Statement more info
located_in lysosomal membrane	TAS Traceable Author Statement more info
located_in lysosome	ISS Inferred from Sequence or Structural Similarity more info
part_of macrophage migration inhibitory factor receptor complex	IDA Inferred from Direct Assay more info	PubMed
located_in membrane	HDA more info	PubMed
located_in membrane	IDA Inferred from Direct Assay more info	PubMed
located_in multivesicular body	IEA Inferred from Electronic Annotation more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info
part_of protein-containing complex	IDA Inferred from Direct Assay more info	PubMed
located_in trans-Golgi network membrane	TAS Traceable Author Statement more info
located_in transport vesicle membrane	TAS Traceable Author Statement more info
located_in vacuole	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: HLA class II histocompatibility antigen gamma chain

Names: CD74 antigen (invariant polypeptide of major histocompatibility complex, class II antigen-associated); CD74 molecule, major histocompatibility complex, class II invariant chain; HLA-DR antigens-associated invariant chain; HLA-DR-gamma; Ia-associated invariant chain; MHC HLA-DR gamma chain; class II MHC-associated invariant chain peptide; gamma chain of class II antigens

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_029730.1 RefSeqGene

Range

5027..16298

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001025158.3 → NP_001020329.1 HLA class II histocompatibility antigen gamma chain isoform c

See identical proteins and their annotated locations for NP_001020329.1

Status: REVIEWED

Source sequence(s)

AC011372, AC011388

Consensus CDS

CCDS34276.1

UniProtKB/TrEMBL

H0YBZ8

Related

ENSP00000367026.3, ENST00000377795.7

Conserved Domains (1) summary

pfam09307
Location:17 → 128

MHC2-interact; CLIP, MHC2 interacting
NM_001025159.3 → NP_001020330.1 HLA class II histocompatibility antigen gamma chain isoform a

See identical proteins and their annotated locations for NP_001020330.1

Status: REVIEWED

Source sequence(s)

AC011372, AC011388

Consensus CDS

CCDS47309.1

UniProtKB/Swiss-Prot

A8K7R1, B4DNE8, D3DQG3, D3DQG4, P04233, Q14597, Q29832, Q5U0J8, Q8SNA0, Q8WLP6

Related

ENSP00000009530.7, ENST00000009530.13

Conserved Domains (3) summary

cd00191
Location:212 → 271

TY; Thyroglobulin type I repeats.; The N-terminal region of human thyroglobulin contains 11 type-1 repeats TY repeats are proposed to be inhibitors of cysteine proteases

pfam08831
Location:136 → 204

MHCassoc_trimer; Class II MHC-associated invariant chain trimerization domain

pfam09307
Location:17 → 128

MHC2-interact; CLIP, MHC2 interacting
NM_001364083.3 → NP_001351012.1 HLA class II histocompatibility antigen gamma chain isoform d

Status: REVIEWED

Source sequence(s)

AC011372, AC011388

Conserved Domains (2) summary

pfam08831
Location:127 → 183

MHCassoc_trimer; Class II MHC-associated invariant chain trimerisation domain

pfam09307
Location:17 → 126

MHC2-interact; CLIP, MHC2 interacting
NM_001364084.3 → NP_001351013.1 HLA class II histocompatibility antigen gamma chain isoform e

Status: REVIEWED

Source sequence(s)

AC011372, AC011388

Conserved Domains (2) summary

pfam08831
Location:136 → 184

MHCassoc_trimer; Class II MHC-associated invariant chain trimerisation domain

pfam09307
Location:17 → 128

MHC2-interact; CLIP, MHC2 interacting
NM_004355.4 → NP_004346.1 HLA class II histocompatibility antigen gamma chain isoform b

See identical proteins and their annotated locations for NP_004346.1

Status: REVIEWED

Source sequence(s)

AC011372, AC011388

Consensus CDS

CCDS47308.1

UniProtKB/Swiss-Prot

P04233

Related

ENSP00000230685.6, ENST00000353334.11

Conserved Domains (2) summary

pfam08831
Location:136 → 204

MHCassoc_trimer; Class II MHC-associated invariant chain trimerisation domain

pfam09307
Location:17 → 128

MHC2-interact; CLIP, MHC2 interacting