CD74 CD74 molecule, major histocompatibility complex, class II invariant chain [Homo sapiens] - Gene

Help top of page

Summary

Official Symbol: CD74provided by HGNC
Official Full Name: CD74 molecule, major histocompatibility complex, class II invariant chainprovided by HGNC
Primary source: HGNC:1697
See related: Ensembl:ENSG00000019582; HPRD:00825; MIM:142790; Vega:OTTHUMG00000163559
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; DHLAG; HLADG; Ia-GAMMA; FLJ98970
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]

Help top of page

Genomic context

Location :: 5q32

Sequence :: Chromosome: 5; NC_000005.9 (149781200..149792332, complement)

See CD74 in Epigenomics, MapViewer

Chromosome 5 - NC_000005.9 Genomic Context describing neighboring genes

Help top of page

Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

Help top of page

Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

This is the first study reporting that Ii chain up-regulation occurs on naturally infected antigen presenting cells obtained directly from HIV(+) subjects.
Title: HIV-mediated up-regulation of invariant chain (CD74) correlates with generalized immune activation in HIV+ subjects.
Epstein-Barr virus evades CD4+ T cell responses in lytic cycle through BZLF1-mediated downregulation of CD74 and the cooperation of vBcl-2.
Title: Epstein-Barr virus evades CD4+ T cell responses in lytic cycle through BZLF1-mediated downregulation of CD74 and the cooperation of vBcl-2.
These results suggest that cancer cells in the PNI areas could acquired a growth advantage that could be triggered by the growth factor receptors EGFR and CD74.
Title: Biological significance of perineural invasion (PNI) in prostate cancer.
Class I homozygosity at 5'VNTR is a significant risk factor of T1DM and acts independently from HLA haplotype in determining the actual risk of diabetes in children.
Title: Increased risk of type 1 diabetes in Polish children - association with INS-IGF2 5'VNTR and lack of association with HLA haplotype.
Data show that FTY720-mediated disruption of the autophagic-lysosomal pathway led to increased levels of CD74, a potential therapeutic target in mantle cell lymphoma (MCL) that is degraded in the lysosomal compartment.
Title: FTY720 increases CD74 expression and sensitizes mantle cell lymphoma cells to milatuzumab-mediated cell death.
overexpression of MIF and CD74 in cervical squamous cell carcinomas and its precancerous lesions and upregulation of VEGF secretion in cervical cancer cells indicate MIF and CD74 may play critical roles in pathogenesis and angiogenesis of cervical cancer
Title: Expression of macrophage migration inhibitory factor and CD74 in cervical squamous cell carcinoma.
HIV-1 glycoprotein 41 ectodomain induces activation of the CD74 protein-mediated extracellular signal-regulated kinase/mitogen-activated protein kinase pathway to enhance viral infection.
Title: HIV-1 glycoprotein 41 ectodomain induces activation of the CD74 protein-mediated extracellular signal-regulated kinase/mitogen-activated protein kinase pathway to enhance viral infection.
Studies indicate that in chronic lymphocytic leukemia cells, binding of MIF to CD74 induces nuclear factor-kappaB activation and up-regulation of TAp63 expression, resulting in the secretion of interleukin 8, which in turn promotes cell survival.
Title: The secret second life of an innocent chaperone: the story of CD74 and B cell/chronic lymphocytic leukemia cell survival.
Synergistic TLR agonist stimulation in combination with IFN-alpha and IFN-gamma was the best method for regulating CD38 and CD74 expression
Title: Type I and II interferons enhance dendritic cell maturation and migration capacity by regulating CD38 and CD74 that have synergistic effects with TLR agonists.
CatG was found to be dispensable in invariant chain conversion within intact primary human B cells and dendritic cells.
Title: Invariant chain processing is independent of cathepsin variation between primary human B cells/dendritic cells and B-lymphoblastoid cells.

Submit: New GeneRIF Correction See all (44)

Help top of page

Phenotypes

Review eQTL and phenotype association data in this region using PheGenI

Help top of page

HIV-1 protein interactions

Protein	Gene	Interaction	Pubs
Nef	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
	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 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

Go to the HIV-1, Human Protein Interaction Database

Help top of page

Products	Interactant	Other Gene	Source	Pubs	Description
NP_004346.1	NP_002406.1	MIF	BIND	PubMed	MIF interacts with CD74
P04233	P15813	CD1D	HPRD	PubMed
P04233	P16070	CD44	HPRD	PubMed
P04233	P04233	CD74	HPRD	PubMed
P04233	Q9UBX1	CTSF	HPRD	PubMed
P04233	P07711	CTSL1	HPRD	PubMed
P04233	P28067	HLA-DMA	HPRD	PubMed
P04233	P28068	HLA-DMB	HPRD	PubMed
P04233	P20036	HLA-DPA1	HPRD	PubMed
P04233	P04440	HLA-DPB1	HPRD	PubMed
P04233	P01909	HLA-DQA1	HPRD	PubMed
P04233	P01918	HLA-DQB1	HPRD	PubMed
P04233	P01903	HLA-DRA	HPRD	PubMed
P04233	P14174	MIF	HPRD	PubMed
BioGRID:107410	BioGRID:107410	CD74	BioGRID	PubMed	Co-purification
BioGRID:107410	BioGRID:110428	MIF	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:107410	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS; Affinity Capture-Western

Function	Evidence Code	Pubs
MHC class II protein binding	ISS Inferred from Sequence or Structural Similarity more info
MHC class II protein binding	NAS Non-traceable Author Statement more info	PubMed
beta-amyloid binding	IPI Inferred from Physical Interaction more info	PubMed
cytokine binding	IPI Inferred from Physical Interaction more info	PubMed
cytokine receptor activity	IDA Inferred from Direct Assay more info	PubMed
identical protein binding	TAS Traceable Author Statement more info	PubMed
nitric-oxide synthase binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
T cell selection	NAS Non-traceable Author Statement more info	PubMed
activation of MAPK activity	IEA Inferred from Electronic Annotation more info
antigen processing and presentation of endogenous antigen	NAS Non-traceable Author Statement more info	PubMed
antigen processing and presentation of exogenous peptide antigen via MHC class II	IEA Inferred from Electronic Annotation more info
cell proliferation	IDA Inferred from Direct Assay more info	PubMed
chaperone mediated protein folding requiring cofactor	IEA Inferred from Electronic Annotation more info
cytokine-mediated signaling pathway	IDA Inferred from Direct Assay more info	PubMed
defense response	IEA Inferred from Electronic Annotation more info
immune response	IEA Inferred from Electronic Annotation more info
immunoglobulin mediated immune response	ISS Inferred from Sequence or Structural Similarity more info
intracellular protein transport	ISS Inferred from Sequence or Structural Similarity more info
macrophage migration inhibitory factor signaling pathway	IEA Inferred from Electronic Annotation more info
negative regulation of DNA damage response, signal transduction by p53 class mediator	IDA Inferred from Direct Assay more info	PubMed
negative regulation of T cell differentiation	IEA Inferred from Electronic Annotation more info
negative regulation of apoptotic process	IDA Inferred from Direct Assay more info	PubMed
negative regulation of apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of mature B cell apoptosis	IEA Inferred from Electronic Annotation more info
negative regulation of peptide secretion	IDA Inferred from Direct Assay more info	PubMed
negative thymic T cell selection	IEA Inferred from Electronic Annotation more info
positive regulation of B cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of ERK1 and ERK2 cascade	IDA Inferred from Direct Assay more info	PubMed
positive regulation of ERK1 and ERK2 cascade	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of T cell differentiation	IEA Inferred from Electronic Annotation more info
positive regulation of chemokine (C-X-C motif) ligand 2 production	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of cytokine-mediated signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of dendritic cell antigen processing and presentation	IEA Inferred from Electronic Annotation more info
positive regulation of fibroblast proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of macrophage cytokine production	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of neutrophil chemotaxis	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of peptidyl-tyrosine phosphorylation	IDA Inferred from Direct Assay more info	PubMed
positive regulation of type 2 immune response	IEA Inferred from Electronic Annotation more info
positive thymic T cell selection	IEA Inferred from Electronic Annotation more info
prostaglandin biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
protein complex assembly	ISS Inferred from Sequence or Structural Similarity more info
regulation of macrophage activation	NAS Non-traceable Author Statement more info	PubMed
signal transduction	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
Golgi apparatus	IEA Inferred from Electronic Annotation more info
colocalizes_with MHC class II protein complex	ISS Inferred from Sequence or Structural Similarity more info
NOS2-CD74 complex	IEA Inferred from Electronic Annotation more info
cell surface	IDA Inferred from Direct Assay more info	PubMed
endoplasmic reticulum	IEA Inferred from Electronic Annotation more info
endoplasmic reticulum membrane	IEA Inferred from Electronic Annotation more info
external side of plasma membrane	IEA Inferred from Electronic Annotation more info
integral to membrane	IDA Inferred from Direct Assay more info	PubMed
intracellular	ISS Inferred from Sequence or Structural Similarity more info
intracellular	TAS Traceable Author Statement more info	PubMed
lysosome	IEA Inferred from Electronic Annotation more info
macrophage migration inhibitory factor receptor complex	IEA Inferred from Electronic Annotation more info
multivesicular body	IEA Inferred from Electronic Annotation more info
plasma membrane	IEA Inferred from Electronic Annotation more info
receptor complex	IDA Inferred from Direct Assay more info	PubMed
vacuole	IDA Inferred from Direct Assay more info	PubMed

General protein information

Preferred Names: HLA class II histocompatibility antigen gamma chain

Names: HLA class II histocompatibility antigen gamma chain; p33; HLA-DR-gamma; MHC HLA-DR gamma chain; Ia-associated invariant chain; gamma chain of class II antigens; HLA-DR antigens-associated invariant chain; CD74 antigen (invariant polypeptide of major histocompatibility complex, class II antigen-associated)

Help top of page

NCBI Reference Sequences (RefSeq)

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

5001..16300

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001025158.2 → NP_001020329.1 HLA class II histocompatibility antigen gamma chain isoform c

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks three consecutive exons in the 3' coding region, which results in a frame-shift, compared to variant 1. The resulting isoform (c) has a shorter and distinct C-terminus, compared to isoform a.

Source sequence(s)

BC024272, DC354760

Consensus CDS

CCDS34276.1

UniProtKB/Swiss-Prot

P04233

Related

ENSP00000367026, OTTHUMP00000224284, ENST00000377795, OTTHUMT00000374177

Conserved Domains (1) summary

pfam09307
Location:17 – 129
Blast Score: 311

MHC2-interact; CLIP, MHC2 interacting
NM_001025159.2 → NP_001020330.1 HLA class II histocompatibility antigen gamma chain isoform a

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longest isoform (a).

Source sequence(s)

AK297889, BC024272, DC354760

Consensus CDS

CCDS47309.1

UniProtKB/Swiss-Prot

P04233

Related

ENSP00000009530, OTTHUMP00000224285, ENST00000009530, OTTHUMT00000374178

Conserved Domains (3) summary

cd00191
Location:212 – 271
Blast Score: 182

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 – 207
Blast Score: 330

MHCassoc_trimer; Class II MHC-associated invariant chain trimerisation domain

pfam09307
Location:17 – 129
Blast Score: 341

MHC2-interact; CLIP, MHC2 interacting
NM_004355.3 → NP_004346.1 HLA class II histocompatibility antigen gamma chain isoform b

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an in-frame exon in the 3' coding region, compared to variant 1. The resulting isoform (b) lacks an internal segment in the C-terminal region, compared to isoform a.

Source sequence(s)

BC018726, BC024272, DC354760

Consensus CDS

CCDS47308.1

UniProtKB/Swiss-Prot

P04233

Related

ENSP00000230685, OTTHUMP00000224283, ENST00000353334, OTTHUMT00000374176

Conserved Domains (2) summary

pfam08831
Location:136 – 207
Blast Score: 312

MHCassoc_trimer; Class II MHC-associated invariant chain trimerisation domain

pfam09307
Location:17 – 129
Blast Score: 316

MHC2-interact; CLIP, MHC2 interacting

RefSeqs of Annotated Genomes: Build 37.3

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000005.9 Reference GRCh37.p5 Primary Assembly

Range

149781200..149792332, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000137.1 Alternate HuRef

Range

144928781..144939913, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Help top of page

Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AC011372.7 (183267..183329)	None
genomic	AC011388.7 (46524..57593)	None
genomic	CH471062.2	EAW61727.1
		EAW61728.1
		EAW61729.1
		EAW61730.1
		EAW61731.1
genomic	M13560.1	AAA36033.1
genomic	X03339.1	CAA27046.1
genomic	X03340.1	CAA27047.1
mRNA	AK292076.1	BAF84765.1
mRNA	AK297889.1	BAG60210.1
mRNA	AK300669.1	BAG62354.1
mRNA	AK308929.1	None
mRNA	BC018726.1	AAH18726.1
mRNA	BC024272.1	AAH24272.1
mRNA	BF796148.1	None
mRNA	BT019505.1	AAV38312.1
mRNA	DC354760.1	None
mRNA	K01144.1	AAA36304.1
mRNA	M28588.1	AAA58655.1
mRNA	M28590.1	AAA35996.1
mRNA	X00497.1	CAA25192.1
		CAA25193.1
other-genetic	DQ892005.2	ABM82931.1
other-genetic	DQ895194.2	ABM86120.1

Protein Accession	Links
Protein Accession	GenPept Link	UniProtKB Link
O19685	GenPept	UniProtKB/TrEMBL:O19685
O78208	GenPept	UniProtKB/TrEMBL:O78208
P04233.3	GenPept	UniProtKB/Swiss-Prot:P04233