CD74 Gene (Protein Coding)

CD74 Molecule

GC05M150378
GIFtS:
43
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. ... See more...

Aliases for CD74 Gene

Aliases for CD74 Gene

  • CD74 Molecule 2 3 5
  • CD74 Antigen (Invariant Polypeptide Of Major Histocompatibility Complex, Class II Antigen-Associated) 2 3
  • CD74 Molecule, Major Histocompatibility Complex, Class II Invariant Chain 2 3
  • HLA Class II Histocompatibility Antigen Gamma Chain 3 4
  • HLA-DR Antigens-Associated Invariant Chain 3 4
  • Gamma Chain Of Class II Antigens 2 3
  • Ia-Associated Invariant Chain 2 3
  • MHC HLA-DR Gamma Chain 2 3
  • HLA-DR-Gamma 2 3
  • DHLAG 3 4
  • P33 3 4
  • Ia Antigen-Associated Invariant Chain 4
  • CD74 Antigen 4
  • Ia-GAMMA 3
  • HLADG 3
  • CD74 5
  • II 3
  • Ii 4

External Ids for CD74 Gene

Previous HGNC Symbols for CD74 Gene

  • DHLAG

Previous GeneCards Identifiers for CD74 Gene

  • GC05M149850
  • GC05M149764
  • GC05M149809
  • GC05M149753
  • GC05M144928

Summaries for CD74 Gene

Entrez Gene Summary for CD74 Gene

  • 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]

GeneCards Summary for CD74 Gene

CD74 (CD74 Molecule) is a Protein Coding gene. Diseases associated with CD74 include Mucinous Lung Adenocarcinoma and Lung Cancer Susceptibility 3. Among its related pathways are Tuberculosis and Cell surface interactions at the vascular wall. Gene Ontology (GO) annotations related to this gene include identical protein binding and amyloid-beta binding.

UniProtKB/Swiss-Prot Summary for CD74 Gene

  • Plays a critical role in MHC class II antigen processing by stabilizing peptide-free class II alpha/beta heterodimers in a complex soon after their synthesis and directing transport of the complex from the endoplasmic reticulum to the endosomal/lysosomal system where the antigen processing and binding of antigenic peptides to MHC class II takes place. Serves as cell surface receptor for the cytokine MIF.
  • [Class-II-associated invariant chain peptide]: Binds to the peptide-binding site of MHC class II alpha/beta heterodimers forming an alpha-beta-CLIP complex, thereby preventing the loading of antigenic peptides to the MHC class II complex until its release by HLA-DM in the endosome.

Gene Wiki entry for CD74 Gene

Additional gene information for CD74 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for CD74 Gene

Genomics for CD74 Gene

GeneHancer (GH) Regulatory Elements Pubs

Download GeneHancer 2017 data
Promoters and enhancers for CD74 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around CD74 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for CD74

Top Transcription factor binding sites by QIAGEN in the CD74 gene promoter:
  • AP-2gamma
  • NF-kappaB1
  • Pax-6

Genomic Locations for CD74 Gene

Genomic Locations for CD74 Gene
chr5:150,400,041-150,412,936
(GRCh38/hg38)
Size:
12,896 bases
Orientation:
Minus strand
chr5:149,781,200-149,792,492
(GRCh37/hg19)
Size:
11,293 bases
Orientation:
Minus strand

Genomic View for CD74 Gene

Genes around CD74 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
CD74 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for CD74 Gene
GeneLoc Logo Genomic Neighborhood • Exon Structure • Gene Density

RefSeq DNA sequence for CD74 Gene

Proteins for CD74 Gene

Products:

  1. Antibody
  2. Protein
  3. Assay

  • Protein details for CD74 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P04233-HG2A_HUMAN
    Recommended name:
    HLA class II histocompatibility antigen gamma chain
    Protein Accession:
    P04233
    Secondary Accessions:
    • A8K7R1
    • B4DNE8
    • D3DQG3
    • D3DQG4
    • Q14597
    • Q29832
    • Q5U0J8
    • Q8SNA0
    • Q8WLP6

    Protein attributes for CD74 Gene

    Size:
    296 amino acids
    Molecular mass:
    33516 Da
    Quaternary structure:
    • Homotrimer. In the endoplasmic reticulum (ER) it forms a heterononameric MHC II-Ii complex: 3 MHC class II molecules (heterodimers of an alpha and a beta subunit) bind to the CD74 homotrimer (also known as invariant chain or HLA class II histocompatibility antigen gamma chain). In the endosomal/lysosomal system, the CD74 component undergoes sequential degradation by various proteases, including CTSS and CTSL, leaving a small fragment termed CLIP (class-II-associated invariant chain peptide) attached to the MHC class II molecule (alpha-beta-CLIP complex). This processed complex interacts with HLA_DM and HLA_DO heterodimers in order to release CLIP and facilitate the binding of antigenic peptides to the MHC class II molecules. Interacts with CD44; this complex is essential for the MIF-induced signaling cascade that results in B cell survival.
    SequenceCaution:
    • Sequence=AAA36304.1; Type=Erroneous initiation; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for CD74 Gene

    Alternative splice isoforms for CD74 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for CD74 Gene

Protein Expression for CD74 Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

Post-translational modifications for CD74 Gene

  • N- and O-glycosylated. O-glycosylated with core 1 or possibly core 8 glycans.
  • Glycosylation at Asn130, Asn136, Ser197, Thr203, Ser281, and Asn256
  • Ubiquitination at Lys159 and Lys170
  • Modification sites at PhosphoSitePlus
  • Glycosylation from GlyConnect
    • HG2A_HUMAN (659)

Other Protein References for CD74 Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

  • Abcam antibodies for CD74

No data available for DME Specific Peptides for CD74 Gene

Domains & Families for CD74 Gene

Gene Families for CD74 Gene

HGNC:
Human Protein Atlas (HPA):
  • Cancer-related genes
  • CD markers
  • Disease related genes
  • Predicted membrane proteins

Protein Domains for CD74 Gene

InterPro:
Blocks:
  • Thyroglobulin type-1
ProtoNet:

Suggested Antigen Peptide Sequences for CD74 Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ54063, highly similar to Homo sapiens CD74 antigen, transcript variant 2, mRNA (B4DUJ2_HUMAN)
  • p33 (HG2A_HUMAN)
genes like me logo Genes that share domains with CD74: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for CD74 Gene

Function for CD74 Gene

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  2. CRISPR
  3. miRNA
  4. Inhibitory RNA
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  6. Cell Line

Molecular function for CD74 Gene

UniProtKB/Swiss-Prot Function:
Plays a critical role in MHC class II antigen processing by stabilizing peptide-free class II alpha/beta heterodimers in a complex soon after their synthesis and directing transport of the complex from the endoplasmic reticulum to the endosomal/lysosomal system where the antigen processing and binding of antigenic peptides to MHC class II takes place. Serves as cell surface receptor for the cytokine MIF.
UniProtKB/Swiss-Prot Function:
[Class-II-associated invariant chain peptide]: Binds to the peptide-binding site of MHC class II alpha/beta heterodimers forming an alpha-beta-CLIP complex, thereby preventing the loading of antigenic peptides to the MHC class II complex until its release by HLA-DM in the endosome.
GENATLAS Biochemistry:
cell differentiation antigen CD74,MHC class II associated invariant chain,identified by monoclonal antibodies LN2,BU-43,BU-45,chain Ii,31kDa

Phenotypes From GWAS Catalog for CD74 Gene

Gene Ontology (GO) - Molecular Function for CD74 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001540 amyloid-beta binding IPI 19849849
GO:0004896 cytokine receptor activity IDA 17045821
GO:0005515 protein binding IPI 17357109
GO:0019955 cytokine binding IPI 17567581
GO:0023026 MHC class II protein complex binding IDA 1448172
genes like me logo Genes that share ontologies with CD74: view
genes like me logo Genes that share phenotypes with CD74: view

Animal Models for CD74 Gene

MGI Knock Outs for CD74:

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for CD74

Clone Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , miRNA , Transcription Factor Targets and HOMER Transcription for CD74 Gene

Localization for CD74 Gene

Subcellular locations from UniProtKB/Swiss-Prot for CD74 Gene

Cell membrane. Single-pass type II membrane protein. Endoplasmic reticulum membrane. Golgi apparatus, trans-Golgi network. Endosome. Lysosome. Note=Transits through a number of intracellular compartments in the endocytic pathway. It can either undergo proteolysis or reach the cell membrane.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for CD74 gene
Compartment Confidence
plasma membrane 5
nucleus 5
endoplasmic reticulum 5
endosome 5
lysosome 5
golgi apparatus 5
extracellular 4
cytoskeleton 4
mitochondrion 2
cytosol 2
peroxisome 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Golgi apparatus (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for CD74 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000139 Golgi membrane TAS --
GO:0005634 nucleus IDA 19423618
GO:0005737 cytoplasm IDA 22952837
GO:0005764 lysosome IEA --
GO:0005765 lysosomal membrane TAS --
genes like me logo Genes that share ontologies with CD74: view

Pathways & Interactions for CD74 Gene

genes like me logo Genes that share pathways with CD74: view

Pathways by source for CD74 Gene

2 GeneGo (Thomson Reuters) pathways for CD74 Gene
  • Immune response Antigen presentation by MHC class II
  • Immune response MIF-mediated glucocorticoid regulation
1 Cell Signaling Technology pathway for CD74 Gene

SIGNOR curated interactions for CD74 Gene

Activates:
Is activated by:

Gene Ontology (GO) - Biological Process for CD74 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000187 activation of MAPK activity IEA --
GO:0001516 prostaglandin biosynthetic process IDA 12782713
GO:0001934 positive regulation of protein phosphorylation IDA 24942581
GO:0001961 positive regulation of cytokine-mediated signaling pathway IMP 12782713
GO:0002250 adaptive immune response IEA --
genes like me logo Genes that share ontologies with CD74: view

Drugs & Compounds for CD74 Gene

Products:

  1. Drug

(1) Drugs for CD74 Gene - From: DGIdb

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
milatuzumab Investigational Pharma antibody Therapeutic Antibodies 0
genes like me logo Genes that share compounds with CD74: view

Transcripts for CD74 Gene

Products:

  1. CRISPR
  2. miRNA
  3. Inhibitory RNA
  4. Clone

mRNA/cDNA for CD74 Gene

5 REFSEQ mRNAs :
14 NCBI additional mRNA sequence :
12 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for CD74

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for CD74 Gene

ExUns: 1a · 1b · 1c · 1d ^ 2a · 2b ^ 3a · 3b ^ 4a · 4b · 4c ^ 5 ^ 6a · 6b ^ 7a · 7b ^ 8 ^ 9 ^ 10a · 10b · 10c ^ 11a · 11b · 11c ^ 12a · 12b
SP1: - - - - - - - -
SP2: - - - - - - - - -
SP3: - - - - - - - - - - - -
SP4: - - - - - -
SP5: - - - - - - -
SP6: - - - - - - - -
SP7: - - - - - - - - - - - -
SP8: - - - -
SP9: - - - - - - - - -
SP10: - - - - - - - - - - - - - -
SP11: - -
SP12: -
SP13: - - - - - -
SP14: - - - - - - - - - - - -

Relevant External Links for CD74 Gene

GeneLoc Exon Structure for
CD74

Expression for CD74 Gene

Products:

  1. Primer
  2. Gene Expression Assay

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for CD74 Gene

mRNA expression in normal human tissues for CD74 Gene
mRNA expression by GTEx for CD74 GenemRNA expression by BioGPS for CD74 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for CD74 Gene

This gene is overexpressed in Spleen (x5.3) and Whole Blood (x4.6).

Protein differential expression in normal tissues from HIPED for CD74 Gene

This gene is overexpressed in Lymph node (16.0), Blymphocyte (12.6), and Nasal epithelium (8.1).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for CD74 Gene



Protein tissue co-expression partners for CD74 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for CD74

SOURCE GeneReport for Unigene cluster for CD74 Gene:

Hs.436568

Evidence on tissue expression from TISSUES for CD74 Gene

  • Nervous system(5)
  • Spleen(5)
  • Intestine(4.9)
  • Heart(4.9)
  • Liver(4.9)
  • Lung(4.9)
  • Pancreas(4.6)
  • Blood(4.6)
  • Stomach(4.6)
  • Eye(4.2)
  • Lymph node(4.1)
  • Muscle(3.7)
  • Bone(3.7)
  • Skin(3.6)
  • Bone marrow(3.6)
  • Kidney(3.5)
  • Adrenal gland(3.1)
  • Thyroid gland(3)
  • Gall bladder(2.9)
genes like me logo Genes that share expression patterns with CD74: view

No data available for mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for CD74 Gene

Orthologs for CD74 Gene

This gene was present in the common ancestor of chordates.

Orthologs for CD74 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
 Mammalia CD74 30 31
  • 99.14 (n)
 OneToOne
Dog
(Canis familiaris)
 Mammalia CD74 30 31
  • 88.36 (n)
 OneToOne
Mouse
(Mus musculus)
 Mammalia Cd74 30 17 31
  • 82.13 (n)
 OneToOne
Rat
(Rattus norvegicus)
 Mammalia Cd74 30
  • 81.85 (n)
Cow
(Bos Taurus)
 Mammalia CD74 31
  • 79 (a)
 OneToOne
Oppossum
(Monodelphis domestica)
 Mammalia CD74 31
  • 58 (a)
 OneToOne
Platypus
(Ornithorhynchus anatinus)
 Mammalia CD74 31
  • 54 (a)
 OneToOne
Chicken
(Gallus gallus)
 Aves CD74 30
  • 60.58 (n)
II 31
  • 43 (a)
 OneToOne
Lizard
(Anolis carolinensis)
 Reptilia CD74 31
  • 42 (a)
 OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
 Amphibia cd74 30
  • 50.2 (n)
African clawed frog
(Xenopus laevis)
 Amphibia Xl.10251 30
Zebrafish
(Danio rerio)
 Actinopterygii cd74a 31
  • 30 (a)
 OneToOne
Species where no ortholog for CD74 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for CD74 Gene

ENSEMBL:
Gene Tree for CD74 (if available)
TreeFam:
Gene Tree for CD74 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for CD74: view image

Paralogs for CD74 Gene

(3) SIMAP similar genes for CD74 Gene using alignment to 6 proteins:

  • HG2A_HUMAN
  • E7EQJ3_HUMAN
  • E7ER71_HUMAN
  • E7ESL3_HUMAN
  • H0YBZ2_HUMAN
  • H0YBZ8_HUMAN
genes like me logo Genes that share paralogs with CD74: view

No data available for Paralogs for CD74 Gene

Variants for CD74 Gene

Products:

  1. SNP Genotyping and Copy Number Assay

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for CD74 Gene

SNP ID Clinical significance and condition Chr 05 pos Variation AA Info Type
rs188910406 Likely Benign: Treacher Collins Syndrome, Dominant 150,400,217(-) C/T THREE_PRIME_UTR_VARIANT
rs533518443 Likely Benign: Treacher Collins Syndrome, Dominant 150,400,243(-) G/GT THREE_PRIME_UTR_VARIANT
rs55784390 Likely Benign: Treacher Collins Syndrome, Dominant 150,400,177(-) C/T THREE_PRIME_UTR_VARIANT
rs558770704 Uncertain Significance: Treacher Collins Syndrome, Dominant 150,400,178(-) G/A THREE_PRIME_UTR_VARIANT
rs886060268 Uncertain Significance: Treacher Collins Syndrome, Dominant 150,400,244(-) T/G THREE_PRIME_UTR_VARIANT

Additional dbSNP identifiers (rs#s) for CD74 Gene

Structural Variations from Database of Genomic Variants (DGV) for CD74 Gene

Variant ID Type Subtype PubMed ID
nsv1022057 CNV gain 25217958
nsv599957 CNV loss 21841781
nsv599958 CNV loss 21841781

Variation tolerance for CD74 Gene

Residual Variation Intolerance Score: 78.1% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for CD74 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
CD74

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for CD74 Gene

Disorders for CD74 Gene

MalaCards: The human disease database

(2) MalaCards diseases for CD74 Gene - From: DISEASES

- elite association - COSMIC cancer census association via MalaCards
Search CD74 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

HG2A_HUMAN
  • Note=A chromosomal aberration involving CD74 is found in a non-small cell lung tumor. Results in the formation of a CD74-ROS1 chimeric protein. {ECO:0000269 PubMed:12661006}.

Additional Disease Information for CD74

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with CD74: view

No data available for Genatlas for CD74 Gene

Publications for CD74 Gene

  1. Structure of the human gene encoding the invariant gamma-chain of class II histocompatibility antigens. (PMID: 3001652) Kudo J … Saunders GF (Nucleic acids research 1985) 2 3 4
  2. cDNA clone for the human invariant gamma chain of class II histocompatibility antigens and its implications for the protein structure. (PMID: 6324166) Claesson L … Peterson PA (Proceedings of the National Academy of Sciences of the United States of America 1983) 2 3 4
  3. Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study. (PMID: 20628086) Bailey SD … DREAM investigators (Diabetes care 2010) 3 41
  4. Fine mapping of the CELIAC2 locus on chromosome 5q31-q33 in the Finnish and Hungarian populations. (PMID: 19845895) Koskinen LL … Saavalainen P (Tissue antigens 2009) 3 41
  5. CD44 is the signaling component of the macrophage migration inhibitory factor-CD74 receptor complex. (PMID: 17045821) Shi X … Bucala R (Immunity 2006) 3 23

ExternalLinks

View latest publications for CD74 gene in Mastermind

Products for CD74 Gene

  • Signalway ELISA kits for CD74
  • Signalway Proteins for CD74

Sources for CD74 Gene