Seroatlas · Human Serome Atlas

CD74

HLA class II histocompatibility antigen gamma chain

Also known as: CLIP, DHLAG, HG2A_HUMAN

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession
P04233
Gene
CD74
Ensembl
ENSG00000019582
Chromosome
5
Canonical length
296 aa
Protein class
Cancer-related genes, CD markers, Disease related genes, Potential drug targets, Predicted membrane proteins, Transporters
Subcellular location
Golgi apparatus
Secretome location
Secreted to blood
Quaternary structure
Homotrimer

OverviewNCBI 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]

Canonical amino-acid sequenceUniProt

296 residues, UniProt reviewed canonical sequence.

>P04233|CD74
     1  MHRRRSRSCR EDQKPVMDDQ RDLISNNEQL PMLGRRPGAP ESKCSRGALY TGFSILVTLL
    61  LAGQATTAYF LYQQQGRLDK LTVTSQNLQL ENLRMKLPKP PKPVSKMRMA TPLLMQALPM
   121  GALPQGPMQN ATKYGNMTED HVMHLLQNAD PLKVYPPLKG SFPENLRHLK NTMETIDWKV
   181  FESWMHHWLL FEMSRHSLEQ KPTDAPPKVL TKCQEEVSHI PAVHPGSFRP KCDENGNYLP
   241  LQCYGSIGYC WCVFPNGTEV PNTRSRGHHN CSESLELEDP SSGLGVTKQD LGPVPM

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against CD74 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability
Cell surface
Secreted
No
Transmembrane segments
1
Mean surface accessibility (rSASA)
0.56
Highest tissue expression
4,925 nTPM

Expression across tissuesHPA

Tissue

  • tonsil: 4,925 nTPM
  • lymph node: 4,695 nTPM
  • spleen: 4,646 nTPM
  • lung: 3,693 nTPM
  • appendix: 2,625 nTPM
  • small intestine: 2,357 nTPM

Single-cell type

  • cdc: 14,450 nCPM
  • macrophages: 5,933 nCPM
  • kupffer cells: 5,171 nCPM
  • enterocytes: 4,957 nCPM
  • pdcs: 4,090 nCPM
  • b-cells: 3,923 nCPM

Immune cell

  • naive B-cell: 28,193 nTPM
  • memory B-cell: 27,121 nTPM
  • myeloid DC: 23,966 nTPM
  • total PBMC: 17,862 nTPM
  • plasmacytoid DC: 17,016 nTPM
  • intermediate monocyte: 16,175 nTPM

Brain region

  • white matter: 1,390 nTPM
  • medulla oblongata: 1,001 nTPM
  • spinal cord: 808 nTPM
  • thalamus: 795 nTPM
  • hypothalamus: 780 nTPM
  • pons: 654 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about CD74.

Disease | ImmuneIEDB

Conditions an epitope on CD74 was assayed in.

Disease | AutoantibodyPubMed

Conditions in which antibodies against CD74 are reported. Each links to that disease's full target list.

Showing 2 of 4 — disease pages carrying at least 10 antigens.

ReferencesPubMed · IEDB

Publications for CD74 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Reference: AutoantibodyPubMed

20 publications

Show 15 more

Reference: T cellIEDB

3 publications

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)
0.56
gnomAD pLI
0.25
gnomAD missense Z
1.4
DepMap mean gene effect
0.02
DepMap dependency class
selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of CD74 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads CD74 as an antibody target. Whether an autoantibody or antibody against CD74 could matter depends on whether native CD74 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

CD74 is annotated at the cell surface, where native CD74 is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.

Annotation status

The present source text does not explicitly label CD74 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/CD74. Study-independent annotations aggregated from UniProt, Human Protein Atlas, PubMed, IEDB, Pfam, InterPro, Gene Ontology, AlphaFold, gnomAD, DepMap, ClinVar, TCGA. Catalog release seroatlas-reviewed-human-uniprot-20260313.

Seroatlas is the reference for exploring autoantibody and antibody serology at the human-protein level: the autoreactome and human serome, multiplex serology (HuProt, HuScan, VirScan, PhIP-Seq).

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