{"results":[{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"P04233","secondaryAccessions":["A8K7R1","B4DNE8","D3DQG3","D3DQG4","Q14597","Q29832","Q5U0J8","Q8SNA0","Q8WLP6"],"uniProtkbId":"HG2A_HUMAN","entryAudit":{"firstPublicDate":"1987-03-20","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2002-04-16","entryVersion":250,"sequenceVersion":3},"annotationScore":5.0,"organism":{"scientificName":"Homo sapiens","commonName":"Human","taxonId":9606,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Primates","Haplorrhini","Catarrhini","Hominidae","Homo"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"HLA class II histocompatibility antigen gamma chain"}},"alternativeNames":[{"fullName":{"value":"HLA-DR antigens-associated invariant chain"}},{"fullName":{"value":"Ia antigen-associated invariant chain"},"shortNames":[{"value":"Ii"}]}],"cdAntigenNames":[{"value":"CD74"}],"contains":[{"recommendedName":{"fullName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"1448172"}],"value":"Class-II-associated invariant chain peptide"},"shortNames":[{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"1448172"}],"value":"CLIP"}]}}]},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000312","source":"HGNC","id":"HGNC:1697"}],"value":"CD74"},"synonyms":[{"value":"DHLAG"}]}],"comments":[{"texts":[{"value":"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"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"1448172"}],"value":"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"}],"commentType":"FUNCTION","molecule":"Class-II-associated invariant chain peptide"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P04441"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"32855215"}],"value":"Stabilizes the conformation of mature CTSL by binding to its active site and serving as a chaperone to help maintain a pool of mature enzyme in endocytic compartments and extracellular space of antigen-presenting cells (APCs). Has antiviral activity by stymieing the endosomal entry of Ebola virus and coronaviruses, including SARS-CoV-2 (PubMed:32855215). Disrupts cathepsin-mediated Ebola virus glycoprotein processing, which prevents viral fusion and entry. This antiviral activity is specific to p41 isoform (PubMed:32855215)"}],"commentType":"FUNCTION","molecule":"Isoform p41"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P04441"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12782713"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"7477400"}],"value":"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"}],"commentType":"SUBUNIT"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10022822"}],"value":"Interacts with the mature form of CTSL; the complex survive in neutral pH environment"}],"commentType":"SUBUNIT","molecule":"Isoform 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It can either undergo proteolysis or reach the cell membrane"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Cell membrane","id":"SL-0039"},"topology":{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Single-pass type II membrane protein","id":"SL-9906"}},{"location":{"value":"Endoplasmic reticulum membrane","id":"SL-0097"}},{"location":{"value":"Golgi apparatus, trans-Golgi network","id":"SL-0266"}},{"location":{"value":"Endosome","id":"SL-0101"}},{"location":{"value":"Lysosome","id":"SL-0158"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25326458"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"36213313"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"37453717"}],"value":"Secreted","id":"SL-0243"}}]},{"commentType":"SUBCELLULAR LOCATION","molecule":"Isoform p41","subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P04441"}],"value":"Late endosome","id":"SL-0152"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P04441"}],"value":"Lysosome","id":"SL-0158"}}]},{"commentType":"ALTERNATIVE PRODUCTS","events":["Alternative splicing","Alternative initiation"],"isoforms":[{"name":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"3104027"}],"value":"p45"},"synonyms":[{"value":"Long"}],"isoformIds":["P04233-1"],"isoformSequenceStatus":"Displayed"},{"name":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"3104027"}],"value":"p35"},"synonyms":[{"value":"Short"}],"isoformIds":["P04233-2"],"sequenceIds":["VSP_005331"],"isoformSequenceStatus":"Described"},{"name":{"value":"3"},"isoformIds":["P04233-3"],"sequenceIds":["VSP_037869","VSP_037870"],"isoformSequenceStatus":"Described"},{"name":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"3104027"}],"value":"p41"},"isoformIds":["P04233-4"],"sequenceIds":["VSP_060904"],"isoformSequenceStatus":"Described"},{"name":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"3104027"}],"value":"p33"},"isoformIds":["P04233-5"],"sequenceIds":["VSP_060904","VSP_005331"],"isoformSequenceStatus":"Described"}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25326458"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"36213313"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"37453717"}],"value":"Detected in urine (at protein level)"}],"commentType":"TISSUE SPECIFICITY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"3104027"}],"value":"In B cells, represents 10% of total CD74 expression"}],"commentType":"TISSUE SPECIFICITY","molecule":"Isoform p41"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"3104027"}],"value":"In B cells, represents 70% of total CD74 expression"}],"commentType":"TISSUE SPECIFICITY","molecule":"Isoform p33"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"32855215"}],"value":"Antiviral activity requires delivery of the thyroglobulin domain to the endosomal membrane"}],"commentType":"DOMAIN"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22171320"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23234360"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25326458"}],"value":"O-glycosylated with core 1 or possibly core 8 glycans (PubMed:22171320, PubMed:23234360). Contains chondroitin sulfate (PubMed:25326458)"}],"commentType":"PTM"},{"commentType":"DISEASE","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12661006"}],"value":"A chromosomal aberration involving CD74 is found in a non-small cell lung tumor. 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