Query author contributions in Reactome
Reactome depends on collaboration between our curation team and outside experts to assemble and peer-review its pathway modules. The integration of ORCID within Reactome enables us to meet a key challenge with authoring, curating and reviewing biological information by incentivizing and crediting the external experts that contribute their expertise and time to the Reactome curation process. More information is available at ORCID and Reactome.
If you have an ORCID ID that is not listed on this page, please forward this information to us and we will update your Reactome pathway records.
Details on Person UniProt:P04233 CD74
| Class:Id | ReferenceGeneProduct:56488 |
|---|---|
| _chainChangeLog | chain:1-296 added on Fri February 6 2015;peptide:97-120 for 56488 added on Fri May 15 2020 |
| _displayName | UniProt:P04233 CD74 |
| _timestamp | 2024-11-03 20:19:23 |
| chain | chain:1-296 peptide:97-120 |
| checksum | 27A13F252D5FB91D |
| comment | 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.FUNCTION 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.FUNCTION 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).SUBUNIT 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.SUBUNIT Interacts with the mature form of CTSL; the complex survive in neutral pH environment.INTERACTION Transits through a number of intracellular compartments in the endocytic pathway. It can either undergo proteolysis or reach the cell membrane.SUBCELLULAR LOCATION Detected in urine (at protein level).TISSUE SPECIFICITY In B cells, represents 10% of total CD74 expression.TISSUE SPECIFICITY In B cells, represents 70% of total CD74 expression.DOMAIN Antiviral activity requires delivery of the thyroglobulin domain to the endosomal membrane.PTM O-glycosylated with core 1 or possibly core 8 glycans (PubMed:22171320, PubMed:23234360). Contains chondroitin sulfate (PubMed:25326458).DISEASE A chromosomal aberration involving CD74 is found in a non-small cell lung tumor. Results in the formation of a CD74-ROS1 chimeric protein.SEQUENCE CAUTION Truncated N-terminus. |
| description | recommendedName: fullName evidence="26"HLA class II histocompatibility antigen gamma chain alternativeName: HLA-DR antigens-associated invariant chain alternativeName: Ia antigen-associated invariant chain shortName: Ii cdAntigenNameCD74/cdAntigenName component recommendedName: fullName evidence="19"Class-II-associated invariant chain peptide shortName evidence="19"CLIP /component |
| geneName | CD74 DHLAG |
| identifier | P04233 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Adaptive immunity Alternative initiation Alternative splicing Cell membrane Chaperone Direct protein sequencing Disulfide bond Endoplasmic reticulum Endosome Glycoprotein Golgi apparatus Immunity Lysosome Membrane Phosphoprotein Proteoglycan Proteomics identification Reference proteome Secreted Signal-anchor Transmembrane Transmembrane helix |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9862192] Weiser, Joel, 2024-02-26 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 |
| name | CD74 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:8962568] ENSEMBL:ENSG00000019582 CD74 [Homo sapiens] |
| secondaryIdentifier | HG2A_HUMAN A8K7R1 B4DNE8 D3DQG3 D3DQG4 Q14597 Q29832 Q5U0J8 Q8SNA0 Q8WLP6 |
| sequenceLength | 296 |
| species | [Species:48887] Homo sapiens |
| (isoformParent) | [ReferenceIsoform:148380] UniProt:P04233-2 CD74 [Homo sapiens] [ReferenceIsoform:402371] UniProt:P04233-1 CD74 [Homo sapiens] [ReferenceIsoform:436160] UniProt:P04233-3 CD74 [Homo sapiens] [ReferenceIsoform:9715576] UniProt:P04233-4 CD74 [Homo sapiens] [ReferenceIsoform:9715577] UniProt:P04233-5 CD74 [Homo sapiens] |
| (referenceEntity) | [EntityWithAccessionedSequence:1181241] CD74 [lumenal side of endoplasmic reticulum membrane] [Homo sapiens] [EntityWithAccessionedSequence:2130320] CD74 [lysosomal membrane] [Homo sapiens] [EntityWithAccessionedSequence:2130446] CD74(81-104) [lysosomal membrane] [Homo sapiens] [EntityWithAccessionedSequence:2130456] CD74 [ER to Golgi transport vesicle membrane] [Homo sapiens] [EntityWithAccessionedSequence:2130460] CD74 [endocytic vesicle membrane] [Homo sapiens] [EntityWithAccessionedSequence:2130493] CD74 [trans-Golgi network membrane] [Homo sapiens] [EntityWithAccessionedSequence:2130522] CD74 [clathrin-coated endocytic vesicle membrane] [Homo sapiens] [EntityWithAccessionedSequence:2130602] CD74(1-176) [lysosomal membrane] [Homo sapiens] [EntityWithAccessionedSequence:2130624] CD74 [transport vesicle membrane] [Homo sapiens] [EntityWithAccessionedSequence:2130632] CD74(1-117) [lysosomal membrane] [Homo sapiens] |
| [Change default viewing format] | |
No pathways have been reviewed or authored by UniProt:P04233 CD74 (56488)
