MGP Database

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MGP000471

UniProt Annotations

Entry Information
Gene NameCD74 molecule, major histocompatibility complex, class II invariant chain
Protein EntryHG2A_HUMAN
UniProt IDP04233
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=3; Name=1; Synonyms=Long; IsoId=P04233-1; Sequence=Displayed; Name=2; Synonyms=Short; IsoId=P04233-2; Sequence=VSP_005331; Name=3; IsoId=P04233-3; Sequence=VSP_037869, VSP_037870;
DiseaseNote=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}.
FunctionPlays 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.
InteractionP61073:CXCR4; NbExp=4; IntAct=EBI-2622890, EBI-489411;
PtmN- and O-glycosylated. O-glycosylated with core 1 or possibly core 8 glycans. {ECO:0000269|PubMed:10022822, ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:22171320, ECO:0000269|PubMed:23234360}.
Sequence CautionSequence=AAA36304.1; Type=Erroneous initiation; Evidence={ECO:0000305};
SimilarityContains 1 thyroglobulin type-1 domain. {ECO:0000255|PROSITE-ProRule:PRU00500}.
Subcellular LocationCell membrane {ECO:0000305}; Single-pass type II membrane protein {ECO:0000305}. 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.
SubunitHomotrimer. 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. {ECO:0000269|PubMed:12782713, ECO:0000269|PubMed:7477400}.
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