General Information of Target

Target ID LDTP01917
Target Name HLA class II histocompatibility antigen, DQ alpha 1 chain (HLA-DQA1)
Gene Name HLA-DQA1
Gene ID 3117
Synonyms
HLA class II histocompatibility antigen, DQ alpha 1 chain; DC-1 alpha chain; DC-alpha; HLA-DCA; MHC class II DQA1
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Sequence
MILNKALMLGALALTTVMSPCGGEDIVADHVASYGVNLYQSYGPSGQYTHEFDGDEQFYV
DLGRKETVWCLPVLRQFRFDPQFALTNIAVLKHNLNSLIKRSNSTAATNEVPEVTVFSKS
PVTLGQPNILICLVDNIFPPVVNITWLSNGHSVTEGVSETSFLSKSDHSFFKISYLTLLP
SAEESYDCKVEHWGLDKPLLKHWEPEIPAPMSELTETVVCALGLSVGLVGIVVGTVFIIR
GLRSVGASRHQGPL
Target Type
Literature-reported
Target Bioclass
Immunoglobulin
Family
MHC class II family
Subcellular location
Cell membrane
Function
Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells. The peptide binding cleft accommodates peptides of 10-30 residues. The peptides presented by MHC class II molecules are generated mostly by degradation of proteins that access the endocytic route, where they are processed by lysosomal proteases and other hydrolases. Exogenous antigens that have been endocytosed by the APC are thus readily available for presentation via MHC II molecules, and for this reason this antigen presentation pathway is usually referred to as exogenous. As membrane proteins on their way to degradation in lysosomes as part of their normal turn-over are also contained in the endosomal/lysosomal compartments, exogenous antigens must compete with those derived from endogenous components. Autophagy is also a source of endogenous peptides, autophagosomes constitutively fuse with MHC class II loading compartments. In addition to APCs, other cells of the gastrointestinal tract, such as epithelial cells, express MHC class II molecules and CD74 and act as APCs, which is an unusual trait of the GI tract. To produce a MHC class II molecule that presents an antigen, three MHC class II molecules (heterodimers of an alpha and a beta chain) associate with a CD74 trimer in the ER to form a heterononamer. Soon after the entry of this complex into the endosomal/lysosomal system where antigen processing occurs, CD74 undergoes a sequential degradation by various proteases, including CTSS and CTSL, leaving a small fragment termed CLIP (class-II-associated invariant chain peptide). The removal of CLIP is facilitated by HLA-DM via direct binding to the alpha-beta-CLIP complex so that CLIP is released. HLA-DM stabilizes MHC class II molecules until primary high affinity antigenic peptides are bound. The MHC II molecule bound to a peptide is then transported to the cell membrane surface. In B-cells, the interaction between HLA-DM and MHC class II molecules is regulated by HLA-DO. Primary dendritic cells (DCs) also to express HLA-DO. Lysosomal microenvironment has been implicated in the regulation of antigen loading into MHC II molecules, increased acidification produces increased proteolysis and efficient peptide loading.
TTD ID
T50768
Uniprot ID
P01909
DrugMap ID
TTU2I3J
Ensemble ID
ENST00000343139.11
HGNC ID
HGNC:4942
ChEMBL ID
CHEMBL4105884

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 1 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
DBIA
 Probe Info 
C70(3.44)  LDD3372  [1]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0022  KB02 HG-3 C70(1.88)  LDD2355  [1]
 LDCM0023  KB03 MEC-1 C70(3.41)  LDD2876  [1]
 LDCM0024  KB05 OCI-Ly3 C70(3.44)  LDD3372  [1]

References

1 DrugMap: A quantitative pan-cancer analysis of cysteine ligandability. Cell. 2024 May 9;187(10):2536-2556.e30. doi: 10.1016/j.cell.2024.03.027. Epub 2024 Apr 22.
Mass spectrometry data entry: PXD047840