General Information of Target

Target ID LDTP02028
Target Name HLA class II histocompatibility antigen gamma chain (CD74)
Gene Name CD74
Gene ID 972
Synonyms
DHLAG; HLA class II histocompatibility antigen gamma chain; HLA-DR antigens-associated invariant chain; Ia antigen-associated invariant chain; Ii; CD antigen CD74) [Cleaved into: Class-II-associated invariant chain peptide; CLIP)]
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MHRRRSRSCREDQKPVMDDQRDLISNNEQLPMLGRRPGAPESKCSRGALYTGFSILVTLL
LAGQATTAYFLYQQQGRLDKLTVTSQNLQLENLRMKLPKPPKPVSKMRMATPLLMQALPM
GALPQGPMQNATKYGNMTEDHVMHLLQNADPLKVYPPLKGSFPENLRHLKNTMETIDWKV
FESWMHHWLLFEMSRHSLEQKPTDAPPKVLTKCQEEVSHIPAVHPGSFRPKCDENGNYLP
LQCYGSIGYCWCVFPNGTEVPNTRSRGHHNCSESLELEDPSSGLGVTKQDLGPVPM
Target Type
Clinical trial
Target Bioclass
Transporter and channel
Subcellular location
Cell membrane; Late endosome
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.; [Class-II-associated invariant chain peptide]: 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.; [Isoform p41]: 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. Disrupts cathepsin-mediated Ebola virus glycoprotein processing, which prevents viral fusion and entry. This antiviral activity is specific to p41 isoform.
TTD ID
T08231
Uniprot ID
P04233
DrugMap ID
TTI6LBU
Ensemble ID
ENST00000009530.13
HGNC ID
HGNC:1697
ChEMBL ID
CHEMBL4692

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
HSC4 SNV: p.E199Ter .
JURKAT SNV: p.L97I .

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 4 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
STPyne
 Probe Info 
K43(8.09)  LDD0277  [1]
ONAyne
 Probe Info 
K43(6.79)  LDD0275  [1]
EA-probe
 Probe Info 
N.A.  LDD0440  [2]
IA-alkyne
 Probe Info 
C9(1.20)  LDD2182  [3]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0175  Ethacrynic acid HeLa N.A.  LDD0440  [2]
 LDCM0625  F8 Ramos C9(1.66)  LDD2187  [3]
 LDCM0572  Fragment10 Ramos C9(1.12)  LDD2189  [3]
 LDCM0573  Fragment11 Ramos C9(2.66)  LDD2190  [3]
 LDCM0574  Fragment12 Ramos C9(0.28)  LDD2191  [3]
 LDCM0575  Fragment13 Ramos C9(0.87)  LDD2192  [3]
 LDCM0576  Fragment14 Ramos C9(0.61)  LDD2193  [3]
 LDCM0579  Fragment20 Ramos C9(0.40)  LDD2194  [3]
 LDCM0580  Fragment21 Ramos C9(0.50)  LDD2195  [3]
 LDCM0578  Fragment27 Ramos C9(0.80)  LDD2197  [3]
 LDCM0586  Fragment28 Ramos C9(0.77)  LDD2198  [3]
 LDCM0588  Fragment30 Ramos C9(0.65)  LDD2199  [3]
 LDCM0589  Fragment31 Ramos C9(0.42)  LDD2200  [3]
 LDCM0468  Fragment33 Ramos C9(0.32)  LDD2202  [3]
 LDCM0596  Fragment38 Ramos C9(0.63)  LDD2203  [3]
 LDCM0566  Fragment4 Ramos C9(0.89)  LDD2184  [3]
 LDCM0610  Fragment52 Ramos C9(0.34)  LDD2204  [3]
 LDCM0614  Fragment56 Ramos C9(0.41)  LDD2205  [3]
 LDCM0569  Fragment7 Ramos C9(1.09)  LDD2186  [3]
 LDCM0571  Fragment9 Ramos C9(0.32)  LDD2188  [3]
 LDCM0022  KB02 Ramos C9(1.20)  LDD2182  [3]
 LDCM0023  KB03 Ramos C9(0.86)  LDD2183  [3]
 LDCM0024  KB05 Ramos C9(0.77)  LDD2185  [3]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Enzyme
Click To Hide/Show 4 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Protein O-linked-mannose beta-1,2-N-acetylglucosaminyltransferase 1 (POMGNT1) Glycosyltransferase 13 family Q8WZA1
Phospholipid phosphatase 4 (PLPP4) PA-phosphatase related phosphoesterase family Q5VZY2
Pepsin A-4 (PGA4) Peptidase A1 family P0DJD7
Squalene synthase (FDFT1) Phytoene/squalene synthase family P37268
Transporter and channel
Click To Hide/Show 8 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
FXYD domain-containing ion transport regulator 6 (FXYD6) FXYD family Q9H0Q3
Importin subunit beta-1 (KPNB1) Importin beta family Q14974
Solute carrier family 35 member B1 (SLC35B1) Nucleotide-sugar transporter family P78383
Small integral membrane protein 1 (SMIM1) SMIM1 family B2RUZ4
Sigma intracellular receptor 2 (TMEM97) TMEM97/sigma-2 receptor family Q5BJF2
Uroplakin-2 (UPK2) Uroplakin-2 family O00526
CD44 antigen (CD44) . P16070
Transmembrane protein 60 (TMEM60) . Q9H2L4
GPCR
Click To Hide/Show 2 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
C-X-C chemokine receptor type 2 (CXCR2) G-protein coupled receptor 1 family P25025
Lysophosphatidic acid receptor 3 (LPAR3) G-protein coupled receptor 1 family Q9UBY5
Cytokine and receptor
Click To Hide/Show 2 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
CKLF-like MARVEL transmembrane domain-containing protein 7 (CMTM7) Chemokine-like factor family Q96FZ5
C-X-C chemokine receptor type 4 (CXCR4) G-protein coupled receptor 1 family P61073
Other
Click To Hide/Show 11 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
BET1 homolog (BET1) BET1 family O15155
Eukaryotic translation initiation factor 3 subunit E (EIF3E) EIF-3 subunit E family P60228
Ergosterol biosynthetic protein 28 homolog (ERG28) ERG28 family Q9UKR5
Stress-associated endoplasmic reticulum protein 1 (SERP1) RAMP4 family Q9Y6X1
Vesicle-trafficking protein SEC22a (SEC22A) Synaptobrevin family Q96IW7
Transmembrane protein 120B (TMEM120B) TMEM120 family A0PK00
Transmembrane protein 243 (TMEM243) TMEM243 family Q9BU79
Receptor-transporting protein 2 (RTP2) TMEM7 family Q5QGT7
Epididymal secretory protein E3-beta (EDDM3B) . P56851
Nutritionally-regulated adipose and cardiac enriched protein homolog (NRAC) . Q8N912
Transmembrane protein 254 (TMEM254) . Q8TBM7

References

1 A Paal-Knorr agent for chemoproteomic profiling of targets of isoketals in cells. Chem Sci. 2021 Oct 15;12(43):14557-14563. doi: 10.1039/d1sc02230j. eCollection 2021 Nov 10.
Mass spectrometry data entry: PXD028270
2 Chemoproteomic Profiling Reveals Ethacrynic Acid Targets Adenine Nucleotide Translocases to Impair Mitochondrial Function. Mol Pharm. 2018 Jun 4;15(6):2413-2422. doi: 10.1021/acs.molpharmaceut.8b00250. Epub 2018 May 15.
3 Site-specific quantitative cysteine profiling with data-independent acquisition-based mass spectrometry. Methods Enzymol. 2023;679:295-322. doi: 10.1016/bs.mie.2022.07.037. Epub 2022 Sep 7.
Mass spectrometry data entry: PXD027578