Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTO16X4Q)

• DOT Name: HLA class II histocompatibility antigen gamma chain (CD74)
• Synonyms: HLA-DR antigens-associated invariant chain; Ia antigen-associated invariant chain; Ii; CD antigen CD74
• Gene Name: CD74
• UniProt ID: HG2A_HUMAN
• PDB ID: 1A6A; 1ICF; 1IIE; 1L3H; 1MUJ; 3PDO; 3PGC; 3PGD; 3QXA; 3QXD; 4AEN; 4AH2; 4X5W; 5KSU; 5KSV; 7YX9; 7YXB; 7Z0Q
• Pfam ID: PF09307 ; PF08831 ; PF00086
• Sequence:
  MHRRRSRSCREDQKPVMDDQRDLISNNEQLPMLGRRPGAPESKCSRGALYTGFSILVTLL
  LAGQATTAYFLYQQQGRLDKLTVTSQNLQLENLRMKLPKPPKPVSKMRMATPLLMQALPM
  GALPQGPMQNATKYGNMTEDHVMHLLQNADPLKVYPPLKGSFPENLRHLKNTMETIDWKV
  FESWMHHWLLFEMSRHSLEQKPTDAPPKVLTKCQEEVSHIPAVHPGSFRPKCDENGNYLP
  LQCYGSIGYCWCVFPNGTEVPNTRSRGHHNCSESLELEDPSSGLGVTKQDLGPVPM
• 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.
• Tissue Specificity: Detected in urine (at protein level).; [Isoform p41]: In B cells, represents 10% of total CD74 expression.; [Isoform p33]: In B cells, represents 70% of total CD74 expression.
• KEGG Pathway:
  Antigen processing and presentation (hsa04612)
  Tuberculosis (hsa05152)
  Herpes simplex virus 1 infection (hsa05168)
• Reactome Pathway:
  MHC class II antigen presentation (R-HSA-2132295)
  Cell surface interactions at the vascular wall (R-HSA-202733)

Molecular Interaction Atlas (MIA) of This DOT

26 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of HLA class II histocompatibility antigen gamma chain (CD74).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of HLA class II histocompatibility antigen gamma chain (CD74).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of HLA class II histocompatibility antigen gamma chain (CD74).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of HLA class II histocompatibility antigen gamma chain (CD74).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of HLA class II histocompatibility antigen gamma chain (CD74).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of HLA class II histocompatibility antigen gamma chain (CD74).	[6]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of HLA class II histocompatibility antigen gamma chain (CD74).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of HLA class II histocompatibility antigen gamma chain (CD74).	[8]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of HLA class II histocompatibility antigen gamma chain (CD74).	[9]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of HLA class II histocompatibility antigen gamma chain (CD74).	[10]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of HLA class II histocompatibility antigen gamma chain (CD74).	[11]
Selenium	DM25CGV	Approved	Selenium increases the expression of HLA class II histocompatibility antigen gamma chain (CD74).	[12]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of HLA class II histocompatibility antigen gamma chain (CD74).	[13]
Aspirin	DM672AH	Approved	Aspirin decreases the expression of HLA class II histocompatibility antigen gamma chain (CD74).	[14]
Diphenylpyraline	DMW4X37	Approved	Diphenylpyraline increases the expression of HLA class II histocompatibility antigen gamma chain (CD74).	[15]
Bupropion	DM5PCS7	Approved	Bupropion affects the expression of HLA class II histocompatibility antigen gamma chain (CD74).	[16]
Trimethoprim	DMM7CHK	Approved	Trimethoprim affects the expression of HLA class II histocompatibility antigen gamma chain (CD74).	[16]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of HLA class II histocompatibility antigen gamma chain (CD74).	[10]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene increases the expression of HLA class II histocompatibility antigen gamma chain (CD74).	[17]
MLN4924	DMP36KD	Phase 3	MLN4924 affects the expression of HLA class II histocompatibility antigen gamma chain (CD74).	[18]
Flavonoid derivative 1	DMCQP0B	Patented	Flavonoid derivative 1 decreases the expression of HLA class II histocompatibility antigen gamma chain (CD74).	[7]
Nobiletin	DM7R3B6	Preclinical	Nobiletin decreases the expression of HLA class II histocompatibility antigen gamma chain (CD74).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of HLA class II histocompatibility antigen gamma chain (CD74).	[21]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of HLA class II histocompatibility antigen gamma chain (CD74).	[22]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of HLA class II histocompatibility antigen gamma chain (CD74).	[23]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN affects the expression of HLA class II histocompatibility antigen gamma chain (CD74).	[24]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of HLA class II histocompatibility antigen gamma chain (CD74).	[19]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of HLA class II histocompatibility antigen gamma chain (CD74).	[20]

References

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