Details of Drug Off-Target (DOT)

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

• DOT Name: Protein SAAL1 (SAAL1)
• Synonyms: Synoviocyte proliferation-associated in collagen-induced arthritis protein 1; SPACIA1
• Gene Name: SAAL1
• Related Disease:
  Osteoarthritis
  Synovitis
  Rheumatoid arthritis
• UniProt ID: SAAL1_HUMAN
• Sequence:
  MDRNPSPPPPGRDKEEEEEVAGGDCIGSTVYSKHWLFGVLSGLIQIVSPENTKSSSDDEE
  QLTELDEEMENEICRVWDMSMDEDVALFLQEFNAPDIFMGVLAKSKCPRLREICVGILGN
  MACFQEICVSISSDKNLGQVLLHCLYDSDPPTLLETSRLLLTCLSQAEVASVWVERIQEH
  PAIYDSICFIMSSSTNVDLLVKVGEVVDKLFDLDEKLMLEWVRNGAAQPLDQPQEESEEQ
  PVFRLVPCILEAAKQVRSENPEWLDVYMHILQLLTTVDDGIQAIVHCPDTGKDIWNLLFD
  LVCHEFCQSDDPPIILQEQKTVLASVFSVLSAIYASQTEQEYLKIEKVDLPLIDSLIRVL
  QNMEQCQKKPENSAESNTEETKRTDLTQDDFHLKILKDILCEFLSNIFQALTKETVAQGV
  KEGQLSKQKCSSAFQNLLPFYSPVVEDFIKILREVDKALADDLEKNFPSLKVQT
• Function: Plays a role in promoting the proliferation of synovial fibroblasts in response to pro-inflammatory stimuli.
• Tissue Specificity: Highly expressed in testis and ovary, and to a lesser extent in the lung, spleen and the heart (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Osteoarthritis	DIS05URM	Strong	Biomarker	[1]
Synovitis	DISW2GPY	Strong	Biomarker	[1]
Rheumatoid arthritis	DISTSB4J	Limited	Biomarker	[2]

5 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 Protein SAAL1 (SAAL1).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Protein SAAL1 (SAAL1).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Protein SAAL1 (SAAL1).	[5]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Protein SAAL1 (SAAL1).	[7]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Protein SAAL1 (SAAL1).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Protein SAAL1 (SAAL1).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Protein SAAL1 (SAAL1).	[8]

References

• [1] Overexpression of SPACIA1/SAAL1, a newly identified gene that is involved in synoviocyte proliferation, accelerates the progression of synovitis in mice and humans.Arthritis Rheum. 2011 Dec;63(12):3833-42. doi: 10.1002/art.30617.
• [2] SPACIA1/SAAL1 Deletion Results in a Moderate Delay in Collagen-Induced Arthritis Activity, along with mRNA Decay of Cyclin-dependent Kinase 6 Gene.Int J Mol Sci. 2018 Nov 30;19(12):3828. doi: 10.3390/ijms19123828.
• [3] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [4] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [7] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [8] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [9] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.