Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCE1WXO)

• DOT Name: Serum amyloid A-4 protein (SAA4)
• Synonyms: Constitutively expressed serum amyloid A protein; C-SAA
• Gene Name: SAA4
• Related Disease:
  Amyloidosis
  Bone osteosarcoma
  Carcinoma
  Glioma
  Osteosarcoma
  Ovarian cancer
  Rheumatoid arthritis
• UniProt ID: SAA4_HUMAN
• Pfam ID: PF00277
• Sequence:
  MRLFTGIVFCSLVMGVTSESWRSFFKEALQGVGDMGRAYWDIMISNHQNSNRYLYARGNY
  DAAQRGPGGVWAAKLISRSRVYLQGLIDCYLFGNSSTVLEDSKSNEKAEEWGRSGKDPDR
  FRPDGLPKKY
• Function: Major acute phase reactant.
• Tissue Specificity: Expressed by the liver; secreted in plasma.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Amyloidosis	DISHTAI2	Strong	Genetic Variation	[1]
Bone osteosarcoma	DIST1004	Strong	Altered Expression	[2]
Carcinoma	DISH9F1N	Strong	Altered Expression	[3]
Glioma	DIS5RPEH	Strong	Genetic Variation	[4]
Osteosarcoma	DISLQ7E2	Strong	Altered Expression	[2]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[5]
Rheumatoid arthritis	DISTSB4J	Disputed	Biomarker	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Serum amyloid A-4 protein (SAA4).	[7]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Serum amyloid A-4 protein (SAA4).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Serum amyloid A-4 protein (SAA4).	[9]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Serum amyloid A-4 protein (SAA4).	[8]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Serum amyloid A-4 protein (SAA4).	[10]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Serum amyloid A-4 protein (SAA4).	[11]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Serum amyloid A-4 protein (SAA4).	[12]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Serum amyloid A-4 protein (SAA4).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Serum amyloid A-4 protein (SAA4).	[14]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Serum amyloid A-4 protein (SAA4).	[15]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID decreases the expression of Serum amyloid A-4 protein (SAA4).	[16]

References

• [1] AA amyloidosis associated with a mutated serum amyloid A4 protein.Amyloid. 2009;16(2):84-8. doi: 10.1080/13506120902879905.
• [2] Expression of serum amyloid A transcripts in human bone tissues, differentiated osteoblast-like stem cells and human osteosarcoma cell lines.J Cell Biochem. 2008 Feb 15;103(3):994-1004. doi: 10.1002/jcb.21472.
• [3] Expression of serum amyloid A, in normal, dysplastic, and neoplastic human colonic mucosa: implication for a role in colonic tumorigenesis.J Histochem Cytochem. 2006 Jan;54(1):63-73. doi: 10.1369/jhc.5A6645.2005. Epub 2005 Aug 22.
• [4] Senescence-associated-gene signature identifies genes linked to age, prognosis, and progression of human gliomas.J Geriatr Oncol. 2014 Oct 1;5(4):389-99. doi: 10.1016/j.jgo.2014.08.003. Epub 2014 Sep 11.
• [5] Expression of serum amyloid a in human ovarian epithelial tumors: implication for a role in ovarian tumorigenesis.J Histochem Cytochem. 2010 Nov;58(11):1015-23. doi: 10.1369/jhc.2010.956821. Epub 2010 Aug 16.
• [6] Identification and Validation of SAA4 as a Rheumatoid Arthritis Prescreening Marker by Liquid Chromatography Tandem-mass Spectrometry.Molecules. 2017 May 14;22(5):805. doi: 10.3390/molecules22050805.
• [7] Integrated 'omics analysis reveals new drug-induced mitochondrial perturbations in human hepatocytes. Toxicol Lett. 2018 Jun 1;289:1-13.
• [8] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [9] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [10] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [11] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [12] Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
• [13] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [14] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [15] Regulation of chromatin assembly and cell transformation by formaldehyde exposure in human cells. Environ Health Perspect. 2017 Sep 21;125(9):097019.
• [16] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.