Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQ7WFYW)

DOT Name	45 kDa calcium-binding protein (SDF4)
Synonyms	Cab45; Stromal cell-derived factor 4; SDF-4
Gene Name	SDF4
Related Disease	Acute myelogenous leukaemia ( ) Advanced cancer ( ) Allergic asthma ( ) Alzheimer disease ( ) Amyloidosis ( ) Asthma ( ) Atopic dermatitis ( ) Carney complex ( ) Cholangiocarcinoma ( ) Classic galactosemia ( ) Clear cell renal carcinoma ( ) Colon cancer ( ) Colon carcinoma ( ) Colorectal carcinoma ( ) Cystic fibrosis ( ) Dermatitis ( ) Gastric cancer ( ) Graves disease ( ) Melanoma ( ) Multiple sclerosis ( ) Myositis disease ( ) Neoplasm ( ) Non-small-cell lung cancer ( ) Pancreatitis ( ) Prostate cancer ( ) Prostate carcinoma ( ) Psoriasis ( ) Renal cell carcinoma ( ) Rhabdomyosarcoma ( ) Schizophrenia ( ) Skin disease ( ) Stomach cancer ( ) Bone osteosarcoma ( ) Breast cancer ( ) Breast carcinoma ( ) Lung cancer ( ) Lung carcinoma ( ) Osteosarcoma ( ) Pancreatic cancer ( ) Peripheral arterial disease ( ) Colon adenocarcinoma ( ) Metastatic malignant neoplasm ( ) Tauopathy ( ) Thyroid cancer ( ) Thyroid gland carcinoma ( ) Thyroid tumor ( )
UniProt ID	CAB45_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
Pfam ID	PF13202 ; PF13499
Sequence	MVWPWVAMASRWGPLIGLAPCCLWLLGAVLLMDASARPANHSSTRERVANREENEILPPD HLNGVKLEMDGHLNRGFHQEVFLGKDLGGFDEDAEPRRSRRKLMVIFSKVDVNTDRKISA KEMQRWIMEKTAEHFQEAMEESKTHFRAVDPDGDGHVSWDEYKVKFLASKGHSEKEVADA IRLNEELKVDEETQEVLENLKDRWYQADSPPADLLLTEEEFLSFLHPEHSRGMLRFMVKE IVRDLDQDGDKQLSVPEFISLPVGTVENQQGQDIDDNWVKDRKKEFEELIDSNHDGIVTA EELESYMDPMNEYNALNEAKQMIAVADENQNHHLEPEEVLKYSEFFTGSKLVDYARSVHE EF
Function	May regulate calcium-dependent activities in the endoplasmic reticulum lumen or post-ER compartment; Isoform 5 may be involved in the exocytosis of zymogens by pancreatic acini.
Tissue Specificity	Ubiquitous. Isoform 5 is expressed in pancreas.

Molecular Interaction Atlas (MIA) of This DOT

46 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Acute myelogenous leukaemia	DISCSPTN	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Allergic asthma	DISHF0H3	Strong	Biomarker	[3]
Alzheimer disease	DISF8S70	Strong	Biomarker	[4]
Amyloidosis	DISHTAI2	Strong	Biomarker	[5]
Asthma	DISW9QNS	Strong	Biomarker	[3]
Atopic dermatitis	DISTCP41	Strong	Altered Expression	[6]
Carney complex	DISVL3IP	Strong	Biomarker	[7]
Cholangiocarcinoma	DIS71F6X	Strong	Genetic Variation	[8]
Classic galactosemia	DISX7P8M	Strong	Genetic Variation	[9]
Clear cell renal carcinoma	DISBXRFJ	Strong	Altered Expression	[10]
Colon cancer	DISVC52G	Strong	Biomarker	[11]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[11]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[12]
Cystic fibrosis	DIS2OK1Q	Strong	Biomarker	[13]
Dermatitis	DISY5SZC	Strong	Genetic Variation	[6]
Gastric cancer	DISXGOUK	Strong	Genetic Variation	[14]
Graves disease	DISU4KOQ	Strong	Biomarker	[15]
Melanoma	DIS1RRCY	Strong	Biomarker	[16]
Multiple sclerosis	DISB2WZI	Strong	Altered Expression	[17]
Myositis disease	DISCIXF0	Strong	Biomarker	[15]
Neoplasm	DISZKGEW	Strong	Biomarker	[18]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[19]
Pancreatitis	DIS0IJEF	Strong	Biomarker	[20]
Prostate cancer	DISF190Y	Strong	Biomarker	[21]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[21]
Psoriasis	DIS59VMN	Strong	Altered Expression	[6]
Renal cell carcinoma	DISQZ2X8	Strong	Altered Expression	[10]
Rhabdomyosarcoma	DISNR7MS	Strong	Altered Expression	[22]
Schizophrenia	DISSRV2N	Strong	Biomarker	[23]
Skin disease	DISDW8R6	Strong	Biomarker	[6]
Stomach cancer	DISKIJSX	Strong	Genetic Variation	[14]
Bone osteosarcoma	DIST1004	moderate	Biomarker	[18]
Breast cancer	DIS7DPX1	moderate	Genetic Variation	[24]
Breast carcinoma	DIS2UE88	moderate	Genetic Variation	[24]
Lung cancer	DISCM4YA	moderate	Biomarker	[25]
Lung carcinoma	DISTR26C	moderate	Biomarker	[25]
Osteosarcoma	DISLQ7E2	moderate	Biomarker	[18]
Pancreatic cancer	DISJC981	moderate	Altered Expression	[26]
Peripheral arterial disease	DIS78WFB	moderate	Biomarker	[27]
Colon adenocarcinoma	DISDRE0J	Limited	Biomarker	[28]
Metastatic malignant neoplasm	DIS86UK6	Limited	Altered Expression	[29]
Tauopathy	DISY2IPA	Limited	Biomarker	[30]
Thyroid cancer	DIS3VLDH	Limited	Altered Expression	[31]
Thyroid gland carcinoma	DISMNGZ0	Limited	Altered Expression	[31]
Thyroid tumor	DISLVKMD	Limited	Altered Expression	[31]
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⏷ Show the Full List of 46 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	45 kDa calcium-binding protein (SDF4) affects the response to substance of Methotrexate.	[36]
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2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of 45 kDa calcium-binding protein (SDF4).	[32]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of 45 kDa calcium-binding protein (SDF4).	[34]
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2 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of 45 kDa calcium-binding protein (SDF4).	[33]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of 45 kDa calcium-binding protein (SDF4).	[35]
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References

1	The angiogenesis inhibitor vasostatin is regulated by neutrophil elastase-dependent cleavage of calreticulin in AML patients.Blood. 2012 Sep 27;120(13):2690-9. doi: 10.1182/blood-2012-02-412759. Epub 2012 Aug 22.
2	Psoriasin (S100A7) is a positive regulator of survival and invasion of prostate cancer cells.Urol Oncol. 2013 Nov;31(8):1576-83. doi: 10.1016/j.urolonc.2012.05.006. Epub 2012 Jun 12.
3	Transgenic expression of human S100A12 induces structural airway abnormalities and limited lung inflammation in a mouse model of allergic inflammation.Clin Exp Allergy. 2011 Jun;41(6):878-89. doi: 10.1111/j.1365-2222.2011.03714.x. Epub 2011 Mar 21.
4	Curcuminoid submicron particle ameliorates cognitive deficits and decreases amyloid pathology in Alzheimer's disease mouse model.Oncotarget. 2018 Jan 31;9(12):10681-10697. doi: 10.18632/oncotarget.24369. eCollection 2018 Feb 13.
5	Chaperoning Against Amyloid Aggregation: Monitoring In Vitro and In Vivo.Methods Mol Biol. 2019;1929:135-154. doi: 10.1007/978-1-4939-9030-6_10.
6	Human S100A15 splice variants are differentially expressed in inflammatory skin diseases and regulated through Th1 cytokines and calcium.Exp Dermatol. 2007 Aug;16(8):685-91. doi: 10.1111/j.1600-0625.2007.00587.x.
7	Cancer-related diseases of the eye: the role of calcium and calcium-binding proteins.Biochem Biophys Res Commun. 2004 Oct 1;322(4):1153-65. doi: 10.1016/j.bbrc.2004.07.109.
8	Calcium-binding protein S100P is a novel diagnostic marker of cholangiocarcinoma.Cancer Sci. 2011 Jan;102(1):150-6. doi: 10.1111/j.1349-7006.2010.01757.x. Epub 2010 Oct 13.
9	Galactosemia, a single gene disorder with epigenetic consequences.Pediatr Res. 2010 Mar;67(3):286-92. doi: 10.1203/PDR.0b013e3181cbd542.
10	Induced transcriptional expression of calcium-binding protein S100A1 and S100A10 genes in human renal cell carcinoma.Cancer Lett. 2002 Jan 10;175(1):71-7. doi: 10.1016/s0304-3835(01)00724-8.
11	S100A4-induced cell motility and metastasis is restricted by the Wnt/-catenin pathway inhibitor calcimycin in colon cancer cells.Mol Biol Cell. 2011 Sep;22(18):3344-54. doi: 10.1091/mbc.E10-09-0739. Epub 2011 Jul 27.
12	Calbindin 2 (CALB2) regulates 5-fluorouracil sensitivity in colorectal cancer by modulating the intrinsic apoptotic pathway.PLoS One. 2011;6(5):e20276. doi: 10.1371/journal.pone.0020276. Epub 2011 May 24.
13	Serum concentrations of a granulocyte-derived calcium-binding protein in cystic fibrosis patients and heterozygotes.Clin Chim Acta. 1987 Nov 30;170(1):45-55. doi: 10.1016/0009-8981(87)90382-2.
14	Downregulation of 425G>a variant of calcium-binding protein S100A14 associated with poor differentiation and prognosis in gastric cancer.J Cancer Res Clin Oncol. 2015 Apr;141(4):691-703. doi: 10.1007/s00432-014-1830-0. Epub 2014 Sep 30.
15	A 63 kDa skeletal muscle protein associated with eye muscle inflammation in Graves' disease is identified as the calcium binding protein calsequestrin.Autoimmunity. 1999;29(1):1-9. doi: 10.3109/08916939908995967.
16	The calcium-binding protein S100B down-regulates p53 and apoptosis in malignant melanoma.J Biol Chem. 2010 Aug 27;285(35):27487-27498. doi: 10.1074/jbc.M110.155382. Epub 2010 Jun 29.
17	Intravitreal S100B Injection Leads to Progressive Glaucoma Like Damage in Retina and Optic Nerve.Front Cell Neurosci. 2018 Sep 26;12:312. doi: 10.3389/fncel.2018.00312. eCollection 2018.
18	Clinicopathologic significance of S100A4 expression in osteosarcoma.Eur Rev Med Pharmacol Sci. 2014;18(6):833-9.
19	Clinical significance of calcium-binding protein S100A8 and S100A9 expression in non-small cell lung cancer.Thorac Cancer. 2018 Jul;9(7):800-804. doi: 10.1111/1759-7714.12649. Epub 2018 May 7.
20	The calcium binding protein S100A9 is essential for pancreatic leukocyte infiltration and induces disruption of cell-cell contacts.J Cell Physiol. 2008 Aug;216(2):558-67. doi: 10.1002/jcp.21433.
21	DNA methylation and immunohistochemical analysis of the S100A4 calcium binding protein in human prostate cancer.Prostate. 2007 Mar 1;67(4):341-7. doi: 10.1002/pros.20401.
22	Expression of memory, differentiation, and repression of c-myc and p53 genes in human RD/TE-671 cells induced by a ureido-derivative of pyridine (UDP-4).Cell Growth Differ. 1996 Jun;7(6):797-809.
23	Increased exonic de novo mutation rate in individuals with schizophrenia. Nat Genet. 2011 Jul 10;43(9):860-3. doi: 10.1038/ng.886.
24	The histone demethylase LSD1 is required for estrogen-dependent S100A7 gene expression in human breast cancer cells.Biochem Biophys Res Commun. 2012 Oct 19;427(2):336-42. doi: 10.1016/j.bbrc.2012.09.057. Epub 2012 Sep 18.
25	Reversing effect and mechanism of soluble resistance-related calcium-binding protein on multidrug resistance in human lung cancer A549/DDP cells.Mol Med Rep. 2015 Mar;11(3):2118-24. doi: 10.3892/mmr.2014.2936. Epub 2014 Nov 13.
26	Expression of S100A2 calcium-binding protein predicts response to pancreatectomy for pancreatic cancer.Gastroenterology. 2009 Aug;137(2):558-68, 568.e1-11. doi: 10.1053/j.gastro.2009.04.009. Epub 2009 Apr 16.
27	Platelet-Derived MRP-14 Induces Monocyte Activation in Patients With Symptomatic Peripheral Artery Disease.J Am Coll Cardiol. 2018 Jan 2;71(1):53-65. doi: 10.1016/j.jacc.2017.10.072.
28	The calcium-binding protein calretinin-22k, an alternative splicing product of the calretinin gene is expressed in several colon adeno carcinoma cell lines.Cell Calcium. 1996 Jul;20(1):63-72. doi: 10.1016/s0143-4160(96)90051-2.
29	Nuclear factor of activated T cells 5 maintained by Hotair suppression of miR-568 upregulates S100 calcium binding protein A4 to promote breast cancer metastasis.Breast Cancer Res. 2014 Oct 14;16(5):454. doi: 10.1186/s13058-014-0454-2.
30	A novel calcium-binding protein is associated with tau proteins in tauopathy.J Neurochem. 2008 Jul;106(1):96-106. doi: 10.1111/j.1471-4159.2008.05339.x. Epub 2008 Jul 1.
31	RAGE Mediates the Pro-Migratory Response of Extracellular S100A4 in Human Thyroid Cancer Cells.Thyroid. 2015 May;25(5):514-27. doi: 10.1089/thy.2014.0257. Epub 2015 Apr 3.
32	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.
33	Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
34	Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
35	Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
36	Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.