Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7ZWSSD)

• DOT Name: C-C chemokine receptor type 10 (CCR10)
• Synonyms: C-C CKR-10; CC-CKR-10; CCR-10; G-protein coupled receptor 2
• Gene Name: CCR10
• Related Disease:
  Asthma
  Adult glioblastoma
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Colitis
  Dermatitis
  Glioblastoma multiforme
  Glioma
  IgA nephropathy
  Inflammation
  Neoplasm
  Plasma cell myeloma
  Potassium-aggravated myotonia
  Primary cutaneous T-cell lymphoma
  Psoriasis
  Pulmonary fibrosis
  Rheumatoid arthritis
  Sezary syndrome
  Skin disease
  Status epilepticus seizure
  Stevens-Johnson syndrome
  Toxic epidermal necrolysis
  Osteoarthritis
  Arthritis
  Adult T-cell leukemia/lymphoma
  Allergic contact dermatitis
  Atopic dermatitis
  Granular corneal dystrophy type II
  Hepatocellular carcinoma
  Lymphoproliferative syndrome
  Mycosis fungoides
• UniProt ID: CCR10_HUMAN
• Pfam ID: PF00001
• Sequence:
  MGTEATEQVSWGHYSGDEEDAYSAEPLPELCYKADVQAFSRAFQPSVSLTVAALGLAGNG
  LVLATHLAARRAARSPTSAHLLQLALADLLLALTLPFAAAGALQGWSLGSATCRTISGLY
  SASFHAGFLFLACISADRYVAIARALPAGPRPSTPGRAHLVSVIVWLLSLLLALPALLFS
  QDGQREGQRRCRLIFPEGLTQTVKGASAVAQVALGFALPLGVMVACYALLGRTLLAARGP
  ERRRALRVVVALVAAFVVLQLPYSLALLLDTADLLAARERSCPASKRKDVALLVTSGLAL
  ARCGLNPVLYAFLGLRFRQDLRRLLRGGSCPSGPQPRRGCPRRPRLSSCSAPTETHSLSW
  DN
• Function: Receptor for chemokines SCYA27 and SCYA28. Subsequently transduces a signal by increasing the intracellular calcium ions level and stimulates chemotaxis in a pre-B cell line.
• Tissue Specificity: Expressed at high levels in adult testis, small intestine, fetal lung, fetal kidney. Weaker expression was observed in many other adult tissues including spleen, thymus, lymph node, Peyer patches, colon, heart, ovary, peripheral blood lymphocytes, thyroid and spinal cord. Also expressed by melanocytes, dermal fibroblasts, dermal microvascular endothelial cells. Also detected in T-cells and in skin-derived Langerhans cells.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  Viral protein interaction with cytokine and cytokine receptor (hsa04061)
  Chemokine sig.ling pathway (hsa04062)
  Intesti.l immune network for IgA production (hsa04672)
• Reactome Pathway:
  G alpha (i) signalling events (R-HSA-418594)
  Chemokine receptors bind chemokines (R-HSA-380108)

Molecular Interaction Atlas (MIA) of This DOT

32 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Asthma	DISW9QNS	Definitive	Biomarker	[1]
Adult glioblastoma	DISVP4LU	Strong	Altered Expression	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Breast cancer	DIS7DPX1	Strong	Biomarker	[4]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[4]
Colitis	DISAF7DD	Strong	Altered Expression	[5]
Dermatitis	DISY5SZC	Strong	Biomarker	[6]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[2]
Glioma	DIS5RPEH	Strong	Altered Expression	[2]
IgA nephropathy	DISZ8MTK	Strong	Biomarker	[7]
Inflammation	DISJUQ5T	Strong	Biomarker	[8]
Neoplasm	DISZKGEW	Strong	Biomarker	[9]
Plasma cell myeloma	DIS0DFZ0	Strong	Altered Expression	[10]
Potassium-aggravated myotonia	DISRO6ZH	Strong	Genetic Variation	[11]
Primary cutaneous T-cell lymphoma	DIS35WVW	Strong	Altered Expression	[12]
Psoriasis	DIS59VMN	Strong	Biomarker	[13]
Pulmonary fibrosis	DISQKVLA	Strong	Biomarker	[14]
Rheumatoid arthritis	DISTSB4J	Strong	Altered Expression	[15]
Sezary syndrome	DISFMTC7	Strong	Biomarker	[16]
Skin disease	DISDW8R6	Strong	Biomarker	[8]
Status epilepticus seizure	DISY3BIC	Strong	Biomarker	[17]
Stevens-Johnson syndrome	DISZG4YX	Strong	Biomarker	[18]
Toxic epidermal necrolysis	DISIWPFR	Strong	Biomarker	[18]
Osteoarthritis	DIS05URM	moderate	Altered Expression	[15]
Arthritis	DIST1YEL	Disputed	Altered Expression	[19]
Adult T-cell leukemia/lymphoma	DIS882XU	Limited	Biomarker	[20]
Allergic contact dermatitis	DISFFVF9	Limited	Altered Expression	[21]
Atopic dermatitis	DISTCP41	Limited	Altered Expression	[22]
Granular corneal dystrophy type II	DISAEE20	Limited	Biomarker	[21]
Hepatocellular carcinoma	DIS0J828	Limited	Altered Expression	[9]
Lymphoproliferative syndrome	DISMVL8O	Limited	Biomarker	[23]
Mycosis fungoides	DIS62RB8	Limited	Biomarker	[20]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of C-C chemokine receptor type 10 (CCR10).	[24]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of C-C chemokine receptor type 10 (CCR10).	[25]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of C-C chemokine receptor type 10 (CCR10).	[26]

1 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 C-C chemokine receptor type 10 (CCR10).	[27]

References

• [1] CCR10(+) ILC2s with ILC1-like properties exhibit a protective function in severe allergic asthma.Allergy. 2019 May;74(5):933-943. doi: 10.1111/all.13679. Epub 2018 Dec 28.
• [2] Upregulation of chemokine receptor CCR10 is essential for glioma proliferation, invasion and patient survival.Oncotarget. 2014 Aug 30;5(16):6576-83. doi: 10.18632/oncotarget.2134.
• [3] Genes associated with inflammation and the cell cycle may serve as biomarkers for the diagnosis and prognosis of acute myocardial infarction in a Chinese population.Mol Med Rep. 2018 Aug;18(2):1311-1322. doi: 10.3892/mmr.2018.9077. Epub 2018 May 25.
• [4] CCR10 activation stimulates the invasion and migration of breast cancer cells through the ERK1/2/MMP-7 signaling pathway.Int Immunopharmacol. 2017 Oct;51:124-130. doi: 10.1016/j.intimp.2017.07.018. Epub 2017 Aug 19.
• [5] Functional characterization of CXCR4 in mediating the expression of protein C system in experimental ulcerative colitis.Am J Transl Res. 2017 Nov 15;9(11):4821-4835. eCollection 2017.
• [6] CCR10 regulates balanced maintenance and function of resident regulatory and effector T cells to promote immune homeostasis in the skin.J Allergy Clin Immunol. 2014 Sep;134(3):634-644.e10. doi: 10.1016/j.jaci.2014.03.010. Epub 2014 Apr 24.
• [7] Intrinsic renal cells induce lymphocytosis of Th22 cells from IgA nephropathy patients through B7-CTLA-4 and CCL-CCR pathways.Mol Cell Biochem. 2018 Apr;441(1-2):191-199. doi: 10.1007/s11010-017-3185-8. Epub 2017 Sep 5.
• [8] Lymphatic precollectors contain a novel, specialized subpopulation of podoplanin low, CCL27-expressing lymphatic endothelial cells.Am J Pathol. 2008 Oct;173(4):1202-9. doi: 10.2353/ajpath.2008.080101. Epub 2008 Sep 4.
• [9] The chemokine receptor CCR10 promotes inflammation-driven hepatocarcinogenesis via PI3K/Akt pathway activation.Cell Death Dis. 2018 Feb 14;9(2):232. doi: 10.1038/s41419-018-0267-9.
• [10] CCR10/CCL27 crosstalk contributes to failure of proteasome-inhibitors in multiple myeloma.Oncotarget. 2016 Nov 29;7(48):78605-78618. doi: 10.18632/oncotarget.12522.
• [11] Chemokine Receptor Expression Pattern Correlates to Progression of Conjunctival Melanocytic Lesions.Invest Ophthalmol Vis Sci. 2019 Jul 1;60(8):2950-2957. doi: 10.1167/iovs.19-27162.
• [12] Expression of CCR3 and CCR4 Suggests a Poor Prognosis in Mycosis Fungoides and Szary Syndrome.Acta Derm Venereol. 2019 Jul 1;99(9):809-812. doi: 10.2340/00015555-3207.
• [13] c-Kit-positive ILC2s exhibit an ILC3-like signature that may contribute to IL-17-mediated pathologies.Nat Immunol. 2019 Aug;20(8):992-1003. doi: 10.1038/s41590-019-0423-0. Epub 2019 Jul 1.
• [14] CCR10+ epithelial cells from idiopathic pulmonary fibrosis lungs drive remodeling.JCI Insight. 2018 Aug 23;3(16):e122211. doi: 10.1172/jci.insight.122211. eCollection 2018 Aug 23.
• [15] Th22 Cells Promote Osteoclast Differentiation via Production of IL-22 in Rheumatoid Arthritis.Front Immunol. 2018 Dec 10;9:2901. doi: 10.3389/fimmu.2018.02901. eCollection 2018.
• [16] Chemokine receptor expression by leukemic T cells of cutaneous T-cell lymphoma: clinical and histopathological correlations.J Invest Dermatol. 2007 Dec;127(12):2882-92. doi: 10.1038/sj.jid.5700916. Epub 2007 Jun 28.
• [17] CCR7, CCR8, CCR9 and CCR10 in the mouse hippocampal CA1 area and the dentate gyrus during and after pilocarpine-induced status epilepticus.J Neurochem. 2007 Feb;100(4):1072-88. doi: 10.1111/j.1471-4159.2006.04272.x. Epub 2007 Dec 20.
• [18] Involvement of CCL27-CCR10 interactions in drug-induced cutaneous reactions.J Allergy Clin Immunol. 2004 Aug;114(2):335-40. doi: 10.1016/j.jaci.2004.04.034.
• [19] Characterising the expression and function of CCL28 and its corresponding receptor, CCR10, in RA pathogenesis.Ann Rheum Dis. 2015 Oct;74(10):1898-906. doi: 10.1136/annrheumdis-2013-204530. Epub 2014 May 15.
• [20] Microarray analysis of gene expression by microdissected epidermis and dermis in mycosis fungoides and adult T-cell leukemia/lymphoma.Int J Oncol. 2014 Sep;45(3):1200-8. doi: 10.3892/ijo.2014.2524. Epub 2014 Jun 26.
• [21] Increased CCL27-CCR10 expression in allergic contact dermatitis: implications for local skin memory.J Pathol. 2004 Sep;204(1):39-46. doi: 10.1002/path.1619.
• [22] T helper 22 cells from Han Chinese patients with atopic dermatitis exhibit high expression of inducible T-cell costimulator.Br J Dermatol. 2020 Mar;182(3):648-657. doi: 10.1111/bjd.18040. Epub 2019 Aug 19.
• [23] CCR10 is expressed in cutaneous T-cell lymphoma.Int J Cancer. 2005 Jul 1;115(4):641-7. doi: 10.1002/ijc.20922.
• [24] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [25] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [26] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [27] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.