Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTS79FNF)

DOT Name CD177 antigen (CD177)
Synonyms Human neutrophil alloantigen 2a; HNA-2a; NB1 glycoprotein; NB1 GP; Polycythemia rubra vera protein 1; PRV-1; CD antigen CD177
Gene Name CD177
Related Disease
Acute myelogenous leukaemia ( )
Alzheimer disease ( )
Anti-neutrophil cytoplasmic antibody-associated vasculitis ( )
Autoimmune disease ( )
Benign prostatic hyperplasia ( )
Beta thalassemia ( )
Campomelic dysplasia ( )
Colitis ( )
Craniometaphyseal dysplasia, autosomal dominant ( )
Gastric cancer ( )
Influenza ( )
Matthew-Wood syndrome ( )
Metastatic malignant neoplasm ( )
Myelodysplastic syndrome ( )
Myelofibrosis ( )
Myeloproliferative neoplasm ( )
Myositis disease ( )
Non-small-cell lung cancer ( )
Ocular melanoma ( )
Polycythemia ( )
Primary myelofibrosis ( )
Prostate cancer ( )
Prostate carcinoma ( )
Prostate neoplasm ( )
Skin and skin-structure infection ( )
Stomach cancer ( )
Thalassemia ( )
Thrombocythemia ( )
Thrombocytosis disease ( )
Vasculitis ( )
Leukopenia ( )
Neoplasm ( )
Advanced cancer ( )
Breast cancer ( )
Breast carcinoma ( )
Colorectal carcinoma ( )
Gastritis ( )
Multiple sclerosis ( )
Neuroblastoma ( )
Thrombosis ( )
UniProt ID
CD177_HUMAN
3D Structure
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2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Pfam ID
PF00021
Sequence
MSAVLLLALLGFILPLPGVQALLCQFGTVQHVWKVSDLPRQWTPKNTSCDSGLGCQDTLM
LIESGPQVSLVLSKGCTEAKDQEPRVTEHRMGPGLSLISYTFVCRQEDFCNNLVNSLPLW
APQPPADPGSLRCPVCLSMEGCLEGTTEEICPKGTTHCYDGLLRLRGGGIFSNLRVQGCM
PQPGCNLLNGTQEIGPVGMTENCNRKDFLTCHRGTTIMTHGNLAQEPTDWTTSNTEMCEV
GQVCQETLLLLDVGLTSTLVGTKGCSTVGAQNSQKTTIHSAPPGVLVASYTHFCSSDLCN
SASSSSVLLNSLPPQAAPVPGDRQCPTCVQPLGTCSSGSPRMTCPRGATHCYDGYIHLSG
GGLSTKMSIQGCVAQPSSFLLNHTRQIGIFSAREKRDVQPPASQHEGGGAEGLESLTWGV
GLALAPALWWGVVCPSC
Function
In association with beta-2 integrin heterodimer ITGAM/CD11b and ITGB2/CD18, mediates activation of TNF-alpha primed neutrophils including degranulation and superoxide production. In addition, by preventing beta-2 integrin internalization and attenuating chemokine signaling favors adhesion over migration. Heterophilic interaction with PECAM1 on endothelial cells plays a role in neutrophil transendothelial migration in vitro. However, appears to be dispensable for neutrophil recruitment caused by bacterial infection in vivo. Acts as a receptor for the mature form of protease PRTN3 allowing its display at the cell surface of neutrophils. By displaying PRTN3 at the neutrophil cell surface, may play a role in enhancing endothelial cell junctional integrity and thus vascular integrity during neutrophil diapedesis.
Tissue Specificity
Highly expressed in normal bone marrow and weakly expressed in fetal liver . During neutrophil differentiation, expression begins at the metamyelocyte stage and continues throughout the subsequent stages (at protein level) . Expressed by a subset of mature neutrophils (at protein level) . The percentage of neutrophils expressing CD177 varies across the population . Expressed in granulocytes of patients with polycythemia vera (PV) and with essential thrombocythemia (ET) .
Reactome Pathway
Cell surface interactions at the vascular wall (R-HSA-202733 )
Neutrophil degranulation (R-HSA-6798695 )
Common Pathway of Fibrin Clot Formation (R-HSA-140875 )

Molecular Interaction Atlas (MIA) of This DOT

40 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Acute myelogenous leukaemia DISCSPTN Strong Altered Expression [1]
Alzheimer disease DISF8S70 Strong Altered Expression [2]
Anti-neutrophil cytoplasmic antibody-associated vasculitis DISBEQIT Strong Altered Expression [3]
Autoimmune disease DISORMTM Strong Biomarker [4]
Benign prostatic hyperplasia DISI3CW2 Strong Altered Expression [5]
Beta thalassemia DIS5RCQK Strong Altered Expression [6]
Campomelic dysplasia DISVTW53 Strong Altered Expression [7]
Colitis DISAF7DD Strong Biomarker [8]
Craniometaphyseal dysplasia, autosomal dominant DISU12OO Strong Altered Expression [7]
Gastric cancer DISXGOUK Strong Biomarker [9]
Influenza DIS3PNU3 Strong Biomarker [10]
Matthew-Wood syndrome DISA7HR7 Strong Altered Expression [11]
Metastatic malignant neoplasm DIS86UK6 Strong Biomarker [12]
Myelodysplastic syndrome DISYHNUI Strong Altered Expression [13]
Myelofibrosis DISIMP21 Strong Genetic Variation [14]
Myeloproliferative neoplasm DIS5KAPA Strong Genetic Variation [14]
Myositis disease DISCIXF0 Strong Biomarker [15]
Non-small-cell lung cancer DIS5Y6R9 Strong Altered Expression [16]
Ocular melanoma DISOHHFC Strong Genetic Variation [17]
Polycythemia DIS8B6VW Strong Genetic Variation [18]
Primary myelofibrosis DIS6L0CN Strong Genetic Variation [14]
Prostate cancer DISF190Y Strong Altered Expression [19]
Prostate carcinoma DISMJPLE Strong Altered Expression [19]
Prostate neoplasm DISHDKGQ Strong Altered Expression [5]
Skin and skin-structure infection DIS3F9EY Strong Biomarker [20]
Stomach cancer DISKIJSX Strong Biomarker [9]
Thalassemia DIS76XZB Strong Altered Expression [6]
Thrombocythemia DISL38J3 Strong Biomarker [21]
Thrombocytosis disease DISNG0P4 Strong Altered Expression [22]
Vasculitis DISQRKDX Strong Biomarker [23]
Leukopenia DISJMBMM moderate Biomarker [24]
Neoplasm DISZKGEW moderate Biomarker [25]
Advanced cancer DISAT1Z9 Limited Biomarker [8]
Breast cancer DIS7DPX1 Limited Biomarker [26]
Breast carcinoma DIS2UE88 Limited Biomarker [26]
Colorectal carcinoma DIS5PYL0 Limited Biomarker [12]
Gastritis DIS8G07K Limited Biomarker [27]
Multiple sclerosis DISB2WZI Limited Biomarker [28]
Neuroblastoma DISVZBI4 Limited Altered Expression [29]
Thrombosis DIS2TXP8 Limited Altered Expression [30]
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⏷ Show the Full List of 40 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
3 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 CD177 antigen (CD177). [31]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide increases the expression of CD177 antigen (CD177). [32]
Methamphetamine DMPM4SK Approved Methamphetamine increases the expression of CD177 antigen (CD177). [33]
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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 increases the methylation of CD177 antigen (CD177). [34]
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References

1 Cloning of PRV-1, a novel member of the uPAR receptor superfamily, which is overexpressed in polycythemia rubra vera.Blood. 2000 Apr 15;95(8):2569-76.
2 Polymorphonuclear Neutrophil Functions are Differentially Altered in Amnestic Mild Cognitive Impairment and Mild Alzheimer's Disease Patients.J Alzheimers Dis. 2017;60(1):23-42. doi: 10.3233/JAD-170124.
3 Differential expression of granulopoiesis related genes in neutrophil subsets distinguished by membrane expression of CD177.PLoS One. 2014 Jun 13;9(6):e99671. doi: 10.1371/journal.pone.0099671. eCollection 2014.
4 Gene silencing and a novel monoallelic expression pattern in distinct CD177 neutrophil subsets.J Exp Med. 2017 Jul 3;214(7):2089-2101. doi: 10.1084/jem.20161093. Epub 2017 May 30.
5 Epidermal growth factor receptor mRNA levels in human prostatic tumors and cell lines.J Urol. 1990 Jun;143(6):1272-4. doi: 10.1016/s0022-5347(17)40253-9.
6 Increased CD177 (PRV1) expression in thalassaemia and the underlying erythropoietic activity.Br J Haematol. 2008 Apr;141(1):100-4. doi: 10.1111/j.1365-2141.2008.06993.x.
7 Clinical significance of neutrophil CD177 mRNA expression in Ph-negative chronic myeloproliferative disorders.Br J Haematol. 2004 Sep;126(5):650-6. doi: 10.1111/j.1365-2141.2004.05098.x.
8 CD177+ neutrophils suppress epithelial cell tumourigenesis in colitis-associated cancer and predict good prognosis in colorectal cancer.Carcinogenesis. 2018 Feb 9;39(2):272-282. doi: 10.1093/carcin/bgx142.
9 Gene expression analysis of a Helicobacter pylori-infected and high-salt diet-treated mouse gastric tumor model: identification of CD177 as a novel prognostic factor in patients with gastric cancer.BMC Gastroenterol. 2013 Jul 30;13:122. doi: 10.1186/1471-230X-13-122.
10 Receptor binding by a ferret-transmissible H5 avian influenza virus.Nature. 2013 May 16;497(7449):392-6. doi: 10.1038/nature12144. Epub 2013 Apr 24.
11 Neutrophils infiltrating pancreatic ductal adenocarcinoma indicate higher malignancy and worse prognosis.Biochem Biophys Res Commun. 2018 Jun 18;501(1):313-319. doi: 10.1016/j.bbrc.2018.05.024. Epub 2018 May 9.
12 Tumour-infiltrating neutrophils counteract anti-VEGF therapy in metastatic colorectal cancer.Br J Cancer. 2019 Jan;120(1):69-78. doi: 10.1038/s41416-018-0198-3. Epub 2018 Oct 31.
13 Overexpression of the polycythemia rubra vera-1 gene in essential thrombocythemia.J Clin Oncol. 2002 Oct 15;20(20):4249-54. doi: 10.1200/JCO.2002.11.507.
14 Deregulation of apoptosis-related genes is associated with PRV1 overexpression and JAK2 V617F allele burden in Essential Thrombocythemia and Myelofibrosis.J Hematol Oncol. 2012 Feb 2;5:2. doi: 10.1186/1756-8722-5-2.
15 Detection of piscine orthoreoviruses (PRV-1 and PRV-3) in Atlantic salmon and rainbow trout farmed in Germany.Transbound Emerg Dis. 2019 Jan;66(1):14-21. doi: 10.1111/tbed.13018. Epub 2018 Nov 23.
16 CD117 expression is a predictive marker for poor prognosis in patients with non-small cell lung cancer.Oncol Lett. 2017 May;13(5):3703-3708. doi: 10.3892/ol.2017.5925. Epub 2017 Mar 27.
17 KIT mutations in ocular melanoma: frequency and anatomic distribution.Mod Pathol. 2011 Aug;24(8):1031-5. doi: 10.1038/modpathol.2011.57. Epub 2011 Apr 8.
18 Dynamic ligand modulation of EPO receptor pools, and dysregulation by polycythemia-associated EPOR alleles.PLoS One. 2012;7(1):e29064. doi: 10.1371/journal.pone.0029064. Epub 2012 Jan 12.
19 Erythropoietin stimulates growth and STAT5 phosphorylation in human prostate epithelial and prostate cancer cells.Prostate. 2006 Feb 1;66(2):135-45. doi: 10.1002/pros.20310.
20 Characterization of a novel mouse model with genetic deletion of CD177.Protein Cell. 2015 Feb;6(2):117-26. doi: 10.1007/s13238-014-0109-1. Epub 2014 Oct 31.
21 Comparison of molecular markers in a cohort of patients with chronic myeloproliferative disorders.Blood. 2003 Sep 1;102(5):1869-71. doi: 10.1182/blood-2003-03-0744. Epub 2003 May 1.
22 Discrimination of polycythemias and thrombocytoses by novel, simple, accurate clonality assays and comparison with PRV-1 expression and BFU-E response to erythropoietin.Blood. 2003 Apr 15;101(8):3294-301. doi: 10.1182/blood-2002-07-2287. Epub 2002 Dec 19.
23 Lessons from a double-transgenic neutrophil approach to induce antiproteinase 3 antibody-mediated vasculitis in mice.J Leukoc Biol. 2016 Dec;100(6):1443-1452. doi: 10.1189/jlb.5A0116-037R. Epub 2016 Jun 30.
24 Prolonged neutropenia due to antihuman neutrophil antigen 2 (CD177) antibody after bone marrow transplantation.Pediatr Blood Cancer. 2017 Jul;64(7). doi: 10.1002/pbc.26388. Epub 2016 Dec 1.
25 Interaction between Tumor Cell Surface Receptor RAGE and Proteinase 3 Mediates Prostate Cancer Metastasis to Bone.Cancer Res. 2017 Jun 15;77(12):3144-3150. doi: 10.1158/0008-5472.CAN-16-0708. Epub 2017 Apr 20.
26 Role of TGF- receptor III localization in polarity and breast cancer progression.Mol Biol Cell. 2014 Aug 1;25(15):2291-304. doi: 10.1091/mbc.E14-03-0825. Epub 2014 May 28.
27 CD177 Expression and Inflammation Grade in Helicobacter pylori-Infected Wild-Type and CD177(-/-) C57BL/6 Mice.Anal Cell Pathol (Amst). 2019 Apr 4;2019:9506863. doi: 10.1155/2019/9506863. eCollection 2019.
28 Expression of the activation marker urokinase plasminogen-activator receptor in cultured human central nervous system microglia.J Neurosci Res. 1996 Aug 15;45(4):392-9. doi: 10.1002/(SICI)1097-4547(19960815)45:4<392::AID-JNR8>3.0.CO;2-4.
29 Bone marrow-infiltrating human neuroblastoma cells express high levels of calprotectin and HLA-G proteins.PLoS One. 2012;7(1):e29922. doi: 10.1371/journal.pone.0029922. Epub 2012 Jan 9.
30 Thrombotic and bleeding complications in four subpopulations of patients with essential thrombocythemia defined by c-Mpl protein expression and PRV-1 mRNA levels.Haematologica. 2005 Jun;90(6):851-3.
31 Effects of lithium and valproic acid on gene expression and phenotypic markers in an NT2 neurosphere model of neural development. PLoS One. 2013;8(3):e58822.
32 Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
33 Methamphetamine alters the normal progression by inducing cell cycle arrest in astrocytes. PLoS One. 2014 Oct 7;9(10):e109603.
34 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.