General Information of Drug Off-Target (DOT) (ID: OTXWR9TJ)

DOT Name Hyaluronan and proteoglycan link protein 1 (HAPLN1)
Synonyms Cartilage-linking protein 1; Cartilage-link protein; Proteoglycan link protein
Gene Name HAPLN1
Related Disease
Colon cancer ( )
Colon carcinoma ( )
Colonic neoplasm ( )
Colorectal carcinoma ( )
Congenital deformities of limbs ( )
Epithelial ovarian cancer ( )
Hepatocellular carcinoma ( )
Intervertebral disc degeneration ( )
Lung cancer ( )
Malignant pleural mesothelioma ( )
Mesothelioma ( )
Neoplasm ( )
Osteoarthritis ( )
Ovarian cancer ( )
Ovarian neoplasm ( )
Spinal muscular atrophy ( )
Spondyloepimetaphyseal dysplasia ( )
Spondyloepiphyseal dysplasia congenita ( )
Wagner disease ( )
Clear cell renal carcinoma ( )
Plasma cell myeloma ( )
Pseudoachondroplasia ( )
Colorectal neoplasm ( )
Ankylosing spondylitis ( )
Rheumatoid arthritis ( )
UniProt ID
HPLN1_HUMAN
3D Structure
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2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Pfam ID
PF07686 ; PF00193
Sequence
MKSLLLLVLISICWADHLSDNYTLDHDRAIHIQAENGPHLLVEAEQAKVFSHRGGNVTLP
CKFYRDPTAFGSGIHKIRIKWTKLTSDYLKEVDVFVSMGYHKKTYGGYQGRVFLKGGSDS
DASLVITDLTLEDYGRYKCEVIEGLEDDTVVVALDLQGVVFPYFPRLGRYNLNFHEAQQA
CLDQDAVIASFDQLYDAWRGGLDWCNAGWLSDGSVQYPITKPREPCGGQNTVPGVRNYGF
WDKDKSRYDVFCFTSNFNGRFYYLIHPTKLTYDEAVQACLNDGAQIAKVGQIFAAWKILG
YDRCDAGWLADGSVRYPISRPRRRCSPTEAAVRFVGFPDKKHKLYGVYCFRAYN
Function Stabilizes the aggregates of proteoglycan monomers with hyaluronic acid in the extracellular cartilage matrix.
Tissue Specificity Widely expressed. Weakly expressed in the brain.
Reactome Pathway
ECM proteoglycans (R-HSA-3000178 )

Molecular Interaction Atlas (MIA) of This DOT

25 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Colon cancer DISVC52G Strong Biomarker [1]
Colon carcinoma DISJYKUO Strong Biomarker [1]
Colonic neoplasm DISSZ04P Strong Biomarker [1]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [2]
Congenital deformities of limbs DISP4N1Q Strong Biomarker [3]
Epithelial ovarian cancer DIS56MH2 Strong Biomarker [4]
Hepatocellular carcinoma DIS0J828 Strong Biomarker [5]
Intervertebral disc degeneration DISG3AIM Strong Genetic Variation [6]
Lung cancer DISCM4YA Strong Altered Expression [7]
Malignant pleural mesothelioma DIST2R60 Strong Biomarker [7]
Mesothelioma DISKWK9M Strong Altered Expression [7]
Neoplasm DISZKGEW Strong Genetic Variation [7]
Osteoarthritis DIS05URM Strong Genetic Variation [8]
Ovarian cancer DISZJHAP Strong Biomarker [4]
Ovarian neoplasm DISEAFTY Strong Biomarker [4]
Spinal muscular atrophy DISTLKOB Strong Biomarker [9]
Spondyloepimetaphyseal dysplasia DISO4L5A Strong Genetic Variation [10]
Spondyloepiphyseal dysplasia congenita DISLC6W8 Strong Biomarker [11]
Wagner disease DISAJ1K0 Strong Biomarker [12]
Clear cell renal carcinoma DISBXRFJ moderate Biomarker [13]
Plasma cell myeloma DIS0DFZ0 moderate Biomarker [14]
Pseudoachondroplasia DISVJW4A moderate Genetic Variation [15]
Colorectal neoplasm DISR1UCN Disputed Biomarker [2]
Ankylosing spondylitis DISRC6IR Limited Genetic Variation [16]
Rheumatoid arthritis DISTSB4J Limited Biomarker [17]
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⏷ Show the Full List of 25 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the methylation of Hyaluronan and proteoglycan link protein 1 (HAPLN1). [18]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Hyaluronan and proteoglycan link protein 1 (HAPLN1). [25]
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12 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Tretinoin DM49DUI Approved Tretinoin increases the expression of Hyaluronan and proteoglycan link protein 1 (HAPLN1). [19]
Estradiol DMUNTE3 Approved Estradiol affects the expression of Hyaluronan and proteoglycan link protein 1 (HAPLN1). [20]
Vorinostat DMWMPD4 Approved Vorinostat increases the expression of Hyaluronan and proteoglycan link protein 1 (HAPLN1). [21]
Triclosan DMZUR4N Approved Triclosan decreases the expression of Hyaluronan and proteoglycan link protein 1 (HAPLN1). [22]
Progesterone DMUY35B Approved Progesterone decreases the expression of Hyaluronan and proteoglycan link protein 1 (HAPLN1). [23]
Panobinostat DM58WKG Approved Panobinostat increases the expression of Hyaluronan and proteoglycan link protein 1 (HAPLN1). [21]
Cytarabine DMZD5QR Approved Cytarabine decreases the expression of Hyaluronan and proteoglycan link protein 1 (HAPLN1). [24]
Belinostat DM6OC53 Phase 2 Belinostat increases the expression of Hyaluronan and proteoglycan link protein 1 (HAPLN1). [21]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Hyaluronan and proteoglycan link protein 1 (HAPLN1). [26]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Hyaluronan and proteoglycan link protein 1 (HAPLN1). [27]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Hyaluronan and proteoglycan link protein 1 (HAPLN1). [28]
Lithium chloride DMHYLQ2 Investigative Lithium chloride increases the expression of Hyaluronan and proteoglycan link protein 1 (HAPLN1). [29]
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⏷ Show the Full List of 12 Drug(s)

References

1 Gene expression profiling following constitutive activation of MEK1 and transformation of rat intestinal epithelial cells.Mol Cancer. 2006 Nov 17;5:63. doi: 10.1186/1476-4598-5-63.
2 Genomic and epigenomic integration identifies a prognostic signature in colon cancer.Clin Cancer Res. 2011 Mar 15;17(6):1535-45. doi: 10.1158/1078-0432.CCR-10-2509. Epub 2011 Jan 28.
3 Mice lacking link protein develop dwarfism and craniofacial abnormalities.Nat Genet. 1999 Feb;21(2):225-9. doi: 10.1038/6016.
4 A natural entkaurane diterpenoid induces antiproliferation in ovarian cancer cells via ERK1/2 regulation and inhibition of cellular migration and invasion.Mol Med Rep. 2018 Oct;18(4):3898-3906. doi: 10.3892/mmr.2018.9377. Epub 2018 Aug 9.
5 De novo HAPLN1 expression hallmarks Wnt-induced stem cell and fibrogenic networks leading to aggressive human hepatocellular carcinomas.Oncotarget. 2016 Jun 28;7(26):39026-39043. doi: 10.18632/oncotarget.9346.
6 Single-nucleotide polymorphism in the hyaluronan and proteoglycan link protein 1 (HAPLN1) gene is associated with spinal osteophyte formation and disc degeneration in Japanese women.Eur Spine J. 2011 Apr;20(4):572-7. doi: 10.1007/s00586-010-1598-0. Epub 2010 Oct 15.
7 Protumorigenic role of HAPLN1 and its IgV domain in malignant pleural mesothelioma.Clin Cancer Res. 2009 Apr 15;15(8):2602-11. doi: 10.1158/1078-0432.CCR-08-2755. Epub 2009 Apr 7.
8 Investigation of the association of the CRTM and CRTL1 genes with radiographically evident osteoarthritis in subjects from the Rotterdam study.Arthritis Rheum. 1997 Oct;40(10):1760-5. doi: 10.1002/art.1780401006.
9 Do Perineuronal Net Elements Contribute to Pathophysiology of Spinal Muscular Atrophy? In Vitro and Transcriptomics Insights.OMICS. 2018 Sep;22(9):598-606. doi: 10.1089/omi.2018.0106. Epub 2018 Aug 14.
10 Linkage studies of a Missouri kindred with autosomal dominant spondyloepimetaphyseal dysplasia (SEMD) indicate genetic heterogeneity.J Bone Miner Res. 1997 Aug;12(8):1204-9. doi: 10.1359/jbmr.1997.12.8.1204.
11 Genetic rescue of chondrodysplasia and the perinatal lethal effect of cartilage link protein deficiency.J Biol Chem. 2003 Oct 3;278(40):39214-23. doi: 10.1074/jbc.M303329200. Epub 2003 May 5.
12 Refined genetic and physical localization of the Wagner disease (WGN1) locus and the genes CRTL1 and CSPG2 to a 2- to 2.5-cM region of chromosome 5q14.3. Genomics. 1999 Apr 15;57(2):219-26. doi: 10.1006/geno.1999.5766.
13 Identification of potential pathogenic biomarkers in clear cell renal cell carcinoma.Oncol Lett. 2018 Jun;15(6):8491-8499. doi: 10.3892/ol.2018.8398. Epub 2018 Mar 30.
14 Hyaluronan and proteoglycan link protein 1 (HAPLN1) activates bortezomib-resistant NF-B activity and increases drug resistance in multiple myeloma.J Biol Chem. 2018 Feb 16;293(7):2452-2465. doi: 10.1074/jbc.RA117.000667. Epub 2017 Dec 26.
15 Exclusion of human proteoglycan link protein (CRTL1) and type II collagen (COL2A1) genes in pseudoachondroplasia.Am J Med Genet. 1992 Nov 1;44(4):420-4. doi: 10.1002/ajmg.1320440406.
16 Association study of polymorphisms rs4552569 and rs17095830 and the risk of ankylosing spondylitis in a Taiwanese population.PLoS One. 2013;8(1):e52801. doi: 10.1371/journal.pone.0052801. Epub 2013 Jan 4.
17 Distinctive gene expression signatures in rheumatoid arthritis synovial tissue fibroblast cells: correlates with disease activity.Genes Immun. 2007 Sep;8(6):480-91. doi: 10.1038/sj.gene.6364400. Epub 2007 Jun 14.
18 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.
19 Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
20 Estradiol and selective estrogen receptor modulators differentially regulate target genes with estrogen receptors alpha and beta. Mol Biol Cell. 2004 Mar;15(3):1262-72. doi: 10.1091/mbc.e03-06-0360. Epub 2003 Dec 29.
21 A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
22 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
23 Effects of progesterone treatment on expression of genes involved in uterine quiescence. Reprod Sci. 2011 Aug;18(8):781-97.
24 Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
25 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.
26 Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
27 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.
28 From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
29 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.