Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMPOB4E)

DOT Name Hyaluronidase PH-20 (SPAM1)
Synonyms Hyal-PH20; EC 3.2.1.35; Hyaluronoglucosaminidase PH-20; Sperm adhesion molecule 1; Sperm surface protein PH-20
Gene Name SPAM1
Related Disease
Bladder cancer ( )
Breast cancer ( )
Breast carcinoma ( )
Ductal breast carcinoma in situ ( )
Endometrial cancer ( )
Endometrial carcinoma ( )
Invasive breast carcinoma ( )
Melanoma ( )
Metastatic malignant neoplasm ( )
Morquio syndrome ( )
Mucopolysaccharidosis ( )
Nasal polyp ( )
Prostate cancer ( )
Prostate carcinoma ( )
Urinary bladder cancer ( )
Urinary bladder neoplasm ( )
Chronic obstructive pulmonary disease ( )
Epithelial ovarian cancer ( )
Neoplasm ( )
Squamous cell carcinoma ( )
UniProt ID
HYALP_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
EC Number
3.2.1.35
Pfam ID
PF01630
Sequence
MGVLKFKHIFFRSFVKSSGVSQIVFTFLLIPCCLTLNFRAPPVIPNVPFLWAWNAPSEFC
LGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISL
QDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLS
LTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHHYKKPGYNGSCFN
VEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPV
FAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGTLSIMRSMKSCLLLDNYMET
ILNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK
PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAFLKPPMETEEPQI
FYNASPSTLSATMFIVSILFLIISSVASL
Function
Involved in sperm-egg adhesion. Upon fertilization sperm must first penetrate a layer of cumulus cells that surrounds the egg before reaching the zona pellucida. The cumulus cells are embedded in a matrix containing hyaluronic acid which is formed prior to ovulation. This protein aids in penetrating the layer of cumulus cells by digesting hyaluronic acid.
Tissue Specificity Testis.
KEGG Pathway
Glycosaminoglycan degradation (hsa00531 )
Metabolic pathways (hsa01100 )
Lysosome (hsa04142 )
Reactome Pathway
Interaction With Cumulus Cells And The Zona Pellucida (R-HSA-2534343 )
BioCyc Pathway
MetaCyc:HS02884-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

20 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Bladder cancer DISUHNM0 Strong Biomarker [1]
Breast cancer DIS7DPX1 Strong Biomarker [2]
Breast carcinoma DIS2UE88 Strong Altered Expression [2]
Ductal breast carcinoma in situ DISLCJY7 Strong Altered Expression [2]
Endometrial cancer DISW0LMR Strong Altered Expression [3]
Endometrial carcinoma DISXR5CY Strong Biomarker [3]
Invasive breast carcinoma DISANYTW Strong Altered Expression [2]
Melanoma DIS1RRCY Strong Biomarker [4]
Metastatic malignant neoplasm DIS86UK6 Strong Biomarker [2]
Morquio syndrome DIS2Y2P2 Strong Altered Expression [5]
Mucopolysaccharidosis DISB083T Strong Altered Expression [5]
Nasal polyp DISLP3XE Strong Biomarker [6]
Prostate cancer DISF190Y Strong Biomarker [7]
Prostate carcinoma DISMJPLE Strong Biomarker [7]
Urinary bladder cancer DISDV4T7 Strong Biomarker [1]
Urinary bladder neoplasm DIS7HACE Strong Biomarker [1]
Chronic obstructive pulmonary disease DISQCIRF Limited Altered Expression [8]
Epithelial ovarian cancer DIS56MH2 Limited Altered Expression [9]
Neoplasm DISZKGEW Limited Biomarker [10]
Squamous cell carcinoma DISQVIFL Limited Altered Expression [11]
------------------------------------------------------------------------------------
⏷ Show the Full List of 20 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
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 Hyaluronidase PH-20 (SPAM1). [12]
------------------------------------------------------------------------------------

References

1 Antitumor activity of sulfated hyaluronic acid fragments in pre-clinical models of bladder cancer.Oncotarget. 2017 Apr 11;8(15):24262-24274. doi: 10.18632/oncotarget.10529.
2 Expression of PH-20 in normal and neoplastic breast tissue.J Surg Res. 2002 Apr;103(2):203-7. doi: 10.1006/jsre.2002.6351.
3 Expression patterns of hyaluronan, hyaluronan synthases and hyaluronidases indicate a role for hyaluronan in the progression of endometrial cancer.Gynecol Oncol. 2005 Aug;98(2):193-202. doi: 10.1016/j.ygyno.2005.02.031.
4 Hyaluronidase expression by an oncolytic adenovirus enhances its intratumoral spread and suppresses tumor growth.Mol Ther. 2010 Jul;18(7):1275-83. doi: 10.1038/mt.2010.79. Epub 2010 May 4.
5 Serum hyaluronidase aberrations in metabolic and morphogenetic disorders.Glycoconj J. 2005 Nov;22(7-9):395-400. doi: 10.1007/s10719-005-1390-2.
6 Hyaluronan synthases and hyaluronidases in nasal polyps.Eur Arch Otorhinolaryngol. 2016 Jul;273(7):1801-8. doi: 10.1007/s00405-015-3848-6. Epub 2015 Dec 10.
7 Hyaluronidase gene profiling and role of hyal-1 overexpression in an orthotopic model of prostate cancer.Int J Cancer. 2002 Feb 1;97(4):416-24. doi: 10.1002/ijc.1638.
8 Serum levels of hyaluronic acid are associated with COPD severity and predict survival.Eur Respir J. 2019 Mar 7;53(3):1801183. doi: 10.1183/13993003.01183-2018. Print 2019 Mar.
9 Subtype specific elevated expression of hyaluronidase-1 (HYAL-1) in epithelial ovarian cancer.PLoS One. 2011;6(6):e20705. doi: 10.1371/journal.pone.0020705. Epub 2011 Jun 10.
10 Degradation of tumour stromal hyaluronan by small extracellular vesicle-PH20 stimulates CD103(+) dendritic cells and in combination with PD-L1 blockade boosts anti-tumour immunity.J Extracell Vesicles. 2019 Sep 28;8(1):1670893. doi: 10.1080/20013078.2019.1670893. eCollection 2019.
11 The investigation of hyaluronic acid and hyaluronidase-1 levels as tumour marker in larynx cancer.Clin Otolaryngol. 2019 Nov;44(6):914-918. doi: 10.1111/coa.13390. Epub 2019 Aug 1.
12 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.