Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTK80FYN)

• DOT Name: Cell migration-inducing and hyaluronan-binding protein (CEMIP)
• Synonyms: EC 3.2.1.35; Hyaluronan binding protein involved in hyaluronan depolymerization
• Gene Name: CEMIP
• Related Disease:
  Thyroid gland papillary carcinoma
  Adenoma
  Advanced cancer
  Breast neoplasm
  Clear cell renal carcinoma
  Colon carcinoma
  Colonic neoplasm
  Colorectal carcinoma
  Colorectal neoplasm
  Epithelial ovarian cancer
  Gastric cancer
  Matthew-Wood syndrome
  Multiple sclerosis
  Neoplasm
  Nervous system inflammation
  Non-small-cell lung cancer
  Oral cancer
  Osteoarthritis
  Ovarian cancer
  Ovarian neoplasm
  Pancreatic ductal carcinoma
  Pneumonia
  Pneumonitis
  Prostate cancer
  Prostate carcinoma
  Renal cell carcinoma
  Retinoblastoma
  Rheumatoid arthritis
  Stomach cancer
  Breast cancer
  Breast carcinoma
  Metastatic malignant neoplasm
  Colon cancer
  Invasive breast carcinoma
  Nonsyndromic genetic hearing loss
  Acute myelogenous leukaemia
  Adenocarcinoma
  Hepatocellular carcinoma
  Human papillomavirus infection
  Pancreatic cancer
  Triple negative breast cancer
• UniProt ID: CEMIP_HUMAN
• EC Number: 3.2.1.35
• Pfam ID: PF10162 ; PF15711 ; PF13330
• Sequence:
  MGAAGRQDFLFKAMLTISWLTLTCFPGATSTVAAGCPDQSPELQPWNPGHDQDHHVHIGQ
  GKTLLLTSSATVYSIHISEGGKLVIKDHDEPIVLRTRHILIDNGGELHAGSALCPFQGNF
  TIILYGRADEGIQPDPYYGLKYIGVGKGGALELHGQKKLSWTFLNKTLHPGGMAEGGYFF
  ERSWGHRGVIVHVIDPKSGTVIHSDRFDTYRSKKESERLVQYLNAVPDGRILSVAVNDEG
  SRNLDDMARKAMTKLGSKHFLHLGFRHPWSFLTVKGNPSSSVEDHIEYHGHRGSAAARVF
  KLFQTEHGEYFNVSLSSEWVQDVEWTEWFDHDKVSQTKGGEKISDLWKAHPGKICNRPID
  IQATTMDGVNLSTEVVYKKGQDYRFACYDRGRACRSYRVRFLCGKPVRPKLTVTIDTNVN
  STILNLEDNVQSWKPGDTLVIASTDYSMYQAEEFQVLPCRSCAPNQVKVAGKPMYLHIGE
  EIDGVDMRAEVGLLSRNIIVMGEMEDKCYPYRNHICNFFDFDTFGGHIKFALGFKAAHLE
  GTELKHMGQQLVGQYPIHFHLAGDVDERGGYDPPTYIRDLSIHHTFSRCVTVHGSNGLLI
  KDVVGYNSLGHCFFTEDGPEERNTFDHCLGLLVKSGTLLPSDRDSKMCKMITEDSYPGYI
  PKPRQDCNAVSTFWMANPNNNLINCAAAGSEETGFWFIFHHVPTGPSVGMYSPGYSEHIP
  LGKFYNNRAHSNYRAGMIIDNGVKTTEASAKDKRPFLSIISARYSPHQDADPLKPREPAI
  IRHFIAYKNQDHGAWLRGGDVWLDSCRFADNGIGLTLASGGTFPYDDGSKQEIKNSLFVG
  ESGNVGTEMMDNRIWGPGGLDHSGRTLPIGQNFPIRGIQLYDGPINIQNCTFRKFVALEG
  RHTSALAFRLNNAWQSCPHNNVTGIAFEDVPITSRVFFGEPGPWFNQLDMDGDKTSVFHD
  VDGSVSEYPGSYLTKNDNWLVRHPDCINVPDWRGAICSGCYAQMYIQAYKTSNLRMKIIK
  NDFPSHPLYLEGALTRSTHYQQYQPVVTLQKGYTIHWDQTAPAELAIWLINFNKGDWIRV
  GLCYPRGTTFSILSDVHNRLLKQTSKTGVFVRTLQMDKVEQSYPGRSHYYWDEDSGLLFL
  KLKAQNEREKFAFCSMKGCERIKIKALIPKNAGVSDCTATAYPKFTERAVVDVPMPKKLF
  GSQLKTKDHFLEVKMESSKQHFFHLWNDFAYIEVDGKKYPSSEDGIQVVVIDGNQGRVVS
  HTSFRNSILQGIPWQLFNYVATIPDNSIVLMASKGRYVSRGPWTRVLEKLGADRGLKLKE
  QMAFVGFKGSFRPIWVTLDTEDHKAKIFQVVPIPVVKKKKL
• Function: Mediates depolymerization of hyaluronic acid (HA) via the cell membrane-associated clathrin-coated pit endocytic pathway. Binds to hyaluronic acid. Hydrolyzes high molecular weight hyaluronic acid to produce an intermediate-sized product, a process that may occur through rapid vesicle endocytosis and recycling without intracytoplasmic accumulation or digestion in lysosomes. Involved in hyaluronan catabolism in the dermis of the skin and arthritic synovium. Positively regulates epithelial-mesenchymal transition (EMT), and hence tumor cell growth, invasion and cancer dissemination. In collaboration with HSPA5/BIP, promotes cancer cell migration in a calcium and PKC-dependent manner. May be involved in hearing.
• Tissue Specificity: Expressed in dermal and in synovial fibroblasts. Strongly expressed in gastric cancers compared with the paired normal tissues. Strongly expressed in both ductal carcinoma and invasive breast cancer cells compared with benign epithelial cells (at protein level). Strongly expressed in brain, placenta, prostate, breast, lung and testis. Expressed in fibroblasts, epithelial cells and cancer cells. In ear, it is specifically expressed in inner ear. Expressed in cochlea and vestibule tissues. Strongly expressed in gastric cancers compared with the paired normal tissues. Strongly expressed in colon adenocarcinomas compared with normal colonic mucosas. Strongly expressed in breast cancer as compared to normal breast tissue.
• Reactome Pathway: Hyaluronan biosynthesis and export (R-HSA-2142850)

Molecular Interaction Atlas (MIA) of This DOT

41 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Thyroid gland papillary carcinoma	DIS48YMM	Definitive	Biomarker	[1]
Adenoma	DIS78ZEV	Strong	Altered Expression	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[3]
Clear cell renal carcinoma	DISBXRFJ	Strong	Altered Expression	[4]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[5]
Colonic neoplasm	DISSZ04P	Strong	Biomarker	[5]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[6]
Colorectal neoplasm	DISR1UCN	Strong	Altered Expression	[7]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[8]
Gastric cancer	DISXGOUK	Strong	Biomarker	[9]
Matthew-Wood syndrome	DISA7HR7	Strong	Biomarker	[10]
Multiple sclerosis	DISB2WZI	Strong	Altered Expression	[11]
Neoplasm	DISZKGEW	Strong	Biomarker	[12]
Nervous system inflammation	DISB3X5A	Strong	Biomarker	[11]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[13]
Oral cancer	DISLD42D	Strong	Biomarker	[14]
Osteoarthritis	DIS05URM	Strong	Altered Expression	[15]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[8]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[8]
Pancreatic ductal carcinoma	DIS26F9Q	Strong	Altered Expression	[10]
Pneumonia	DIS8EF3M	Strong	Biomarker	[16]
Pneumonitis	DIS88E0K	Strong	Biomarker	[16]
Prostate cancer	DISF190Y	Strong	Altered Expression	[17]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[17]
Renal cell carcinoma	DISQZ2X8	Strong	Altered Expression	[4]
Retinoblastoma	DISVPNPB	Strong	Biomarker	[18]
Rheumatoid arthritis	DISTSB4J	Strong	Altered Expression	[19]
Stomach cancer	DISKIJSX	Strong	Biomarker	[9]
Breast cancer	DIS7DPX1	moderate	Biomarker	[12]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[12]
Metastatic malignant neoplasm	DIS86UK6	moderate	Biomarker	[20]
Colon cancer	DISVC52G	Disputed	Biomarker	[21]
Invasive breast carcinoma	DISANYTW	Disputed	Altered Expression	[22]
Nonsyndromic genetic hearing loss	DISZX61P	Disputed	Autosomal recessive	[23]
Acute myelogenous leukaemia	DISCSPTN	Limited	Genetic Variation	[24]
Adenocarcinoma	DIS3IHTY	Limited	Altered Expression	[25]
Hepatocellular carcinoma	DIS0J828	Limited	Biomarker	[26]
Human papillomavirus infection	DISX61LX	Limited	Altered Expression	[27]
Pancreatic cancer	DISJC981	Limited	Biomarker	[28]
Triple negative breast cancer	DISAMG6N	Limited	Biomarker	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Cell migration-inducing and hyaluronan-binding protein (CEMIP).	[29]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Cell migration-inducing and hyaluronan-binding protein (CEMIP).	[30]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Cell migration-inducing and hyaluronan-binding protein (CEMIP).	[31]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Cell migration-inducing and hyaluronan-binding protein (CEMIP).	[32]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Cell migration-inducing and hyaluronan-binding protein (CEMIP).	[33]
Quercetin	DM3NC4M	Approved	Quercetin affects the expression of Cell migration-inducing and hyaluronan-binding protein (CEMIP).	[34]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Cell migration-inducing and hyaluronan-binding protein (CEMIP).	[35]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Cell migration-inducing and hyaluronan-binding protein (CEMIP).	[36]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Cell migration-inducing and hyaluronan-binding protein (CEMIP).	[37]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Cell migration-inducing and hyaluronan-binding protein (CEMIP).	[38]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Cell migration-inducing and hyaluronan-binding protein (CEMIP).	[39]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Cell migration-inducing and hyaluronan-binding protein (CEMIP).	[40]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Cell migration-inducing and hyaluronan-binding protein (CEMIP).	[42]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Cell migration-inducing and hyaluronan-binding protein (CEMIP).	[43]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Cell migration-inducing and hyaluronan-binding protein (CEMIP).	[45]
Octanal	DMTN0OK	Investigative	Octanal increases the expression of Cell migration-inducing and hyaluronan-binding protein (CEMIP).	[46]

2 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 Cell migration-inducing and hyaluronan-binding protein (CEMIP).	[41]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Cell migration-inducing and hyaluronan-binding protein (CEMIP).	[44]

References

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