Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHNH6Y8)

• DOT Name: C4b-binding protein alpha chain (C4BPA)
• Synonyms: C4bp; Proline-rich protein; PRP
• Gene Name: C4BPA
• Related Disease:
  Familial hypercholesterolemia
  Fatal familial insomnia
  Hypercholesterolemia, familial, 1
  Lung neoplasm
  Non-small-cell lung cancer
  Tendinopathy
  Acquired immune deficiency syndrome
  Acute leukaemia
  Adult glioblastoma
  Advanced cancer
  Amyloidosis
  Autoimmune disease
  Behcet disease
  Bernard-Soulier syndrome
  Breast cancer
  Breast carcinoma
  Chondrosarcoma
  Creutzfeldt Jacob disease
  Dental caries
  Diphtheria
  Epithelial ovarian cancer
  Essential hypertension
  Gerstmann-Straussler-Scheinker syndrome
  Glioblastoma multiforme
  Haemophilia A
  Hepatitis B virus infection
  IgA nephropathy
  Influenza
  Knee osteoarthritis
  leukaemia
  Leukemia
  Neoplasm
  Osteoarthritis
  Prion disease
  Synovitis
  Venous thromboembolism
  Vitiligo
  Alopecia
  Hepatocellular carcinoma
  Juvenile idiopathic arthritis
  Gastric cancer
  Glaucoma/ocular hypertension
  Gonorrhea
  High blood pressure
  Meningitis
  Neoplasm of esophagus
  Stomach cancer
• UniProt ID: C4BPA_HUMAN
• PDB ID: 2A55; 4B0F; 5HYP; 5HYT; 5HYU; 5HZP; 5I0Q
• Pfam ID: PF18453 ; PF00084
• Sequence:
  MHPPKTPSGALHRKRKMAAWPFSRLWKVSDPILFQMTLIAALLPAVLGNCGPPPTLSFAA
  PMDITLTETRFKTGTTLKYTCLPGYVRSHSTQTLTCNSDGEWVYNTFCIYKRCRHPGELR
  NGQVEIKTDLSFGSQIEFSCSEGFFLIGSTTSRCEVQDRGVGWSHPLPQCEIVKCKPPPD
  IRNGRHSGEENFYAYGFSVTYSCDPRFSLLGHASISCTVENETIGVWRPSPPTCEKITCR
  KPDVSHGEMVSGFGPIYNYKDTIVFKCQKGFVLRGSSVIHCDADSKWNPSPPACEPNSCI
  NLPDIPHASWETYPRPTKEDVYVVGTVLRYRCHPGYKPTTDEPTTVICQKNLRWTPYQGC
  EALCCPEPKLNNGEITQHRKSRPANHCVYFYGDEISFSCHETSRFSAICQGDGTWSPRTP
  SCGDICNFPPKIAHGHYKQSSSYSFFKEEIIYECDKGYILVGQAKLSCSYSHWSAPAPQC
  KALCRKPELVNGRLSVDKDQYVEPENVTIQCDSGYGVVGPQSITCSGNRTWYPEVPKCEW
  ETPEGCEQVLTGKRLMQCLPNPEDVKMALEVYKLSLEIEQLELQRDSARQSTLDKEL
• Function: Controls the classical pathway of complement activation. It binds as a cofactor to C3b/C4b inactivator (C3bINA), which then hydrolyzes the complement fragment C4b. It also accelerates the degradation of the C4bC2a complex (C3 convertase) by dissociating the complement fragment C2a. Alpha chain binds C4b. It interacts also with anticoagulant protein S and with serum amyloid P component.
• Tissue Specificity: Chylomicrons in the plasma.
• KEGG Pathway:
  Complement and coagulation cascades (hsa04610)
  Pertussis (hsa05133)
• Reactome Pathway: Regulation of Complement cascade (R-HSA-977606)

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Familial hypercholesterolemia	DISC06IX	Definitive	Genetic Variation	[1]
Fatal familial insomnia	DIS1FL1J	Definitive	Genetic Variation	[2]
Hypercholesterolemia, familial, 1	DISU411W	Definitive	Genetic Variation	[1]
Lung neoplasm	DISVARNB	Definitive	Biomarker	[3]
Non-small-cell lung cancer	DIS5Y6R9	Definitive	Biomarker	[3]
Tendinopathy	DISJH7UX	Definitive	Biomarker	[4]
Acquired immune deficiency syndrome	DISL5UOX	Strong	Biomarker	[5]
Acute leukaemia	DISDQFDI	Strong	Biomarker	[6]
Adult glioblastoma	DISVP4LU	Strong	Altered Expression	[7]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[8]
Amyloidosis	DISHTAI2	Strong	Biomarker	[9]
Autoimmune disease	DISORMTM	Strong	Biomarker	[10]
Behcet disease	DISSYMBS	Strong	Biomarker	[11]
Bernard-Soulier syndrome	DISLD1FU	Strong	Biomarker	[12]
Breast cancer	DIS7DPX1	Strong	Biomarker	[13]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[14]
Chondrosarcoma	DIS4I7JB	Strong	Biomarker	[8]
Creutzfeldt Jacob disease	DISCB6RX	Strong	Genetic Variation	[15]
Dental caries	DISRBCMD	Strong	Biomarker	[16]
Diphtheria	DISZWM55	Strong	Genetic Variation	[17]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[18]
Essential hypertension	DIS7WI98	Strong	Altered Expression	[19]
Gerstmann-Straussler-Scheinker syndrome	DISIO6KC	Strong	Genetic Variation	[20]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[7]
Haemophilia A	DIS0RQ2E	Strong	Biomarker	[21]
Hepatitis B virus infection	DISLQ2XY	Strong	Genetic Variation	[17]
IgA nephropathy	DISZ8MTK	Strong	Biomarker	[22]
Influenza	DIS3PNU3	Strong	Biomarker	[17]
Knee osteoarthritis	DISLSNBJ	Strong	Biomarker	[23]
leukaemia	DISS7D1V	Strong	Biomarker	[24]
Leukemia	DISNAKFL	Strong	Biomarker	[24]
Neoplasm	DISZKGEW	Strong	Biomarker	[25]
Osteoarthritis	DIS05URM	Strong	Biomarker	[26]
Prion disease	DISOUMB0	Strong	Genetic Variation	[27]
Synovitis	DISW2GPY	Strong	Biomarker	[28]
Venous thromboembolism	DISUR7CR	Strong	Genetic Variation	[29]
Vitiligo	DISR05SL	Strong	Biomarker	[30]
Alopecia	DIS37HU4	moderate	Biomarker	[31]
Hepatocellular carcinoma	DIS0J828	moderate	Biomarker	[32]
Juvenile idiopathic arthritis	DISQZGBV	moderate	Biomarker	[33]
Gastric cancer	DISXGOUK	Limited	Biomarker	[34]
Glaucoma/ocular hypertension	DISLBXBY	Limited	Biomarker	[35]
Gonorrhea	DISQ5AO6	Limited	Biomarker	[36]
High blood pressure	DISY2OHH	Limited	Biomarker	[37]
Meningitis	DISQABAA	Limited	Biomarker	[38]
Neoplasm of esophagus	DISOLKAQ	Limited	Altered Expression	[39]
Stomach cancer	DISKIJSX	Limited	Biomarker	[34]

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 C4b-binding protein alpha chain (C4BPA).	[40]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of C4b-binding protein alpha chain (C4BPA).	[46]

9 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 C4b-binding protein alpha chain (C4BPA).	[41]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of C4b-binding protein alpha chain (C4BPA).	[42]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of C4b-binding protein alpha chain (C4BPA).	[41]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of C4b-binding protein alpha chain (C4BPA).	[43]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of C4b-binding protein alpha chain (C4BPA).	[44]
Ursodeoxycholic acid	DMCUT21	Approved	Ursodeoxycholic acid affects the expression of C4b-binding protein alpha chain (C4BPA).	[45]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of C4b-binding protein alpha chain (C4BPA).	[47]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of C4b-binding protein alpha chain (C4BPA).	[48]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of C4b-binding protein alpha chain (C4BPA).	[49]

References

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