Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4BVCRU)

• DOT Name: Calcium and integrin-binding protein 1 (CIB1)
• Synonyms: CIB; Calcium- and integrin-binding protein; CIBP; Calmyrin; DNA-PKcs-interacting protein; Kinase-interacting protein; KIP; SNK-interacting protein 2-28; SIP2-28
• Gene Name: CIB1
• Related Disease:
  Epithelial ovarian cancer
  Glioma
  Lung adenocarcinoma
  Multiple endocrine neoplasia type 1
  Pancreatic cancer
  Urinary bladder neoplasm
  Acute myelogenous leukaemia
  Adenoma
  Adult glioblastoma
  Adult lymphoma
  Advanced cancer
  Alzheimer disease
  Anaplastic large cell lymphoma
  Bone osteosarcoma
  Breast cancer
  Breast carcinoma
  Carcinoma of esophagus
  Clear cell renal carcinoma
  Colorectal carcinoma
  Endometriosis
  Epidermodysplasia verruciformis, susceptibility to, 3
  Glioblastoma multiforme
  Hepatocellular carcinoma
  Leukemia
  Lung cancer
  Lung carcinoma
  Mantle cell lymphoma
  Non-insulin dependent diabetes
  Non-small-cell lung cancer
  Osteosarcoma
  Ovarian cancer
  Pediatric lymphoma
  Plasma cell myeloma
  Prostate adenocarcinoma
  Prostate neoplasm
  Renal cell carcinoma
  Squamous cell carcinoma
  Thyroid gland papillary carcinoma
  leukaemia
  Epidermodysplasia verruciformis
  Acute lymphocytic leukaemia
  B-cell lymphoma
  B-cell neoplasm
  Carcinoma
  Endometrial cancer
  Endometrial carcinoma
  Melanoma
  Multiple endocrine neoplasia
• UniProt ID: CIB1_HUMAN
• PDB ID: 1DGU; 1DGV; 1XO5; 1Y1A; 2L4H; 2L4I; 2LM5; 6OCX; 6OD0
• Pfam ID: PF13499
• Sequence:
  MGGSGSRLSKELLAEYQDLTFLTKQEILLAHRRFCELLPQEQRSVESSLRAQVPFEQILS
  LPELKANPFKERICRVFSTSPAKDSLSFEDFLDLLSVFSDTATPDIKSHYAFRIFDFDDD
  GTLNREDLSRLVNCLTGEGEDTRLSASEMKQLIDNILEESDIDRDGTINLSEFQHVISRS
  PDFASSFKIVL
• Function: Calcium-binding protein that plays a role in the regulation of numerous cellular processes, such as cell differentiation, cell division, cell proliferation, cell migration, thrombosis, angiogenesis, cardiac hypertrophy and apoptosis. Involved in bone marrow megakaryocyte differentiation by negatively regulating thrombopoietin-mediated signaling pathway. Participates in the endomitotic cell cycle of megakaryocyte, a form of mitosis in which both karyokinesis and cytokinesis are interrupted. Plays a role in integrin signaling by negatively regulating alpha-IIb/beta3 activation in thrombin-stimulated megakaryocytes preventing platelet aggregation. Up-regulates PTK2/FAK1 activity, and is also needed for the recruitment of PTK2/FAK1 to focal adhesions; it thus appears to play an important role in focal adhesion formation. Positively regulates cell migration on fibronectin in a CDC42-dependent manner, the effect being negatively regulated by PAK1. Functions as a negative regulator of stress activated MAP kinase (MAPK) signaling pathways. Down-regulates inositol 1,4,5-trisphosphate receptor-dependent calcium signaling. Involved in sphingosine kinase SPHK1 translocation to the plasma membrane in a N-myristoylation-dependent manner preventing TNF-alpha-induced apoptosis. Regulates serine/threonine-protein kinase PLK3 activity for proper completion of cell division progression. Plays a role in microtubule (MT) dynamics during neuronal development; disrupts the MT depolymerization activity of STMN2 attenuating NGF-induced neurite outgrowth and the MT reorganization at the edge of lamellipodia. Promotes cardiomyocyte hypertrophy via activation of the calcineurin/NFAT signaling pathway. Stimulates calcineurin PPP3R1 activity by mediating its anchoring to the sarcolemma. In ischemia-induced (pathological or adaptive) angiogenesis, stimulates endothelial cell proliferation, migration and microvessel formation by activating the PAK1 and ERK1/ERK2 signaling pathway. Promotes also cancer cell survival and proliferation. May regulate cell cycle and differentiation of spermatogenic germ cells, and/or differentiation of supporting Sertoli cells.; [Isoform 2]: Plays a regulatory role in angiogenesis and tumor growth by mediating PKD/PRKD2-induced vascular endothelial growth factor A (VEGFA) secretion; (Microbial infection) Involved in keratinocyte-intrinsic immunity to human beta-papillomaviruses (HPVs).
• Tissue Specificity: Ubiquitously expressed. Expressed in the epidermis, hair follicles and keratinocytes . Detected in platelets and in cell lines of megakaryocytic and erythrocytic lineages. Both isoform 1 and isoform 2 are detected in various cancer cell lines, with isoform 2 being the predominant form (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Epithelial ovarian cancer	DIS56MH2	Definitive	Altered Expression	[1]
Glioma	DIS5RPEH	Definitive	Biomarker	[2]
Lung adenocarcinoma	DISD51WR	Definitive	Biomarker	[3]
Multiple endocrine neoplasia type 1	DIS0RJRK	Definitive	Altered Expression	[4]
Pancreatic cancer	DISJC981	Definitive	Biomarker	[5]
Urinary bladder neoplasm	DIS7HACE	Definitive	Genetic Variation	[6]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[7]
Adenoma	DIS78ZEV	Strong	Altered Expression	[8]
Adult glioblastoma	DISVP4LU	Strong	Altered Expression	[9]
Adult lymphoma	DISK8IZR	Strong	Biomarker	[10]
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[11]
Alzheimer disease	DISF8S70	Strong	Altered Expression	[12]
Anaplastic large cell lymphoma	DISP4D1R	Strong	Altered Expression	[13]
Bone osteosarcoma	DIST1004	Strong	Biomarker	[14]
Breast cancer	DIS7DPX1	Strong	Biomarker	[15]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[15]
Carcinoma of esophagus	DISS6G4D	Strong	Altered Expression	[16]
Clear cell renal carcinoma	DISBXRFJ	Strong	Altered Expression	[17]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[18]
Endometriosis	DISX1AG8	Strong	Altered Expression	[19]
Epidermodysplasia verruciformis, susceptibility to, 3	DIS5O5HQ	Strong	Autosomal recessive	[20]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[9]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[21]
Leukemia	DISNAKFL	Strong	Altered Expression	[22]
Lung cancer	DISCM4YA	Strong	Altered Expression	[23]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[23]
Mantle cell lymphoma	DISFREOV	Strong	Altered Expression	[24]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[25]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[26]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[14]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[1]
Pediatric lymphoma	DIS51BK2	Strong	Biomarker	[10]
Plasma cell myeloma	DIS0DFZ0	Strong	Altered Expression	[27]
Prostate adenocarcinoma	DISBZYU8	Strong	Altered Expression	[28]
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[29]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[30]
Squamous cell carcinoma	DISQVIFL	Strong	Altered Expression	[31]
Thyroid gland papillary carcinoma	DIS48YMM	Strong	Biomarker	[32]
leukaemia	DISS7D1V	moderate	Altered Expression	[22]
Epidermodysplasia verruciformis	DIS54WBS	Supportive	Autosomal recessive	[20]
Acute lymphocytic leukaemia	DISPX75S	Disputed	Genetic Variation	[33]
B-cell lymphoma	DISIH1YQ	Disputed	Biomarker	[34]
B-cell neoplasm	DISVY326	Limited	Biomarker	[35]
Carcinoma	DISH9F1N	Limited	Biomarker	[36]
Endometrial cancer	DISW0LMR	Limited	Biomarker	[37]
Endometrial carcinoma	DISXR5CY	Limited	Biomarker	[37]
Melanoma	DIS1RRCY	Limited	Biomarker	[38]
Multiple endocrine neoplasia	DISZGBKW	Limited	Genetic Variation	[39]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Capecitabine	DMTS85L	Approved	Calcium and integrin-binding protein 1 (CIB1) increases the response to substance of Capecitabine.	[51]

3 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Calcium and integrin-binding protein 1 (CIB1).	[40]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Calcium and integrin-binding protein 1 (CIB1).	[46]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Calcium and integrin-binding protein 1 (CIB1).	[47]

8 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 Calcium and integrin-binding protein 1 (CIB1).	[41]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Calcium and integrin-binding protein 1 (CIB1).	[42]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Calcium and integrin-binding protein 1 (CIB1).	[43]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Calcium and integrin-binding protein 1 (CIB1).	[44]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Calcium and integrin-binding protein 1 (CIB1).	[45]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Calcium and integrin-binding protein 1 (CIB1).	[48]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Calcium and integrin-binding protein 1 (CIB1).	[49]
Paraquat	DMR8O3X	Investigative	Paraquat decreases the expression of Calcium and integrin-binding protein 1 (CIB1).	[50]

References

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