Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3SZIWM)

• DOT Name: KN motif and ankyrin repeat domain-containing protein 2 (KANK2)
• Synonyms: Ankyrin repeat domain-containing protein 25; Matrix-remodeling-associated protein 3; SRC-1-interacting protein; SIP; SRC-interacting protein; SRC1-interacting protein
• Gene Name: KANK2
• Related Disease:
  Anxiety
  Anxiety disorder
  Breast cancer
  Breast carcinoma
  Cardiovascular disease
  Clear cell renal carcinoma
  Colon cancer
  Colon carcinoma
  Depression
  Familial hypercholesterolemia
  Gastric cancer
  Glioma
  Neoplasm
  Renal cell carcinoma
  Stomach cancer
  Type-1/2 diabetes
  Varicose veins
  Coronary heart disease
  Major depressive disorder
  Melanoma
  Nephrotic syndrome
  Wooly hair-palmoplantar keratoderma syndrome
  Dermatomyositis
  Generalized anxiety disorder
  Metastatic malignant neoplasm
  Nephrotic syndrome 16
  Neuroblastoma
  Pancreatic cancer
  Small lymphocytic lymphoma
  Stroke
• UniProt ID: KANK2_HUMAN
• PDB ID: 4HBD; 5YBV; 6TMD
• Pfam ID: PF00023 ; PF12796 ; PF12075
• Sequence:
  MAQVLHVPAPFPGTPGPASPPAFPAKDPDPPYSVETPYGYRLDLDFLKYVDDIEKGHTLR
  RVAVQRRPRLSSLPRGPGSWWTSTESLCSNASGDSRHSAYSYCGRGFYPQYGALETRGGF
  NPRVERTLLDARRRLEDQAATPTGLGSLTPSAAGSTASLVGVGLPPPTPRSSGLSTPVPP
  SAGHLAHVREQMAGALRKLRQLEEQVKLIPVLQVKLSVLQEEKRQLTVQLKSQKFLGHPT
  AGRGRSELCLDLPDPPEDPVALETRSVGTWVRERDLGMPDGEAALAAKVAVLETQLKKAL
  QELQAAQARQADPQPQAWPPPDSPVRVDTVRVVEGPREVEVVASTAAGAPAQRAQSLEPY
  GTGLRALAMPGRPESPPVFRSQEVVETMCPVPAAATSNVHMVKKISITERSCDGAAGLPE
  VPAESSSSPPGSEVASLTQPEKSTGRVPTQEPTHREPTRQAASQESEEAGGTGGPPAGVR
  SIMKRKEEVADPTAHRRSLQFVGVNGGYESSSEDSSTAENISDNDSTENEAPEPRERVPS
  VAEAPQLRPAGTAAAKTSRQECQLSRESQHIPTAEGASGSNTEEEIRMELSPDLISACLA
  LEKYLDNPNALTERELKVAYTTVLQEWLRLACRSDAHPELVRRHLVTFRAMSARLLDYVV
  NIADSNGNTALHYSVSHANFPVVQQLLDSGVCKVDKQNRAGYSPIMLTALATLKTQDDIE
  TVLQLFRLGNINAKASQAGQTALMLAVSHGRVDVVKALLACEADVNVQDDDGSTALMCAC
  EHGHKEIAGLLLAVPSCDISLTDRDGSTALMVALDAGQSEIASMLYSRMNIKCSFAPMSD
  DESPTSSSAEE
• Function: Involved in transcription regulation by sequestering in the cytoplasm nuclear receptor coactivators such as NCOA1, NCOA2 and NCOA3. Involved in regulation of caspase-independent apoptosis by sequestering the proapoptotic factor AIFM1 in mitochondria. Pro-apoptotic stimuli can induce its proteasomal degradation allowing the translocation of AIFM1 to the nucleus to induce apoptosis. Involved in the negative control of vitamin D receptor signaling pathway. Involved in actin stress fibers formation through its interaction with ARHGDIA and the regulation of the Rho signaling pathway. May thereby play a role in cell adhesion and migration, regulating for instance podocytes migration during development of the kidney. Through the Rho signaling pathway may also regulate cell proliferation.
• Tissue Specificity: Strongly expressed in cervix, colon, heart, kidney and lung. Expressed in kidney glomerular podocytes and mesangial cells (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

30 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Anxiety	DISIJDBA	Strong	Biomarker	[1]
Anxiety disorder	DISBI2BT	Strong	Biomarker	[1]
Breast cancer	DIS7DPX1	Strong	Biomarker	[2]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[2]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[3]
Clear cell renal carcinoma	DISBXRFJ	Strong	Altered Expression	[4]
Colon cancer	DISVC52G	Strong	Genetic Variation	[5]
Colon carcinoma	DISJYKUO	Strong	Genetic Variation	[5]
Depression	DIS3XJ69	Strong	Biomarker	[1]
Familial hypercholesterolemia	DISC06IX	Strong	Genetic Variation	[6]
Gastric cancer	DISXGOUK	Strong	Biomarker	[7]
Glioma	DIS5RPEH	Strong	Biomarker	[8]
Neoplasm	DISZKGEW	Strong	Biomarker	[9]
Renal cell carcinoma	DISQZ2X8	Strong	Altered Expression	[4]
Stomach cancer	DISKIJSX	Strong	Biomarker	[7]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[10]
Varicose veins	DISIMBN2	Strong	Biomarker	[11]
Coronary heart disease	DIS5OIP1	moderate	Genetic Variation	[12]
Major depressive disorder	DIS4CL3X	moderate	Genetic Variation	[13]
Melanoma	DIS1RRCY	moderate	Biomarker	[14]
Nephrotic syndrome	DISSPSC2	moderate	Biomarker	[15]
Wooly hair-palmoplantar keratoderma syndrome	DISVR3QA	Supportive	Autosomal recessive	[16]
Dermatomyositis	DIS50C5O	Limited	Biomarker	[17]
Generalized anxiety disorder	DISPSQCW	Limited	Genetic Variation	[13]
Metastatic malignant neoplasm	DIS86UK6	Limited	Biomarker	[9]
Nephrotic syndrome 16	DISDPK1Q	Limited	Unknown	[15]
Neuroblastoma	DISVZBI4	Limited	Altered Expression	[18]
Pancreatic cancer	DISJC981	Limited	Biomarker	[19]
Small lymphocytic lymphoma	DIS30POX	Limited	Altered Expression	[20]
Stroke	DISX6UHX	Limited	Biomarker	[21]

7 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 KN motif and ankyrin repeat domain-containing protein 2 (KANK2).	[22]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of KN motif and ankyrin repeat domain-containing protein 2 (KANK2).	[28]
Quercetin	DM3NC4M	Approved	Quercetin increases the phosphorylation of KN motif and ankyrin repeat domain-containing protein 2 (KANK2).	[29]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of KN motif and ankyrin repeat domain-containing protein 2 (KANK2).	[34]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of KN motif and ankyrin repeat domain-containing protein 2 (KANK2).	[29]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of KN motif and ankyrin repeat domain-containing protein 2 (KANK2).	[36]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of KN motif and ankyrin repeat domain-containing protein 2 (KANK2).	[29]

12 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 KN motif and ankyrin repeat domain-containing protein 2 (KANK2).	[23]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of KN motif and ankyrin repeat domain-containing protein 2 (KANK2).	[24]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of KN motif and ankyrin repeat domain-containing protein 2 (KANK2).	[25]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of KN motif and ankyrin repeat domain-containing protein 2 (KANK2).	[26]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of KN motif and ankyrin repeat domain-containing protein 2 (KANK2).	[27]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of KN motif and ankyrin repeat domain-containing protein 2 (KANK2).	[30]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of KN motif and ankyrin repeat domain-containing protein 2 (KANK2).	[31]
Isotretinoin	DM4QTBN	Approved	Isotretinoin increases the expression of KN motif and ankyrin repeat domain-containing protein 2 (KANK2).	[32]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of KN motif and ankyrin repeat domain-containing protein 2 (KANK2).	[33]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of KN motif and ankyrin repeat domain-containing protein 2 (KANK2).	[35]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of KN motif and ankyrin repeat domain-containing protein 2 (KANK2).	[37]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of KN motif and ankyrin repeat domain-containing protein 2 (KANK2).	[38]

References

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