Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT24UORN)

• DOT Name: NCK-interacting protein with SH3 domain (NCKIPSD)
• Synonyms: 54 kDa VacA-interacting protein; 54 kDa vimentin-interacting protein; VIP54; 90 kDa SH3 protein interacting with Nck; AF3p21; Dia-interacting protein 1; DIP-1; Diaphanous protein-interacting protein; SH3 adapter protein SPIN90; WASP-interacting SH3-domain protein; WISH; Wiskott-Aldrich syndrome protein-interacting protein
• Gene Name: NCKIPSD
• Related Disease:
  Bladder transitional cell carcinoma
  Cervical cancer
  Cervical carcinoma
  Adult T-cell leukemia/lymphoma
  Angioimmunoblastic T-cell Lymphoma
  Anorexia nervosa cachexia
  Autosomal dominant familial periodic fever
  Breast cancer
  Breast carcinoma
  Classic Hodgkin lymphoma
  Colorectal carcinoma
  Fibrosarcoma
  Gastroenteritis
  Glioblastoma multiforme
  Hepatitis
  Hepatitis A virus infection
  Hepatitis C virus infection
  Hepatitis E virus infection
  Hepatocellular carcinoma
  Herpes simplex infection
  Huntington disease
  Leukemia
  Neoplasm
  Progressive multifocal leukoencephalopathy
  Rheumatoid arthritis
  Systemic lupus erythematosus
  T-cell leukaemia
  Tuberculosis
  Ulcerative colitis
  Wiskott-Aldrich syndrome
  Advanced cancer
  Human T-lymphotropic virus 1 infectious disease
  Spastic paralysis
  Childhood kidney Wilms tumor
  Wilms tumor
• UniProt ID: SPN90_HUMAN
• PDB ID: 6DEC; 6DED; 6DEE
• Pfam ID: PF00018 ; PF09431
• Sequence:
  MYRALYAFRSAEPNALAFAAGETFLVLERSSAHWWLAARARSGETGYVPPAYLRRLQGLE
  QDVLQAIDRAIEAVHNTAMRDGGKYSLEQRGVLQKLIHHRKETLSRRGPSASSVAVMTSS
  TSDHHLDAAAARQPNGVCRAGFERQHSLPSSEHLGADGGLYQIPLPSSQIPPQPRRAAPT
  TPPPPVKRRDREALMASGSGGHNTMPSGGNSVSSGSSVSSTSLDTLYTSSSPSEPGSSCS
  PTPPPVPRRGTHTTVSQVQPPPSKASAPEPPAEEEVATGTTSASDDLEALGTLSLGTTEE
  KAAAEAAVPRTIGAELMELVRRNTGLSHELCRVAIGIIVGHIQASVPASSPVMEQVLLSL
  VEGKDLSMALPSGQVCHDQQRLEVIFADLARRKDDAQQRSWALYEDEGVIRCYLEELLHI
  LTDADPEVCKKMCKRNEFESVLALVAYYQMEHRASLRLLLLKCFGAMCSLDAAIISTLVS
  SVLPVELARDMQTDTQDHQKLCYSALILAMVFSMGEAVPYAHYEHLGTPFAQFLLNIVED
  GLPLDTTEQLPDLCVNLLLALNLHLPAADQNVIMAALSKHANVKIFSEKLLLLLNRGDDP
  VRIFKHEPQPPHSVLKFLQDVFGSPATAAIFYHTDMMALIDITVRHIADLSPGDKLRMEY
  LSLMHAIVRTTPYLQHRHRLPDLQAILRRILNEEETSPQCQMDRMIVREMCKEFLVLGEA
  PS
• Function: Has an important role in stress fiber formation induced by active diaphanous protein homolog 1 (DRF1). Induces microspike formation, in vivo. In vitro, stimulates N-WASP-induced ARP2/3 complex activation in the absence of CDC42. May play an important role in the maintenance of sarcomeres and/or in the assembly of myofibrils into sarcomeres. Implicated in regulation of actin polymerization and cell adhesion. Plays a role in angiogenesis.
• Tissue Specificity: Highest expression in heart, brain, skeletal muscle, kidney and liver. Lower levels in placenta, lung, small intestine and leukocytes. Weak expression in colon, thymus and spleen.
• Reactome Pathway:
  RHO GTPases Activate WASPs and WAVEs (R-HSA-5663213)
  FCGR3A-mediated phagocytosis (R-HSA-9664422)
  Regulation of actin dynamics for phagocytic cup formation (R-HSA-2029482)

Molecular Interaction Atlas (MIA) of This DOT

35 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bladder transitional cell carcinoma	DISNL46A	Definitive	Biomarker	[1]
Cervical cancer	DISFSHPF	Definitive	Biomarker	[2]
Cervical carcinoma	DIST4S00	Definitive	Biomarker	[2]
Adult T-cell leukemia/lymphoma	DIS882XU	Strong	Biomarker	[3]
Angioimmunoblastic T-cell Lymphoma	DISZPFTL	Strong	Biomarker	[4]
Anorexia nervosa cachexia	DISFO5RQ	Strong	Genetic Variation	[5]
Autosomal dominant familial periodic fever	DISCRNV1	Strong	Genetic Variation	[6]
Breast cancer	DIS7DPX1	Strong	Biomarker	[7]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[7]
Classic Hodgkin lymphoma	DISV1LU6	Strong	Genetic Variation	[8]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[9]
Fibrosarcoma	DISWX7MU	Strong	Biomarker	[4]
Gastroenteritis	DISXQCG5	Strong	Biomarker	[10]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[4]
Hepatitis	DISXXX35	Strong	Biomarker	[11]
Hepatitis A virus infection	DISUMFQV	Strong	Biomarker	[11]
Hepatitis C virus infection	DISQ0M8R	Strong	Genetic Variation	[12]
Hepatitis E virus infection	DIS0TXIR	Strong	Biomarker	[13]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[14]
Herpes simplex infection	DISL1SAV	Strong	Biomarker	[15]
Huntington disease	DISQPLA4	Strong	Genetic Variation	[8]
Leukemia	DISNAKFL	Strong	Biomarker	[3]
Neoplasm	DISZKGEW	Strong	Biomarker	[16]
Progressive multifocal leukoencephalopathy	DISX02WS	Strong	Altered Expression	[17]
Rheumatoid arthritis	DISTSB4J	Strong	Biomarker	[18]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[18]
T-cell leukaemia	DISJ6YIF	Strong	Biomarker	[19]
Tuberculosis	DIS2YIMD	Strong	Biomarker	[20]
Ulcerative colitis	DIS8K27O	Strong	Biomarker	[21]
Wiskott-Aldrich syndrome	DISATMDB	Strong	Biomarker	[22]
Advanced cancer	DISAT1Z9	moderate	Altered Expression	[7]
Human T-lymphotropic virus 1 infectious disease	DISN5C4M	moderate	Genetic Variation	[23]
Spastic paralysis	DISVQ6I2	Disputed	Genetic Variation	[23]
Childhood kidney Wilms tumor	DIS0NMK3	Limited	Biomarker	[24]
Wilms tumor	DISB6T16	Limited	Biomarker	[24]

8 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 NCK-interacting protein with SH3 domain (NCKIPSD).	[25]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of NCK-interacting protein with SH3 domain (NCKIPSD).	[26]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of NCK-interacting protein with SH3 domain (NCKIPSD).	[27]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of NCK-interacting protein with SH3 domain (NCKIPSD).	[28]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of NCK-interacting protein with SH3 domain (NCKIPSD).	[29]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of NCK-interacting protein with SH3 domain (NCKIPSD).	[30]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of NCK-interacting protein with SH3 domain (NCKIPSD).	[31]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of NCK-interacting protein with SH3 domain (NCKIPSD).	[33]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of NCK-interacting protein with SH3 domain (NCKIPSD).	[32]

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