Details of Drug Off-Target (DOT)

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

• DOT Name: Cysteine and glycine-rich protein 3 (CSRP3)
• Synonyms: Cardiac LIM protein; Cysteine-rich protein 3; CRP3; LIM domain protein, cardiac; Muscle LIM protein
• Gene Name: CSRP3
• Related Disease:
  Gastric cancer
  Hypertrophic cardiomyopathy
  Isolated Pierre-Robin syndrome
  Rheumatoid arthritis
  Stomach cancer
  Autoimmune disease
  Bone osteosarcoma
  Breast cancer
  Breast carcinoma
  Cardiac failure
  Cleft soft palate
  Colitis
  Colon cancer
  Colon carcinoma
  Congestive heart failure
  Dilated cardiomyopathy 1A
  Drug dependence
  Early-onset anterior polar cataract
  Familial dilated cardiomyopathy
  Glioma
  Hypertrophic cardiomyopathy 12
  Lung adenocarcinoma
  Lung neoplasm
  Myopathy
  Neuromuscular disease
  Obstructive lung disease
  Oral lichen planus
  Osteosarcoma
  Polycythemia vera
  Stroke
  Substance abuse
  Substance dependence
  Triple negative breast cancer
  Tuberculosis
  Obsolete familial isolated dilated cardiomyopathy
  Cardiomyopathy
  Dental caries
  Dilated cardiomyopathy
  Dilated cardiomyopathy 1M
  Mesothelioma
  Neural tube defect
  Parkinson disease
  Venous thromboembolism
• UniProt ID: CSRP3_HUMAN
• PDB ID: 2O10; 2O13
• Pfam ID: PF00412
• Sequence:
  MPNWGGGAKCGACEKTVYHAEEIQCNGRSFHKTCFHCMACRKALDSTTVAAHESEIYCKV
  CYGRRYGPKGIGYGQGAGCLSTDTGEHLGLQFQQSPKPARSVTTSNPSKFTAKFGESEKC
  PRCGKSVYAAEKVMGGGKPWHKTCFRCAICGKSLESTNVTDKDGELYCKVCYAKNFGPTG
  IGFGGLTQQVEKKE
• Function: Positive regulator of myogenesis. Acts as a cofactor for myogenic bHLH transcription factors such as MYOD1, and probably MYOG and MYF6. Enhances the DNA-binding activity of the MYOD1:TCF3 isoform E47 complex and may promote formation of a functional MYOD1:TCF3 isoform E47:MEF2A complex involved in myogenesis. Plays a crucial and specific role in the organization of cytosolic structures in cardiomyocytes. Could play a role in mechanical stretch sensing. May be a scaffold protein that promotes the assembly of interacting proteins at Z-line structures. It is essential for calcineurin anchorage to the Z line. Required for stress-induced calcineurin-NFAT activation. The role in regulation of cytoskeleton dynamics by association with CFL2 is reported conflictingly: Shown to enhance CFL2-mediated F-actin depolymerization dependent on the CSRP3:CFL2 molecular ratio, and also shown to reduce the ability of CLF1 and CFL2 to enhance actin depolymerization. Proposed to contribute to the maintenance of muscle cell integrity through an actin-based mechanism. Can directly bind to actin filaments, cross-link actin filaments into bundles without polarity selectivity and protect them from dilution- and cofilin-mediated depolymerization; the function seems to involve its self-association. In vitro can inhibit PKC/PRKCA activity. Proposed to be involved in cardiac stress signaling by down-regulating excessive PKC/PRKCA signaling; [Isoform 2]: May play a role in early sarcomere organization. Overexpression in myotubes negatively regulates myotube differentiation. By association with isoform 1 and thus changing the CSRP3 isoform 1:CFL2 stoichiometry is proposed to down-regulate CFL2-mediated F-actin depolymerization.
• Tissue Specificity: Cardiac and slow-twitch skeletal muscles. Isoform 2 is expressed in striated muscle. Isoform 2 is specifically expressed at higher levels in patients with neuromuscular diseases, such as limb-girdle muscular dystrophy 2A (LGMD2A), Duchenne muscular dystrophy (DMD) and dermatomyositis .
• KEGG Pathway: Cytoskeleton in muscle cells (hsa04820)

Molecular Interaction Atlas (MIA) of This DOT

43 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Gastric cancer	DISXGOUK	Definitive	Biomarker	[1]
Hypertrophic cardiomyopathy	DISQG2AI	Definitive	Semidominant	[2]
Isolated Pierre-Robin syndrome	DISVEHG7	Definitive	Biomarker	[3]
Rheumatoid arthritis	DISTSB4J	Definitive	Biomarker	[4]
Stomach cancer	DISKIJSX	Definitive	Biomarker	[1]
Autoimmune disease	DISORMTM	Strong	Biomarker	[5]
Bone osteosarcoma	DIST1004	Strong	Biomarker	[6]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[7]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[7]
Cardiac failure	DISDC067	Strong	Biomarker	[8]
Cleft soft palate	DISCN11I	Strong	Biomarker	[9]
Colitis	DISAF7DD	Strong	Biomarker	[10]
Colon cancer	DISVC52G	Strong	Biomarker	[6]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[6]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[8]
Dilated cardiomyopathy 1A	DIS0RK9Z	Strong	Genetic Variation	[11]
Drug dependence	DIS9IXRC	Strong	Biomarker	[12]
Early-onset anterior polar cataract	DISTOPIY	Strong	Altered Expression	[13]
Familial dilated cardiomyopathy	DISBHDU9	Strong	GermlineCausalMutation	[14]
Glioma	DIS5RPEH	Strong	Biomarker	[15]
Hypertrophic cardiomyopathy 12	DIS9GQ2Q	Strong	Autosomal dominant	[16]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[17]
Lung neoplasm	DISVARNB	Strong	Biomarker	[18]
Myopathy	DISOWG27	Strong	Biomarker	[8]
Neuromuscular disease	DISQTIJZ	Strong	Genetic Variation	[19]
Obstructive lung disease	DIS4IIDZ	Strong	Biomarker	[20]
Oral lichen planus	DISVEAJA	Strong	Biomarker	[5]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[6]
Polycythemia vera	DISB5FPO	Strong	Biomarker	[21]
Stroke	DISX6UHX	Strong	Genetic Variation	[22]
Substance abuse	DIS327VW	Strong	Biomarker	[12]
Substance dependence	DISDRAAR	Strong	Biomarker	[12]
Triple negative breast cancer	DISAMG6N	Strong	Biomarker	[23]
Tuberculosis	DIS2YIMD	Strong	Biomarker	[24]
Obsolete familial isolated dilated cardiomyopathy	DIS4FXO4	Supportive	Autosomal dominant	[14]
Cardiomyopathy	DISUPZRG	Limited	Genetic Variation	[8]
Dental caries	DISRBCMD	Limited	Biomarker	[25]
Dilated cardiomyopathy	DISX608J	Limited	Autosomal dominant	[2]
Dilated cardiomyopathy 1M	DISV0987	Limited	Autosomal dominant	[26]
Mesothelioma	DISKWK9M	Limited	Altered Expression	[27]
Neural tube defect	DIS5J95E	Limited	Biomarker	[28]
Parkinson disease	DISQVHKL	Limited	Genetic Variation	[29]
Venous thromboembolism	DISUR7CR	Limited	Genetic Variation	[30]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Temozolomide	DMKECZD	Approved	Cysteine and glycine-rich protein 3 (CSRP3) affects the response to substance of Temozolomide.	[39]
DTI-015	DMXZRW0	Approved	Cysteine and glycine-rich protein 3 (CSRP3) affects the response to substance of DTI-015.	[39]

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 Cysteine and glycine-rich protein 3 (CSRP3).	[31]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Cysteine and glycine-rich protein 3 (CSRP3).	[36]

6 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 Cysteine and glycine-rich protein 3 (CSRP3).	[32]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Cysteine and glycine-rich protein 3 (CSRP3).	[33]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Cysteine and glycine-rich protein 3 (CSRP3).	[34]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Cysteine and glycine-rich protein 3 (CSRP3).	[35]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Cysteine and glycine-rich protein 3 (CSRP3).	[37]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Cysteine and glycine-rich protein 3 (CSRP3).	[38]

References

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