Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT80HHQ2)

• DOT Name: Neuronal cell adhesion molecule (NRCAM)
• Synonyms: Nr-CAM; Neuronal surface protein Bravo; hBravo; NgCAM-related cell adhesion molecule; Ng-CAM-related
• Gene Name: NRCAM
• Related Disease:
  Adenoma
  Alzheimer disease
  Autism spectrum disorder
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Colon cancer
  Colon carcinoma
  Colonic neoplasm
  Colorectal carcinoma
  Drug dependence
  Mental disorder
  Neurodevelopmental disorder with neuromuscular and skeletal abnormalities
  Schizophrenia
  Substance abuse
  Substance dependence
  Thyroid gland papillary carcinoma
  Thyroid tumor
  Colorectal neoplasm
  Neoplasm
  Intellectual disability
  Melanoma
  Thyroid cancer
  Thyroid gland carcinoma
  Weaver syndrome
  X-linked hydrocephalus with stenosis of the aqueduct of Sylvius
• UniProt ID: NRCAM_HUMAN
• PDB ID: 1UEN; 1UEY
• Pfam ID: PF13882 ; PF00041 ; PF07679 ; PF13927
• Sequence:
  MQLKIMPKKKRLSAGRVPLILFLCQMISALEVPLDPKLLEDLVQPPTITQQSPKDYIIDP
  RENIVIQCEAKGKPPPSFSWTRNGTHFDIDKDPLVTMKPGTGTLIINIMSEGKAETYEGV
  YQCTARNERGAAVSNNIVVRPSRSPLWTKEKLEPITLQSGQSLVLPCRPPIGLPPPIIFW
  MDNSFQRLPQSERVSQGLNGDLYFSNVLPEDTREDYICYARFNHTQTIQQKQPISVKVIS
  VDELNDTIAANLSDTEFYGAKSSRERPPTFLTPEGNASNKEELRGNVLSLECIAEGLPTP
  IIYWAKEDGMLPKNRTVYKNFEKTLQIIHVSEADSGNYQCIAKNALGAIHHTISVRVKAA
  PYWITAPQNLVLSPGEDGTLICRANGNPKPRISWLTNGVPIEIAPDDPSRKIDGDTIIFS
  NVQERSSAVYQCNASNEYGYLLANAFVNVLAEPPRILTPANTLYQVIANRPALLDCAFFG
  SPLPTIEWFKGAKGSALHEDIYVLHENGTLEIPVAQKDSTGTYTCVARNKLGMAKNEVHL
  EIKDPTWIVKQPEYAVVQRGSMVSFECKVKHDHTLSLTVLWLKDNRELPSDERFTVDKDH
  LVVADVSDDDSGTYTCVANTTLDSVSASAVLSVVAPTPTPAPVYDVPNPPFDLELTDQLD
  KSVQLSWTPGDDNNSPITKFIIEYEDAMHKPGLWHHQTEVSGTQTTAQLKLSPYVNYSFR
  VMAVNSIGKSLPSEASEQYLTKASEPDKNPTAVEGLGSEPDNLVITWKPLNGFESNGPGL
  QYKVSWRQKDGDDEWTSVVVANVSKYIVSGTPTFVPYLIKVQALNDMGFAPEPAVVMGHS
  GEDLPMVAPGNVRVNVVNSTLAEVHWDPVPLKSIRGHLQGYRIYYWKTQSSSKRNRRHIE
  KKILTFQGSKTHGMLPGLEPFSHYTLNVRVVNGKGEGPASPDRVFNTPEGVPSAPSSLKI
  VNPTLDSLTLEWDPPSHPNGILTEYTLKYQPINSTHELGPLVDLKIPANKTRWTLKNLNF
  STRYKFYFYAQTSAGSGSQITEEAVTTVDEAGILPPDVGAGKVQAVNPRISNLTAAAAET
  YANISWEYEGPEHVNFYVEYGVAGSKEEWRKEIVNGSRSFFGLKGLMPGTAYKVRVGAVG
  DSGFVSSEDVFETGPAMASRQVDIATQGWFIGLMCAVALLILILLIVCFIRRNKGGKYPV
  KEKEDAHADPEIQPMKEDDGTFGEYSDAEDHKPLKKGSRTPSDRTVKKEDSDDSLVDYGE
  GVNGQFNEDGSFIGQYSGKKEKEPAEGNESSEAPSPVNAMNSFV
• Function: Cell adhesion protein that is required for normal responses to cell-cell contacts in brain and in the peripheral nervous system. Plays a role in neurite outgrowth in response to contactin binding. Plays a role in mediating cell-cell contacts between Schwann cells and axons. Plays a role in the formation and maintenance of the nodes of Ranvier on myelinated axons. Nodes of Ranvier contain clustered sodium channels that are crucial for the saltatory propagation of action potentials along myelinated axons. During development, nodes of Ranvier are formed by the fusion of two heminodes. Required for normal clustering of sodium channels at heminodes; not required for the formation of mature nodes with normal sodium channel clusters. Required, together with GLDN, for maintaining NFASC and sodium channel clusters at mature nodes of Ranvier.
• Tissue Specificity: Detected in all the examined tissues. In the brain it was detected in the amygdala, caudate nucleus, corpus callosum, hippocampus, hypothalamus, substantia nigra, subthalamic nucleus and thalamus.
• KEGG Pathway: Cell adhesion molecules (hsa04514)
• Reactome Pathway:
  NrCAM interactions (R-HSA-447038)
  Neurofascin interactions (R-HSA-447043)
  Interaction between L1 and Ankyrins (R-HSA-445095)

Molecular Interaction Atlas (MIA) of This DOT

26 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenoma	DIS78ZEV	Strong	Altered Expression	[1]
Alzheimer disease	DISF8S70	Strong	Altered Expression	[2]
Autism spectrum disorder	DISXK8NV	Strong	Biomarker	[3]
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[4]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[4]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[5]
Colon cancer	DISVC52G	Strong	Altered Expression	[6]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[6]
Colonic neoplasm	DISSZ04P	Strong	Altered Expression	[6]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[7]
Drug dependence	DIS9IXRC	Strong	Genetic Variation	[8]
Mental disorder	DIS3J5R8	Strong	Genetic Variation	[8]
Neurodevelopmental disorder with neuromuscular and skeletal abnormalities	DIS484OJ	Strong	Autosomal recessive	[9]
Schizophrenia	DISSRV2N	Strong	Biomarker	[10]
Substance abuse	DIS327VW	Strong	Biomarker	[11]
Substance dependence	DISDRAAR	Strong	Biomarker	[11]
Thyroid gland papillary carcinoma	DIS48YMM	Strong	Biomarker	[12]
Thyroid tumor	DISLVKMD	Strong	Biomarker	[12]
Colorectal neoplasm	DISR1UCN	Disputed	Biomarker	[7]
Neoplasm	DISZKGEW	Disputed	Biomarker	[12]
Intellectual disability	DISMBNXP	Limited	Genetic Variation	[13]
Melanoma	DIS1RRCY	Limited	Biomarker	[14]
Thyroid cancer	DIS3VLDH	Limited	Biomarker	[12]
Thyroid gland carcinoma	DISMNGZ0	Limited	Biomarker	[12]
Weaver syndrome	DIS2CE7R	Limited	Genetic Variation	[15]
X-linked hydrocephalus with stenosis of the aqueduct of Sylvius	DIS6QXIR	Limited	Genetic Variation	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ethanol	DMDRQZU	Approved	Neuronal cell adhesion molecule (NRCAM) increases the response to substance of Ethanol.	[11]

19 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Neuronal cell adhesion molecule (NRCAM).	[17]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Neuronal cell adhesion molecule (NRCAM).	[18]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Neuronal cell adhesion molecule (NRCAM).	[19]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Neuronal cell adhesion molecule (NRCAM).	[20]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Neuronal cell adhesion molecule (NRCAM).	[21]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Neuronal cell adhesion molecule (NRCAM).	[22]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Neuronal cell adhesion molecule (NRCAM).	[23]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Neuronal cell adhesion molecule (NRCAM).	[24]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Neuronal cell adhesion molecule (NRCAM).	[25]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Neuronal cell adhesion molecule (NRCAM).	[27]
Aspirin	DM672AH	Approved	Aspirin decreases the expression of Neuronal cell adhesion molecule (NRCAM).	[28]
Indomethacin	DMSC4A7	Approved	Indomethacin decreases the expression of Neuronal cell adhesion molecule (NRCAM).	[29]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Neuronal cell adhesion molecule (NRCAM).	[30]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Neuronal cell adhesion molecule (NRCAM).	[31]
PD-0325901	DM27D4J	Phase 2	PD-0325901 decreases the expression of Neuronal cell adhesion molecule (NRCAM).	[32]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Neuronal cell adhesion molecule (NRCAM).	[34]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Neuronal cell adhesion molecule (NRCAM).	[36]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Neuronal cell adhesion molecule (NRCAM).	[37]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Neuronal cell adhesion molecule (NRCAM).	[38]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Neuronal cell adhesion molecule (NRCAM).	[26]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Neuronal cell adhesion molecule (NRCAM).	[33]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Neuronal cell adhesion molecule (NRCAM).	[35]

References

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• [16] X-linked hydrocephalus: a novel missense mutation in the L1CAM gene.Pediatr Neurol. 2002 Oct;27(4):293-6. doi: 10.1016/s0887-8994(02)00440-x.
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• [22] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
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• [35] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [36] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.
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• [38] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.
• [39] NrCAM in addiction vulnerability: positional cloning, drug-regulation, haplotype-specific expression, and altered drug reward in knockout mice. Neuropsychopharmacology. 2006 Mar;31(3):572-84. doi: 10.1038/sj.npp.1300855.