Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLA925F)

• DOT Name: Baculoviral IAP repeat-containing protein 1 (NAIP)
• Synonyms: Neuronal apoptosis inhibitory protein
• Gene Name: NAIP
• Related Disease:
  B-cell neoplasm
  Multiple sclerosis
  Advanced cancer
  Alcoholic hepatitis
  Autoimmune disease
  Bacterial infection
  Benign prostatic hyperplasia
  Bladder cancer
  Breast neoplasm
  Colon cancer
  Colon carcinoma
  Huntington disease
  Inflammation
  Legionnaires' disease
  Leukemia
  Motor neurone disease
  Neoplasm
  Neuromuscular disease
  Prostate cancer
  Prostate carcinoma
  Spinal muscular atrophy
  Spinal muscular atrophy, type 1
  Spinal muscular atrophy, type II
  Transitional cell carcinoma
  Urinary bladder cancer
  Urinary bladder neoplasm
  Urothelial carcinoma
  Vitiligo
  Arthrogryposis
  Follicular lymphoma
  MALT lymphoma
  Spinal muscular atrophy, type III
  Adenocarcinoma
  Breast cancer
  Breast carcinoma
  Cystitis
  Fabry disease
• UniProt ID: BIRC1_HUMAN
• PDB ID: 2VM5
• Pfam ID: PF00653 ; PF05729 ; PF17889 ; PF17779
• Sequence:
  MATQQKASDERISQFDHNLLPELSALLGLDAVQLAKELEEEEQKERAKMQKGYNSQMRSE
  AKRLKTFVTYEPYSSWIPQEMAAAGFYFTGVKSGIQCFCCSLILFGAGLTRLPIEDHKRF
  HPDCGFLLNKDVGNIAKYDIRVKNLKSRLRGGKMRYQEEEARLASFRNWPFYVQGISPCV
  LSEAGFVFTGKQDTVQCFSCGGCLGNWEEGDDPWKEHAKWFPKCEFLRSKKSSEEITQYI
  QSYKGFVDITGEHFVNSWVQRELPMASAYCNDSIFAYEELRLDSFKDWPRESAVGVAALA
  KAGLFYTGIKDIVQCFSCGGCLEKWQEGDDPLDDHTRCFPNCPFLQNMKSSAEVTPDLQS
  RGELCELLETTSESNLEDSIAVGPIVPEMAQGEAQWFQEAKNLNEQLRAAYTSASFRHMS
  LLDISSDLATDHLLGCDLSIASKHISKPVQEPLVLPEVFGNLNSVMCVEGEAGSGKTVLL
  KKIAFLWASGCCPLLNRFQLVFYLSLSSTRPDEGLASIICDQLLEKEGSVTEMCVRNIIQ
  QLKNQVLFLLDDYKEICSIPQVIGKLIQKNHLSRTCLLIAVRTNRARDIRRYLETILEIK
  AFPFYNTVCILRKLFSHNMTRLRKFMVYFGKNQSLQKIQKTPLFVAAICAHWFQYPFDPS
  FDDVAVFKSYMERLSLRNKATAEILKATVSSCGELALKGFFSCCFEFNDDDLAEAGVDED
  EDLTMCLMSKFTAQRLRPFYRFLSPAFQEFLAGMRLIELLDSDRQEHQDLGLYHLKQINS
  PMMTVSAYNNFLNYVSSLPSTKAGPKIVSHLLHLVDNKESLENISENDDYLKHQPEISLQ
  MQLLRGLWQICPQAYFSMVSEHLLVLALKTAYQSNTVAACSPFVLQFLQGRTLTLGALNL
  QYFFDHPESLSLLRSIHFPIRGNKTSPRAHFSVLETCFDKSQVPTIDQDYASAFEPMNEW
  ERNLAEKEDNVKSYMDMQRRASPDLSTGYWKLSPKQYKIPCLEVDVNDIDVVGQDMLEIL
  MTVFSASQRIELHLNHSRGFIESIRPALELSKASVTKCSISKLELSAAEQELLLTLPSLE
  SLEVSGTIQSQDQIFPNLDKFLCLKELSVDLEGNINVFSVIPEEFPNFHHMEKLLIQISA
  EYDPSKLVKLIQNSPNLHVFHLKCNFFSDFGSLMTMLVSCKKLTEIKFSDSFFQAVPFVA
  SLPNFISLKILNLEGQQFPDEETSEKFAYILGSLSNLEELILPTGDGIYRVAKLIIQQCQ
  QLHCLRVLSFFKTLNDDSVVEIAKVAISGGFQKLENLKLSINHKITEEGYRNFFQALDNM
  PNLQELDISRHFTECIKAQATTVKSLSQCVLRLPRLIRLNMLSWLLDADDIALLNVMKER
  HPQSKYLTILQKWILPFSPIIQK
• Function: Anti-apoptotic protein which acts by inhibiting the activities of CASP3, CASP7 and CASP9. Can inhibit the autocleavage of pro-CASP9 and cleavage of pro-CASP3 by CASP9. Capable of inhibiting CASP9 autoproteolysis at 'Asp-315' and decreasing the rate of auto proteolysis at 'Asp-330'. Acts as a mediator of neuronal survival in pathological conditions. Prevents motor-neuron apoptosis induced by a variety of signals. Possible role in the prevention of spinal muscular atrophy that seems to be caused by inappropriate persistence of motor-neuron apoptosis: mutated or deleted forms of NAIP have been found in individuals with severe spinal muscular atrophy.; Acts as a sensor component of the NLRC4 inflammasome that specifically recognizes and binds needle protein CprI from pathogenic bacteria C.violaceum. Association of pathogenic bacteria proteins drives in turn drive assembly and activation of the NLRC4 inflammasome, promoting caspase-1 activation, cytokine production and macrophage pyroptosis. The NLRC4 inflammasome is activated as part of the innate immune response to a range of intracellular bacteria such as C.violaceum and L.pneumophila.
• Tissue Specificity: Expressed in motor neurons, but not in sensory neurons. Found in liver and placenta, and to a lesser extent in spinal cord.
• KEGG Pathway:
  NOD-like receptor sig.ling pathway (hsa04621)
  Pathogenic Escherichia coli infection (hsa05130)
  Shigellosis (hsa05131)
  Salmonella infection (hsa05132)
  Legionellosis (hsa05134)

Molecular Interaction Atlas (MIA) of This DOT

37 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
B-cell neoplasm	DISVY326	Definitive	Biomarker	[1]
Multiple sclerosis	DISB2WZI	Definitive	Genetic Variation	[2]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[3]
Alcoholic hepatitis	DISA7SH0	Strong	Altered Expression	[4]
Autoimmune disease	DISORMTM	Strong	Genetic Variation	[5]
Bacterial infection	DIS5QJ9S	Strong	Biomarker	[6]
Benign prostatic hyperplasia	DISI3CW2	Strong	Altered Expression	[7]
Bladder cancer	DISUHNM0	Strong	Biomarker	[8]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[9]
Colon cancer	DISVC52G	Strong	Altered Expression	[10]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[10]
Huntington disease	DISQPLA4	Strong	Biomarker	[11]
Inflammation	DISJUQ5T	Strong	Biomarker	[12]
Legionnaires' disease	DIS8V4GQ	Strong	Genetic Variation	[13]
Leukemia	DISNAKFL	Strong	Altered Expression	[14]
Motor neurone disease	DISUHWUI	Strong	Genetic Variation	[15]
Neoplasm	DISZKGEW	Strong	Biomarker	[10]
Neuromuscular disease	DISQTIJZ	Strong	Genetic Variation	[16]
Prostate cancer	DISF190Y	Strong	Altered Expression	[17]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[17]
Spinal muscular atrophy	DISTLKOB	Strong	Biomarker	[18]
Spinal muscular atrophy, type 1	DISYCWUG	Strong	GermlineModifyingMutation	[19]
Spinal muscular atrophy, type II	DIS3GNQ4	Strong	GermlineModifyingMutation	[19]
Transitional cell carcinoma	DISWVVDR	Strong	Biomarker	[8]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[8]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[8]
Urothelial carcinoma	DISRTNTN	Strong	Biomarker	[8]
Vitiligo	DISR05SL	Strong	Genetic Variation	[5]
Arthrogryposis	DISC81CM	moderate	Genetic Variation	[20]
Follicular lymphoma	DISVEUR6	moderate	Biomarker	[21]
MALT lymphoma	DIS1AVVE	moderate	Biomarker	[21]
Spinal muscular atrophy, type III	DISNG3SD	moderate	Genetic Variation	[22]
Adenocarcinoma	DIS3IHTY	Limited	Altered Expression	[23]
Breast cancer	DIS7DPX1	Limited	Altered Expression	[24]
Breast carcinoma	DIS2UE88	Limited	Altered Expression	[24]
Cystitis	DIS2D4B9	Limited	Altered Expression	[25]
Fabry disease	DISUUQJF	Limited	Altered Expression	[26]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Deoxycholic acid	DM3GYAL	Approved	Baculoviral IAP repeat-containing protein 1 (NAIP) decreases the response to substance of Deoxycholic acid.	[48]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Baculoviral IAP repeat-containing protein 1 (NAIP).	[27]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Baculoviral IAP repeat-containing protein 1 (NAIP).	[28]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Baculoviral IAP repeat-containing protein 1 (NAIP).	[29]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Baculoviral IAP repeat-containing protein 1 (NAIP).	[30]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Baculoviral IAP repeat-containing protein 1 (NAIP).	[31]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Baculoviral IAP repeat-containing protein 1 (NAIP).	[32]
Zoledronate	DMIXC7G	Approved	Zoledronate affects the expression of Baculoviral IAP repeat-containing protein 1 (NAIP).	[33]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Baculoviral IAP repeat-containing protein 1 (NAIP).	[34]
Bortezomib	DMNO38U	Approved	Bortezomib affects the expression of Baculoviral IAP repeat-containing protein 1 (NAIP).	[35]
Menthol	DMG2KW7	Approved	Menthol increases the expression of Baculoviral IAP repeat-containing protein 1 (NAIP).	[36]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Baculoviral IAP repeat-containing protein 1 (NAIP).	[37]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Baculoviral IAP repeat-containing protein 1 (NAIP).	[38]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of Baculoviral IAP repeat-containing protein 1 (NAIP).	[39]
IB-MECA	DM9G5XD	Phase 3	IB-MECA decreases the expression of Baculoviral IAP repeat-containing protein 1 (NAIP).	[40]
Pelitinib	DMIW453	Phase 2	Pelitinib decreases the expression of Baculoviral IAP repeat-containing protein 1 (NAIP).	[41]
L-745,870	DMTGR25	Phase 2	L-745,870 increases the expression of Baculoviral IAP repeat-containing protein 1 (NAIP).	[42]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Baculoviral IAP repeat-containing protein 1 (NAIP).	[43]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Baculoviral IAP repeat-containing protein 1 (NAIP).	[44]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Baculoviral IAP repeat-containing protein 1 (NAIP).	[45]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Baculoviral IAP repeat-containing protein 1 (NAIP).	[46]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of Baculoviral IAP repeat-containing protein 1 (NAIP).	[47]

References

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