Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8OB7CG)

• DOT Name: Antizyme inhibitor 2 (AZIN2)
• Synonyms: AzI2; Arginine decarboxylase; ADC; ARGDC; Ornithine decarboxylase-like protein; ODC-like protein; ornithine decarboxylase paralog; ODC-p
• Gene Name: AZIN2
• Related Disease:
  Melanoma
  Acute myocardial infarction
  Adult glioblastoma
  Advanced cancer
  Alzheimer disease
  Brain neoplasm
  Breast neoplasm
  Cardiac failure
  Cholangiocarcinoma
  Chromosomal disorder
  Colitis
  Congestive heart failure
  Crohn disease
  Cytomegalovirus infection
  Esophageal squamous cell carcinoma
  Glioblastoma multiforme
  Glioma
  Head-neck squamous cell carcinoma
  Hepatocellular carcinoma
  Liver cirrhosis
  Lung neoplasm
  Malignant glioma
  Prostate neoplasm
  Rectal carcinoma
  Retinoblastoma
  Small-cell lung cancer
  Stroke
  Trigeminal neuralgia
  Ulcerative colitis
  Carcinoma
  Intrahepatic cholangiocarcinoma
  Metastatic malignant neoplasm
  Adenocarcinoma
  Amyotrophic lateral sclerosis
  Breast cancer
  Breast carcinoma
  Chronic kidney disease
  Chronic obstructive pulmonary disease
  Clear cell renal carcinoma
  Colorectal carcinoma
  Endometrial cancer
  Endometrial carcinoma
  Myocardial infarction
  Nasopharyngeal carcinoma
  Pancreatic cancer
  Plasma cell myeloma
  Prostate cancer
  Prostate carcinoma
• UniProt ID: AZIN2_HUMAN
• Pfam ID: PF02784 ; PF00278
• Sequence:
  MAGYLSESDFVMVEEGFSTRDLLKELTLGASQATTDEVAAFFVADLGAIVRKHFCFLKCL
  PRVRPFYAVKCNSSPGVLKVLAQLGLGFSCANKAEMELVQHIGIPASKIICANPCKQIAQ
  IKYAAKHGIQLLSFDNEMELAKVVKSHPSAKMVLCIATDDSHSLSCLSLKFGVSLKSCRH
  LLENAKKHHVEVVGVSFHIGSGCPDPQAYAQSIADARLVFEMGTELGHKMHVLDLGGGFP
  GTEGAKVRFEEIASVINSALDLYFPEGCGVDIFAELGRYYVTSAFTVAVSIIAKKEVLLD
  QPGREEENGSTSKTIVYHLDEGVYGIFNSVLFDNICPTPILQKKPSTEQPLYSSSLWGPA
  VDGCDCVAEGLWLPQLHVGDWLVFDNMGAYTVGMGSPFWGTQACHITYAMSRVAWEALRR
  QLMAAEQEDDVEGVCKPLSCGWEITDTLCVGPVFTPASIM
• Function: Antizyme inhibitor (AZI) protein that positively regulates ornithine decarboxylase (ODC) activity and polyamine uptake. AZI is an enzymatically inactive ODC homolog that counteracts the negative effect of ODC antizymes (AZs) OAZ1, OAZ2 and OAZ3 on ODC activity by competing with ODC for antizyme-binding. Inhibits antizyme-dependent ODC degradation and releases ODC monomers from their inactive complex with antizymes, leading to formation of the catalytically active ODC homodimer and restoring polyamine production. Participates in the morphological integrity of the trans-Golgi network (TGN) and functions as a regulator of intracellular secretory vesicle trafficking.
• Tissue Specificity: Expressed in the neocortex, thalamus, hippocampus, cerebellum, medulla oblongata, gray and white matter. Expressed in neurons, oligodendrocytes, basket, Purkinje and pyramidal cells. Expressed in spermatocytes and Leydig cells of the testis. Expressed in luteal theca cells lining corpus luteum cysts and in hilus cells of the ovary. Expressed in primary and neoplastic mast cells (MC) (at protein level). Highly expressed in brain. Also expressed in testis.
• KEGG Pathway:
  Arginine and proline metabolism (hsa00330)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Agmatine biosynthesis (R-HSA-351143)
• BioCyc Pathway: MetaCyc:HS06971-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Melanoma	DIS1RRCY	Definitive	Biomarker	[1]
Acute myocardial infarction	DISE3HTG	Strong	Biomarker	[2]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[3]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[4]
Alzheimer disease	DISF8S70	Strong	Biomarker	[5]
Brain neoplasm	DISY3EKS	Strong	Biomarker	[6]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[7]
Cardiac failure	DISDC067	Strong	Biomarker	[8]
Cholangiocarcinoma	DIS71F6X	Strong	Biomarker	[9]
Chromosomal disorder	DISM5BB5	Strong	Genetic Variation	[10]
Colitis	DISAF7DD	Strong	Biomarker	[11]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[8]
Crohn disease	DIS2C5Q8	Strong	Biomarker	[12]
Cytomegalovirus infection	DISCEMGC	Strong	Biomarker	[13]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[14]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[15]
Glioma	DIS5RPEH	Strong	Biomarker	[16]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Biomarker	[17]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[4]
Liver cirrhosis	DIS4G1GX	Strong	Biomarker	[18]
Lung neoplasm	DISVARNB	Strong	Biomarker	[19]
Malignant glioma	DISFXKOV	Strong	Biomarker	[20]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[21]
Rectal carcinoma	DIS8FRR7	Strong	Biomarker	[22]
Retinoblastoma	DISVPNPB	Strong	Biomarker	[23]
Small-cell lung cancer	DISK3LZD	Strong	Biomarker	[24]
Stroke	DISX6UHX	Strong	Biomarker	[25]
Trigeminal neuralgia	DIS31ZY6	Strong	Biomarker	[26]
Ulcerative colitis	DIS8K27O	Strong	Biomarker	[11]
Carcinoma	DISH9F1N	moderate	Altered Expression	[27]
Intrahepatic cholangiocarcinoma	DIS6GOC8	moderate	Biomarker	[28]
Metastatic malignant neoplasm	DIS86UK6	Disputed	Biomarker	[29]
Adenocarcinoma	DIS3IHTY	Limited	Biomarker	[30]
Amyotrophic lateral sclerosis	DISF7HVM	Limited	Biomarker	[31]
Breast cancer	DIS7DPX1	Limited	Biomarker	[32]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[32]
Chronic kidney disease	DISW82R7	Limited	Biomarker	[33]
Chronic obstructive pulmonary disease	DISQCIRF	Limited	Biomarker	[34]
Clear cell renal carcinoma	DISBXRFJ	Limited	Biomarker	[35]
Colorectal carcinoma	DIS5PYL0	Limited	Biomarker	[36]
Endometrial cancer	DISW0LMR	Limited	Biomarker	[37]
Endometrial carcinoma	DISXR5CY	Limited	Biomarker	[37]
Myocardial infarction	DIS655KI	Limited	Biomarker	[38]
Nasopharyngeal carcinoma	DISAOTQ0	Limited	Biomarker	[39]
Pancreatic cancer	DISJC981	Limited	Biomarker	[40]
Plasma cell myeloma	DIS0DFZ0	Limited	Biomarker	[41]
Prostate cancer	DISF190Y	Limited	Biomarker	[42]
Prostate carcinoma	DISMJPLE	Limited	Biomarker	[42]

10 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 Antizyme inhibitor 2 (AZIN2).	[43]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Antizyme inhibitor 2 (AZIN2).	[44]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Antizyme inhibitor 2 (AZIN2).	[45]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Antizyme inhibitor 2 (AZIN2).	[46]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Antizyme inhibitor 2 (AZIN2).	[47]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Antizyme inhibitor 2 (AZIN2).	[48]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Antizyme inhibitor 2 (AZIN2).	[47]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Antizyme inhibitor 2 (AZIN2).	[49]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Antizyme inhibitor 2 (AZIN2).	[50]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Antizyme inhibitor 2 (AZIN2).	[53]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Antizyme inhibitor 2 (AZIN2).	[51]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Antizyme inhibitor 2 (AZIN2).	[52]

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