Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFVXD7H)

DOT Name	Perforin-1 (PRF1)
Synonyms	P1; Cytolysin; Lymphocyte pore-forming protein; PFP
Gene Name	PRF1
Related Disease	B-cell neoplasm ( ) Familial hemophagocytic lymphohistiocytosis 2 ( ) Acute lymphocytic leukaemia ( ) Adult lymphoma ( ) Advanced cancer ( ) Anaplastic large cell lymphoma ( ) Asthma ( ) Autism ( ) Autoimmune disease ( ) Colon carcinoma ( ) Endophthalmitis ( ) Ewing sarcoma ( ) Glomerulonephritis ( ) Hepatitis C virus infection ( ) HIV infectious disease ( ) Idiopathic aplastic anemia ( ) Immunodeficiency ( ) Inflammatory bowel disease ( ) Lymphoma ( ) Multiple sclerosis ( ) Myocardial infarction ( ) Neoplasm ( ) Nervous system disease ( ) Non-alcoholic fatty liver disease ( ) Non-alcoholic steatohepatitis ( ) Promyelocytic leukaemia ( ) Systemic lupus erythematosus ( ) Triple negative breast cancer ( ) Type-1 diabetes ( ) Bladder cancer ( ) High blood pressure ( ) leukaemia ( ) Leukemia ( ) Malignant soft tissue neoplasm ( ) Pancytopenia ( ) Pediatric lymphoma ( ) Sarcoma ( ) Urinary bladder cancer ( ) Urinary bladder neoplasm ( ) Fatal post-viral neurodegenerative disorder ( ) Hereditary hemophagocytic lymphohistiocytosis ( ) Childhood acute lymphoblastic leukemia ( ) Autoimmune lymphoproliferative syndrome type 1 ( ) Bacterial infection ( ) Clear cell renal carcinoma ( ) Lymphoma, non-Hodgkin, familial ( ) Meningitis ( ) Pneumococcal meningitis ( ) Rheumatoid arthritis ( ) Tuberculosis ( )
UniProt ID	PERF_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
Pfam ID	PF00168 ; PF01823
Sequence	MAARLLLLGILLLLLPLPVPAPCHTAARSECKRSHKFVPGAWLAGEGVDVTSLRRSGSFP VDTQRFLRPDGTCTLCENALQEGTLQRLPLALTNWRAQGSGCQRHVTRAKVSSTEAVARD AARSIRNDWKVGLDVTPKPTSNVHVSVAGSHSQAANFAAQKTHQDQYSFSTDTVECRFYS FHVVHTPPLHPDFKRALGDLPHHFNASTQPAYLRLISNYGTHFIRAVELGGRISALTALR TCELALEGLTDNEVEDCLTVEAQVNIGIHGSISAEAKACEEKKKKHKMTASFHQTYRERH SEVVGGHHTSINDLLFGIQAGPEQYSAWVNSLPGSPGLVDYTLEPLHVLLDSQDPRREAL RRALSQYLTDRARWRDCSRPCPPGRQKSPRDPCQCVCHGSAVTTQDCCPRQRGLAQLEVT FIQAWGLWGDWFTATDAYVKLFFGGQELRTSTVWDNNNPIWSVRLDFGDVLLATGGPLRL QVWDQDSGRDDDLLGTCDQAPKSGSHEVRCNLNHGHLKFRYHARCLPHLGGGTCLDYVPQ MLLGEPPGNRSGAVW
Function	Pore-forming protein that plays a key role in granzyme-mediated programmed cell death, and in defense against virus-infected or neoplastic cells. Plays an important role in killing other cells that are recognized as non-self by the immune system, e.g. in transplant rejection or some forms of autoimmune disease. Can insert into the membrane of target cells in its calcium-bound form, oligomerize and form large pores. Promotes cytolysis and apoptosis of target cells by mediating the passage and uptake of cytotoxic granzymes. Facilitates the delivery of cationic cargo protein, while anionic or neural proteins are not delivered efficiently. Perforin pores allow the release of mature caspase-7 (CASP7) into the extracellular milieu.
KEGG Pathway	Apoptosis (hsa04210 ) .tural killer cell mediated cytotoxicity (hsa04650 ) Type I diabetes mellitus (hsa04940 ) Autoimmune thyroid disease (hsa05320 ) Allograft rejection (hsa05330 ) Graft-versus-host disease (hsa05332 ) Viral myocarditis (hsa05416 )

Molecular Interaction Atlas (MIA) of This DOT

50 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
B-cell neoplasm	DISVY326	Definitive	Genetic Variation	[1]
Familial hemophagocytic lymphohistiocytosis 2	DISBBSGH	Definitive	Autosomal recessive	[2]
Acute lymphocytic leukaemia	DISPX75S	Strong	Genetic Variation	[3]
Adult lymphoma	DISK8IZR	Strong	Genetic Variation	[4]
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[5]
Anaplastic large cell lymphoma	DISP4D1R	Strong	Genetic Variation	[6]
Asthma	DISW9QNS	Strong	Biomarker	[7]
Autism	DISV4V1Z	Strong	Biomarker	[8]
Autoimmune disease	DISORMTM	Strong	Genetic Variation	[9]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[10]
Endophthalmitis	DISCQV4J	Strong	Biomarker	[11]
Ewing sarcoma	DISQYLV3	Strong	Biomarker	[12]
Glomerulonephritis	DISPZIQ3	Strong	Biomarker	[13]
Hepatitis C virus infection	DISQ0M8R	Strong	Altered Expression	[14]
HIV infectious disease	DISO97HC	Strong	Biomarker	[15]
Idiopathic aplastic anemia	DISVFTJ9	Strong	SusceptibilityMutation	[16]
Immunodeficiency	DIS093I0	Strong	Biomarker	[17]
Inflammatory bowel disease	DISGN23E	Strong	Biomarker	[18]
Lymphoma	DISN6V4S	Strong	Genetic Variation	[4]
Multiple sclerosis	DISB2WZI	Strong	Biomarker	[19]
Myocardial infarction	DIS655KI	Strong	Biomarker	[20]
Neoplasm	DISZKGEW	Strong	Biomarker	[21]
Nervous system disease	DISJ7GGT	Strong	Genetic Variation	[4]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Biomarker	[22]
Non-alcoholic steatohepatitis	DIST4788	Strong	Biomarker	[22]
Promyelocytic leukaemia	DISYGG13	Strong	Biomarker	[23]
Systemic lupus erythematosus	DISI1SZ7	Strong	Altered Expression	[24]
Triple negative breast cancer	DISAMG6N	Strong	Biomarker	[25]
Type-1 diabetes	DIS7HLUB	Strong	Genetic Variation	[26]
Bladder cancer	DISUHNM0	moderate	Altered Expression	[27]
High blood pressure	DISY2OHH	moderate	Genetic Variation	[28]
leukaemia	DISS7D1V	moderate	Genetic Variation	[29]
Leukemia	DISNAKFL	moderate	Genetic Variation	[29]
Malignant soft tissue neoplasm	DISTC6NO	moderate	Genetic Variation	[29]
Pancytopenia	DISVKEHV	moderate	Altered Expression	[16]
Pediatric lymphoma	DIS51BK2	moderate	Genetic Variation	[4]
Sarcoma	DISZDG3U	moderate	Genetic Variation	[29]
Urinary bladder cancer	DISDV4T7	moderate	Altered Expression	[27]
Urinary bladder neoplasm	DIS7HACE	moderate	Altered Expression	[27]
Fatal post-viral neurodegenerative disorder	DISP80MM	Supportive	Autosomal recessive	[30]
Hereditary hemophagocytic lymphohistiocytosis	DISQP21Z	Supportive	Autosomal recessive	[31]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Disputed	Genetic Variation	[3]
Autoimmune lymphoproliferative syndrome type 1	DISAFGRA	Limited	Genetic Variation	[26]
Bacterial infection	DIS5QJ9S	Limited	Biomarker	[11]
Clear cell renal carcinoma	DISBXRFJ	Limited	Altered Expression	[32]
Lymphoma, non-Hodgkin, familial	DISCXYIZ	Limited	Unknown	[33]
Meningitis	DISQABAA	Limited	Biomarker	[34]
Pneumococcal meningitis	DISM5U0L	Limited	Biomarker	[35]
Rheumatoid arthritis	DISTSB4J	Limited	Biomarker	[36]
Tuberculosis	DIS2YIMD	Limited	Genetic Variation	[37]
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⏷ Show the Full List of 50 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Pentoxifylline	DMU3DNC	Approved	Perforin-1 (PRF1) increases the Cell death ADR of Pentoxifylline.	[50]
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2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Perforin-1 (PRF1).	[38]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Perforin-1 (PRF1).	[46]
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9 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Perforin-1 (PRF1).	[39]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Perforin-1 (PRF1).	[40]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the expression of Perforin-1 (PRF1).	[41]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Perforin-1 (PRF1).	[42]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Perforin-1 (PRF1).	[43]
Menthol	DMG2KW7	Approved	Menthol decreases the expression of Perforin-1 (PRF1).	[44]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Perforin-1 (PRF1).	[45]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Perforin-1 (PRF1).	[47]
Rapamycin Immunosuppressant Drug	DM678IB	Investigative	Rapamycin Immunosuppressant Drug decreases the expression of Perforin-1 (PRF1).	[49]
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⏷ Show the Full List of 9 Drug(s)

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-49	DMTUC9E	Patented	PMID28870136-Compound-49 decreases the secretion of Perforin-1 (PRF1).	[48]
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References

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