Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRJ6S6K)

DOT Name	Pyrin (MEFV)
Synonyms	Marenostrin
Gene Name	MEFV
Related Disease	Advanced cancer ( ) Autosomal recessive familial Mediterranean fever ( ) Colitis ( ) Familial Mediterranean fever ( ) Pyoderma gangrenosum ( ) Relapsing fever ( ) Acne vulgaris ( ) Acute myelogenous leukaemia ( ) Ankylosing spondylitis ( ) Arteriosclerosis ( ) Atherosclerosis ( ) Autoimmune disease ( ) Behcet disease ( ) Brucellosis ( ) Coronary heart disease ( ) Crohn disease ( ) Familial Mediterranean fever, autosomal dominant ( ) Fibromyalgia ( ) Hepatocellular carcinoma ( ) Hereditary periodic fever syndrome ( ) Hidradenitis suppurativa ( ) Inflammation ( ) Juvenile idiopathic arthritis ( ) Mevalonate kinase deficiency ( ) Myocardial infarction ( ) Neoplasm ( ) Nephropathy ( ) Non-insulin dependent diabetes ( ) Osteoarthritis ( ) Pyogenic arthritis-pyoderma gangrenosum-acne syndrome ( ) Vasculitis ( ) Chronic kidney disease ( ) Cryopyrin-associated periodic syndrome ( ) Diabetic kidney disease ( ) Hyperimmunoglobulinemia D with periodic fever ( ) Psoriatic arthritis ( ) Nephrotic syndrome ( ) Alzheimer disease ( ) Arthritis ( ) Autoinflammatory syndrome ( ) Autosomal dominant familial periodic fever ( ) CINCA syndrome ( ) Muckle-Wells syndrome ( ) Parkinson disease ( ) Periodic fever syndrome ( ) Ulcerative colitis ( )
UniProt ID	MEFV_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	2MPC; 2WL1; 4CG4
Pfam ID	PF13765 ; PF02758 ; PF00622 ; PF00643
Sequence	MAKTPSDHLLSTLEELVPYDFEKFKFKLQNTSVQKEHSRIPRSQIQRARPVKMATLLVTY YGEEYAVQLTLQVLRAINQRLLAEELHRAAIQEYSTQENGTDDSAASSSLGENKPRSLKT PDHPEGNEGNGPRPYGGGAASLRCSQPEAGRGLSRKPLSKRREKASEGLDAQGKPRTRSP ALPGGRSPGPCRALEGGQAEVRLRRNASSAGRLQGLAGGAPGQKECRPFEVYLPSGKMRP RSLEVTISTGEKAPANPEILLTLEEKTAANLDSATEPRARPTPDGGASADLKEGPGNPEH SVTGRPPDTAASPRCHAQEGDPVDGTCVRDSCSFPEAVSGHPQASGSRSPGCPRCQDSHE RKSPGSLSPQPLPQCKRHLKQVQLLFCEDHDEPICLICSLSQEHQGHRVRPIEEVALEHK KKIQKQLEHLKKLRKSGEEQRSYGEEKAVSFLKQTEALKQRVQRKLEQVYYFLEQQEHFF VASLEDVGQMVGQIRKAYDTRVSQDIALLDALIGELEAKECQSEWELLQDIGDILHRAKT VPVPEKWTTPQEIKQKIQLLHQKSEFVEKSTKYFSETLRSEMEMFNVPELIGAQAHAVNV ILDAETAYPNLIFSDDLKSVRLGNKWERLPDGPQRFDSCIIVLGSPSFLSGRRYWEVEVG DKTAWILGACKTSISRKGNMTLSPENGYWVVIMMKENEYQASSVPPTRLLIKEPPKRVGI FVDYRVGSISFYNVTARSHIYTFASCSFSGPLQPIFSPGTRDGGKNTAPLTICPVGGQGP D
Function	Involved in the regulation of innate immunity and the inflammatory response in response to IFNG/IFN-gamma. Organizes autophagic machinery by serving as a platform for the assembly of ULK1, Beclin 1/BECN1, ATG16L1, and ATG8 family members and recognizes specific autophagy targets, thus coordinating target recognition with assembly of the autophagic apparatus and initiation of autophagy. Acts as an autophagy receptor for the degradation of several inflammasome components, including CASP1, NLRP1 and NLRP3, hence preventing excessive IL1B- and IL18-mediated inflammation. However, it can also have a positive effect in the inflammatory pathway, acting as an innate immune sensor that triggers PYCARD/ASC specks formation, caspase-1 activation, and IL1B and IL18 production. Together with AIM2, also acts as a mediator of pyroptosis, necroptosis and apoptosis (PANoptosis), an integral part of host defense against pathogens, in response to bacterial infection. It is required for PSTPIP1-induced PYCARD/ASC oligomerization and inflammasome formation. Recruits PSTPIP1 to inflammasomes, and is required for PSTPIP1 oligomerization.
Tissue Specificity	Expressed in peripheral blood leukocytes, particularly in mature granulocytes and to a lesser extent in monocytes but not in lymphocytes. Detected in spleen, lung and muscle, probably as a result of leukocyte infiltration in these tissues. Not expressed in thymus, prostate, testis, ovary, small intestine, colon, heart, brain, placenta, liver, kidney, pancreas. Expression detected in several myeloid leukemic, colon cancer, and prostate cancer cell lines.
KEGG Pathway	NOD-like receptor sig.ling pathway (hsa04621 ) Cytosolic D.-sensing pathway (hsa04623 ) Yersinia infection (hsa05135 )
Reactome Pathway	Purinergic signaling in leishmaniasis infection (R-HSA-9660826 ) The NLRP3 inflammasome (R-HSA-844456 )

Molecular Interaction Atlas (MIA) of This DOT

46 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Advanced cancer	DISAT1Z9	Definitive	Altered Expression	[1]
Autosomal recessive familial Mediterranean fever	DISRY2WI	Definitive	Autosomal recessive	[2]
Colitis	DISAF7DD	Definitive	Biomarker	[3]
Familial Mediterranean fever	DISVP5WP	Definitive	Autosomal recessive	[4]
Pyoderma gangrenosum	DIS8QVTT	Definitive	Genetic Variation	[5]
Relapsing fever	DISEA4L7	Definitive	Genetic Variation	[6]
Acne vulgaris	DISKW8PI	Strong	Biomarker	[7]
Acute myelogenous leukaemia	DISCSPTN	Strong	Genetic Variation	[8]
Ankylosing spondylitis	DISRC6IR	Strong	Genetic Variation	[9]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[10]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[10]
Autoimmune disease	DISORMTM	Strong	Biomarker	[11]
Behcet disease	DISSYMBS	Strong	Genetic Variation	[12]
Brucellosis	DISEAYGH	Strong	Genetic Variation	[13]
Coronary heart disease	DIS5OIP1	Strong	Altered Expression	[14]
Crohn disease	DIS2C5Q8	Strong	Genetic Variation	[15]
Familial Mediterranean fever, autosomal dominant	DIS1AYEJ	Strong	Autosomal recessive	[16]
Fibromyalgia	DISZJDS2	Strong	Altered Expression	[17]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[18]
Hereditary periodic fever syndrome	DISS9RWQ	Strong	Genetic Variation	[3]
Hidradenitis suppurativa	DIS3ZNAK	Strong	Genetic Variation	[19]
Inflammation	DISJUQ5T	Strong	Biomarker	[20]
Juvenile idiopathic arthritis	DISQZGBV	Strong	Genetic Variation	[21]
Mevalonate kinase deficiency	DISSTRVK	Strong	Genetic Variation	[22]
Myocardial infarction	DIS655KI	Strong	Biomarker	[23]
Neoplasm	DISZKGEW	Strong	Biomarker	[24]
Nephropathy	DISXWP4P	Strong	Biomarker	[25]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Altered Expression	[14]
Osteoarthritis	DIS05URM	Strong	Biomarker	[26]
Pyogenic arthritis-pyoderma gangrenosum-acne syndrome	DIS7E15X	Strong	Biomarker	[27]
Vasculitis	DISQRKDX	Strong	Biomarker	[28]
Chronic kidney disease	DISW82R7	moderate	Biomarker	[29]
Cryopyrin-associated periodic syndrome	DISPXXOZ	moderate	Genetic Variation	[30]
Diabetic kidney disease	DISJMWEY	moderate	Biomarker	[31]
Hyperimmunoglobulinemia D with periodic fever	DISWB92Q	moderate	Biomarker	[32]
Psoriatic arthritis	DISLWTG2	moderate	Genetic Variation	[33]
Nephrotic syndrome	DISSPSC2	Disputed	Biomarker	[34]
Alzheimer disease	DISF8S70	Limited	Biomarker	[35]
Arthritis	DIST1YEL	Limited	Genetic Variation	[27]
Autoinflammatory syndrome	DISCMCGL	Limited	Biomarker	[36]
Autosomal dominant familial periodic fever	DISCRNV1	Limited	Genetic Variation	[37]
CINCA syndrome	DISU6RZC	Limited	Genetic Variation	[38]
Muckle-Wells syndrome	DISMT3TQ	Limited	Biomarker	[39]
Parkinson disease	DISQVHKL	Limited	Biomarker	[40]
Periodic fever syndrome	DIS9MNYC	Limited	Biomarker	[28]
Ulcerative colitis	DIS8K27O	Limited	Genetic Variation	[41]
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⏷ Show the Full List of 46 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
Beclomethasone dipropionate	DM5NW1E	Phase 4	Pyrin (MEFV) increases the response to substance of Beclomethasone dipropionate.	[45]
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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 Pyrin (MEFV).	[42]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Pyrin (MEFV).	[43]
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1 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Pyrin (MEFV).	[44]
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References

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