Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTIUB1B3)

• DOT Name: Lysosomal-trafficking regulator (LYST)
• Synonyms: Beige homolog
• Gene Name: LYST
• Related Disease:
  Chediak-Higashi syndrome
  Chronic kidney disease
  Hermansky-Pudlak syndrome
  Advanced cancer
  Albinism
  Arteriosclerosis
  Atherosclerosis
  Atrial fibrillation
  Cardiac failure
  Congestive heart failure
  Hemophagocytic syndrome
  Hermansky-Pudlak syndrome 1
  Nasal polyp
  Neoplasm
  Oculocutaneous albinism
  Onychomycosis
  Parkinsonian disorder
  Piebaldism
  Platelet storage pool deficiency
  Schizophrenia
  Trichohepatoenteric syndrome
  X-linked lymphoproliferative syndrome
  Cohen syndrome
  Immunodeficiency
  Attenuated Chdiak-Higashi syndrome
  Chordoma
  Epstein barr virus infection
  Plasma cell myeloma
  Systemic lupus erythematosus
• UniProt ID: LYST_HUMAN
• Pfam ID: PF02138 ; PF14844 ; PF00400
• Sequence:
  MSTDSNSLAREFLTDVNRLCNAVVQRVEAREEEEEETHMATLGQYLVHGRGFLLLTKLNS
  IIDQALTCREELLTLLLSLLPLVWKIPVQEEKATDFNLPLSADIILTKEKNSSSQRSTQE
  KLHLEGSALSSQVSAKVNVFRKSRRQRKITHRYSVRDARKTQLSTSDSEANSDEKGIAMN
  KHRRPHLLHHFLTSFPKQDHPKAKLDRLATKEQTPPDAMALENSREIIPRQGSNTDILSE
  PAALSVISNMNNSPFDLCHVLLSLLEKVCKFDVTLNHNSPLAASVVPTLTEFLAGFGDCC
  SLSDNLESRVVSAGWTEEPVALIQRMLFRTVLHLLSVDVSTAEMMPENLRKNLTELLRAA
  LKIRICLEKQPDPFAPRQKKTLQEVQEDFVFSKYRHRALLLPELLEGVLQILICCLQSAA
  SNPFYFSQAMDLVQEFIQHHGFNLFETAVLQMEWLVLRDGVPPEASEHLKALINSVMKIM
  STVKKVKSEQLHHSMCTRKRHRRCEYSHFMHHHRDLSGLLVSAFKNQVSKNPFEETADGD
  VYYPERCCCIAVCAHQCLRLLQQASLSSTCVQILSGVHNIGICCCMDPKSVIIPLLHAFK
  LPALKNFQQHILNILNKLILDQLGGAEISPKIKKAACNICTVDSDQLAQLEETLQGNLCD
  AELSSSLSSPSYRFQGILPSSGSEDLLWKWDALKAYQNFVFEEDRLHSIQIANHICNLIQ
  KGNIVVQWKLYNYIFNPVLQRGVELAHHCQHLSVTSAQSHVCSHHNQCLPQDVLQIYVKT
  LPILLKSRVIRDLFLSCNGVSQIIELNCLNGIRSHSLKAFETLIISLGEQQKDASVPDID
  GIDIEQKELSSVHVGTSFHHQQAYSDSPQSLSKFYAGLKEAYPKRRKTVNQDVHINTINL
  FLCVAFLCVSKEAESDRESANDSEDTSGYDSTASEPLSHMLPCISLESLVLPSPEHMHQA
  ADIWSMCRWIYMLSSVFQKQFYRLGGFRVCHKLIFMIIQKLFRSHKEEQGKKEGDTSVNE
  NQDLNRISQPKRTMKEDLLSLAIKSDPIPSELGSLKKSADSLGKLELQHISSINVEEVSA
  TEAAPEEAKLFTSQESETSLQSIRLLEALLAICLHGARTSQQKMELELPNQNLSVESILF
  EMRDHLSQSKVIETQLAKPLFDALLRVALGNYSADFEHNDAMTEKSHQSAEELSSQPGDF
  SEEAEDSQCCSFKLLVEEEGYEADSESNPEDGETQDDGVDLKSETEGFSASSSPNDLLEN
  LTQGEIIYPEICMLELNLLSASKAKLDVLAHVFESFLKIIRQKEKNVFLLMQQGTVKNLL
  GGFLSILTQDDSDFQACQRVLVDLLVSLMSSRTCSEELTLLLRIFLEKSPCTKILLLGIL
  KIIESDTTMSPSQYLTFPLLHAPNLSNGVSSQKYPGILNSKAMGLLRRARVSRSKKEADR
  ESFPHRLLSSWHIAPVHLPLLGQNCWPHLSEGFSVSLWFNVECIHEAESTTEKGKKIKKR
  NKSLILPDSSFDGTESDRPEGAEYINPGERLIEEGCIHIISLGSKALMIQVWADPHNATL
  IFRVCMDSNDDMKAVLLAQVESQENIFLPSKWQHLVLTYLQQPQGKRRIHGKISIWVSGQ
  RKPDVTLDFMLPRKTSLSSDSNKTFCMIGHCLSSQEEFLQLAGKWDLGNLLLFNGAKVGS
  QEAFYLYACGPNHTSVMPCKYGKPVNDYSKYINKEILRCEQIRELFMTKKDVDIGLLIES
  LSVVYTTYCPAQYTIYEPVIRLKGQMKTQLSQRPFSSKEVQSILLEPHHLKNLQPTEYKT
  IQGILHEIGGTGIFVFLFARVVELSSCEETQALALRVILSLIKYNQQRVHELENCNGLSM
  IHQVLIKQKCIVGFYILKTLLEGCCGEDIIYMNENGEFKLDVDSNAIIQDVKLLEELLLD
  WKIWSKAEQGVWETLLAALEVLIRADHHQQMFNIKQLLKAQVVHHFLLTCQVLQEYKEGQ
  LTPMPREVCRSFVKIIAEVLGSPPDLELLTIIFNFLLAVHPPTNTYVCHNPTNFYFSLHI
  DGKIFQEKVRSIMYLRHSSSGGRSLMSPGFMVISPSGFTASPYEGENSSNIIPQQMAAHM
  LRSRSLPAFPTSSLLTQSQKLTGSLGCSIDRLQNIADTYVATQSKKQNSLGSSDTLKKGK
  EDAFISSCESAKTVCEMEAVLSAQVSVSDVPKGVLGFPVVKADHKQLGAEPRSEDDSPGD
  ESCPRRPDYLKGLASFQRSHSTIASLGLAFPSQNGSAAVGRWPSLVDRNTDDWENFAYSL
  GYEPNYNRTASAHSVTEDCLVPICCGLYELLSGVLLILPDVLLEDVMDKLIQADTLLVLV
  NHPSPAIQQGVIKLLDAYFARASKEQKDKFLKNRGFSLLANQLYLHRGTQELLECFIEMF
  FGRHIGLDEEFDLEDVRNMGLFQKWSVIPILGLIETSLYDNILLHNALLLLLQILNSCSK
  VADMLLDNGLLYVLCNTVAALNGLEKNIPMSEYKLLACDIQQLFIAVTIHACSSSGSQYF
  RVIEDLIVMLGYLQNSKNKRTQNMAVALQLRVLQAAMEFIRTTANHDSENLTDSLQSPSA
  PHHAVVQKRKSIAGPRKFPLAQTESLLMKMRSVANDELHVMMQRRMSQENPSQATETELA
  QRLQRLTVLAVNRIIYQEFNSDIIDILRTPENVTQSKTSVFQTEISEENIHHEQSSVFNP
  FQKEIFTYLVEGFKVSIGSSKASGSKQQWTKILWSCKETFRMQLGRLLVHILSPAHAAQE
  RKQIFEIVHEPNHQEILRDCLSPSLQHGAKLVLYLSELIHNHQGELTEEELGTAELLMNA
  LKLCGHKCIPPSASTKADLIKMIKEEQKKYETEEGVNKAAWQKTVNNNQQSLFQRLDSKS
  KDISKIAADITQAVSLSQGNERKKVIQHIRGMYKVDLSASRHWQELIQQLTHDRAVWYDP
  IYYPTSWQLDPTEGPNRERRRLQRCYLTIPNKYLLRDRQKSEDVVKPPLSYLFEDKTHSS
  FSSTVKDKAASESIRVNRRCISVAPSRETAGELLLGKCGMYFVEDNASDTVESSSLQGEL
  EPASFSWTYEEIKEVHKRWWQLRDNAVEIFLTNGRTLLLAFDNTKVRDDVYHNILTNNLP
  NLLEYGNITALTNLWYTGQITNFEYLTHLNKHAGRSFNDLMQYPVFPFILADYVSETLDL
  NDLLIYRNLSKPIAVQYKEKEDRYVDTYKYLEEEYRKGAREDDPMPPVQPYHYGSHYSNS
  GTVLHFLVRMPPFTKMFLAYQDQSFDIPDRTFHSTNTTWRLSSFESMTDVKELIPEFFYL
  PEFLVNREGFDFGVRQNGERVNHVNLPPWARNDPRLFILIHRQALESDYVSQNICQWIDL
  VFGYKQKGKASVQAINVFHPATYFGMDVSAVEDPVQRRALETMIKTYGQTPRQLFHMAHV
  SRPGAKLNIEGELPAAVGLLVQFAFRETREQVKEITYPSPLSWIKGLKWGEYVGSPSAPV
  PVVCFSQPHGERFGSLQALPTRAICGLSRNFCLLMTYSKEQGVRSMNSTDIQWSAILSWG
  YADNILRLKSKQSEPPVNFIQSSQQYQVTSCAWVPDSCQLFTGSKCGVITAYTNRFTSST
  PSEIEMETQIHLYGHTEEITSLFVCKPYSILISVSRDGTCIIWDLNRLCYVQSLAGHKSP
  VTAVSASETSGDIATVCDSAGGGSDLRLWTVNGDLVGHVHCREIICSVAFSNQPEGVSIN
  VIAGGLENGIVRLWSTWDLKPVREITFPKSNKPIISLTFSCDGHHLYTANSDGTVIAWCR
  KDQQRLKQPMFYSFLSSYAAG
• Function: Adapter protein that regulates and/or fission of intracellular vesicles such as lysosomes. Might regulate trafficking of effectors involved in exocytosis. In cytotoxic T-cells and natural killer (NK) cells, has role in the regulation of size, number and exocytosis of lytic granules. In macrophages and dendritic cells, regulates phagosome maturation by controlling the conversion of early phagosomal compartments into late phagosomes. In macrophages and dendritic cells, specifically involved in TLR3- and TLR4-induced production of pro-inflammatory cytokines by regulating the endosomal TLR3- TICAM1/TRIF and TLR4- TICAM1/TRIF signaling pathways.
• Tissue Specificity: Abundantly expressed in adult and fetal thymus, peripheral blood leukocytes, bone marrow and several regions of the adult brain.

Molecular Interaction Atlas (MIA) of This DOT

29 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Chediak-Higashi syndrome	DISPJLLO	Definitive	Autosomal recessive	[1]
Chronic kidney disease	DISW82R7	Definitive	Biomarker	[2]
Hermansky-Pudlak syndrome	DISCY0HQ	Definitive	Genetic Variation	[3]
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[4]
Albinism	DIS5D82I	Strong	Biomarker	[5]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[6]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[6]
Atrial fibrillation	DIS15W6U	Strong	Genetic Variation	[7]
Cardiac failure	DISDC067	Strong	Genetic Variation	[7]
Congestive heart failure	DIS32MEA	Strong	Genetic Variation	[7]
Hemophagocytic syndrome	DIS3TMN4	Strong	Genetic Variation	[8]
Hermansky-Pudlak syndrome 1	DIS966LQ	Strong	Genetic Variation	[9]
Nasal polyp	DISLP3XE	Strong	Biomarker	[10]
Neoplasm	DISZKGEW	Strong	Biomarker	[11]
Oculocutaneous albinism	DISJS7CU	Strong	Genetic Variation	[12]
Onychomycosis	DISE4C4D	Strong	Biomarker	[13]
Parkinsonian disorder	DISHGY45	Strong	Biomarker	[5]
Piebaldism	DISDLDF2	Strong	Biomarker	[14]
Platelet storage pool deficiency	DISHODOH	Strong	Biomarker	[15]
Schizophrenia	DISSRV2N	Strong	Biomarker	[16]
Trichohepatoenteric syndrome	DISL3ODF	Strong	Biomarker	[17]
X-linked lymphoproliferative syndrome	DISA7MJ4	Strong	Biomarker	[18]
Cohen syndrome	DISOOFEZ	moderate	Biomarker	[19]
Immunodeficiency	DIS093I0	moderate	Biomarker	[20]
Attenuated Chdiak-Higashi syndrome	DISGRPVO	Supportive	Autosomal recessive	[8]
Chordoma	DISCHJE7	Disputed	Genetic Variation	[4]
Epstein barr virus infection	DISOO0WT	Limited	Genetic Variation	[21]
Plasma cell myeloma	DIS0DFZ0	Limited	Biomarker	[22]
Systemic lupus erythematosus	DISI1SZ7	Limited	Genetic Variation	[23]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Lysosomal-trafficking regulator (LYST).	[24]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Lysosomal-trafficking regulator (LYST).	[37]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Lysosomal-trafficking regulator (LYST).	[39]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Lysosomal-trafficking regulator (LYST).	[25]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Lysosomal-trafficking regulator (LYST).	[26]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Lysosomal-trafficking regulator (LYST).	[27]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Lysosomal-trafficking regulator (LYST).	[28]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Lysosomal-trafficking regulator (LYST).	[29]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Lysosomal-trafficking regulator (LYST).	[30]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Lysosomal-trafficking regulator (LYST).	[31]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Lysosomal-trafficking regulator (LYST).	[32]
Amphotericin B	DMTAJQE	Approved	Amphotericin B increases the expression of Lysosomal-trafficking regulator (LYST).	[33]
Melphalan	DMOLNHF	Approved	Melphalan decreases the expression of Lysosomal-trafficking regulator (LYST).	[34]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Lysosomal-trafficking regulator (LYST).	[35]
Seocalcitol	DMKL9QO	Phase 3	Seocalcitol increases the expression of Lysosomal-trafficking regulator (LYST).	[36]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Lysosomal-trafficking regulator (LYST).	[38]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Lysosomal-trafficking regulator (LYST).	[40]

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