Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTEURA8N)

• DOT Name: Guanine nucleotide exchange factor DBS (MCF2L)
• Synonyms: DBL's big sister; MCF2-transforming sequence-like protein
• Gene Name: MCF2L
• Related Disease:
  Bone osteosarcoma
  Hypogonadotropic hypogonadism 7 with or without anosmia
  Osteosarcoma
  Advanced cancer
  African trypanosomiasis
  Alzheimer disease
  Arteriosclerosis
  Atherosclerosis
  Autism
  Breast cancer
  Breast carcinoma
  Cardiovascular disease
  Cerebral palsy
  Clear cell renal carcinoma
  Cytomegalovirus infection
  Delirium
  Dystonia
  Epilepsy
  Essential tremor
  Hepatitis C virus infection
  Immunodeficiency
  Impulse control disorder
  Major depressive disorder
  Neoplasm
  Non-alcoholic fatty liver disease
  Osteoarthritis
  Pantothenate kinase-associated neurodegeneration
  Parkinsonian disorder
  Prostate cancer
  Prostate carcinoma
  Renal cell carcinoma
  Restless legs syndrome
  Tardive dyskinesia
  Tourette syndrome
  Chronic renal failure
  Coronary heart disease
  Fabry disease
  Influenza
  Capillary malformation
  Depression
  Mental disorder
  Nervous system disease
  Obsessive compulsive disorder
  Osteoporosis
  Sleep disorder
  Substance withdrawal syndrome
  Type-1/2 diabetes
• UniProt ID: MCF2L_HUMAN
• Pfam ID: PF13716 ; PF00169 ; PF00621 ; PF07653 ; PF00435
• Sequence:
  MFDCWRFILCKRPGSNSYSSPQRPNEAKKEETDHQIDVSDVIRLVQDTPEATAMATDEIM
  HQDIVPLCAADIQDQLKKRFAYLSGGRGQDGSPVITFPDYPAFSEIPDKEFQNVMTYLTS
  IPSLQDAGIGFILVIDRRRDKWTSVKASVLRIAASFPANLQLVLVLRPTGFFQRTLSDIA
  FKFNRDDFKMKVPVIMLSSVPDLHGYIDKSQLTEDLGGTLDYCHSRWLCQRTAIESFALM
  VKQTAQMLQSFGTELAETELPNDVQSTSSVLCAHTEKKDKAKEDLRLALKEGHSVLESLR
  ELQAEGSEPSVNQDQLDNQATVQRLLAQLNETEAAFDEFWAKHQQKLEQCLQLRHFEQGF
  REVKAILDAASQKIATFTDIGNSLAHVEHLLRDLASFEEKSGVAVERARALSLDGEQLIG
  NKHYAVDSIRPKCQELRHLCDQFSAEIARRRGLLSKSLELHRRLETSMKWCDEGIYLLAS
  QPVDKCQSQDGAEAALQEIEKFLETGAENKIQELNAIYKEYESILNQDLMEHVRKVFQKQ
  ASMEEVFHRRQASLKKLAARQTRPVQPVAPRPEALAKSPCPSPGIRRGSENSSSEGGALR
  RGPYRRAKSEMSESRQGRGSAGEEEESLAILRRHVMSELLDTERAYVEELLCVLEGYAAE
  MDNPLMAHLLSTGLHNKKDVLFGNMEEIYHFHNRIFLRELENYTDCPELVGRCFLERMED
  FQIYEKYCQNKPRSESLWRQCSDCPFFQECQRKLDHKLSLDSYLLKPVQRITKYQLLLKE
  MLKYSRNCEGAEDLQEALSSILGILKAVNDSMHLIAITGYDGNLGDLGKLLMQGSFSVWT
  DHKRGHTKVKELARFKPMQRHLFLHEKAVLFCKKREENGEGYEKAPSYSYKQSLNMAAVG
  ITENVKGDAKKFEIWYNAREEVYIVQAPTPEIKAAWVNEIRKVLTSQLQACREASQHRAL
  EQSQSLPLPAPTSTSPSRGNSRNIKKLEERKTDPLSLEGYVSSAPLTKPPEKGKGWSKTS
  HSLEAPEDDGGWSSAEEQINSSDAEEDGGLGPKKLVPGKYTVVADHEKGGPDALRVRSGD
  VVELVQEGDEGLWYVRDPTTGKEGWVPASSLSVRLGPSGSAQCLSSSGKAHVPRAHP
• Function: Guanine nucleotide exchange factor that catalyzes guanine nucleotide exchange on RHOA and CDC42, and thereby contributes to the regulation of RHOA and CDC42 signaling pathways. Seems to lack activity with RAC1. Becomes activated and highly tumorigenic by truncation of the N-terminus. Isoform 5 activates CDC42 ; [Isoform 3]: Does not catalyze guanine nucleotide exchange on CDC42.
• Reactome Pathway:
  G alpha (12/13) signalling events (R-HSA-416482)
  RHOA GTPase cycle (R-HSA-8980692)
  RHOB GTPase cycle (R-HSA-9013026)
  RHOC GTPase cycle (R-HSA-9013106)
  CDC42 GTPase cycle (R-HSA-9013148)
  RAC1 GTPase cycle (R-HSA-9013149)
  RHOG GTPase cycle (R-HSA-9013408)
  NRAGE signals death through JNK (R-HSA-193648)

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bone osteosarcoma	DIST1004	Definitive	Altered Expression	[1]
Hypogonadotropic hypogonadism 7 with or without anosmia	DISPBWEU	Definitive	Genetic Variation	[2]
Osteosarcoma	DISLQ7E2	Definitive	Altered Expression	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
African trypanosomiasis	DISBIXK4	Strong	Biomarker	[4]
Alzheimer disease	DISF8S70	Strong	Biomarker	[5]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[6]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[6]
Autism	DISV4V1Z	Strong	Biomarker	[3]
Breast cancer	DIS7DPX1	Strong	Biomarker	[7]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[7]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[8]
Cerebral palsy	DIS82ODL	Strong	Biomarker	[9]
Clear cell renal carcinoma	DISBXRFJ	Strong	Genetic Variation	[10]
Cytomegalovirus infection	DISCEMGC	Strong	Biomarker	[11]
Delirium	DIS2OKP1	Strong	Genetic Variation	[12]
Dystonia	DISJLFGW	Strong	Biomarker	[13]
Epilepsy	DISBB28L	Strong	Biomarker	[14]
Essential tremor	DIS7GBKQ	Strong	Biomarker	[15]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[16]
Immunodeficiency	DIS093I0	Strong	Biomarker	[17]
Impulse control disorder	DISRIYJ5	Strong	Biomarker	[18]
Major depressive disorder	DIS4CL3X	Strong	Biomarker	[19]
Neoplasm	DISZKGEW	Strong	Biomarker	[20]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Biomarker	[21]
Osteoarthritis	DIS05URM	Strong	Genetic Variation	[22]
Pantothenate kinase-associated neurodegeneration	DIS50V55	Strong	Biomarker	[23]
Parkinsonian disorder	DISHGY45	Strong	Biomarker	[24]
Prostate cancer	DISF190Y	Strong	Biomarker	[25]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[25]
Renal cell carcinoma	DISQZ2X8	Strong	Genetic Variation	[10]
Restless legs syndrome	DISNWY00	Strong	Biomarker	[26]
Tardive dyskinesia	DISKA5RC	Strong	Genetic Variation	[27]
Tourette syndrome	DISX9D54	Strong	Biomarker	[28]
Chronic renal failure	DISGG7K6	moderate	Biomarker	[29]
Coronary heart disease	DIS5OIP1	moderate	Genetic Variation	[30]
Fabry disease	DISUUQJF	moderate	Biomarker	[29]
Influenza	DIS3PNU3	moderate	Biomarker	[31]
Capillary malformation	DISR6ZSG	Limited	Biomarker	[32]
Depression	DIS3XJ69	Limited	Biomarker	[33]
Mental disorder	DIS3J5R8	Limited	Biomarker	[34]
Nervous system disease	DISJ7GGT	Limited	Biomarker	[35]
Obsessive compulsive disorder	DIS1ZMM2	Limited	Biomarker	[36]
Osteoporosis	DISF2JE0	Limited	Biomarker	[37]
Sleep disorder	DIS3JP1U	Limited	Biomarker	[38]
Substance withdrawal syndrome	DISTT24U	Limited	Biomarker	[39]
Type-1/2 diabetes	DISIUHAP	Limited	Biomarker	[40]

14 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 Guanine nucleotide exchange factor DBS (MCF2L).	[41]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Guanine nucleotide exchange factor DBS (MCF2L).	[42]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Guanine nucleotide exchange factor DBS (MCF2L).	[43]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Guanine nucleotide exchange factor DBS (MCF2L).	[45]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Guanine nucleotide exchange factor DBS (MCF2L).	[46]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Guanine nucleotide exchange factor DBS (MCF2L).	[47]
Selenium	DM25CGV	Approved	Selenium increases the expression of Guanine nucleotide exchange factor DBS (MCF2L).	[48]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Guanine nucleotide exchange factor DBS (MCF2L).	[49]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of Guanine nucleotide exchange factor DBS (MCF2L).	[51]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Guanine nucleotide exchange factor DBS (MCF2L).	[52]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Guanine nucleotide exchange factor DBS (MCF2L).	[53]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Guanine nucleotide exchange factor DBS (MCF2L).	[55]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Guanine nucleotide exchange factor DBS (MCF2L).	[56]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Guanine nucleotide exchange factor DBS (MCF2L).	[57]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Guanine nucleotide exchange factor DBS (MCF2L).	[44]
Fulvestrant	DM0YZC6	Approved	Fulvestrant affects the methylation of Guanine nucleotide exchange factor DBS (MCF2L).	[50]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Guanine nucleotide exchange factor DBS (MCF2L).	[50]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of Guanine nucleotide exchange factor DBS (MCF2L).	[54]

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