Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFSTN6A)

• DOT Name: Dedicator of cytokinesis protein 11 (DOCK11)
• Synonyms: Activated Cdc42-associated guanine nucleotide exchange factor; ACG; Zizimin-2
• Gene Name: DOCK11
• Related Disease:
  Achondrogenesis
  Acute myelogenous leukaemia
  Alcoholic liver diseases
  Allergic rhinitis
  Alpha thalassemia
  Atelosteogenesis type II
  Autism
  Autosomal dominant familial periodic fever
  Breast cancer
  Breast carcinoma
  Crohn disease
  Endometriosis
  Fibromyalgia
  Fragile X-associated tremor/ataxia syndrome
  Hepatitis B virus infection
  Hereditary hemochromatosis
  Hypospadias
  Inflammatory bowel disease
  Lupus
  Medullary thyroid gland carcinoma
  Multiple endocrine neoplasia type 2B
  Orthostatic hypotension
  Signet ring cell carcinoma
  Systemic lupus erythematosus
  Ulcerative colitis
  Acute graft versus host disease
  Carcinoma of esophagus
  Graves disease
  Hashimoto thyroiditis
  Small lymphocytic lymphoma
  Autoinflammatory disease, multisystem, with immune dysregulation, X-linked
  Coronary heart disease
  Familial medullary thyroid carcinoma
  Li-Fraumeni syndrome
  Type-1 diabetes
• UniProt ID: DOC11_HUMAN
• Pfam ID: PF06920 ; PF20422 ; PF20421 ; PF14429 ; PF11878 ; PF00169
• Sequence:
  MAEVRKFTKRLSKPGTAAELRQSVSEAVRGSVVLEKAKVVEPLDYENVIAQRKTQIYSDP
  LRDLLMFPMEDISISVIGRQRRTVQSTVPEDAEKRAQSLFVKECIKTYSTDWHVVNYKYE
  DFSGDFRMLPCKSLRPEKIPNHVFEIDEDCEKDEDSSSLCSQKGGVIKQGWLHKANVNST
  ITVTMKVFKRRYFYLTQLPDGSYILNSYKDEKNSKESKGCIYLDACIDVVQCPKMRRHAF
  ELKMLDKYSHYLAAETEQEMEEWLITLKKIIQINTDSLVQEKKETVETAQDDETSSQGKA
  ENIMASLERSMHPELMKYGRETEQLNKLSRGDGRQNLFSFDSEVQRLDFSGIEPDIKPFE
  EKCNKRFLVNCHDLTFNILGQIGDNAKGPPTNVEPFFINLALFDVKNNCKISADFHVDLN
  PPSVREMLWGSSTQLASDGSPKGSSPESYIHGIAESQLRYIQQGIFSVTNPHPEIFLVAR
  IEKVLQGNITHCAEPYIKNSDPVKTAQKVHRTAKQVCSRLGQYRMPFAWAARPIFKDTQG
  SLDLDGRFSPLYKQDSSKLSSEDILKLLSEYKKPEKTKLQIIPGQLNITVECVPVDLSNC
  ITSSYVPLKPFEKNCQNITVEVEEFVPEMTKYCYPFTIYKNHLYVYPLQLKYDSQKTFAK
  ARNIAVCVEFRDSDESDASALKCIYGKPAGSVFTTNAYAVVSHHNQNPEFYDEIKIELPI
  HLHQKHHLLFTFYHVSCEINTKGTTKKQDTVETPVGFAWVPLLKDGRIITFEQQLPVSAN
  LPPGYLNLNDAESRRQCNVDIKWVDGAKPLLKIKSHLESTIYTQDLHVHKFFHHCQLIQS
  GSKEVPGELIKYLKCLHAMEIQVMIQFLPVILMQLFRVLTNMTHEDDVPINCTMVLLHIV
  SKCHEEGLDSYLRSFIKYSFRPEKPSAPQAQLIHETLATTMIAILKQSADFLSINKLLKY
  SWFFFEIIAKSMATYLLEENKIKLPRGQRFPETYHHVLHSLLLAIIPHVTIRYAEIPDES
  RNVNYSLASFLKRCLTLMDRGFIFNLINDYISGFSPKDPKVLAEYKFEFLQTICNHEHYI
  PLNLPMAFAKPKLQRVQDSNLEYSLSDEYCKHHFLVGLLLRETSIALQDNYEIRYTAISV
  IKNLLIKHAFDTRYQHKNQQAKIAQLYLPFVGLLLENIQRLAGRDTLYSCAAMPNSASRD
  EFPCGFTSPANRGSLSTDKDTAYGSFQNGHGIKREDSRGSLIPEGATGFPDQGNTGENTR
  QSSTRSSVSQYNRLDQYEIRSLLMCYLYIVKMISEDTLLTYWNKVSPQELINILILLEVC
  LFHFRYMGKRNIARVHDAWLSKHFGIDRKSQTMPALRNRSGVMQARLQHLSSLESSFTLN
  HSSTTTEADIFHQALLEGNTATEVSLTVLDTISFFTQCFKTQLLNNDGHNPLMKKVFDIH
  LAFLKNGQSEVSLKHVFASLRAFISKFPSAFFKGRVNMCAAFCYEVLKCCTSKISSTRNE
  ASALLYLLMRNNFEYTKRKTFLRTHLQIIIAVSQLIADVALSGGSRFQESLFIINNFANS
  DRPMKATAFPAEVKDLTKRIRTVLMATAQMKEHEKDPEMLIDLQYSLAKSYASTPELRKT
  WLDSMAKIHVKNGDFSEAAMCYVHVAALVAEFLHRKKLFPNGCSAFKKITPNIDEEGAMK
  EDAGMMDVHYSEEVLLELLEQCVDGLWKAERYEIISEISKLIVPIYEKRREFEKLTQVYR
  TLHGAYTKILEVMHTKKRLLGTFFRVAFYGQSFFEEEDGKEYIYKEPKLTGLSEISLRLV
  KLYGEKFGTENVKIIQDSDKVNAKELDPKYAHIQVTYVKPYFDDKELTERKTEFERNHNI
  SRFVFEAPYTLSGKKQGCIEEQCKRRTILTTSNSFPYVKKRIPINCEQQINLKPIDVATD
  EIKDKTAELQKLCSSTDVDMIQLQLKLQGCVSVQVNAGPLAYARAFLNDSQASKYPPKKV
  SELKDMFRKFIQACSIALELNERLIKEDQVEYHEGLKSNFRDMVKELSDIIHEQILQEDT
  MHSPWMSNTLHVFCAISGTSSDRGYGSPRYAEV
• Function: Guanine nucleotide-exchange factor (GEF) that activates CDC42 by exchanging bound GDP for free GTP. Required for marginal zone (MZ) B-cell development, is associated with early bone marrow B-cell development, MZ B-cell formation, MZ B-cell number and marginal metallophilic macrophages morphology. Facilitates filopodia formation through the activation of CDC42.
• Reactome Pathway:
  RAC1 GTPase cycle (R-HSA-9013149)
  Factors involved in megakaryocyte development and platelet production (R-HSA-983231)
  CDC42 GTPase cycle (R-HSA-9013148)

Molecular Interaction Atlas (MIA) of This DOT

35 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Achondrogenesis	DISCBQB8	Strong	Genetic Variation	[1]
Acute myelogenous leukaemia	DISCSPTN	Strong	Altered Expression	[2]
Alcoholic liver diseases	DISXEPHQ	Strong	Biomarker	[3]
Allergic rhinitis	DIS3U9HN	Strong	Genetic Variation	[4]
Alpha thalassemia	DIS5XGK0	Strong	Genetic Variation	[5]
Atelosteogenesis type II	DIS903NR	Strong	Genetic Variation	[1]
Autism	DISV4V1Z	Strong	Altered Expression	[6]
Autosomal dominant familial periodic fever	DISCRNV1	Strong	Genetic Variation	[7]
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[8]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[8]
Crohn disease	DIS2C5Q8	Strong	Biomarker	[9]
Endometriosis	DISX1AG8	Strong	Genetic Variation	[10]
Fibromyalgia	DISZJDS2	Strong	Genetic Variation	[11]
Fragile X-associated tremor/ataxia syndrome	DISKB25R	Strong	Biomarker	[12]
Hepatitis B virus infection	DISLQ2XY	Strong	Genetic Variation	[13]
Hereditary hemochromatosis	DISVG5MT	Strong	Biomarker	[14]
Hypospadias	DIS48CCP	Strong	Genetic Variation	[15]
Inflammatory bowel disease	DISGN23E	Strong	Biomarker	[16]
Lupus	DISOKJWA	Strong	Genetic Variation	[17]
Medullary thyroid gland carcinoma	DISHBL3K	Strong	Genetic Variation	[18]
Multiple endocrine neoplasia type 2B	DIS6FT6I	Strong	Genetic Variation	[19]
Orthostatic hypotension	DISBKQGT	Strong	Genetic Variation	[20]
Signet ring cell carcinoma	DISVCUCR	Strong	Genetic Variation	[21]
Systemic lupus erythematosus	DISI1SZ7	Strong	Genetic Variation	[17]
Ulcerative colitis	DIS8K27O	Strong	Biomarker	[22]
Acute graft versus host disease	DIS8KLVM	moderate	Genetic Variation	[23]
Carcinoma of esophagus	DISS6G4D	moderate	Genetic Variation	[24]
Graves disease	DISU4KOQ	moderate	Genetic Variation	[25]
Hashimoto thyroiditis	DIS77CDF	moderate	Genetic Variation	[25]
Small lymphocytic lymphoma	DIS30POX	moderate	Biomarker	[26]
Autoinflammatory disease, multisystem, with immune dysregulation, X-linked	DIS0GVFL	Limited	X-linked	[27]
Coronary heart disease	DIS5OIP1	Limited	Genetic Variation	[28]
Familial medullary thyroid carcinoma	DIS01PWX	Limited	Genetic Variation	[18]
Li-Fraumeni syndrome	DISR64XA	Limited	Biomarker	[29]
Type-1 diabetes	DIS7HLUB	Limited	Genetic Variation	[30]

4 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 Dedicator of cytokinesis protein 11 (DOCK11).	[31]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Dedicator of cytokinesis protein 11 (DOCK11).	[39]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Dedicator of cytokinesis protein 11 (DOCK11).	[41]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Dedicator of cytokinesis protein 11 (DOCK11).	[39]

11 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 Dedicator of cytokinesis protein 11 (DOCK11).	[32]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Dedicator of cytokinesis protein 11 (DOCK11).	[33]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Dedicator of cytokinesis protein 11 (DOCK11).	[34]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Dedicator of cytokinesis protein 11 (DOCK11).	[35]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Dedicator of cytokinesis protein 11 (DOCK11).	[36]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Dedicator of cytokinesis protein 11 (DOCK11).	[37]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Dedicator of cytokinesis protein 11 (DOCK11).	[38]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Dedicator of cytokinesis protein 11 (DOCK11).	[40]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Dedicator of cytokinesis protein 11 (DOCK11).	[42]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Dedicator of cytokinesis protein 11 (DOCK11).	[43]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Dedicator of cytokinesis protein 11 (DOCK11).	[44]

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