Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOZAR14)

• DOT Name: A-kinase anchor protein 13 (AKAP13)
• Synonyms: AKAP-13; AKAP-Lbc; Breast cancer nuclear receptor-binding auxiliary protein; Guanine nucleotide exchange factor Lbc; Human thyroid-anchoring protein 31; Lymphoid blast crisis oncogene; LBC oncogene; Non-oncogenic Rho GTPase-specific GTP exchange factor; Protein kinase A-anchoring protein 13; PRKA13; p47
• Gene Name: AKAP13
• Related Disease:
  Esophageal cancer
  Neoplasm of esophagus
  Acute monocytic leukemia
  Acute myelogenous leukaemia
  Adenocarcinoma
  Adult T-cell leukemia/lymphoma
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Chronic granulomatous disease
  Clear cell renal carcinoma
  Colitis
  Coronary heart disease
  Endometriosis
  Fuchs' endothelial dystrophy
  Haematological malignancy
  Hereditary breast carcinoma
  Human T-lymphotropic virus 1 infectious disease
  Immunodeficiency
  Leiomyoma
  leukaemia
  Leukemia
  Liver cirrhosis
  Myelodysplastic syndrome
  Obesity
  Obsessive compulsive disorder
  Ovarian cancer
  Papillary renal cell carcinoma
  Prostate carcinoma
  Prostate neoplasm
  Renal cell carcinoma
  T-cell lymphoma
  Tuberculosis
  Uterine fibroids
  Vibrio cholerae infection
  Asthma
  Malaria
  Non-insulin dependent diabetes
  Prostate cancer
  Thyroid gland papillary carcinoma
  Type-1/2 diabetes
• UniProt ID: AKP13_HUMAN
• PDB ID: 2DRN; 2LG1; 4D0N; 4D0O; 6BCA
• Pfam ID: PF17838 ; PF00621 ; PF10522
• Sequence:
  MKLNPQQAPLYGDCVVTVLLAEEDKAEDDVVFYLVFLGSTLRHCTSTRKVSSDTLETIAP
  GHDCCETVKVQLCASKEGLPVFVVAEEDFHFVQDEAYDAAQFLATSAGNQQALNFTRFLD
  QSGPPSGDVNSLDKKLVLAFRHLKLPTEWNVLGTDQSLHDAGPRETLMHFAVRLGLLRLT
  WFLLQKPGGRGALSIHNQEGATPVSLALERGYHKLHQLLTEENAGEPDSWSSLSYEIPYG
  DCSVRHHRELDIYTLTSESDSHHEHPFPGDGCTGPIFKLMNIQQQLMKTNLKQMDSLMPL
  MMTAQDPSSAPETDGQFLPCAPEPTDPQRLSSSEETESTQCCPGSPVAQTESPCDLSSIV
  EEENTDRSCRKKNKGVERKGEEVEPAPIVDSGTVSDQDSCLQSLPDCGVKGTEGLSSCGN
  RNEETGTKSSGMPTDQESLSSGDAVLQRDLVMEPGTAQYSSGGELGGISTTNVSTPDTAG
  EMEHGLMNPDATVWKNVLQGGESTKERFENSNIGTAGASDVHVTSKPVDKISVPNCAPAA
  SSLDGNKPAESSLAFSNEETSTEKTAETETSRSREESADAPVDQNSVVIPAAAKDKISDG
  LEPYTLLAAGIGEAMSPSDLALLGLEEDVMPHQNSETNSSHAQSQKGKSSPICSTTGDDK
  LCADSACQQNTVTSSGDLVAKLCDNIVSESESTTARQPSSQDPPDASHCEDPQAHTVTSD
  PVRDTQERADFCPFKVVDNKGQRKDVKLDKPLTNMLEVVSHPHPVVPKMEKELVPDQAVI
  SDSTFSLANSPGSESVTKDDALSFVPSQKEKGTATPELHTATDYRDGPDGNSNEPDTRPL
  EDRAVGLSTSSTAAELQHGMGNTSLTGLGGEHEGPAPPAIPEALNIKGNTDSSLQSVGKA
  TLALDSVLTEEGKLLVVSESSAAQEQDKDKAVTCSSIKENALSSGTLQEEQRTPPPGQDT
  QQFHEKSISADCAKDKALQLSNSPGASSAFLKAETEHNKEVAPQVSLLTQGGAAQSLVPP
  GASLATESRQEALGAEHNSSALLPCLLPDGSDGSDALNCSQPSPLDVGVKNTQSQGKTSA
  CEVSGDVTVDVTGVNALQGMAEPRRENISHNTQDILIPNVLLSQEKNAVLGLPVALQDKA
  VTDPQGVGTPEMIPLDWEKGKLEGADHSCTMGDAEEAQIDDEAHPVLLQPVAKELPTDME
  LSAHDDGAPAGVREVMRAPPSGRERSTPSLPCMVSAQDAPLPKGADLIEEAASRIVDAVI
  EQVKAAGALLTEGEACHMSLSSPELGPLTKGLESAFTEKVSTFPPGESLPMGSTPEEATG
  SLAGCFAGREEPEKIILPVQGPEPAAEMPDVKAEDEVDFRASSISEEVAVGSIAATLKMK
  QGPMTQAINRENWCTIEPCPDAASLLASKQSPECENFLDVGLGRECTSKQGVLKRESGSD
  SDLFHSPSDDMDSIIFPKPEEEHLACDITGSSSSTDDTASLDRHSSHGSDVSLSQILKPN
  RSRDRQSLDGFYSHGMGAEGRESESEPADPGDVEEEEMDSITEVPANCSVLRSSMRSLSP
  FRRHSWGPGKNAASDAEMNHRSSMRVLGDVVRRPPIHRRSFSLEGLTGGAGVGNKPSSSL
  EVSSANAEELRHPFSGEERVDSLVSLSEEDLESDQREHRMFDQQICHRSKQQGFNYCTSA
  ISSPLTKSISLMTISHPGLDNSRPFHSTFHNTSANLTESITEENYNFLPHSPSKKDSEWK
  SGTKVSRTFSYIKNKMSSSKKSKEKEKEKDKIKEKEKDSKDKEKDKKTVNGHTFSSIPVV
  GPISCSQCMKPFTNKDAYTCANCSAFVHKGCRESLASCAKVKMKQPKGSLQAHDTSSLPT
  VIMRNKPSQPKERPRSAVLLVDETATTPIFANRRSQQSVSLSKSVSIQNITGVGNDENMS
  NTWKFLSHSTDSLNKISKVNESTESLTDEGVGTDMNEGQLLGDFEIESKQLEAESWSRII
  DSKFLKQQKKDVVKRQEVIYELMQTEFHHVRTLKIMSGVYSQGMMADLLFEQQMVEKLFP
  CLDELISIHSQFFQRILERKKESLVDKSEKNFLIKRIGDVLVNQFSGENAERLKKTYGKF
  CGQHNQSVNYFKDLYAKDKRFQAFVKKKMSSSVVRRLGIPECILLVTQRITKYPVLFQRI
  LQCTKDNEVEQEDLAQSLSLVKDVIGAVDSKVASYEKKVRLNEIYTKTDSKSIMRMKSGQ
  MFAKEDLKRKKLVRDGSVFLKNAAGRLKEVQAVLLTDILVFLQEKDQKYIFASLDQKSTV
  ISLKKLIVREVAHEEKGLFLISMGMTDPEMVEVHASSKEERNSWIQIIQDTINTLNRDED
  EGIPSENEEEKKMLDTRARELKEQLHQKDQKILLLLEEKEMIFRDMAECSTPLPEDCSPT
  HSPRVLFRSNTEEALKGGPLMKSAINEVEILQGLVSGNLGGTLGPTVSSPIEQDVVGPVS
  LPRRAETFGGFDSHQMNASKGGEKEEGDDGQDLRRTESDSGLKKGGNANLVFMLKRNSEQ
  VVQSVVHLYELLSALQGVVLQQDSYIEDQKLVLSERALTRSLSRPSSLIEQEKQRSLEKQ
  RQDLANLQKQQAQYLEEKRRREREWEARERELREREALLAQREEEVQQGQQDLEKEREEL
  QQKKGTYQYDLERLRAAQKQLEREQEQLRREAERLSQRQTERDLCQVSHPHTKLMRIPSF
  FPSPEEPPSPSAPSIAKSGSLDSELSVSPKRNSISRTHKDKGPFHILSSTSQTNKGPEGQ
  SQAPASTSASTRLFGLTKPKEKKEKKKKNKTSRSQPGDGPASEVSAEGEEIFC
• Function: Scaffold protein that plays an important role in assembling signaling complexes downstream of several types of G protein-coupled receptors. Activates RHOA in response to signaling via G protein-coupled receptors via its function as Rho guanine nucleotide exchange factor. May also activate other Rho family members. Part of a kinase signaling complex that links ADRA1A and ADRA1B adrenergic receptor signaling to the activation of downstream p38 MAP kinases, such as MAPK11 and MAPK14. Part of a signaling complex that links ADRA1B signaling to the activation of RHOA and IKBKB/IKKB, leading to increased NF-kappa-B transcriptional activity. Part of a RHOA-dependent signaling cascade that mediates responses to lysophosphatidic acid (LPA), a signaling molecule that activates G-protein coupled receptors and potentiates transcriptional activation of the glucocorticoid receptor NR3C1. Part of a signaling cascade that stimulates MEF2C-dependent gene expression in response to lysophosphatidic acid (LPA). Part of a signaling pathway that activates MAPK11 and/or MAPK14 and leads to increased transcription activation of the estrogen receptors ESR1 and ESR2. Part of a signaling cascade that links cAMP and EGFR signaling to BRAF signaling and to PKA-mediated phosphorylation of KSR1, leading to the activation of downstream MAP kinases, such as MAPK1 or MAPK3. Functions as a scaffold protein that anchors cAMP-dependent protein kinase (PKA) and PRKD1. This promotes activation of PRKD1, leading to increased phosphorylation of HDAC5 and ultimately cardiomyocyte hypertrophy. Has no guanine nucleotide exchange activity on CDC42, Ras or Rac. Required for normal embryonic heart development, and in particular for normal sarcomere formation in the developing cardiomyocytes. Plays a role in cardiomyocyte growth and cardiac hypertrophy in response to activation of the beta-adrenergic receptor by phenylephrine or isoproterenol. Required for normal adaptive cardiac hypertrophy in response to pressure overload. Plays a role in osteogenesis.
• Tissue Specificity: Detected in mammary gland . Detected in heart (at protein level) . Expressed as a 5.3 kb transcript in hematopoietic cells, skeletal muscle, lung, heart, estrogen-responsive reproductive tissues, including breast ductal epithelium. Also found in testis and breast cancer cell lines. Predominantly expressed as a 10 kb transcript in the heart and at lower levels in the lung, placenta, kidney, pancreas, skeletal muscle and liver. Transcripts of between 6-9 kb are also expressed in myeloid and lymphoid lineages, a variety of epithelial tissues, and in skeletal muscle.
• KEGG Pathway:
  Parathyroid hormone synthesis, secretion and action (hsa04928)
  Human cytomegalovirus infection (hsa05163)
• 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)
  NRAGE signals death through JNK (R-HSA-193648)

Molecular Interaction Atlas (MIA) of This DOT

42 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Esophageal cancer	DISGB2VN	Definitive	Biomarker	[1]
Neoplasm of esophagus	DISOLKAQ	Definitive	Biomarker	[1]
Acute monocytic leukemia	DIS28NEL	Strong	Biomarker	[2]
Acute myelogenous leukaemia	DISCSPTN	Strong	Genetic Variation	[2]
Adenocarcinoma	DIS3IHTY	Strong	Altered Expression	[3]
Adult T-cell leukemia/lymphoma	DIS882XU	Strong	Altered Expression	[4]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[5]
Breast cancer	DIS7DPX1	Strong	Biomarker	[6]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[6]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[7]
Chronic granulomatous disease	DIS9ZR24	Strong	Genetic Variation	[8]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[9]
Colitis	DISAF7DD	Strong	Biomarker	[10]
Coronary heart disease	DIS5OIP1	Strong	Genetic Variation	[11]
Endometriosis	DISX1AG8	Strong	Altered Expression	[12]
Fuchs' endothelial dystrophy	DISL7TXC	Strong	Biomarker	[13]
Haematological malignancy	DISCDP7W	Strong	Biomarker	[14]
Hereditary breast carcinoma	DISAEZT5	Strong	Genetic Variation	[15]
Human T-lymphotropic virus 1 infectious disease	DISN5C4M	Strong	Biomarker	[4]
Immunodeficiency	DIS093I0	Strong	Biomarker	[16]
Leiomyoma	DISLDDFN	Strong	Biomarker	[17]
leukaemia	DISS7D1V	Strong	Biomarker	[14]
Leukemia	DISNAKFL	Strong	Biomarker	[14]
Liver cirrhosis	DIS4G1GX	Strong	Biomarker	[5]
Myelodysplastic syndrome	DISYHNUI	Strong	Biomarker	[14]
Obesity	DIS47Y1K	Strong	Altered Expression	[18]
Obsessive compulsive disorder	DIS1ZMM2	Strong	Altered Expression	[18]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[19]
Papillary renal cell carcinoma	DIS25HBV	Strong	Biomarker	[9]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[20]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[21]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[9]
T-cell lymphoma	DISSXRTQ	Strong	Genetic Variation	[22]
Tuberculosis	DIS2YIMD	Strong	Biomarker	[23]
Uterine fibroids	DISBZRMJ	Strong	Biomarker	[17]
Vibrio cholerae infection	DISW7E3U	Strong	Biomarker	[24]
Asthma	DISW9QNS	Limited	Altered Expression	[25]
Malaria	DISQ9Y50	Limited	Biomarker	[26]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Biomarker	[27]
Prostate cancer	DISF190Y	Limited	Biomarker	[21]
Thyroid gland papillary carcinoma	DIS48YMM	Limited	Biomarker	[28]
Type-1/2 diabetes	DISIUHAP	Limited	Altered Expression	[29]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Camptothecin	DM6CHNJ	Phase 3	A-kinase anchor protein 13 (AKAP13) decreases the response to substance of Camptothecin.	[54]

6 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 A-kinase anchor protein 13 (AKAP13).	[30]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of A-kinase anchor protein 13 (AKAP13).	[45]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of A-kinase anchor protein 13 (AKAP13).	[48]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of A-kinase anchor protein 13 (AKAP13).	[49]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of A-kinase anchor protein 13 (AKAP13).	[48]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid decreases the phosphorylation of A-kinase anchor protein 13 (AKAP13).	[52]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of A-kinase anchor protein 13 (AKAP13).	[31]
Acetaminophen	DMUIE76	Approved	Acetaminophen affects the expression of A-kinase anchor protein 13 (AKAP13).	[32]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of A-kinase anchor protein 13 (AKAP13).	[33]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of A-kinase anchor protein 13 (AKAP13).	[34]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of A-kinase anchor protein 13 (AKAP13).	[35]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of A-kinase anchor protein 13 (AKAP13).	[36]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of A-kinase anchor protein 13 (AKAP13).	[37]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of A-kinase anchor protein 13 (AKAP13).	[38]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of A-kinase anchor protein 13 (AKAP13).	[39]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of A-kinase anchor protein 13 (AKAP13).	[40]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate increases the expression of A-kinase anchor protein 13 (AKAP13).	[41]
Seocalcitol	DMKL9QO	Phase 3	Seocalcitol increases the expression of A-kinase anchor protein 13 (AKAP13).	[42]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of A-kinase anchor protein 13 (AKAP13).	[43]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of A-kinase anchor protein 13 (AKAP13).	[46]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of A-kinase anchor protein 13 (AKAP13).	[47]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of A-kinase anchor protein 13 (AKAP13).	[50]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of A-kinase anchor protein 13 (AKAP13).	[36]
GALLICACID	DM6Y3A0	Investigative	GALLICACID increases the expression of A-kinase anchor protein 13 (AKAP13).	[51]
ORG2058	DMH1M6N	Investigative	ORG2058 increases the expression of A-kinase anchor protein 13 (AKAP13).	[53]

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 A-kinase anchor protein 13 (AKAP13).	[44]

References

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