Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTL4Z99V)

• DOT Name: A-kinase anchor protein 4 (AKAP4)
• Synonyms: AKAP-4; A-kinase anchor protein 82 kDa; AKAP 82; hAKAP82; Major sperm fibrous sheath protein; HI; Protein kinase A-anchoring protein 4; PRKA4
• Gene Name: AKAP4
• Related Disease:
  Cervical cancer
  Cervical carcinoma
  Squamous cell carcinoma
  Advanced cancer
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Male infertility
  Non-small-cell lung cancer
  Pituitary tumor
  Testicular cancer
  Breast cancer
  Breast carcinoma
  Breast lobular carcinoma
  Gastric cancer
  Neoplasm
  Stomach cancer
  Thyroid cancer
  Thyroid gland carcinoma
  Thyroid tumor
• UniProt ID: AKAP4_HUMAN
• Pfam ID: PF05716 ; PF10522
• Sequence:
  MMAYSDTTMMSDDIDWLRSHRGVCKVDLYNPEGQQDQDRKVICFVDVSTLNVEDKDYKDA
  ASSSSEGNLNLGSLEEKEIIVIKDTEKKDQSKTEGSVCLFKQAPSDPVSVLNWLLSDLQK
  YALGFQHALSPSTSTCKHKVGDTEGEYHRASSENCYSVYADQVNIDYLMNRPQNLRLEMT
  AAKNTNNNQSPSAPPAKPPSTQRAVISPDGECSIDDLSFYVNRLSSLVIQMAHKEIKEKL
  EGKSKCLHHSICPSPGNKERISPRTPASKIASEMAYEAVELTAAEMRGTGEESREGGQKS
  FLYSELSNKSKSGDKQMSQRESKEFADSISKGLMVYANQVASDMMVSLMKTLKVHSSGKP
  IPASVVLKRVLLRHTKEIVSDLIDSCMKNLHNITGVLMTDSDFVSAVKRNLFNQWKQNAT
  DIMEAMLKRLVSALIGEEKETKSQSLSYASLKAGSHDPKCRNQSLEFSTMKAEMKERDKG
  KMKSDPCKSLTSAEKVGEHILKEGLTIWNQKQGNSCKVATKACSNKDEKGEKINASTDSL
  AKDLIVSALKLIQYHLTQQTKGKDTCEEDCPGSTMGYMAQSTQYEKCGGGQSAKALSVKQ
  LESHRAPGPSTCQKENQHLDSQKMDMSNIVLMLIQKLLNENPFKCEDPCEGENKCSEPRA
  SKAASMSNRSDKAEEQCQEHQELDCTSGMKQANGQFIDKLVESVMKLCLIMAKYSNDGAA
  LAELEEQAASANKPNFRGTRCIHSGAMPQNYQDSLGHEVIVNNQCSTNSLQKQLQAVLQW
  IAASQFNVPMLYFMGDKDGQLEKLPQVSAKAAEKGYSVGGLLQEVMKFAKERQPDEAVGK
  VARKQLLDWLLANL
• Function: Major structural component of sperm fibrous sheath. Plays a role in sperm motility.
• Tissue Specificity: Testis specific; only expressed in round spermatids.

Molecular Interaction Atlas (MIA) of This DOT

20 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cervical cancer	DISFSHPF	Definitive	Altered Expression	[1]
Cervical carcinoma	DIST4S00	Definitive	Altered Expression	[1]
Squamous cell carcinoma	DISQVIFL	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Colon cancer	DISVC52G	Strong	Altered Expression	[3]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[3]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[3]
Male infertility	DISY3YZZ	Strong	Biomarker	[4]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[5]
Pituitary tumor	DISN67JD	Strong	Biomarker	[5]
Testicular cancer	DIS6HNYO	Strong	Biomarker	[6]
Breast cancer	DIS7DPX1	Limited	Altered Expression	[7]
Breast carcinoma	DIS2UE88	Limited	Altered Expression	[7]
Breast lobular carcinoma	DISBY98Q	Limited	Genetic Variation	[7]
Gastric cancer	DISXGOUK	Limited	Biomarker	[8]
Neoplasm	DISZKGEW	Limited	Biomarker	[9]
Stomach cancer	DISKIJSX	Limited	Biomarker	[8]
Thyroid cancer	DIS3VLDH	Limited	Biomarker	[9]
Thyroid gland carcinoma	DISMNGZ0	Limited	Biomarker	[9]
Thyroid tumor	DISLVKMD	Limited	Biomarker	[9]

2 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 4 (AKAP4).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of A-kinase anchor protein 4 (AKAP4).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of A-kinase anchor protein 4 (AKAP4).	[12]

References

• [1] Gene silencing of A-kinase anchor protein 4 inhibits cervical cancer growth in vitro and in vivo.Cancer Gene Ther. 2013 Jul;20(7):413-20. doi: 10.1038/cgt.2013.32. Epub 2013 Jun 14.
• [2] Genome-wide analysis of cancer/testis gene expression.Proc Natl Acad Sci U S A. 2008 Dec 23;105(51):20422-7. doi: 10.1073/pnas.0810777105. Epub 2008 Dec 16.
• [3] A-kinase anchor protein 4 (AKAP4) a promising therapeutic target of colorectal cancer.J Exp Clin Cancer Res. 2015 Nov 21;34:142. doi: 10.1186/s13046-015-0258-y.
• [4] A-kinase anchor protein 4 precursor (pro-AKAP4) in human spermatozoa.Andrology. 2018 Nov;6(6):854-859. doi: 10.1111/andr.12524. Epub 2018 Jul 8.
• [5] Novel antigens in non-small cell lung cancer: SP17, AKAP4, and PTTG1 are potential immunotherapeutic targets.Oncotarget. 2015 Feb 20;6(5):2812-26. doi: 10.18632/oncotarget.2802.
• [6] Role of A-Kinase anchor protein (AKAP4) in growth and survival of ovarian cancer cells.Oncotarget. 2017 May 24;8(32):53124-53136. doi: 10.18632/oncotarget.18163. eCollection 2017 Aug 8.
• [7] A novel cancer testis antigen, A-kinase anchor protein 4 (AKAP4) is a potential biomarker for breast cancer.PLoS One. 2013;8(2):e57095. doi: 10.1371/journal.pone.0057095. Epub 2013 Feb 22.
• [8] Knockdown of A-kinase anchor protein 4 inhibits hypoxia-induced epithelial-to-mesenchymal transition via suppression of the Wnt/-catenin pathway in human gastric cancer cells.J Cell Biochem. 2018 Dec;119(12):10013-10020. doi: 10.1002/jcb.27331. Epub 2018 Aug 26.
• [9] Silencing of A-Kinase Anchor Protein 4 (AKAP4) Inhibits Proliferation and Progression of Thyroid Cancer.Oncol Res. 2017 Jul 5;25(6):873-878. doi: 10.3727/096504016X14783701102564. Epub 2016 Nov 8.
• [10] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [11] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [12] Cellular reactions to long-term volatile organic compound (VOC) exposures. Sci Rep. 2016 Dec 1;6:37842. doi: 10.1038/srep37842.