Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT45AHMB)

• DOT Name: C-Jun-amino-terminal kinase-interacting protein 4 (SPAG9)
• Synonyms: JIP-4; JNK-interacting protein 4; Cancer/testis antigen 89; CT89; Human lung cancer oncogene 6 protein; HLC-6; JNK-associated leucine-zipper protein; JLP; Mitogen-activated protein kinase 8-interacting protein 4; Proliferation-inducing protein 6; Protein highly expressed in testis; PHET; Sperm surface protein; Sperm-associated antigen 9; Sperm-specific protein; Sunday driver 1
• Gene Name: SPAG9
• Related Disease:
  Astrocytoma
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Acute lymphocytic leukaemia
  Adult glioblastoma
  Advanced cancer
  Alzheimer disease
  Bladder cancer
  Bladder transitional cell carcinoma
  Burkitt lymphoma
  Carcinoma of liver and intrahepatic biliary tract
  Cervical cancer
  Cervical carcinoma
  Childhood acute lymphoblastic leukemia
  Clear cell renal carcinoma
  Epithelial ovarian cancer
  Glioblastoma multiforme
  Hepatitis
  Hepatitis A virus infection
  Hepatocellular carcinoma
  leukaemia
  Leukemia
  Liver cancer
  Lung cancer
  Lung carcinoma
  Major depressive disorder
  Neoplasm
  Non-small-cell lung cancer
  Ovarian cancer
  Ovarian neoplasm
  Renal cell carcinoma
  Squamous cell carcinoma
  Systemic sclerosis
  Testicular cancer
  Thyroid cancer
  Thyroid gland carcinoma
  Thyroid gland undifferentiated (anaplastic) carcinoma
  Thyroid tumor
  Urinary bladder cancer
  Urinary bladder neoplasm
  Breast cancer
  Breast carcinoma
  Prostate cancer
  Prostate carcinoma
  Triple negative breast cancer
  Ankylosing spondylitis
  Breast neoplasm
  Cardiomyopathy
  Schizophrenia
• UniProt ID: JIP4_HUMAN
• PDB ID: 2W83
• Pfam ID: PF16471 ; PF09744 ; PF19056
• Sequence:
  MELEDGVVYQEEPGGSGAVMSERVSGLAGSIYREFERLIGRYDEEVVKELMPLVVAVLEN
  LDSVFAQDQEHQVELELLRDDNEQLITQYEREKALRKHAEEKFIEFEDSQEQEKKDLQTR
  VESLESQTRQLELKAKNYADQISRLEEREAELKKEYNALHQRHTEMIHNYMEHLERTKLH
  QLSGSDQLESTAHSRIRKERPISLGIFPLPAGDGLLTPDAQKGGETPGSEQWKFQELSQP
  RSHTSLKVSNSPEPQKAVEQEDELSDVSQGGSKATTPASTANSDVATIPTDTPLKEENEG
  FVKVTDAPNKSEISKHIEVQVAQETRNVSTGSAENEEKSEVQAIIESTPELDMDKDLSGY
  KGSSTPTKGIENKAFDRNTESLFEELSSAGSGLIGDVDEGADLLGMGREVENLILENTQL
  LETKNALNIVKNDLIAKVDELTCEKDVLQGELEAVKQAKLKLEEKNRELEEELRKARAEA
  EDARQKAKDDDDSDIPTAQRKRFTRVEMARVLMERNQYKERLMELQEAVRWTEMIRASRE
  NPAMQEKKRSSIWQFFSRLFSSSSNTTKKPEPPVNLKYNAPTSHVTPSVKKRSSTLSQLP
  GDKSKAFDFLSEETEASLASRREQKREQYRQVKAHVQKEDGRVQAFGWSLPQKYKQVTNG
  QGENKMKNLPVPVYLRPLDEKDTSMKLWCAVGVNLSGGKTRDGGSVVGASVFYKDVAGLD
  TEGSKQRSASQSSLDKLDQELKEQQKELKNQEELSSLVWICTSTHSATKVLIIDAVQPGN
  ILDSFTVCNSHVLCIASVPGARETDYPAGEDLSESGQVDKASLCGSMTSNSSAETDSLLG
  GITVVGCSAEGVTGAATSPSTNGASPVMDKPPEMEAENSEVDENVPTAEEATEATEGNAG
  SAEDTVDISQTGVYTEHVFTDPLGVQIPEDLSPVYQSSNDSDAYKDQISVLPNEQDLVRE
  EAQKMSSLLPTMWLGAQNGCLYVHSSVAQWRKCLHSIKLKDSILSIVHVKGIVLVALADG
  TLAIFHRGVDGQWDLSNYHLLDLGRPHHSIRCMTVVHDKVWCGYRNKIYVVQPKAMKIEK
  SFDAHPRKESQVRQLAWVGDGVWVSIRLDSTLRLYHAHTYQHLQDVDIEPYVSKMLGTGK
  LGFSFVRITALMVSCNRLWVGTGNGVIISIPLTETNKTSGVPGNRPGSVIRVYGDENSDK
  VTPGTFIPYCSMAHAQLCFHGHRDAVKFFVAVPGQVISPQSSSSGTDLTGDKAGPSAQEP
  GSQTPLKSMLVISGGEGYIDFRMGDEGGESELLGEDLPLEPSVTKAERSHLIVWQVMYGN
  E
• Function: The JNK-interacting protein (JIP) group of scaffold proteins selectively mediates JNK signaling by aggregating specific components of the MAPK cascade to form a functional JNK signaling module. Regulates lysosomal positioning by acting as an adapter protein which links PIP4P1-positive lysosomes to the dynein-dynactin complex. Assists PIKFYVE selective functionality in microtubule-based endosome-to-TGN trafficking.
• Tissue Specificity: Expressed only in testis on the round spermatids of stage I, II and II. Absent in spermatogonia and spermatocyte.; [Isoform 4]: Expressed in testis and in acute myeloid leukemia (AML) patients.; [Isoform 3]: Expressed in testis.
• Reactome Pathway: Myogenesis (R-HSA-525793)

Molecular Interaction Atlas (MIA) of This DOT

50 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Astrocytoma	DISL3V18	Definitive	Biomarker	[1]
Colon cancer	DISVC52G	Definitive	Biomarker	[2]
Colon carcinoma	DISJYKUO	Definitive	Biomarker	[2]
Colorectal carcinoma	DIS5PYL0	Definitive	Biomarker	[2]
Acute lymphocytic leukaemia	DISPX75S	Strong	Genetic Variation	[3]
Adult glioblastoma	DISVP4LU	Strong	Altered Expression	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[4]
Alzheimer disease	DISF8S70	Strong	Biomarker	[5]
Bladder cancer	DISUHNM0	Strong	Altered Expression	[6]
Bladder transitional cell carcinoma	DISNL46A	Strong	Altered Expression	[7]
Burkitt lymphoma	DIS9D5XU	Strong	Biomarker	[8]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Strong	Altered Expression	[9]
Cervical cancer	DISFSHPF	Strong	Biomarker	[10]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[10]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Strong	Genetic Variation	[3]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[11]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[12]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[1]
Hepatitis	DISXXX35	Strong	Altered Expression	[13]
Hepatitis A virus infection	DISUMFQV	Strong	Altered Expression	[13]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[14]
leukaemia	DISS7D1V	Strong	Genetic Variation	[3]
Leukemia	DISNAKFL	Strong	Genetic Variation	[3]
Liver cancer	DISDE4BI	Strong	Altered Expression	[9]
Lung cancer	DISCM4YA	Strong	Altered Expression	[13]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[13]
Major depressive disorder	DIS4CL3X	Strong	Biomarker	[15]
Neoplasm	DISZKGEW	Strong	Biomarker	[16]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[17]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[12]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[12]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[11]
Squamous cell carcinoma	DISQVIFL	Strong	Altered Expression	[10]
Systemic sclerosis	DISF44L6	Strong	Altered Expression	[18]
Testicular cancer	DIS6HNYO	Strong	Biomarker	[16]
Thyroid cancer	DIS3VLDH	Strong	Altered Expression	[19]
Thyroid gland carcinoma	DISMNGZ0	Strong	Altered Expression	[19]
Thyroid gland undifferentiated (anaplastic) carcinoma	DISYBB1W	Strong	Altered Expression	[20]
Thyroid tumor	DISLVKMD	Strong	Altered Expression	[19]
Urinary bladder cancer	DISDV4T7	Strong	Altered Expression	[6]
Urinary bladder neoplasm	DIS7HACE	Strong	Altered Expression	[6]
Breast cancer	DIS7DPX1	moderate	Altered Expression	[21]
Breast carcinoma	DIS2UE88	moderate	Altered Expression	[21]
Prostate cancer	DISF190Y	moderate	Altered Expression	[16]
Prostate carcinoma	DISMJPLE	moderate	Altered Expression	[16]
Triple negative breast cancer	DISAMG6N	moderate	Biomarker	[21]
Ankylosing spondylitis	DISRC6IR	Limited	Biomarker	[22]
Breast neoplasm	DISNGJLM	Limited	Biomarker	[23]
Cardiomyopathy	DISUPZRG	Limited	Biomarker	[24]
Schizophrenia	DISSRV2N	Limited	Autosomal dominant	[25]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Topotecan	DMP6G8T	Approved	C-Jun-amino-terminal kinase-interacting protein 4 (SPAG9) affects the response to substance of Topotecan.	[46]

19 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 C-Jun-amino-terminal kinase-interacting protein 4 (SPAG9).	[26]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of C-Jun-amino-terminal kinase-interacting protein 4 (SPAG9).	[27]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of C-Jun-amino-terminal kinase-interacting protein 4 (SPAG9).	[28]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of C-Jun-amino-terminal kinase-interacting protein 4 (SPAG9).	[29]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of C-Jun-amino-terminal kinase-interacting protein 4 (SPAG9).	[30]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of C-Jun-amino-terminal kinase-interacting protein 4 (SPAG9).	[31]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of C-Jun-amino-terminal kinase-interacting protein 4 (SPAG9).	[32]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of C-Jun-amino-terminal kinase-interacting protein 4 (SPAG9).	[33]
Marinol	DM70IK5	Approved	Marinol increases the expression of C-Jun-amino-terminal kinase-interacting protein 4 (SPAG9).	[34]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of C-Jun-amino-terminal kinase-interacting protein 4 (SPAG9).	[35]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of C-Jun-amino-terminal kinase-interacting protein 4 (SPAG9).	[36]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of C-Jun-amino-terminal kinase-interacting protein 4 (SPAG9).	[37]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of C-Jun-amino-terminal kinase-interacting protein 4 (SPAG9).	[38]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of C-Jun-amino-terminal kinase-interacting protein 4 (SPAG9).	[39]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of C-Jun-amino-terminal kinase-interacting protein 4 (SPAG9).	[40]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of C-Jun-amino-terminal kinase-interacting protein 4 (SPAG9).	[42]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of C-Jun-amino-terminal kinase-interacting protein 4 (SPAG9).	[43]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of C-Jun-amino-terminal kinase-interacting protein 4 (SPAG9).	[44]
crotylaldehyde	DMTWRQI	Investigative	crotylaldehyde increases the expression of C-Jun-amino-terminal kinase-interacting protein 4 (SPAG9).	[45]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of C-Jun-amino-terminal kinase-interacting protein 4 (SPAG9).	[41]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of C-Jun-amino-terminal kinase-interacting protein 4 (SPAG9).	[41]

References

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