Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCLJ56M)

• DOT Name: Sperm-associated antigen 5 (SPAG5)
• Synonyms: Astrin; Deepest; Mitotic spindle-associated protein p126; MAP126
• Gene Name: SPAG5
• Related Disease:
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Cervical cancer
  Cervical carcinoma
  Gastric cancer
  Hepatocellular carcinoma
  Hypogonadism, male
  Lung neoplasm
  Lung squamous cell carcinoma
  Neoplasm
  Non-small-cell lung cancer
  Stomach cancer
  Thyroid gland undifferentiated (anaplastic) carcinoma
  Bladder transitional cell carcinoma
  Lung adenocarcinoma
  Triple negative breast cancer
  Cryptorchidism
  Lung cancer
  Lung carcinoma
  Prostate cancer
  Prostate carcinoma
• UniProt ID: SPAG5_HUMAN
• Sequence:
  MWRVKKLSLSLSPSPQTGKPSMRTPLRELTLQPGALTNSGKRSPACSSLTPSLCKLGLQE
  GSNNSSPVDFVNNKRTDLSSEHFSHSSKWLETCQHESDEQPLDPIPQISSTPKTSEEAVD
  PLGNYMVKTIVLVPSPLGQQQDMIFEARLDTMAETNSISLNGPLRTDDLVREEVAPCMGD
  RFSEVAAVSEKPIFQESPSHLLEESPPNPCSEQLHCSKESLSSRTEAVREDLVPSESNAF
  LPSSVLWLSPSTALAADFRVNHVDPEEEIVEHGAMEEREMRFPTHPKESETEDQALVSSV
  EDILSTCLTPNLVEMESQEAPGPAVEDVGRILGSDTESWMSPLAWLEKGVNTSVMLENLR
  QSLSLPSMLRDAAIGTTPFSTCSVGTWFTPSAPQEKSTNTSQTGLVGTKHSTSETEQLLC
  GRPPDLTALSRHDLEDNLLSSLVILEVLSRQLRDWKSQLAVPHPETQDSSTQTDTSHSGI
  TNKLQHLKESHEMGQALQQARNVMQSWVLISKELISLLHLSLLHLEEDKTTVSQESRRAE
  TLVCCCFDLLKKLRAKLQSLKAEREEARHREEMALRGKDAAEIVLEAFCAHASQRISQLE
  QDLASMREFRGLLKDAQTQLVGLHAKQEELVQQTVSLTSTLQQDWRSMQLDYTTWTALLS
  RSRQLTEKLTVKSQQALQERDVAIEEKQEVSRVLEQVSAQLEECKGQTEQLELENSRLAT
  DLRAQLQILANMDSQLKELQSQHTHCAQDLAMKDELLCQLTQSNEEQAAQWQKEEMALKH
  MQAELQQQQAVLAKEVRDLKETLEFADQENQVAHLELGQVECQLKTTLEVLRERSLQCEN
  LKDTVENLTAKLASTIADNQEQDLEKTRQYSQKLGLLTEQLQSLTLFLQTKLKEKTEQET
  LLLSTACPPTQEHPLPNDRTFLGSILTAVADEEPESTPVPLLGSDKSAFTRVASMVSLQP
  AETPGMEESLAEMSIMTTELQSLCSLLQESKEEAIRTLQRKICELQARLQAQEEQHQEVQ
  KAKEADIEKLNQALCLRYKNEKELQEVIQQQNEKILEQIDKSGELISLREEVTHLTRSLR
  RAETETKVLQEALAGQLDSNCQPMATNWIQEKVWLSQEVDKLRVMFLEMKNEKEKLMIKF
  QSHRNILEENLRRSDKELEKLDDIVQHIYKTLLSIPEVVRGCKELQGLLEFLS
• Function: Essential component of the mitotic spindle required for normal chromosome segregation and progression into anaphase. Required for chromosome alignment, normal timing of sister chromatid segregation, and maintenance of spindle pole architecture. In complex with SKAP, promotes stable microtubule-kinetochore attachments. May contribute to the regulation of separase activity. May regulate AURKA localization to mitotic spindle, but not to centrosomes and CCNB1 localization to both mitotic spindle and centrosomes. Involved in centriole duplication. Required for CDK5RAP2, CEP152, WDR62 and CEP63 centrosomal localization and promotes the centrosomal localization of CDK2. In non-mitotic cells, upon stress induction, inhibits mammalian target of rapamycin complex 1 (mTORC1) association and recruits the mTORC1 component RPTOR to stress granules (SGs), thereby preventing mTORC1 hyperactivation-induced apoptosis. May enhance GSK3B-mediated phosphorylation of other substrates, such as MAPT/TAU.
• Tissue Specificity: Highly expressed in testis. Detected at low levels in placenta, liver, pancreas, thymus and colon.

Molecular Interaction Atlas (MIA) of This DOT

22 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Breast cancer	DIS7DPX1	Strong	Biomarker	[1]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[1]
Cervical cancer	DISFSHPF	Strong	Biomarker	[2]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[2]
Gastric cancer	DISXGOUK	Strong	Biomarker	[3]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[4]
Hypogonadism, male	DISV1F5R	Strong	Genetic Variation	[5]
Lung neoplasm	DISVARNB	Strong	Biomarker	[6]
Lung squamous cell carcinoma	DISXPIBD	Strong	Biomarker	[7]
Neoplasm	DISZKGEW	Strong	Biomarker	[8]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[9]
Stomach cancer	DISKIJSX	Strong	Biomarker	[3]
Thyroid gland undifferentiated (anaplastic) carcinoma	DISYBB1W	Strong	Altered Expression	[10]
Bladder transitional cell carcinoma	DISNL46A	moderate	Biomarker	[8]
Lung adenocarcinoma	DISD51WR	moderate	Altered Expression	[11]
Triple negative breast cancer	DISAMG6N	moderate	Altered Expression	[8]
Cryptorchidism	DISYUD2P	Limited	Altered Expression	[12]
Lung cancer	DISCM4YA	Limited	Biomarker	[13]
Lung carcinoma	DISTR26C	Limited	Biomarker	[13]
Prostate cancer	DISF190Y	Limited	Altered Expression	[13]
Prostate carcinoma	DISMJPLE	Limited	Altered Expression	[13]

3 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 Sperm-associated antigen 5 (SPAG5).	[14]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Sperm-associated antigen 5 (SPAG5).	[35]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Sperm-associated antigen 5 (SPAG5).	[35]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Sperm-associated antigen 5 (SPAG5).	[15]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Sperm-associated antigen 5 (SPAG5).	[16]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Sperm-associated antigen 5 (SPAG5).	[17]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Sperm-associated antigen 5 (SPAG5).	[18]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Sperm-associated antigen 5 (SPAG5).	[19]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Sperm-associated antigen 5 (SPAG5).	[20]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Sperm-associated antigen 5 (SPAG5).	[21]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Sperm-associated antigen 5 (SPAG5).	[22]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Sperm-associated antigen 5 (SPAG5).	[23]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Sperm-associated antigen 5 (SPAG5).	[23]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Sperm-associated antigen 5 (SPAG5).	[24]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Sperm-associated antigen 5 (SPAG5).	[25]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Sperm-associated antigen 5 (SPAG5).	[22]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Sperm-associated antigen 5 (SPAG5).	[26]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Sperm-associated antigen 5 (SPAG5).	[27]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Sperm-associated antigen 5 (SPAG5).	[28]
Lucanthone	DMZLBUO	Approved	Lucanthone decreases the expression of Sperm-associated antigen 5 (SPAG5).	[29]
Genistein	DM0JETC	Phase 2/3	Genistein affects the expression of Sperm-associated antigen 5 (SPAG5).	[30]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of Sperm-associated antigen 5 (SPAG5).	[31]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Sperm-associated antigen 5 (SPAG5).	[32]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Sperm-associated antigen 5 (SPAG5).	[33]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Sperm-associated antigen 5 (SPAG5).	[34]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Sperm-associated antigen 5 (SPAG5).	[36]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Sperm-associated antigen 5 (SPAG5).	[37]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Sperm-associated antigen 5 (SPAG5).	[38]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Sperm-associated antigen 5 (SPAG5).	[19]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Sperm-associated antigen 5 (SPAG5).	[39]
Lithium chloride	DMHYLQ2	Investigative	Lithium chloride decreases the expression of Sperm-associated antigen 5 (SPAG5).	[40]

References

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