Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHXQCX7)

• DOT Name: Very large A-kinase anchor protein (CRYBG3)
• Synonyms: vlAKAP; Beta/gamma crystallin domain-containing protein 3
• Gene Name: CRYBG3
• Related Disease:
  Lung cancer
  Advanced cancer
  Neoplasm
  Non-small-cell lung cancer
  Lung carcinoma
• UniProt ID: CRBG3_HUMAN
• Pfam ID: PF00030 ; PF00652
• Sequence:
  MSSGRRRGSAPWHSFSRFFAPRSPSRDKEEEEEERPGTSPPPAPGRSAASVENEPMSTSQ
  KKENVLSSEAVKIRQSEDKRNHAEKPVTLPVQEDPKKAYDLSSSTSDTKIGESDRQPKES
  FFQFLGNLFNISGKSSLGEAKQSSFKDDQDKTEKDLQNPSDHHEDGIKREREIFSGSLRT
  QTHPTEEQDSNSSELSDAFSLDTTQDSDQETTNLLKQIDGKPEKPSVTYATYRGPRHIGK
  YLKQQTGLATVNTLDRENESSDSSTNRHIDPGSEIEAGVLPLLLSASTDSSMKGNLLEGP
  LEDSDCSKTSFNKENSLTNNPELQNIASSNNLLNKNAWGSIERNRSSPSSVTNSSYDGES
  DSQHHLSCEPVSQTNRNLVCSALLTGSNHRKVPCSPDFQRVTTTENTIKENSTVMSNRTL
  VQREELVEPQGPAISDFSCSKSDGSDTTEQESTNLPSPNKSIRHEHLQLPESECSDKQTI
  DSSSKQAATHTNIIALQRHAVTDTEFVNEGKRLSAQDSQKNVAVREIRRETESASAGESI
  ASSHVKAPEDKIESLPKDTDQYFETKAKKLDFRSHDKIPHIRMNKKDLASLNYISESAVV
  ASLGNENAPELKFELNRSHISETPLDSESPQQAEVSPDAKTSLSLDCKKLNFSISPPTFV
  SGVGMLSKLDIPDLMNEGSPVPIETGNVNIVGISYQPRKCKEENVKNHVEAAGRKSPPPS
  FCLEYTSAIFEFKEVLSNSEKCQVLPGSEASGPHLTGLELLSFDSGNLSKDCSSILSQDP
  NRVELVSSNTKANMSIIEKSDSLSLEAKTANIVSKAEIDGQNNVLVESHSGRGKTISLSK
  VSLSKVEPRNISQDKMSSFPLKITHVPEKPILSELTFLEVEQGKRFQSINHNEIGEKCSD
  AGLKENCQAELSPAASKYEDKPEPEVDALGSPPALLKSNISWILPPIHDEKISRQMAQNC
  EAHTCVFHQSLDICGTKKISGHSEMAELSLTNISPKFQETGSMKVNSPFLDSDSSLEKNS
  SASEDSSFLKVPSVLKLEKKSSSYRKKENIHFLNGGIDSVSSSSSYPEEVSMIVNSHKPQ
  NNLDSIQVTKDLTHEGTSVTNLLYPTTSYLEFETSVSIGTEVTPFQEHFGIYTGKISIDF
  PTAAQFDNLVEAETGAVAGPAASVNSSGQQCSEASAEHIEARRRAHDQLLDLKSSLLKKA
  DTLIGEIFNSVREELKFKHTVSTCQEHIAIEGIMNLGTLKEDISEKNPSEVTLTEIQQTE
  GLEEQGMENMSEVKEKPCVSPTVGEKNLLVDPNSMNVSCLLEDKARELVNEIIYVAQEKL
  RNDTFEDTEDTWDSELQANTSKILNSDSVKPHDVVREFLVSEQPVNQSTQISENKVLNEF
  FSLSNLASGTESIKGGEIVLYQKSLFSGNGSGLSDSINLQESDTVLLAEDMSHKRLDDRV
  KTHLFRSEDCNETMEIENVDNNKTETEDRRTLVLNFKWPPLVNDDIHAPGTSKSSLSDSL
  VCISEKNLPGHSKNTPLAMSDVGKVHKKDNEINIGKIELIPSMLETGKTNKKDAELNILK
  YEAVPPMIEMGRIHKMDAELNVTKTEPKANVFKMGEVYQMDAESCIEKTEGSAVILGMEK
  AYKMKDTEGDIGKIEVIPMMPEVKNIHQKDAEGDIVKTEMTPVTVDMENIYQTHAEGDIG
  KTGTIALSEVENIHQKGGEGISEKAEVIPVTLAMENTYQKDAEGDIGKAEVMPVRLEMEN
  TYPKDTERDGGKTEVMPLALEVVNTYQKNAKGFTGNTEGSVLKMEATYRKTAEEVIKNTE
  IVPCVLKVKEAHETAPAPLEMEKACKRDVKETIGATVSTPSVIEMEKISPEDRGENIGKH
  KVLPAVVDIEKIHGTGLELTTKQGEAMLPAFESKTPQEYAEGSVEETKEEPTEIKEGLIA
  HENRLPTYFRGYESPTLSKDYEGYPAPAMPDFQPGDTTVRLDKRMSLTAIYDKRRETDYS
  DKGYNLAFVSQDEQENSSFTILYEEPLQEEDKYASAEARQTQSVLFHDTSADSMPVLACE
  RSESRTDLVHHFEKGTKLGETFDSDSSEMFLSVEAKRYKIYPLALSPIYEDDSSQEDILS
  SEVSPGHHGPRKSRDSENQSSSVLSLLQSVSERLKMNFDEDDREAADEEEEEEEAAVLHK
  GDLRAGSGERVTFQLPDPSITFYPDDQESVGISKNSYVMPNEPTTSNLQVGLWPEKTSFL
  QKSDLTSKLHSSLKSAYHQYLQTSQSHSSEKGARFGGIFQEPVSKYFRVQDSPGRLSPFI
  ENVDKQTLRCNPRPGKMVIYDLHESTYKQEVYCNIPDATSWSFPNGVLIKVVRGCWILYE
  KPHFRGQKCVLEEGEKVLNRDWILQNRRHPQRNFILGSLKRVLKDCSIPEIELFPQSDPA
  CCPVYIQRAVPNLEELNISKSVSFTVKSGVWLAYPDINFKGQATVLEEDHGLFEISTAEM
  KSLHPLQMGGLKVEMPMNLKVIIYEKPHFHGQAKEFSEHIDSVPNFLKNNGDFHRIGSIR
  VIGGVWVAYEKEHFKGQQFLLEEGDFEDSNACGALSSPILSFRYLQANFIESSVTLFESD
  LESGKFIDITNQEISDLEEIGFGSKTRSIHVKSGVWVAYQQKFFCGEQYILEKGKYKCFF
  DWGGSNNIIMSIRPIQLEPLGINEPPHLLKAFSKPGFQGECIDFTEETSDLTSLMPCSFK
  VLRGCWLLYYQEDMFVNHCVLEEGLYADLTSCGCPASKVKSLKPIDYVFEEPSISLFALE
  HCEGRELHLEEAVNSVLNKDLHFYTQSVWVKSGLWIAYEGSNFLGRQILLRPNEIPNWTA
  FSRWKTIGSLRPMKQPAVYIRIKNRAQGEYLTVTGSLADTRATSVCISPYSGKNTQIWYY
  CRGLFKSKASDTCLDVIGGRDTPGAKVALWTEHGQFRQKWRLNKNGTISSYLSDQLVLDV
  KGGNYCDKTHVIVNQPLEGEETQKWDIEIL
• Function: [Isoform vlAKAP]: Anchoring protein that mediates the subcellular compartmentation of protein kinase A (PKA).

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lung cancer	DISCM4YA	Definitive	Altered Expression	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[3]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[3]
Lung carcinoma	DISTR26C	Disputed	Altered Expression	[1]

9 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 Very large A-kinase anchor protein (CRYBG3).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Very large A-kinase anchor protein (CRYBG3).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Very large A-kinase anchor protein (CRYBG3).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Very large A-kinase anchor protein (CRYBG3).	[7]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Very large A-kinase anchor protein (CRYBG3).	[8]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Very large A-kinase anchor protein (CRYBG3).	[9]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Very large A-kinase anchor protein (CRYBG3).	[10]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Very large A-kinase anchor protein (CRYBG3).	[11]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Very large A-kinase anchor protein (CRYBG3).	[13]

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 Very large A-kinase anchor protein (CRYBG3).	[12]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Very large A-kinase anchor protein (CRYBG3).	[12]

References

• [1] Long non-coding RNA CRYBG3 regulates glycolysis of lung cancer cells by interacting with lactate dehydrogenase A.J Cancer. 2018 Jun 23;9(14):2580-2588. doi: 10.7150/jca.24896. eCollection 2018.
• [2] Long Noncoding RNA CRYBG3 Blocks Cytokinesis by Directly Binding G-Actin.Cancer Res. 2018 Aug 15;78(16):4563-4572. doi: 10.1158/0008-5472.CAN-18-0988. Epub 2018 Jun 22.
• [3] LNC CRYBG3 inhibits tumor growth by inducing M phase arrest.J Cancer. 2019 Jun 2;10(12):2764-2770. doi: 10.7150/jca.31703. eCollection 2019.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [6] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [9] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [12] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [13] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.