Details of Drug Off-Target (DOT)

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

• DOT Name: Germinal center-associated signaling and motility protein (GCSAM)
• Synonyms: Germinal center B-cell-expressed transcript 2 protein; Germinal center-associated lymphoma protein; hGAL
• Gene Name: GCSAM
• Related Disease:
  Follicular lymphoma
  Adult lymphoma
  Advanced cancer
  Amyloidosis
  B-cell lymphoma
  Burkitt lymphoma
  Classic Hodgkin lymphoma
  Lymphoma
  Neoplasm
  Non-small-cell lung cancer
  Pediatric lymphoma
  Acute lymphocytic leukaemia
  B-cell neoplasm
  Lymphoid leukemia
  MALT lymphoma
  Marginal zone lymphoma
• UniProt ID: GCSAM_HUMAN
• Pfam ID: PF15666
• Sequence:
  MGNSLLRENRRQQNTQEMPWNVRMQSPKQRTSRCWDHHIAEGCFCLPWKKILIFEKRQDS
  QNENERMSSTPIQDNVDQTYSEELCYTLINHRVLCTRPSGNSAEEYYENVPCKAERPRES
  LGGTETEYSLLHMPSTDPRHARSPEDEYELLMPHRISSHFLQQPRPLMAPSETQFSHL
• Function: Involved in the negative regulation of lymphocyte motility. It mediates the migration-inhibitory effects of IL6. Serves as a positive regulator of the RhoA signaling pathway. Enhancement of RhoA activation results in inhibition of lymphocyte and lymphoma cell motility by activation of its downstream effector ROCK. Is a regulator of B-cell receptor signaling, that acts through SYK kinase activation.
• Tissue Specificity: Expressed in diffuse large B-cell lymphoma (DLBCL) and several germinal center (GC)-like lymphoma cell lines (at protein level). Highly expressed in normal GC lymphocytes and GC-derived malignancies. Expressed in thymus and spleen.

Molecular Interaction Atlas (MIA) of This DOT

16 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Follicular lymphoma	DISVEUR6	Definitive	Biomarker	[1]
Adult lymphoma	DISK8IZR	Strong	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Amyloidosis	DISHTAI2	Strong	Biomarker	[4]
B-cell lymphoma	DISIH1YQ	Strong	Biomarker	[2]
Burkitt lymphoma	DIS9D5XU	Strong	Biomarker	[5]
Classic Hodgkin lymphoma	DISV1LU6	Strong	Altered Expression	[6]
Lymphoma	DISN6V4S	Strong	Altered Expression	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[7]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[8]
Pediatric lymphoma	DIS51BK2	Strong	Biomarker	[2]
Acute lymphocytic leukaemia	DISPX75S	Limited	Altered Expression	[9]
B-cell neoplasm	DISVY326	Limited	Altered Expression	[10]
Lymphoid leukemia	DIS65TYQ	Limited	Altered Expression	[9]
MALT lymphoma	DIS1AVVE	Limited	Biomarker	[11]
Marginal zone lymphoma	DISLZ4AO	Limited	Biomarker	[11]

1 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 Germinal center-associated signaling and motility protein (GCSAM).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Germinal center-associated signaling and motility protein (GCSAM).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Germinal center-associated signaling and motility protein (GCSAM).	[14]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Germinal center-associated signaling and motility protein (GCSAM).	[15]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Germinal center-associated signaling and motility protein (GCSAM).	[16]

References

• [1] Usefulness of HGAL and LMO2 immunohistochemistry in the identification of follicular lymphomas of the non-gastric gastrointestinal tract.Appl Immunohistochem Mol Morphol. 2013 May;21(3):200-4. doi: 10.1097/PAI.0b013e31826399aa.
• [2] miR-155 regulates HGAL expression and increases lymphoma cell motility.Blood. 2012 Jan 12;119(2):513-20. doi: 10.1182/blood-2011-08-370536. Epub 2011 Nov 16.
• [3] Studies of a germinal centre B-cell expressed gene, GCET2, suggest its role as a membrane associated adapter protein.Br J Haematol. 2007 Jun;137(6):578-90. doi: 10.1111/j.1365-2141.2007.06597.x. Epub 2007 May 9.
• [4] Germinal centre protein HGAL promotes lymphoid hyperplasia and amyloidosis via BCR-mediated Syk activation.Nat Commun. 2013;4:1338. doi: 10.1038/ncomms2334.
• [5] Expression of the human germinal center-associated lymphoma (HGAL) protein, a new marker of germinal center B-cell derivation.Blood. 2005 May 15;105(10):3979-86. doi: 10.1182/blood-2004-08-3112. Epub 2005 Jan 27.
• [6] Germinal center-specific protein human germinal center associated lymphoma directly interacts with both myosin and actin and increases the binding of myosin to actin.FEBS J. 2011 Jun;278(11):1922-31. doi: 10.1111/j.1742-4658.2011.08109.x. Epub 2011 Apr 20.
• [7] Adenovirus-mediated ribonucleotide reductase R1 gene therapy of human colon adenocarcinoma.Clin Cancer Res. 2003 Oct 1;9(12):4553-61.
• [8] The TGF-induced lncRNA TBILA promotes non-small cell lung cancer progression in vitro and in vivo via cis-regulating HGAL and activating S100A7/JAB1 signaling.Cancer Lett. 2018 Sep 28;432:156-168. doi: 10.1016/j.canlet.2018.06.013. Epub 2018 Jun 15.
• [9] BCL6 expression correlates with the t(1;19) translocation in B-lymphoblastic leukemia.Am J Clin Pathol. 2015 Apr;143(4):547-57. doi: 10.1309/AJCPO4U4VYAAOTEL.
• [10] Expression of HGAL in primary cutaneous large B-cell lymphomas: evidence for germinal center derivation of primary cutaneous follicular lymphoma.Mod Pathol. 2008 Jun;21(6):653-9. doi: 10.1038/modpathol.2008.30. Epub 2008 Feb 8.
• [11] The efficacy of HGAL and LMO2 in the separation of lymphomas derived from small B cells in nodal and extranodal sites, including the bone marrow.Am J Clin Pathol. 2011 May;135(5):697-708. doi: 10.1309/AJCP7Z2BIBUNQPLZ.
• [12] 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.
• [13] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [14] Genome-wide transcriptional and functional analysis of human T lymphocytes treated with benzo[alpha]pyrene. Int J Mol Sci. 2018 Nov 17;19(11).
• [15] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [16] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.