Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTS2PWT4)

• DOT Name: Small G protein signaling modulator 1 (SGSM1)
• Synonyms: RUN and TBC1 domain-containing protein 2
• Gene Name: SGSM1
• Related Disease:
  Advanced cancer
  Sclerosing cholangitis
  Nasopharyngeal carcinoma
• UniProt ID: SGSM1_HUMAN
• Pfam ID: PF12068 ; PF00566 ; PF02759
• Sequence:
  MASAPAEAETRQRLLRTVKKEVKQIMEEAVTRKFVHEDSSHIISFCAAVEACVLHGLRRR
  AAGFLRSNKIAALFMKVGKNFPPAEDLSRKVQDLEQLIESARNQIQGLQENVRKLPKLPN
  LSPLAIKHLWIRTALFEKVLDKIVHYLVENSSKYYEKEALLMDPVDGPILASLLVGPCAL
  EYTKMKTADHFWTDPSADELVQRHRIHSSHVRQDSPTKRPALCIQKRHSSGSMDDRPSLS
  ARDYVESLHQNSRATLLYGKNNVLVQPRDDMEAVPGYLSLHQTADVMTLKWTPNQLMNGS
  VGDLDYEKSVYWDYAMTIRLEEIVYLHCHQQVDSGGTVVLVSQDGIQRPPFRFPKGGHLL
  QFLSCLENGLLPHGQLDPPLWSQRGKGKVFPKLRKRSPQGSAESTSSDKDDDEATDYVFR
  IIYPGMQSEFVAPDFLGSTSSVSVGPAWMMVPAGRSMLVVARGSQWEPARWDTTLPTPSP
  KEQPPMPQDLMDVSVSNLPSLWQPSPRKSSCSSCSQSGSADGSSTNGCNHERAPLKLLCD
  NMKYQILSRAFYGWLAYCRHLSTVRTHLSALVNHMIVSPDLPCDAGQGLTARIWEQYLHD
  STSYEEQELLRLIYYGGIQPEIRKAVWPFLLGHYQFGMTETERKEVDEQIHACYAQTMAE
  WLGCEAIVRQRERESHAAALAKCSSGASLDSHLHRMLHRDSTISNESSQSCSSGRQNIRL
  HSDSSSSTQVFESVDEVEQVEAEGRLEEKQPKIPNGNLVNGTCSPDSGHPSSHNFSSGLS
  EHSEPSLSTEDSVLDAQRNTPTVLRPRDGSVDDRQSSEATTSQDEAPREELAVQDSLESD
  LLANESMDEFMSITGSLDMALPEKDDVVMEGWRSSETEKHGQADSEDNLSEEPEMESLFP
  ALASLAVTTSANEVSPVSSSGVTYSPELLDLYTVNLHRIEKDVQRCDRNYWYFTPANLEK
  LRNIMCSYIWQHIEIGYVQGMCDLLAPLLVILDDEALAFSCFTELMKRMNQNFPHGGAMD
  THFANMRSLIQILDSELFELMHQNGDYTHFYFCYRWFLLDFKRELVYDDVFLVWETIWAA
  KHVSSAHYVLFIALALVEVYRDIILENNMDFTDIIKFFNEMAERHNTKQVLKLARDLVYK
  VQTLIENK
• Function: Interacts with numerous Rab family members, functioning as Rab effector for some, and as GTPase activator for others. Promotes GTP hydrolysis by RAB34 and RAB36. Probably functions as a GTPase effector with RAB9A and RAB9B; does not stimulate GTP hydrolysis with RAB9A and RAB9B.
• Tissue Specificity: Mainly expressed in brain, heart and testis.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Sclerosing cholangitis	DIS7GZNB	Strong	Genetic Variation	[2]
Nasopharyngeal carcinoma	DISAOTQ0	Limited	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Small G protein signaling modulator 1 (SGSM1).	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Small G protein signaling modulator 1 (SGSM1).	[5]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Small G protein signaling modulator 1 (SGSM1).	[6]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Small G protein signaling modulator 1 (SGSM1).	[5]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Small G protein signaling modulator 1 (SGSM1).	[7]

References

• [1] Small G protein signalling modulator 2 (SGSM2) is involved in oestrogen receptor-positive breast cancer metastasis through enhancement of migratory cell adhesion via interaction with E-cadherin.Cell Adh Migr. 2019 Dec;13(1):120-137. doi: 10.1080/19336918.2019.1568139. Epub 2019 Feb 11.
• [2] Genome-wide association study of primary sclerosing cholangitis identifies new risk loci and quantifies the genetic relationship with inflammatory bowel disease.Nat Genet. 2017 Feb;49(2):269-273. doi: 10.1038/ng.3745. Epub 2016 Dec 19.
• [3] Hypermethylation of SHISA3 Promotes Nasopharyngeal Carcinoma Metastasis by Reducing SGSM1 Stability.Cancer Res. 2019 Feb 15;79(4):747-759. doi: 10.1158/0008-5472.CAN-18-1754. Epub 2018 Dec 20.
• [4] 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.
• [5] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [6] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [7] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.