Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTVOJAI)

• DTT Name: Protein arginine methyltransferase 1 (PRMT1)
• Synonyms: Protein arginine N-methyltransferase 1; Interferon receptor 1-bound protein 4; IR1B4; Histone-arginine N-methyltransferase PRMT1; HRMT1L2; HMT2
• Gene Name: PRMT1
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Methyltransferase
• UniProt ID: ANM1_HUMAN
• TTD ID: T16808
• EC Number: EC 2.1.1.319
• Sequence:
  MAAAEAANCIMENFVATLANGMSLQPPLEEVSCGQAESSEKPNAEDMTSKDYYFDSYAHF
  GIHEEMLKDEVRTLTYRNSMFHNRHLFKDKVVLDVGSGTGILCMFAAKAGARKVIGIECS
  SISDYAVKIVKANKLDHVVTIIKGKVEEVELPVEKVDIIISEWMGYCLFYESMLNTVLYA
  RDKWLAPDGLIFPDRATLYVTAIEDRQYKDYKIHWWENVYGFDMSCIKDVAIKEPLVDVV
  DPKQLVTNACLIKEVDIYTVKVEDLTFTSPFCLQVKRNDYVHALVAYFNIEFTRCHKRTG
  FSTSPESPYTHWKQTVFYMEDYLTVKTGEEIFGTIGMRPNAKNNRDLDFTIDLDFKGQLC
  ELSCSTDYRMR
• Function: Constitutes the main enzyme that mediates monomethylation and asymmetric dimethylation of histone H4 'Arg-4' (H4R3me1 and H4R3me2a, respectively), a specific tag for epigenetic transcriptional activation. May be involved in the regulation of TAF15 transcriptional activity, act as an activator of estrogen receptor (ER)-mediated transactivation, play a key role in neurite outgrowth and act as a negative regulator of megakaryocytic differentiation, by modulating p38 MAPK pathway. Methylates RBM15, promoting ubiquitination and degradation of RBM15. Methylates FOXO1 and retains it in the nucleus increasing its transcriptional activity. Methylates CHTOP and this methylation is critical for its 5-hydroxymethylcytosine (5hmC)-binding activity. Methylates H4R3 in genes involved in glioblastomagenesis in a CHTOP- and/or TET1-dependent manner. Arginine methyltransferase that methylates (mono and asymmetric dimethylation) the guanidino nitrogens of arginyl residues present in proteins such as ESR1, histone H2, H3 and H4, ILF3, HNRNPA1, HNRNPD, NFATC2IP, SUPT5H, TAF15, EWS, HABP4 and SERBP1.
• KEGG Pathway:
  FoxO signaling pathway (hsa04068)
  Glucagon signaling pathway (hsa04922)
• Reactome Pathway:
  TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest (R-HSA-6804114)
  RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function (R-HSA-8936459)
  Extra-nuclear estrogen signaling (R-HSA-9009391)
  Estrogen-dependent gene expression (R-HSA-9018519)
  Maturation of nucleoprotein (R-HSA-9694631)
  RMTs methylate histone arginines (R-HSA-3214858)
• BioCyc Pathway: MetaCyc:HS05019-MON

Molecular Interaction Atlas (MIA) of This DTT

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
GSK3368715	DMVEGND	Solid tumour/cancer	2A00-2F9Z	Phase 1	[2]

2 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AMI-1	DM4MXOB	Discovery agent	N.A.	Investigative	[3]
RM65	DMJU5A9	Discovery agent	N.A.	Investigative	[1]

References

• [1] A novel arginine methyltransferase inhibitor with cellular activity. Bioorg Med Chem Lett. 2007 Aug 1;17(15):4150-3.
• [2] National Cancer Institute Drug Dictionary (drug name GSK6097608).
• [3] Small molecule regulators of protein arginine methyltransferases. J Biol Chem. 2004 Jun 4;279(23):23892-9.