Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

PRMT1 (Q99873) - Overview - Molecular Target Synopsis

Protein


PRMT1, Protein arginine N-methyltransferase 1
Enzyme Classification 2.1.1.319
UniProt Q99873

Also Known as ANM1_HUMAN, PRMT1, HMT2, HRMT1L2, IR1B4

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 (PubMed:10749851, PubMed:16879614, PubMed:26876602). 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 (PubMed:26575292). 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 (PubMed:25284789). Methylates H4R3 in genes involved in glioblastomagenesis in a CHTOP- and/or TET1-dependent manner (PubMed:25284789). Homodimer (PubMed:16879614, PubMed:26876602). Homooctamer; individual homodimers associates to form a homooctamer (PubMed:26876602). Individual homodimers can associate to form a homohexamer. Heterodimer with PRMT8. Interacts with BTG1, BTG2, NFATC2IP and IFNAR1 (By similarity). Interacts with and methylates CHTOP, thereby enabling the interaction of CHTOP with the 5FMC complex (PubMed:25284789). Interacts with ILF3 and SUPT5H. Interacts with and methylates FOXO1, leading to the nuclear retention of FOXO1 and the stimulation of FOXO1 transcriptional activity. Methylation of FOXO1 is increased upon oxidative stress. Interacts with and probably methylates ATXN2L (PubMed:25748791). Component of the methylosome, a 20S complex containing at least CLNS1A/pICln, PRMT5/SKB1, WDR77/MEP50, PRMT1 and ERH (PubMed:25284789). Interacts with DHX9 (via RGG region) (PubMed:15084609). Interacts (via N-terminus) with HABP4 (PubMed:16879614).

6NT2
TYPE 1 PRMT IN COMPLEX WITH THE INHIBITOR GSK3368715
RCSB/PDB
Inspect Structure
See all 3D Structures for PRMT1

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: PRMT1 is active in the following subcellular-locations: cytoplasm, cytosol, nucleoplasm, nucleus.
GO terms: PRMT1 is active in the following subcellular-locations: cytoplasm, cytosol, methylosome, nucleoplasm, nucleus.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project PRMT1 has gain in 3 cell-lines, loss in 1 cell-lines and no signal in 1000 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: A549, PC_3, HCT_116

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: CAL-120, RI-1, KMM-1

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: A549, SK-N-SH, HMEC

(see details)

3D Structures


For PRMT1 there are:
1 structures (4 chains) solved
1 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


PRMT1 has been screened with 384 compounds (611 bioactivities), 23 compounds have bioactivities that show binding affinity of <= 500nM (25 bioactivities). (see details)