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

CARM1 (Q86X55) - Overview - Molecular Target Synopsis

Protein


CARM1, Histone-arginine methyltransferase CARM1
Enzyme Classification 2.1.1.319
UniProt Q86X55

Also Known as CARM1_HUMAN, CARM1, PRMT4

Methylates (mono- and asymmetric dimethylation) the guanidino nitrogens of arginyl residues in several proteins involved in DNA packaging, transcription regulation, pre-mRNA splicing, and mRNA stability. Recruited to promoters upon gene activation together with histone acetyltransferases from EP300/P300 and p160 families, methylates histone H3 at 'Arg-17' (H3R17me), forming mainly asymmetric dimethylarginine (H3R17me2a), leading to activate transcription via chromatin remodeling. During nuclear hormone receptor activation and TCF7L2/TCF4 activation, acts synergically with EP300/P300 and either one of the p160 histone acetyltransferases NCOA1/SRC1, NCOA2/GRIP1 and NCOA3/ACTR or CTNNB1/beta-catenin to activate transcription. During myogenic transcriptional activation, acts together with NCOA3/ACTR as a coactivator for MEF2C. During monocyte inflammatory stimulation, acts together with EP300/P300 as a coactivator for NF-kappa-B. Acts as coactivator for PPARG, promotes adipocyte differentiation and the accumulation of brown fat tissue. Plays a role in the regulation of pre-mRNA alternative splicing by methylation of splicing factors. Also seems to be involved in p53/TP53 transcriptional activation. Methylates EP300/P300, both at 'Arg-2142', which may loosen its interaction with NCOA2/GRIP1, and at 'Arg-580' and 'Arg-604' in the KIX domain, which impairs its interaction with CREB and inhibits CREB-dependent transcriptional activation. Also methylates arginine residues in RNA-binding proteins PABPC1, ELAVL1 and ELAV4, which may affect their mRNA-stabilizing properties and the half-life of their target mRNAs. Homodimer (Probable). Interacts with the C-terminus of NCOA2/GRIP1, NCO3/ACTR and NCOA1/SRC1. Part of a complex consisting of CARM1, EP300/P300 and NCOA2/GRIP1. Interacts with FLII, TP53, myogenic factor MEF2, EP300/P300, TRIM24, CREBBP and CTNNB1. Identified in a complex containing CARM1, TRIM24 and NCOA2/GRIP1. Interacts with NCOA3/SRC3. Interacts with SNRPC (By similarity). Interacts with NR1H4. Interacts with RELA.

6DVR
CRYSTAL STRUCTURE OF HUMAN CARM1 WITH (R)-SKI-72
RCSB/PDB
Inspect Structure
See all 3D Structures for CARM1

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: CARM1 is active in the following subcellular-locations: cytoplasm, nucleus.
GO terms: CARM1 is active in the following subcellular-locations: cytoplasm, cytosol, nucleoplasm, nucleus, RNA polymerase II transcription factor complex.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project CARM1 has gain in 1 cell-lines, loss in 0 cell-lines and no signal in 1004 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: HCT_116, BT_549, HCT_15

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: HGC-27, BFTC-905, GTL-16

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: SK-N-SH, HMEC, A549

(see details)

3D Structures


For CARM1 there are:
44 structures (178 chains) solved
41 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


CARM1 has been screened with 155 compounds (221 bioactivities), 32 compounds have bioactivities that show binding affinity of <= 500nM (38 bioactivities). (see details)