Histone-arginine methyltransferase CARM1 (CARM1)
The protein contains 608 amino acids for an estimated molecular weight of 65854 Da.
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-bind (updated: April 1, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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Biological Process
Aging
Cellular lipid metabolic process
Chromatin organization
DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest
Endochondral bone morphogenesis
Histone arginine methylation
Histone H3-R17 methylation
Histone H3-R2 methylation
Histone methylation
Intracellular estrogen receptor signaling pathway
Negative regulation of dendrite development
Negative regulation of protein binding
Pathogenesis
Peptidyl-arginine methylation, to asymmetrical-dimethyl arginine
Positive regulation of cell population proliferation
Positive regulation of fat cell differentiation
Positive regulation of NF-kappaB transcription factor activity
Positive regulation of transcription by RNA polymerase II
Protein localization to chromatin
Regulation of growth plate cartilage chondrocyte proliferation
Regulation of intracellular estrogen receptor signaling pathway
Regulation of lipid metabolic process
Regulation of mRNA binding
Regulation of transcription, DNA-templated
Response to cAMP
Small molecule metabolic process
Transcription, DNA-templated
Viral process
Cellular Component
Cytoplasm
Cytosol
Nucleoplasm
Nucleus
RNA polymerase II transcription regulator complex
Molecular Function
Beta-catenin binding
Histone methyltransferase activity
Histone methyltransferase activity (H3-R17 specific)
Histone-arginine N-methyltransferase activity
Lysine-acetylated histone binding
Nuclear receptor coactivator activity
Protein homodimerization activity
Protein methyltransferase activity
Protein-arginine N-methyltransferase activity
Protein-arginine omega-N asymmetric methyltransferase activity
RNA polymerase II transcription coactivator activity
Transcription cis-regulatory region binding
Transcription coactivator activity
Transcription regulatory region DNA binding
The reference OMIM entry for this protein is 603934
Coactivator-associated arginine methyltransferase 1; carm1
Protein arginine n-methyltransferase 4; prmt4
DESCRIPTION
Protein arginine N-methyltransferases, such as CARM1, catalyze the transfer of a methyl group from S-adenosyl-L-methionine to the side chain nitrogens of arginine residues within proteins to form methylated arginine derivatives and S-adenosyl-L-homocysteine. Protein arginine methylation has been implicated in signal transduction, metabolism of nascent pre-RNA, and transcriptional activation (Frankel et al., 2002).CLONING
Members of the p160 family of proteins, which includes SRC1 (NCOA1; 602691) and GRIP1 (NCOA2; 601993), mediate transcriptional activation by nuclear hormone receptors. The AD2 activation domain, found in the C-terminal region of p160 proteins, plays an important role in p160 coactivator function. Using a yeast 2-hybrid system to screen a mouse 17 day-embryo cDNA library, Chen et al. (1999) isolated a cDNA clone encoding a 608-amino acid protein that bound to the C-terminal amino acids of GRIP1. The central portion of the coding region had extensive homology to a family of proteins with arginine-specific protein methyltransferase activity. The protein, coactivator-associated arginine methyltransferase-1 (CARM1), has a 3.8-kb mRNA that is widely but not evenly expressed in adult mouse tissues. Ohkura et al. (2005) identified 4 alternatively-spliced rat Carm1 cDNAs, Carm1-v1 through Carm1-v4. The deduced proteins have between 573 and 608 amino acids. All contain the arginine methyltransferase domain and Grip1-binding domain, but they differ in their C-terminal domains. RT-PCR detected tissue-specific expression of the 4 transcripts. By database analysis, Frankel et al. (2002) identified human PRMT4, which encodes a 608-amino acid protein. The catalytic core region of PRMT4 shares 29 to 36% amino acid identity with those of other PRMTs.GENE FUNCTION
Because CARM1 is homologous to protein arginine methyltransferases, Chen et al. (1999) tested it for methyltransferase activity. Protein arginine methyltransferases transfer a methyl group from S-adenosylmethionine to the guanidino group nitrogen atoms in arginine residues of specific proteins. In vitro protein substrates for these enzymes include histones (see 142711) and proteins involved in RNA metabolism such as hnRNPA1 (164017), fibrillarin (134795), and nucleolin (164035). CARM1 preferentially methylated histone H3, either in a bulk histone preparation or in individually purified form. CARM1 coactivator function was specific for AD2 and correlated with its ability to bind GRIP1. CARM1 enhanced GRIP1 coactivator function for nuclear hormone receptors. The presence of both protein methyltransferase and transcriptional coactivator activities in CARM1 suggested that methylation of histones or other proteins, or both, may play a role in transcriptional regulation. CARM1 cDNA with the mutation in the putative S-adenosylmethionine-binding domain substantially reduced both methyltransferase and coactivator activities. In addition to GRIP1, CARM1 was also able to interact with other members of the p160 family of coactivators, including SRC1. Thus, coactivator-mediated methylation of proteins in the transcription machinery may contribute to transcriptional regulation. Xu et al. (2001) described a molecular switch based on the controlled methylation of nucleosomes and the transcriptional cofactors, CBP (CREBBP; 600140)/p300 (EP300; 602700). These proteins share a methylation site localized to an arginine residue that is essential for sta ... More on the omim web site
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 603934 was added.
Feb. 24, 2016: Protein entry updated
Automatic update: model status changed