CARM1

CARM1 (coactivator-associated arginine methyltransferase 1), also known as PRMT4 (protein arginine N-methyltransferase 4), is an enzyme (EC 2.1.1.125) encoded by the CARM1 gene found in human beings, as well as many other mammals.^[2] It has a polypeptide (L) chain type that is 348 residues long, and is made up of alpha helices and beta sheets.^[3] Its main function includes catalyzing the transfer of a methyl group from S-Adenosyl methionine to the side chain nitrogens of arginine residues within proteins to form methylated arginine derivatives and S-Adenosyl-L-homocysteine.^[4] CARM1 is a secondary coactivator through its association with p160 family (SRC-1, GRIP1, AIB) of coactivators. It is responsible for moving cells toward the inner cell mass in developing blastocysts.^[5]

coactivator-associated arginine methyltransferase 1
Crystal Structure of Coactivator Associated Arginine Methyltransferase 1[1]
Identifiers
Symbol	CARM1
NCBI gene	10498
HGNC	23393
OMIM	603934
RefSeq	XM_032719
UniProt	Q86X55
Other data
EC number	2.1.1.125
Locus	Chr. 19 p13.2
Search for Structures Swiss-model Domains InterPro

coactivator associated arginine methyltransferase 1-like
Identifiers
Symbol	CARM1L
NCBI gene	256280
HGNC	23392
RefSeq	XM_171224
UniProt	Q5SZY8
Other data
Locus	Chr. 9 p24.2
Search for Structures Swiss-model Domains InterPro

Clinical significance

CARM1 plays an important role in androgen receptors and may play a role in prostate cancer progression.^[6][7]

CARM1 exerts both oncogenic and tumor-suppressive functions. In breast cancer, CARM1 methylates chromatin remodeling factor BAF155 to enhance tumor progression and metastasis.^[8] In pancreatic cancer, CARM1 methylates and inhibits MDH1 by disrupting its dimerization, which represses mitochondria respiration and inhibits glutamine utilization. CARM1-mediated MDH1 methylation reduces cellular NADPH level and sensitizes cells to oxidative stress, thereby suppressing cell proliferation and colony formation.^[9]

See also

• histone-arginine N-methyltransferase

External links

• coactivator-associated arginine methyltransferase 1 at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• NURSA C30

References

1. "RCSB Protein Data Bank - Structure Summary for 2Y1W - CRYSTAL STRUCTURE OF COACTIVATOR ASSOCIATED ARGININE METHYLTRANSFERASE 1 (CARM1) IN COMPLEX WITH SINEFUNGIN AND INDOLE INHIBITOR".
2. Chen D, Ma H, Hong H, Koh SS, Huang SM, Schurter BT, Aswad DW, Stallcup MR (1999). "Regulation of transcription by a protein methyltransferase". Science. 284 (5423): 2174–7. doi:10.1126/science.284.5423.2174. PMID 10381882.
3. "RCSB Protein Data Bank - Sequence / Structure Details for 2Y1W - CRYSTAL STRUCTURE OF COACTIVATOR ASSOCIATED ARGININE METHYLTRANSFERASE 1 (CARM1) IN COMPLEX WITH SINEFUNGIN AND INDOLE INHIBITOR". Archived from the original on 2015-09-24. Retrieved 2011-04-13.
4. "CARM1 Gene - GeneCards | CARM1 Protein | CARM1 Antibody".
5. Torres-Padilla ME, Parfitt DE, Kouzarides T, Zernicka-Goetz M (2007). "Histone arginine methylation regulates pluripotency in the early mouse embryo". Nature. 445 (7124): 214–8. Bibcode:2007Natur.445..214T. doi:10.1038/nature05458. PMC 3353120. PMID 17215844.
6. Hong H, Kao C, Jeng MH, Eble JN, Koch MO, Gardner TA, Zhang S, Li L, Pan CX, Hu Z, MacLennan GT, Cheng L (2004). "Aberrant expression of CARM1, a transcriptional coactivator of androgen receptor, in the development of prostate carcinoma and androgen-independent status". Cancer. 101 (1): 83–9. doi:10.1002/cncr.20327. PMID 15221992. S2CID 274474.
7. Majumder S, Liu Y, Ford OH, Mohler JL, Whang YE (2006). "Involvement of arginine methyltransferase CARM1 in androgen receptor function and prostate cancer cell viability". Prostate. 66 (12): 1292–301. doi:10.1002/pros.20438. PMID 16705743. S2CID 23950904.
8. Wang L, Zhao Z, Meyer MB, Saha S, Yu M, Guo A, Wisinski KB, Huang W, Cai W, Pike JW, Yuan M, Ahlquist P, Xu W (Jul 2016). "CARM1 Methylates Chromatin Remodeling Factor BAF155 to Enhance Tumor Progression and Metastasis". Cancer Cell. 30 (1): 179–180. doi:10.1016/j.ccr.2013.12.007. PMC 4004525. PMID 24434208.
9. Wang YP, Zhou W, Wang J, Huang X, Zuo Y, Wang TS, Gao X, Xu YY, Zou SW, Liu YB, Cheng JK, Lei QY (Nov 2016). "Arginine Methylation of MDH1 by CARM1 Inhibits Glutamine Metabolism and Suppresses Pancreatic Cancer". Molecular Cell. 64 (4): 673–87. doi:10.1016/j.molcel.2016.09.028. PMID 27840030.