Pathway Human Homo sapiens

RMTs methylate histone arginines

R-HSA-3214858 in Reactome release 97: under Chromatin modifying enzymes, with 78 genes placed in it by the mapping files and 0 child pathways in the hierarchy.

The same number in the other species

Reactome writes the mouse and rat events it infers from a human pathway under the human number with the species token. A door opens only where that species' own list in this release holds the id: R-MMU-3214858 (mouse), R-RNO-3214858 (rat). Whether the event was inferred from this one is what the record says.

The record
The genes
Parents and children

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This page reads the pathway's record from its source while you read the rest; with scripts off the card stays at its loading line. Reload with scripts on to see it, or open the source's own page from the link in the card.

01The record

Reactome's own record of this pathway

What this tells you

The pathway list, the hierarchy and the genes on this page are read from the files Reactome publishes for Reactome release 97, built into this site on 2026-09-09: the pathway list, the hierarchy relationship file and the two gene mapping files. The record card is the one live read, Reactome's own record of this pathway.

Reactome's download page describes the mapping files: Mapping files link the source database identifier to the lowest level pathway diagram or subset of the pathway, all levels of the pathway hierarchy or database identifier to all reactions. [R13] The gene list here is the all-levels mapping of NCBI Gene ids, filled from the all-levels mapping of Ensembl ids where the NCBI file has no row for a gene; each row names which file it came from by the shape of its source id. Each row carries the evidence codes the file writes for it, as written and unranked, and both where the file writes both; no page of Reactome's documentation the survey read defines the codes, so this page does not expand them. A gene id the identity files do not name is kept as the source's own id with no door rather than turned into a symbol.

On citing what a search finds, Reactome says: It should be remembered that while we strive to contain the most current and accurate data, Reactome should not be used in citations where other primary sources of information are available. [R12] The record card prints the literature Reactome attaches to a curated pathway for that reason. The data are public domain: All data in the Reactome database and files derived from that data are licensed under the Creative Commons Public Domain Dedication (CC0). User may copy, modify, and distribute these data, even for commercial purposes, without asking for permission. Attribution is encouraged but not required. [R10] The pathway illustrations are licensed apart, under CC BY 4.0, and none is shown here.

A gene on this list is one Reactome places in this pathway in this release, and that is all the row says: it does not say the gene is expressed in a tissue or associated with a disease, which are the other two explorers' questions, read from other sources. Reactome's papers of record are [R01] [R02].

[R01] Ragueneau E, Gong C, Sinquin P, Sevilla C, Beavers D, Grentner A, et al. (2026). The Reactome Knowledgebase 2026. Nucleic Acids Research 54:D673-D681. PMID 41251150, doi 10.1093/nar/gkaf1223.
[R02] Milacic M, Beavers D, Conley P, Gong C, Gillespie M, Griss J, et al. (2024). The Reactome Pathway Knowledgebase 2024. Nucleic Acids Research 52:D672-D678. PMID 37941124, doi 10.1093/nar/gkad1025.
[R10] Reactome, reactome.org. License Agreement. https://reactome.org/license, read 2026-09-09.
[R12] Reactome, reactome.org. Citing us. https://reactome.org/cite, read 2026-09-09.
[R13] Reactome, reactome.org. Download. https://reactome.org/download-data, read 2026-09-09.

Stable id: R-HSA-3214858.4
Class: Pathway
Species: Homo sapiens (human)
Inferred: no: a curated human pathway
Disease pathway: no
Released: 2014-06-10
Last updated: 2021-09-15
Events inside: 22, counted from the record

Arginine methylation is a common post-translational modification; around 2% of arginine residues are methylated in rat liver nuclei (Boffa et al. 1977). Arginine can be methylated in 3 different ways: monomethylarginine (MMA); NG,NG-asymmetric dimethylarginine (ADMA) and NG,N'G-symmetric dimethylarginine (SDMA). The formation of MMA, ADMA and SDMA in mammalian cells is carried out by members of a family of nine protein arginine methyltransferases (PRMTs) (Bedford & Clarke 2009).

Type I, II and III PRMTs generate MMA on one of the two terminal guanidino nitrogen atoms. Subsequent generation of asymmetric dimethylarginine (ADMA) is catalysed by the type I enzymes PRMT1, PRMT2, PRMT3, co-activator-associated arginine methyltransferase 1 (CARM1), PRMT6 and PRMT8. Production of symmetric dimethylarginine (SDMA) is catalysed by the type II enzymes PRMT5 and PRMT7. On certain substrates, PRMT7 also functions as a type III enzyme, generating MMA only. PRMT9 activity has not been characterized. No known enzyme is capable of both ADMA and SDMA modifications. Arginine methylation is regarded as highly stable; no arginine demethylases are known (Yang & Bedford 2013).

Most PRMTs methylate glycine- and arginine-rich (GAR) motifs in their substrates (Boffa et al. 1977). CARM1 methylates a proline-, glycine- and methionine-rich (PGM) motif (Cheng et al. 2007). PRMT5 can dimethylate arginine residues in GAR and PGM motifs (Cheng et al. 2007, Branscombe et al. 2001).

PRMTs are widely expressed and are constitutively active as purified recombinant proteins. However, PRMT activity can be regulated through PTMs, association with regulatory proteins, subcellular compartmentalization and factors that affect enzyme-substrate interactions. The target sites of PRMTs are influenced by the presence of other PTMs on their substrates. The best characterized examples of this are for histones. Histone H3 lysine-19 acetylation (H3K18ac) primes the histone tail for asymmetric dimethylation at arginine-18 (H3R17me2a) by CARM1 (An et al. 2003, Daujat et al. 2002, Yue et al. 2007). H3 lysine-10 acetylation (H3K9ac) blocks arginine-9 symmetric dimethylation (H3R8me2s) by PRMT5 (Pal et al. 2004). H4R3me2a catalyzed by PRMT1 favours subsequent acetylation of the histone H4 tail (Huang et al. 2005). At the same time histone H4 lysine-5 acetylation (H4K5ac) makes the H4R3 motif a better substrate for PRMT5 compared with PRMT1, thereby moving the balance from an activating ADMA mark to a suppressive SDMA mark at the H4R3 motif (Feng et al. 2011). Finally methylation of Histone H3 on arginine-3 (H3R2me2a) by PRMT6 blocks methylation of H3 lysine-5 by the MLL complex (H3K4me3), and vice versa, methylation of H3K4me3 prevents H3R2me2a methylation (Guccione et al. 2007, Kirmizis et al. 2007, Hyllus et al. 2007). N.B. The coordinates of post-translational modifications represented and described here follow UniProt standard practice whereby coordinates refer to the translated protein before any further processing. Histone literature typically refers to coordinates of the protein after the initiating methionine has been removed. Therefore the coordinates of post-translated residues in the Reactome database and described here are frequently +1 when compared with the literature.

Literature Reactome attaches

Protein arginine methylation in mammals: who, what, and whyMol. Cell, 2009, vol. 33, p. 1-13PubMed 19150423
Protein arginine methyltransferases and cancerNat. Rev. Cancer, 2013, vol. 13, p. 37-50PubMed 23235912

Reactome's record lists 14 orthologous events, R-MMU-3214858 (Mus musculus), R-RNO-3214858 (Rattus norvegicus) among the species this site serves, and 12 in species this site opens no page for.

Reactome ContentService, this pathway's record · Reactome v97 · read 2026-09-30 ET · Reactome pathway browser"RMTs methylate histone arginines". Reactome, release 97, https://reactome.org/PathwayBrowser/#/R-HSA-3214858 with StableID: R-HSA-3214858.4 (accessed 2026-09-30 ET). Reactome version 97 (CC0).

Reading this pathway's record from Reactome (the pathway record).Still reading. A first read of a pathway can take a while; this page waits up to 35 seconds for it, and its scripts then bring in the panel, or a line saying what did not arrive.

02The genes

Genes Reactome places in this human pathway

The mapping files place 78 genes in this human pathway; showing 1 to 78, in pages of 100, sorted by symbol for reading. The order carries no ranking.

Genes Reactome places in this human pathway, page 1 of 1
Gene	Authority id	Mapping file id	Evidence codes
GeneACTL6A	AuthorityHGNC:24124	Mapping file id86 NCBI file	EvidenceTAS
GeneACTL6B	AuthorityHGNC:160	Mapping file id51412 NCBI file	EvidenceTAS
GeneARID1A	AuthorityHGNC:11110	Mapping file id8289 NCBI file	EvidenceTAS
GeneARID1B	AuthorityHGNC:18040	Mapping file id57492 NCBI file	EvidenceTAS
GeneARID2	AuthorityHGNC:18037	Mapping file id196528 NCBI file	EvidenceTAS
GeneCARM1	AuthorityHGNC:23393	Mapping file id10498 NCBI file	EvidenceTAS
GeneCCND1	AuthorityHGNC:1582	Mapping file id595 NCBI file	EvidenceTAS
GeneCDK4	AuthorityHGNC:1773	Mapping file id1019 NCBI file	EvidenceTAS
GeneCOPRS	AuthorityHGNC:28848	Mapping file id55352 NCBI file	EvidenceTAS
GeneDNMT3A	AuthorityHGNC:2978	Mapping file id1788 NCBI file	EvidenceTAS
GeneH2AB1	AuthorityHGNC:22516	Mapping file id474382 NCBI file	EvidenceTAS
GeneH2AC1	AuthorityHGNC:18729	Mapping file id221613 NCBI file	EvidenceTAS
GeneH2AC11	AuthorityHGNC:4737	Mapping file id8969 NCBI file	EvidenceTAS
GeneH2AC12	AuthorityHGNC:13671	Mapping file id85235 NCBI file	EvidenceTAS
GeneH2AC13	AuthorityHGNC:4725	Mapping file id8329 NCBI file	EvidenceTAS
GeneH2AC14	AuthorityHGNC:4727	Mapping file id8331 NCBI file	EvidenceTAS
GeneH2AC15	AuthorityHGNC:4726	Mapping file id8330 NCBI file	EvidenceTAS
GeneH2AC16	AuthorityHGNC:4730	Mapping file id8332 NCBI file	EvidenceTAS
GeneH2AC17	AuthorityHGNC:4735	Mapping file id8336 NCBI file	EvidenceTAS
GeneH2AC18	AuthorityHGNC:4736	Mapping file id8337 NCBI file	EvidenceTAS
GeneH2AC19	AuthorityHGNC:29668	Mapping file id723790 NCBI file	EvidenceTAS
GeneH2AC20	AuthorityHGNC:4738	Mapping file id8338 NCBI file	EvidenceTAS
GeneH2AC21	AuthorityHGNC:20508	Mapping file id317772 NCBI file	EvidenceTAS
GeneH2AC25	AuthorityHGNC:20507	Mapping file id92815 NCBI file	EvidenceTAS
GeneH2AC4	AuthorityHGNC:4734	Mapping file id8335 NCBI file	EvidenceTAS
GeneH2AC6	AuthorityHGNC:4733	Mapping file id8334 NCBI file	EvidenceTAS
GeneH2AC7	AuthorityHGNC:4729	Mapping file id3013 NCBI file	EvidenceTAS
GeneH2AC8	AuthorityHGNC:4724	Mapping file id3012 NCBI file	EvidenceTAS
GeneH2AJ	AuthorityHGNC:14456	Mapping file id55766 NCBI file	EvidenceTAS
GeneH2AX	AuthorityHGNC:4739	Mapping file id3014 NCBI file	EvidenceTAS
GeneH2AZ2	AuthorityHGNC:20664	Mapping file id94239 NCBI file	EvidenceTAS
GeneH3C1	AuthorityHGNC:4766	Mapping file id8350 NCBI file	EvidenceTAS
GeneH3C10	AuthorityHGNC:4775	Mapping file id8357 NCBI file	EvidenceTAS
GeneH3C11	AuthorityHGNC:4771	Mapping file id8354 NCBI file	EvidenceTAS
GeneH3C12	AuthorityHGNC:4774	Mapping file id8356 NCBI file	EvidenceTAS
GeneH3C13	AuthorityHGNC:25311	Mapping file id653604 NCBI file	EvidenceTAS
GeneH3C14	AuthorityHGNC:20503	Mapping file id126961 NCBI file	EvidenceTAS
GeneH3C15	AuthorityHGNC:20505	Mapping file id333932 NCBI file	EvidenceTAS
GeneH3C2	AuthorityHGNC:4776	Mapping file id8358 NCBI file	EvidenceTAS
GeneH3C3	AuthorityHGNC:4768	Mapping file id8352 NCBI file	EvidenceTAS
GeneH3C4	AuthorityHGNC:4767	Mapping file id8351 NCBI file	EvidenceTAS
GeneH3C6	AuthorityHGNC:4769	Mapping file id8353 NCBI file	EvidenceTAS
GeneH3C7	AuthorityHGNC:4773	Mapping file id8968 NCBI file	EvidenceTAS
GeneH3C8	AuthorityHGNC:4772	Mapping file id8355 NCBI file	EvidenceTAS
GeneH4C1	AuthorityHGNC:4781	Mapping file id8359 NCBI file	EvidenceTAS
GeneH4C11	AuthorityHGNC:4785	Mapping file id8363 NCBI file	EvidenceTAS
GeneH4C12	AuthorityHGNC:4784	Mapping file id8362 NCBI file	EvidenceTAS
GeneH4C13	AuthorityHGNC:4791	Mapping file id8368 NCBI file	EvidenceTAS
GeneH4C14	AuthorityHGNC:4794	Mapping file id8370 NCBI file	EvidenceTAS
GeneH4C15	AuthorityHGNC:29607	Mapping file id554313 NCBI file	EvidenceTAS
GeneH4C16	AuthorityHGNC:20510	Mapping file id121504 NCBI file	EvidenceTAS
GeneH4C2	AuthorityHGNC:4789	Mapping file id8366 NCBI file	EvidenceTAS
GeneH4C3	AuthorityHGNC:4787	Mapping file id8364 NCBI file	EvidenceTAS
GeneH4C4	AuthorityHGNC:4782	Mapping file id8360 NCBI file	EvidenceTAS
GeneH4C5	AuthorityHGNC:4790	Mapping file id8367 NCBI file	EvidenceTAS
GeneH4C6	AuthorityHGNC:4783	Mapping file id8361 NCBI file	EvidenceTAS
GeneH4C8	AuthorityHGNC:4788	Mapping file id8365 NCBI file	EvidenceTAS
GeneH4C9	AuthorityHGNC:4793	Mapping file id8294 NCBI file	EvidenceTAS
GeneJAK2	AuthorityHGNC:6192	Mapping file id3717 NCBI file	EvidenceTAS
GenePBRM1	AuthorityHGNC:30064	Mapping file id55193 NCBI file	EvidenceTAS
GenePRMT1	AuthorityHGNC:5187	Mapping file id3276 NCBI file	EvidenceTAS
GenePRMT3	AuthorityHGNC:30163	Mapping file id10196 NCBI file	EvidenceTAS
GenePRMT5	AuthorityHGNC:10894	Mapping file id10419 NCBI file	EvidenceTAS
GenePRMT6	AuthorityHGNC:18241	Mapping file id55170 NCBI file	EvidenceTAS
GenePRMT7	AuthorityHGNC:25557	Mapping file id54496 NCBI file	EvidenceTAS
GeneRBBP7	AuthorityHGNC:9890	Mapping file id5931 NCBI file	EvidenceTAS
GeneRPS2	AuthorityHGNC:10404	Mapping file id6187 NCBI file	EvidenceTAS
GeneSMARCA2	AuthorityHGNC:11098	Mapping file id6595 NCBI file	EvidenceTAS
GeneSMARCA4	AuthorityHGNC:11100	Mapping file id6597 NCBI file	EvidenceTAS
GeneSMARCB1	AuthorityHGNC:11103	Mapping file id6598 NCBI file	EvidenceTAS
GeneSMARCC1	AuthorityHGNC:11104	Mapping file id6599 NCBI file	EvidenceTAS
GeneSMARCC2	AuthorityHGNC:11105	Mapping file id6601 NCBI file	EvidenceTAS
GeneSMARCD1	AuthorityHGNC:11106	Mapping file id6602 NCBI file	EvidenceTAS
GeneSMARCD2	AuthorityHGNC:11107	Mapping file id6603 NCBI file	EvidenceTAS
GeneSMARCD3	AuthorityHGNC:11108	Mapping file id6604 NCBI file	EvidenceTAS
GeneSMARCE1	AuthorityHGNC:11109	Mapping file id6605 NCBI file	EvidenceTAS
GeneWDR5	AuthorityHGNC:12757	Mapping file id11091 NCBI file	EvidenceTAS
GeneWDR77	AuthorityHGNC:29652	Mapping file id79084 NCBI file	EvidenceTAS

Evidence codes on this page: TAS, as the mapping file writes them; a row carrying two was written twice by the file, once under each. The mapping file id says which file placed the gene: an NCBI Gene id from NCBI2Reactome_All_Levels.txt, an Ensembl gene id from Ensembl2Reactome_All_Levels.txt. The two files can disagree about a code, so a row's codes are the one file's view. Measured by this site's build over this release on 2026-09-09: of the 138,908 human pathway-gene pairs both files place, 207 (0.149 per cent, over 47 genes) carry TAS in the Ensembl file where the NCBI rows carry IEA alone.

Reactome mapping files, the human rows for this pathway · Reactome release 97 · read 2026-09-09 · Reactome downloads"NCBI2Reactome_All_Levels.txt" and "Ensembl2Reactome_All_Levels.txt", Reactome, release 97, https://reactome.org/download-data/ (date of access 2026-09-09). Data CC0; attribution encouraged.

03The hierarchy

Parents and children in this release's hierarchy

Parents

Chromatin modifying enzymesR-HSA-3247509272 genes

Children

None: no pathway of this release's list names this one as a parent.

Reactome's hierarchy is a graph rather than a tree: a pathway can sit under more than one parent, and the gene counts are each pathway's own placements at every level under it, so a parent's count is not the sum of its children's.

Reactome, the human pathway list and hierarchy relationship file · Reactome release 97 · read 2026-09-09 · Reactome downloads"ReactomePathways.txt" and "ReactomePathwaysRelation.txt", Reactome, release 97, https://reactome.org/download-data/ (date of access 2026-09-09). Data CC0; attribution encouraged.