Search results for PRMT5

Showing 18 results out of 28

×

Species

Types

Compartments

Reaction types

Search properties

Species

Types

Compartments

Reaction types

Search properties

Protein (4 results from a total of 4)

Identifier: R-HSA-5205609
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: UniProt: PRMT5: O14744
Identifier: R-HSA-191876
Species: Homo sapiens
Compartment: cytosol
Primary external reference: UniProt: PRMT5: O14744
Identifier: R-HSA-5211300
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: UniProt: PRMT5: O14744
Identifier: R-HSA-5212681
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: UniProt: COPRS: Q9NQ92

Reaction (5 results from a total of 14)

Identifier: R-HSA-3215406
Species: Homo sapiens
Compartment: nucleoplasm
In mammalian cells, PRMT5 is tightly bound by WDR77 (MEP50). This interaction is required for PRMT5 activity (Friesen et al. 2002). The structure of PRMT5 and WDR77 (MEP50) was determined, bound to an S-adenosylmethionine analog and a peptide substrate derived from histone H4. The structure reveals a hetero-octameric complex formation, with close interaction between the seven-bladed beta-propeller WDR77 (MEP50) and the N-terminal domain of human PRMT5 (Antonysamy et al. 2012, Ho et al. 2013)
Identifier: R-HSA-6804379
Species: Homo sapiens
Compartment: nucleoplasm
TTC5 (Strap) recruits protein arginine methyltransferase PRMT5 to TP53 (p53) (Jansson et al. 2008).
Identifier: R-HSA-6804383
Species: Homo sapiens
Compartment: nucleoplasm
Protein arginine methyltransferase PRMT5, recruited to TP53 (p53) by TTC5 (Strap), monomethylates TP53 on arginine residue R333 and dimethylates TP53 arginine residues R335 and R337. PRMT5-mediated methylation of TP53 modulates the affinity of TP53 for target promoters, promoting expression of cell cycle arrest genes rather than cell death genes (Jansson et al. 2008).
Identifier: R-HSA-3215391
Species: Homo sapiens
Compartment: nucleoplasm
Tyrosine phosphorylation of PRMT5 can block WDR77 (MEP50) binding, which attenuates PRMT5 activity (Liu et al. 2011). The kinase JAK2 is constitutively activated by the mutation V617F, observed in most patients with non-chronic myelogenous leukemia (nCML) myeloproliferative neoplasms (MPNs) (Liu et al. 2011). JAK2 V617F can phosphorylate STAT5 in the absence of upstream signals, which confers cytokine-independent growth to Ba/F3 cells and induces a myeloproliferative disease in mouse models (Akada et al. 2010, Marty et al., 2010, Mullally et al. 2010). JAK2 V617F phosphorylates PRMT5 predominantly at tyrosines 297, 304, and 307, significantly reducing the activity-enhancing interaction between PRMT5 and WDR77 (MEP50) (Liu et al. 2011).
Identifier: R-HSA-3215426
Species: Homo sapiens
Compartment: nucleoplasm
The histone-binding protein cooperator of PRMT5 (COPRS) guides PRMT5:WDR77 to methylate histone H4 arginine-4 (H4R3) rather than histone H3 arginine-9 (H3R8) (Lacroix et al. 2008).

Complex (5 results from a total of 6)

Identifier: R-HSA-5205601
Species: Homo sapiens
Compartment: nucleoplasm
Identifier: R-HSA-5205617
Species: Homo sapiens
Compartment: nucleoplasm
Identifier: R-HSA-5205612
Species: Homo sapiens
Compartment: nucleoplasm
Identifier: R-HSA-5205604
Species: Homo sapiens
Compartment: nucleoplasm
Identifier: R-HSA-5212675
Species: Homo sapiens
Compartment: nucleoplasm

Set (1 results from a total of 1)

Identifier: R-HSA-5225622
Species: Homo sapiens
Compartment: nucleoplasm

Pathway (2 results from a total of 2)

Identifier: R-HSA-3214858
Species: Homo sapiens
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.
Identifier: R-HSA-6804760
Species: Homo sapiens
TP53 (p53) undergoes methylation on several lysine and arginine residues, which modulates its transcriptional activity.

PRMT5, recruited to TP53 as part of the ATM-activated complex that includes TTC5, JMY and EP300 (p300), methylates TP53 arginine residues R333, R335 and R337. PRMT5-mediated methylation promotes TP53-stimulated expression of cell cycle arrest genes (Shikama et al. 1999, Demonacos et al. 2001, Demonacos et al. 2004, Adams et al. 2008, Adams et al. 2012). SETD9 (SET9) methylates TP53 at lysine residue K372, resulting in increased stability and activity of TP53 (Chuikov et al. 2004, Couture et al. 2006, Bai et al. 2011).

TP53 transcriptional activity is repressed by SMYD2-mediated methylation of TP53 at lysine residue K370 (Huang et al. 2006). Dimethylation of TP53 at lysine residue K373 by the complex of methyltransferases EHMT1 and EHMT2 also represses TP53-mediated transcription (Huang et al. 2010). The chromatin compaction factor L3MBTL1 binds TP53 monomethylated at lysine K382 by SETD8 (SET8) and, probably through changing local chromatin architecture, represses transcription of TP53 targets (West et al. 2010). The histone lysine-specific demethylase LSD1 interacts with TP53 and represses p53-mediated transcriptional activation (Huang et al. 2007). PRMT1 and CARM1 can also modulate p53 functions in a cooperative manner (An et al. 2004).

Icon (1 results from a total of 1)

Species: Homo sapiens
Protein arginine N-methyltransferase 5
Cite Us!