2.1.1.320: type II protein arginine methyltransferase
This is an abbreviated version!
For detailed information about type II protein arginine methyltransferase, go to the full flat file.
Word Map on EC 2.1.1.320
-
2.1.1.320
-
histone
-
methyltransferases
-
chromatin
-
prmts
-
dimethylarginine
-
tumorigenesis
-
h4r3me2s
-
monomethylation
-
spliceosomal
-
mep50
-
methylosome
-
ribonucleoproteins
-
non-histone
-
pre-mrna
-
snrnps
-
picln
-
monomethylarginine
-
methylthioadenosine
-
tudor
-
menin
-
protein-arginine
-
medicine
- 2.1.1.320
- histone
- methyltransferases
- chromatin
-
prmts
- dimethylarginine
- tumorigenesis
-
h4r3me2s
-
monomethylation
-
spliceosomal
- mep50
-
methylosome
- ribonucleoproteins
-
non-histone
- pre-mrna
-
snrnps
-
picln
-
monomethylarginine
- methylthioadenosine
-
tudor
-
menin
- protein-arginine
- medicine
Reaction
2 S-adenosyl-L-methionine
+
Synonyms
At4g31120, EC 2.1.1.124, EC 2.1.1.125, EC 2.1.1.126, EC 2.1.1.23, Hsl7, Jak-binding protein 1, Janus kinase-binding protein 1, JBP1, PRMT-5, PRMT-9, PRMT15, PRMT5, PRMT7, PRMT9, protein arginine methyltransferase 5, Skb1
ECTree
2.1.1.320 type II protein arginine methyltransferaseAdvanced search results
results (
results (General Information
General Information on EC 2.1.1.320 - type II protein arginine methyltransferase
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
top
GENERAL INFORMATION 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
drug target
malfunction
prmt5 loss in zebrafish leads to the expression of an infertile male phenotype due to a reduction in germ cell number, an increase in germ cell apoptosis and the failure of gonads to differentiate into normal testes or ovaries. Arginine methylation of the germ cell-specific proteins Zili and Vasa, as well as histones H3 (H3R8me2s) and H4 (H4R3me2s), is reduced in the gonads of prmt5-null zebrafish
physiological function
drug target
targeting PRMT5 offers a great opportunity to combat cancer in an efficient and selective way
drug target
the enzyme is a promising therapeutic target for human cancer
physiological function
arginine methyltransferases type II PRMT5 and type I PRMT4 mutants show similar alterations in flowering time, photomorphogenic responses and salt stress tolerance, while only prmt5 mutants exhibited alterations in circadian rhythms. PRMT5 and PRMT4s coregulate the expression and splicing of key regulatory genes associated with transcription, RNA processing, responses to light, flowering, and abiotic stress tolerance
physiological function
at 10 hours post-fertilization, Prmt7 morphants display an epibolic delay defects phenotype compared with control embryos that have completed epiboly and entirely enclosed the yolk sphere. Both shape and orientation of enveloping layer cells in Prmt7 morphants are altered. In control embryos, enveloping layer cells are elongated and regularly aligned. Enveloping layer cells in Prmt7 morphants are mostly round, small, and irregularly aligned more disorganized and fail to align their cell bodies along the direction of epibolic movement
physiological function
both PRMT5 alone and PRMT5 in complex with MEP50 are able to generate di-methylated H4 peptide product. The PRMT5:MEP50 complex consistently has a higher level of methyltransferase activity compared with PRMT5
physiological function
Caenorhabditis elegans lacking PRMT-5 are hypersensitive to dilute octanol. PRMT-5 contributes to the regulation of locomotion by both exogenous and endogenous dopamine
physiological function
-
deletion of Prmt5 results in germ cell depletion in adult mice. Germ cell loss is first observed between embryonic days 12.5 and 13.5, and very few of these cells remain at birth. Oct4, Sox2, and Nanog are abundantly expressed in Prmt5-deficient germ cells, whereas their expression is dramatically decreased in control germ cells. The expression of meiosis-associated genes is virtually absent in Prmt5-deficient female germ cells at embryonic day 13.5 , whereas the expression of other germ cell-specific genes is not changed. Methylation of histine H4R3 is completely absent after Prmt5 inactivation, whereas the level of histone H3R2 is not changed
physiological function
inactivation of isoform Prmt5 in skeletal muscle stem cells of adult mice prevents expansion of skeletal muscle stem cells, abolishes long-term skeletal muscle stem cells maintenance and abrogates skeletal muscle regeneration. Prmt5 is dispensable for proliferation and differentiation of Pax7+ myogenic progenitor cells during mouse embryonic development. Prmt5 controls proliferation of adult skeletal muscle stem cells by direct epigenetic silencing of the cell cycle inhibitor p21
physiological function
isoform PRMT5 binds to a nuclear protein, called cooperator of PRMT5, i.e. COPR5. COPR5 modulates the substrate specificity of nuclear PRMT5-containing complexes, at least towards histones. Rcombinant COPR5 binds to the amino terminus of histone H4 and is required to recruit PRMT5 to reconstituted nucleosomes in vitro. COPR5 depletion in cells strongly reduces PRMT5 recruitment on chromatin at the PRMT5 target gene cyclin E1 in vivo
physiological function
isoform Prmt5 forms a complex with methylosome protein Mep50 that specifically methylates predeposition histones H2A/H2A.X-F and H4 and the histone chaperone nucleoplasmin on a conserved motif (GRGXK). Nucleoplasmin is a potent substrate for Prmt5-Mep50 and modulates Prmt5-Mep50 activity directed toward histones. Histone H2A and nucleoplasmin methylation appears late in oogenesis and is most abundant in the laid egg
physiological function
isoform PRMT5 interacts with candidate tumor suppressor gene RASSF1A. Coexpression of RASSF1A and PRMT5 leads to a redistribution of PRMT5 from the cytosol to stabilized microtubules, where RASSF1A and PRMT5 become colocalized. PRMT5 translocates to bundled microtubules on stabilization by RASSF1A expression
physiological function
isoform PRMT5 interacts with the golgin GM130, and depletion of PRMT5 causes defects in Golgi ribbon formation. PRMT5 methylates N-terminal arginine residues in GM130, and such arginine methylation appears critical for Golgi apparatus ribbon formation
physiological function
isoform PRMT5 is down-regulated by amyloid-beta in primary neurons and SH-SY5Y cells, and this is associated with the up-regulation of the PRMT5 target protein E2F-1. Knockdown of PRMT5 in SH-SY5Y cells over-expressing the Swedish mutant form of human amyloid-beta precursor protein causes activation of E2F-1/p53/Bax, NF-kappaB, and GSK-3beta pathways, which coincides with increased apoptosis. Co-depletion of E2F-1 reduces the activation of p53/Bax, NF-kappaB, and GSK-3beta, and limits cell apoptosis
physiological function
isoform PRMT5 knockdown leads to an enlarged Giantin pattern, which is prevented by the expression of either original isoform PRMT5L or evolutionary emerged splice variant PRMT5S. Rescuing PRMT5S also increases the percentage of cells with an interphase Giantin pattern compacted at one end of the nucleus, consistent with its cell cycle-arresting effect, while rescuing PRMT5L increases that of the mitotic Giantin patterns of dynamically fragmented structures. Both isoforms also similarly regulate over a thousand genes particularly those involved in apoptosis and differentiation
physiological function
knockdown of isoform PRMT5 results in a reduction in symmetric dimethyl arginine modifcation of the SM protein set of small nuclear ribonucleoproteins. A similar effect is observed when cells are treated with siRNAs targeting methylosome protein MEP50. Isoform PRMT7, EC 2.1.1.321, knockdown also causes a reduction in Sm protein symmetric dimethylarginine modification. Double depletion of both PRMT5 and PRMT7 does not disrupt the modification to a greater extent than either single depletion alone. PRMT7 is not able to restore symmetric dimethylarginine modification of the Sm proteins in cells that are depleted of PRMT5. Cytoplasmic small nuclear ribonucleoprotein assembly requires the activities of both PRMT5 and PRMT7, and Sm protein symmetric dimethylarginine modification is primarily required for cytoplasmic small nuclear ribonucleoprotein assembly
physiological function
knockdown of isoform PRMT5 results in more paralysis in a Caenorhabditis elegans model of Alzheimer's disease
physiological function
Loss of PRMT5 in conditional KO mice triggers an initial but transient expansion of hematopoietic stem cells. Prmt5 deletion results in a concurrent loss of hematopoietic progenitor cells, leading to fatal bone marrow aplasia. PRMT5-specific effects on hematopoiesis are cell intrinsic and depend on PRMT5 methyltransferase activity. PRMT5-deficient hematopoietic stem and progenitor cells exhibit severely impaired cytokine signaling as well as upregulation of p53 and expression of its downstream targets
physiological function
prmt5 mutants are impaired in light inhibition of hypocotyl elongation. Loss of PRMT5 function affects both the period and strength of expression of multiple clock genes
physiological function
-
siRNA-mediated depletion of PRMT5 primary oligodendrocyte progenitor cells abrogates oligodendrocyte differentiation. PRMT5-depleted oligodendrocyte progenitor and C6 glioma cells express high levels of the inhibitors of differentiation/DNA binding, Id2 and Id4, known repressors of glial cell differentiation. CpG-rich islands within the Id2 and Id4 genes are bound by PRMT5 and are hypomethylated in PRMT5-deficient cells
physiological function
epigenetic regulation by the type II protein arginine methyltransferase, PRMT5, plays an essential role in the control of cancer cell proliferation and tumorigenesis. PRMT5 governs expression of prosurvival genes by promoting WNT/beta-CATENIN and AKT/GSK3x02 proliferative signaling
physiological function
in stem cells, PRMT5 is only required for proliferation, and not pluripotency, through methylation of the cell cycle-regulated p57. In keratinocyte differentiation involucrin gene expression is partially controlled by PKC-delta suppression of PRMT5. In the human osteosarcoma cell line U2OS, PRMT5, Strap and p53 form a complex in response to DNA damage
physiological function
methylation of KRAB-associated protein 1 (KAP1) arginine residues regulates the KAP1-ZNF224 interaction, thus suggesting that this KAP1 post-translational modification can actively contribute to the regulation of ZNF224-mediated repression
physiological function
PRMT5 and PRMT1 are involved in the interaction between CFLARL (a CASP8 and FADD-like apoptosis regulator) and the E3 ligase ITCH. The PRMT5 silencing and PRMT1 overexpression enhance the interaction between CFLARL and ITCH, leading to an altered ubiquitination level and, eventually, the degradation of CFLARL
physiological function
PRMT5 expression, localization, and activity are altered following denervation-induced inactivity
physiological function
PRMT5 inhibition induces mouse primary lymphoma cell death through inactivation of AKT/GSK3x02 and WNT/beta-CATENIN proliferative signaling
physiological function
protein arginine methyltransferase 5 (Prmt5) symmetrically dimethylates arginine in nuclear and cytoplasmic proteins. Prmt5 is involved in a variety of cellular processes, including ribosome biogenesis, cellular differentiation, germ cell development and tumorigenesis
physiological function
the enzyme (PRMT-5) regulates SER-2 tyramine receptor-mediated behaviors in Caenorhabditis elegans
physiological function
the enzyme (PRMT-9) may play a regulatory role in nematode alternative RNA splicing
physiological function
the enzyme (PRMT5) is a major enzyme responsible for symmetric dimethylation of arginine residues on both histone and non-histone proteins, regulating many biological pathways in mammalian cells
physiological function
the enzyme (PRMT5) is essential for IFN-gamma induced, CIITA-dependent MHC II transactivation by promoting histone H3R2 methylation in macrophages. Over-expression of PRMT5 potentiates IFN-gamma induced activation of MHC II transcription in an enzyme activity-dependent manner. Pathophysiologically relevant role for PRMT5 in MHC II transactivation in macrophages
physiological function
the enzyme (PRMT5) is essential for IFN-gamma induced, CIITA-dependent MHC II transactivation by promoting histone H3R2 methylation in macrophages. Over-expression of PRMT5 potentiates IFN-gamma induced activation of MHC II transcription in an enzyme activity-dependent manner. Pathophysiologically relevant role for PRMT5 in MHC II transactivation in macrophages
physiological function
the enzyme (PRMT5) is involved in tumour initiation, progression, invasion, metastasis as well as poor prognosis in cancer. Increased expression of PRMT5-MEP50 is correlated with the growth of cancer cells
physiological function
the enzyme (PRMT5) may be involved in tachyzoite-bradyzoite transformation
physiological function
the protein arginine methyltransferases 1 and 5 affect Myc properties in glioblastoma stem cells. Myc associates with both PRMT1 and PRMT5 being differentially dimethylated. Symmetric (S) by PRMT1 dimethylation protects Myc from degradation, while asymmetric (AS) dimethylation by PRMT5 allows Myc proper turnover. We hypothesize S-Myc as typical of aggressive glioblastoma stem cells, as S-Myc/AS-Myc ratio decreases in differentiating, less aggressive, cells
physiological function
WD repeat domain 77 (WDR77), also known as p44 forms a stoichiometric complex with PRMT5. The PRMT5/p44 complex is required for cellular proliferation of lung and prostate epithelial cells during earlier stages of development and is re-activated during prostate and lung tumorigenesis. PRMT5 and p44 regulate expression of a specific set of genes encoding growth and anti-growth factors, including receptor tyrosine kinases and antiproliferative proteins. Genes whose expression is suppressed by PRMT5 and p44 encode anti-growth factors and inhibit cell growth when ectopically expressed. Genes whose expression is enhanced by PRMT5 and p44 encode growth factors and increased cell growth when expressed. Altered expression of target genes is associated with reactivation of PRMT5 and p44 during lung tumorigenesis
physiological function
-
the enzyme (PRMT5) may be involved in tachyzoite-bradyzoite transformation
-
