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Information on EC 2.1.1.321 - type III protein arginine methyltransferase and Organism(s) Homo sapiens and UniProt Accession Q9NVM4
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2.1.1.321 type III protein arginine methyltransferaseIUBMB Comments
Type III protein arginine methyltransferases catalyse the single methylation of one of the terminal nitrogen atoms of the guanidino group in an L-arginine residue within a protein. Unlike type I and type II protein arginine methyltransferases, which also catalyse this reaction, type III enzymes do not methylate the substrate any further. cf. EC 2.1.1.319, type I protein arginine methyltransferase, EC 2.1.1.320, type II protein arginine methyltransferase, and EC 2.1.1.322, type IV protein arginine methyltransferase.
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Word Map
- 2.1.1.321
- prmt7
- histone
-
monomethylation
- metastasis
-
monomethylarginine
- dimethylarginine
-
nanog
- adomet
- medicine
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
Synonyms
protein arginine methyltransferase 7, prmt-7, type iii protein arginine methyltransferase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
PRMT7
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SYSTEMATIC NAME
IUBMB Comments
S-adenosyl-L-methionine:[protein]-L-arginine N-methyltransferase ([protein]-Nomega-methyl-L-arginine-forming)
Type III protein arginine methyltransferases catalyse the single methylation of one of the terminal nitrogen atoms of the guanidino group in an L-arginine residue within a protein. Unlike type I and type II protein arginine methyltransferases, which also catalyse this reaction, type III enzymes do not methylate the substrate any further. cf. EC 2.1.1.319, type I protein arginine methyltransferase, EC 2.1.1.320, type II protein arginine methyltransferase, and EC 2.1.1.322, type IV protein arginine methyltransferase.
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
2 S-adenosyl-L-methionine + [protein]-L-arginine
2 S-adenosyl-L-homocysteine + [protein]-Nomega-dimethyl-L-arginine
the enzyme has a strong preference for RXR motifs surrounded by basic amino acids
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-
?
3 S-adenosyl-L-methionine + SGRGKGGKGLGKGGAKRHRK-NH2
3 S-adenosyl-L-homocysteine + SG-(Nomega-Me)RGKGGKGLGKGGAK-(Nomega-Me)RH-(Nomega-Me)RK-NH2
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-
-
?
5 S-adenosyl-L-methionine + AGRGRGKAAILKAQVAARGRGRGMGRGN-NH2
5 S-adenosyl-L-homocysteine + AG-(Nomega-Me)RG-(Nomega-Me)RGKAAILKAQVAA-(Nomega-Me)RG-(Nomega-Me)RGRGMG-(Nomega-Me)RGN-NH2
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?
S-adenosyl-L-methionine + acetyl-GGRGG-NH2
S-adenosyl-L-homocysteine + acetyl-GG-(Nomega-methyl-)RGG-NH2
substrate is a synthetic peptide
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-
?
S-adenosyl-L-methionine + GGFGGRGGFG-NH2
S-adenosyl-L-homocysteine + GGFGG-(Nomega-methyl-)RGGFG-NH2
substrate is a synthetic peptide
product is monomethylated at residue R6
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?
S-adenosyl-L-methionine + GGPGGRGGPGG-NH2
S-adenosyl-L-homocysteine + GGPGG-Nomega-methyl-RGGPGG
substrate is a synthetic peptide
enzyme catalyzes monomethylation of Arg-residues
-
?
S-adenosyl-L-methionine + SG-(Nomega-methyl-)RGKGGKGLGKGGAKRHRK-NH2
S-adenosyl-L-homocysteine + SG-(Nomega-methyl-)RGKGGKGLGKGGAK-(Nomega-methyl-)RHRK-NH2
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-
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?
S-adenosyl-L-methionine + [beta-catenin]-L-arginine
S-adenosyl-L-homocysteine + [beta-catenin]-Nomega-methyl-L-arginine
S-adenosyl-L-methionine + [eukaryotic translation initiation factor 2alpha]-L-arginine
S-adenosyl-L-homocysteine + [eukaryotic translation initiation factor 2alpha]-Nomega-methyl-L-arginine
S-adenosyl-L-methionine + [GST-GAR]-L-arginine
S-adenosyl-L-homocysteine + [GST-GAR]-Nomega-methyl-L-arginine
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-
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?
S-adenosyl-L-methionine + [histone H2A]-L-arginine
S-adenosyl-L-homocysteine + [histone H2A]-Nomega-methyl-L-arginine
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-
-
?
S-adenosyl-L-methionine + [histone H2B]-L-arginine
S-adenosyl-L-homocysteine + [histone H2B]-Nomega-methyl-L-arginine
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-
-
?
S-adenosyl-L-methionine + [histone H3]-L-arginine
S-adenosyl-L-homocysteine + [histone H3]-Nomega-methyl-L-arginine
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-
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?
S-adenosyl-L-methionine + [histone H4R17]-L-arginine
S-adenosyl-L-homocysteine + [histone H4R17]-Nomega-methyl-L-arginine
S-adenosyl-L-methionine + [histone H4R3]-L-arginine
S-adenosyl-L-homocysteine + [histone H4R3]-Nomega-dimethyl-L-arginine
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-
?
S-adenosyl-L-methionine + [myelin basic protein]-L-arginine
S-adenosyl-L-homocysteine + [myelin basic protein]-Nomega-methyl-L-arginine
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?
S-adenosyl-L-methionine + [protein]-L-arginine
S-adenosyl-L-homocysteine + [protein]-Nomega-methyl-L-arginine
substrate preference for arginine residues in R-X-R motifs with additional flanking basic amino acid residues
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-
?
S-adenosyl-L-methionine + [Smb protein]-L-arginine
S-adenosyl-L-homocysteine + [Smb protein]-Nomega-methyl-L-arginine
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-
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?
S-adenosyl-L-methionine + [beta-catenin]-L-arginine
S-adenosyl-L-homocysteine + [beta-catenin]-Nomega-methyl-L-arginine
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-
?
S-adenosyl-L-methionine + [beta-catenin]-L-arginine
S-adenosyl-L-homocysteine + [beta-catenin]-Nomega-methyl-L-arginine
the enzyme (PRMT7) upregulates the expression of C-MYC via methylating beta-catenin and inhibiting the ubiquitin-mediated degradation of beta-catenin
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-
?
S-adenosyl-L-methionine + [eukaryotic translation initiation factor 2alpha]-L-arginine
S-adenosyl-L-homocysteine + [eukaryotic translation initiation factor 2alpha]-Nomega-methyl-L-arginine
PRMT7 methylates eukaryotic translation initiation factor 2alpha (eIF2alpha) and regulates its role in stress granule formation
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-
?
S-adenosyl-L-methionine + [eukaryotic translation initiation factor 2alpha]-L-arginine
S-adenosyl-L-homocysteine + [eukaryotic translation initiation factor 2alpha]-Nomega-methyl-L-arginine
PRMT7 methylates eukaryotic translation initiation factor 2alpha (eIF2alpha) within an RXR motif and regulates its role in stress granule formation
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?
S-adenosyl-L-methionine + [histone H4R17]-L-arginine
S-adenosyl-L-homocysteine + [histone H4R17]-Nomega-methyl-L-arginine
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-
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?
S-adenosyl-L-methionine + [histone H4R17]-L-arginine
S-adenosyl-L-homocysteine + [histone H4R17]-Nomega-methyl-L-arginine
crosstalk between PRMT7 and PRMT5, where methylation of a histone H4 peptide at R17, a PRMT7 substrate, may activate PRMT5 for methylation of R3
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?
S-adenosyl-L-methionine + [histone H4R17]-L-arginine
S-adenosyl-L-homocysteine + [histone H4R17]-Nomega-methyl-L-arginine
PRMT7-mediated monomethylation of histone H4 Arg17 regulates PRMT5 activity at Arg3 in the same protein
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?
additional information
?
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enzyme is capable of forming only omega-NG-monomethylarginine, not asymmetric omega-NG,NG-dimethylarginine or symmetric omega-NG,NG-dimethylarginine. No substrates: SGAGKGGKGLGKGGAKAHAK-NH2, GRG-NH2
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?
additional information
?
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enzyme is capable of forming only omega-NG-monomethylarginine, not asymmetric omega-NG,NG-dimethylarginine or symmetric omega-NG,NG-dimethylarginine. No substrates: SGAGKGGKGLGKGGAKAHAK-NH2, GRG-NH2
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-
?
additional information
?
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no substrate: GST-fibrillarin fusion protein containing fibrillarin residues 1-148, substrate of isoforms PRMT1, PRMT3, PRMT4, PRMT5, EC 2.1.1.319. Isoform PRMT7 neither methylates myelin basic protein or histone H2A, in vitro substrates of PRMT5
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?
additional information
?
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argininosuccinate synthetase (ASS1) specifically interacts with PRMT7 and that mutations in ASS1 at the interaction interface of PRMT7-ASS1 are detrimental. The interaction of PRMT7 with ASS1 implies that ASS1 might be a plausible substrate of PRMT7
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
S-adenosyl-L-methionine + [beta-catenin]-L-arginine
S-adenosyl-L-homocysteine + [beta-catenin]-Nomega-methyl-L-arginine
the enzyme (PRMT7) upregulates the expression of C-MYC via methylating beta-catenin and inhibiting the ubiquitin-mediated degradation of beta-catenin
-
-
?
S-adenosyl-L-methionine + [eukaryotic translation initiation factor 2alpha]-L-arginine
S-adenosyl-L-homocysteine + [eukaryotic translation initiation factor 2alpha]-Nomega-methyl-L-arginine
PRMT7 methylates eukaryotic translation initiation factor 2alpha (eIF2alpha) and regulates its role in stress granule formation
-
-
?
S-adenosyl-L-methionine + [histone H4R17]-L-arginine
S-adenosyl-L-homocysteine + [histone H4R17]-Nomega-methyl-L-arginine
S-adenosyl-L-methionine + [histone H4R3]-L-arginine
S-adenosyl-L-homocysteine + [histone H4R3]-Nomega-dimethyl-L-arginine
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-
-
?
S-adenosyl-L-methionine + [histone H4R17]-L-arginine
S-adenosyl-L-homocysteine + [histone H4R17]-Nomega-methyl-L-arginine
crosstalk between PRMT7 and PRMT5, where methylation of a histone H4 peptide at R17, a PRMT7 substrate, may activate PRMT5 for methylation of R3
-
-
?
S-adenosyl-L-methionine + [histone H4R17]-L-arginine
S-adenosyl-L-homocysteine + [histone H4R17]-Nomega-methyl-L-arginine
PRMT7-mediated monomethylation of histone H4 Arg17 regulates PRMT5 activity at Arg3 in the same protein
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?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
NaCl
sodium chloride strongly inhibits the activity of the human enzyme. Half maximal activity is seen at about 25 mM with a peptide substrate based on histone H2B and about 200 mM for the GST-GAR protein substrate
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
10 - 37
the enzyme is most active from 10°C to 25°C with less than 10% of the optimal activity at 37°C in vitro
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
isoform PRMT7 is expressed during embryonic testis development and interacts with imprinting control region-binding protein CTCFL/BORIS
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug target
overexpressed PRMT7 in clear cell renal cell carcinoma (ccRCC) cells acts as an oncogene to promote the growth of renal cell carcinoma through regulating the beta-catenin/C-MYC axis, thereby providing new strategies and targets for the treatment of ccRCC patients
malfunction
metabolism
overexpression of the PRMT7 gene is correlated with cancer metastasis in humans
physiological function
malfunction
humans lacking PRMT7 are characterized by significant intellectual developmental delays, hypotonia, and facial dysmorphisms
malfunction
humans lacking PRMT7 are characterized by significant intellectual developmental delays, hypotonia, and facial dysmorphisms. The overexpression of the PRMT7 gene is correlated with cancer metastasis in humans
malfunction
stress granule formation, in the face of eIF2alpha-dependent cellular stresses, is significantly diminished in PRMT7-knockdown
physiological function
imprinting control region-binding protein CTCFL/BORIS stimulates the histone-methyltransferase activity of PRMT7 via interactions with both histones and PRMT7
physiological function
knockdown of isoform PRMT5, EC 2.1.1.320, 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 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
PRMT7 negatively regulates expression of genes involved in DNA repair, including ALKBH5, APEX2, POLD1, and POLD2. PRMT7 and dimethylated histones H2AR3 and H4R3are enriched at target DNA repair genes in parental cells, whereas PRMT7 knockdown causes a significant decrease in PRMT7 recruitment and H2AR3/H4R3 methylation. Decreased PRMT7 expression also results in derepression of target DNA repair genes and enhanced cell resistance to DNA-damaging agents. BRG1 colocalizes with PRMT7 on target promoters and expression of a catalytically inactive form of BRG1results in derepression of PRMT7 target DNA repair genes
physiological function
reducing PRMT7 levels in invasive breast cancer cells using RNA interference significantly decreases cell invasion in vitro and metastasis in vivo. Overexpression of PRMT7 in non-aggressive MCF-7 cells enhances their invasiveness. PRMT7 induces the expression of matrix metalloproteinase MMP9. Invasion of aggressive breast cancer cells depleted of PRMT7 may be rescued by the exogenous expression of MMP9
physiological function
in human cell lines PRMT7 expression and subsequent methylation of histone H4R3 leads to repression of DNA damage repair genes such as APEX2, POLD1, and POLD2. The enzyme (PRMT7) is involved in regulation of the DNA repair machinery of the cell
physiological function
PRMT7 methylates eukaryotic translation initiation factor 2alpha and regulates its role in stress granule formation
physiological function
the enzyme (PRMT7) catalyzes the introduction of mono methylation marks at the arginine residues of substrate proteins. PRMT7 plays important roles in the regulation of gene expression, splicing, DNA damage, paternal imprinting, cancer and metastasis
physiological function
the enzyme (PRMT7) regulates the expression of C-MYC, which plays an important role in promoting ccRCC cell proliferation, and it accelerates the tumor development of RCC in a C-MYC-dependent manner. It upregulates the expression of C-MYC via methylating beta-catenin and inhibiting the ubiquitin-mediated degradation of beta-catenin
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). ANM7_HUMAN
692
0
78459
Swiss-Prot
other Location (Reliability: 1)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
truncated proteins consisiting of one of the two putative AdoMet-binding motifs are enzymatically inactive
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
isoform PRMT7 expression is significantly upregulated in both primary breast tumour tissues and in breast cancer lymph node metastases
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
isoform PRMT7 expression is significantly upregulated in both primary breast tumour tissues and in breast cancer lymph node metastases. Reducing PRMT7 levels in invasive breast cancer cells using RNA interference significantly decreases cell invasion in vitro and metastasis in vivo. Overexpression of PRMT7 in non-aggressive MCF-7 cells enhances their invasiveness. PRMT7 induces the expression of matrix metalloproteinase MMP9. Invasion of aggressive breast cancer cells depleted of PRMT7 may be rescued by the exogenous expression of MMP9
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Miranda, T.B.; Miranda, M.; Frankel, A.; Clarke, S.
PRMT7 is a member of the protein arginine methyltransferase family with a distinct substrate specificity
J. Biol. Chem.
279
22902-22907
2004
Homo sapiens (Q9NVM4)
Jelinic, P.; Stehle, J.C.; Shaw, P.
The testis-specific factor CTCFL cooperates with the protein methyltransferase PRMT7 in H19 imprinting control region methylation
PLoS Biol.
4
e355
2006
Homo sapiens (Q9NVM4)
Karkhanis, V.; Wang, L.; Tae, S.; Hu, Y.J.; Imbalzano, A.N.; Sif, S.
Protein arginine methyltransferase 7 regulates cellular response to DNA Damage by Methylating promoter histones H2A and H4 of the polymerase delta catalytic subunit gene, POLD1
J. Biol. Chem.
287
29801-29814
2012
Homo sapiens (Q9NVM4)
Zurita-Lopez, C.; Sandberg, T.; Kelly, R.; Clarke, S.
Human protein arginine methyltransferase 7 (PRMT7) is a type III enzyme forming omega-NG-monomethylated arginine residues
J. Biol. Chem.
287
7859-7870
2012
Homo sapiens (Q9NVM4), Homo sapiens
Gonsalvez, G.B.; Tian, L.; Ospina, J.K.; Boisvert, F.M.; Lamond, A.I.; Matera, A.G.
Two distinct arginine methyltransferases are required for biogenesis of Sm-class ribonucleoproteins
J. Cell Biol.
178
733-740
2007
Homo sapiens (Q9NVM4)
Baldwin, R.M.; Haghandish, N.; Daneshmand, M.; Amin, S.; Paris, G.; Falls, T.J.; Bell, J.C.; Islam, S.; Cote, J.
Protein arginine methyltransferase 7 promotes breast cancer cell invasion through the induction of MMP9 expression
Oncotarget
6
3013-3032
2015
Homo sapiens (Q9NVM4), Homo sapiens
Jain, K.; Clarke, S.G.
PRMT7 as a unique member of the protein arginine methyltransferase family A review
Arch. Biochem. Biophys.
665
36-45
2019
Caenorhabditis elegans (Q9XW42), Homo sapiens (Q9NVM4), Mus musculus (Q922X9), Trypanosoma brucei brucei (Q582G4), Trypanosoma brucei brucei 927 (Q582G4)
Liu, F.; Wan, L.; Zou, H.; Pan, Z.; Zhou, W.; Lu, X.
PRMT7 promotes the growth of renal cell carcinoma through modulating the beta-catenin/C-MYC axis
Int. J. Biochem. Cell Biol.
120
105686
2020
Homo sapiens (Q9NVM4)
Verma, M.; Charles, R.C.M.; Chakrapani, B.; Coumar, M.S.; Govindaraju, G.; Rajavelu, A.; Chavali, S.; Dhayalan, A.
PRMT7 interacts with ASS1 and citrullinemia mutations disrupt the interaction
J. Mol. Biol.
429
2278-2289
2017
Homo sapiens (Q9NVM4)
Haghandish, N.; Baldwin, R.M.; Morettin, A.; Dawit, H.T.; Adhikary, H.; Masson, J.Y.; Mazroui, R.; Trinkle-Mulcahy, L.; Cote, J.
PRMT7 methylates eukaryotic translation initiation factor 2alpha and regulates its role in stress granule formation
Mol. Biol. Cell
30
778-793
2019
Homo sapiens (Q9NVM4)
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