7M05

CryoEM structure of PRMT5 bound to covalent PBM-site inhibitor BRD-6988

Functional Information from GO Data

Chain	GOid	namespace	contents
A	0000387	biological_process	spliceosomal snRNP assembly
A	0000785	cellular_component	chromatin
A	0002039	molecular_function	p53 binding
A	0003714	molecular_function	transcription corepressor activity
A	0005515	molecular_function	protein binding
A	0005634	cellular_component	nucleus
A	0005654	cellular_component	nucleoplasm
A	0005694	cellular_component	chromosome
A	0005737	cellular_component	cytoplasm
A	0005794	cellular_component	Golgi apparatus
A	0005829	cellular_component	cytosol
A	0006325	biological_process	chromatin organization
A	0006338	biological_process	chromatin remodeling
A	0006353	biological_process	DNA-templated transcription termination
A	0006355	biological_process	regulation of DNA-templated transcription
A	0006479	biological_process	protein methylation
A	0007088	biological_process	regulation of mitotic nuclear division
A	0008168	molecular_function	methyltransferase activity
A	0008327	molecular_function	methyl-CpG binding
A	0008469	molecular_function	histone arginine N-methyltransferase activity
A	0010468	biological_process	regulation of gene expression
A	0016274	molecular_function	protein-arginine N-methyltransferase activity
A	0016740	molecular_function	transferase activity
A	0018216	biological_process	peptidyl-arginine methylation
A	0032259	biological_process	methylation
A	0032922	biological_process	circadian regulation of gene expression
A	0032991	cellular_component	protein-containing complex
A	0034709	cellular_component	methylosome
A	0035097	cellular_component	histone methyltransferase complex
A	0035243	molecular_function	protein-arginine omega-N symmetric methyltransferase activity
A	0035246	biological_process	peptidyl-arginine N-methylation
A	0042054	molecular_function	histone methyltransferase activity
A	0042118	biological_process	endothelial cell activation
A	0042802	molecular_function	identical protein binding
A	0043021	molecular_function	ribonucleoprotein complex binding
A	0044020	molecular_function	histone H4R3 methyltransferase activity
A	0044027	biological_process	negative regulation of gene expression via chromosomal CpG island methylation
A	0044877	molecular_function	protein-containing complex binding
A	0045596	biological_process	negative regulation of cell differentiation
A	0045892	biological_process	negative regulation of DNA-templated transcription
A	0046982	molecular_function	protein heterodimerization activity
A	0048026	biological_process	positive regulation of mRNA splicing, via spliceosome
A	0048511	biological_process	rhythmic process
A	0048714	biological_process	positive regulation of oligodendrocyte differentiation
A	0070372	biological_process	regulation of ERK1 and ERK2 cascade
A	0070888	molecular_function	E-box binding
A	0090161	biological_process	Golgi ribbon formation
A	0097421	biological_process	liver regeneration
A	0140938	molecular_function	histone H3 methyltransferase activity
A	1901796	biological_process	regulation of signal transduction by p53 class mediator
A	1904992	biological_process	positive regulation of adenylate cyclase-inhibiting dopamine receptor signaling pathway
B	0000209	biological_process	protein polyubiquitination
B	0000387	biological_process	spliceosomal snRNP assembly
B	0003713	molecular_function	transcription coactivator activity
B	0005515	molecular_function	protein binding
B	0005634	cellular_component	nucleus
B	0005654	cellular_component	nucleoplasm
B	0005737	cellular_component	cytoplasm
B	0005794	cellular_component	Golgi apparatus
B	0005829	cellular_component	cytosol
B	0006357	biological_process	regulation of transcription by RNA polymerase II
B	0006511	biological_process	ubiquitin-dependent protein catabolic process
B	0007309	biological_process	oocyte axis specification
B	0008284	biological_process	positive regulation of cell population proliferation
B	0008285	biological_process	negative regulation of cell population proliferation
B	0008327	molecular_function	methyl-CpG binding
B	0031465	cellular_component	Cul4B-RING E3 ubiquitin ligase complex
B	0034709	cellular_component	methylosome
B	0045893	biological_process	positive regulation of DNA-templated transcription
B	0048026	biological_process	positive regulation of mRNA splicing, via spliceosome
B	0060528	biological_process	secretory columnal luminar epithelial cell differentiation involved in prostate glandular acinus development
B	0060767	biological_process	epithelial cell proliferation involved in prostate gland development
B	0060770	biological_process	negative regulation of epithelial cell proliferation involved in prostate gland development
B	1990234	cellular_component	transferase complex
B	1990756	molecular_function	ubiquitin-like ligase-substrate adaptor activity
C	0000387	biological_process	spliceosomal snRNP assembly
C	0000785	cellular_component	chromatin
C	0002039	molecular_function	p53 binding
C	0003714	molecular_function	transcription corepressor activity
C	0005515	molecular_function	protein binding
C	0005634	cellular_component	nucleus
C	0005654	cellular_component	nucleoplasm
C	0005694	cellular_component	chromosome
C	0005737	cellular_component	cytoplasm
C	0005794	cellular_component	Golgi apparatus
C	0005829	cellular_component	cytosol
C	0006325	biological_process	chromatin organization
C	0006338	biological_process	chromatin remodeling
C	0006353	biological_process	DNA-templated transcription termination
C	0006355	biological_process	regulation of DNA-templated transcription
C	0006479	biological_process	protein methylation
C	0007088	biological_process	regulation of mitotic nuclear division
C	0008168	molecular_function	methyltransferase activity
C	0008327	molecular_function	methyl-CpG binding
C	0008469	molecular_function	histone arginine N-methyltransferase activity
C	0010468	biological_process	regulation of gene expression
C	0016274	molecular_function	protein-arginine N-methyltransferase activity
C	0016740	molecular_function	transferase activity
C	0018216	biological_process	peptidyl-arginine methylation
C	0032259	biological_process	methylation
C	0032922	biological_process	circadian regulation of gene expression
C	0032991	cellular_component	protein-containing complex
C	0034709	cellular_component	methylosome
C	0035097	cellular_component	histone methyltransferase complex
C	0035243	molecular_function	protein-arginine omega-N symmetric methyltransferase activity
C	0035246	biological_process	peptidyl-arginine N-methylation
C	0042054	molecular_function	histone methyltransferase activity
C	0042118	biological_process	endothelial cell activation
C	0042802	molecular_function	identical protein binding
C	0043021	molecular_function	ribonucleoprotein complex binding
C	0044020	molecular_function	histone H4R3 methyltransferase activity
C	0044027	biological_process	negative regulation of gene expression via chromosomal CpG island methylation
C	0044877	molecular_function	protein-containing complex binding
C	0045596	biological_process	negative regulation of cell differentiation
C	0045892	biological_process	negative regulation of DNA-templated transcription
C	0046982	molecular_function	protein heterodimerization activity
C	0048026	biological_process	positive regulation of mRNA splicing, via spliceosome
C	0048511	biological_process	rhythmic process
C	0048714	biological_process	positive regulation of oligodendrocyte differentiation
C	0070372	biological_process	regulation of ERK1 and ERK2 cascade
C	0070888	molecular_function	E-box binding
C	0090161	biological_process	Golgi ribbon formation
C	0097421	biological_process	liver regeneration
C	0140938	molecular_function	histone H3 methyltransferase activity
C	1901796	biological_process	regulation of signal transduction by p53 class mediator
C	1904992	biological_process	positive regulation of adenylate cyclase-inhibiting dopamine receptor signaling pathway
D	0000209	biological_process	protein polyubiquitination
D	0000387	biological_process	spliceosomal snRNP assembly
D	0003713	molecular_function	transcription coactivator activity
D	0005515	molecular_function	protein binding
D	0005634	cellular_component	nucleus
D	0005654	cellular_component	nucleoplasm
D	0005737	cellular_component	cytoplasm
D	0005794	cellular_component	Golgi apparatus
D	0005829	cellular_component	cytosol
D	0006357	biological_process	regulation of transcription by RNA polymerase II
D	0006511	biological_process	ubiquitin-dependent protein catabolic process
D	0007309	biological_process	oocyte axis specification
D	0008284	biological_process	positive regulation of cell population proliferation
D	0008285	biological_process	negative regulation of cell population proliferation
D	0008327	molecular_function	methyl-CpG binding
D	0031465	cellular_component	Cul4B-RING E3 ubiquitin ligase complex
D	0034709	cellular_component	methylosome
D	0045893	biological_process	positive regulation of DNA-templated transcription
D	0048026	biological_process	positive regulation of mRNA splicing, via spliceosome
D	0060528	biological_process	secretory columnal luminar epithelial cell differentiation involved in prostate glandular acinus development
D	0060767	biological_process	epithelial cell proliferation involved in prostate gland development
D	0060770	biological_process	negative regulation of epithelial cell proliferation involved in prostate gland development
D	1990234	cellular_component	transferase complex
D	1990756	molecular_function	ubiquitin-like ligase-substrate adaptor activity
E	0000387	biological_process	spliceosomal snRNP assembly
E	0000785	cellular_component	chromatin
E	0002039	molecular_function	p53 binding
E	0003714	molecular_function	transcription corepressor activity
E	0005515	molecular_function	protein binding
E	0005634	cellular_component	nucleus
E	0005654	cellular_component	nucleoplasm
E	0005694	cellular_component	chromosome
E	0005737	cellular_component	cytoplasm
E	0005794	cellular_component	Golgi apparatus
E	0005829	cellular_component	cytosol
E	0006325	biological_process	chromatin organization
E	0006338	biological_process	chromatin remodeling
E	0006353	biological_process	DNA-templated transcription termination
E	0006355	biological_process	regulation of DNA-templated transcription
E	0006479	biological_process	protein methylation
E	0007088	biological_process	regulation of mitotic nuclear division
E	0008168	molecular_function	methyltransferase activity
E	0008327	molecular_function	methyl-CpG binding
E	0008469	molecular_function	histone arginine N-methyltransferase activity
E	0010468	biological_process	regulation of gene expression
E	0016274	molecular_function	protein-arginine N-methyltransferase activity
E	0016740	molecular_function	transferase activity
E	0018216	biological_process	peptidyl-arginine methylation
E	0032259	biological_process	methylation
E	0032922	biological_process	circadian regulation of gene expression
E	0032991	cellular_component	protein-containing complex
E	0034709	cellular_component	methylosome
E	0035097	cellular_component	histone methyltransferase complex
E	0035243	molecular_function	protein-arginine omega-N symmetric methyltransferase activity
E	0035246	biological_process	peptidyl-arginine N-methylation
E	0042054	molecular_function	histone methyltransferase activity
E	0042118	biological_process	endothelial cell activation
E	0042802	molecular_function	identical protein binding
E	0043021	molecular_function	ribonucleoprotein complex binding
E	0044020	molecular_function	histone H4R3 methyltransferase activity
E	0044027	biological_process	negative regulation of gene expression via chromosomal CpG island methylation
E	0044877	molecular_function	protein-containing complex binding
E	0045596	biological_process	negative regulation of cell differentiation
E	0045892	biological_process	negative regulation of DNA-templated transcription
E	0046982	molecular_function	protein heterodimerization activity
E	0048026	biological_process	positive regulation of mRNA splicing, via spliceosome
E	0048511	biological_process	rhythmic process
E	0048714	biological_process	positive regulation of oligodendrocyte differentiation
E	0070372	biological_process	regulation of ERK1 and ERK2 cascade
E	0070888	molecular_function	E-box binding
E	0090161	biological_process	Golgi ribbon formation
E	0097421	biological_process	liver regeneration
E	0140938	molecular_function	histone H3 methyltransferase activity
E	1901796	biological_process	regulation of signal transduction by p53 class mediator
E	1904992	biological_process	positive regulation of adenylate cyclase-inhibiting dopamine receptor signaling pathway
F	0000209	biological_process	protein polyubiquitination
F	0000387	biological_process	spliceosomal snRNP assembly
F	0003713	molecular_function	transcription coactivator activity
F	0005515	molecular_function	protein binding
F	0005634	cellular_component	nucleus
F	0005654	cellular_component	nucleoplasm
F	0005737	cellular_component	cytoplasm
F	0005794	cellular_component	Golgi apparatus
F	0005829	cellular_component	cytosol
F	0006357	biological_process	regulation of transcription by RNA polymerase II
F	0006511	biological_process	ubiquitin-dependent protein catabolic process
F	0007309	biological_process	oocyte axis specification
F	0008284	biological_process	positive regulation of cell population proliferation
F	0008285	biological_process	negative regulation of cell population proliferation
F	0008327	molecular_function	methyl-CpG binding
F	0031465	cellular_component	Cul4B-RING E3 ubiquitin ligase complex
F	0034709	cellular_component	methylosome
F	0045893	biological_process	positive regulation of DNA-templated transcription
F	0048026	biological_process	positive regulation of mRNA splicing, via spliceosome
F	0060528	biological_process	secretory columnal luminar epithelial cell differentiation involved in prostate glandular acinus development
F	0060767	biological_process	epithelial cell proliferation involved in prostate gland development
F	0060770	biological_process	negative regulation of epithelial cell proliferation involved in prostate gland development
F	1990234	cellular_component	transferase complex
F	1990756	molecular_function	ubiquitin-like ligase-substrate adaptor activity
G	0000387	biological_process	spliceosomal snRNP assembly
G	0000785	cellular_component	chromatin
G	0002039	molecular_function	p53 binding
G	0003714	molecular_function	transcription corepressor activity
G	0005515	molecular_function	protein binding
G	0005634	cellular_component	nucleus
G	0005654	cellular_component	nucleoplasm
G	0005694	cellular_component	chromosome
G	0005737	cellular_component	cytoplasm
G	0005794	cellular_component	Golgi apparatus
G	0005829	cellular_component	cytosol
G	0006325	biological_process	chromatin organization
G	0006338	biological_process	chromatin remodeling
G	0006353	biological_process	DNA-templated transcription termination
G	0006355	biological_process	regulation of DNA-templated transcription
G	0006479	biological_process	protein methylation
G	0007088	biological_process	regulation of mitotic nuclear division
G	0008168	molecular_function	methyltransferase activity
G	0008327	molecular_function	methyl-CpG binding
G	0008469	molecular_function	histone arginine N-methyltransferase activity
G	0010468	biological_process	regulation of gene expression
G	0016274	molecular_function	protein-arginine N-methyltransferase activity
G	0016740	molecular_function	transferase activity
G	0018216	biological_process	peptidyl-arginine methylation
G	0032259	biological_process	methylation
G	0032922	biological_process	circadian regulation of gene expression
G	0032991	cellular_component	protein-containing complex
G	0034709	cellular_component	methylosome
G	0035097	cellular_component	histone methyltransferase complex
G	0035243	molecular_function	protein-arginine omega-N symmetric methyltransferase activity
G	0035246	biological_process	peptidyl-arginine N-methylation
G	0042054	molecular_function	histone methyltransferase activity
G	0042118	biological_process	endothelial cell activation
G	0042802	molecular_function	identical protein binding
G	0043021	molecular_function	ribonucleoprotein complex binding
G	0044020	molecular_function	histone H4R3 methyltransferase activity
G	0044027	biological_process	negative regulation of gene expression via chromosomal CpG island methylation
G	0044877	molecular_function	protein-containing complex binding
G	0045596	biological_process	negative regulation of cell differentiation
G	0045892	biological_process	negative regulation of DNA-templated transcription
G	0046982	molecular_function	protein heterodimerization activity
G	0048026	biological_process	positive regulation of mRNA splicing, via spliceosome
G	0048511	biological_process	rhythmic process
G	0048714	biological_process	positive regulation of oligodendrocyte differentiation
G	0070372	biological_process	regulation of ERK1 and ERK2 cascade
G	0070888	molecular_function	E-box binding
G	0090161	biological_process	Golgi ribbon formation
G	0097421	biological_process	liver regeneration
G	0140938	molecular_function	histone H3 methyltransferase activity
G	1901796	biological_process	regulation of signal transduction by p53 class mediator
G	1904992	biological_process	positive regulation of adenylate cyclase-inhibiting dopamine receptor signaling pathway
H	0000209	biological_process	protein polyubiquitination
H	0000387	biological_process	spliceosomal snRNP assembly
H	0003713	molecular_function	transcription coactivator activity
H	0005515	molecular_function	protein binding
H	0005634	cellular_component	nucleus
H	0005654	cellular_component	nucleoplasm
H	0005737	cellular_component	cytoplasm
H	0005794	cellular_component	Golgi apparatus
H	0005829	cellular_component	cytosol
H	0006357	biological_process	regulation of transcription by RNA polymerase II
H	0006511	biological_process	ubiquitin-dependent protein catabolic process
H	0007309	biological_process	oocyte axis specification
H	0008284	biological_process	positive regulation of cell population proliferation
H	0008285	biological_process	negative regulation of cell population proliferation
H	0008327	molecular_function	methyl-CpG binding
H	0031465	cellular_component	Cul4B-RING E3 ubiquitin ligase complex
H	0034709	cellular_component	methylosome
H	0045893	biological_process	positive regulation of DNA-templated transcription
H	0048026	biological_process	positive regulation of mRNA splicing, via spliceosome
H	0060528	biological_process	secretory columnal luminar epithelial cell differentiation involved in prostate glandular acinus development
H	0060767	biological_process	epithelial cell proliferation involved in prostate gland development
H	0060770	biological_process	negative regulation of epithelial cell proliferation involved in prostate gland development
H	1990234	cellular_component	transferase complex
H	1990756	molecular_function	ubiquitin-like ligase-substrate adaptor activity

Functional Information from PROSITE/UniProt

site_id	PS00678
Number of Residues	15
Details	WD_REPEATS_1 Trp-Asp (WD) repeats signature. AVSGskDiCIKVWDL

Chain	Residue	Details
B	ALA140-LEU154

---

Functional Information from SwissProt/UniProt

site_id	SWS_FT_FI1
Number of Residues	1228
Details	Domain: {"description":"SAM-dependent MTase PRMT-type","evidences":[{"source":"PROSITE-ProRule","id":"PRU01015","evidenceCode":"ECO:0000255"}]}

Chain

Residue

Details

---

site_id	SWS_FT_FI2
Number of Residues	688
Details	Region: {"description":"Beta barrel","evidences":[{"source":"PubMed","id":"23071334","evidenceCode":"ECO:0000269"}]}

Chain

Residue

Details

---

site_id	SWS_FT_FI3
Number of Residues	24
Details	Region: {"description":"Dimerization","evidences":[{"source":"PubMed","id":"23071334","evidenceCode":"ECO:0000269"}]}

Chain

Residue

Details

---

site_id	SWS_FT_FI4
Number of Residues	8
Details	Active site: {"description":"Proton donor/acceptor","evidences":[{"source":"PubMed","id":"23071334","evidenceCode":"ECO:0000305"}]}

Chain

Residue

Details

---

site_id	SWS_FT_FI5
Number of Residues	28
Details	Binding site: {"evidences":[{"source":"PubMed","id":"23071334","evidenceCode":"ECO:0000269"}]}

Chain

Residue

Details

---

site_id	SWS_FT_FI6
Number of Residues	4
Details	Site: {"description":"Critical for specifying symmetric addition of methyl groups","evidences":[{"source":"UniProtKB","id":"P46580","evidenceCode":"ECO:0000250"}]}

Chain

Residue

Details

---

site_id	SWS_FT_FI7
Number of Residues	152
Details	Repeat: {"description":"WD 2","evidences":[{"source":"PROSITE-ProRule","id":"PRU00221","evidenceCode":"ECO:0000255"},{"source":"PubMed","id":"23071334","evidenceCode":"ECO:0000269"}]}

Chain

Residue

Details

---

site_id	SWS_FT_FI8
Number of Residues	156
Details	Repeat: {"description":"WD 3","evidences":[{"source":"PROSITE-ProRule","id":"PRU00221","evidenceCode":"ECO:0000255"},{"source":"PubMed","id":"23071334","evidenceCode":"ECO:0000269"}]}

Chain

Residue

Details

---

site_id	SWS_FT_FI9
Number of Residues	160
Details	Repeat: {"description":"WD 4","evidences":[{"source":"PROSITE-ProRule","id":"PRU00221","evidenceCode":"ECO:0000255"},{"source":"PubMed","id":"23071334","evidenceCode":"ECO:0000269"}]}

Chain

Residue

Details

---

site_id	SWS_FT_FI10
Number of Residues	160
Details	Repeat: {"description":"WD 6","evidences":[{"source":"PROSITE-ProRule","id":"PRU00221","evidenceCode":"ECO:0000255"},{"source":"PubMed","id":"23071334","evidenceCode":"ECO:0000269"}]}

Chain

Residue

Details

---