Q96LA8 · ANM6_HUMAN
- ProteinProtein arginine N-methyltransferase 6
- GenePRMT6
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids375 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Arginine methyltransferase that can catalyze the formation of both omega-N monomethylarginine (MMA) and asymmetrical dimethylarginine (aDMA), with a strong preference for the formation of aDMA (PubMed:17898714, PubMed:18077460, PubMed:18079182, PubMed:19405910, PubMed:30420520).
Preferentially methylates arginyl residues present in a glycine and arginine-rich domain and displays preference for monomethylated substrates (PubMed:17898714, PubMed:18077460, PubMed:18079182, PubMed:19405910).
Specifically mediates the asymmetric dimethylation of histone H3 'Arg-2' to form H3R2me2a (PubMed:17898714, PubMed:18077460, PubMed:18079182).
H3R2me2a represents a specific tag for epigenetic transcriptional repression and is mutually exclusive with methylation on histone H3 'Lys-4' (H3K4me2 and H3K4me3) (PubMed:17898714, PubMed:18077460).
Acts as a transcriptional repressor of various genes such as HOXA2, THBS1 and TP53 (PubMed:19509293).
Repression of TP53 blocks cellular senescence (By similarity).
Also methylates histone H2A and H4 'Arg-3' (H2AR3me and H4R3me, respectively). Acts as a regulator of DNA base excision during DNA repair by mediating the methylation of DNA polymerase beta (POLB), leading to the stimulation of its polymerase activity by enhancing DNA binding and processivity (PubMed:16600869).
Methylates HMGA1 (PubMed:16157300, PubMed:16159886).
Regulates alternative splicing events. Acts as a transcriptional coactivator of a number of steroid hormone receptors including ESR1, ESR2, PGR and NR3C1. Promotes fasting-induced transcriptional activation of the gluconeogenic program through methylation of the CRTC2 transcription coactivator (By similarity).
May play a role in innate immunity against HIV-1 in case of infection by methylating and impairing the function of various HIV-1 proteins such as Tat, Rev and Nucleocapsid protein p7 (NC) (PubMed:17267505).
Methylates GPS2, protecting GPS2 from ubiquitination and degradation (By similarity).
Methylates SIRT7, inhibiting SIRT7 histone deacetylase activity and promoting mitochondria biogenesis (PubMed:30420520).
Preferentially methylates arginyl residues present in a glycine and arginine-rich domain and displays preference for monomethylated substrates (PubMed:17898714, PubMed:18077460, PubMed:18079182, PubMed:19405910).
Specifically mediates the asymmetric dimethylation of histone H3 'Arg-2' to form H3R2me2a (PubMed:17898714, PubMed:18077460, PubMed:18079182).
H3R2me2a represents a specific tag for epigenetic transcriptional repression and is mutually exclusive with methylation on histone H3 'Lys-4' (H3K4me2 and H3K4me3) (PubMed:17898714, PubMed:18077460).
Acts as a transcriptional repressor of various genes such as HOXA2, THBS1 and TP53 (PubMed:19509293).
Repression of TP53 blocks cellular senescence (By similarity).
Also methylates histone H2A and H4 'Arg-3' (H2AR3me and H4R3me, respectively). Acts as a regulator of DNA base excision during DNA repair by mediating the methylation of DNA polymerase beta (POLB), leading to the stimulation of its polymerase activity by enhancing DNA binding and processivity (PubMed:16600869).
Methylates HMGA1 (PubMed:16157300, PubMed:16159886).
Regulates alternative splicing events. Acts as a transcriptional coactivator of a number of steroid hormone receptors including ESR1, ESR2, PGR and NR3C1. Promotes fasting-induced transcriptional activation of the gluconeogenic program through methylation of the CRTC2 transcription coactivator (By similarity).
May play a role in innate immunity against HIV-1 in case of infection by methylating and impairing the function of various HIV-1 proteins such as Tat, Rev and Nucleocapsid protein p7 (NC) (PubMed:17267505).
Methylates GPS2, protecting GPS2 from ubiquitination and degradation (By similarity).
Methylates SIRT7, inhibiting SIRT7 histone deacetylase activity and promoting mitochondria biogenesis (PubMed:30420520).
Catalytic activity
- L-arginyl-[protein] + 2 S-adenosyl-L-methionine = 2 H+ + N(omega),N(omega)-dimethyl-L-arginyl-[protein] + 2 S-adenosyl-L-homocysteineThis reaction proceeds in the forward direction.
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
18.6 μM | AdoMet | |||||
501 μM | WGGYSRGGYGGW peptide | |||||
183.7 μM | WGGYSR(MMA)GGYGGW monomethylated peptide |
Vmax | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|
3.3 nmol/min/mg | with AdoMet as substrate | ||||
1.8 nmol/min/mg | with WGGYSRGGYGGW peptide as substrate | ||||
3.2 nmol/min/mg | with WGGYSR(MMA)GGYGGW monomethylated peptide as substrate |
Features
Showing features for binding site, active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 57 | S-adenosyl-L-methionine (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 66 | S-adenosyl-L-methionine (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 90 | S-adenosyl-L-methionine (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Binding site | 112 | S-adenosyl-L-methionine (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 141 | S-adenosyl-L-methionine (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Active site | 155 | |||||
Sequence: E | ||||||
Active site | 164 | |||||
Sequence: E |
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameProtein arginine N-methyltransferase 6
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ96LA8
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Disease & Variants
Features
Showing features for mutagenesis, natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 35 | Inhibits automethylation but does not affect methylation of other proteins. Reduces protein stability. | ||||
Sequence: R → A | ||||||
Mutagenesis | 86-88 | In PRMT6dn; abolishes histone methyltransferase H3R2me2a and transcriptional coactivator activities and reduces protein stability. This mutation abolishes automethylation. | ||||
Sequence: VLD → KLA | ||||||
Natural variant | VAR_057150 | 194 | in dbSNP:rs2232016 | |||
Sequence: A → V |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 505 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000212332 | 1-375 | UniProt | Protein arginine N-methyltransferase 6 | |||
Sequence: MSQPKKRKLESGGGGEGGEGTEEEDGAEREAALERPRRTKRERDQLYYECYSDVSVHEEMIADRVRTDAYRLGILRNWAALRGKTVLDVGAGTGILSIFCAQAGARRVYAVEASAIWQQAREVVRFNGLEDRVHVLPGPVETVELPEQVDAIVSEWMGYGLLHESMLSSVLHARTKWLKEGGLLLPASAELFIAPISDQMLEWRLGFWSQVKQHYGVDMSCLEGFATRCLMGHSEIVVQGLSGEDVLARPQRFAQLELSRAGLEQELEAGVGGRFRCSCYGSAPMHGFAIWFQVTFPGGESEKPLVLSTSPFHPATHWKQALLYLNEPVQVEQDTDVSGEITLLPSRDNPRRLRVLLRYKVGDQEEKTKDFAMED | |||||||
Modified residue | 21 | UniProt | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 21 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 29 | UniProt | Asymmetric dimethylarginine; by autocatalysis | ||||
Sequence: R | |||||||
Modified residue | 35 | UniProt | Asymmetric dimethylarginine; by autocatalysis | ||||
Sequence: R | |||||||
Modified residue | 37 | UniProt | Asymmetric dimethylarginine; by autocatalysis | ||||
Sequence: R |
Post-translational modification
Automethylation enhances its stability and antiretroviral activity.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Highly expressed in kidney and testis.
Gene expression databases
Organism-specific databases
Interaction
Subunit
Interacts with EPB41L3 and NCOA1.
(Microbial infection) Interacts with (and methylates) HIV-1 Tat, Rev and Nucleocapsid protein p7 (NC).
(Microbial infection) Interacts with human cytomegalovirus protein UL69.
Binary interactions
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-38 | Disordered | ||||
Sequence: MSQPKKRKLESGGGGEGGEGTEEEDGAEREAALERPRR | ||||||
Domain | 44-374 | SAM-dependent MTase PRMT-type | ||||
Sequence: DQLYYECYSDVSVHEEMIADRVRTDAYRLGILRNWAALRGKTVLDVGAGTGILSIFCAQAGARRVYAVEASAIWQQAREVVRFNGLEDRVHVLPGPVETVELPEQVDAIVSEWMGYGLLHESMLSSVLHARTKWLKEGGLLLPASAELFIAPISDQMLEWRLGFWSQVKQHYGVDMSCLEGFATRCLMGHSEIVVQGLSGEDVLARPQRFAQLELSRAGLEQELEAGVGGRFRCSCYGSAPMHGFAIWFQVTFPGGESEKPLVLSTSPFHPATHWKQALLYLNEPVQVEQDTDVSGEITLLPSRDNPRRLRVLLRYKVGDQEEKTKDFAME |
Sequence similarities
Belongs to the class I-like SAM-binding methyltransferase superfamily. Protein arginine N-methyltransferase family. PRMT6 subfamily.
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
Q96LA8-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Length375
- Mass (Da)41,938
- Last updated2001-12-01 v1
- Checksum40AAEC7342C08A38
Q96LA8-2
- Name2
- Differences from canonical
- 26-109: GAEREAALERPRRTKRERDQLYYECYSDVSVHEEMIADRVRTDAYRLGILRNWAALRGKTVLDVGAGTGILSIFCAQAGARRVY → D
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A3B3ITK4 | A0A3B3ITK4_HUMAN | PRMT6 | 313 |
Sequence caution
Features
Showing features for alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_037465 | 26-109 | in isoform 2 | |||
Sequence: GAEREAALERPRRTKRERDQLYYECYSDVSVHEEMIADRVRTDAYRLGILRNWAALRGKTVLDVGAGTGILSIFCAQAGARRVY → D |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AY043278 EMBL· GenBank· DDBJ | AAK85733.1 EMBL· GenBank· DDBJ | mRNA | ||
AK001421 EMBL· GenBank· DDBJ | BAA91681.1 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
AK295541 EMBL· GenBank· DDBJ | BAG58450.1 EMBL· GenBank· DDBJ | mRNA | ||
AL355539 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH471156 EMBL· GenBank· DDBJ | EAW51248.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC002729 EMBL· GenBank· DDBJ | AAH02729.3 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
BC063446 EMBL· GenBank· DDBJ | AAH63446.2 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
BC073866 EMBL· GenBank· DDBJ | AAH73866.1 EMBL· GenBank· DDBJ | mRNA | ||
BX475300 EMBL· GenBank· DDBJ | - | mRNA | No translation available. |