UniProtKB - Q96LA8 (ANM6_HUMAN)
Protein arginine N-methyltransferase 6
PRMT6
Functioni
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:18079182, PubMed:18077460).
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).
By similarity12 PublicationsCatalytic activityi
- L-arginyl-[protein] + 2 S-adenosyl-L-methionine = 2 H+ + Nω,Nω-dimethyl-L-arginyl-[protein] + 2 S-adenosyl-L-homocysteine5 PublicationsEC:2.1.1.3195 PublicationsThis reaction proceeds in the forward5 Publications direction.
Kineticsi
- KM=18.6 µM for AdoMet1 Publication
- KM=501 µM for WGGYSRGGYGGW peptide1 Publication
- KM=183.7 µM for WGGYSR(MMA)GGYGGW monomethylated peptide1 Publication
- Vmax=3.3 nmol/min/mg enzyme with AdoMet as substrate1 Publication
- Vmax=1.8 nmol/min/mg enzyme with WGGYSRGGYGGW peptide as substrate1 Publication
- Vmax=3.2 nmol/min/mg enzyme with WGGYSR(MMA)GGYGGW monomethylated peptide as substrate1 Publication
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 57 | S-adenosyl-L-methionineBy similarity | 1 | |
Binding sitei | 66 | S-adenosyl-L-methionine | 1 | |
Binding sitei | 90 | S-adenosyl-L-methionine; via carbonyl oxygen | 1 | |
Binding sitei | 112 | S-adenosyl-L-methionine | 1 | |
Binding sitei | 141 | S-adenosyl-L-methionine | 1 | |
Active sitei | 155 | By similarity | 1 | |
Active sitei | 164 | By similarity | 1 |
GO - Molecular functioni
- chromatin binding Source: Ensembl
- histone-arginine N-methyltransferase activity Source: CACAO
- histone binding Source: UniProtKB
- histone methyltransferase activity Source: UniProtKB
- histone methyltransferase activity (H2A-R3 specific) Source: UniProtKB
- histone methyltransferase activity (H3-R2 specific) Source: UniProtKB
- histone methyltransferase activity (H4-R3 specific) Source: UniProtKB
- protein-arginine N-methyltransferase activity Source: UniProtKB
- protein-arginine omega-N asymmetric methyltransferase activity Source: UniProtKB
- protein-arginine omega-N monomethyltransferase activity Source: UniProtKB
GO - Biological processi
- base-excision repair Source: UniProtKB
- cellular senescence Source: Ensembl
- chromatin organization Source: UniProtKB-KW
- histone H3-R2 methylation Source: UniProtKB
- histone methylation Source: UniProtKB
- negative regulation of histone deacetylation Source: UniProtKB
- negative regulation of histone H3-K4 methylation Source: Ensembl
- negative regulation of transcription, DNA-templated Source: UniProtKB
- negative regulation of transcription by RNA polymerase II Source: Ensembl
- peptidyl-arginine methylation, to asymmetrical-dimethyl arginine Source: UniProtKB
- regulation of megakaryocyte differentiation Source: Reactome
- regulation of mitochondrion organization Source: UniProtKB
- regulation of signal transduction by p53 class mediator Source: Ensembl
Keywordsi
Molecular function | Chromatin regulator, Methyltransferase, Repressor, Transferase |
Biological process | DNA damage, DNA repair, Host-virus interaction, Transcription, Transcription regulation |
Ligand | S-adenosyl-L-methionine |
Enzyme and pathway databases
BRENDAi | 2.1.1.319, 2681 |
PathwayCommonsi | Q96LA8 |
Reactomei | R-HSA-3214858, RMTs methylate histone arginines R-HSA-8936459, RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function |
SABIO-RKi | Q96LA8 |
SignaLinki | Q96LA8 |
Names & Taxonomyi
Protein namesi | Recommended name: Protein arginine N-methyltransferase 6 (EC:2.1.1.3195 Publications)Alternative name(s): Heterogeneous nuclear ribonucleoprotein methyltransferase-like protein 6 Histone-arginine N-methyltransferase PRMT6 |
Gene namesi | Name:PRMT6 Synonyms:HRMT1L6 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:18241, PRMT6 |
MIMi | 608274, gene |
neXtProti | NX_Q96LA8 |
VEuPathDBi | HostDB:ENSG00000198890 |
Subcellular locationi
Nucleus
- Nucleus 1 Publication
Nucleus
- nucleolus Source: HPA
- nucleoplasm Source: HPA
- nucleus Source: UniProtKB
Keywords - Cellular componenti
NucleusPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 35 | R → A: Inhibits automethylation but does not affect methylation of other proteins. Reduces protein stability. 1 Publication | 1 | |
Mutagenesisi | 86 – 88 | VLD → KLA in PRMT6dn; abolishes histone methyltransferase H3R2me2a and transcriptional coactivator activities and reduces protein stability. This mutation abolishes automethylation. 4 Publications | 3 |
Organism-specific databases
DisGeNETi | 55170 |
OpenTargetsi | ENSG00000198890 |
PharmGKBi | PA134992775 |
Miscellaneous databases
Pharosi | Q96LA8, Tchem |
Chemistry databases
ChEMBLi | CHEMBL1275221 |
GuidetoPHARMACOLOGYi | 1257 |
Genetic variation databases
BioMutai | PRMT6 |
DMDMi | 20137409 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000212332 | 1 – 375 | Protein arginine N-methyltransferase 6Add BLAST | 375 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 21 | PhosphothreonineCombined sources | 1 | |
Modified residuei | 29 | Asymmetric dimethylarginine; by autocatalysis1 Publication | 1 | |
Modified residuei | 35 | Asymmetric dimethylarginine; by autocatalysis1 Publication | 1 | |
Modified residuei | 37 | Asymmetric dimethylarginine; by autocatalysis1 Publication | 1 |
Post-translational modificationi
Keywords - PTMi
Methylation, PhosphoproteinProteomic databases
EPDi | Q96LA8 |
jPOSTi | Q96LA8 |
MassIVEi | Q96LA8 |
MaxQBi | Q96LA8 |
PaxDbi | Q96LA8 |
PeptideAtlasi | Q96LA8 |
PRIDEi | Q96LA8 |
ProteomicsDBi | 77181 [Q96LA8-1] 77182 [Q96LA8-2] |
PTM databases
iPTMneti | Q96LA8 |
PhosphoSitePlusi | Q96LA8 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000198890, Expressed in metanephros and 206 other tissues |
ExpressionAtlasi | Q96LA8, baseline and differential |
Genevisiblei | Q96LA8, HS |
Organism-specific databases
HPAi | ENSG00000198890, Low tissue specificity |
Interactioni
Subunit structurei
Interacts with EPB41L3 and NCOA1.
6 Publications(Microbial infection) Interacts with (and methylates) HIV-1 Tat, Rev and Nucleocapsid protein p7 (NC).
4 Publications(Microbial infection) Interacts with human cytomegalovirus protein UL69.
1 PublicationBinary interactionsi
Q96LA8
GO - Molecular functioni
- histone binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 120469, 164 interactors |
IntActi | Q96LA8, 105 interactors |
MINTi | Q96LA8 |
STRINGi | 9606.ENSP00000359095 |
Chemistry databases
BindingDBi | Q96LA8 |
Miscellaneous databases
RNActi | Q96LA8, protein |
Structurei
Secondary structure
3D structure databases
AlphaFoldDBi | Q96LA8 |
SMRi | Q96LA8 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 44 – 374 | SAM-dependent MTase PRMT-typePROSITE-ProRule annotationAdd BLAST | 331 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 38 | DisorderedSequence analysisAdd BLAST | 38 |
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG1499, Eukaryota |
GeneTreei | ENSGT00940000160961 |
HOGENOMi | CLU_017375_1_2_1 |
InParanoidi | Q96LA8 |
OMAi | SARHICI |
OrthoDBi | 840669at2759 |
PhylomeDBi | Q96LA8 |
TreeFami | TF328817 |
Family and domain databases
Gene3Di | 3.40.50.150, 1 hit |
InterProi | View protein in InterPro IPR025799, Arg_MeTrfase IPR041698, Methyltransf_25 IPR029063, SAM-dependent_MTases |
PANTHERi | PTHR11006, PTHR11006, 1 hit |
Pfami | View protein in Pfam PF13649, Methyltransf_25, 1 hit |
SUPFAMi | SSF53335, SSF53335, 1 hit |
PROSITEi | View protein in PROSITE PS51678, SAM_MT_PRMT, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MSQPKKRKLE SGGGGEGGEG TEEEDGAERE AALERPRRTK RERDQLYYEC
60 70 80 90 100
YSDVSVHEEM IADRVRTDAY RLGILRNWAA LRGKTVLDVG AGTGILSIFC
110 120 130 140 150
AQAGARRVYA VEASAIWQQA REVVRFNGLE DRVHVLPGPV ETVELPEQVD
160 170 180 190 200
AIVSEWMGYG LLHESMLSSV LHARTKWLKE GGLLLPASAE LFIAPISDQM
210 220 230 240 250
LEWRLGFWSQ VKQHYGVDMS CLEGFATRCL MGHSEIVVQG LSGEDVLARP
260 270 280 290 300
QRFAQLELSR AGLEQELEAG VGGRFRCSCY GSAPMHGFAI WFQVTFPGGE
310 320 330 340 350
SEKPLVLSTS PFHPATHWKQ ALLYLNEPVQ VEQDTDVSGE ITLLPSRDNP
360 370
RRLRVLLRYK VGDQEEKTKD FAMED
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketA0A3B3ITK4 | A0A3B3ITK4_HUMAN | Protein arginine N-methyltransferas... | PRMT6 | 313 | Annotation score: |
Sequence cautioni
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_057150 | 194 | A → V1 PublicationCorresponds to variant dbSNP:rs2232016Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_037465 | 26 – 109 | GAERE…ARRVY → D in isoform 2. 1 PublicationAdd BLAST | 84 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AY043278 mRNA Translation: AAK85733.1 AK001421 mRNA Translation: BAA91681.1 Different initiation. AK295541 mRNA Translation: BAG58450.1 AL355539 Genomic DNA No translation available. CH471156 Genomic DNA Translation: EAW51248.1 BC002729 mRNA Translation: AAH02729.3 Different initiation. BC063446 mRNA Translation: AAH63446.2 Different initiation. BC073866 mRNA Translation: AAH73866.1 BX475300 mRNA No translation available. |
CCDSi | CCDS41360.2 [Q96LA8-1] |
RefSeqi | NP_060607.2, NM_018137.2 [Q96LA8-1] |
Genome annotation databases
Ensembli | ENST00000370078.2; ENSP00000359095.1; ENSG00000198890.9 |
GeneIDi | 55170 |
KEGGi | hsa:55170 |
MANE-Selecti | ENST00000370078.2; ENSP00000359095.1; NM_018137.3; NP_060607.2 |
UCSCi | uc010ous.4, human [Q96LA8-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AY043278 mRNA Translation: AAK85733.1 AK001421 mRNA Translation: BAA91681.1 Different initiation. AK295541 mRNA Translation: BAG58450.1 AL355539 Genomic DNA No translation available. CH471156 Genomic DNA Translation: EAW51248.1 BC002729 mRNA Translation: AAH02729.3 Different initiation. BC063446 mRNA Translation: AAH63446.2 Different initiation. BC073866 mRNA Translation: AAH73866.1 BX475300 mRNA No translation available. |
CCDSi | CCDS41360.2 [Q96LA8-1] |
RefSeqi | NP_060607.2, NM_018137.2 [Q96LA8-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
4HC4 | X-ray | 1.97 | A | 1-375 | [»] | |
4QPP | X-ray | 2.52 | A/B/C | 1-375 | [»] | |
4QQK | X-ray | 1.88 | A | 1-375 | [»] | |
4Y2H | X-ray | 2.37 | A/B | 27-375 | [»] | |
4Y30 | X-ray | 2.10 | A/B | 25-375 | [»] | |
5E8R | X-ray | 2.55 | A/B | 1-375 | [»] | |
5EGS | X-ray | 2.15 | A/B/C/D | 1-375 | [»] | |
5HZM | X-ray | 2.02 | A | 1-375 | [»] | |
5WCF | X-ray | 1.98 | A | 1-375 | [»] | |
6P7I | X-ray | 2.00 | A/B/C/D | 1-375 | [»] | |
6W6D | X-ray | 1.91 | A | 1-375 | [»] | |
6WAD | X-ray | 2.45 | A | 1-375 | [»] | |
7NR4 | X-ray | 2.03 | A/B/C/D | 1-375 | [»] | |
AlphaFoldDBi | Q96LA8 | |||||
SMRi | Q96LA8 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 120469, 164 interactors |
IntActi | Q96LA8, 105 interactors |
MINTi | Q96LA8 |
STRINGi | 9606.ENSP00000359095 |
Chemistry databases
BindingDBi | Q96LA8 |
ChEMBLi | CHEMBL1275221 |
GuidetoPHARMACOLOGYi | 1257 |
PTM databases
iPTMneti | Q96LA8 |
PhosphoSitePlusi | Q96LA8 |
Genetic variation databases
BioMutai | PRMT6 |
DMDMi | 20137409 |
Proteomic databases
EPDi | Q96LA8 |
jPOSTi | Q96LA8 |
MassIVEi | Q96LA8 |
MaxQBi | Q96LA8 |
PaxDbi | Q96LA8 |
PeptideAtlasi | Q96LA8 |
PRIDEi | Q96LA8 |
ProteomicsDBi | 77181 [Q96LA8-1] 77182 [Q96LA8-2] |
Protocols and materials databases
Antibodypediai | 21010, 417 antibodies from 42 providers |
DNASUi | 55170 |
Genome annotation databases
Ensembli | ENST00000370078.2; ENSP00000359095.1; ENSG00000198890.9 |
GeneIDi | 55170 |
KEGGi | hsa:55170 |
MANE-Selecti | ENST00000370078.2; ENSP00000359095.1; NM_018137.3; NP_060607.2 |
UCSCi | uc010ous.4, human [Q96LA8-1] |
Organism-specific databases
CTDi | 55170 |
DisGeNETi | 55170 |
GeneCardsi | PRMT6 |
HGNCi | HGNC:18241, PRMT6 |
HPAi | ENSG00000198890, Low tissue specificity |
MIMi | 608274, gene |
neXtProti | NX_Q96LA8 |
OpenTargetsi | ENSG00000198890 |
PharmGKBi | PA134992775 |
VEuPathDBi | HostDB:ENSG00000198890 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG1499, Eukaryota |
GeneTreei | ENSGT00940000160961 |
HOGENOMi | CLU_017375_1_2_1 |
InParanoidi | Q96LA8 |
OMAi | SARHICI |
OrthoDBi | 840669at2759 |
PhylomeDBi | Q96LA8 |
TreeFami | TF328817 |
Enzyme and pathway databases
BRENDAi | 2.1.1.319, 2681 |
PathwayCommonsi | Q96LA8 |
Reactomei | R-HSA-3214858, RMTs methylate histone arginines R-HSA-8936459, RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function |
SABIO-RKi | Q96LA8 |
SignaLinki | Q96LA8 |
Miscellaneous databases
BioGRID-ORCSi | 55170, 16 hits in 1084 CRISPR screens |
ChiTaRSi | PRMT6, human |
GeneWikii | PRMT6 |
GenomeRNAii | 55170 |
Pharosi | Q96LA8, Tchem |
PROi | PR:Q96LA8 |
RNActi | Q96LA8, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000198890, Expressed in metanephros and 206 other tissues |
ExpressionAtlasi | Q96LA8, baseline and differential |
Genevisiblei | Q96LA8, HS |
Family and domain databases
Gene3Di | 3.40.50.150, 1 hit |
InterProi | View protein in InterPro IPR025799, Arg_MeTrfase IPR041698, Methyltransf_25 IPR029063, SAM-dependent_MTases |
PANTHERi | PTHR11006, PTHR11006, 1 hit |
Pfami | View protein in Pfam PF13649, Methyltransf_25, 1 hit |
SUPFAMi | SSF53335, SSF53335, 1 hit |
PROSITEi | View protein in PROSITE PS51678, SAM_MT_PRMT, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | ANM6_HUMAN | |
Accessioni | Q96LA8Primary (citable) accession number: Q96LA8 Secondary accession number(s): A3KME1 Q9NVR8 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | March 27, 2002 |
Last sequence update: | December 1, 2001 | |
Last modified: | May 25, 2022 | |
This is version 184 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human chromosome 1
Human chromosome 1: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families