UniProtKB - Q96LA8 (ANM6_HUMAN)
Protein
Protein arginine N-methyltransferase 6
Gene
PRMT6
Organism
Homo sapiens (Human)
Status
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). 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. 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).By similarity11 Publications
Catalytic activityi
- L-arginyl-[protein] + 2 S-adenosyl-L-methionine = 2 H+ + Nω,Nω-dimethyl-L-arginyl-[protein] + 2 S-adenosyl-L-homocysteine4 PublicationsEC:2.1.1.3194 Publications
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: Reactome
- 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
- histone arginine methylation Source: GO_Central
- histone H3-R2 methylation Source: UniProtKB
- histone methylation 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 signal transduction by p53 class mediator Source: Ensembl
- regulation of transcription, DNA-templated Source: GO_Central
- viral process Source: UniProtKB-KW
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 | 2.1.1.125 2681 |
Reactomei | R-HSA-3214858 RMTs methylate histone arginines R-HSA-8936459 RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function |
SABIO-RKi | Q96LA8 |
Names & Taxonomyi
Protein namesi | Recommended name: Protein arginine N-methyltransferase 6 (EC:2.1.1.3194 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
EuPathDBi | HostDB:ENSG00000198890.7 |
HGNCi | HGNC:18241 PRMT6 |
MIMi | 608274 gene |
neXtProti | NX_Q96LA8 |
Subcellular locationi
Nucleus
- Nucleus 1 Publication
Cytosol
- cytosol Source: GO_Central
Nucleus
- nucleolus Source: HPA
- nucleoplasm Source: Reactome
- 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. 3 Publications | 3 |
Organism-specific databases
DisGeNETi | 55170 |
OpenTargetsi | ENSG00000198890 |
PharmGKBi | PA134992775 |
Chemistry databases
ChEMBLi | CHEMBL1275221 |
GuidetoPHARMACOLOGYi | 1257 |
Polymorphism and mutation 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 | Omega-N-methylated arginine; by autocatalysis1 Publication | 1 | |
Modified residuei | 35 | Omega-N-methylated arginine; by autocatalysis1 Publication | 1 | |
Modified residuei | 37 | Omega-N-methylated arginine; by autocatalysis1 Publication | 1 |
Post-translational modificationi
Automethylation enhances its stability and antiretroviral activity.
Keywords - PTMi
Methylation, PhosphoproteinProteomic databases
EPDi | Q96LA8 |
jPOSTi | Q96LA8 |
MaxQBi | Q96LA8 |
PaxDbi | Q96LA8 |
PeptideAtlasi | Q96LA8 |
PRIDEi | Q96LA8 |
ProteomicsDBi | 77181 77182 [Q96LA8-2] |
PTM databases
iPTMneti | Q96LA8 |
PhosphoSitePlusi | Q96LA8 |
Expressioni
Tissue specificityi
Highly expressed in kidney and testis.1 Publication
Gene expression databases
Bgeei | ENSG00000198890 Expressed in 188 organ(s), highest expression level in metanephros |
Genevisiblei | Q96LA8 HS |
Organism-specific databases
HPAi | HPA059424 |
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 Publication
Binary interactionsi
GO - Molecular functioni
- histone binding Source: UniProtKB
Protein-protein interaction databases
BioGridi | 120469, 130 interactors |
IntActi | Q96LA8, 86 interactors |
MINTi | Q96LA8 |
STRINGi | 9606.ENSP00000359095 |
Chemistry databases
BindingDBi | Q96LA8 |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D 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 | [»] | |
ProteinModelPortali | Q96LA8 | |||||
SMRi | Q96LA8 | |||||
ModBasei | Search... | |||||
MobiDBi | 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 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 12 – 20 | Poly-Gly | 9 |
Sequence similaritiesi
Belongs to the class I-like SAM-binding methyltransferase superfamily. Protein arginine N-methyltransferase family. PRMT6 subfamily.PROSITE-ProRule annotation
Phylogenomic databases
eggNOGi | KOG1499 Eukaryota ENOG410XQYH LUCA |
GeneTreei | ENSGT00940000160961 |
HOGENOMi | HOG000198521 |
HOVERGENi | HBG095907 |
InParanoidi | Q96LA8 |
KOi | K11437 |
OMAi | GVVFHWM |
OrthoDBi | 840669at2759 |
PhylomeDBi | Q96LA8 |
TreeFami | TF328817 |
Family and domain databases
InterProi | View protein in InterPro IPR025799 Arg_MeTrfase IPR029063 SAM-dependent_MTases |
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
Isoform 1 (identifier: Q96LA8-1) [UniParc]FASTAAdd to basket
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.
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
The sequence AAH02729 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence AAH63446 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence BAA91681 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
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] |
UniGenei | Hs.26006 |
Genome annotation databases
Ensembli | ENST00000370078; ENSP00000359095; ENSG00000198890 [Q96LA8-1] |
GeneIDi | 55170 |
KEGGi | hsa:55170 |
UCSCi | uc010ous.4 human [Q96LA8-1] |
Keywords - Coding sequence diversityi
Alternative splicing, PolymorphismSimilar 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] |
UniGenei | Hs.26006 |
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 | [»] | |
ProteinModelPortali | Q96LA8 | |||||
SMRi | Q96LA8 | |||||
ModBasei | Search... | |||||
MobiDBi | Search... |
Protein-protein interaction databases
BioGridi | 120469, 130 interactors |
IntActi | Q96LA8, 86 interactors |
MINTi | Q96LA8 |
STRINGi | 9606.ENSP00000359095 |
Chemistry databases
BindingDBi | Q96LA8 |
ChEMBLi | CHEMBL1275221 |
GuidetoPHARMACOLOGYi | 1257 |
PTM databases
iPTMneti | Q96LA8 |
PhosphoSitePlusi | Q96LA8 |
Polymorphism and mutation databases
BioMutai | PRMT6 |
DMDMi | 20137409 |
Proteomic databases
EPDi | Q96LA8 |
jPOSTi | Q96LA8 |
MaxQBi | Q96LA8 |
PaxDbi | Q96LA8 |
PeptideAtlasi | Q96LA8 |
PRIDEi | Q96LA8 |
ProteomicsDBi | 77181 77182 [Q96LA8-2] |
Protocols and materials databases
DNASUi | 55170 |
Structural Biology Knowledgebase | Search... |
Genome annotation databases
Ensembli | ENST00000370078; ENSP00000359095; ENSG00000198890 [Q96LA8-1] |
GeneIDi | 55170 |
KEGGi | hsa:55170 |
UCSCi | uc010ous.4 human [Q96LA8-1] |
Organism-specific databases
CTDi | 55170 |
DisGeNETi | 55170 |
EuPathDBi | HostDB:ENSG00000198890.7 |
GeneCardsi | PRMT6 |
HGNCi | HGNC:18241 PRMT6 |
HPAi | HPA059424 |
MIMi | 608274 gene |
neXtProti | NX_Q96LA8 |
OpenTargetsi | ENSG00000198890 |
PharmGKBi | PA134992775 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG1499 Eukaryota ENOG410XQYH LUCA |
GeneTreei | ENSGT00940000160961 |
HOGENOMi | HOG000198521 |
HOVERGENi | HBG095907 |
InParanoidi | Q96LA8 |
KOi | K11437 |
OMAi | GVVFHWM |
OrthoDBi | 840669at2759 |
PhylomeDBi | Q96LA8 |
TreeFami | TF328817 |
Enzyme and pathway databases
BRENDAi | 2.1.1.125 2681 |
Reactomei | R-HSA-3214858 RMTs methylate histone arginines R-HSA-8936459 RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function |
SABIO-RKi | Q96LA8 |
Miscellaneous databases
GeneWikii | PRMT6 |
GenomeRNAii | 55170 |
PROi | PR:Q96LA8 |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000198890 Expressed in 188 organ(s), highest expression level in metanephros |
Genevisiblei | Q96LA8 HS |
Family and domain databases
InterProi | View protein in InterPro IPR025799 Arg_MeTrfase IPR029063 SAM-dependent_MTases |
SUPFAMi | SSF53335 SSF53335, 1 hit |
PROSITEi | View protein in PROSITE PS51678 SAM_MT_PRMT, 1 hit |
ProtoNeti | 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: | February 13, 2019 | |
This is version 166 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, Complete proteome, Reference proteomeDocuments
- SIMILARITY comments
Index of protein domains and families - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - Human chromosome 1
Human chromosome 1: entries, gene names and cross-references to MIM - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations - Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations