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Protein

Protein arginine N-methyltransferase 6

Gene

PRMT6

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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. Preferentially methylates arginyl residues present in a glycine and arginine-rich domain and displays preference for monomethylated substrates. Specifically mediates the asymmetric dimethylation of histone H3 'Arg-2' to form H3R2me2a. H3R2me2a represents a specific tag for epigenetic transcriptional repression and is mutually exclusive with methylation on histone H3 'Lys-4' (H3K4me2 and H3K4me3). Acts as a transcriptional repressor of various genes such as HOXA2, THBS1 and TP53. 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. Methylates HMGA1. 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).By similarity11 Publications

Catalytic activityi

2 S-adenosyl-L-methionine + [protein]-L-arginine = 2 S-adenosyl-L-homocysteine + [protein]-N(omega),N(omega)-dimethyl-L-arginine.4 Publications

Kineticsi

  1. KM=18.6 µM for AdoMet1 Publication
  2. KM=501 µM for WGGYSRGGYGGW peptide1 Publication
  3. KM=183.7 µM for WGGYSR(MMA)GGYGGW monomethylated peptide1 Publication
  1. Vmax=3.3 nmol/min/mg enzyme with AdoMet as substrate1 Publication
  2. Vmax=1.8 nmol/min/mg enzyme with WGGYSRGGYGGW peptide as substrate1 Publication
  3. Vmax=3.2 nmol/min/mg enzyme with WGGYSR(MMA)GGYGGW monomethylated peptide as substrate1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei57S-adenosyl-L-methionineBy similarity1
Binding sitei66S-adenosyl-L-methionine1
Binding sitei90S-adenosyl-L-methionine; via carbonyl oxygen1
Binding sitei112S-adenosyl-L-methionine1
Binding sitei141S-adenosyl-L-methionine1
Active sitei155By similarity1
Active sitei164By similarity1

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
  • cell growth Source: Ensembl
  • cellular senescence Source: Ensembl
  • histone H3-R2 methylation Source: UniProtKB
  • histone methylation Source: UniProtKB
  • negative regulation of transcription, DNA-templated Source: UniProtKB
  • negative regulation of transcription from RNA polymerase II promoter Source: Ensembl
  • peptidyl-arginine methylation, to asymmetrical-dimethyl arginine Source: UniProtKB
  • transcription, DNA-templated Source: UniProtKB-KW
  • viral process Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Chromatin regulator, Methyltransferase, Repressor, Transferase

Keywords - Biological processi

DNA damage, DNA repair, Host-virus interaction, Transcription, Transcription regulation

Keywords - Ligandi

S-adenosyl-L-methionine

Enzyme and pathway databases

BioCyciZFISH:HS11391-MONOMER.
BRENDAi2.1.1.125. 2681.
ReactomeiR-HSA-3214858. RMTs methylate histone arginines.
SABIO-RKQ96LA8.

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:18241. PRMT6.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: GO_Central
  • nucleoplasm Source: Reactome
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi35R → A: Inhibits automethylation but does not affect methylation of other proteins. Reduces protein stability. 1 Publication1
Mutagenesisi86 – 88VLD → KLA in PRMT6dn; abolishes histone methyltransferase H3R2me2a and transcriptional coactivator activities and reduces protein stability. This mutation abolishes automethylation. 3 Publications3

Organism-specific databases

DisGeNETi55170.
OpenTargetsiENSG00000198890.
PharmGKBiPA134992775.

Chemistry databases

ChEMBLiCHEMBL1275221.
GuidetoPHARMACOLOGYi1257.

Polymorphism and mutation databases

BioMutaiPRMT6.
DMDMi20137409.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002123321 – 375Protein arginine N-methyltransferase 6Add BLAST375

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei21PhosphothreonineCombined sources1
Modified residuei29Omega-N-methylated arginine; by autocatalysis1 Publication1
Modified residuei35Omega-N-methylated arginine; by autocatalysis1 Publication1
Modified residuei37Omega-N-methylated arginine; by autocatalysis1 Publication1

Post-translational modificationi

Automethylation enhances its stability and antiretroviral activity.

Keywords - PTMi

Methylation, Phosphoprotein

Proteomic databases

EPDiQ96LA8.
MaxQBiQ96LA8.
PaxDbiQ96LA8.
PeptideAtlasiQ96LA8.
PRIDEiQ96LA8.

PTM databases

iPTMnetiQ96LA8.
PhosphoSitePlusiQ96LA8.

Expressioni

Tissue specificityi

Highly expressed in kidney and testis.1 Publication

Gene expression databases

BgeeiENSG00000198890.
CleanExiHS_PRMT6.
GenevisibleiQ96LA8. HS.

Organism-specific databases

HPAiHPA059424.

Interactioni

Subunit structurei

Interacts with (and methylates) HIV-1 Tat, Rev and Nucleocapsid protein p7 (NC). Interacts with EPB41L3 and NCOA1.10 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
A8K9323EBI-912440,EBI-10174671
C8orf74Q6P0472EBI-912440,EBI-8466055
CDCA4Q9BXL82EBI-912440,EBI-1773949
DNAJA3Q96EY12EBI-912440,EBI-356767
DNALI1O146452EBI-912440,EBI-395638
FYCO1Q9BQS82EBI-912440,EBI-2869338
GRHL3Q8TE852EBI-912440,EBI-8469396
GSTCDQ8NEC72EBI-912440,EBI-8469616
GTPBP2Q9BX102EBI-912440,EBI-6115579
HESX1Q9UBX02EBI-912440,EBI-8470369
HMGA1P17096-14EBI-912440,EBI-746854
HMGA2P529262EBI-912440,EBI-912511
KIF9Q9HAQ22EBI-912440,EBI-8472129
KLHL20Q9Y2M52EBI-912440,EBI-714379
LOXL4Q96JB62EBI-912440,EBI-749562
MED28Q9H2042EBI-912440,EBI-514199
NR1D2Q149952EBI-912440,EBI-6144053
OAS1P009732EBI-912440,EBI-3932815
PCGF5Q86SE92EBI-912440,EBI-2827999
PSMD11O002312EBI-912440,EBI-357816
RASSF2P507492EBI-912440,EBI-960081
SERGEFQ9UGK82EBI-912440,EBI-465368
SMAD9O151982EBI-912440,EBI-748763
SNF8Q96H202EBI-912440,EBI-747719
SPSB1Q96BD62EBI-912440,EBI-2659201
STARD10Q9Y3652EBI-912440,EBI-4289836
THEMISQ8N1K52EBI-912440,EBI-2873538
TMED5Q9Y3A62EBI-912440,EBI-7560959

GO - Molecular functioni

  • histone binding Source: UniProtKB

Protein-protein interaction databases

BioGridi120469. 122 interactors.
IntActiQ96LA8. 85 interactors.
MINTiMINT-6631342.
STRINGi9606.ENSP00000359095.

Chemistry databases

BindingDBiQ96LA8.

Structurei

Secondary structure

1375
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi26 – 38Combined sources13
Helixi41 – 49Combined sources9
Helixi51 – 62Combined sources12
Helixi64 – 75Combined sources12
Helixi78 – 81Combined sources4
Beta strandi85 – 90Combined sources6
Helixi95 – 102Combined sources8
Beta strandi106 – 112Combined sources7
Helixi117 – 126Combined sources10
Turni130 – 132Combined sources3
Beta strandi133 – 138Combined sources6
Turni140 – 142Combined sources3
Beta strandi149 – 153Combined sources5
Beta strandi158 – 163Combined sources6
Helixi167 – 177Combined sources11
Beta strandi178 – 186Combined sources9
Beta strandi188 – 196Combined sources9
Helixi199 – 206Combined sources8
Helixi207 – 210Combined sources4
Helixi211 – 215Combined sources5
Helixi220 – 222Combined sources3
Helixi223 – 231Combined sources9
Beta strandi235 – 239Combined sources5
Helixi243 – 245Combined sources3
Beta strandi251 – 257Combined sources7
Helixi263 – 269Combined sources7
Beta strandi271 – 279Combined sources9
Beta strandi283 – 296Combined sources14
Turni299 – 302Combined sources4
Beta strandi305 – 308Combined sources4
Beta strandi320 – 331Combined sources12
Beta strandi336 – 345Combined sources10
Beta strandi352 – 361Combined sources10
Beta strandi367 – 373Combined sources7

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4HC4X-ray1.97A1-375[»]
4QPPX-ray2.52A/B/C1-375[»]
4QQKX-ray1.88A1-375[»]
4Y2HX-ray2.37A/B27-375[»]
4Y30X-ray2.10A/B25-375[»]
5E8RX-ray2.55A/B1-375[»]
5EGSX-ray2.15A/B/C/D1-375[»]
5HZMX-ray2.02A1-375[»]
ProteinModelPortaliQ96LA8.
SMRiQ96LA8.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini44 – 374SAM-dependent MTase PRMT-typePROSITE-ProRule annotationAdd BLAST331

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi12 – 20Poly-Gly9

Sequence similaritiesi

Belongs to the class I-like SAM-binding methyltransferase superfamily. Protein arginine N-methyltransferase family. PRMT6 subfamily.PROSITE-ProRule annotation
Contains 1 SAM-dependent MTase PRMT-type domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG1499. Eukaryota.
ENOG410XQYH. LUCA.
GeneTreeiENSGT00550000074406.
HOGENOMiHOG000198521.
HOVERGENiHBG095907.
InParanoidiQ96LA8.
KOiK11437.
OMAiGRFRFSC.
OrthoDBiEOG091G0A0U.
PhylomeDBiQ96LA8.
TreeFamiTF328817.

Family and domain databases

Gene3Di3.40.50.150. 1 hit.
InterProiIPR025799. Arg_MeTrfase.
IPR029063. SAM-dependent_MTases.
[Graphical view]
PANTHERiPTHR11006. PTHR11006. 1 hit.
SUPFAMiSSF53335. SSF53335. 1 hit.
PROSITEiPS51678. SAM_MT_PRMT. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

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.

« Hide

        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
Length:375
Mass (Da):41,938
Last modified:December 1, 2001 - v1
Checksum:i40AAEC7342C08A38
GO
Isoform 2 (identifier: Q96LA8-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     26-109: GAEREAALER...CAQAGARRVY → D

Note: No experimental confirmation available.
Show »
Length:292
Mass (Da):32,509
Checksum:i9E6341283024795C
GO

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 keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_057150194A → V.1 PublicationCorresponds to variant rs2232016dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_03746526 – 109GAERE…ARRVY → D in isoform 2. 1 PublicationAdd BLAST84

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. Translation: CAI19090.1.
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.
CCDSiCCDS41360.2. [Q96LA8-1]
RefSeqiNP_060607.2. NM_018137.2. [Q96LA8-1]
UniGeneiHs.26006.

Genome annotation databases

EnsembliENST00000370078; ENSP00000359095; ENSG00000198890. [Q96LA8-1]
GeneIDi55170.
KEGGihsa:55170.
UCSCiuc010ous.4. human. [Q96LA8-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

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. Translation: CAI19090.1.
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.
CCDSiCCDS41360.2. [Q96LA8-1]
RefSeqiNP_060607.2. NM_018137.2. [Q96LA8-1]
UniGeneiHs.26006.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4HC4X-ray1.97A1-375[»]
4QPPX-ray2.52A/B/C1-375[»]
4QQKX-ray1.88A1-375[»]
4Y2HX-ray2.37A/B27-375[»]
4Y30X-ray2.10A/B25-375[»]
5E8RX-ray2.55A/B1-375[»]
5EGSX-ray2.15A/B/C/D1-375[»]
5HZMX-ray2.02A1-375[»]
ProteinModelPortaliQ96LA8.
SMRiQ96LA8.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi120469. 122 interactors.
IntActiQ96LA8. 85 interactors.
MINTiMINT-6631342.
STRINGi9606.ENSP00000359095.

Chemistry databases

BindingDBiQ96LA8.
ChEMBLiCHEMBL1275221.
GuidetoPHARMACOLOGYi1257.

PTM databases

iPTMnetiQ96LA8.
PhosphoSitePlusiQ96LA8.

Polymorphism and mutation databases

BioMutaiPRMT6.
DMDMi20137409.

Proteomic databases

EPDiQ96LA8.
MaxQBiQ96LA8.
PaxDbiQ96LA8.
PeptideAtlasiQ96LA8.
PRIDEiQ96LA8.

Protocols and materials databases

DNASUi55170.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000370078; ENSP00000359095; ENSG00000198890. [Q96LA8-1]
GeneIDi55170.
KEGGihsa:55170.
UCSCiuc010ous.4. human. [Q96LA8-1]

Organism-specific databases

CTDi55170.
DisGeNETi55170.
GeneCardsiPRMT6.
HGNCiHGNC:18241. PRMT6.
HPAiHPA059424.
MIMi608274. gene.
neXtProtiNX_Q96LA8.
OpenTargetsiENSG00000198890.
PharmGKBiPA134992775.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1499. Eukaryota.
ENOG410XQYH. LUCA.
GeneTreeiENSGT00550000074406.
HOGENOMiHOG000198521.
HOVERGENiHBG095907.
InParanoidiQ96LA8.
KOiK11437.
OMAiGRFRFSC.
OrthoDBiEOG091G0A0U.
PhylomeDBiQ96LA8.
TreeFamiTF328817.

Enzyme and pathway databases

BioCyciZFISH:HS11391-MONOMER.
BRENDAi2.1.1.125. 2681.
ReactomeiR-HSA-3214858. RMTs methylate histone arginines.
SABIO-RKQ96LA8.

Miscellaneous databases

GeneWikiiPRMT6.
GenomeRNAii55170.
PROiQ96LA8.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000198890.
CleanExiHS_PRMT6.
GenevisibleiQ96LA8. HS.

Family and domain databases

Gene3Di3.40.50.150. 1 hit.
InterProiIPR025799. Arg_MeTrfase.
IPR029063. SAM-dependent_MTases.
[Graphical view]
PANTHERiPTHR11006. PTHR11006. 1 hit.
SUPFAMiSSF53335. SSF53335. 1 hit.
PROSITEiPS51678. SAM_MT_PRMT. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiANM6_HUMAN
AccessioniPrimary (citable) accession number: Q96LA8
Secondary accession number(s): A3KME1
, B4DID8, Q5T5Y5, Q6DKI4, Q9NVR8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 27, 2002
Last sequence update: December 1, 2001
Last modified: November 2, 2016
This is version 146 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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 proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.