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Protein

Protein arginine N-methyltransferase 1

Gene

PRMT1

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

Functioni

Arginine methyltransferase that methylates (mono and asymmetric dimethylation) the guanidino nitrogens of arginyl residues present in proteins such as ESR1, histone H2, H3 and H4, PIAS1, HNRNPA1, HNRNPD, NFATC2IP, SUPT5H, TAF15 and EWS. Constitutes the main enzyme that mediates monomethylation and asymmetric dimethylation of histone H4 'Arg-4' (H4R3me1 and H4R3me2a, respectively), a specific tag for epigenetic transcriptional activation. Together with dimethylated PIAS1, represses STAT1 transcriptional activity, in the late phase of interferon gamma (IFN-gamma) signaling. May be involved in the regulation of TAF15 transcriptional activity, act as an activator of estrogen receptor (ER)-mediated transactivation, play a key role in neurite outgrowth and act as a negative regulator of megakaryocytic differentiation, by modulating p38 MAPK pathway. Methylates FOXO1 and retains it in the nucleus increasing its transcriptional activity. Methylates CHTOP and this methylation is critical for its 5-hydroxymethylcytosine (5hmC)-binding activity (PubMed:25284789). Methylates H4R3 in genes involved in glioblastomagenesis in a CHTOP- and/or TET1-dependent manner (PubMed:25284789).11 Publications

Catalytic activityi

2 S-adenosyl-L-methionine + [protein]-L-arginine = 2 S-adenosyl-L-homocysteine + [protein]-N(omega),N(omega)-dimethyl-L-arginine.3 Publications

Enzyme regulationi

By BTG1, BTG2 and ILF3.

Kineticsi

  1. KM=1 µM for AdoMet1 Publication
  2. KM=4.2 µM for H41 Publication
  1. Vmax=1.2 nmol/min/mg enzyme toward AdoMet1 Publication
  2. Vmax=1.24 nmol/min/mg enzyme toward H41 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei53S-adenosyl-L-methionineBy similarity1
Binding sitei62S-adenosyl-L-methionineBy similarity1
Binding sitei86S-adenosyl-L-methionine; via carbonyl oxygenBy similarity1
Binding sitei108S-adenosyl-L-methionineBy similarity1
Binding sitei137S-adenosyl-L-methionineBy similarity1
Active sitei152By similarity1
Active sitei161By similarity1

GO - Molecular functioni

  • enzyme binding Source: UniProtKB
  • histone methyltransferase activity Source: UniProtKB
  • histone methyltransferase activity (H4-R3 specific) Source: UniProtKB
  • identical protein binding Source: IntAct
  • methyl-CpG binding Source: UniProtKB
  • methyltransferase activity Source: ProtInc
  • mitogen-activated protein kinase p38 binding Source: BHF-UCL
  • N-methyltransferase activity Source: UniProtKB
  • protein-arginine N-methyltransferase activity Source: MGI
  • protein-arginine omega-N asymmetric methyltransferase activity Source: UniProtKB
  • protein methyltransferase activity Source: UniProtKB
  • RNA binding Source: UniProtKB

GO - Biological processi

  • cell surface receptor signaling pathway Source: ProtInc
  • DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest Source: Reactome
  • histone H4-R3 methylation Source: UniProtKB
  • histone methylation Source: UniProtKB
  • negative regulation of megakaryocyte differentiation Source: UniProtKB
  • neuron projection development Source: UniProtKB
  • peptidyl-arginine methylation Source: UniProtKB
  • positive regulation of erythrocyte differentiation Source: BHF-UCL
  • positive regulation of hemoglobin biosynthetic process Source: BHF-UCL
  • positive regulation of p38MAPK cascade Source: BHF-UCL
  • protein methylation Source: ProtInc
  • regulation of transcription, DNA-templated Source: GO_Central

Keywordsi

Molecular functionMethyltransferase, Transferase
LigandS-adenosyl-L-methionine

Enzyme and pathway databases

BioCyciMetaCyc:HS05019-MONOMER.
BRENDAi2.1.1.126. 2681.
ReactomeiR-HSA-3214858. RMTs methylate histone arginines.
R-HSA-6804114. TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest.
SABIO-RKiQ99873.
SignaLinkiQ99873.
SIGNORiQ99873.

Names & Taxonomyi

Protein namesi
Recommended name:
Protein arginine N-methyltransferase 1 (EC:2.1.1.3193 Publications)
Alternative name(s):
Histone-arginine N-methyltransferase PRMT1
Interferon receptor 1-bound protein 4
Gene namesi
Name:PRMT1
Synonyms:HMT2, HRMT1L2, IR1B4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:5187. PRMT1.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: ProtInc
  • cytosol Source: GO_Central
  • methylosome Source: UniProtKB
  • nucleoplasm Source: Reactome
  • nucleus Source: MGI

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi82V → A: Loss of FOXO1 methylation, its nuclear retention, and transcriptional activity. 1 Publication1
Mutagenesisi83L → A: Loss of FOXO1 methylation, its nuclear retention, and transcriptional activity. 1 Publication1
Mutagenesisi84D → A: Loss of FOXO1 methylation, its nuclear retention, and transcriptional activity. 1 Publication1

Organism-specific databases

DisGeNETi3276.
MalaCardsiPRMT1.
OpenTargetsiENSG00000126457.
PharmGKBiPA29461.

Chemistry databases

ChEMBLiCHEMBL5524.
DrugBankiDB01752. S-Adenosyl-L-Homocysteine.
GuidetoPHARMACOLOGYi1252.

Polymorphism and mutation databases

DMDMi161789011.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002123211 – 361Protein arginine N-methyltransferase 1Add BLAST361

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei124N6-succinyllysineBy similarity1
Modified residuei294PhosphoserineCombined sources1
Modified residuei297PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ99873.
MaxQBiQ99873.
PaxDbiQ99873.
PeptideAtlasiQ99873.
PRIDEiQ99873.

PTM databases

iPTMnetiQ99873.
PhosphoSitePlusiQ99873.
SwissPalmiQ99873.

Expressioni

Tissue specificityi

Widely expressed.1 Publication

Gene expression databases

BgeeiENSG00000126457.
CleanExiHS_PRMT1.
ExpressionAtlasiQ99873. baseline and differential.
GenevisibleiQ99873. HS.

Organism-specific databases

HPAiCAB022550.
HPA069769.
HPA072136.

Interactioni

Subunit structurei

Homodimer and heterodimer with PRMT8. Individual homodimers can associate to form a homohexamer. Interacts with BTG1, BTG2, NFATC2IP and IFNAR1 (By similarity). Interacts with and methylates CHTOP, thereby enabling the interaction of CHTOP with the 5FMC complex (PubMed:25284789). Interacts with ILF3 and SUPT5H. Interacts with and methylates FOXO1, leading to the nuclear retention of FOXO1 and the stimulation of FOXO1 transcriptional activity. Methylation of FOXO1 is increased upon oxidative stress. Interacts with and probably methylates ATXN2L (PubMed:25748791). Component of the methylosome, a 20S complex containing at least CLNS1A/pICln, PRMT5/SKB1, WDR77/MEP50, PRMT1 and ERH (PubMed:25284789).By similarity7 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • enzyme binding Source: UniProtKB
  • identical protein binding Source: IntAct
  • mitogen-activated protein kinase p38 binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi109512. 157 interactors.
DIPiDIP-30878N.
IntActiQ99873. 92 interactors.
MINTiMINT-4861475.
STRINGi9606.ENSP00000406162.

Chemistry databases

BindingDBiQ99873.

Structurei

3D structure databases

ProteinModelPortaliQ99873.
SMRiQ99873.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini40 – 361SAM-dependent MTase PRMT-typePROSITE-ProRule annotationAdd BLAST322

Sequence similaritiesi

Belongs to the class I-like SAM-binding methyltransferase superfamily. Protein arginine N-methyltransferase family.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG1499. Eukaryota.
ENOG410XQYH. LUCA.
GeneTreeiENSGT00550000074406.
HOGENOMiHOG000198521.
HOVERGENiHBG001793.
InParanoidiQ99873.
KOiK11434.
PhylomeDBiQ99873.

Family and domain databases

InterProiView protein in InterPro
IPR025799. Arg_MeTrfase.
IPR029063. SAM-dependent_MTases.
SUPFAMiSSF53335. SSF53335. 1 hit.
PROSITEiView protein in PROSITE
PS51678. SAM_MT_PRMT. 1 hit.

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q99873-1) [UniParc]FASTAAdd to basket
Also known as: V2

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
MENFVATLAN GMSLQPPLEE VSCGQAESSE KPNAEDMTSK DYYFDSYAHF
60 70 80 90 100
GIHEEMLKDE VRTLTYRNSM FHNRHLFKDK VVLDVGSGTG ILCMFAAKAG
110 120 130 140 150
ARKVIGIECS SISDYAVKIV KANKLDHVVT IIKGKVEEVE LPVEKVDIII
160 170 180 190 200
SEWMGYCLFY ESMLNTVLYA RDKWLAPDGL IFPDRATLYV TAIEDRQYKD
210 220 230 240 250
YKIHWWENVY GFDMSCIKDV AIKEPLVDVV DPKQLVTNAC LIKEVDIYTV
260 270 280 290 300
KVEDLTFTSP FCLQVKRNDY VHALVAYFNI EFTRCHKRTG FSTSPESPYT
310 320 330 340 350
HWKQTVFYME DYLTVKTGEE IFGTIGMRPN AKNNRDLDFT IDLDFKGQLC
360
ELSCSTDYRM R
Length:361
Mass (Da):41,516
Last modified:December 4, 2007 - v2
Checksum:iA286D99B5AFC1860
GO
Isoform 2 (identifier: Q99873-2) [UniParc]FASTAAdd to basket
Also known as: V3

The sequence of this isoform differs from the canonical sequence as follows:
     1-19: MENFVATLANGMSLQPPLE → MVGVA

Show »
Length:347
Mass (Da):39,929
Checksum:i2546A25EF744E265
GO
Isoform 3 (identifier: Q99873-3) [UniParc]FASTAAdd to basket
Also known as: V1

The sequence of this isoform differs from the canonical sequence as follows:
     1-19: MENFVATLANGMSLQPPLE → M

Show »
Length:343
Mass (Da):39,602
Checksum:iDFC413AC52F49754
GO
Isoform 4 (identifier: Q99873-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-19: MENFVATLANGMSLQPPLE → MAAAEAANCIM

Show »
Length:353
Mass (Da):40,548
Checksum:i1704BA3762F3E264
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti108E → V in CAA71763 (PubMed:9545638).Curated1
Sequence conflicti108E → V in CAA71764 (PubMed:9545638).Curated1
Sequence conflicti108E → V in CAA71765 (PubMed:9545638).Curated1
Sequence conflicti108E → V in BAA11029 (PubMed:8675017).Curated1
Sequence conflicti147 – 175DIIIS…RDKWL → ASSSASGWATASSTSPCSTP CSMPGTSV in BAA11029 (PubMed:8675017).CuratedAdd BLAST29
Sequence conflicti202K → E in BAG65435 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03750178K → M. Corresponds to variant dbSNP:rs1804486Ensembl.1
Natural variantiVAR_037502158L → F. Corresponds to variant dbSNP:rs11673683Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0052081 – 19MENFV…QPPLE → MVGVA in isoform 2. 1 PublicationAdd BLAST19
Alternative sequenceiVSP_0052091 – 19MENFV…QPPLE → M in isoform 3. 1 PublicationAdd BLAST19
Alternative sequenceiVSP_0463341 – 19MENFV…QPPLE → MAAAEAANCIM in isoform 4. 2 PublicationsAdd BLAST19

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y10805 mRNA. Translation: CAA71763.1.
Y10806 mRNA. Translation: CAA71764.1.
Y10807 mRNA. Translation: CAA71765.1.
D66904 mRNA. Translation: BAA11029.1.
AF222689 Genomic DNA. Translation: AAF62893.1.
AF222689 Genomic DNA. Translation: AAF62894.1.
AF222689 Genomic DNA. Translation: AAF62895.1.
AK304660 mRNA. Translation: BAG65435.1.
CR407608 mRNA. Translation: CAG28536.1.
AC011495 Genomic DNA. No translation available.
CH471177 Genomic DNA. Translation: EAW52521.1.
BC019268 mRNA. Translation: AAH19268.2.
BC109282 mRNA. Translation: AAI09283.2.
BC109283 mRNA. Translation: AAI09284.2.
CCDSiCCDS42592.1. [Q99873-4]
RefSeqiNP_001527.3. NM_001536.5.
NP_938074.2. NM_198318.4. [Q99873-4]
XP_016882223.1. XM_017026734.1. [Q99873-2]
XP_016882224.1. XM_017026735.1. [Q99873-2]
UniGeneiHs.20521.

Genome annotation databases

EnsembliENST00000391851; ENSP00000375724; ENSG00000126457. [Q99873-4]
GeneIDi3276.
KEGGihsa:3276.
UCSCiuc002ppe.4. human. [Q99873-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiANM1_HUMAN
AccessioniPrimary (citable) accession number: Q99873
Secondary accession number(s): B4E3C3
, G5E9B6, Q15529, Q2VP93, Q6LEU5, Q8WUW5, Q99872, Q99874, Q9NZ04, Q9NZ05, Q9NZ06
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: December 4, 2007
Last modified: August 30, 2017
This is version 160 of the entry and version 2 of the sequence. See 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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: 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. SIMILARITY comments
    Index of protein domains and families