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Protein

Protein arginine N-methyltransferase 1

Gene

PRMT1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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, EWS, HABP4 and SERBP1 (PubMed:16879614, PubMed:26876602). 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 RBM15, promoting ubiquitination and degradation of RBM15 (PubMed:26575292). 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).15 Publications

Catalytic activityi

2 S-adenosyl-L-methionine + [protein]-L-arginine = 2 S-adenosyl-L-homocysteine + [protein]-N(omega),N(omega)-dimethyl-L-arginine.5 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 sitei63S-adenosyl-L-methionineBy similarity1
Binding sitei72S-adenosyl-L-methionineBy similarity1
Binding sitei96S-adenosyl-L-methionine; via carbonyl oxygenBy similarity1
Binding sitei118S-adenosyl-L-methionineBy similarity1
Binding sitei147S-adenosyl-L-methionineBy similarity1
Active sitei162By similarity1
Active sitei171By 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: UniProtKB
  • 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-arginine omega-N monomethyltransferase activity Source: UniProtKB
  • protein methyltransferase activity Source: UniProtKB
  • RNA binding Source: UniProtKB
  • S-adenosyl-L-methionine 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 cell proliferation 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 homooligomerization Source: UniProtKB
  • protein methylation Source: UniProtKB
  • regulation of megakaryocyte differentiation Source: UniProtKB
  • 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
R-HSA-8936459 RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function
R-HSA-9018519 Estrogen-dependent gene expression
SABIO-RKiQ99873
SignaLinkiQ99873
SIGNORiQ99873

Names & Taxonomyi

Protein namesi
Recommended name:
Protein arginine N-methyltransferase 1Curated (EC:2.1.1.3195 Publications)
Alternative name(s):
Histone-arginine N-methyltransferase PRMT1
Interferon receptor 1-bound protein 4
Gene namesi
Name:PRMT1Imported
Synonyms:HMT2, HRMT1L22 Publications, IR1B4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

EuPathDBiHostDB:ENSG00000126457.21
HGNCiHGNC:5187 PRMT1
MIMi602950 gene
neXtProtiNX_Q99873

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi92V → A: Loss of FOXO1 methylation, its nuclear retention, and transcriptional activity. 1 Publication1
Mutagenesisi93L → A: Loss of FOXO1 methylation, its nuclear retention, and transcriptional activity. 1 Publication1
Mutagenesisi94D → A: Loss of FOXO1 methylation, its nuclear retention, and transcriptional activity. 1 Publication1
Mutagenesisi280Y → A: No effect on S-adenosyl-L-methionine binding but reduced EWS protein methylation; when associated with A-322 and A-359. No effect on homodimerization but loss of homooligomerization; when associated with A-322 and A-359. 1 Publication1
Mutagenesisi322Y → A: No effect on S-adenosyl-L-methionine binding but reduced EWS protein methylation; when associated with A-280 and A-359. No effect on homodimerization but loss of homooligomerization; when associated with A-280 and A-359. 1 Publication1
Mutagenesisi359L → A: No effect on S-adenosyl-L-methionine binding but reduced EWS protein methylation; when associated with A-280 and A-322. No effect on homodimerization but loss of homooligomerization; when associated with A-280 and A-322. 1 Publication1

Organism-specific databases

DisGeNETi3276
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 – 371Protein arginine N-methyltransferase 1Add BLAST371

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei134N6-succinyllysineBy similarity1
Modified residuei304PhosphoserineCombined sources1
Modified residuei307PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ99873
MaxQBiQ99873
PaxDbiQ99873
PeptideAtlasiQ99873
PRIDEiQ99873
ProteomicsDBi78511
78512 [Q99873-2]
78513 [Q99873-3]

PTM databases

iPTMnetiQ99873
PhosphoSitePlusiQ99873
SwissPalmiQ99873

Expressioni

Tissue specificityi

Widely expressed (PubMed:11097842). Expressed strongly in colorectal cancer cells (at protein level) (PubMed:28040436). Expressed strongly in colorectal cancer tissues compared to wild-type colon samples (at protein level) (PubMed:28040436). Expressed strongly in colorectal cancer tissues compared to wild-type colon samples (PubMed:28040436).2 Publications

Gene expression databases

BgeeiENSG00000126457
CleanExiHS_PRMT1
ExpressionAtlasiQ99873 baseline and differential
GenevisibleiQ99873 HS

Organism-specific databases

HPAiCAB022550
HPA069769
HPA072136

Interactioni

Subunit structurei

Homodimer (PubMed:16879614, PubMed:26876602). Homooctamer; individual homodimers associates to form a homooctamer (PubMed:26876602). Individual homodimers can associate to form a homohexamer. Heterodimer with PRMT8. 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). Interacts with DHX9 (via RGG region) (PubMed:15084609). Interacts (via N-terminus) with HABP4 (PubMed:16879614).By similarity10 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

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

Protein-protein interaction databases

BioGridi109512, 217 interactors
CORUMiQ99873
DIPiDIP-30878N
IntActiQ99873, 105 interactors
MINTiQ99873
STRINGi9606.ENSP00000406162

Chemistry databases

BindingDBiQ99873

Structurei

3D structure databases

ProteinModelPortaliQ99873
SMRiQ99873
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini50 – 361SAM-dependent MTase PRMT-typePROSITE-ProRule annotationAdd BLAST312

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
OMAiRCHKRIG
OrthoDBiEOG091G0ADC
PhylomeDBiQ99873
TreeFamiTF300608

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
MAAAEAANCI MENFVATLAN GMSLQPPLEE VSCGQAESSE KPNAEDMTSK
60 70 80 90 100
DYYFDSYAHF GIHEEMLKDE VRTLTYRNSM FHNRHLFKDK VVLDVGSGTG
110 120 130 140 150
ILCMFAAKAG ARKVIGIECS SISDYAVKIV KANKLDHVVT IIKGKVEEVE
160 170 180 190 200
LPVEKVDIII SEWMGYCLFY ESMLNTVLYA RDKWLAPDGL IFPDRATLYV
210 220 230 240 250
TAIEDRQYKD YKIHWWENVY GFDMSCIKDV AIKEPLVDVV DPKQLVTNAC
260 270 280 290 300
LIKEVDIYTV KVEDLTFTSP FCLQVKRNDY VHALVAYFNI EFTRCHKRTG
310 320 330 340 350
FSTSPESPYT HWKQTVFYME DYLTVKTGEE IFGTIGMRPN AKNNRDLDFT
360 370
IDLDFKGQLC ELSCSTDYRM R
Length:371
Mass (Da):42,462
Last modified:March 28, 2018 - v3
Checksum:i544349801B0E1396
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:
     1-29: MAAAEAANCIMENFVATLANGMSLQPPLE → 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:
     11-30: MENFVATLANGMSLQPPLEE → ME

Show »
Length:353
Mass (Da):40,548
Checksum:i1704BA3762F3E264
GO
Isoform 4 (identifier: Q99873-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     13-30: Missing.
     186-253: Missing.

Show »
Length:285
Mass (Da):32,693
Checksum:i7D985F187D73F7E3
GO

Sequence cautioni

The sequence AAF62894 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence AAF62895 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence AAI09283 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence AAI09284 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAA11029 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence CAA71764 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence CAA71765 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti118E → V in CAA71763 (PubMed:9545638).Curated1
Sequence conflicti118E → V in CAA71764 (PubMed:9545638).Curated1
Sequence conflicti118E → V in CAA71765 (PubMed:9545638).Curated1
Sequence conflicti118E → V in BAA11029 (PubMed:8675017).Curated1
Sequence conflicti157 – 185DIIIS…RDKWL → ASSSASGWATASSTSPCSTP CSMPGTSV in BAA11029 (PubMed:8675017).CuratedAdd BLAST29
Sequence conflicti212K → E in BAG65435 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03750188K → M. Corresponds to variant dbSNP:rs1804486Ensembl.1
Natural variantiVAR_037502168L → F. Corresponds to variant dbSNP:rs11673683Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0052081 – 29MAAAE…QPPLE → MVGVA in isoform 2. 1 PublicationAdd BLAST29
Alternative sequenceiVSP_00520911 – 30MENFV…PPLEE → ME in isoform 3. 2 PublicationsAdd BLAST20
Alternative sequenceiVSP_05941913 – 30Missing in isoform 4. Add BLAST18
Alternative sequenceiVSP_059420186 – 253Missing in isoform 4. Add BLAST68

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y10805 mRNA Translation: CAA71763.1
Y10806 mRNA Translation: CAA71764.1 Different initiation.
Y10807 mRNA Translation: CAA71765.1 Different initiation.
D66904 mRNA Translation: BAA11029.1 Different initiation.
AF222689 Genomic DNA Translation: AAF62893.1
AF222689 Genomic DNA Translation: AAF62894.1 Different initiation.
AF222689 Genomic DNA Translation: AAF62895.1 Different initiation.
AK304660 mRNA Translation: BAG65435.1
CR407608 mRNA Translation: CAG28536.1
AC011495 Genomic DNA No translation available.
CH471177 Genomic DNA Translation: EAW52521.1
CH471177 Genomic DNA Translation: EAW52519.1
BC019268 mRNA Translation: AAH19268.2
BC109282 mRNA Translation: AAI09283.2 Different initiation.
BC109283 mRNA Translation: AAI09284.2 Different initiation.
CCDSiCCDS42592.1 [Q99873-3]
CCDS46145.1 [Q99873-1]
CCDS74425.1 [Q99873-5]
RefSeqiNP_001193971.1, NM_001207042.2 [Q99873-5]
NP_001527.3, NM_001536.5 [Q99873-1]
NP_938074.2, NM_198318.4 [Q99873-3]
XP_016882223.1, XM_017026734.1 [Q99873-2]
XP_016882224.1, XM_017026735.1 [Q99873-2]
UniGeneiHs.20521

Genome annotation databases

EnsembliENST00000391851; ENSP00000375724; ENSG00000126457 [Q99873-3]
ENST00000454376; ENSP00000406162; ENSG00000126457 [Q99873-1]
ENST00000610806; ENSP00000484505; ENSG00000126457 [Q99873-5]
GeneIDi3276
UCSCiuc002ppe.4 human [Q99873-1]
uc010enf.3 human

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiANM1_HUMAN
AccessioniPrimary (citable) accession number: Q99873
Secondary accession number(s): A0A087X1W2
, B4E3C3, G5E9B6, H7C2I1, Q15529, Q2VP93, Q6LEU5, Q8WUW5, Q99872, Q99874, Q9NZ04, Q9NZ05, Q9NZ06
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: March 28, 2018
Last modified: July 18, 2018
This is version 168 of the entry and version 3 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

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