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Q99873

- ANM1_HUMAN

UniProt

Q99873 - ANM1_HUMAN

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Protein
Protein arginine N-methyltransferase 1
Gene
PRMT1, HMT2, HRMT1L2, IR1B4
Organism
Homo sapiens (Human)
Status
Reviewed - 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.10 Publications

Catalytic activityi

S-adenosyl-L-methionine + arginine-[histone] = S-adenosyl-L-homocysteine + N(omega)-methyl-arginine-[histone].3 Publications

Enzyme regulationi

By BTG1, BTG2 and ILF3.

Kineticsi

  1. KM=1 µM for AdoMet1 Publication
  2. KM=4.2 µM for H4

Vmax=1.2 nmol/min/mg enzyme toward AdoMet

Vmax=1.24 nmol/min/mg enzyme toward H4

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei53 – 531S-adenosyl-L-methionine By similarity
Binding sitei62 – 621S-adenosyl-L-methionine By similarity
Binding sitei86 – 861S-adenosyl-L-methionine; via carbonyl oxygen By similarity
Binding sitei108 – 1081S-adenosyl-L-methionine By similarity
Binding sitei137 – 1371S-adenosyl-L-methionine By similarity
Active sitei152 – 1521 By similarity
Active sitei161 – 1611 By similarity

GO - Molecular functioni

  1. N-methyltransferase activity Source: UniProtKB
  2. histone methyltransferase activity Source: UniProtKB
  3. histone methyltransferase activity (H4-R3 specific) Source: UniProtKB
  4. identical protein binding Source: IntAct
  5. methyltransferase activity Source: ProtInc
  6. poly(A) RNA binding Source: UniProtKB
  7. protein binding Source: UniProtKB
  8. protein-arginine omega-N asymmetric methyltransferase activity Source: RefGenome

GO - Biological processi

  1. cell surface receptor signaling pathway Source: ProtInc
  2. histone H4-R3 methylation Source: UniProtKB
  3. histone methylation Source: UniProtKB
  4. negative regulation of megakaryocyte differentiation Source: UniProtKB
  5. neuron projection development Source: UniProtKB
  6. peptidyl-arginine methylation Source: UniProtKB
  7. peptidyl-arginine methylation, to asymmetrical-dimethyl arginine Source: RefGenome
  8. protein methylation Source: ProtInc
  9. regulation of transcription, DNA-templated Source: RefGenome
Complete GO annotation...

Keywords - Molecular functioni

Methyltransferase, Transferase

Keywords - Ligandi

S-adenosyl-L-methionine

Enzyme and pathway databases

SABIO-RKQ99873.
SignaLinkiQ99873.

Names & Taxonomyi

Protein namesi
Recommended name:
Protein arginine N-methyltransferase 1 (EC:2.1.1.-)
Alternative name(s):
Histone-arginine N-methyltransferase PRMT1 (EC:2.1.1.125)
Interferon receptor 1-bound protein 4
Gene namesi
Name:PRMT1
Synonyms:HMT2, HRMT1L2, IR1B4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 19

Organism-specific databases

HGNCiHGNC:5187. PRMT1.

Subcellular locationi

Nucleus. Nucleusnucleoplasm By similarity. Cytoplasmcytosol By similarity
Note: Mostly found in the cytoplasm. Colocalizes with CHTOP within the nucleus. Low levels detected also in the chromatin fraction By similarity.1 Publication

GO - Cellular componenti

  1. cytoplasm Source: ProtInc
  2. cytosol Source: RefGenome
  3. nucleoplasm Source: UniProtKB-SubCell
  4. nucleus Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi82 – 821V → A: Loss of FOXO1 methylation, its nuclear retention, and transcriptional activity. 1 Publication
Mutagenesisi83 – 831L → A: Loss of FOXO1 methylation, its nuclear retention, and transcriptional activity. 1 Publication
Mutagenesisi84 – 841D → A: Loss of FOXO1 methylation, its nuclear retention, and transcriptional activity. 1 Publication

Organism-specific databases

PharmGKBiPA29461.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 361361Protein arginine N-methyltransferase 1
PRO_0000212321Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei124 – 1241N6-succinyllysine By similarity

Proteomic databases

MaxQBiQ99873.
PaxDbiQ99873.
PRIDEiQ99873.

PTM databases

PhosphoSiteiQ99873.

Expressioni

Tissue specificityi

Widely expressed.1 Publication

Gene expression databases

ArrayExpressiQ99873.
BgeeiQ99873.
CleanExiHS_PRMT1.
GenevestigatoriQ99873.

Organism-specific databases

HPAiCAB022550.

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 By similarity. 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.5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself3EBI-78738,EBI-78738
CHTOPQ9Y3Y22EBI-78738,EBI-347794
DCAF8Q5TAQ92EBI-78738,EBI-740686
DHX9Q082112EBI-78738,EBI-352022
EWSR1Q018442EBI-78738,EBI-739737
FAM9AQ8IZU12EBI-78738,EBI-8468186
gagP045912EBI-78738,EBI-6179727From a different organism.
HABP4Q5JVS02EBI-78738,EBI-523625
HNRNPKP619783EBI-78738,EBI-304185
ILF3Q129062EBI-78738,EBI-78756
NRIP1P485524EBI-78738,EBI-746484
OFCC1Q8IZS52EBI-78738,EBI-8477661
PRMT8Q9NR223EBI-78738,EBI-745545
SCN5AQ145242EBI-78738,EBI-726858
SPSB1Q96BD62EBI-78738,EBI-2659201
SPSB2Q996192EBI-78738,EBI-2323209
SYNCRIPO605062EBI-78738,EBI-1024357
VHLP403372EBI-78738,EBI-301246

Protein-protein interaction databases

BioGridi109512. 128 interactions.
DIPiDIP-30878N.
IntActiQ99873. 72 interactions.
MINTiMINT-4861475.

Structurei

3D structure databases

ProteinModelPortaliQ99873.
SMRiQ99873. Positions 49-361.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini40 – 361322SAM-dependent MTase PRMT-type
Add
BLAST

Sequence similaritiesi

Phylogenomic databases

eggNOGiCOG0500.
HOVERGENiHBG001793.
InParanoidiQ99873.
KOiK11434.
PhylomeDBiQ99873.

Family and domain databases

Gene3Di3.40.50.150. 1 hit.
InterProiIPR025799. Arg_MeTrfase.
IPR025714. Methyltranfer_dom.
IPR029063. SAM-dependent_MTases-like.
[Graphical view]
PANTHERiPTHR11006. PTHR11006. 1 hit.
PfamiPF13847. Methyltransf_31. 1 hit.
[Graphical view]
SUPFAMiSSF53335. SSF53335. 1 hit.
PROSITEiPS51678. SAM_MT_PRMT. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. Align

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

MENFVATLAN GMSLQPPLEE VSCGQAESSE KPNAEDMTSK DYYFDSYAHF    50
GIHEEMLKDE VRTLTYRNSM FHNRHLFKDK VVLDVGSGTG ILCMFAAKAG 100
ARKVIGIECS SISDYAVKIV KANKLDHVVT IIKGKVEEVE LPVEKVDIII 150
SEWMGYCLFY ESMLNTVLYA RDKWLAPDGL IFPDRATLYV TAIEDRQYKD 200
YKIHWWENVY GFDMSCIKDV AIKEPLVDVV DPKQLVTNAC LIKEVDIYTV 250
KVEDLTFTSP FCLQVKRNDY VHALVAYFNI EFTRCHKRTG FSTSPESPYT 300
HWKQTVFYME DYLTVKTGEE IFGTIGMRPN AKNNRDLDFT IDLDFKGQLC 350
ELSCSTDYRM R 361
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

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti78 – 781K → M.
Corresponds to variant rs1804486 [ dbSNP | Ensembl ].
VAR_037501
Natural varianti158 – 1581L → F.
Corresponds to variant rs11673683 [ dbSNP | Ensembl ].
VAR_037502

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 1919MENFV…QPPLE → MVGVA in isoform 2.
VSP_005208Add
BLAST
Alternative sequencei1 – 1919MENFV…QPPLE → M in isoform 3.
VSP_005209Add
BLAST
Alternative sequencei1 – 1919MENFV…QPPLE → MAAAEAANCIM in isoform 4.
VSP_046334Add
BLAST

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti108 – 1081E → V in CAA71763. 1 Publication
Sequence conflicti108 – 1081E → V in CAA71764. 1 Publication
Sequence conflicti108 – 1081E → V in CAA71765. 1 Publication
Sequence conflicti108 – 1081E → V in BAA11029. 1 Publication
Sequence conflicti147 – 17529DIIIS…RDKWL → ASSSASGWATASSTSPCSTP CSMPGTSV in BAA11029. 1 Publication
Add
BLAST
Sequence conflicti202 – 2021K → E in BAG65435. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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]
UniGeneiHs.20521.

Genome annotation databases

EnsembliENST00000391851; ENSP00000375724; ENSG00000126457. [Q99873-4]
GeneIDi3276.
KEGGihsa:3276.
UCSCiuc002ppe.3. human.
uc021uxu.1. human. [Q99873-2]

Polymorphism databases

DMDMi161789011.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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 .
CCDSi CCDS42592.1. [Q99873-4 ]
RefSeqi NP_001527.3. NM_001536.5.
NP_938074.2. NM_198318.4. [Q99873-4 ]
UniGenei Hs.20521.

3D structure databases

ProteinModelPortali Q99873.
SMRi Q99873. Positions 49-361.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 109512. 128 interactions.
DIPi DIP-30878N.
IntActi Q99873. 72 interactions.
MINTi MINT-4861475.

Chemistry

BindingDBi Q99873.
ChEMBLi CHEMBL5524.
GuidetoPHARMACOLOGYi 1252.

PTM databases

PhosphoSitei Q99873.

Polymorphism databases

DMDMi 161789011.

Proteomic databases

MaxQBi Q99873.
PaxDbi Q99873.
PRIDEi Q99873.

Protocols and materials databases

DNASUi 3276.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000391851 ; ENSP00000375724 ; ENSG00000126457 . [Q99873-4 ]
GeneIDi 3276.
KEGGi hsa:3276.
UCSCi uc002ppe.3. human.
uc021uxu.1. human. [Q99873-2 ]

Organism-specific databases

CTDi 3276.
GeneCardsi GC19P050181.
HGNCi HGNC:5187. PRMT1.
HPAi CAB022550.
MIMi 602950. gene.
neXtProti NX_Q99873.
PharmGKBi PA29461.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG0500.
HOVERGENi HBG001793.
InParanoidi Q99873.
KOi K11434.
PhylomeDBi Q99873.

Enzyme and pathway databases

SABIO-RK Q99873.
SignaLinki Q99873.

Miscellaneous databases

ChiTaRSi PRMT1. human.
GeneWikii PRMT1.
GenomeRNAii 3276.
NextBioi 13013.
PROi Q99873.
SOURCEi Search...

Gene expression databases

ArrayExpressi Q99873.
Bgeei Q99873.
CleanExi HS_PRMT1.
Genevestigatori Q99873.

Family and domain databases

Gene3Di 3.40.50.150. 1 hit.
InterProi