Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.

UniProtKB - O14744 (ANM5_HUMAN)

Protein

Protein arginine N-methyltransferase 5

Gene

PRMT5

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

Functioni

Arginine methyltransferase that can both catalyze the formation of omega-N monomethylarginine (MMA) and symmetrical dimethylarginine (sDMA), with a preference for the formation of MMA (PubMed:10531356, PubMed:11152681, PubMed:11747828, PubMed:12411503, PubMed:15737618, PubMed:17709427, PubMed:20159986, PubMed:20810653, PubMed:21258366, PubMed:21917714, PubMed:22269951, PubMed:21081503). Specifically mediates the symmetrical dimethylation of arginine residues in the small nuclear ribonucleoproteins Sm D1 (SNRPD1) and Sm D3 (SNRPD3); such methylation being required for the assembly and biogenesis of snRNP core particles (PubMed:12411503, PubMed:11747828, PubMed:17709427). Methylates SUPT5H and may regulate its transcriptional elongation properties (PubMed:12718890). Mono- and dimethylates arginine residues of myelin basic protein (MBP) in vitro. May play a role in cytokine-activated transduction pathways. Negatively regulates cyclin E1 promoter activity and cellular proliferation. Methylates histone H2A and H4 'Arg-3' during germ cell development. Methylates histone H3 'Arg-8', which may repress transcription. Methylates the Piwi proteins (PIWIL1, PIWIL2 and PIWIL4), methylation of Piwi proteins being required for the interaction with Tudor domain-containing proteins and subsequent localization to the meiotic nuage (By similarity). Methylates RPS10. Attenuates EGF signaling through the MAPK1/MAPK3 pathway acting at 2 levels. First, monomethylates EGFR; this enhances EGFR 'Tyr-1197' phosphorylation and PTPN6 recruitment, eventually leading to reduced SOS1 phosphorylation (PubMed:21917714, PubMed:21258366). Second, methylates RAF1 and probably BRAF, hence destabilizing these 2 signaling proteins and reducing their catalytic activity (PubMed:21917714). Required for induction of E-selectin and VCAM-1, on the endothelial cells surface at sites of inflammation. Methylates HOXA9 (PubMed:22269951). Methylates and regulates SRGAP2 which is involved in cell migration and differentiation (PubMed:20810653). Acts as a transcriptional corepressor in CRY1-mediated repression of the core circadian component PER1 by regulating the H4R3 dimethylation at the PER1 promoter (By similarity). Methylates GM130/GOLGA2, regulating Golgi ribbon formation (PubMed:20421892). Methylates H4R3 in genes involved in glioblastomagenesis in a CHTOP- and/or TET1-dependent manner (PubMed:25284789). Symmetrically methylates POLR2A, a modification that allows the recruitment to POLR2A of proteins including SMN1/SMN2 and SETX. This is required for resolving RNA-DNA hybrids created by RNA polymerase II, that form R-loop in transcription terminal regions, an important step in proper transcription termination (PubMed:26700805). Along with LYAR, binds the promoter of gamma-globin HBG1/HBG2 and represses its expression (PubMed:25092918). Symmetrically methylates NCL (PubMed:21081503).By similarity17 Publications

Catalytic activityi

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

Activity regulationi

Activity is increased by EGF, HGF, FGF1 or FGF2 treatments, and slightly decreased by NGF treatment.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei304Peptide substrate1 Publication1
Binding sitei307Peptide substrate1 Publication1
Binding sitei324S-adenosyl-L-methionine1 Publication1
Sitei327Critical for specifying symmetric addition of methyl groupsBy similarity1
Binding sitei392S-adenosyl-L-methionine1 Publication1
Active sitei435Proton donor/acceptor1 Publication1
Active sitei444Proton donor/acceptor1 Publication1

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionChromatin regulator, Methyltransferase, Repressor, Transferase
Biological processBiological rhythms, Transcription, Transcription regulation
LigandS-adenosyl-L-methionine

Enzyme and pathway databases

BioCyciMetaCyc:HS02092-MONOMER
BRENDAi2.1.1.125 2681
ReactomeiR-HSA-191859 snRNP Assembly
R-HSA-3214858 RMTs methylate histone arginines
R-HSA-6804760 Regulation of TP53 Activity through Methylation
SIGNORiO14744

Names & Taxonomyi

Protein namesi
Recommended name:
Protein arginine N-methyltransferase 5 (EC:2.1.1.3202 Publications)
Alternative name(s):
72 kDa ICln-binding protein
Histone-arginine N-methyltransferase PRMT5
Jak-binding protein 1
Shk1 kinase-binding protein 1 homolog
Short name:
SKB1 homolog
Short name:
SKB1Hs
Cleaved into the following chain:
Protein arginine N-methyltransferase 5, N-terminally processed
Gene namesi
Name:PRMT5
Synonyms:HRMT1L5, IBP72, JBP1, SKB1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 14

Organism-specific databases

EuPathDBiHostDB:ENSG00000100462.15
HGNCiHGNC:10894 PRMT5
MIMi604045 gene
neXtProtiNX_O14744

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, Golgi apparatus, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi365 – 369Missing : Increased MAPK1/MAPK3 phosphorylation in response to EGF. 1 Publication5
Mutagenesisi367 – 368GR → AA: Abolishes enzymatic activity. 1 Publication2

Organism-specific databases

DisGeNETi10419
OpenTargetsiENSG00000100462
PharmGKBiPA35794

Chemistry databases

ChEMBLiCHEMBL1795116
GuidetoPHARMACOLOGYi1256

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002123421 – 637Protein arginine N-methyltransferase 5Add BLAST637
Initiator methionineiRemoved; alternateCombined sources2 Publications
ChainiPRO_00004176022 – 637Protein arginine N-methyltransferase 5, N-terminally processedAdd BLAST636

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanine; in Protein arginine N-methyltransferase 5, N-terminally processedCombined sources1 Publication1

Keywords - PTMi

Acetylation

Proteomic databases

EPDiO14744
MaxQBiO14744
PaxDbiO14744
PeptideAtlasiO14744
PRIDEiO14744
ProteomicsDBi48200
48201 [O14744-2]

PTM databases

iPTMnetiO14744
PhosphoSitePlusiO14744
SwissPalmiO14744

Expressioni

Tissue specificityi

Ubiquitous.1 Publication

Gene expression databases

BgeeiENSG00000100462 Expressed in 215 organ(s), highest expression level in testis
CleanExiHS_PRMT5
ExpressionAtlasiO14744 baseline and differential
GenevisibleiO14744 HS

Organism-specific databases

HPAiCAB012459
HPA005525
HPA064708

Interactioni

Subunit structurei

Forms, at least, homodimers and homotetramers. Component of the methylosome complex, composed of PRMT5, WDR77 and CLNS1A (PubMed:21081503). Found in a complex composed of PRMT5, WDR77 and RIOK1 (PubMed:21081503). RIOK1 and CLNS1A associate with PRMT5 in a mutually exclusive fashion, which allows the recruitment of distinct methylation substrates, such as nucleolin/NCL and Sm proteins, respectively (PubMed:21081503). Interacts with PRDM1 (By similarity). Identified in a complex composed of methylosome and PRMT1 and ERH (PubMed:25284789). Interacts with EGFR; methylates EGFR and stimulates EGFR-mediated ERK activation. Interacts with HOXA9. Interacts with SRGAP2. Found in a complex with COPRS, RUNX1 AND CBFB. Interacts with CHTOP; the interaction symmetrically methylates CHTOP, but seems to require the presence of PRMT1 (PubMed:25284789). Interacts with EPB41L3; this modulates methylation of target proteins. Component of a high molecular weight E2F-pocket protein complex, CERC (cyclin E1 repressor complex). Associates with SWI/SNF remodeling complexes containing SMARCA2 and SMARCA4. Interacts with JAK2, SSTR1, SUPT5H, BRAF and with active RAF1. Interacts with LSM11, PRMT7 and SNRPD3 (PubMed:17709427, PubMed:16087681). Interacts with COPRS; promoting its recruitment on histone H4. Interacts with CLNS1A/pICln (PubMed:21081503, PubMed:9556550). Identified in a complex with CLNS1A/pICln and Sm proteins. Interacts with RPS10 (PubMed:20159986). Interacts with WDR77. Interacts with IWS1. Interacts with CRY1. Interacts with POLR2A (PubMed:26700805). Interacts with SMN1/SMN2 (PubMed:26700805). Interacts with LYAR; this interaction is direct (PubMed:25092918).By similarity23 Publications

Binary interactionsi

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi115688, 190 interactors
ComplexPortaliCPX-696 Methylosome
CORUMiO14744
DIPiDIP-33172N
IntActiO14744, 102 interactors
MINTiO14744
STRINGi9606.ENSP00000319169

Chemistry databases

BindingDBiO14744

Structurei

Secondary structure

1637
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliO14744
SMRiO14744
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini308 – 615SAM-dependent MTase PRMT-typePROSITE-ProRule annotationAdd BLAST308

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni13 – 292TIM barrel1 PublicationAdd BLAST280
Regioni333 – 334S-adenosyl-L-methionine binding1 Publication2
Regioni419 – 420S-adenosyl-L-methionine binding1 Publication2
Regioni465 – 637Beta barrel1 PublicationAdd BLAST173
Regioni488 – 494Dimerization1 Publication7

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiKOG0822 Eukaryota
ENOG410XNZM LUCA
GeneTreeiENSGT00390000001141
HOGENOMiHOG000175933
HOVERGENiHBG057083
InParanoidiO14744
KOiK02516
OMAiFPMFFPT
OrthoDBiEOG091G03PD
PhylomeDBiO14744
TreeFamiTF300626

Family and domain databases

InterProiView protein in InterPro
IPR025799 Arg_MeTrfase
IPR007857 Arg_MeTrfase_PRMT5
IPR035075 PRMT5
IPR035248 PRMT5_C
IPR035247 PRMT5_TIM
IPR029063 SAM-dependent_MTases
PANTHERiPTHR10738 PTHR10738, 1 hit
PfamiView protein in Pfam
PF05185 PRMT5, 1 hit
PF17286 PRMT5_C, 1 hit
PF17285 PRMT5_TIM, 1 hit
PIRSFiPIRSF015894 Skb1_MeTrfase, 1 hit
SUPFAMiSSF53335 SSF53335, 1 hit
PROSITEiView protein in PROSITE
PS51678 SAM_MT_PRMT, 1 hit

Sequences (5+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket
Note: Additional isoforms seems to exist. According to EST sequences.

This entry has 5 described isoforms and 14 potential isoforms that are computationally mapped.iShow all

Isoform 1 (identifier: O14744-1) [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
MAAMAVGGAG GSRVSSGRDL NCVPEIADTL GAVAKQGFDF LCMPVFHPRF 
        60         70         80         90        100
KREFIQEPAK NRPGPQTRSD LLLSGRDWNT LIVGKLSPWI RPDSKVEKIR 
       110        120        130        140        150
RNSEAAMLQE LNFGAYLGLP AFLLPLNQED NTNLARVLTN HIHTGHHSSM 
       160        170        180        190        200
FWMRVPLVAP EDLRDDIIEN APTTHTEEYS GEEKTWMWWH NFRTLCDYSK 
       210        220        230        240        250
RIAVALEIGA DLPSNHVIDR WLGEPIKAAI LPTSIFLTNK KGFPVLSKMH 
       260        270        280        290        300
QRLIFRLLKL EVQFIITGTN HHSEKEFCSY LQYLEYLSQN RPPPNAYELF 
       310        320        330        340        350
AKGYEDYLQS PLQPLMDNLE SQTYEVFEKD PIKYSQYQQA IYKCLLDRVP 
       360        370        380        390        400
EEEKDTNVQV LMVLGAGRGP LVNASLRAAK QADRRIKLYA VEKNPNAVVT 
       410        420        430        440        450
LENWQFEEWG SQVTVVSSDM REWVAPEKAD IIVSELLGSF ADNELSPECL 
       460        470        480        490        500
DGAQHFLKDD GVSIPGEYTS FLAPISSSKL YNEVRACREK DRDPEAQFEM 
       510        520        530        540        550
PYVVRLHNFH QLSAPQPCFT FSHPNRDPMI DNNRYCTLEF PVEVNTVLHG 
       560        570        580        590        600
FAGYFETVLY QDITLSIRPE THSPGMFSWF PILFPIKQPI TVREGQTICV 
       610        620        630 
RFWRCSNSKK VWYEWAVTAP VCSAIHNPTG RSYTIGL
Length:637
Mass (Da):72,684
Last modified:January 23, 2007 - v4
Checksum:i522E255B384F25E7
GO
Isoform 2 (identifier: O14744-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-34: MAAMAVGGAGGSRVSSGRDLNCVPEIADTLGAVA → MRGPNSGTEKGRLVIPE

Note: No experimental confirmation available.
Show »
Length:620
Mass (Da):71,320
Checksum:i0E489272643DD83C
GO
Isoform 4 (identifier: O14744-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-34: MAAMAVGGAGGSRVSSGRDLNCVPEIADTLGAVA → MRGPNSGTEKGRLVIPE
     106-259: Missing.

Note: No experimental confirmation available.
Show »
Length:466
Mass (Da):53,580
Checksum:i62386C5B867CF619
GO
Isoform 5 (identifier: O14744-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     77-120: Missing.

Note: No experimental confirmation available.
Show »
Length:593
Mass (Da):67,674
Checksum:iD609BFECAFB7D108
GO
Isoform 3 (identifier: O14744-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-34: MAAMAVGGAGGSRVSSGRDLNCVPEIADTLGAVA → MRGPNSGTEKGRLVIPE
     77-120: Missing.

Note: No experimental confirmation available.
Show »
Length:576
Mass (Da):66,311
Checksum:i988C2D288FC214A1
GO

Computationally mapped potential isoform sequencesi

There are 14 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H0YJD3H0YJD3_HUMAN
Protein arginine N-methyltransferas...
PRMT5
177Annotation score:
H7BZ44H7BZ44_HUMAN
Protein arginine N-methyltransferas...
PRMT5
179Annotation score:
H0YJY6H0YJY6_HUMAN
Protein arginine N-methyltransferas...
PRMT5
61Annotation score:
G3V2L6G3V2L6_HUMAN
Protein arginine N-methyltransferas...
PRMT5
183Annotation score:
H0YJX6H0YJX6_HUMAN
Protein arginine N-methyltransferas...
PRMT5
279Annotation score:
G3V5T6G3V5T6_HUMAN
Protein arginine N-methyltransferas...
PRMT5
104Annotation score:
H0YJ77H0YJ77_HUMAN
Protein arginine N-methyltransferas...
PRMT5
138Annotation score:
G3V2X6G3V2X6_HUMAN
Protein arginine N-methyltransferas...
PRMT5
185Annotation score:
C9JSX3C9JSX3_HUMAN
Protein arginine N-methyltransferas...
PRMT5
186Annotation score:
G3V580G3V580_HUMAN
Protein arginine N-methyltransferas...
PRMT5
180Annotation score:
There are more potential isoformsShow all

Sequence cautioni

The sequence BC005820 differs from that shown. Reason: Frameshift at position 370.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti183E → K in BAG63592 (PubMed:14702039).Curated1
Sequence conflicti247S → F in AAB66581 (PubMed:9843966).Curated1
Sequence conflicti420M → T in BAG63592 (PubMed:14702039).Curated1
Sequence conflicti553G → V in AAB66581 (PubMed:9843966).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0433821 – 34MAAMA…LGAVA → MRGPNSGTEKGRLVIPE in isoform 2, isoform 3 and isoform 4. 2 PublicationsAdd BLAST34
Alternative sequenceiVSP_05468577 – 120Missing in isoform 3 and isoform 5. 1 PublicationAdd BLAST44
Alternative sequenceiVSP_054768106 – 259Missing in isoform 4. 1 PublicationAdd BLAST154

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF015913 mRNA Translation: AAB66581.1
AF167572 mRNA Translation: AAF04502.1
AK075251 mRNA Translation: BAG52095.1
AK301812 mRNA Translation: BAG63261.1
AK302240 mRNA Translation: BAG63592.1
CR456741 mRNA Translation: CAG33022.1
AB451246 mRNA Translation: BAG70060.1
AB451370 mRNA Translation: BAG70184.1
AL132780 Genomic DNA No translation available.
CH471078 Genomic DNA Translation: EAW66218.1
CH471078 Genomic DNA Translation: EAW66219.1
CH471078 Genomic DNA Translation: EAW66220.1
CH471078 Genomic DNA Translation: EAW66221.1
BC005820 mRNA No translation available.
BC025979 mRNA Translation: AAH25979.1
CCDSiCCDS41922.1 [O14744-2]
CCDS61394.1 [O14744-3]
CCDS61395.1 [O14744-4]
CCDS61396.1 [O14744-5]
CCDS9579.1 [O14744-1]
PIRiT03842
RefSeqiNP_001034708.1, NM_001039619.2 [O14744-2]
NP_001269882.1, NM_001282953.1 [O14744-3]
NP_001269884.1, NM_001282955.1 [O14744-5]
NP_001269885.1, NM_001282956.1 [O14744-4]
NP_006100.2, NM_006109.4 [O14744-1]
UniGeneiHs.367854

Genome annotation databases

EnsembliENST00000216350; ENSP00000216350; ENSG00000100462 [O14744-3]
ENST00000324366; ENSP00000319169; ENSG00000100462 [O14744-1]
ENST00000397440; ENSP00000380582; ENSG00000100462 [O14744-4]
ENST00000397441; ENSP00000380583; ENSG00000100462 [O14744-2]
ENST00000553897; ENSP00000452555; ENSG00000100462 [O14744-5]
GeneIDi10419
KEGGihsa:10419
UCSCiuc001whl.3 human [O14744-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiANM5_HUMAN
AccessioniPrimary (citable) accession number: O14744
Secondary accession number(s): A8MTP3
, A8MZ91, B4DX49, B4DY30, B5BU10, D3DS33, E2QRE7, Q6IBR1, Q9UKH1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 20, 2003
Last sequence update: January 23, 2007
Last modified: September 12, 2018
This is version 173 of the entry and version 4 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

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again