ID ANM5_PONAB Reviewed; 637 AA.
AC Q5R698;
DT 22-NOV-2005, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 08-NOV-2023, entry version 108.
DE RecName: Full=Protein arginine N-methyltransferase 5;
DE Short=PRMT5;
DE EC=2.1.1.320 {ECO:0000250|UniProtKB:O14744};
DE AltName: Full=Histone-arginine N-methyltransferase PRMT5;
DE AltName: Full=Shk1 kinase-binding protein 1 homolog;
DE Short=SKB1 homolog;
GN Name=PRMT5; Synonyms=SKB1;
OS Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain cortex;
RG The German cDNA consortium;
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Arginine methyltransferase that can both catalyze the
CC formation of omega-N monomethylarginine (MMA) and symmetrical
CC dimethylarginine (sDMA), with a preference for the formation of MMA.
CC Specifically mediates the symmetrical dimethylation of arginine
CC residues in the small nuclear ribonucleoproteins Sm D1 (SNRPD1) and Sm
CC D3 (SNRPD3); such methylation being required for the assembly and
CC biogenesis of snRNP core particles. Methylates SUPT5H and may regulate
CC its transcriptional elongation properties (By similarity). May
CC methylate the N-terminal region of MBD2 (By similarity). Mono- and
CC dimethylates arginine residues of myelin basic protein (MBP) in vitro.
CC May play a role in cytokine-activated transduction pathways. Negatively
CC regulates cyclin E1 promoter activity and cellular proliferation.
CC Methylates histone H2A and H4 'Arg-3' during germ cell development (By
CC similarity). Methylates histone H3 'Arg-8', which may repress
CC transcription (By similarity). Methylates the Piwi proteins (PIWIL1,
CC PIWIL2 and PIWIL4), methylation of Piwi proteins being required for the
CC interaction with Tudor domain-containing proteins and subsequent
CC localization to the meiotic nuage (By similarity). Methylates RPS10.
CC Attenuates EGF signaling through the MAPK1/MAPK3 pathway acting at 2
CC levels. First, monomethylates EGFR; this enhances EGFR 'Tyr-1197'
CC phosphorylation and PTPN6 recruitment, eventually leading to reduced
CC SOS1 phosphorylation. Second, methylates RAF1 and probably BRAF, hence
CC destabilizing these 2 signaling proteins and reducing their catalytic
CC activity. Required for induction of E-selectin and VCAM-1, on the
CC endothelial cells surface at sites of inflammation. Methylates HOXA9.
CC Methylates and regulates SRGAP2 which is involved in cell migration and
CC differentiation (By similarity). Acts as a transcriptional corepressor
CC in CRY1-mediated repression of the core circadian component PER1 by
CC regulating the H4R3 dimethylation at the PER1 promoter (By similarity).
CC Methylates GM130/GOLGA2, regulating Golgi ribbon formation. Methylates
CC H4R3 in genes involved in glioblastomagenesis in a CHTOP- and/or TET1-
CC dependent manner. Symmetrically methylates POLR2A, a modification that
CC allows the recruitment to POLR2A of proteins including SMN1/SMN2 and
CC SETX. This is required for resolving RNA-DNA hybrids created by RNA
CC polymerase II, that form R-loop in transcription terminal regions, an
CC important step in proper transcription termination. Along with LYAR,
CC binds the promoter of gamma-globin HBG1/HBG2 and represses its
CC expression. Symmetrically methylates NCL. Methylates p53/TP53;
CC methylation might possibly affect p53/TP53 target gene specificity (By
CC similarity). Involved in spliceosome maturation and mRNA splicing in
CC prophase I spermatocytes through the catalysis of the symmetrical
CC arginine dimethylation of SNRPB (small nuclear ribonucleoprotein-
CC associated protein) and the interaction with tudor domain-containing
CC protein TDRD6 (By similarity). {ECO:0000250|UniProtKB:O14744,
CC ECO:0000250|UniProtKB:Q8CIG8}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-arginyl-[protein] + 2 S-adenosyl-L-methionine = 2 H(+) +
CC N(omega),N(omega)'-dimethyl-L-arginyl-[protein] + 2 S-adenosyl-L-
CC homocysteine; Xref=Rhea:RHEA:48108, Rhea:RHEA-COMP:10532, Rhea:RHEA-
CC COMP:11992, ChEBI:CHEBI:15378, ChEBI:CHEBI:29965, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:88221; EC=2.1.1.320;
CC Evidence={ECO:0000250|UniProtKB:O14744};
CC -!- ACTIVITY REGULATION: Activity is increased by EGF, HGF, FGF1 or FGF2
CC treatments, and slightly decreased by NGF treatment. {ECO:0000250}.
CC -!- SUBUNIT: Forms, at least, homodimers and homotetramers. Component of
CC the methylosome complex, composed of PRMT5, WDR77 and CLNS1A. Found in
CC a complex composed of PRMT5, WDR77 and RIOK1. RIOK1 and CLNS1A
CC associate with PRMT5 in a mutually exclusive fashion, which allows the
CC recruitment of distinct methylation substrates, such as nucleolin/NCL
CC and Sm proteins, respectively (By similarity). Interacts with PRDM1 (By
CC similarity). Identified in a complex composed of methylosome and PRMT1
CC and ERH. Interacts with EGFR; methylates EGFR and stimulates EGFR-
CC mediated ERK activation. Interacts with HOXA9. Interacts with SRGAP2.
CC Found in a complex with COPRS, RUNX1 and CBFB. Interacts with CHTOP;
CC the interaction symmetrically methylates CHTOP, but seems to require
CC the presence of PRMT1. Interacts with EPB41L3; this modulates
CC methylation of target proteins. Component of a high molecular weight
CC E2F-pocket protein complex, CERC (cyclin E1 repressor complex).
CC Associates with SWI/SNF remodeling complexes containing SMARCA2 and
CC SMARCA4. Interacts with JAK2, SSTR1, SUPT5H, BRAF and with active RAF1.
CC Interacts with LSM11, PRMT7 and SNRPD3. Interacts with COPRS; promoting
CC its recruitment on histone H4. Interacts with CLNS1A/pICln. Identified
CC in a complex with CLNS1A/pICln and Sm proteins. Interacts with RPS10.
CC Interacts with WDR77. Interacts with IWS1. Interacts with CRY1.
CC Interacts with POLR2A. Interacts with SMN1/SMN2. Interacts with LYAR;
CC this interaction is direct. Interacts with TTC5/STRAP; this interaction
CC is DNA damage-dependent and promotes PRMT5 interaction with p53/TP53.
CC Interacts with p53/TP53 in response to DNA damage; the interaction is
CC TTC5/STRAP dependent. Interacts with FAM47E; the interaction is direct,
CC promotes PRMT5 localization to chromatin, and does not disrupt its
CC association with WDR77 or STUB1 (By similarity). Interacts with TDRD6
CC (By similarity). Interacts with STUB1 (By similarity). Interacts with
CC MBD2 (By similarity). Does not interact with MBD3 (By similarity).
CC {ECO:0000250|UniProtKB:O14744, ECO:0000250|UniProtKB:Q8CIG8}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:O14744}. Nucleus
CC {ECO:0000250|UniProtKB:O14744}. Golgi apparatus
CC {ECO:0000250|UniProtKB:O14744}. Note=Localizes to promoter regions of
CC target genes on chromosomes (By similarity). Localizes to methylated
CC chromatin (By similarity). {ECO:0000250|UniProtKB:O14744}.
CC -!- SIMILARITY: Belongs to the class I-like SAM-binding methyltransferase
CC superfamily. Protein arginine N-methyltransferase family.
CC {ECO:0000255|PROSITE-ProRule:PRU01015}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; CR860596; CAH92718.1; -; mRNA.
DR RefSeq; NP_001126589.1; NM_001133117.1.
DR AlphaFoldDB; Q5R698; -.
DR SMR; Q5R698; -.
DR STRING; 9601.ENSPPYP00000006422; -.
DR GeneID; 100173581; -.
DR KEGG; pon:100173581; -.
DR CTD; 10419; -.
DR eggNOG; KOG0822; Eukaryota.
DR InParanoid; Q5R698; -.
DR OrthoDB; 5489665at2759; -.
DR Proteomes; UP000001595; Unplaced.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
DR GO; GO:0034709; C:methylosome; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0070888; F:E-box binding; ISS:UniProtKB.
DR GO; GO:0044020; F:histone H4R3 methyltransferase activity; ISS:UniProtKB.
DR GO; GO:0008327; F:methyl-CpG binding; ISS:UniProtKB.
DR GO; GO:0016274; F:protein-arginine N-methyltransferase activity; ISS:UniProtKB.
DR GO; GO:0035243; F:protein-arginine omega-N symmetric methyltransferase activity; ISS:UniProtKB.
DR GO; GO:0003714; F:transcription corepressor activity; ISS:UniProtKB.
DR GO; GO:0032922; P:circadian regulation of gene expression; ISS:UniProtKB.
DR GO; GO:0006353; P:DNA-templated transcription termination; ISS:UniProtKB.
DR GO; GO:0042118; P:endothelial cell activation; ISS:UniProtKB.
DR GO; GO:0090161; P:Golgi ribbon formation; ISS:UniProtKB.
DR GO; GO:0018216; P:peptidyl-arginine methylation; ISS:UniProtKB.
DR GO; GO:0000387; P:spliceosomal snRNP assembly; ISS:UniProtKB.
DR CDD; cd02440; AdoMet_MTases; 1.
DR Gene3D; 3.20.20.150; Divalent-metal-dependent TIM barrel enzymes; 1.
DR Gene3D; 2.70.160.11; Hnrnp arginine n-methyltransferase1; 1.
DR Gene3D; 3.40.50.150; Vaccinia Virus protein VP39; 1.
DR InterPro; IPR025799; Arg_MeTrfase.
DR InterPro; IPR007857; Arg_MeTrfase_PRMT5.
DR InterPro; IPR035075; PRMT5.
DR InterPro; IPR035248; PRMT5_C.
DR InterPro; IPR035247; PRMT5_TIM.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR PANTHER; PTHR10738; PROTEIN ARGININE N-METHYLTRANSFERASE 5; 1.
DR PANTHER; PTHR10738:SF0; PROTEIN ARGININE N-METHYLTRANSFERASE 5; 1.
DR Pfam; PF05185; PRMT5; 1.
DR Pfam; PF17286; PRMT5_C; 1.
DR Pfam; PF17285; PRMT5_TIM; 1.
DR PIRSF; PIRSF015894; Skb1_MeTrfase; 1.
DR SUPFAM; SSF53335; S-adenosyl-L-methionine-dependent methyltransferases; 1.
DR PROSITE; PS51678; SAM_MT_PRMT; 1.
PE 2: Evidence at transcript level;
KW Acetylation; Biological rhythms; Chromatin regulator; Cytoplasm;
KW Golgi apparatus; Methyltransferase; Nucleus; Reference proteome; Repressor;
KW S-adenosyl-L-methionine; Transcription; Transcription regulation;
KW Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:O14744"
FT CHAIN 2..637
FT /note="Protein arginine N-methyltransferase 5"
FT /id="PRO_0000212345"
FT DOMAIN 308..615
FT /note="SAM-dependent MTase PRMT-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01015"
FT REGION 13..292
FT /note="TIM barrel"
FT /evidence="ECO:0000250|UniProtKB:O14744"
FT REGION 465..637
FT /note="Beta barrel"
FT /evidence="ECO:0000250|UniProtKB:O14744"
FT REGION 488..494
FT /note="Dimerization"
FT /evidence="ECO:0000250|UniProtKB:O14744"
FT ACT_SITE 435
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250|UniProtKB:O14744"
FT ACT_SITE 444
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250|UniProtKB:O14744"
FT BINDING 324
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:O14744"
FT BINDING 327
FT /ligand="a protein"
FT /ligand_id="ChEBI:CHEBI:16541"
FT /ligand_note="substrate"
FT /ligand_part="L-arginine residue"
FT /ligand_part_id="ChEBI:CHEBI:29965"
FT /evidence="ECO:0000250|UniProtKB:O14744"
FT BINDING 333..334
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:O14744"
FT BINDING 392
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:O14744"
FT BINDING 419..420
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:O14744"
FT BINDING 435
FT /ligand="a protein"
FT /ligand_id="ChEBI:CHEBI:16541"
FT /ligand_note="substrate"
FT /ligand_part="L-arginine residue"
FT /ligand_part_id="ChEBI:CHEBI:29965"
FT /evidence="ECO:0000250|UniProtKB:O14744"
FT BINDING 444
FT /ligand="a protein"
FT /ligand_id="ChEBI:CHEBI:16541"
FT /ligand_note="substrate"
FT /ligand_part="L-arginine residue"
FT /ligand_part_id="ChEBI:CHEBI:29965"
FT /evidence="ECO:0000250|UniProtKB:O14744"
FT SITE 327
FT /note="Critical for specifying symmetric addition of methyl
FT groups"
FT /evidence="ECO:0000250|UniProtKB:P46580"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:O14744"
SQ SEQUENCE 637 AA; 72666 MW; 2195B04C72EF47D2 CRC64;
MAAMAVGGAG GSRVSSGRDL NCVPEIADTL GAVAKQGFDF LCMPVFHPRF KREFIQEPAK
NRPGPQTRSD LLLSGRDWNT LIVGKLSPWI RPDSEVEKIR RNSEAAMLQE LNFGAYLGLP
AFLLPLNQED NTNLARVLTN HIHTGHHSSM FWMRVPLVAP EDLRDDIIEN APTTHTQEYS
GEEKTWIWWH NFRTLCDYSK RIAVALEIGA DLPSNHVIDR WLGEPIKAAI LPTSIFLTNK
KGFPVLSKMH QRLIFRLLKL EVQFIITGTN HHSEKEFCSY LQYLEYLSQN RPPPNAYELF
AKGYEDYLQS PLQPLMDNLE SQTYEVFEKD PIKYSQYQQA IYKCLLDRVP EEEKDTNVQV
LMVLGAGRGP LVNASLRAAK QADRRIKLYA VEKNPNAVVT LENWQFEEWG SQVTVVSSDM
REWVAPEKAD IIVSELLGSF ADNELSPECL DGAQHFLKDD GVSIPGEYTS FLAPISSSKL
YNEVRACREK DRDPEAQFEM PYVVRLHNFH QLSAPQPCFT FSHPNRDPMI DNNRYCTLEF
PVEVNTVLHG FAGYFETVLY QDITLSIRPE THSPGMFSWF PILFPIKQPI TVREGQTICV
RFWRCSNSKK VWYEWAVTAP VCSAIHNPTG RSYTIGL
//
