CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-000288
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Protein arginine N-methyltransferase 5 
Protein Synonyms/Alias
 72 kDa ICln-binding protein; Histone-arginine N-methyltransferase PRMT5; Jak-binding protein 1; Shk1 kinase-binding protein 1 homolog; SKB1 homolog; SKB1Hs; Protein arginine N-methyltransferase 5, N-terminally processed 
Gene Name
 PRMT5 
Gene Synonyms/Alias
 HRMT1L5; IBP72; JBP1; SKB1 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
60EFIQEPAKNRPGPQTubiquitination[1, 2, 3]
85WNTLIVGKLSPWIRPubiquitination[1, 2, 3]
95PWIRPDSKVEKIRRNubiquitination[2, 4, 5]
200RTLCDYSKRIAVALEacetylation[6]
200RTLCDYSKRIAVALEubiquitination[2]
227RWLGEPIKAAILPTSubiquitination[1, 2, 3, 4, 5, 7]
240TSIFLTNKKGFPVLSubiquitination[1, 2, 3, 4, 5]
241SIFLTNKKGFPVLSKubiquitination[2]
329QTYEVFEKDPIKYSQubiquitination[1]
333VFEKDPIKYSQYQQAubiquitination[1, 3]
387KQADRRIKLYAVEKNubiquitination[1, 2]
479LAPISSSKLYNEVRAubiquitination[1, 3]
490EVRACREKDRDPEAQubiquitination[1, 2, 3]
Reference
 [1] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [2] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [3] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [4] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [5] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [6] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
 [7] Ubiquitin ligase substrate identification through quantitative proteomics at both the protein and peptide levels.
 Lee KA, Hammerle LP, Andrews PS, Stokes MP, Mustelin T, Silva JC, Black RA, Doedens JR.
 J Biol Chem. 2011 Dec 2;286(48):41530-8. [PMID: 21987572] 
Functional Description
 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. 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. Methylates SUPT5H. Mono- and dimethylates arginine residues of myelin basic protein (MBP) in vitro. Plays a role in the assembly of snRNP core particles. May play a role in cytokine-activated transduction pathways. Negatively regulates cyclin E1 promoter activity and cellular proliferation. May regulate the SUPT5H transcriptional elongation properties. May be part of a pathway that is connected to a chloride current, possibly through cytoskeletal rearrangement. 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. 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. Second, methylates RAF1 and probably BRAF, hence destabilizing these 2 signaling proteins and reducing their catalytic activity. Required for induction of E-selectin and VCAM-1, on the endothelial cells surface at sites of inflammation. Methylates HOXA9. Methylates and regulates SRGAP2 which is involved in cell migration and differentiation. 
Sequence Annotation
 REGION 13 292 TIM barrel.
 REGION 333 334 S-adenosyl-L-methionine binding.
 REGION 419 420 S-adenosyl-L-methionine binding.
 REGION 465 637 Beta barrel.
 REGION 488 494 Dimerization.
 ACT_SITE 435 435 Proton donor/acceptor (Probable).
 ACT_SITE 444 444 Proton donor/acceptor (Probable).
 BINDING 304 304 Peptide substrate.
 BINDING 307 307 Peptide substrate.
 BINDING 324 324 S-adenosyl-L-methionine.
 BINDING 392 392 S-adenosyl-L-methionine.
 MOD_RES 2 2 N-acetylalanine.  
Keyword
 3D-structure; Acetylation; Alternative splicing; Chromatin regulator; Complete proteome; Cytoplasm; Direct protein sequencing; Methyltransferase; Nucleus; Reference proteome; S-adenosyl-L-methionine; Transcription; Transcription regulation; Transferase. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 637 AA 
Protein Sequence
MAAMAVGGAG GSRVSSGRDL NCVPEIADTL GAVAKQGFDF LCMPVFHPRF KREFIQEPAK 60
NRPGPQTRSD LLLSGRDWNT LIVGKLSPWI RPDSKVEKIR RNSEAAMLQE LNFGAYLGLP 120
AFLLPLNQED NTNLARVLTN HIHTGHHSSM FWMRVPLVAP EDLRDDIIEN APTTHTEEYS 180
GEEKTWMWWH NFRTLCDYSK RIAVALEIGA DLPSNHVIDR WLGEPIKAAI LPTSIFLTNK 240
KGFPVLSKMH QRLIFRLLKL EVQFIITGTN HHSEKEFCSY LQYLEYLSQN RPPPNAYELF 300
AKGYEDYLQS PLQPLMDNLE SQTYEVFEKD PIKYSQYQQA IYKCLLDRVP EEEKDTNVQV 360
LMVLGAGRGP LVNASLRAAK QADRRIKLYA VEKNPNAVVT LENWQFEEWG SQVTVVSSDM 420
REWVAPEKAD IIVSELLGSF ADNELSPECL DGAQHFLKDD GVSIPGEYTS FLAPISSSKL 480
YNEVRACREK DRDPEAQFEM PYVVRLHNFH QLSAPQPCFT FSHPNRDPMI DNNRYCTLEF 540
PVEVNTVLHG FAGYFETVLY QDITLSIRPE THSPGMFSWF PILFPIKQPI TVREGQTICV 600
RFWRCSNSKK VWYEWAVTAP VCSAIHNPTG RSYTIGL 637 
Gene Ontology
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0005634; C:nucleus; NAS:UniProtKB.
 GO:0043234; C:protein complex; IEA:Compara.
 GO:0003682; F:chromatin binding; IEA:Compara.
 GO:0008469; F:histone-arginine N-methyltransferase activity; IEA:EC.
 GO:0035243; F:protein-arginine omega-N symmetric methyltransferase activity; IMP:UniProtKB.
 GO:0043021; F:ribonucleoprotein complex binding; IPI:UniProtKB.
 GO:0008283; P:cell proliferation; TAS:ProtInc.
 GO:0042118; P:endothelial cell activation; IMP:UniProtKB.
 GO:0043985; P:histone H4-R3 methylation; NAS:UniProtKB.
 GO:0034660; P:ncRNA metabolic process; TAS:Reactome.
 GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IEA:Compara.
 GO:0007088; P:regulation of mitosis; TAS:ProtInc.
 GO:0000387; P:spliceosomal snRNP assembly; IMP:UniProtKB.
 GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW. 
Interpro
 IPR025799; Arg_MeTrfase.
 IPR007857; Arg_MeTrfase_PRMT5. 
Pfam
 PF05185; PRMT5 
SMART
  
PROSITE
  
PRINTS