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Q8CIG8 (ANM5_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 101. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Protein arginine N-methyltransferase 5

EC=2.1.1.-
Alternative name(s):
Histone-arginine N-methyltransferase PRMT5
EC=2.1.1.125
Jak-binding protein 1
Shk1 kinase-binding protein 1 homolog
Short name=SKB1 homolog
Gene names
Name:Prmt5
Synonyms:Jbp1, Skb1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length637 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.4 Ref.6 Ref.7 Ref.8

Catalytic activity

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

Enzyme regulation

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

Subunit structure

Forms, at least, homodimers and homotetramers. Component of the methylosome, a 20S complex containing at least CLNS1A/pICln, PRMT5/SKB1 and WDR77/MEP50. Component of a high molecular weight E2F-pocket protein complex, CERC (cyclin E1 repressor complex). Also interacts with Sm proteins, JAK2 and SSTR1. Associates with SWI/SNF remodeling complexes containing SMARCA2 and SMARCA4. Interacts with LSM11, PRMT7 and SNRPD3. Interacts with COPRS; promoting its recruitment on histone H4 By similarity. Interacts with PRDM1. Interacts with RPS10. Interacts with EGFR; methylates EGFR and stimulates EGFR-mediated ERK activation By similarity. Interacts with BRAF and with active RAF1 By similarity. Interacts with HOXA9 By similarity. Interacts with SRGAP2. Interacts with EPB41L3; this modulates methylation of target proteins By similarity. 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. Interacts with IWS1 By similarity. Ref.5 Ref.7 Ref.9 Ref.10

Subcellular location

Cytoplasm By similarity. Nucleus Ref.9.

Sequence similarities

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

Contains 1 SAM-dependent MTase PRMT-type domain.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   LigandS-adenosyl-L-methionine
   Molecular functionChromatin regulator
Methyltransferase
Transferase
   PTMAcetylation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processendothelial cell activation

Inferred from electronic annotation. Source: Ensembl

histone arginine methylation

Inferred from Biological aspect of Ancestor. Source: RefGenome

negative regulation of transcription from RNA polymerase II promoter

Inferred from mutant phenotype PubMed 18347060. Source: MGI

peptidyl-arginine N-methylation

Inferred from sequence orthology PubMed 15369763. Source: MGI

peptidyl-arginine methylation

Inferred from sequence or structural similarity. Source: UniProtKB

peptidyl-arginine methylation, to symmetrical-dimethyl arginine

Inferred from Biological aspect of Ancestor. Source: RefGenome

spliceosomal snRNP assembly

Inferred from sequence or structural similarity. Source: UniProtKB

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcytosol

Inferred from sequence or structural similarity. Source: UniProtKB

methylosome

Inferred from sequence or structural similarity. Source: UniProtKB

nucleus

Inferred from direct assay PubMed 16787967. Source: UniProtKB

   Molecular_functionchromatin binding

Inferred from mutant phenotype PubMed 18347060. Source: MGI

histone-arginine N-methyltransferase activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

methyltransferase activity

Inferred from sequence orthology PubMed 15369763. Source: MGI

protein binding

Inferred from physical interaction Ref.10. Source: UniProtKB

protein-arginine omega-N symmetric methyltransferase activity

Inferred from sequence or structural similarity. Source: UniProtKB

ribonucleoprotein complex binding

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 637636Protein arginine N-methyltransferase 5
PRO_0000212344

Regions

Domain308 – 615308SAM-dependent MTase PRMT-type
Region13 – 292280TIM barrel By similarity
Region333 – 3342S-adenosyl-L-methionine binding By similarity
Region419 – 4202S-adenosyl-L-methionine binding By similarity
Region465 – 637173Beta barrel By similarity
Region488 – 4947Dimerization By similarity

Sites

Active site4351Proton donor/acceptor By similarity
Active site4441Proton donor/acceptor By similarity
Binding site3041Peptide substrate By similarity
Binding site3071Peptide substrate By similarity
Binding site3241S-adenosyl-L-methionine By similarity
Binding site3921S-adenosyl-L-methionine By similarity
Site3271Critical for specifying symmetric addition of methyl groups By similarity

Amino acid modifications

Modified residue21N-acetylalanine By similarity

Experimental info

Sequence conflict1691A → E in BAE21155. Ref.1
Sequence conflict1691A → E in BAE38057. Ref.1
Sequence conflict3761L → F in AAF04503. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Q8CIG8 [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: E8014CA172B30543

FASTA63772,680
        10         20         30         40         50         60 
MAAMAVGGAG GSRVSSGRDL NCVPEIADTL GAVAKQGFDF LCMPVFHPRF KREFIQEPAK 

        70         80         90        100        110        120 
NRPGPQTRSD LLLSGRDWNT LIVGKLSPWI HPDSKVEKIR RNSEAAMLQE LNFGAYLGLP 

       130        140        150        160        170        180 
AFLLPLNQED NTNLARVLTN HIHTGHHSSM FWMRVPLVAP EDLRDDVIAN APTTHTEEYS 

       190        200        210        220        230        240 
GEEKTWMWWH NFRTLCDYSK RIAVALEIGA DLPSNHVIDR WLGEPIKAAI LPTSIFLTNK 

       250        260        270        280        290        300 
KGFPVLSKVQ QRLIFRLLKL EVQFIITGTN HHSEKEFCSY LQYLEYLSQN RPPPNAYELF 

       310        320        330        340        350        360 
AKGYEDYLQS PLQPLMDNLE SQTYEVFEKD PIKYSQYQQA IYKCLLDRVP EEEKETNVQV 

       370        380        390        400        410        420 
LMVLGAGRGP LVNASLRAAK QAERRIRLYA VEKNPNAVVT LENWQFEEWG SQVTVVSSDM 

       430        440        450        460        470        480 
REWVAPEKAD IIVSELLGSF ADNELSPECL DGAQHFLKDD GVSIPGEYTS FLAPISSSKL 

       490        500        510        520        530        540 
YNEVRACREK DRDPEAQFEM PYVVRLHNFH QLSAPKPCFT FSHPNRDPMI DNNRYCTLEF 

       550        560        570        580        590        600 
PVEVNTVLHG FAGYFETVLY RDITLSIRPE THSPGMFSWF PIFFPIKQPI TVHEGQNICV 

       610        620        630 
RFWRCSNSKK VWYEWAVTAP VCSSIHNPTG RSYTIGL 

« Hide

References

« Hide 'large scale' references
[1]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6J.
Tissue: Skin.
[2]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: FVB/N.
Tissue: Mammary tumor.
[3]"The human homologue of the yeast proteins Skb1 and Hsl7p interacts with Jak kinases and contains protein methyltransferase activity."
Pollack B.P., Kotenko S.V., He W., Izotova L.S., Barnoski B.L., Pestka S.
J. Biol. Chem. 274:31531-31542(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 7-637.
[4]"Human SWI/SNF-associated PRMT5 methylates histone H3 arginine 8 and negatively regulates expression of ST7 and NM23 tumor suppressor genes."
Pal S., Vishwanath S.N., Erdjument-Bromage H., Tempst P., Sif S.
Mol. Cell. Biol. 24:9630-9645(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN METHYLATION OF HISTONE H3.
[5]"Blimp1 associates with Prmt5 and directs histone arginine methylation in mouse germ cells."
Ancelin K., Lange U.C., Hajkova P., Schneider R., Bannister A.J., Kouzarides T., Surani M.A.
Nat. Cell Biol. 8:623-630(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PRDM1.
[6]"Proteomic analysis of murine Piwi proteins reveals a role for arginine methylation in specifying interaction with Tudor family members."
Vagin V.V., Wohlschlegel J., Qu J., Jonsson Z., Huang X., Chuma S., Girard A., Sachidanandam R., Hannon G.J., Aravin A.A.
Genes Dev. 23:1749-1762(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN METHYLATION OF PIWI PROTEINS.
[7]"Friend of Prmt1, a novel chromatin target of protein arginine methyltransferases."
van Dijk T.B., Gillemans N., Stein C., Fanis P., Demmers J., van de Corput M., Essers J., Grosveld F., Bauer U.M., Philipsen S.
Mol. Cell. Biol. 30:260-272(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH CHTOP.
[8]"Protein arginine methyltransferase 5 regulates ERK1/2 signal transduction amplitude and cell fate through CRAF."
Andreu-Perez P., Esteve-Puig R., de Torre-Minguela C., Lopez-Fauqued M., Bech-Serra J.J., Tenbaum S., Garcia-Trevijano E.R., Canals F., Merlino G., Avila M.A., Recio J.A.
Sci. Signal. 4:RA58-RA58(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN THE REGULATION OF MAPK1/MAPK3 SIGNALING PATHWAY, RAF1 METHYLATION.
[9]"Five friends of methylated chromatin target of protein-arginine-methyltransferase[prmt]-1 (chtop), a complex linking arginine methylation to desumoylation."
Fanis P., Gillemans N., Aghajanirefah A., Pourfarzad F., Demmers J., Esteghamat F., Vadlamudi R.K., Grosveld F., Philipsen S., van Dijk T.B.
Mol. Cell. Proteomics 11:1263-1273(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CHTOP, SUBCELLULAR LOCATION.
[10]"The histone- and PRMT5-associated protein COPR5 is required for myogenic differentiation."
Paul C., Sardet C., Fabbrizio E.
Cell Death Differ. 19:900-908(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH COPRS, IDENTIFICATION IN A COMPLEX WITH PRMT5; RUNX1 AND CBFB.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AK132414 mRNA. Translation: BAE21155.1.
AK165165 mRNA. Translation: BAE38057.1.
BC023905 mRNA. Translation: AAH23905.1.
AF167573 mRNA. Translation: AAF04503.1.
CCDSCCDS27091.1.
RefSeqNP_038796.2. NM_013768.3.
UniGeneMm.196585.

3D structure databases

ProteinModelPortalQ8CIG8.
SMRQ8CIG8. Positions 13-637.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid205181. 14 interactions.
IntActQ8CIG8. 7 interactions.

PTM databases

PhosphoSiteQ8CIG8.

Proteomic databases

MaxQBQ8CIG8.
PaxDbQ8CIG8.
PRIDEQ8CIG8.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000023873; ENSMUSP00000023873; ENSMUSG00000023110.
GeneID27374.
KEGGmmu:27374.
UCSCuc007twf.2. mouse.

Organism-specific databases

CTD10419.
MGIMGI:1351645. Prmt5.

Phylogenomic databases

eggNOGNOG291156.
GeneTreeENSGT00390000001141.
HOGENOMHOG000175933.
HOVERGENHBG057083.
InParanoidQ8CIG8.
KOK02516.
OrthoDBEOG7X6KZR.
PhylomeDBQ8CIG8.
TreeFamTF300626.

Gene expression databases

ArrayExpressQ8CIG8.
BgeeQ8CIG8.
CleanExMM_PRMT5.
GenevestigatorQ8CIG8.

Family and domain databases

Gene3D3.40.50.150. 1 hit.
InterProIPR025799. Arg_MeTrfase.
IPR007857. Arg_MeTrfase_PRMT5.
IPR029063. SAM-dependent_MTases-like.
[Graphical view]
PANTHERPTHR10738. PTHR10738. 1 hit.
PfamPF05185. PRMT5. 1 hit.
[Graphical view]
PIRSFPIRSF015894. Skb1_MeTrfase. 1 hit.
SUPFAMSSF53335. SSF53335. 1 hit.
PROSITEPS51678. SAM_MT_PRMT. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio305288.
PROQ8CIG8.
SOURCESearch...

Entry information

Entry nameANM5_MOUSE
AccessionPrimary (citable) accession number: Q8CIG8
Secondary accession number(s): Q3TNN1, Q9QZS9
Entry history
Integrated into UniProtKB/Swiss-Prot: June 20, 2003
Last sequence update: January 23, 2007
Last modified: July 9, 2014
This is version 101 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot