Reviewed, UniProtKB/Swiss-Prot O14744 (ANM5_HUMAN)

Names and origin

Protein names

Recommended name:
    Protein arginine N-methyltransferase 5
    EC=2.1.1.-
Alternative name(s):
    Histone-arginine N-methyltransferase PRMT5
    EC=2.1.1.125
    Shk1 kinase-binding protein 1 homolog
    SKB1Hs
    Jak-binding protein 1
    72 kDa ICln-binding protein

Gene names

Name:	PRMT5
Synonyms:	HRMT1L5, IBP72, JBP1, SKB1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	637 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.
Catalytic activity	S-adenosyl-L-methionine + histone-arginine = S-adenosyl-L-homocysteine + histone-N(omega)-methyl-arginine.
Subunit structure	Forms, at least, homodimers and homotetramers. Interacts with PRDM1 By similarity. Component of the methylosome, a 20S complex containing at least pICLn, PRMT1/SKB1 and MEP50. Component of a high molecular weight E2F-pocket protein complex, CERC (cyclin E1 repressor complex). Also interacts with Sm proteins, JAK2, SSTR1 and SUPT5H. Associates with SWI/SNF remodeling complexes containing SMARCA2 and SMARCA4. Interacts with PRMT7 and SNRPD3. Interacts with COPR5/C17orf79; promoting its recruitment on histone H4.
Subcellular location	Cytoplasm. Nucleus.
Tissue specificity	Ubiquitous.
Post-translational modification	Disulfide bonds and non-covalent association mediate homooligomers formation.
Sequence similarities	Belongs to the protein arginine N-methyltransferase family.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
Ligand	S-adenosyl-L-methionine
Molecular function	Chromatin regulator Methyltransferase Transferase
PTM	Acetylation Disulfide bond
Technical term	Direct protein sequencing
Gene Ontology (GO)
Biological process	cell proliferation Ref.2 Traceable author statement. Source: ProtInc histone H4-R3 methylation Ref.15 Non-traceable author statement. Source: UniProtKB peptidyl-arginine N-methylation Inferred from direct assay. Source: MGI regulation of mitosis Ref.2 Traceable author statement. Source: ProtInc regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW spliceosomal snRNP biogenesis Ref.14 Inferred from mutant phenotype. Source: UniProtKB transcription Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Ref.15 Non-traceable author statement. Source: UniProtKB
Molecular function	histone-arginine N-methyltransferase activity Inferred from electronic annotation. Source: EC protein binding Ref.15 Inferred from physical interaction. Source: UniProtKB protein-arginine omega-N symmetric methyltransferase activity Ref.14 Inferred from mutant phenotype. Source: UniProtKB ribonucleoprotein binding Ref.14 Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 1 isoform produced by alternative splicing. [Select]

Note: A number of isoforms are produced. According to EST sequences.

Isoform 1 (identifier: O14744-1)

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.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed Ref.6 Ref.7
	Chain	2 – 637	636	Protein arginine N-methyltransferase 5		PRO_0000212342
Amino acid modifications
	Modified residue	2	1	N-acetylalanine Ref.7
Experimental info
	Mutagenesis	367 – 368	2	GR → AA: Abolishes enzymatic activity. Ref.13
	Sequence conflict	247	1	S → F in AAB66581. Ref.2
	Sequence conflict	553	1	G → V in AAB66581. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 23, 2007. Version 4. Checksum: 522E255B384F25E7	FASTA	637	72,684
	10 20 30 40 50 60 MAAMAVGGAG GSRVSSGRDL NCVPEIADTL GAVAKQGFDF LCMPVFHPRF KREFIQEPAK 70 80 90 100 110 120 NRPGPQTRSD LLLSGRDWNT LIVGKLSPWI RPDSKVEKIR RNSEAAMLQE LNFGAYLGLP 130 140 150 160 170 180 AFLLPLNQED NTNLARVLTN HIHTGHHSSM FWMRVPLVAP EDLRDDIIEN APTTHTEEYS 190 200 210 220 230 240 GEEKTWMWWH NFRTLCDYSK RIAVALEIGA DLPSNHVIDR WLGEPIKAAI LPTSIFLTNK 250 260 270 280 290 300 KGFPVLSKMH QRLIFRLLKL EVQFIITGTN HHSEKEFCSY LQYLEYLSQN RPPPNAYELF 310 320 330 340 350 360 AKGYEDYLQS PLQPLMDNLE SQTYEVFEKD PIKYSQYQQA IYKCLLDRVP EEEKDTNVQV 370 380 390 400 410 420 LMVLGAGRGP LVNASLRAAK QADRRIKLYA VEKNPNAVVT LENWQFEEWG SQVTVVSSDM 430 440 450 460 470 480 REWVAPEKAD IIVSELLGSF ADNELSPECL DGAQHFLKDD GVSIPGEYTS FLAPISSSKL 490 500 510 520 530 540 YNEVRACREK DRDPEAQFEM PYVVRLHNFH QLSAPQPCFT FSHPNRDPMI DNNRYCTLEF 550 560 570 580 590 600 PVEVNTVLHG FAGYFETVLY QDITLSIRPE THSPGMFSWF PILFPIKQPI TVREGQTICV 610 620 630 RFWRCSNSKK VWYEWAVTAP VCSAIHNPTG RSYTIGL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"pICln binds to a mammalian homolog of a yeast protein involved in regulation of cell morphology." Krapivinsky G., Pu W., Wickman K., Krapivinsky L., Clapham D.E. J. Biol. Chem. 273:10811-10814(1998) [PubMed: 9556550] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH CLNS1A.
[2]	"Negative regulation of mitosis in fission yeast by the shk1 interacting protein skb1 and its human homolog, Skb1Hs." Gilbreth M., Yang P., Bartholomeusz G., Pimental R.A., Kansra S., Gadiraju R., Marcus S. Proc. Natl. Acad. Sci. U.S.A. 95:14781-14786(1998) [PubMed: 9843966] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[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: 10531356] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH JAK2.
[4]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Skin.
[6]	"Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides." Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R., Vandekerckhove J. Nat. Biotechnol. 21:566-569(2003) [PubMed: 12665801] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-13. Tissue: Platelet.
[7]	Bienvenut W.V., Calvo F., Matallanas D., Cooper W.N., Kolch W., Boldt K., von Kriegsheim A.F. Submitted (FEB-2008) to UniProtKB Cited for: PROTEIN SEQUENCE OF 2-13; 19-49; 52-60; 69-95; 155-193; 201-248; 334-343; 349-377; 386-393; 422-428; 459-485 AND 489-526, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, MASS SPECTROMETRY. Tissue: Hepatoma and Mammary carcinoma.
[8]	"Interaction of the somatostatin receptor subtype 1 with the human homolog of the Shk1 kinase-binding protein from yeast." Schwaerzler A., Kreienkamp H.-J., Richter D. J. Biol. Chem. 275:9557-9562(2000) [PubMed: 10734105] [Abstract] Cited for: INTERACTION WITH SSTR1.
[9]	"Prmt5, which forms distinct homo-oligomers, is a member of the protein-arginine methyltransferase family." Rho J., Choi S., Seong Y.R., Cho W.-K., Kim S.H., Im D.-S. J. Biol. Chem. 276:11393-11401(2001) [PubMed: 11152681] [Abstract] Cited for: FUNCTION, SUBUNIT.
[10]	"Methylation of Sm proteins by a complex containing PRMT5 and the putative U snRNP assembly factor pICln." Meister G., Eggert C., Buehler D., Brahms H., Kambach C., Fischer U. Curr. Biol. 11:1990-1994(2001) [PubMed: 11747828] [Abstract] Cited for: FUNCTION IN THE METHYLATION AT SNRPD1 AND SNRPD3.
[11]	"Negative regulation of transcription by the type II arginine methyltransferase PRMT5." Fabbrizio E., El Messaoudi S., Polanowska J., Paul C., Cook J.R., Lee J.-H., Negre V., Rousset M., Pestka S., Le Cam A., Sardet C. EMBO Rep. 3:641-645(2002) [PubMed: 12101096] [Abstract] Cited for: COMPONENT OF THE CERC COMPLEX.
[12]	"Methylation of SPT5 regulates its interaction with RNA polymerase II and transcriptional elongation properties." Kwak Y.T., Guo J., Prajapati S., Park K.-J., Surabhi R.M., Miller B., Gehrig P., Gaynor R.B. Mol. Cell 11:1055-1066(2003) [PubMed: 12718890] [Abstract] Cited for: INTERACTION WITH SUPT5H.
[13]	"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: 15485929] [Abstract] Cited for: INTERACTION WITH THE SWI/SNF COMPLEX, MUTAGENESIS OF 367-GLY-ARG-368, METHYLATION OF HISTONE H3.
[14]	"Two distinct arginine methyltransferases are required for biogenesis of Sm-class ribonucleoproteins." Gonsalvez G.B., Tian L., Ospina J.K., Boisvert F.-M., Lamond A.I., Matera A.G. J. Cell Biol. 178:733-740(2007) [PubMed: 17709427] [Abstract] Cited for: FUNCTION, INTERACTION WITH PRMT7 AND SNRPD3.
[15]	"The histone-binding protein COPR5 is required for nuclear functions of the protein arginine methyltransferase PRMT5." Lacroix M., Messaoudi S.E., Rodier G., Le Cam A., Sardet C., Fabbrizio E. EMBO Rep. 9:452-458(2008) [PubMed: 18404153] [Abstract] Cited for: INTERACTION WITH C17ORF79, SUBCELLULAR LOCATION.
[16]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF015913 mRNA. Translation: AAB66581.1. AF167572 mRNA. Translation: AAF04502.1. CR456741 mRNA. Translation: CAG33022.1. BC025979 mRNA. Translation: AAH25979.1.
IPI	IPI00441473.
PIR	T03842.
RefSeq	NP_001034708.1. NP_006100.2.
UniGene	Hs.367854
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	O14744. 9 interactions.
PTM databases
PhosphoSite	O14744.
Proteomic databases
PeptideAtlas	O14744.
PRIDE	O14744.
Genome annotation databases
Ensembl	ENSG00000100462. Homo sapiens. [Contig view]
GeneID	10419.
KEGG	hsa:10419.
Organism-specific databases
GeneCards	GC14M022460.
H-InvDB	HIX0011525.
HGNC	HGNC:10894. PRMT5.
HPA	CAB012459. HPA005525.
MIM	604045. gene.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	O14744.
HOVERGEN	O14744.
OMA	O14744. FETPYVV.
Enzyme and pathway databases
BRENDA	2.1.1.125. 247.
Pathway_Interaction_DB	hdac_classi_pathway. Signaling events mediated by HDAC Class I.
Reactome	REACT_11052. Metabolism of non-coding RNA.
Gene expression databases
ArrayExpress	O14744.
Bgee	O14744.
CleanEx	HS_PRMT5.
GermOnline	ENSG00000100462. Homo sapiens.
Family and domain databases
InterPro	IPR007857. Skb1_MeTrfase. [Graphical view]
PANTHER	PTHR10738. Skb1_mtfrase. 1 hit.
Pfam	PF05185. PRMT5. 1 hit. [Graphical view]
PIRSF	PIRSF015894. Skb1_MeTrfase. 1 hit.
ProtoNet	Search...
Other Resources
NextBio	39486.
SOURCE	Search...

Entry information

Entry name

ANM5_HUMAN

Accession

Primary (citable) accession number: O14744
Secondary accession number(s): Q6IBR1, Q9UKH1

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 20, 2003
Last sequence update:	January 23, 2007
Last modified:	June 16, 2009
This is version 71 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)