Reviewed, UniProtKB/Swiss-Prot Q9NR22 (ANM8_HUMAN)

Names and origin

Protein names

Recommended name:
    Protein arginine N-methyltransferase 8
    EC=2.1.1.-
Alternative name(s):
    Heterogeneous nuclear ribonucleoprotein methyltransferase-like protein 4

Gene names

Name:	PRMT8
Synonyms:	HRMT1L3, HRMT1L4

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	394 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	Membrane-associated arginine methyltransferase that can both catalyze the formation of omega-N monomethylarginine (MMA) and asymmetrical dimethylarginine (aDMA). Able to mono- and dimethylate EWS protein; however its precise role toward EWS remains unclear as it still interacts with fully methylated EWS.
Subunit structure	Homodimers and heterodimers with PRMT1 or PRMT2, recruiting PRMT1 to the cell membrane. Interacts with PRMT2 and FYN (via the SH3 domain). Interacts with EWS; independently of EWS methylation status.
Subcellular location	Cell membrane; Lipid-anchor; Cytoplasmic side. Ref.5
Tissue specificity	Brain-specific.
Domain	The SH3-binding motifs mediate the interaction with SH3 domain-containing proteins such as PRMT2 and FYN, possibly leading to displace the N-terminal domain and activate the protein. The N-terminal region (1-60) inhibits the enzymatic activity.
Sequence similarities	Belongs to the protein arginine N-methyltransferase family. PRMT8 subfamily.
biophysicochemical properties	Kinetic parameters: KM=1.3 µM for GRGGFGGRGGFRGGRGG-NH2
Sequence caution	The sequence BAG37987.1 differs from that shown. Reason: Frameshift at position 45.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing
Domain	Repeat
Ligand	S-adenosyl-L-methionine
Molecular function	Methyltransferase Transferase
PTM	Lipoprotein Methylation Myristate
Gene Ontology (GO)
Biological process	histone methylation Ref.5 Inferred from direct assay. Source: HGNC peptidyl-arginine methylation, to asymmetrical-dimethyl arginine Ref.5 Inferred from direct assay. Source: HGNC regulation of protein binding Ref.5 Traceable author statement. Source: HGNC
Cellular component	plasma membrane Ref.5 Ref.7 Inferred from direct assay. Source: UniProtKB
Molecular function	histone-arginine N-methyltransferase activity Ref.5 Inferred from direct assay. Source: HGNC protein heterodimerization activity Ref.5 Inferred from direct assay. Source: HGNC protein homodimerization activity Ref.5 Inferred from direct assay. Source: HGNC protein-arginine omega-N asymmetric methyltransferase activity Ref.5 Ref.7 Inferred from direct assay. Source: UniProtKB protein-arginine omega-N monomethyltransferase activity Ref.5 Ref.7 Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9NR22-1)

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.

Isoform 2 (identifier: Q9NR22-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-25: MGMKHSSRCLLLRRKMAENAAESTE → MESLASDGFKLKEVSS

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed
	Chain	2 – 394	393	Protein arginine N-methyltransferase 8		PRO_0000212329
Regions
	Motif	29 – 42	14	SH3-binding 1
	Motif	53 – 58	6	SH3-binding 2
Sites
	Binding site	86	1	S-adenosyl-L-methionine By similarity
	Binding site	95	1	S-adenosyl-L-methionine By similarity
	Binding site	119	1	S-adenosyl-L-methionine; via carbonyl oxygen By similarity
	Binding site	141	1	S-adenosyl-L-methionine By similarity
	Binding site	170	1	S-adenosyl-L-methionine By similarity
Amino acid modifications
	Modified residue	58	1	Omega-N-methylarginine; by PRMT8
	Modified residue	73	1	Asymmetric dimethylarginine; by PRMT8
	Lipidation	2	1	N-myristoyl glycine
Natural variations
	Alternative sequence	1 – 25	25	MGMKH…AESTE → MESLASDGFKLKEVSS in isoform 2.		VSP_037466
Experimental info
	Mutagenesis	2	1	G → A: Loss of cell membrane localization. Ref.5
	Sequence conflict	150	1	E → Q in AAH22458. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified February 21, 2006. Version 2. Checksum: 44B55438D16394CD	FASTA	394	45,291
	10 20 30 40 50 60 MGMKHSSRCL LLRRKMAENA AESTEVNSPP SQPPQPVVPA KPVQCVHHVS TQPSCPGRGK 70 80 90 100 110 120 MSKLLNPEEM TSRDYYFDSY AHFGIHEEML KDEVRTLTYR NSMYHNKHVF KDKVVLDVGS 130 140 150 160 170 180 GTGILSMFAA KAGAKKVFGI ECSSISDYSE KIIKANHLDN IITIFKGKVE EVELPVEKVD 190 200 210 220 230 240 IIISEWMGYC LFYESMLNTV IFARDKWLKP GGLMFPDRAA LYVVAIEDRQ YKDFKIHWWE 250 260 270 280 290 300 NVYGFDMTCI RDVAMKEPLV DIVDPKQVVT NACLIKEVDI YTVKTEELSF TSAFCLQIQR 310 320 330 340 350 360 NDYVHALVTY FNIEFTKCHK KMGFSTAPDA PYTHWKQTVF YLEDYLTVRR GEEIYGTISM 370 380 390 KPNAKNVRDL DFTVDLDFKG QLCETSVSND YKMR
	Isoform 2. Checksum: 20E4A89EFD1C520D	FASTA	385	44,169
	10 20 30 40 50 60 MESLASDGFK LKEVSSVNSP PSQPPQPVVP AKPVQCVHHV STQPSCPGRG KMSKLLNPEE 70 80 90 100 110 120 MTSRDYYFDS YAHFGIHEEM LKDEVRTLTY RNSMYHNKHV FKDKVVLDVG SGTGILSMFA 130 140 150 160 170 180 AKAGAKKVFG IECSSISDYS EKIIKANHLD NIITIFKGKV EEVELPVEKV DIIISEWMGY 190 200 210 220 230 240 CLFYESMLNT VIFARDKWLK PGGLMFPDRA ALYVVAIEDR QYKDFKIHWW ENVYGFDMTC 250 260 270 280 290 300 IRDVAMKEPL VDIVDPKQVV TNACLIKEVD IYTVKTEELS FTSAFCLQIQ RNDYVHALVT 310 320 330 340 350 360 YFNIEFTKCH KKMGFSTAPD APYTHWKQTV FYLEDYLTVR RGEEIYGTIS MKPNAKNVRD 370 380 LDFTVDLDFK GQLCETSVSN DYKMR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Neuroepithelioma.
[2]	"The finished DNA sequence of human chromosome 12." Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R. , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A. Nature 440:346-351(2006) [PubMed: 16541075] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"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] (ISOFORM 1). Tissue: Brain.
[4]	"Transcripts in human map region 12p13.3." Lorenz B., Strom T.M. Submitted (MAY-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 37-394 (ISOFORM 1). Tissue: Brain.
[5]	"PRMT8, a new membrane-bound tissue-specific member of the protein arginine methyltransferase family." Lee J., Sayegh J., Daniel J., Clarke S., Bedford M.T. J. Biol. Chem. 280:32890-32896(2005) [PubMed: 16051612] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, MYRISTOYLATION AT GLY-2, MUTAGENESIS OF GLY-2.
[6]	"Regulation of protein arginine methyltransferase 8 (PRMT8) activity by its N-terminal domain." Sayegh J., Webb K., Cheng D., Bedford M.T., Clarke S.G. J. Biol. Chem. 282:36444-36453(2007) [PubMed: 17925405] [Abstract] Cited for: FUNCTION, N-TERMINAL REGION DOMAIN, SH3-BINDING MOTIF DOMAIN, AUTOMETHYLATION AT ARG-58 AND ARG-73, INTERACTION WITH PRMT2 AND FYN.
[7]	"Identification of proteins interacting with protein arginine methyltransferase 8: the Ewing sarcoma (EWS) protein binds independent of its methylation state." Pahlich S., Zakaryan R.P., Gehring H. Proteins 72:1125-1137(2008) [PubMed: 18320585] [Abstract] Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION, INTERACTION WITH EWS.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AK315619 mRNA. Translation: BAG37987.1. Frameshift. AC005831 Genomic DNA. No translation available. AC005908 Genomic DNA. No translation available. AC005925 Genomic DNA. No translation available. BC022458 mRNA. Translation: AAH22458.2. AF263539 mRNA. Translation: AAF91390.1. Different initiation.
IPI	IPI00549813.
RefSeq	NP_062828.3.
UniGene	Hs.504530
3D structure databases
HSSP	HSSP built from PDB template 1ORI based on UniProtKB Q63009.
SMR	Q9NR22. Positions 79-394.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9NR22. 2 interactions.
PTM databases
PhosphoSite	Q9NR22.
Proteomic databases
PRIDE	Q9NR22.
Genome annotation databases
Ensembl	ENSG00000111218. Homo sapiens. [Contig view]
GeneID	56341.
KEGG	hsa:56341.
Organism-specific databases
GeneCards	GC12P003470.
HGNC	HGNC:5188. PRMT8.
MIM	610086. gene.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	Q9NR22.
HOVERGEN	Q9NR22.
OMA	Q9NR22. LIFPDKC.
Gene expression databases
ArrayExpress	Q9NR22.
Bgee	Q9NR22.
CleanEx	HS_PRMT8.
GermOnline	ENSG00000111218. Homo sapiens.
Family and domain databases
ProtoNet	Search...
Other Resources
NextBio	61985.
SOURCE	Search...

Entry information

Entry name

ANM8_HUMAN

Accession

Primary (citable) accession number: Q9NR22
Secondary accession number(s): B2RDP0, Q8TBJ8

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 11, 2001
Last sequence update:	February 21, 2006
Last modified:	June 16, 2009
This is version 52 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)