ID ANM8_HUMAN Reviewed; 394 AA. AC Q9NR22; B2RDP0; Q8TBJ8; DT 11-JAN-2001, integrated into UniProtKB/Swiss-Prot. DT 21-FEB-2006, sequence version 2. DT 09-DEC-2015, entry version 118. DE RecName: Full=Protein arginine N-methyltransferase 8; DE EC=2.1.1.-; DE AltName: Full=Heterogeneous nuclear ribonucleoprotein methyltransferase-like protein 4; GN Name=PRMT8; Synonyms=HRMT1L3, HRMT1L4; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Neuroepithelioma; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16541075; DOI=10.1038/nature04569; RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., RA Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., RA Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., RA Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., RA Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., RA Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., RA Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., RA Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., RA Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., RA Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., RA Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., RA Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., RA Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., RA Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., RA Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., RA Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., RA Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., RA Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., RA Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., RA Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., RA Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., RA Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., RA Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., RA Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., RA Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., RA Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., RA Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., RA Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., RA Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., RA Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., RA Kucherlapati R., Weinstock G., Gibbs R.A.; RT "The finished DNA sequence of human chromosome 12."; RL Nature 440:346-351(2006). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] OF 37-394 (ISOFORM 1). RC TISSUE=Brain; RA Lorenz B., Strom T.M.; RT "Transcripts in human map region 12p13.3."; RL Submitted (MAY-2000) to the EMBL/GenBank/DDBJ databases. RN [5] RP FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, MYRISTOYLATION AT RP GLY-2, AND MUTAGENESIS OF GLY-2. RX PubMed=16051612; DOI=10.1074/jbc.M506944200; RA Lee J., Sayegh J., Daniel J., Clarke S., Bedford M.T.; RT "PRMT8, a new membrane-bound tissue-specific member of the protein RT arginine methyltransferase family."; RL J. Biol. Chem. 280:32890-32896(2005). RN [6] RP FUNCTION, N-TERMINAL REGION DOMAIN, DOMAIN SH3-BINDING MOTIF, RP METHYLATION AT ARG-58 AND ARG-73, AND INTERACTION WITH PRMT2 AND FYN. RX PubMed=17925405; DOI=10.1074/jbc.M704650200; RA Sayegh J., Webb K., Cheng D., Bedford M.T., Clarke S.G.; RT "Regulation of protein arginine methyltransferase 8 (PRMT8) activity RT by its N-terminal domain."; RL J. Biol. Chem. 282:36444-36453(2007). RN [7] RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION, AND RP INTERACTION WITH EWS. RX PubMed=18320585; DOI=10.1002/prot.22004; RA Pahlich S., Zakaryan R.P., Gehring H.; RT "Identification of proteins interacting with protein arginine RT methyltransferase 8: the Ewing sarcoma (EWS) protein binds independent RT of its methylation state."; RL Proteins 72:1125-1137(2008). CC -!- FUNCTION: Membrane-associated arginine methyltransferase that can CC both catalyze the formation of omega-N monomethylarginine (MMA) CC and asymmetrical dimethylarginine (aDMA). Able to mono- and CC dimethylate EWS protein; however its precise role toward EWS CC remains unclear as it still interacts with fully methylated EWS. CC {ECO:0000269|PubMed:16051612, ECO:0000269|PubMed:17925405, CC ECO:0000269|PubMed:18320585}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=1.3 uM for GRGGFGGRGGFRGGRGG-NH2 CC {ECO:0000269|PubMed:18320585}; CC -!- SUBUNIT: Homodimers and heterodimers with PRMT1 or PRMT2, CC recruiting PRMT1 to the cell membrane. Interacts with PRMT2 and CC FYN (via the SH3 domain). Interacts with EWS; independently of EWS CC methylation status. {ECO:0000269|PubMed:17925405, CC ECO:0000269|PubMed:18320585}. CC -!- INTERACTION: CC Self; NbExp=4; IntAct=EBI-745545, EBI-745545; CC Q99873:PRMT1; NbExp=5; IntAct=EBI-10186886, EBI-78738; CC O60506:SYNCRIP; NbExp=3; IntAct=EBI-745545, EBI-1024357; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:16051612, CC ECO:0000269|PubMed:18320585}; Lipid-anchor CC {ECO:0000269|PubMed:16051612, ECO:0000269|PubMed:18320585}; CC Cytoplasmic side {ECO:0000269|PubMed:16051612, CC ECO:0000269|PubMed:18320585}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q9NR22-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9NR22-2; Sequence=VSP_037466; CC Note=No experimental confirmation available.; CC -!- TISSUE SPECIFICITY: Brain-specific. {ECO:0000269|PubMed:16051612}. CC -!- DOMAIN: The SH3-binding motifs mediate the interaction with SH3 CC domain-containing proteins such as PRMT2 and FYN, possibly leading CC to displace the N-terminal domain and activate the protein. CC {ECO:0000269|PubMed:17925405}. CC -!- DOMAIN: The N-terminal region (1-60) inhibits the enzymatic CC activity. {ECO:0000269|PubMed:17925405}. CC -!- SIMILARITY: Belongs to the class I-like SAM-binding CC methyltransferase superfamily. Protein arginine N- CC methyltransferase family. PRMT8 subfamily. {ECO:0000255|PROSITE- CC ProRule:PRU01015}. CC -!- SIMILARITY: Contains 1 SAM-dependent MTase PRMT-type domain. CC {ECO:0000255|PROSITE-ProRule:PRU01015}. CC -!- SEQUENCE CAUTION: CC Sequence=AAF91390.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=BAG37987.1; Type=Frameshift; Positions=45; Evidence={ECO:0000305}; 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; AK315619; BAG37987.1; ALT_FRAME; mRNA. DR EMBL; AC005831; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC005908; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC005925; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC022458; AAH22458.2; -; mRNA. DR EMBL; AF263539; AAF91390.1; ALT_INIT; mRNA. DR CCDS; CCDS58200.1; -. [Q9NR22-2] DR CCDS; CCDS8521.2; -. [Q9NR22-1] DR RefSeq; NP_001243465.1; NM_001256536.1. [Q9NR22-2] DR RefSeq; NP_062828.3; NM_019854.4. [Q9NR22-1] DR UniGene; Hs.504530; -. DR ProteinModelPortal; Q9NR22; -. DR SMR; Q9NR22; 82-394. DR BioGrid; 121140; 39. DR IntAct; Q9NR22; 11. DR MINT; MINT-3072538; -. DR STRING; 9606.ENSP00000372067; -. DR ChEMBL; CHEMBL3108648; -. DR PhosphoSite; Q9NR22; -. DR BioMuta; PRMT8; -. DR DMDM; 88983969; -. DR MaxQB; Q9NR22; -. DR PaxDb; Q9NR22; -. DR PRIDE; Q9NR22; -. DR DNASU; 56341; -. DR Ensembl; ENST00000382622; ENSP00000372067; ENSG00000111218. [Q9NR22-1] DR Ensembl; ENST00000452611; ENSP00000414507; ENSG00000111218. [Q9NR22-2] DR GeneID; 56341; -. DR KEGG; hsa:56341; -. DR UCSC; uc001qmf.4; human. [Q9NR22-1] DR UCSC; uc009zed.3; human. [Q9NR22-2] DR CTD; 56341; -. DR GeneCards; PRMT8; -. DR H-InvDB; HIX0010342; -. DR HGNC; HGNC:5188; PRMT8. DR HPA; HPA039747; -. DR MIM; 610086; gene. DR neXtProt; NX_Q9NR22; -. DR PharmGKB; PA134903406; -. DR eggNOG; KOG1499; Eukaryota. DR eggNOG; ENOG410XQYH; LUCA. DR GeneTree; ENSGT00550000074406; -. DR HOGENOM; HOG000198521; -. DR HOVERGEN; HBG001793; -. DR InParanoid; Q9NR22; -. DR KO; K11439; -. DR OMA; QMKPNER; -. DR OrthoDB; EOG7S7SDJ; -. DR PhylomeDB; Q9NR22; -. DR TreeFam; TF300608; -. DR BRENDA; 2.1.1.125; 2681. DR SABIO-RK; Q9NR22; -. DR ChiTaRS; PRMT8; human. DR GenomeRNAi; 56341; -. DR NextBio; 61985; -. DR PRO; PR:Q9NR22; -. DR Proteomes; UP000005640; Chromosome 12. DR Bgee; Q9NR22; -. DR CleanEx; HS_PRMT8; -. DR Genevisible; Q9NR22; HS. DR GO; GO:0005829; C:cytosol; IBA:GO_Central. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0044020; F:histone methyltransferase activity (H4-R3 specific); IBA:GO_Central. DR GO; GO:0008469; F:histone-arginine N-methyltransferase activity; IDA:HGNC. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0046982; F:protein heterodimerization activity; IDA:HGNC. DR GO; GO:0042803; F:protein homodimerization activity; IDA:HGNC. DR GO; GO:0035242; F:protein-arginine omega-N asymmetric methyltransferase activity; IDA:UniProtKB. DR GO; GO:0035241; F:protein-arginine omega-N monomethyltransferase activity; IDA:UniProtKB. DR GO; GO:0008757; F:S-adenosylmethionine-dependent methyltransferase activity; IDA:HGNC. DR GO; GO:0034969; P:histone arginine methylation; IDA:GOC. DR GO; GO:0043985; P:histone H4-R3 methylation; IBA:GOC. DR GO; GO:0016571; P:histone methylation; IDA:HGNC. DR GO; GO:0018216; P:peptidyl-arginine methylation; IDA:UniProtKB. DR GO; GO:0019919; P:peptidyl-arginine methylation, to asymmetrical-dimethyl arginine; IDA:HGNC. DR GO; GO:0043393; P:regulation of protein binding; TAS:HGNC. DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IBA:GO_Central. DR Gene3D; 3.40.50.150; -; 1. DR InterPro; IPR025799; Arg_MeTrfase. DR InterPro; IPR029063; SAM-dependent_MTases. DR PANTHER; PTHR11006; PTHR11006; 1. DR SUPFAM; SSF53335; SSF53335; 1. DR PROSITE; PS51678; SAM_MT_PRMT; 1. PE 1: Evidence at protein level; KW Alternative splicing; Cell membrane; Complete proteome; Lipoprotein; KW Membrane; Methylation; Methyltransferase; Myristate; KW Reference proteome; Repeat; S-adenosyl-L-methionine; Transferase. FT INIT_MET 1 1 Removed. FT CHAIN 2 394 Protein arginine N-methyltransferase 8. FT /FTId=PRO_0000212329. FT DOMAIN 73 394 SAM-dependent MTase PRMT-type. FT {ECO:0000255|PROSITE-ProRule:PRU01015}. FT MOTIF 29 42 SH3-binding 1. FT MOTIF 53 58 SH3-binding 2. FT ACT_SITE 185 185 {ECO:0000250}. FT ACT_SITE 194 194 {ECO:0000250}. FT BINDING 86 86 S-adenosyl-L-methionine. {ECO:0000250}. FT BINDING 95 95 S-adenosyl-L-methionine. {ECO:0000250}. FT BINDING 119 119 S-adenosyl-L-methionine; via carbonyl FT oxygen. {ECO:0000250}. FT BINDING 141 141 S-adenosyl-L-methionine. {ECO:0000250}. FT BINDING 170 170 S-adenosyl-L-methionine. {ECO:0000250}. FT MOD_RES 58 58 Omega-N-methylarginine; by autocatalysis. FT {ECO:0000269|PubMed:17925405}. FT MOD_RES 73 73 Asymmetric dimethylarginine; by FT autocatalysis. FT {ECO:0000269|PubMed:17925405}. FT LIPID 2 2 N-myristoyl glycine. FT {ECO:0000269|PubMed:16051612}. FT VAR_SEQ 1 25 MGMKHSSRCLLLRRKMAENAAESTE -> MESLASDGFKLK FT EVSS (in isoform 2). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_037466. FT MUTAGEN 2 2 G->A: Loss of cell membrane localization. FT {ECO:0000269|PubMed:16051612}. FT CONFLICT 150 150 E -> Q (in Ref. 3; AAH22458). FT {ECO:0000305}. SQ SEQUENCE 394 AA; 45291 MW; 44B55438D16394CD CRC64; MGMKHSSRCL LLRRKMAENA AESTEVNSPP SQPPQPVVPA KPVQCVHHVS TQPSCPGRGK MSKLLNPEEM TSRDYYFDSY AHFGIHEEML KDEVRTLTYR NSMYHNKHVF KDKVVLDVGS GTGILSMFAA KAGAKKVFGI ECSSISDYSE KIIKANHLDN IITIFKGKVE EVELPVEKVD IIISEWMGYC LFYESMLNTV IFARDKWLKP GGLMFPDRAA LYVVAIEDRQ YKDFKIHWWE NVYGFDMTCI RDVAMKEPLV DIVDPKQVVT NACLIKEVDI YTVKTEELSF TSAFCLQIQR NDYVHALVTY FNIEFTKCHK KMGFSTAPDA PYTHWKQTVF YLEDYLTVRR GEEIYGTISM KPNAKNVRDL DFTVDLDFKG QLCETSVSND YKMR //