ANM6_HUMAN
ID ANM6_HUMAN Reviewed; 375 AA.
AC Q96LA8; A3KME1; B4DID8; Q5T5Y5; Q6DKI4; Q9NVR8;
DT 27-MAR-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 185.
DE RecName: Full=Protein arginine N-methyltransferase 6;
DE EC=2.1.1.319 {ECO:0000269|PubMed:17898714, ECO:0000269|PubMed:18077460, ECO:0000269|PubMed:18079182, ECO:0000269|PubMed:19405910, ECO:0000269|PubMed:30420520};
DE AltName: Full=Heterogeneous nuclear ribonucleoprotein methyltransferase-like protein 6;
DE AltName: Full=Histone-arginine N-methyltransferase PRMT6;
GN Name=PRMT6; Synonyms=HRMT1L6;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY,
RP SUBCELLULAR LOCATION, AND METHYLATION AT ARG-35.
RC TISSUE=Kidney;
RX PubMed=11724789; DOI=10.1074/jbc.m108786200;
RA Frankel A., Yadav N., Lee J., Branscombe T.L., Clarke S., Bedford M.T.;
RT "The novel human protein arginine N-methyltransferase PRMT6 is a nuclear
RT enzyme displaying unique substrate specificity.";
RL J. Biol. Chem. 277:3537-3543(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 25-375 (ISOFORM 1).
RC TISSUE=Hippocampus, and Teratocarcinoma;
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., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., 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., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA 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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT VAL-194.
RC TISSUE=Blood, Eye, and Placenta;
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 230-375 (ISOFORMS 1/2).
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [7]
RP INTERACTION WITH EPB41L3.
RX PubMed=15334060; DOI=10.1038/sj.onc.1208057;
RA Singh V., Miranda T.B., Jiang W., Frankel A., Roemer M.E., Robb V.A.,
RA Gutmann D.H., Herschman H.R., Clarke S., Newsham I.F.;
RT "DAL-1/4.1B tumor suppressor interacts with protein arginine N-
RT methyltransferase 3 (PRMT3) and inhibits its ability to methylate
RT substrates in vitro and in vivo.";
RL Oncogene 23:7761-7771(2004).
RN [8]
RP INTERACTION WITH HIV-1 TAT (MICROBIAL INFECTION).
RX PubMed=15596808; DOI=10.1128/jvi.79.1.124-131.2005;
RA Boulanger M.C., Liang C., Russell R.S., Lin R., Bedford M.T.,
RA Wainberg M.A., Richard S.;
RT "Methylation of Tat by PRMT6 regulates human immunodeficiency virus type 1
RT gene expression.";
RL J. Virol. 79:124-131(2005).
RN [9]
RP FUNCTION, AND INTERACTION WITH HMGA1.
RX PubMed=16157300; DOI=10.1016/j.bbrc.2005.08.179;
RA Miranda T.B., Webb K.J., Edberg D.D., Reeves R., Clarke S.;
RT "Protein arginine methyltransferase 6 specifically methylates the
RT nonhistone chromatin protein HMGA1a.";
RL Biochem. Biophys. Res. Commun. 336:831-835(2005).
RN [10]
RP FUNCTION, AND INTERACTION WITH HMGA1.
RX PubMed=16159886; DOI=10.1074/jbc.m502458200;
RA Herrmann F., Lee J., Bedford M.T., Fackelmayer F.O.;
RT "Dynamics of human protein arginine methyltransferase 1(PRMT1) in vivo.";
RL J. Biol. Chem. 280:38005-38010(2005).
RN [11]
RP FUNCTION, AND INTERACTION WITH POLB.
RX PubMed=16600869; DOI=10.1016/j.molcel.2006.02.013;
RA El-Andaloussi N., Valovka T., Toueille M., Steinacher R., Focke F.,
RA Gehrig P., Covic M., Hassa P.O., Schaer P., Huebscher U., Hottiger M.O.;
RT "Arginine methylation regulates DNA polymerase beta.";
RL Mol. Cell 22:51-62(2006).
RN [12]
RP INTERACTION WITH HIV-1 REV (MICROBIAL INFECTION).
RX PubMed=17176473; DOI=10.1186/1742-4690-3-93;
RA Invernizzi C.F., Xie B., Richard S., Wainberg M.A.;
RT "PRMT6 diminishes HIV-1 Rev binding to and export of viral RNA.";
RL Retrovirology 3:93-93(2006).
RN [13]
RP INTERACTION WITH HIV-1 NC (MICROBIAL INFECTION).
RX PubMed=17415034; DOI=10.1097/qad.0b013e32803277ae;
RA Invernizzi C.F., Xie B., Frankel F.A., Feldhammer M., Roy B.B., Richard S.,
RA Wainberg M.A.;
RT "Arginine methylation of the HIV-1 nucleocapsid protein results in its
RT diminished function.";
RL AIDS 21:795-805(2007).
RN [14]
RP FUNCTION, AND INTERACTION WITH HIV-1 TAT (MICROBIAL INFECTION).
RX PubMed=17267505; DOI=10.1128/jvi.01888-06;
RA Xie B., Invernizzi C.F., Richard S., Wainberg M.A.;
RT "Arginine methylation of the human immunodeficiency virus type 1 Tat
RT protein by PRMT6 negatively affects Tat Interactions with both cyclin T1
RT and the Tat transactivation region.";
RL J. Virol. 81:4226-4234(2007).
RN [15]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF 86-VAL--ASP-88.
RX PubMed=17898714; DOI=10.1038/nature06166;
RA Guccione E., Bassi C., Casadio F., Martinato F., Cesaroni M.,
RA Schuchlautz H., Luescher B., Amati B.;
RT "Methylation of histone H3R2 by PRMT6 and H3K4 by an MLL complex are
RT mutually exclusive.";
RL Nature 449:933-937(2007).
RN [16]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=18079182; DOI=10.1101/gad.447007;
RA Hyllus D., Stein C., Schnabel K., Schiltz E., Imhof A., Dou Y., Hsieh J.,
RA Bauer U.M.;
RT "PRMT6-mediated methylation of R2 in histone H3 antagonizes H3 K4
RT trimethylation.";
RL Genes Dev. 21:3369-3380(2007).
RN [17]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=18077460; DOI=10.1074/jbc.c700192200;
RA Iberg A.N., Espejo A., Cheng D., Kim D., Michaud-Levesque J., Richard S.,
RA Bedford M.T.;
RT "Arginine methylation of the histone H3 tail impedes effector binding.";
RL J. Biol. Chem. 283:3006-3010(2008).
RN [18]
RP BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=18263580; DOI=10.1074/jbc.m710176200;
RA Lakowski T.M., Frankel A.;
RT "A kinetic study of human protein arginine N-methyltransferase 6 reveals a
RT distributive mechanism.";
RL J. Biol. Chem. 283:10015-10025(2008).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-21, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [20]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=19405910; DOI=10.1042/bj20090268;
RA Lakowski T.M., Frankel A.;
RT "Kinetic analysis of human protein arginine N-methyltransferase 2:
RT formation of monomethyl- and asymmetric dimethyl-arginine residues on
RT histone H4.";
RL Biochem. J. 421:253-261(2009).
RN [21]
RP FUNCTION.
RX PubMed=19509293; DOI=10.1074/jbc.m109.005322;
RA Michaud-Levesque J., Richard S.;
RT "Thrombospondin-1 is a transcriptional repression target of PRMT6.";
RL J. Biol. Chem. 284:21338-21346(2009).
RN [22]
RP FUNCTION, INTERACTION WITH NCOA1, AND MUTAGENESIS OF 86-VAL--ASP-88.
RX PubMed=20047962; DOI=10.1093/nar/gkp1203;
RA Harrison M.J., Tang Y.H., Dowhan D.H.;
RT "Protein arginine methyltransferase 6 regulates multiple aspects of gene
RT expression.";
RL Nucleic Acids Res. 38:2201-2216(2010).
RN [23]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-21, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [25]
RP METHYLATION AT ARG-29; ARG-35 AND ARG-37, AND MUTAGENESIS OF ARG-35 AND
RP 86-VAL--ASP-88.
RX PubMed=23866860; DOI=10.1186/1742-4690-10-73;
RA Singhroy D.N., Mesplede T., Sabbah A., Quashie P.K., Falgueyret J.P.,
RA Wainberg M.A.;
RT "Automethylation of protein arginine methyltransferase 6 (PRMT6) regulates
RT its stability and its anti-HIV-1 activity.";
RL Retrovirology 10:73-73(2013).
RN [26]
RP INTERACTION WITH HUMAN CYTOMEGALOVIRUS PROTEIN UL69.
RX PubMed=26178996; DOI=10.1128/jvi.01399-15;
RA Thomas M., Sonntag E., Mueller R., Schmidt S., Zielke B., Fossen T.,
RA Stamminger T.;
RT "pUL69 of human cytomegalovirus recruits the cellular protein arginine
RT methyltransferase 6 via a domain that is crucial for mRNA export and
RT efficient viral replication.";
RL J. Virol. 89:9601-9615(2015).
RN [27]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF 86-VAL--ASP-88.
RX PubMed=30420520; DOI=10.15252/embr.201846377;
RA Yan W.W., Liang Y.L., Zhang Q.X., Wang D., Lei M.Z., Qu J., He X.H.,
RA Lei Q.Y., Wang Y.P.;
RT "Arginine methylation of SIRT7 couples glucose sensing with mitochondria
RT biogenesis.";
RL EMBO Rep. 19:0-0(2018).
RN [28]
RP X-RAY CRYSTALLOGRAPHY (1.97 ANGSTROMS) IN COMPLEX WITH
RP S-ADENOSYLHOMOCYSTEINE.
RG Structural genomics consortium (SGC);
RT "The crystal structure of human HMT1 HNRNP methyltransferase-like protein 6
RT in complex with SAH.";
RL Submitted (OCT-2012) to the PDB data bank.
CC -!- FUNCTION: Arginine methyltransferase that can catalyze the formation of
CC both omega-N monomethylarginine (MMA) and asymmetrical dimethylarginine
CC (aDMA), with a strong preference for the formation of aDMA
CC (PubMed:17898714, PubMed:18077460, PubMed:18079182, PubMed:19405910,
CC PubMed:30420520). Preferentially methylates arginyl residues present in
CC a glycine and arginine-rich domain and displays preference for
CC monomethylated substrates (PubMed:17898714, PubMed:18077460,
CC PubMed:18079182, PubMed:19405910). Specifically mediates the asymmetric
CC dimethylation of histone H3 'Arg-2' to form H3R2me2a (PubMed:17898714,
CC PubMed:18079182, PubMed:18077460). H3R2me2a represents a specific tag
CC for epigenetic transcriptional repression and is mutually exclusive
CC with methylation on histone H3 'Lys-4' (H3K4me2 and H3K4me3)
CC (PubMed:17898714, PubMed:18077460). Acts as a transcriptional repressor
CC of various genes such as HOXA2, THBS1 and TP53 (PubMed:19509293).
CC Repression of TP53 blocks cellular senescence (By similarity). Also
CC methylates histone H2A and H4 'Arg-3' (H2AR3me and H4R3me,
CC respectively). Acts as a regulator of DNA base excision during DNA
CC repair by mediating the methylation of DNA polymerase beta (POLB),
CC leading to the stimulation of its polymerase activity by enhancing DNA
CC binding and processivity (PubMed:16600869). Methylates HMGA1
CC (PubMed:16157300, PubMed:16159886). Regulates alternative splicing
CC events. Acts as a transcriptional coactivator of a number of steroid
CC hormone receptors including ESR1, ESR2, PGR and NR3C1. Promotes
CC fasting-induced transcriptional activation of the gluconeogenic program
CC through methylation of the CRTC2 transcription coactivator (By
CC similarity). May play a role in innate immunity against HIV-1 in case
CC of infection by methylating and impairing the function of various HIV-1
CC proteins such as Tat, Rev and Nucleocapsid protein p7 (NC)
CC (PubMed:17267505). Methylates GPS2, protecting GPS2 from ubiquitination
CC and degradation (By similarity). Methylates SIRT7, inhibiting SIRT7
CC histone deacetylase activity and promoting mitochondria biogenesis
CC (PubMed:30420520). {ECO:0000250|UniProtKB:Q6NZB1,
CC ECO:0000269|PubMed:11724789, ECO:0000269|PubMed:16157300,
CC ECO:0000269|PubMed:16159886, ECO:0000269|PubMed:16600869,
CC ECO:0000269|PubMed:17267505, ECO:0000269|PubMed:17898714,
CC ECO:0000269|PubMed:18077460, ECO:0000269|PubMed:18079182,
CC ECO:0000269|PubMed:19405910, ECO:0000269|PubMed:19509293,
CC ECO:0000269|PubMed:20047962, ECO:0000269|PubMed:30420520}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-arginyl-[protein] + 2 S-adenosyl-L-methionine = 2 H(+) +
CC N(omega),N(omega)-dimethyl-L-arginyl-[protein] + 2 S-adenosyl-L-
CC homocysteine; Xref=Rhea:RHEA:48096, Rhea:RHEA-COMP:10532, Rhea:RHEA-
CC COMP:11991, ChEBI:CHEBI:15378, ChEBI:CHEBI:29965, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:61897; EC=2.1.1.319;
CC Evidence={ECO:0000269|PubMed:17898714, ECO:0000269|PubMed:18077460,
CC ECO:0000269|PubMed:18079182, ECO:0000269|PubMed:19405910,
CC ECO:0000269|PubMed:30420520};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48097;
CC Evidence={ECO:0000269|PubMed:17898714, ECO:0000269|PubMed:18077460,
CC ECO:0000269|PubMed:18079182, ECO:0000269|PubMed:19405910,
CC ECO:0000269|PubMed:30420520};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=18.6 uM for AdoMet {ECO:0000269|PubMed:18263580};
CC KM=501 uM for WGGYSRGGYGGW peptide {ECO:0000269|PubMed:18263580};
CC KM=183.7 uM for WGGYSR(MMA)GGYGGW monomethylated peptide
CC {ECO:0000269|PubMed:18263580};
CC Vmax=3.3 nmol/min/mg enzyme with AdoMet as substrate
CC {ECO:0000269|PubMed:18263580};
CC Vmax=1.8 nmol/min/mg enzyme with WGGYSRGGYGGW peptide as substrate
CC {ECO:0000269|PubMed:18263580};
CC Vmax=3.2 nmol/min/mg enzyme with WGGYSR(MMA)GGYGGW monomethylated
CC peptide as substrate {ECO:0000269|PubMed:18263580};
CC -!- SUBUNIT: Interacts with EPB41L3 and NCOA1.
CC {ECO:0000269|PubMed:15334060, ECO:0000269|PubMed:16157300,
CC ECO:0000269|PubMed:16159886, ECO:0000269|PubMed:16600869,
CC ECO:0000269|PubMed:20047962, ECO:0000269|Ref.28}.
CC -!- SUBUNIT: (Microbial infection) Interacts with (and methylates) HIV-1
CC Tat, Rev and Nucleocapsid protein p7 (NC).
CC {ECO:0000269|PubMed:15596808, ECO:0000269|PubMed:17176473,
CC ECO:0000269|PubMed:17267505, ECO:0000269|PubMed:17415034}.
CC -!- SUBUNIT: (Microbial infection) Interacts with human cytomegalovirus
CC protein UL69. {ECO:0000269|PubMed:26178996}.
CC -!- INTERACTION:
CC Q96LA8; Q6P047: C8orf74; NbExp=2; IntAct=EBI-912440, EBI-8466055;
CC Q96LA8; Q9BXL8: CDCA4; NbExp=2; IntAct=EBI-912440, EBI-1773949;
CC Q96LA8; Q96EY1: DNAJA3; NbExp=2; IntAct=EBI-912440, EBI-356767;
CC Q96LA8; O14645: DNALI1; NbExp=2; IntAct=EBI-912440, EBI-395638;
CC Q96LA8; Q9BQS8: FYCO1; NbExp=2; IntAct=EBI-912440, EBI-2869338;
CC Q96LA8; Q8TE85: GRHL3; NbExp=2; IntAct=EBI-912440, EBI-8469396;
CC Q96LA8; Q8NEC7: GSTCD; NbExp=2; IntAct=EBI-912440, EBI-8469616;
CC Q96LA8; Q9BX10: GTPBP2; NbExp=2; IntAct=EBI-912440, EBI-6115579;
CC Q96LA8; Q9UBX0: HESX1; NbExp=2; IntAct=EBI-912440, EBI-8470369;
CC Q96LA8; P17096-1: HMGA1; NbExp=4; IntAct=EBI-912440, EBI-746854;
CC Q96LA8; P52926: HMGA2; NbExp=2; IntAct=EBI-912440, EBI-912511;
CC Q96LA8; Q9HAQ2: KIF9; NbExp=2; IntAct=EBI-912440, EBI-8472129;
CC Q96LA8; Q9Y2M5: KLHL20; NbExp=2; IntAct=EBI-912440, EBI-714379;
CC Q96LA8; Q96JB6: LOXL4; NbExp=2; IntAct=EBI-912440, EBI-749562;
CC Q96LA8; Q9H204: MED28; NbExp=2; IntAct=EBI-912440, EBI-514199;
CC Q96LA8; Q14995: NR1D2; NbExp=2; IntAct=EBI-912440, EBI-6144053;
CC Q96LA8; P00973: OAS1; NbExp=2; IntAct=EBI-912440, EBI-3932815;
CC Q96LA8; Q86SE9: PCGF5; NbExp=2; IntAct=EBI-912440, EBI-2827999;
CC Q96LA8; O00231: PSMD11; NbExp=2; IntAct=EBI-912440, EBI-357816;
CC Q96LA8; P50749: RASSF2; NbExp=2; IntAct=EBI-912440, EBI-960081;
CC Q96LA8; Q9UGK8: SERGEF; NbExp=2; IntAct=EBI-912440, EBI-465368;
CC Q96LA8; O15198: SMAD9; NbExp=2; IntAct=EBI-912440, EBI-748763;
CC Q96LA8; Q96H20: SNF8; NbExp=2; IntAct=EBI-912440, EBI-747719;
CC Q96LA8; Q96BD6: SPSB1; NbExp=2; IntAct=EBI-912440, EBI-2659201;
CC Q96LA8; Q9Y365: STARD10; NbExp=2; IntAct=EBI-912440, EBI-4289836;
CC Q96LA8; Q8N1K5: THEMIS; NbExp=2; IntAct=EBI-912440, EBI-2873538;
CC Q96LA8; Q9Y3A6: TMED5; NbExp=2; IntAct=EBI-912440, EBI-7560959;
CC Q96LA8; A8K932; NbExp=3; IntAct=EBI-912440, EBI-10174671;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11724789}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q96LA8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96LA8-2; Sequence=VSP_037465;
CC -!- TISSUE SPECIFICITY: Highly expressed in kidney and testis.
CC {ECO:0000269|PubMed:11724789}.
CC -!- PTM: Automethylation enhances its stability and antiretroviral
CC activity.
CC -!- SIMILARITY: Belongs to the class I-like SAM-binding methyltransferase
CC superfamily. Protein arginine N-methyltransferase family. PRMT6
CC subfamily. {ECO:0000255|PROSITE-ProRule:PRU01015}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH02729.3; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAH63446.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAA91681.1; Type=Erroneous initiation; Note=Extended N-terminus.; 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; AY043278; AAK85733.1; -; mRNA.
DR EMBL; AK001421; BAA91681.1; ALT_INIT; mRNA.
DR EMBL; AK295541; BAG58450.1; -; mRNA.
DR EMBL; AL355539; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471156; EAW51248.1; -; Genomic_DNA.
DR EMBL; BC002729; AAH02729.3; ALT_INIT; mRNA.
DR EMBL; BC063446; AAH63446.2; ALT_INIT; mRNA.
DR EMBL; BC073866; AAH73866.1; -; mRNA.
DR EMBL; BX475300; -; NOT_ANNOTATED_CDS; mRNA.
DR CCDS; CCDS41360.2; -. [Q96LA8-1]
DR RefSeq; NP_060607.2; NM_018137.2. [Q96LA8-1]
DR PDB; 4HC4; X-ray; 1.97 A; A=1-375.
DR PDB; 4QPP; X-ray; 2.52 A; A/B/C=1-375.
DR PDB; 4QQK; X-ray; 1.88 A; A=1-375.
DR PDB; 4Y2H; X-ray; 2.37 A; A/B=27-375.
DR PDB; 4Y30; X-ray; 2.10 A; A/B=25-375.
DR PDB; 5E8R; X-ray; 2.55 A; A/B=1-375.
DR PDB; 5EGS; X-ray; 2.15 A; A/B/C/D=1-375.
DR PDB; 5HZM; X-ray; 2.02 A; A=1-375.
DR PDB; 5WCF; X-ray; 1.98 A; A=1-375.
DR PDB; 6P7I; X-ray; 2.00 A; A/B/C/D=1-375.
DR PDB; 6W6D; X-ray; 1.91 A; A=1-375.
DR PDB; 6WAD; X-ray; 2.45 A; A=1-375.
DR PDB; 7NR4; X-ray; 2.03 A; A/B/C/D=1-375.
DR PDBsum; 4HC4; -.
DR PDBsum; 4QPP; -.
DR PDBsum; 4QQK; -.
DR PDBsum; 4Y2H; -.
DR PDBsum; 4Y30; -.
DR PDBsum; 5E8R; -.
DR PDBsum; 5EGS; -.
DR PDBsum; 5HZM; -.
DR PDBsum; 5WCF; -.
DR PDBsum; 6P7I; -.
DR PDBsum; 6W6D; -.
DR PDBsum; 6WAD; -.
DR PDBsum; 7NR4; -.
DR AlphaFoldDB; Q96LA8; -.
DR SMR; Q96LA8; -.
DR BioGRID; 120469; 164.
DR IntAct; Q96LA8; 105.
DR MINT; Q96LA8; -.
DR STRING; 9606.ENSP00000359095; -.
DR BindingDB; Q96LA8; -.
DR ChEMBL; CHEMBL1275221; -.
DR GuidetoPHARMACOLOGY; 1257; -.
DR iPTMnet; Q96LA8; -.
DR PhosphoSitePlus; Q96LA8; -.
DR BioMuta; PRMT6; -.
DR DMDM; 20137409; -.
DR EPD; Q96LA8; -.
DR jPOST; Q96LA8; -.
DR MassIVE; Q96LA8; -.
DR MaxQB; Q96LA8; -.
DR PaxDb; Q96LA8; -.
DR PeptideAtlas; Q96LA8; -.
DR PRIDE; Q96LA8; -.
DR ProteomicsDB; 77181; -. [Q96LA8-1]
DR ProteomicsDB; 77182; -. [Q96LA8-2]
DR Antibodypedia; 21010; 434 antibodies from 42 providers.
DR DNASU; 55170; -.
DR Ensembl; ENST00000370078.2; ENSP00000359095.1; ENSG00000198890.9. [Q96LA8-1]
DR GeneID; 55170; -.
DR KEGG; hsa:55170; -.
DR MANE-Select; ENST00000370078.2; ENSP00000359095.1; NM_018137.3; NP_060607.2.
DR UCSC; uc010ous.4; human. [Q96LA8-1]
DR CTD; 55170; -.
DR DisGeNET; 55170; -.
DR GeneCards; PRMT6; -.
DR HGNC; HGNC:18241; PRMT6.
DR HPA; ENSG00000198890; Low tissue specificity.
DR MIM; 608274; gene.
DR neXtProt; NX_Q96LA8; -.
DR OpenTargets; ENSG00000198890; -.
DR PharmGKB; PA134992775; -.
DR VEuPathDB; HostDB:ENSG00000198890; -.
DR eggNOG; KOG1499; Eukaryota.
DR GeneTree; ENSGT00940000160961; -.
DR HOGENOM; CLU_017375_1_2_1; -.
DR InParanoid; Q96LA8; -.
DR OMA; SARHICI; -.
DR OrthoDB; 840669at2759; -.
DR PhylomeDB; Q96LA8; -.
DR TreeFam; TF328817; -.
DR BioCyc; MetaCyc:HS11391-MON; -.
DR BRENDA; 2.1.1.319; 2681.
DR PathwayCommons; Q96LA8; -.
DR Reactome; R-HSA-3214858; RMTs methylate histone arginines.
DR Reactome; R-HSA-8936459; RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function.
DR SABIO-RK; Q96LA8; -.
DR SignaLink; Q96LA8; -.
DR BioGRID-ORCS; 55170; 16 hits in 1084 CRISPR screens.
DR ChiTaRS; PRMT6; human.
DR GeneWiki; PRMT6; -.
DR GenomeRNAi; 55170; -.
DR Pharos; Q96LA8; Tchem.
DR PRO; PR:Q96LA8; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q96LA8; protein.
DR Bgee; ENSG00000198890; Expressed in islet of Langerhans and 171 other tissues.
DR ExpressionAtlas; Q96LA8; baseline and differential.
DR Genevisible; Q96LA8; HS.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; IEA:Ensembl.
DR GO; GO:0042393; F:histone binding; IDA:UniProtKB.
DR GO; GO:0042054; F:histone methyltransferase activity; IDA:UniProtKB.
DR GO; GO:0070612; F:histone methyltransferase activity (H2A-R3 specific); IDA:UniProtKB.
DR GO; GO:0070611; F:histone methyltransferase activity (H3-R2 specific); IDA:UniProtKB.
DR GO; GO:0044020; F:histone methyltransferase activity (H4-R3 specific); IDA:UniProtKB.
DR GO; GO:0008469; F:histone-arginine N-methyltransferase activity; IDA:CACAO.
DR GO; GO:0016274; F:protein-arginine N-methyltransferase activity; IDA:UniProtKB.
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:0006284; P:base-excision repair; TAS:UniProtKB.
DR GO; GO:0090398; P:cellular senescence; IEA:Ensembl.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0034970; P:histone H3-R2 methylation; IDA:UniProtKB.
DR GO; GO:0016571; P:histone methylation; IDA:UniProtKB.
DR GO; GO:0031064; P:negative regulation of histone deacetylation; IDA:UniProtKB.
DR GO; GO:0051572; P:negative regulation of histone H3-K4 methylation; IEA:Ensembl.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0019919; P:peptidyl-arginine methylation, to asymmetrical-dimethyl arginine; IDA:UniProtKB.
DR GO; GO:0045652; P:regulation of megakaryocyte differentiation; TAS:Reactome.
DR GO; GO:0010821; P:regulation of mitochondrion organization; IDA:UniProtKB.
DR GO; GO:1901796; P:regulation of signal transduction by p53 class mediator; IEA:Ensembl.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR025799; Arg_MeTrfase.
DR InterPro; IPR041698; Methyltransf_25.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR PANTHER; PTHR11006; PTHR11006; 1.
DR Pfam; PF13649; Methyltransf_25; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR PROSITE; PS51678; SAM_MT_PRMT; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Chromatin regulator; DNA damage;
KW DNA repair; Host-virus interaction; Methylation; Methyltransferase;
KW Nucleus; Phosphoprotein; Reference proteome; Repressor;
KW S-adenosyl-L-methionine; Transcription; Transcription regulation;
KW Transferase.
FT CHAIN 1..375
FT /note="Protein arginine N-methyltransferase 6"
FT /id="PRO_0000212332"
FT DOMAIN 44..374
FT /note="SAM-dependent MTase PRMT-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01015"
FT REGION 1..38
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 155
FT /evidence="ECO:0000250"
FT ACT_SITE 164
FT /evidence="ECO:0000250"
FT BINDING 57
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
FT BINDING 66
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT BINDING 90
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT BINDING 112
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT BINDING 141
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT MOD_RES 21
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 29
FT /note="Asymmetric dimethylarginine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:23866860"
FT MOD_RES 35
FT /note="Asymmetric dimethylarginine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:23866860"
FT MOD_RES 37
FT /note="Asymmetric dimethylarginine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:23866860"
FT VAR_SEQ 26..109
FT /note="GAEREAALERPRRTKRERDQLYYECYSDVSVHEEMIADRVRTDAYRLGILRN
FT WAALRGKTVLDVGAGTGILSIFCAQAGARRVY -> D (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_037465"
FT VARIANT 194
FT /note="A -> V (in dbSNP:rs2232016)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_057150"
FT MUTAGEN 35
FT /note="R->A: Inhibits automethylation but does not affect
FT methylation of other proteins. Reduces protein stability."
FT /evidence="ECO:0000269|PubMed:23866860"
FT MUTAGEN 86..88
FT /note="VLD->KLA: In PRMT6dn; abolishes histone
FT methyltransferase H3R2me2a and transcriptional coactivator
FT activities and reduces protein stability. This mutation
FT abolishes automethylation."
FT /evidence="ECO:0000269|PubMed:17898714,
FT ECO:0000269|PubMed:20047962, ECO:0000269|PubMed:23866860,
FT ECO:0000269|PubMed:30420520"
FT HELIX 26..38
FT /evidence="ECO:0007829|PDB:4Y30"
FT HELIX 40..50
FT /evidence="ECO:0007829|PDB:6P7I"
FT HELIX 51..62
FT /evidence="ECO:0007829|PDB:4QQK"
FT HELIX 64..75
FT /evidence="ECO:0007829|PDB:4QQK"
FT HELIX 78..81
FT /evidence="ECO:0007829|PDB:4QQK"
FT STRAND 85..90
FT /evidence="ECO:0007829|PDB:4QQK"
FT HELIX 95..102
FT /evidence="ECO:0007829|PDB:4QQK"
FT STRAND 106..112
FT /evidence="ECO:0007829|PDB:4QQK"
FT HELIX 117..126
FT /evidence="ECO:0007829|PDB:4QQK"
FT TURN 130..132
FT /evidence="ECO:0007829|PDB:4QQK"
FT STRAND 133..138
FT /evidence="ECO:0007829|PDB:4QQK"
FT TURN 140..142
FT /evidence="ECO:0007829|PDB:4QQK"
FT STRAND 149..153
FT /evidence="ECO:0007829|PDB:4QQK"
FT STRAND 158..163
FT /evidence="ECO:0007829|PDB:4QQK"
FT HELIX 167..177
FT /evidence="ECO:0007829|PDB:4QQK"
FT STRAND 178..186
FT /evidence="ECO:0007829|PDB:4QQK"
FT STRAND 188..196
FT /evidence="ECO:0007829|PDB:4QQK"
FT HELIX 199..206
FT /evidence="ECO:0007829|PDB:4QQK"
FT HELIX 207..210
FT /evidence="ECO:0007829|PDB:4QQK"
FT HELIX 211..215
FT /evidence="ECO:0007829|PDB:4QQK"
FT HELIX 220..222
FT /evidence="ECO:0007829|PDB:4QQK"
FT HELIX 223..231
FT /evidence="ECO:0007829|PDB:4QQK"
FT STRAND 235..239
FT /evidence="ECO:0007829|PDB:4QQK"
FT HELIX 243..245
FT /evidence="ECO:0007829|PDB:4QQK"
FT STRAND 251..257
FT /evidence="ECO:0007829|PDB:4QQK"
FT HELIX 263..269
FT /evidence="ECO:0007829|PDB:4QQK"
FT STRAND 271..279
FT /evidence="ECO:0007829|PDB:4QQK"
FT STRAND 283..296
FT /evidence="ECO:0007829|PDB:4QQK"
FT TURN 299..302
FT /evidence="ECO:0007829|PDB:4Y30"
FT STRAND 305..308
FT /evidence="ECO:0007829|PDB:4QQK"
FT STRAND 320..331
FT /evidence="ECO:0007829|PDB:4QQK"
FT STRAND 336..345
FT /evidence="ECO:0007829|PDB:4QQK"
FT STRAND 348..350
FT /evidence="ECO:0007829|PDB:6W6D"
FT STRAND 352..361
FT /evidence="ECO:0007829|PDB:4QQK"
FT STRAND 367..373
FT /evidence="ECO:0007829|PDB:4QQK"
SQ SEQUENCE 375 AA; 41938 MW; 40AAEC7342C08A38 CRC64;
MSQPKKRKLE SGGGGEGGEG TEEEDGAERE AALERPRRTK RERDQLYYEC YSDVSVHEEM
IADRVRTDAY RLGILRNWAA LRGKTVLDVG AGTGILSIFC AQAGARRVYA VEASAIWQQA
REVVRFNGLE DRVHVLPGPV ETVELPEQVD AIVSEWMGYG LLHESMLSSV LHARTKWLKE
GGLLLPASAE LFIAPISDQM LEWRLGFWSQ VKQHYGVDMS CLEGFATRCL MGHSEIVVQG
LSGEDVLARP QRFAQLELSR AGLEQELEAG VGGRFRCSCY GSAPMHGFAI WFQVTFPGGE
SEKPLVLSTS PFHPATHWKQ ALLYLNEPVQ VEQDTDVSGE ITLLPSRDNP RRLRVLLRYK
VGDQEEKTKD FAMED
