PEMT_HUMAN
ID PEMT_HUMAN Reviewed; 199 AA.
AC Q9UBM1; A8MZ66; B4DY41; D3DXC3; Q6IAQ5; Q86VL3; Q9BW86; Q9UHY6; Q9Y6V9;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 12-JUN-2007, sequence version 4.
DT 03-AUG-2022, entry version 173.
DE RecName: Full=Phosphatidylethanolamine N-methyltransferase {ECO:0000303|PubMed:12431977, ECO:0000303|PubMed:20860552};
DE Short=PEAMT {ECO:0000255|HAMAP-Rule:MF_03216};
DE Short=PEMT {ECO:0000303|PubMed:12431977, ECO:0000303|PubMed:20860552};
DE EC=2.1.1.17 {ECO:0000305|PubMed:12431977, ECO:0000305|PubMed:20860552};
DE EC=2.1.1.71 {ECO:0000269|PubMed:12431977, ECO:0000269|PubMed:20860552};
DE AltName: Full=PEMT2;
DE AltName: Full=Phospholipid methyltransferase {ECO:0000255|HAMAP-Rule:MF_03216};
DE Short=PLMT {ECO:0000255|HAMAP-Rule:MF_03216};
GN Name=PEMT {ECO:0000255|HAMAP-Rule:MF_03216}; Synonyms=PEMPT, PNMT;
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), AND VARIANT MET-175.
RC TISSUE=Liver;
RX PubMed=9989271; DOI=10.1016/s0005-2760(98)00147-7;
RA Walkey C.J., Shields D.J., Vance D.E.;
RT "Identification of three novel cDNAs for human phosphatidylethanolamine N-
RT methyltransferase and localization of the human gene on chromosome
RT 17p11.2.";
RL Biochim. Biophys. Acta 1436:405-412(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT MET-175.
RX PubMed=11420179; DOI=10.1016/s1388-1981(01)00122-6;
RA Shields D.J., Agellon L.B., Vance D.E.;
RT "Structure, expression profile and alternative processing of the human
RT phosphatidylethanolamine N-methyltransferase (PEMT) gene.";
RL Biochim. Biophys. Acta 1532:105-114(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS ILE-58 AND MET-175.
RC TISSUE=Liver;
RA Maeda E., Watanabe M., Wang J., Kasuga M.;
RT "Homo sapiens phosphatidylethanolamine N-methyltransferase mRNA.";
RL Submitted (JUL-1999) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Hypothalamus;
RX PubMed=10931946; DOI=10.1073/pnas.160270997;
RA Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X.,
RA Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H., Gu B.-W.,
RA Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M., Zhou J., Xu S.-H., Gu J.,
RA Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M., Huang G.-Y., Chen Z.,
RA Chen M.-D., Chen J.-L.;
RT "Gene expression profiling in the human hypothalamus-pituitary-adrenal axis
RT and full-length cDNA cloning.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND VARIANT ILE-58.
RC TISSUE=Testis;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS ILE-58 AND
RP MET-175.
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS TRP-3; ILE-58; MET-175 AND
RP ARG-194 (ISOFORM 1), AND VARIANT ALA-11 (ISOFORM 2).
RG NIEHS SNPs program;
RL Submitted (MAR-2008) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT MET-175.
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 [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANTS ILE-58 AND
RP MET-175.
RC TISSUE=Brain, and Skin;
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 [11]
RP SUBCELLULAR LOCATION, CATALYTIC ACTIVITY, FUNCTION, PATHWAY, AND TISSUE
RP SPECIFICITY.
RX PubMed=12431977; DOI=10.1074/jbc.m210904200;
RA Shields D.J., Lehner R., Agellon L.B., Vance D.E.;
RT "Membrane topography of human phosphatidylethanolamine N-
RT methyltransferase.";
RL J. Biol. Chem. 278:2956-2962(2003).
RN [12]
RP MUTAGENESIS OF GLY-98; GLY-100; GLU-180 AND GLU-181.
RX PubMed=12842883; DOI=10.1074/jbc.m306308200;
RA Shields D.J., Altarejos J.Y., Wang X., Agellon L.B., Vance D.E.;
RT "Molecular dissection of the S-adenosylmethionine-binding site of
RT phosphatidylethanolamine N-methyltransferase.";
RL J. Biol. Chem. 278:35826-35836(2003).
RN [13]
RP FUNCTION, CATALYTIC ACTIVITY, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=15927961; DOI=10.1074/jbc.m504658200;
RA Shields D.J., Lingrell S., Agellon L.B., Brosnan J.T., Vance D.E.;
RT "Localization-independent regulation of homocysteine secretion by
RT phosphatidylethanolamine N-methyltransferase.";
RL J. Biol. Chem. 280:27339-27344(2005).
RN [14]
RP ALTERNATIVE SPLICING.
RX PubMed=17456783; DOI=10.1096/fj.07-8227com;
RA Resseguie M., Song J., Niculescu M.D., da Costa K.A., Randall T.A.,
RA Zeisel S.H.;
RT "Phosphatidylethanolamine N-methyltransferase (PEMT) gene expression is
RT induced by estrogen in human and mouse primary hepatocytes.";
RL FASEB J. 21:2622-2632(2007).
RN [15]
RP ALTERNATIVE SPLICING, TOPOLOGY, GLYCOSYLATION (ISOFORM 2), SUBCELLULAR
RP LOCATION (ISOFORMS 1 AND 2), FUNCTION (ISOFORMS 1 AND 2), AND CATALYTIC
RP ACTIVITY (ISOFORMS 1 AND 2).
RX PubMed=20860552; DOI=10.1042/bj20100490;
RA Morita S.Y., Takeuchi A., Kitagawa S.;
RT "Functional analysis of two isoforms of phosphatidylethanolamine N-
RT methyltransferase.";
RL Biochem. J. 432:387-398(2010).
CC -!- FUNCTION: Catalyzes the three sequential steps of the methylation
CC pathway for the biosynthesis of phosphatidylcholine, a critical and
CC essential component for membrane structure (PubMed:12431977,
CC PubMed:15927961). Uses S-adenosylmethionine (S-adenosyl-L-methionine,
CC SAM or AdoMet) as the methyl group donor for the methylation of
CC phosphatidylethanolamine (1,2-diacyl-sn-glycero-3-phosphoethanolamine,
CC PE) to phosphatidylmonomethylethanolamine (1,2-diacyl-sn-glycero-3-
CC phospho-N-methylethanolamine, PMME), PMME to
CC phosphatidyldimethylethanolamine (1,2-diacyl-sn-glycero-3-phospho-N,N-
CC dimethylethanolamine, PDME), and PDME to phosphatidylcholine (1,2-
CC diacyl-sn-glycero-3-phosphocholine, PC), producing S-adenosyl-L-
CC homocysteine in each step (PubMed:12431977, PubMed:15927961).
CC Responsible for approximately 30% of hepatic PC with the CDP-choline
CC pathway accounting for the other 70% (Probable).
CC {ECO:0000269|PubMed:12431977, ECO:0000269|PubMed:15927961,
CC ECO:0000305|PubMed:12431977}.
CC -!- FUNCTION: [Isoform 1]: Catalyzes the three sequential steps of the
CC methylation of 1,2-diacyl-sn-glycero-3-phospho-N-methylethanolamine
CC (PMME) to 1,2-diacyl-sn-glycero-3-phospho-N,N-dimethylethanolamine
CC (PDME) more efficiently than isoform 2 (PubMed:20860552). Induces
CC increase in PC species with longer polyunsaturated chains than isoform
CC 2 (PubMed:20860552). {ECO:0000269|PubMed:20860552}.
CC -!- FUNCTION: [Isoform 2]: Produces a higher increase in the level of PC
CC species containing long chains with three double bonds than isoform 1.
CC {ECO:0000269|PubMed:20860552}.
CC -!- CATALYTIC ACTIVITY: [Isoform 1]:
CC Reaction=1,2-diacyl-sn-glycero-3-phospho-N-methylethanolamine + S-
CC adenosyl-L-methionine = 1,2-diacyl-sn-glycero-3-phospho-N,N-
CC dimethylethanolamine + H(+) + S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:32735, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:64572, ChEBI:CHEBI:64573; EC=2.1.1.71;
CC Evidence={ECO:0000269|PubMed:12431977, ECO:0000269|PubMed:15927961,
CC ECO:0000269|PubMed:20860552};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:32736;
CC Evidence={ECO:0000269|PubMed:15927961, ECO:0000305|PubMed:12431977,
CC ECO:0000305|PubMed:20860552};
CC -!- CATALYTIC ACTIVITY: [Isoform 2]:
CC Reaction=1,2-diacyl-sn-glycero-3-phospho-N-methylethanolamine + S-
CC adenosyl-L-methionine = 1,2-diacyl-sn-glycero-3-phospho-N,N-
CC dimethylethanolamine + H(+) + S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:32735, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:64572, ChEBI:CHEBI:64573; EC=2.1.1.71;
CC Evidence={ECO:0000269|PubMed:20860552};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:32736;
CC Evidence={ECO:0000305|PubMed:20860552};
CC -!- CATALYTIC ACTIVITY: [Isoform 1]:
CC Reaction=1,2-diacyl-sn-glycero-3-phospho-N,N-dimethylethanolamine + S-
CC adenosyl-L-methionine = a 1,2-diacyl-sn-glycero-3-phosphocholine +
CC H(+) + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:32739,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57643, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:64572; EC=2.1.1.71;
CC Evidence={ECO:0000305|PubMed:12431977, ECO:0000305|PubMed:15927961,
CC ECO:0000305|PubMed:20860552};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:32740;
CC Evidence={ECO:0000305|PubMed:12431977, ECO:0000305|PubMed:15927961,
CC ECO:0000305|PubMed:20860552};
CC -!- CATALYTIC ACTIVITY: [Isoform 2]:
CC Reaction=1,2-diacyl-sn-glycero-3-phospho-N,N-dimethylethanolamine + S-
CC adenosyl-L-methionine = a 1,2-diacyl-sn-glycero-3-phosphocholine +
CC H(+) + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:32739,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57643, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:64572; EC=2.1.1.71;
CC Evidence={ECO:0000305|PubMed:20860552};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:32740;
CC Evidence={ECO:0000305|PubMed:20860552};
CC -!- CATALYTIC ACTIVITY: [Isoform 1]:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phosphoethanolamine + S-adenosyl-L-
CC methionine = 1,2-diacyl-sn-glycero-3-phospho-N-methylethanolamine +
CC H(+) + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:11164,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:64573, ChEBI:CHEBI:64612; EC=2.1.1.17;
CC Evidence={ECO:0000305|PubMed:12431977, ECO:0000305|PubMed:15927961,
CC ECO:0000305|PubMed:20860552};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11165;
CC Evidence={ECO:0000305|PubMed:12431977, ECO:0000305|PubMed:15927961,
CC ECO:0000305|PubMed:20860552};
CC -!- CATALYTIC ACTIVITY: [Isoform 2]:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phosphoethanolamine + S-adenosyl-L-
CC methionine = 1,2-diacyl-sn-glycero-3-phospho-N-methylethanolamine +
CC H(+) + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:11164,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:64573, ChEBI:CHEBI:64612; EC=2.1.1.17;
CC Evidence={ECO:0000305|PubMed:20860552};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11165;
CC Evidence={ECO:0000305|PubMed:20860552};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphoethanolamine + S-
CC adenosyl-L-methionine = 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-
CC phospho-N-methylethanolamine + H(+) + S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:70619, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:74986, ChEBI:CHEBI:85679;
CC Evidence={ECO:0000250|UniProtKB:Q08388};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70620;
CC Evidence={ECO:0000250|UniProtKB:Q08388};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phospho-N-
CC methylethanolamine + S-adenosyl-L-methionine = 1,2-di-(9Z-
CC octadecenoyl)-sn-glycero-3-phospho-N,N-dimethylethanolamine + H(+) +
CC S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:46112, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:85679,
CC ChEBI:CHEBI:85680; Evidence={ECO:0000250|UniProtKB:Q08388};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46113;
CC Evidence={ECO:0000250|UniProtKB:Q08388};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phospho-N,N-
CC dimethylethanolamine + S-adenosyl-L-methionine = 1,2-di-(9Z-
CC octadecenoyl)-sn-glycero-3-phosphocholine + H(+) + S-adenosyl-L-
CC homocysteine; Xref=Rhea:RHEA:70623, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:74669,
CC ChEBI:CHEBI:85680; Evidence={ECO:0000250|UniProtKB:Q08388};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70624;
CC Evidence={ECO:0000250|UniProtKB:Q08388};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-di-(9Z,12Z-octadecadienoyl)-sn-glycero-3-
CC phosphoethanolamine + S-adenosyl-L-methionine = 1,2-di-(9Z,12Z-
CC octadecadienoyl)-sn-glycero-3-phospho-N-methylethanolamine + H(+) +
CC S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:70739, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:172403,
CC ChEBI:CHEBI:189848; Evidence={ECO:0000250|UniProtKB:Q08388};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70740;
CC Evidence={ECO:0000250|UniProtKB:Q08388};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-di-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phospho-N-
CC methylethanolamine + S-adenosyl-L-methionine = 1,2-di-(9Z,12Z-
CC octadecadienoyl)-sn-glycero-3-phospho-N,N-dimethylethanolamine + H(+)
CC + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:70743, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:189848,
CC ChEBI:CHEBI:189849; Evidence={ECO:0000250|UniProtKB:Q08388};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70744;
CC Evidence={ECO:0000250|UniProtKB:Q08388};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-di-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phospho-N,N-
CC dimethylethanolamine + S-adenosyl-L-methionine = 1,2-di-(9Z,12Z-
CC octadecadienoyl)-sn-glycero-3-phosphocholine + H(+) + S-adenosyl-L-
CC homocysteine; Xref=Rhea:RHEA:70747, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:42027, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:189849; Evidence={ECO:0000250|UniProtKB:Q08388};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70748;
CC Evidence={ECO:0000250|UniProtKB:Q08388};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-di-(9Z,12Z,15Z-octadecatrienoyl)-sn-glycero-3-
CC phosphoethanolamine + S-adenosyl-L-methionine = 1,2-di-(9Z,12Z,15Z-
CC octadecatrienoyl)-sn-glycero-3-phospho-N-methylethanolamine + H(+) +
CC S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:70751, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:189858,
CC ChEBI:CHEBI:189859; Evidence={ECO:0000250|UniProtKB:Q08388};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70752;
CC Evidence={ECO:0000250|UniProtKB:Q08388};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-di-(9Z,12Z,15Z-octadecatrienoyl)-sn-glycero-3-phospho-N-
CC methylethanolamine + S-adenosyl-L-methionine = 1,2-di-(9Z,12Z,15Z-
CC octadecatrienoyl)-sn-glycero-3-phospho-N,N-dimethylethanolamine +
CC H(+) + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:70755,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:189859, ChEBI:CHEBI:189860;
CC Evidence={ECO:0000250|UniProtKB:Q08388};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70756;
CC Evidence={ECO:0000250|UniProtKB:Q08388};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-di-(9Z,12Z,15Z-octadecatrienoyl)-sn-glycero-3-phospho-N,N-
CC dimethylethanolamine + S-adenosyl-L-methionine = 1,2-di-(9Z,12Z,15Z-
CC octadecatrienoyl)-sn-glycero-3-phosphocholine + H(+) + S-adenosyl-L-
CC homocysteine; Xref=Rhea:RHEA:70759, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:86161,
CC ChEBI:CHEBI:189860; Evidence={ECO:0000250|UniProtKB:Q08388};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70760;
CC Evidence={ECO:0000250|UniProtKB:Q08388};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-hexadecanoyl-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-
CC glycero-3-phosphoethanolamine + S-adenosyl-L-methionine = 1-
CC hexadecanoyl-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-glycero-3-
CC phospho-N-methylethanolamine + H(+) + S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:70763, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:78261, ChEBI:CHEBI:189861;
CC Evidence={ECO:0000250|UniProtKB:Q08388};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70764;
CC Evidence={ECO:0000250|UniProtKB:Q08388};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-hexadecanoyl-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-
CC glycero-3-phospho-N-methylethanolamine + S-adenosyl-L-methionine = 1-
CC hexadecanoyl-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-glycero-3-
CC phospho-N,N-dimethylethanolamine + H(+) + S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:70767, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:189861, ChEBI:CHEBI:189862;
CC Evidence={ECO:0000250|UniProtKB:Q08388};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70768;
CC Evidence={ECO:0000250|UniProtKB:Q08388};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-hexadecanoyl-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-
CC glycero-3-phospho-N,N-dimethylethanolamine + S-adenosyl-L-methionine
CC = 1-hexadecanoyl-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-
CC glycero-3-phosphocholine + H(+) + S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:70771, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:74963, ChEBI:CHEBI:189862;
CC Evidence={ECO:0000250|UniProtKB:Q08388};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70772;
CC Evidence={ECO:0000250|UniProtKB:Q08388};
CC -!- ACTIVITY REGULATION: The first methylation is rate-limiting.
CC -!- PATHWAY: Phospholipid metabolism; phosphatidylcholine biosynthesis.
CC {ECO:0000305|PubMed:12431977}.
CC -!- INTERACTION:
CC Q9UBM1-2; Q13520: AQP6; NbExp=3; IntAct=EBI-17513590, EBI-13059134;
CC Q9UBM1-2; P27105: STOM; NbExp=3; IntAct=EBI-17513590, EBI-1211440;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum
CC {ECO:0000269|PubMed:15927961}. Note=localized in the endoplasmic
CC reticulum (ER) of the liver and in a lipid metabolism-rich region of
CC the ER known as mitochondria-associated membranes (PubMed:15927961).
CC Adopts a topography within the ER membrane that positions both termini
CC in the cytosol (PubMed:12431977). {ECO:0000269|PubMed:12431977,
CC ECO:0000303|PubMed:15927961}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:20860552}; Multi-pass membrane protein
CC {ECO:0000255|HAMAP-Rule:MF_03216}. Mitochondrion membrane
CC {ECO:0000255|HAMAP-Rule:MF_03216}; Multi-pass membrane protein
CC {ECO:0000255|HAMAP-Rule:MF_03216}. Note=Found in endoplasmic reticulum
CC where most PEMT activity is generated and in mitochondria.
CC {ECO:0000269|PubMed:12431977}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:20860552}; Multi-pass membrane protein
CC {ECO:0000255|HAMAP-Rule:MF_03216}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=PEMT-S;
CC IsoId=Q9UBM1-1; Sequence=Displayed;
CC Name=2; Synonyms=PEMT-L;
CC IsoId=Q9UBM1-2; Sequence=VSP_037311;
CC Name=3;
CC IsoId=Q9UBM1-3; Sequence=VSP_037311, VSP_046034;
CC -!- TISSUE SPECIFICITY: Primarily expressed in liver (at protein level).
CC {ECO:0000269|PubMed:12431977}.
CC -!- PTM: Isoform 2 is N-glycosylated with high-mannose oligosaccharides.
CC {ECO:0000269|PubMed:20860552}.
CC -!- SIMILARITY: Belongs to the class VI-like SAM-binding methyltransferase
CC superfamily. PEMT/PEM2 methyltransferase family. {ECO:0000255|HAMAP-
CC Rule:MF_03216}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/pemt/";
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DR EMBL; AF176807; AAD53292.1; -; mRNA.
DR EMBL; AF176806; AAD53291.1; -; mRNA.
DR EMBL; AF294468; AAK19172.1; -; Genomic_DNA.
DR EMBL; AF294463; AAK19172.1; JOINED; Genomic_DNA.
DR EMBL; AF294464; AAK19172.1; JOINED; Genomic_DNA.
DR EMBL; AF294465; AAK19172.1; JOINED; Genomic_DNA.
DR EMBL; AF294466; AAK19172.1; JOINED; Genomic_DNA.
DR EMBL; AF294467; AAK19172.1; JOINED; Genomic_DNA.
DR EMBL; AB029821; BAA82407.1; -; mRNA.
DR EMBL; AF113126; AAF14867.1; -; mRNA.
DR EMBL; AK302251; BAG63603.1; -; mRNA.
DR EMBL; CR457099; CAG33380.1; -; mRNA.
DR EMBL; EU574003; ACB21050.1; -; Genomic_DNA.
DR EMBL; AC020558; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471196; EAW55701.1; -; Genomic_DNA.
DR EMBL; CH471196; EAW55702.1; -; Genomic_DNA.
DR EMBL; BC000557; AAH00557.1; -; mRNA.
DR EMBL; BC050593; AAH50593.1; -; mRNA.
DR CCDS; CCDS11186.1; -. [Q9UBM1-2]
DR CCDS; CCDS11187.1; -. [Q9UBM1-1]
DR CCDS; CCDS58520.1; -. [Q9UBM1-3]
DR RefSeq; NP_001254480.1; NM_001267551.1.
DR RefSeq; NP_001254481.1; NM_001267552.1. [Q9UBM1-3]
DR RefSeq; NP_009100.2; NM_007169.2. [Q9UBM1-1]
DR RefSeq; NP_680477.1; NM_148172.2. [Q9UBM1-2]
DR RefSeq; NP_680478.1; NM_148173.1. [Q9UBM1-1]
DR AlphaFoldDB; Q9UBM1; -.
DR BioGRID; 115672; 41.
DR IntAct; Q9UBM1; 2.
DR STRING; 9606.ENSP00000255389; -.
DR SwissLipids; SLP:000001199; -. [Q9UBM1-1]
DR iPTMnet; Q9UBM1; -.
DR BioMuta; PEMT; -.
DR DMDM; 148887406; -.
DR jPOST; Q9UBM1; -.
DR MassIVE; Q9UBM1; -.
DR MaxQB; Q9UBM1; -.
DR PaxDb; Q9UBM1; -.
DR PeptideAtlas; Q9UBM1; -.
DR PRIDE; Q9UBM1; -.
DR ProteomicsDB; 2457; -.
DR ProteomicsDB; 84006; -. [Q9UBM1-1]
DR ProteomicsDB; 84007; -. [Q9UBM1-2]
DR TopDownProteomics; Q9UBM1-1; -. [Q9UBM1-1]
DR Antibodypedia; 25461; 183 antibodies from 24 providers.
DR DNASU; 10400; -.
DR Ensembl; ENST00000255389.10; ENSP00000255389.5; ENSG00000133027.18. [Q9UBM1-2]
DR Ensembl; ENST00000395781.6; ENSP00000379127.2; ENSG00000133027.18. [Q9UBM1-3]
DR Ensembl; ENST00000395782.5; ENSP00000379128.1; ENSG00000133027.18. [Q9UBM1-1]
DR Ensembl; ENST00000395783.5; ENSP00000379129.1; ENSG00000133027.18. [Q9UBM1-1]
DR GeneID; 10400; -.
DR KEGG; hsa:10400; -.
DR MANE-Select; ENST00000255389.10; ENSP00000255389.5; NM_148172.3; NP_680477.1. [Q9UBM1-2]
DR UCSC; uc002grj.3; human. [Q9UBM1-1]
DR CTD; 10400; -.
DR DisGeNET; 10400; -.
DR GeneCards; PEMT; -.
DR HGNC; HGNC:8830; PEMT.
DR HPA; ENSG00000133027; Tissue enhanced (epididymis, liver).
DR MIM; 602391; gene.
DR neXtProt; NX_Q9UBM1; -.
DR OpenTargets; ENSG00000133027; -.
DR PharmGKB; PA33175; -.
DR VEuPathDB; HostDB:ENSG00000133027; -.
DR eggNOG; KOG4142; Eukaryota.
DR GeneTree; ENSGT00390000007041; -.
DR HOGENOM; CLU_086119_0_1_1; -.
DR InParanoid; Q9UBM1; -.
DR OMA; VITSTWA; -.
DR OrthoDB; 1395721at2759; -.
DR PhylomeDB; Q9UBM1; -.
DR TreeFam; TF300198; -.
DR BRENDA; 2.1.1.17; 2681.
DR PathwayCommons; Q9UBM1; -.
DR Reactome; R-HSA-1483191; Synthesis of PC.
DR SignaLink; Q9UBM1; -.
DR UniPathway; UPA00753; -.
DR BioGRID-ORCS; 10400; 9 hits in 1079 CRISPR screens.
DR ChiTaRS; PEMT; human.
DR GeneWiki; Phosphatidyl_ethanolamine_methyltransferase; -.
DR GenomeRNAi; 10400; -.
DR Pharos; Q9UBM1; Tbio.
DR PRO; PR:Q9UBM1; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q9UBM1; protein.
DR Bgee; ENSG00000133027; Expressed in corpus epididymis and 170 other tissues.
DR ExpressionAtlas; Q9UBM1; baseline and differential.
DR Genevisible; Q9UBM1; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HPA.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0031966; C:mitochondrial membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0080101; F:phosphatidyl-N-dimethylethanolamine N-methyltransferase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0000773; F:phosphatidyl-N-methylethanolamine N-methyltransferase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0004608; F:phosphatidylethanolamine N-methyltransferase activity; IBA:GO_Central.
DR GO; GO:0001835; P:blastocyst hatching; IEA:Ensembl.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0006656; P:phosphatidylcholine biosynthetic process; IBA:GO_Central.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:YuBioLab.
DR GO; GO:0006686; P:sphingomyelin biosynthetic process; IEA:Ensembl.
DR HAMAP; MF_03216; PLMT; 1.
DR InterPro; IPR024960; PEMT/MFAP.
DR InterPro; IPR007318; Phopholipid_MeTrfase.
DR PANTHER; PTHR15458; PTHR15458; 1.
DR Pfam; PF04191; PEMT; 1.
DR PIRSF; PIRSF005444; PEMT; 1.
DR PROSITE; PS51599; SAM_PEMT_PEM2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Endoplasmic reticulum; Lipid biosynthesis;
KW Lipid metabolism; Membrane; Methyltransferase; Mitochondrion;
KW Phospholipid biosynthesis; Phospholipid metabolism; Reference proteome;
KW S-adenosyl-L-methionine; Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1..199
FT /note="Phosphatidylethanolamine N-methyltransferase"
FT /id="PRO_0000193920"
FT TOPO_DOM 1..12
FT /note="Lumenal"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03216,
FT ECO:0000305|PubMed:20860552"
FT INTRAMEM 13..33
FT /note="Helical"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03216,
FT ECO:0000305|PubMed:20860552"
FT TOPO_DOM 34..45
FT /note="Lumenal"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03216,
FT ECO:0000269|PubMed:12431977, ECO:0000305|PubMed:20860552"
FT TRANSMEM 46..66
FT /note="Helical"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03216"
FT TOPO_DOM 67..93
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03216,
FT ECO:0000305|PubMed:20860552"
FT TRANSMEM 94..114
FT /note="Helical"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03216"
FT TOPO_DOM 115..157
FT /note="Lumenal"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03216,
FT ECO:0000269|PubMed:12431977, ECO:0000305|PubMed:20860552"
FT TRANSMEM 158..178
FT /note="Helical"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03216"
FT TOPO_DOM 179..199
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03216,
FT ECO:0000269|PubMed:12431977, ECO:0000305|PubMed:20860552"
FT BINDING 98..100
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03216,
FT ECO:0000305|PubMed:12842883"
FT BINDING 180..181
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03216,
FT ECO:0000305|PubMed:12842883"
FT VAR_SEQ 1
FT /note="M -> MKRSGNPGAEVTNSSVAGPDCCGGLGNIDFRQADFCVM (in
FT isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_037311"
FT VAR_SEQ 156..199
FT /note="MHASPTGLLLTVLVALTYIVALLYEEPFTAEIYRQKASGSHKRS -> IPAP
FT AGAVGSEARQPHGPAPDGAGGPHLHSGSPIRRALHR (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_046034"
FT VARIANT 3
FT /note="R -> W (in dbSNP:rs70959686)"
FT /id="VAR_055372"
FT VARIANT 58
FT /note="V -> I (in dbSNP:rs897453)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|Ref.3,
FT ECO:0000269|Ref.6"
FT /id="VAR_032771"
FT VARIANT 58
FT /note="V -> L (in dbSNP:rs897453)"
FT /id="VAR_060083"
FT VARIANT 175
FT /note="V -> M (in dbSNP:rs7946)"
FT /evidence="ECO:0000269|PubMed:11420179,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:9989271,
FT ECO:0000269|Ref.3, ECO:0000269|Ref.6, ECO:0000269|Ref.9"
FT /id="VAR_016093"
FT VARIANT 194
FT /note="G -> R (in dbSNP:rs70965427)"
FT /id="VAR_055373"
FT MUTAGEN 98
FT /note="G->E: Impairs binding to S-adenosyl-L-methionine."
FT /evidence="ECO:0000269|PubMed:12842883"
FT MUTAGEN 100
FT /note="G->D: Abolishes binding to S-adenosyl-L-methionine."
FT /evidence="ECO:0000269|PubMed:12842883"
FT MUTAGEN 180
FT /note="E->D: Abolishes binding to S-adenosyl-L-methionine."
FT /evidence="ECO:0000269|PubMed:12842883"
FT MUTAGEN 181
FT /note="E->D: Impairs binding to S-adenosyl-L-methionine."
FT /evidence="ECO:0000269|PubMed:12842883"
FT VARIANT Q9UBM1-2:11
FT /note="V -> A (in dbSNP:rs7215880)"
FT /evidence="ECO:0000269|Ref.7"
FT /id="VAR_082891"
FT CONFLICT Q9UBM1-3:222
FT /note="S -> N (in Ref. 5; BAG63603)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 199 AA; 22134 MW; 98C07AB54B3B4E6A CRC64;
MTRLLGYVDP LDPSFVAAVI TITFNPLYWN VVARWEHKTR KLSRAFGSPY LACYSLSVTI
LLLNFLRSHC FTQAMLSQPR MESLDTPAAY SLGLALLGLG VVLVLSSFFA LGFAGTFLGD
YFGILKEARV TVFPFNILDN PMYWGSTANY LGWAIMHASP TGLLLTVLVA LTYIVALLYE
EPFTAEIYRQ KASGSHKRS
