METK2_HUMAN
ID METK2_HUMAN Reviewed; 395 AA.
AC P31153; A8K511; B4DN45; D6W5L1; Q53SP5;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1993, sequence version 1.
DT 03-AUG-2022, entry version 218.
DE RecName: Full=S-adenosylmethionine synthase isoform type-2;
DE Short=AdoMet synthase 2;
DE EC=2.5.1.6 {ECO:0000269|PubMed:10644686, ECO:0000269|PubMed:23189196, ECO:0000269|PubMed:25075345};
DE AltName: Full=Methionine adenosyltransferase 2;
DE Short=MAT 2 {ECO:0000303|PubMed:10644686};
DE AltName: Full=Methionine adenosyltransferase II;
DE Short=MAT-II;
GN Name=MAT2A; Synonyms=AMS2, MATA2;
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 TISSUE SPECIFICITY.
RC TISSUE=Kidney;
RX PubMed=1426236; DOI=10.1016/0014-5793(92)81405-b;
RA Horikawa S., Tsukada K.;
RT "Molecular cloning and developmental expression of a human kidney S-
RT adenosylmethionine synthetase.";
RL FEBS Lett. 312:37-41(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Lung;
RX PubMed=16413417; DOI=10.1016/j.freeradbiomed.2005.09.004;
RA Panayiotidis M.I., Stabler S.P., Ahmad A., Pappa A., Legros L.H. Jr.,
RA Hernandez-Saavedra D., Schneider B.K., Allen R.H., Vasiliou V.,
RA McCord J.M., Kotb M., White C.W.;
RT "Activation of a novel isoform of methionine adenosyl transferase 2A and
RT increased S-adenosylmethionine turnover in lung epithelial cells exposed to
RT hyperoxia.";
RL Free Radic. Biol. Med. 40:348-358(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [5]
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Muscle;
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 [7]
RP FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, AND PATHWAY.
RX PubMed=10644686; DOI=10.1074/jbc.275.4.2359;
RA LeGros H.L., Halim A.-B., Geller A.M., Kotb M.;
RT "Cloning, expression, and functional characterization of the beta
RT regulatory subunit of human methionine adenosyltransferase (MAT II).";
RL J. Biol. Chem. 275:2359-2366(2000).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-114, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [9]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-81, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [10]
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 [11]
RP CATALYTIC ACTIVITY, SUBUNIT, PATHWAY, AND FUNCTION.
RX PubMed=23189196; DOI=10.1371/journal.pone.0050329;
RA Gonzalez B., Garrido F., Ortega R., Martinez-Julvez M.,
RA Revilla-Guarinos A., Perez-Pertejo Y., Velazquez-Campoy A.,
RA Sanz-Aparicio J., Pajares M.A.;
RT "NADP+ binding to the regulatory subunit of methionine adenosyltransferase
RT II increases intersubunit binding affinity in the hetero-trimer.";
RL PLoS ONE 7:E50329-E50329(2012).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-384, 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 [13]
RP POST-TRANSCRIPTIONAL REGULATION.
RX PubMed=28525753; DOI=10.1016/j.cell.2017.05.003;
RA Pendleton K.E., Chen B., Liu K., Hunter O.V., Xie Y., Tu B.P., Conrad N.K.;
RT "The U6 snRNA m(6)A methyltransferase METTL16 regulates SAM synthetase
RT intron retention.";
RL Cell 169:824-835(2017).
RN [14]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-228 AND LYS-234, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [15]
RP POST-TRANSCRIPTIONAL REGULATION.
RX PubMed=33930289; DOI=10.1016/j.cell.2021.03.062;
RA Mendel M., Delaney K., Pandey R.R., Chen K.M., Wenda J.M., Vaagboe C.B.,
RA Steiner F.A., Homolka D., Pillai R.S.;
RT "Splice site m6A methylation prevents binding of U2AF35 to inhibit RNA
RT splicing.";
RL Cell 0:0-0(2021).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (1.21 ANGSTROMS) IN COMPLEX WITH
RP S-ADENOSYLMETHIONINE.
RX PubMed=23425511; DOI=10.1042/bj20121580;
RA Shafqat N., Muniz J.R., Pilka E.S., Papagrigoriou E., von Delft F.,
RA Oppermann U., Yue W.W.;
RT "Insight into S-adenosylmethionine biosynthesis from the crystal structures
RT of the human methionine adenosyltransferase catalytic and regulatory
RT subunits.";
RL Biochem. J. 452:27-36(2013).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (2.34 ANGSTROMS) IN COMPLEXES WITH ATP ANALOG;
RP S-ADENOSYL-L-METHIONINE AND MAGNESIUM, FUNCTION, CATALYTIC ACTIVITY,
RP PATHWAY, AND SUBUNIT.
RX PubMed=25075345; DOI=10.1107/s2052252514012585;
RA Murray B., Antonyuk S.V., Marina A., Van Liempd S.M., Lu S.C., Mato J.M.,
RA Hasnain S.S., Rojas A.L.;
RT "Structure and function study of the complex that synthesizes S-
RT adenosylmethionine.";
RL IUCrJ 1:240-249(2014).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (1.09 ANGSTROMS) IN COMPLEXTES WITH ATP ANALOG;
RP S-ADENOSYL-L-METHIONINE; MAGNESIUM AND POTASSIUM, AND COFACTOR.
RX PubMed=26858410; DOI=10.1073/pnas.1510959113;
RA Murray B., Antonyuk S.V., Marina A., Lu S.C., Mato J.M., Hasnain S.S.,
RA Rojas A.L.;
RT "Crystallography captures catalytic steps in human methionine
RT adenosyltransferase enzymes.";
RL Proc. Natl. Acad. Sci. U.S.A. 113:2104-2109(2016).
CC -!- FUNCTION: Catalyzes the formation of S-adenosylmethionine from
CC methionine and ATP. The reaction comprises two steps that are both
CC catalyzed by the same enzyme: formation of S-adenosylmethionine
CC (AdoMet) and triphosphate, and subsequent hydrolysis of the
CC triphosphate. {ECO:0000269|PubMed:10644686,
CC ECO:0000269|PubMed:23189196, ECO:0000269|PubMed:25075345}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + L-methionine = diphosphate + phosphate + S-
CC adenosyl-L-methionine; Xref=Rhea:RHEA:21080, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:57844, ChEBI:CHEBI:59789; EC=2.5.1.6;
CC Evidence={ECO:0000269|PubMed:10644686, ECO:0000269|PubMed:23189196,
CC ECO:0000269|PubMed:25075345};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P0A817};
CC Note=Binds 2 magnesium ions per subunit. The magnesium ions interact
CC primarily with the substrate. {ECO:0000269|PubMed:25075345,
CC ECO:0000269|PubMed:26858410};
CC -!- COFACTOR:
CC Name=K(+); Xref=ChEBI:CHEBI:29103;
CC Evidence={ECO:0000250|UniProtKB:P0A817};
CC Note=Binds 1 potassium ion per subunit. The potassium ion interacts
CC primarily with the substrate. {ECO:0000269|PubMed:26858410};
CC -!- PATHWAY: Amino-acid biosynthesis; S-adenosyl-L-methionine biosynthesis;
CC S-adenosyl-L-methionine from L-methionine: step 1/1.
CC {ECO:0000269|PubMed:10644686, ECO:0000269|PubMed:23189196,
CC ECO:0000269|PubMed:25075345}.
CC -!- SUBUNIT: Heterotrimer; composed of a catalytic MAT2A homodimer that
CC binds one regulatory MAT2B chain (PubMed:10644686, PubMed:23189196).
CC Heterohexamer; composed of a central, catalytic MAT2A homotetramer
CC flanked on either side by a regulatory MAT2B chain (PubMed:25075345).
CC {ECO:0000269|PubMed:10644686, ECO:0000269|PubMed:25075345,
CC ECO:0000305|PubMed:23189196}.
CC -!- INTERACTION:
CC P31153; Q96IK1-2: BOD1; NbExp=3; IntAct=EBI-1050743, EBI-18924329;
CC P31153; Q96NX5: CAMK1G; NbExp=3; IntAct=EBI-1050743, EBI-3920838;
CC P31153; Q6ZP82: CCDC141; NbExp=3; IntAct=EBI-1050743, EBI-928795;
CC P31153; Q8IUI8: CRLF3; NbExp=3; IntAct=EBI-1050743, EBI-2872414;
CC P31153; Q6P1L5: FAM117B; NbExp=3; IntAct=EBI-1050743, EBI-3893327;
CC P31153; P15976-2: GATA1; NbExp=3; IntAct=EBI-1050743, EBI-9090198;
CC P31153; P80217-2: IFI35; NbExp=3; IntAct=EBI-1050743, EBI-12823003;
CC P31153; Q8WZ19: KCTD13; NbExp=3; IntAct=EBI-1050743, EBI-742916;
CC P31153; Q9UIH9: KLF15; NbExp=3; IntAct=EBI-1050743, EBI-2796400;
CC P31153; Q00266: MAT1A; NbExp=7; IntAct=EBI-1050743, EBI-967087;
CC P31153; P31153: MAT2A; NbExp=8; IntAct=EBI-1050743, EBI-1050743;
CC P31153; Q9NZL9: MAT2B; NbExp=3; IntAct=EBI-1050743, EBI-10317491;
CC P31153; P02795: MT2A; NbExp=3; IntAct=EBI-1050743, EBI-996616;
CC P31153; Q9BRX2: PELO; NbExp=3; IntAct=EBI-1050743, EBI-1043580;
CC P31153; O43663: PRC1; NbExp=3; IntAct=EBI-1050743, EBI-741137;
CC P31153; O43741: PRKAB2; NbExp=3; IntAct=EBI-1050743, EBI-1053424;
CC P31153; P57052: RBM11; NbExp=3; IntAct=EBI-1050743, EBI-741332;
CC P31153; Q8N488: RYBP; NbExp=3; IntAct=EBI-1050743, EBI-752324;
CC P31153; P08195-4: SLC3A2; NbExp=3; IntAct=EBI-1050743, EBI-12832276;
CC P31153; Q13573: SNW1; NbExp=3; IntAct=EBI-1050743, EBI-632715;
CC P31153; Q86W54-2: SPATA24; NbExp=3; IntAct=EBI-1050743, EBI-12041693;
CC P31153; O95789-4: ZMYM6; NbExp=3; IntAct=EBI-1050743, EBI-12949277;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P31153-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P31153-2; Sequence=VSP_056186, VSP_056187;
CC -!- TISSUE SPECIFICITY: Detected in kidney. {ECO:0000269|PubMed:1426236}.
CC -!- MISCELLANEOUS: Protein expression is regulated by post-transcriptional
CC regulation: in presence of S-adenosyl-L-methionine, METTL16 binds and
CC methylates the first hairpin of the 3'-UTR region of MAT2A mRNA,
CC preventing recognition of their 3'-splice site by U2AF1/U2AF35, thereby
CC inhibiting splicing and protein production of S-adenosylmethionine
CC synthase (PubMed:28525753, PubMed:33930289). In S-adenosyl-L-
CC methionine-limiting conditions, METTL16 binds the 3'-UTR region of
CC MAT2A mRNA without methylating it due to the lack of a methyl donor,
CC preventing N6-methylation and promoting expression of MAT2A
CC (PubMed:28525753). {ECO:0000269|PubMed:28525753,
CC ECO:0000269|PubMed:33930289}.
CC -!- SIMILARITY: Belongs to the AdoMet synthase family. {ECO:0000305}.
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DR EMBL; X68836; CAA48726.1; -; mRNA.
DR EMBL; DQ083239; AAY85355.1; -; mRNA.
DR EMBL; AK291126; BAF83815.1; -; mRNA.
DR EMBL; AK297758; BAG60107.1; -; mRNA.
DR EMBL; AK316411; BAH14782.1; -; mRNA.
DR EMBL; AC016753; AAY24339.1; -; Genomic_DNA.
DR EMBL; CH471053; EAW99511.1; -; Genomic_DNA.
DR EMBL; CH471053; EAW99513.1; -; Genomic_DNA.
DR EMBL; BC001686; AAH01686.1; -; mRNA.
DR EMBL; BC001854; AAH01854.1; -; mRNA.
DR CCDS; CCDS1977.1; -. [P31153-1]
DR PIR; S27257; S27257.
DR RefSeq; NP_005902.1; NM_005911.5. [P31153-1]
DR PDB; 2P02; X-ray; 1.21 A; A=1-395.
DR PDB; 4KTT; X-ray; 2.59 A; A/B/C/D=1-395.
DR PDB; 4KTV; X-ray; 3.30 A; A/B/C/D=1-395.
DR PDB; 4NDN; X-ray; 2.34 A; A/B/C/D=1-395.
DR PDB; 5A19; X-ray; 2.34 A; A=1-395.
DR PDB; 5A1G; X-ray; 1.83 A; A=1-395.
DR PDB; 5A1I; X-ray; 1.09 A; A=1-395.
DR PDB; 5UGH; X-ray; 2.06 A; A/B/C/D=1-395.
DR PDB; 6FAJ; X-ray; 1.95 A; A/B=1-395.
DR PDB; 6FBN; X-ray; 2.70 A; A/B=1-395.
DR PDB; 6FBO; X-ray; 1.80 A; A=1-395.
DR PDB; 6FBP; X-ray; 1.65 A; A/B=1-395.
DR PDB; 6FCB; X-ray; 2.70 A; A=1-395.
DR PDB; 6FCD; X-ray; 1.70 A; A=1-395.
DR PDB; 6FWB; X-ray; 1.79 A; A/B/C/D=1-394.
DR PDB; 6G6R; X-ray; 1.35 A; A=1-395.
DR PDB; 6P9V; X-ray; 2.05 A; A=1-395.
DR PDB; 6WKB; X-ray; 2.55 A; A/B=1-395.
DR PDB; 7BHR; X-ray; 1.08 A; A=1-395.
DR PDB; 7BHS; X-ray; 1.05 A; A=1-395.
DR PDB; 7BHT; X-ray; 1.05 A; A=1-395.
DR PDB; 7BHU; X-ray; 1.15 A; A=1-395.
DR PDB; 7BHV; X-ray; 1.16 A; A=1-395.
DR PDB; 7BHW; X-ray; 1.15 A; A=1-395.
DR PDB; 7BHX; X-ray; 1.08 A; A=1-395.
DR PDB; 7KCC; X-ray; 1.32 A; A=1-395.
DR PDB; 7KCE; X-ray; 1.14 A; A=1-395.
DR PDB; 7KCF; X-ray; 1.10 A; A=1-395.
DR PDB; 7KDA; X-ray; 1.24 A; A=1-395.
DR PDB; 7KDB; X-ray; 1.24 A; A=1-395.
DR PDB; 7L1A; X-ray; 1.25 A; A=1-395.
DR PDB; 7LNH; X-ray; 2.50 A; A/B=1-395.
DR PDB; 7RW5; X-ray; 2.48 A; A/B/C/D=1-395.
DR PDB; 7RW7; X-ray; 1.19 A; A=1-395.
DR PDB; 7RWG; X-ray; 0.97 A; A=1-395.
DR PDB; 7RWH; X-ray; 1.17 A; A=1-395.
DR PDB; 7RXV; X-ray; 1.07 A; A=1-395.
DR PDB; 7RXW; X-ray; 1.07 A; A=1-395.
DR PDB; 7RXX; X-ray; 1.25 A; A=1-395.
DR PDBsum; 2P02; -.
DR PDBsum; 4KTT; -.
DR PDBsum; 4KTV; -.
DR PDBsum; 4NDN; -.
DR PDBsum; 5A19; -.
DR PDBsum; 5A1G; -.
DR PDBsum; 5A1I; -.
DR PDBsum; 5UGH; -.
DR PDBsum; 6FAJ; -.
DR PDBsum; 6FBN; -.
DR PDBsum; 6FBO; -.
DR PDBsum; 6FBP; -.
DR PDBsum; 6FCB; -.
DR PDBsum; 6FCD; -.
DR PDBsum; 6FWB; -.
DR PDBsum; 6G6R; -.
DR PDBsum; 6P9V; -.
DR PDBsum; 6WKB; -.
DR PDBsum; 7BHR; -.
DR PDBsum; 7BHS; -.
DR PDBsum; 7BHT; -.
DR PDBsum; 7BHU; -.
DR PDBsum; 7BHV; -.
DR PDBsum; 7BHW; -.
DR PDBsum; 7BHX; -.
DR PDBsum; 7KCC; -.
DR PDBsum; 7KCE; -.
DR PDBsum; 7KCF; -.
DR PDBsum; 7KDA; -.
DR PDBsum; 7KDB; -.
DR PDBsum; 7L1A; -.
DR PDBsum; 7LNH; -.
DR PDBsum; 7RW5; -.
DR PDBsum; 7RW7; -.
DR PDBsum; 7RWG; -.
DR PDBsum; 7RWH; -.
DR PDBsum; 7RXV; -.
DR PDBsum; 7RXW; -.
DR PDBsum; 7RXX; -.
DR AlphaFoldDB; P31153; -.
DR SMR; P31153; -.
DR BioGRID; 110314; 121.
DR ComplexPortal; CPX-948; S-adenosylmethionine synthase, MAT2A-MAT2B variant.
DR CORUM; P31153; -.
DR IntAct; P31153; 75.
DR MINT; P31153; -.
DR STRING; 9606.ENSP00000303147; -.
DR BindingDB; P31153; -.
DR ChEMBL; CHEMBL3313835; -.
DR DrugBank; DB00118; Ademetionine.
DR DrugBank; DB00134; Methionine.
DR GlyGen; P31153; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P31153; -.
DR MetOSite; P31153; -.
DR PhosphoSitePlus; P31153; -.
DR SwissPalm; P31153; -.
DR BioMuta; MAT2A; -.
DR DMDM; 400245; -.
DR REPRODUCTION-2DPAGE; IPI00010157; -.
DR CPTAC; CPTAC-234; -.
DR CPTAC; CPTAC-235; -.
DR EPD; P31153; -.
DR jPOST; P31153; -.
DR MassIVE; P31153; -.
DR MaxQB; P31153; -.
DR PaxDb; P31153; -.
DR PeptideAtlas; P31153; -.
DR PRIDE; P31153; -.
DR ProteomicsDB; 4670; -.
DR ProteomicsDB; 54763; -. [P31153-1]
DR Antibodypedia; 31867; 373 antibodies from 31 providers.
DR DNASU; 4144; -.
DR Ensembl; ENST00000306434.8; ENSP00000303147.3; ENSG00000168906.13. [P31153-1]
DR Ensembl; ENST00000409017.1; ENSP00000386353.1; ENSG00000168906.13. [P31153-2]
DR GeneID; 4144; -.
DR KEGG; hsa:4144; -.
DR MANE-Select; ENST00000306434.8; ENSP00000303147.3; NM_005911.6; NP_005902.1.
DR UCSC; uc002spr.4; human. [P31153-1]
DR CTD; 4144; -.
DR DisGeNET; 4144; -.
DR GeneCards; MAT2A; -.
DR HGNC; HGNC:6904; MAT2A.
DR HPA; ENSG00000168906; Tissue enhanced (pancreas).
DR MalaCards; MAT2A; -.
DR MIM; 601468; gene.
DR neXtProt; NX_P31153; -.
DR OpenTargets; ENSG00000168906; -.
DR Orphanet; 91387; Familial thoracic aortic aneurysm and aortic dissection.
DR PharmGKB; PA30647; -.
DR VEuPathDB; HostDB:ENSG00000168906; -.
DR eggNOG; KOG1506; Eukaryota.
DR GeneTree; ENSGT00950000183185; -.
DR HOGENOM; CLU_041802_0_1_1; -.
DR InParanoid; P31153; -.
DR OMA; MPYLRPD; -.
DR PhylomeDB; P31153; -.
DR TreeFam; TF300511; -.
DR BioCyc; MetaCyc:HS09847-MON; -.
DR BRENDA; 2.5.1.6; 2681.
DR PathwayCommons; P31153; -.
DR Reactome; R-HSA-156581; Methylation.
DR SignaLink; P31153; -.
DR UniPathway; UPA00315; UER00080.
DR BioGRID-ORCS; 4144; 770 hits in 1087 CRISPR screens.
DR ChiTaRS; MAT2A; human.
DR EvolutionaryTrace; P31153; -.
DR GenomeRNAi; 4144; -.
DR Pharos; P31153; Tchem.
DR PRO; PR:P31153; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; P31153; protein.
DR Bgee; ENSG00000168906; Expressed in body of pancreas and 207 other tissues.
DR ExpressionAtlas; P31153; baseline and differential.
DR Genevisible; P31153; HS.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0048269; C:methionine adenosyltransferase complex; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004478; F:methionine adenosyltransferase activity; IDA:UniProtKB.
DR GO; GO:1990830; P:cellular response to leukemia inhibitory factor; IEA:Ensembl.
DR GO; GO:0006730; P:one-carbon metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0051291; P:protein heterooligomerization; IDA:UniProtKB.
DR GO; GO:0034214; P:protein hexamerization; IDA:UniProtKB.
DR GO; GO:0006556; P:S-adenosylmethionine biosynthetic process; IDA:UniProtKB.
DR DisProt; DP02825; -.
DR HAMAP; MF_00086; S_AdoMet_synth1; 1.
DR InterPro; IPR022631; ADOMET_SYNTHASE_CS.
DR InterPro; IPR022630; S-AdoMet_synt_C.
DR InterPro; IPR022629; S-AdoMet_synt_central.
DR InterPro; IPR022628; S-AdoMet_synt_N.
DR InterPro; IPR002133; S-AdoMet_synthetase.
DR InterPro; IPR022636; S-AdoMet_synthetase_sfam.
DR PANTHER; PTHR11964; PTHR11964; 1.
DR Pfam; PF02773; S-AdoMet_synt_C; 1.
DR Pfam; PF02772; S-AdoMet_synt_M; 1.
DR Pfam; PF00438; S-AdoMet_synt_N; 1.
DR PIRSF; PIRSF000497; MAT; 1.
DR SUPFAM; SSF55973; SSF55973; 3.
DR TIGRFAMs; TIGR01034; metK; 1.
DR PROSITE; PS00376; ADOMET_SYNTHASE_1; 1.
DR PROSITE; PS00377; ADOMET_SYNTHASE_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; ATP-binding;
KW Isopeptide bond; Magnesium; Metal-binding; Nucleotide-binding;
KW One-carbon metabolism; Phosphoprotein; Potassium; Reference proteome;
KW Transferase; Ubl conjugation.
FT CHAIN 1..395
FT /note="S-adenosylmethionine synthase isoform type-2"
FT /id="PRO_0000174435"
FT REGION 113..125
FT /note="Flexible loop"
FT /evidence="ECO:0000250|UniProtKB:P0A817"
FT BINDING 29
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /note="in other chain"
FT /evidence="ECO:0000305|PubMed:25075345,
FT ECO:0000305|PubMed:26858410, ECO:0007744|PDB:4NDN,
FT ECO:0007744|PDB:5A19"
FT BINDING 31
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000305|PubMed:25075345,
FT ECO:0000305|PubMed:26858410, ECO:0007744|PDB:4KTT,
FT ECO:0007744|PDB:4NDN, ECO:0007744|PDB:5A19,
FT ECO:0007744|PDB:5A1G, ECO:0007744|PDB:5A1I"
FT BINDING 57
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /evidence="ECO:0000250|UniProtKB:P0A817"
FT BINDING 70
FT /ligand="L-methionine"
FT /ligand_id="ChEBI:CHEBI:57844"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /note="in other chain"
FT /evidence="ECO:0000305|PubMed:25075345,
FT ECO:0007744|PDB:4NDN"
FT BINDING 113
FT /ligand="L-methionine"
FT /ligand_id="ChEBI:CHEBI:57844"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /note="in other chain"
FT /evidence="ECO:0000305|PubMed:25075345"
FT BINDING 179..181
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /note="in other chain"
FT /evidence="ECO:0000305|PubMed:25075345,
FT ECO:0000305|PubMed:26858410, ECO:0007744|PDB:4KTT,
FT ECO:0007744|PDB:4NDN, ECO:0007744|PDB:5A19,
FT ECO:0007744|PDB:5A1G, ECO:0007744|PDB:5A1I"
FT BINDING 247..250
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /note="in other chain"
FT /evidence="ECO:0000305|PubMed:25075345,
FT ECO:0000305|PubMed:26858410, ECO:0007744|PDB:4KTT,
FT ECO:0007744|PDB:4NDN, ECO:0007744|PDB:5A1G,
FT ECO:0007744|PDB:5A1I"
FT BINDING 258
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /note="in other chain"
FT /evidence="ECO:0000305|PubMed:25075345,
FT ECO:0000305|PubMed:26858410, ECO:0007744|PDB:4KTT,
FT ECO:0007744|PDB:5A19, ECO:0007744|PDB:5A1G,
FT ECO:0007744|PDB:5A1I"
FT BINDING 258
FT /ligand="L-methionine"
FT /ligand_id="ChEBI:CHEBI:57844"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /evidence="ECO:0000305|PubMed:25075345,
FT ECO:0000305|PubMed:26858410, ECO:0007744|PDB:4NDN,
FT ECO:0007744|PDB:5A1I"
FT BINDING 264..265
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /note="in other chain"
FT /evidence="ECO:0000305|PubMed:25075345,
FT ECO:0000305|PubMed:26858410, ECO:0007744|PDB:4NDN,
FT ECO:0007744|PDB:5A19"
FT BINDING 281
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /evidence="ECO:0000305|PubMed:25075345,
FT ECO:0007744|PDB:4NDN"
FT BINDING 285
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /evidence="ECO:0000305|PubMed:25075345,
FT ECO:0000305|PubMed:26858410, ECO:0007744|PDB:4NDN"
FT BINDING 289
FT /ligand="L-methionine"
FT /ligand_id="ChEBI:CHEBI:57844"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:P0A817"
FT BINDING 291
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /evidence="ECO:0000305|PubMed:25075345,
FT ECO:0000305|PubMed:26858410, ECO:0007744|PDB:4NDN"
FT MOD_RES 81
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 114
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 384
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT CROSSLNK 228
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 234
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VAR_SEQ 1..63
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056186"
FT VAR_SEQ 363..395
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056187"
FT HELIX 14..16
FT /evidence="ECO:0007829|PDB:6FWB"
FT STRAND 17..25
FT /evidence="ECO:0007829|PDB:7BHS"
FT HELIX 30..48
FT /evidence="ECO:0007829|PDB:7BHS"
FT STRAND 53..61
FT /evidence="ECO:0007829|PDB:7BHS"
FT STRAND 64..72
FT /evidence="ECO:0007829|PDB:7BHS"
FT HELIX 79..90
FT /evidence="ECO:0007829|PDB:7BHS"
FT HELIX 95..97
FT /evidence="ECO:0007829|PDB:7BHS"
FT TURN 101..103
FT /evidence="ECO:0007829|PDB:7BHS"
FT STRAND 104..111
FT /evidence="ECO:0007829|PDB:7BHS"
FT HELIX 115..121
FT /evidence="ECO:0007829|PDB:7BHS"
FT TURN 122..124
FT /evidence="ECO:0007829|PDB:7BHS"
FT HELIX 127..129
FT /evidence="ECO:0007829|PDB:7BHS"
FT STRAND 132..134
FT /evidence="ECO:0007829|PDB:7BHS"
FT STRAND 136..143
FT /evidence="ECO:0007829|PDB:7BHS"
FT HELIX 152..169
FT /evidence="ECO:0007829|PDB:7BHS"
FT STRAND 171..173
FT /evidence="ECO:0007829|PDB:4NDN"
FT STRAND 176..191
FT /evidence="ECO:0007829|PDB:7BHS"
FT STRAND 194..209
FT /evidence="ECO:0007829|PDB:7BHS"
FT STRAND 211..213
FT /evidence="ECO:0007829|PDB:7BHS"
FT HELIX 215..224
FT /evidence="ECO:0007829|PDB:7BHS"
FT HELIX 227..230
FT /evidence="ECO:0007829|PDB:7BHS"
FT HELIX 233..235
FT /evidence="ECO:0007829|PDB:7BHS"
FT STRAND 241..245
FT /evidence="ECO:0007829|PDB:7BHS"
FT HELIX 254..256
FT /evidence="ECO:0007829|PDB:7BHS"
FT STRAND 259..261
FT /evidence="ECO:0007829|PDB:6FBP"
FT TURN 266..273
FT /evidence="ECO:0007829|PDB:7BHS"
FT HELIX 290..307
FT /evidence="ECO:0007829|PDB:7BHS"
FT STRAND 312..320
FT /evidence="ECO:0007829|PDB:7BHS"
FT STRAND 328..333
FT /evidence="ECO:0007829|PDB:7BHS"
FT HELIX 342..352
FT /evidence="ECO:0007829|PDB:7BHS"
FT HELIX 357..364
FT /evidence="ECO:0007829|PDB:7BHS"
FT TURN 365..367
FT /evidence="ECO:0007829|PDB:7BHS"
FT HELIX 371..374
FT /evidence="ECO:0007829|PDB:7BHS"
FT STRAND 375..377
FT /evidence="ECO:0007829|PDB:7BHS"
FT STRAND 379..382
FT /evidence="ECO:0007829|PDB:7BHS"
FT STRAND 383..385
FT /evidence="ECO:0007829|PDB:6FAJ"
FT HELIX 386..388
FT /evidence="ECO:0007829|PDB:7BHS"
SQ SEQUENCE 395 AA; 43661 MW; 2E7D1B91CC4F7BDD CRC64;
MNGQLNGFHE AFIEEGTFLF TSESVGEGHP DKICDQISDA VLDAHLQQDP DAKVACETVA
KTGMILLAGE ITSRAAVDYQ KVVREAVKHI GYDDSSKGFD YKTCNVLVAL EQQSPDIAQG
VHLDRNEEDI GAGDQGLMFG YATDETEECM PLTIVLAHKL NAKLAELRRN GTLPWLRPDS
KTQVTVQYMQ DRGAVLPIRV HTIVISVQHD EEVCLDEMRD ALKEKVIKAV VPAKYLDEDT
IYHLQPSGRF VIGGPQGDAG LTGRKIIVDT YGGWGAHGGG AFSGKDYTKV DRSAAYAARW
VAKSLVKGGL CRRVLVQVSY AIGVSHPLSI SIFHYGTSQK SERELLEIVK KNFDLRPGVI
VRDLDLKKPI YQRTAAYGHF GRDSFPWEVP KKLKY
