ASML_HUMAN
ID ASML_HUMAN Reviewed; 621 AA.
AC O95671; B4DX75; F5GXH4; J3JS33; Q5JQ53; Q8NBH5; Q96G02; Q9BUL6;
DT 23-APR-2003, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2006, sequence version 3.
DT 03-AUG-2022, entry version 186.
DE RecName: Full=Probable bifunctional dTTP/UTP pyrophosphatase/methyltransferase protein {ECO:0000305};
DE Includes:
DE RecName: Full=dTTP/UTP pyrophosphatase {ECO:0000305};
DE Short=dTTPase/UTPase {ECO:0000305};
DE EC=3.6.1.9 {ECO:0000269|PubMed:24210219};
DE AltName: Full=Nucleoside triphosphate pyrophosphatase {ECO:0000303|PubMed:24210219};
DE AltName: Full=Nucleotide pyrophosphatase {ECO:0000303|PubMed:24210219};
DE Short=Nucleotide PPase {ECO:0000305};
DE Includes:
DE RecName: Full=N-acetylserotonin O-methyltransferase-like protein;
DE Short=ASMTL;
DE EC=2.1.1.-;
GN Name=ASMTL;
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 [GENOMIC DNA], AND VARIANT LYS-541.
RC TISSUE=Bone marrow, Colon, Fetal brain, Pancreas, and Placenta;
RX PubMed=9736779; DOI=10.1093/hmg/7.11.1771;
RA Ried K., Rao E., Schiebel K., Rappold G.A.;
RT "Gene duplications as a recurrent theme in the evolution of the human
RT pseudoautosomal region 1: isolation of the gene ASMTL.";
RL Hum. Mol. Genet. 7:1771-1778(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
RC TISSUE=Adrenal gland, and 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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS MET-458
RP AND LYS-541.
RC TISSUE=Colon adenocarcinoma;
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 [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-239, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-239, 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 [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-239, 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 [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-239, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=18318008; DOI=10.1002/pmic.200700884;
RA Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D.,
RA Zou H., Gu J.;
RT "Large-scale phosphoproteome analysis of human liver tissue by enrichment
RT and fractionation of phosphopeptides with strong anion exchange
RT chromatography.";
RL Proteomics 8:1346-1361(2008).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-239, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-239, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [12]
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 [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-239, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [14]
RP FUNCTION AS A PYROPHOSPHATASE, CATALYTIC ACTIVITY, COFACTOR,
RP BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, ACTIVE SITE, AND MUTAGENESIS OF
RP SER-19; SER-21; ARG-23; ARG-24; GLU-44; TYR-57; LYS-65; ASP-88; GLU-99 AND
RP GLN-179.
RX PubMed=24210219; DOI=10.1016/j.chembiol.2013.09.011;
RA Tchigvintsev A., Tchigvintsev D., Flick R., Popovic A., Dong A., Xu X.,
RA Brown G., Lu W., Wu H., Cui H., Dombrowski L., Joo J.C., Beloglazova N.,
RA Min J., Savchenko A., Caudy A.A., Rabinowitz J.D., Murzin A.G.,
RA Yakunin A.F.;
RT "Biochemical and structural studies of conserved Maf proteins revealed
RT nucleotide pyrophosphatases with a preference for modified nucleotides.";
RL Chem. Biol. 20:1386-1398(2013).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-21; SER-239 AND SER-421, AND
RP IDENTIFICATION BY 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 [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-21; SER-228; THR-234 AND
RP SER-239, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 10-239.
RG Structural genomics consortium (SGC);
RT "Crystal structure of maf domain of human N-acetylserotonin O-
RT methyltransferase-like protein.";
RL Submitted (MAR-2007) to the PDB data bank.
CC -!- FUNCTION: Nucleoside triphosphate pyrophosphatase that hydrolyzes dTTP
CC and UTP. Can also hydrolyze CTP and the modified nucleotides pseudo-
CC UTP, 5-methyl-UTP (m(5)UTP) and 5-methyl-CTP (m(5)CTP). Has weak
CC activity with dCTP, 8-oxo-GTP and N(4)-methyl-dCTP (PubMed:24210219).
CC May have a dual role in cell division arrest and in preventing the
CC incorporation of modified nucleotides into cellular nucleic acids
CC (PubMed:24210219). In addition, the presence of the putative catalytic
CC domain of S-adenosyl-L-methionine binding in the C-terminal region
CC argues for a methyltransferase activity (Probable).
CC {ECO:0000269|PubMed:24210219, ECO:0000305}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=dTTP + H2O = diphosphate + dTMP + H(+); Xref=Rhea:RHEA:28534,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:37568, ChEBI:CHEBI:63528; EC=3.6.1.9;
CC Evidence={ECO:0000269|PubMed:24210219};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + UTP = diphosphate + H(+) + UMP; Xref=Rhea:RHEA:29395,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:46398, ChEBI:CHEBI:57865; EC=3.6.1.9;
CC Evidence={ECO:0000269|PubMed:24210219};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=CTP + H2O = CMP + diphosphate + H(+); Xref=Rhea:RHEA:27762,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:37563, ChEBI:CHEBI:60377; EC=3.6.1.9;
CC Evidence={ECO:0000269|PubMed:24210219};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + psi-UTP = diphosphate + H(+) + psi-UMP;
CC Xref=Rhea:RHEA:58740, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:58380, ChEBI:CHEBI:142798;
CC Evidence={ECO:0000269|PubMed:24210219};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + TTP = 5-methyl-UMP + diphosphate + H(+);
CC Xref=Rhea:RHEA:58736, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:63527, ChEBI:CHEBI:142797;
CC Evidence={ECO:0000269|PubMed:24210219};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5-methyl-CTP + H2O = 5-methyl-CMP + diphosphate + H(+);
CC Xref=Rhea:RHEA:58732, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:142795, ChEBI:CHEBI:142796;
CC Evidence={ECO:0000269|PubMed:24210219};
CC -!- COFACTOR:
CC Name=a divalent metal cation; Xref=ChEBI:CHEBI:60240;
CC Evidence={ECO:0000269|PubMed:24210219};
CC Note=Pyrophosphatase activity requires a divalent metal cation.
CC {ECO:0000269|PubMed:24210219};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=32.7 uM for dTTP {ECO:0000269|PubMed:24210219};
CC KM=41.2 uM for UTP {ECO:0000269|PubMed:24210219};
CC KM=17.4 uM for CTP {ECO:0000269|PubMed:24210219};
CC KM=22.8 uM for dCTP {ECO:0000269|PubMed:24210219};
CC KM=16.1 uM for m(5)UTP {ECO:0000269|PubMed:24210219};
CC KM=39.4 uM for m(5)CTP {ECO:0000269|PubMed:24210219};
CC KM=18.7 uM for pseudo-UTP {ECO:0000269|PubMed:24210219};
CC KM=10.7 uM for 8-oxo-GTP {ECO:0000269|PubMed:24210219};
CC KM=10.3 uM for N(4)-methyl-dCTP {ECO:0000269|PubMed:24210219};
CC Note=kcat is 0.7 sec(-1) with dTTP as substrate. kcat is 0.7 sec(-1)
CC with UTP as substrate. kcat is 0.8 sec(-1) with CTP as substrate.
CC kcat is 0.3 sec(-1) with dCTP as substrate. kcat is 1.5 sec(-1) with
CC m(5)UTP as substrate. kcat is 3.7 sec(-1) with m(5)CTP as substrate.
CC kcat is 2.5 sec(-1) with pseudo-UTP as substrate. kcat is 0.2 sec(-1)
CC with 8-oxo-GTP as substrate. kcat is 0.3 sec(-1) with N(4)-methyl-
CC dCTP as substrate. {ECO:0000269|PubMed:24210219};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:24210219}.
CC -!- INTERACTION:
CC O95671; Q14203-5: DCTN1; NbExp=3; IntAct=EBI-743231, EBI-25840379;
CC O95671; Q9H8Y8: GORASP2; NbExp=3; IntAct=EBI-743231, EBI-739467;
CC O95671; Q15323: KRT31; NbExp=6; IntAct=EBI-743231, EBI-948001;
CC O95671; O76011: KRT34; NbExp=3; IntAct=EBI-743231, EBI-1047093;
CC O95671; Q6A162: KRT40; NbExp=3; IntAct=EBI-743231, EBI-10171697;
CC O95671; Q96CV9: OPTN; NbExp=3; IntAct=EBI-743231, EBI-748974;
CC O95671; Q8ND90: PNMA1; NbExp=3; IntAct=EBI-743231, EBI-302345;
CC O95671; Q04864-2: REL; NbExp=3; IntAct=EBI-743231, EBI-10829018;
CC O95671; P48775: TDO2; NbExp=11; IntAct=EBI-743231, EBI-743494;
CC O95671; Q8N720: ZNF655; NbExp=3; IntAct=EBI-743231, EBI-625509;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=O95671-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O95671-2; Sequence=VSP_007213;
CC Name=3;
CC IsoId=O95671-3; Sequence=VSP_047412;
CC -!- TISSUE SPECIFICITY: Widely expressed. In adult, highly expressed in
CC pancreas, placenta, fibroblast, thymus, prostate, testis, ovary and
CC colon. Expressed at lower levels in spleen, small intestine and
CC leukocytes. In fetus, expressed at high levels in the lung and kidney
CC and at lower level in brain and liver.
CC -!- MISCELLANEOUS: The gene coding for this protein is located in the
CC pseudoautosomal region 1 (PAR1) of X and Y chromosomes. It represents a
CC unique fusion product of 2 different genes of different evolutionary
CC origin and function. The N-terminus is homologous to the bacterial
CC maf/orfE genes and the C-terminus is homologous to ASMT. Exon
CC duplication, exon shuffling and gene fusion seem to be common
CC characteristics of the PAR1 region.
CC -!- SIMILARITY: In the N-terminal section; belongs to the Maf family. YhdE
CC subfamily. {ECO:0000305|PubMed:24210219}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the class I-like SAM-
CC binding methyltransferase superfamily. Cation-independent O-
CC methyltransferase family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA75675.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=CAA75676.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; Y15521; CAA75675.1; ALT_FRAME; Genomic_DNA.
DR EMBL; Y15521; CAA75676.1; ALT_FRAME; Genomic_DNA.
DR EMBL; AK090498; BAC03468.1; -; mRNA.
DR EMBL; AK301844; BAG63287.1; -; mRNA.
DR EMBL; AL683870; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC002508; AAH02508.1; -; mRNA.
DR EMBL; BC010089; AAH10089.1; -; mRNA.
DR CCDS; CCDS43917.1; -. [O95671-1]
DR CCDS; CCDS55362.1; -. [O95671-3]
DR CCDS; CCDS55363.1; -. [O95671-2]
DR RefSeq; NP_001166944.1; NM_001173473.1. [O95671-3]
DR RefSeq; NP_001166945.1; NM_001173474.1. [O95671-2]
DR RefSeq; NP_004183.2; NM_004192.3. [O95671-1]
DR RefSeq; XP_005274491.1; XM_005274434.3. [O95671-1]
DR RefSeq; XP_005274840.1; XM_005274783.3. [O95671-1]
DR PDB; 2P5X; X-ray; 2.00 A; A/B=10-239.
DR PDB; 6XI4; X-ray; 2.22 A; A/B=10-239.
DR PDB; 6XI5; X-ray; 2.61 A; A/B=10-239.
DR PDBsum; 2P5X; -.
DR PDBsum; 6XI4; -.
DR PDBsum; 6XI5; -.
DR AlphaFoldDB; O95671; -.
DR SMR; O95671; -.
DR BioGRID; 114178; 36.
DR IntAct; O95671; 19.
DR MINT; O95671; -.
DR STRING; 9606.ENSP00000370718; -.
DR GlyGen; O95671; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O95671; -.
DR MetOSite; O95671; -.
DR PhosphoSitePlus; O95671; -.
DR BioMuta; ASMTL; -.
DR EPD; O95671; -.
DR jPOST; O95671; -.
DR MassIVE; O95671; -.
DR MaxQB; O95671; -.
DR PaxDb; O95671; -.
DR PeptideAtlas; O95671; -.
DR PRIDE; O95671; -.
DR ProteomicsDB; 24424; -.
DR ProteomicsDB; 50984; -. [O95671-1]
DR ProteomicsDB; 50985; -. [O95671-2]
DR Antibodypedia; 587; 203 antibodies from 26 providers.
DR DNASU; 8623; -.
DR Ensembl; ENST00000381317.9; ENSP00000370718.3; ENSG00000169093.16. [O95671-1]
DR Ensembl; ENST00000381333.9; ENSP00000370734.4; ENSG00000169093.16. [O95671-2]
DR Ensembl; ENST00000534940.6; ENSP00000446410.1; ENSG00000169093.16. [O95671-3]
DR GeneID; 8623; -.
DR KEGG; hsa:8623; -.
DR MANE-Select; ENST00000381317.9; ENSP00000370718.3; NM_004192.4; NP_004183.2.
DR UCSC; uc004cpx.3; human. [O95671-1]
DR CTD; 8623; -.
DR DisGeNET; 8623; -.
DR GeneCards; ASMTL; -.
DR HGNC; HGNC:751; ASMTL.
DR HPA; ENSG00000169093; Low tissue specificity.
DR MIM; 300162; gene.
DR MIM; 400011; gene.
DR neXtProt; NX_O95671; -.
DR OpenTargets; ENSG00000169093; -.
DR PharmGKB; PA25050; -.
DR VEuPathDB; HostDB:ENSG00000169093; -.
DR eggNOG; KOG1509; Eukaryota.
DR eggNOG; KOG3178; Eukaryota.
DR GeneTree; ENSGT00940000162413; -.
DR HOGENOM; CLU_032774_0_0_1; -.
DR InParanoid; O95671; -.
DR OMA; VLCHEKD; -.
DR PhylomeDB; O95671; -.
DR TreeFam; TF314574; -.
DR PathwayCommons; O95671; -.
DR SignaLink; O95671; -.
DR BioGRID-ORCS; 8623; 5 hits in 575 CRISPR screens.
DR ChiTaRS; ASMTL; human.
DR EvolutionaryTrace; O95671; -.
DR GeneWiki; ASMTL; -.
DR GenomeRNAi; 8623; -.
DR Pharos; O95671; Tbio.
DR PRO; PR:O95671; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; O95671; protein.
DR Bgee; ENSG00000169093; Expressed in palpebral conjunctiva and 207 other tissues.
DR Genevisible; O95671; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0036218; F:dTTP diphosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0035529; F:NADH pyrophosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0047429; F:nucleoside-triphosphate diphosphatase activity; IBA:GO_Central.
DR GO; GO:0008171; F:O-methyltransferase activity; IEA:InterPro.
DR GO; GO:0036221; F:UTP diphosphatase activity; IEA:RHEA.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0009117; P:nucleotide metabolic process; IEA:UniProtKB-KW.
DR CDD; cd00555; Maf; 1.
DR Gene3D; 1.10.10.10; -; 1.
DR Gene3D; 3.40.50.150; -; 1.
DR Gene3D; 3.90.950.10; -; 1.
DR HAMAP; MF_00528; Maf; 1.
DR InterPro; IPR031725; ASMT_dimerisation.
DR InterPro; IPR016461; COMT-like.
DR InterPro; IPR029001; ITPase-like_fam.
DR InterPro; IPR003697; Maf-like.
DR InterPro; IPR001077; O_MeTrfase_dom.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR PANTHER; PTHR43213; PTHR43213; 1.
DR Pfam; PF16864; Dimerisation2; 1.
DR Pfam; PF02545; Maf; 1.
DR Pfam; PF00891; Methyltransf_2; 1.
DR SUPFAM; SSF46785; SSF46785; 1.
DR SUPFAM; SSF52972; SSF52972; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR TIGRFAMs; TIGR00172; maf; 1.
DR PROSITE; PS51683; SAM_OMT_II; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Hydrolase; Methyltransferase;
KW Nucleotide metabolism; Phosphoprotein; Reference proteome;
KW S-adenosyl-L-methionine; Transferase.
FT CHAIN 1..621
FT /note="Probable bifunctional dTTP/UTP
FT pyrophosphatase/methyltransferase protein"
FT /id="PRO_0000064702"
FT REGION 11..223
FT /note="MAF-like"
FT REGION 235..279
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 277..621
FT /note="ASMT-like"
FT ACT_SITE 88
FT /note="Proton acceptor; for pyrophosphatase activity"
FT /evidence="ECO:0000305|PubMed:24210219"
FT BINDING 482
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
FT BINDING 508..510
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
FT BINDING 525
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
FT SITE 23
FT /note="Important for substrate specificity; for
FT pyrophosphatase activity"
FT /evidence="ECO:0000305|PubMed:24210219"
FT SITE 89
FT /note="Important for substrate specificity; for
FT pyrophosphatase activity"
FT /evidence="ECO:0000305|PubMed:24210219"
FT SITE 179
FT /note="Important for substrate specificity; for
FT pyrophosphatase activity"
FT /evidence="ECO:0000305|PubMed:24210219"
FT MOD_RES 21
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 228
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 234
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 239
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:18318008, ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 421
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1..58
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_047412"
FT VAR_SEQ 76..91
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_007213"
FT VARIANT 458
FT /note="V -> M (in dbSNP:rs4503285)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_054802"
FT VARIANT 541
FT /note="R -> K (in dbSNP:rs1127297)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:9736779"
FT /id="VAR_054803"
FT MUTAGEN 19
FT /note="S->A: Loss of pyrophosphatase activity."
FT /evidence="ECO:0000269|PubMed:24210219"
FT MUTAGEN 21
FT /note="S->A: Loss of pyrophosphatase activity."
FT /evidence="ECO:0000269|PubMed:24210219"
FT MUTAGEN 23
FT /note="R->A: Decrease in pyrophosphatase activity."
FT /evidence="ECO:0000269|PubMed:24210219"
FT MUTAGEN 24
FT /note="R->A: Loss of pyrophosphatase activity."
FT /evidence="ECO:0000269|PubMed:24210219"
FT MUTAGEN 44
FT /note="E->A: Loss of pyrophosphatase activity."
FT /evidence="ECO:0000269|PubMed:24210219"
FT MUTAGEN 57
FT /note="Y->A: Loss of pyrophosphatase activity."
FT /evidence="ECO:0000269|PubMed:24210219"
FT MUTAGEN 65
FT /note="K->A: Loss of pyrophosphatase activity."
FT /evidence="ECO:0000269|PubMed:24210219"
FT MUTAGEN 88
FT /note="D->A,N: Loss of pyrophosphatase activity."
FT /evidence="ECO:0000269|PubMed:24210219"
FT MUTAGEN 99
FT /note="E->A: Loss of pyrophosphatase activity."
FT /evidence="ECO:0000269|PubMed:24210219"
FT MUTAGEN 179
FT /note="Q->A: Loss of pyrophosphatase activity."
FT /evidence="ECO:0000269|PubMed:24210219"
FT MUTAGEN 179
FT /note="Q->E: Strong decrease in pyrophosphatase activity."
FT /evidence="ECO:0000269|PubMed:24210219"
FT CONFLICT 228
FT /note="S -> P (in Ref. 2; BAG63287)"
FT /evidence="ECO:0000305"
FT CONFLICT 364
FT /note="Y -> H (in Ref. 2; BAG63287)"
FT /evidence="ECO:0000305"
FT CONFLICT 434
FT /note="G -> S (in Ref. 2; BAG63287)"
FT /evidence="ECO:0000305"
FT STRAND 15..17
FT /evidence="ECO:0007829|PDB:2P5X"
FT HELIX 22..30
FT /evidence="ECO:0007829|PDB:2P5X"
FT HELIX 48..50
FT /evidence="ECO:0007829|PDB:2P5X"
FT STRAND 51..53
FT /evidence="ECO:0007829|PDB:2P5X"
FT HELIX 54..77
FT /evidence="ECO:0007829|PDB:2P5X"
FT STRAND 82..93
FT /evidence="ECO:0007829|PDB:2P5X"
FT STRAND 96..98
FT /evidence="ECO:0007829|PDB:2P5X"
FT HELIX 104..114
FT /evidence="ECO:0007829|PDB:2P5X"
FT STRAND 117..133
FT /evidence="ECO:0007829|PDB:2P5X"
FT STRAND 136..152
FT /evidence="ECO:0007829|PDB:2P5X"
FT HELIX 157..166
FT /evidence="ECO:0007829|PDB:2P5X"
FT HELIX 168..171
FT /evidence="ECO:0007829|PDB:2P5X"
FT HELIX 173..175
FT /evidence="ECO:0007829|PDB:2P5X"
FT STRAND 178..180
FT /evidence="ECO:0007829|PDB:2P5X"
FT HELIX 181..184
FT /evidence="ECO:0007829|PDB:2P5X"
FT STRAND 186..191
FT /evidence="ECO:0007829|PDB:2P5X"
FT HELIX 193..197
FT /evidence="ECO:0007829|PDB:2P5X"
FT HELIX 201..212
FT /evidence="ECO:0007829|PDB:2P5X"
SQ SEQUENCE 621 AA; 68857 MW; 564C2D538F4919EC CRC64;
MVLCPVIGKL LHKRVVLASA SPRRQEILSN AGLRFEVVPS KFKEKLDKAS FATPYGYAME
TAKQKALEVA NRLYQKDLRA PDVVIGADTI VTVGGLILEK PVDKQDAYRM LSRLSGREHS
VFTGVAIVHC SSKDHQLDTR VSEFYEETKV KFSELSEELL WEYVHSGEPM DKAGGYGIQA
LGGMLVESVH GDFLNVVGFP LNHFCKQLVK LYYPPRPEDL RRSVKHDSIP AADTFEDLSD
VEGGGSEPTQ RDAGSRDEKA EAGEAGQATA EAECHRTRET LPPFPTRLLE LIEGFMLSKG
LLTACKLKVF DLLKDEAPQK AADIASKVDA SACGMERLLD ICAAMGLLEK TEQGYSNTET
ANVYLASDGE YSLHGFIMHN NDLTWNLFTY LEFAIREGTN QHHRALGKKA EDLFQDAYYQ
SPETRLRFMR AMHGMTKLTA CQVATAFNLS RFSSACDVGG CTGALARELA REYPRMQVTV
FDLPDIIELA AHFQPPGPQA VQIHFAAGDF FRDPLPSAEL YVLCRILHDW PDDKVHKLLS
RVAESCKPGA GLLLVETLLD EEKRVAQRAL MQSLNMLVQT EGKERSLGEY QCLLELHGFH
QVQVVHLGGV LDAILATKVA P
