Full text data of LCMT1
LCMT1
(LCMT)
[Confidence: low (only semi-automatic identification from reviews)]
Leucine carboxyl methyltransferase 1; 2.1.1.233 (Protein-leucine O-methyltransferase; [Phosphatase 2A protein]-leucine-carboxy methyltransferase 1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Leucine carboxyl methyltransferase 1; 2.1.1.233 (Protein-leucine O-methyltransferase; [Phosphatase 2A protein]-leucine-carboxy methyltransferase 1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q9UIC8
ID LCMT1_HUMAN Reviewed; 334 AA.
AC Q9UIC8; A6NL89; A8K770; Q53FC5; Q96CI5; Q9H6I9; Q9NTG4; Q9Y378;
read moreDT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2000, sequence version 2.
DT 22-JAN-2014, entry version 117.
DE RecName: Full=Leucine carboxyl methyltransferase 1;
DE EC=2.1.1.233;
DE AltName: Full=Protein-leucine O-methyltransferase;
DE AltName: Full=[Phosphatase 2A protein]-leucine-carboxy methyltransferase 1;
GN Name=LCMT1; Synonyms=LCMT; ORFNames=CGI-68;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY,
RP AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=10600115; DOI=10.1021/bi991646a;
RA De Baere I., Derua R., Janssens V., Van Hoof C., Waelkens E.,
RA Merlevede W., Goris J.;
RT "Purification of porcine brain protein phosphatase 2A leucine carboxyl
RT methyltransferase and cloning of the human homologue.";
RL Biochemistry 38:16539-16547(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=10810093; DOI=10.1101/gr.10.5.703;
RA Lai C.-H., Chou C.-Y., Ch'ang L.-Y., Liu C.-S., Lin W.-C.;
RT "Identification of novel human genes evolutionarily conserved in
RT Caenorhabditis elegans by comparative proteomics.";
RL Genome Res. 10:703-713(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Skeletal muscle, 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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Cerebellum;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X.,
RA Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A.,
RA Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J.,
RA Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L.,
RA Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A.,
RA Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D.,
RA Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J.,
RA Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I.,
RA Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W.,
RA Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A.,
RA Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S.,
RA Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L.,
RA Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A.,
RA Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L.,
RA Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N.,
RA Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M.,
RA Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L.,
RA Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D.,
RA Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P.,
RA Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M.,
RA Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Lung, 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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 14-334 (ISOFORM 1).
RC TISSUE=Testis;
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.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [8]
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.,
RA Buerckstuemmer T., 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 [9]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 23-334 IN COMPLEX WITH
RP S-ADENOSYL-L-METHIONINE, AND CATALYTIC ACTIVITY.
RX PubMed=21206058; DOI=10.1107/S0907444910042204;
RA Tsai M.L., Cronin N., Djordjevic S.;
RT "The structure of human leucine carboxyl methyltransferase 1 that
RT regulates protein phosphatase PP2A.";
RL Acta Crystallogr. D 67:14-24(2011).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) ALONE AND IN COMPLEX WITH
RP PPP2CA.
RX PubMed=21292165; DOI=10.1016/j.molcel.2010.12.030;
RA Stanevich V., Jiang L., Satyshur K.A., Li Y., Jeffrey P.D., Li Z.,
RA Menden P., Semmelhack M.F., Xing Y.;
RT "The structural basis for tight control of PP2A methylation and
RT function by LCMT-1.";
RL Mol. Cell 41:331-342(2011).
CC -!- FUNCTION: Methylates the carboxyl group of the C-terminal leucine
CC residue of protein phosphatase 2A catalytic subunits to form
CC alpha-leucine ester residues.
CC -!- CATALYTIC ACTIVITY: S-adenosyl-L-methionine + [phosphatase 2A
CC protein]-leucine = S-adenosyl-L-homocysteine + [phosphatase 2A
CC protein]-leucine methyl ester.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.1 uM for PP2AD;
CC KM=1.3 uM for AdoMet;
CC -!- INTERACTION:
CC P51116:FXR2; NbExp=2; IntAct=EBI-747632, EBI-740459;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9UIC8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9UIC8-2; Sequence=VSP_017428;
CC Name=3;
CC IsoId=Q9UIC8-3; Sequence=VSP_041416;
CC -!- SIMILARITY: Belongs to the methyltransferase superfamily. LCMT
CC family.
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DR EMBL; AF037601; AAF18267.1; -; mRNA.
DR EMBL; AF151826; AAD34063.1; -; mRNA.
DR EMBL; AK025884; BAB15270.1; -; mRNA.
DR EMBL; AK223364; BAD97084.1; -; mRNA.
DR EMBL; AK291885; BAF84574.1; -; mRNA.
DR EMBL; AK314409; BAG37031.1; -; mRNA.
DR EMBL; AC008741; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC133552; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC001214; AAH01214.1; -; mRNA.
DR EMBL; BC014217; AAH14217.1; -; mRNA.
DR EMBL; AL137283; CAB70677.1; -; mRNA.
DR PIR; T46352; T46352.
DR RefSeq; NP_001027563.1; NM_001032391.1.
DR RefSeq; NP_057393.2; NM_016309.2.
DR RefSeq; XP_005255410.1; XM_005255353.1.
DR UniGene; Hs.337730; -.
DR PDB; 3IEI; X-ray; 1.90 A; A/B/C/D/E/F/G/H=1-334.
DR PDB; 3O7W; X-ray; 2.00 A; A=23-334.
DR PDB; 3P71; X-ray; 2.70 A; T=1-334.
DR PDBsum; 3IEI; -.
DR PDBsum; 3O7W; -.
DR PDBsum; 3P71; -.
DR ProteinModelPortal; Q9UIC8; -.
DR SMR; Q9UIC8; 25-334.
DR IntAct; Q9UIC8; 3.
DR MINT; MINT-1448151; -.
DR STRING; 9606.ENSP00000382021; -.
DR DrugBank; DB00149; L-Leucine.
DR PhosphoSite; Q9UIC8; -.
DR DMDM; 12643251; -.
DR PaxDb; Q9UIC8; -.
DR PRIDE; Q9UIC8; -.
DR DNASU; 51451; -.
DR Ensembl; ENST00000380966; ENSP00000370353; ENSG00000205629.
DR Ensembl; ENST00000399069; ENSP00000382021; ENSG00000205629.
DR GeneID; 51451; -.
DR KEGG; hsa:51451; -.
DR UCSC; uc002dnx.1; human.
DR CTD; 51451; -.
DR GeneCards; GC16P025123; -.
DR H-InvDB; HIX0017913; -.
DR H-InvDB; HIX0022158; -.
DR HGNC; HGNC:17557; LCMT1.
DR HPA; HPA041559; -.
DR HPA; HPA043530; -.
DR MIM; 610286; gene.
DR neXtProt; NX_Q9UIC8; -.
DR PharmGKB; PA134928443; -.
DR eggNOG; NOG329644; -.
DR HOVERGEN; HBG052313; -.
DR InParanoid; Q9UIC8; -.
DR OMA; ECVLVYI; -.
DR OrthoDB; EOG7F24T5; -.
DR BioCyc; MetaCyc:MONOMER-16510; -.
DR EvolutionaryTrace; Q9UIC8; -.
DR GeneWiki; Leucine_carboxyl_methyltransferase_1; -.
DR GenomeRNAi; 51451; -.
DR NextBio; 55059; -.
DR PRO; PR:Q9UIC8; -.
DR ArrayExpress; Q9UIC8; -.
DR Bgee; Q9UIC8; -.
DR CleanEx; HS_LCMT1; -.
DR Genevestigator; Q9UIC8; -.
DR GO; GO:0003880; F:protein C-terminal carboxyl O-methyltransferase activity; IDA:MGI.
DR GO; GO:0008757; F:S-adenosylmethionine-dependent methyltransferase activity; TAS:ProtInc.
DR GO; GO:0031333; P:negative regulation of protein complex assembly; IMP:MGI.
DR GO; GO:0042981; P:regulation of apoptotic process; IMP:MGI.
DR GO; GO:0090266; P:regulation of mitotic cell cycle spindle assembly checkpoint; IMP:MGI.
DR InterPro; IPR007213; LCM_MeTrfase.
DR InterPro; IPR016651; Leu_CO_MeTrfase_LCMT1.
DR PANTHER; PTHR13600; PTHR13600; 1.
DR Pfam; PF04072; LCM; 1.
DR PIRSF; PIRSF016305; LCM_mtfrase; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Complete proteome;
KW Methyltransferase; Reference proteome; S-adenosyl-L-methionine;
KW Transferase.
FT CHAIN 1 334 Leucine carboxyl methyltransferase 1.
FT /FTId=PRO_0000204422.
FT REGION 171 172 S-adenosyl-L-methionine binding.
FT BINDING 73 73 S-adenosyl-L-methionine.
FT BINDING 98 98 S-adenosyl-L-methionine; via carbonyl
FT oxygen.
FT BINDING 122 122 S-adenosyl-L-methionine.
FT BINDING 198 198 S-adenosyl-L-methionine; via carbonyl
FT oxygen.
FT VAR_SEQ 1 37 MATRQRESSITSCCSTSSCDADDEGVRGTCEDASLCK ->
FT MLPCARELPSAAPDSTLLLTAQHWVANLFILATLIGWTVRS
FT FFLGRMETCCSHLGLRSGR (in isoform 2).
FT /FTId=VSP_017428.
FT VAR_SEQ 136 190 Missing (in isoform 3).
FT /FTId=VSP_041416.
FT CONFLICT 49 49 P -> S (in Ref. 4; BAD97084).
FT CONFLICT 114 114 L -> P (in Ref. 3; BAB15270).
FT CONFLICT 248 249 RQ -> PS (in Ref. 2; AAD34063).
FT CONFLICT 251 251 D -> E (in Ref. 1; AAF18267).
FT CONFLICT 301 301 F -> L (in Ref. 3; BAB15270).
FT CONFLICT 306 307 EL -> DV (in Ref. 1; AAF18267).
FT CONFLICT 312 313 MR -> NA (in Ref. 1; AAF18267).
FT HELIX 28 43
FT HELIX 51 53
FT HELIX 64 87
FT TURN 88 90
FT STRAND 92 97
FT HELIX 104 110
FT STRAND 116 122
FT HELIX 124 136
FT HELIX 138 147
FT STRAND 148 152
FT STRAND 159 161
FT STRAND 163 169
FT HELIX 175 184
FT STRAND 193 199
FT HELIX 201 203
FT HELIX 206 219
FT STRAND 221 230
FT HELIX 236 246
FT TURN 247 249
FT HELIX 255 259
FT HELIX 261 269
FT TURN 270 272
FT STRAND 274 280
FT HELIX 281 286
FT HELIX 290 299
FT HELIX 305 312
FT STRAND 315 323
FT TURN 325 328
FT HELIX 329 331
SQ SEQUENCE 334 AA; 38379 MW; C8D200118E6F353D CRC64;
MATRQRESSI TSCCSTSSCD ADDEGVRGTC EDASLCKRFA VSIGYWHDPY IQHFVRLSKE
RKAPEINRGY FARVHGVSQL IKAFLRKTEC HCQIVNLGAG MDTTFWRLKD EDLLPSKYFE
VDFPMIVTRK LHSIKCKPPL SSPILELHSE DTLQMDGHIL DSKRYAVIGA DLRDLSELEE
KLKKCNMNTQ LPTLLIAECV LVYMTPEQSA NLLKWAANSF ERAMFINYEQ VNMGDRFGQI
MIENLRRRQC DLAGVETCKS LESQKERLLS NGWETASAVD MMELYNRLPR AEVSRIESLE
FLDEMELLEQ LMRHYCLCWA TKGGNELGLK EITY
//
ID LCMT1_HUMAN Reviewed; 334 AA.
AC Q9UIC8; A6NL89; A8K770; Q53FC5; Q96CI5; Q9H6I9; Q9NTG4; Q9Y378;
read moreDT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2000, sequence version 2.
DT 22-JAN-2014, entry version 117.
DE RecName: Full=Leucine carboxyl methyltransferase 1;
DE EC=2.1.1.233;
DE AltName: Full=Protein-leucine O-methyltransferase;
DE AltName: Full=[Phosphatase 2A protein]-leucine-carboxy methyltransferase 1;
GN Name=LCMT1; Synonyms=LCMT; ORFNames=CGI-68;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY,
RP AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=10600115; DOI=10.1021/bi991646a;
RA De Baere I., Derua R., Janssens V., Van Hoof C., Waelkens E.,
RA Merlevede W., Goris J.;
RT "Purification of porcine brain protein phosphatase 2A leucine carboxyl
RT methyltransferase and cloning of the human homologue.";
RL Biochemistry 38:16539-16547(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=10810093; DOI=10.1101/gr.10.5.703;
RA Lai C.-H., Chou C.-Y., Ch'ang L.-Y., Liu C.-S., Lin W.-C.;
RT "Identification of novel human genes evolutionarily conserved in
RT Caenorhabditis elegans by comparative proteomics.";
RL Genome Res. 10:703-713(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Skeletal muscle, 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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Cerebellum;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X.,
RA Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A.,
RA Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J.,
RA Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L.,
RA Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A.,
RA Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D.,
RA Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J.,
RA Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I.,
RA Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W.,
RA Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A.,
RA Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S.,
RA Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L.,
RA Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A.,
RA Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L.,
RA Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N.,
RA Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M.,
RA Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L.,
RA Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D.,
RA Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P.,
RA Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M.,
RA Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Lung, 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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 14-334 (ISOFORM 1).
RC TISSUE=Testis;
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.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [8]
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.,
RA Buerckstuemmer T., 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 [9]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 23-334 IN COMPLEX WITH
RP S-ADENOSYL-L-METHIONINE, AND CATALYTIC ACTIVITY.
RX PubMed=21206058; DOI=10.1107/S0907444910042204;
RA Tsai M.L., Cronin N., Djordjevic S.;
RT "The structure of human leucine carboxyl methyltransferase 1 that
RT regulates protein phosphatase PP2A.";
RL Acta Crystallogr. D 67:14-24(2011).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) ALONE AND IN COMPLEX WITH
RP PPP2CA.
RX PubMed=21292165; DOI=10.1016/j.molcel.2010.12.030;
RA Stanevich V., Jiang L., Satyshur K.A., Li Y., Jeffrey P.D., Li Z.,
RA Menden P., Semmelhack M.F., Xing Y.;
RT "The structural basis for tight control of PP2A methylation and
RT function by LCMT-1.";
RL Mol. Cell 41:331-342(2011).
CC -!- FUNCTION: Methylates the carboxyl group of the C-terminal leucine
CC residue of protein phosphatase 2A catalytic subunits to form
CC alpha-leucine ester residues.
CC -!- CATALYTIC ACTIVITY: S-adenosyl-L-methionine + [phosphatase 2A
CC protein]-leucine = S-adenosyl-L-homocysteine + [phosphatase 2A
CC protein]-leucine methyl ester.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.1 uM for PP2AD;
CC KM=1.3 uM for AdoMet;
CC -!- INTERACTION:
CC P51116:FXR2; NbExp=2; IntAct=EBI-747632, EBI-740459;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9UIC8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9UIC8-2; Sequence=VSP_017428;
CC Name=3;
CC IsoId=Q9UIC8-3; Sequence=VSP_041416;
CC -!- SIMILARITY: Belongs to the methyltransferase superfamily. LCMT
CC family.
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DR EMBL; AF037601; AAF18267.1; -; mRNA.
DR EMBL; AF151826; AAD34063.1; -; mRNA.
DR EMBL; AK025884; BAB15270.1; -; mRNA.
DR EMBL; AK223364; BAD97084.1; -; mRNA.
DR EMBL; AK291885; BAF84574.1; -; mRNA.
DR EMBL; AK314409; BAG37031.1; -; mRNA.
DR EMBL; AC008741; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC133552; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC001214; AAH01214.1; -; mRNA.
DR EMBL; BC014217; AAH14217.1; -; mRNA.
DR EMBL; AL137283; CAB70677.1; -; mRNA.
DR PIR; T46352; T46352.
DR RefSeq; NP_001027563.1; NM_001032391.1.
DR RefSeq; NP_057393.2; NM_016309.2.
DR RefSeq; XP_005255410.1; XM_005255353.1.
DR UniGene; Hs.337730; -.
DR PDB; 3IEI; X-ray; 1.90 A; A/B/C/D/E/F/G/H=1-334.
DR PDB; 3O7W; X-ray; 2.00 A; A=23-334.
DR PDB; 3P71; X-ray; 2.70 A; T=1-334.
DR PDBsum; 3IEI; -.
DR PDBsum; 3O7W; -.
DR PDBsum; 3P71; -.
DR ProteinModelPortal; Q9UIC8; -.
DR SMR; Q9UIC8; 25-334.
DR IntAct; Q9UIC8; 3.
DR MINT; MINT-1448151; -.
DR STRING; 9606.ENSP00000382021; -.
DR DrugBank; DB00149; L-Leucine.
DR PhosphoSite; Q9UIC8; -.
DR DMDM; 12643251; -.
DR PaxDb; Q9UIC8; -.
DR PRIDE; Q9UIC8; -.
DR DNASU; 51451; -.
DR Ensembl; ENST00000380966; ENSP00000370353; ENSG00000205629.
DR Ensembl; ENST00000399069; ENSP00000382021; ENSG00000205629.
DR GeneID; 51451; -.
DR KEGG; hsa:51451; -.
DR UCSC; uc002dnx.1; human.
DR CTD; 51451; -.
DR GeneCards; GC16P025123; -.
DR H-InvDB; HIX0017913; -.
DR H-InvDB; HIX0022158; -.
DR HGNC; HGNC:17557; LCMT1.
DR HPA; HPA041559; -.
DR HPA; HPA043530; -.
DR MIM; 610286; gene.
DR neXtProt; NX_Q9UIC8; -.
DR PharmGKB; PA134928443; -.
DR eggNOG; NOG329644; -.
DR HOVERGEN; HBG052313; -.
DR InParanoid; Q9UIC8; -.
DR OMA; ECVLVYI; -.
DR OrthoDB; EOG7F24T5; -.
DR BioCyc; MetaCyc:MONOMER-16510; -.
DR EvolutionaryTrace; Q9UIC8; -.
DR GeneWiki; Leucine_carboxyl_methyltransferase_1; -.
DR GenomeRNAi; 51451; -.
DR NextBio; 55059; -.
DR PRO; PR:Q9UIC8; -.
DR ArrayExpress; Q9UIC8; -.
DR Bgee; Q9UIC8; -.
DR CleanEx; HS_LCMT1; -.
DR Genevestigator; Q9UIC8; -.
DR GO; GO:0003880; F:protein C-terminal carboxyl O-methyltransferase activity; IDA:MGI.
DR GO; GO:0008757; F:S-adenosylmethionine-dependent methyltransferase activity; TAS:ProtInc.
DR GO; GO:0031333; P:negative regulation of protein complex assembly; IMP:MGI.
DR GO; GO:0042981; P:regulation of apoptotic process; IMP:MGI.
DR GO; GO:0090266; P:regulation of mitotic cell cycle spindle assembly checkpoint; IMP:MGI.
DR InterPro; IPR007213; LCM_MeTrfase.
DR InterPro; IPR016651; Leu_CO_MeTrfase_LCMT1.
DR PANTHER; PTHR13600; PTHR13600; 1.
DR Pfam; PF04072; LCM; 1.
DR PIRSF; PIRSF016305; LCM_mtfrase; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Complete proteome;
KW Methyltransferase; Reference proteome; S-adenosyl-L-methionine;
KW Transferase.
FT CHAIN 1 334 Leucine carboxyl methyltransferase 1.
FT /FTId=PRO_0000204422.
FT REGION 171 172 S-adenosyl-L-methionine binding.
FT BINDING 73 73 S-adenosyl-L-methionine.
FT BINDING 98 98 S-adenosyl-L-methionine; via carbonyl
FT oxygen.
FT BINDING 122 122 S-adenosyl-L-methionine.
FT BINDING 198 198 S-adenosyl-L-methionine; via carbonyl
FT oxygen.
FT VAR_SEQ 1 37 MATRQRESSITSCCSTSSCDADDEGVRGTCEDASLCK ->
FT MLPCARELPSAAPDSTLLLTAQHWVANLFILATLIGWTVRS
FT FFLGRMETCCSHLGLRSGR (in isoform 2).
FT /FTId=VSP_017428.
FT VAR_SEQ 136 190 Missing (in isoform 3).
FT /FTId=VSP_041416.
FT CONFLICT 49 49 P -> S (in Ref. 4; BAD97084).
FT CONFLICT 114 114 L -> P (in Ref. 3; BAB15270).
FT CONFLICT 248 249 RQ -> PS (in Ref. 2; AAD34063).
FT CONFLICT 251 251 D -> E (in Ref. 1; AAF18267).
FT CONFLICT 301 301 F -> L (in Ref. 3; BAB15270).
FT CONFLICT 306 307 EL -> DV (in Ref. 1; AAF18267).
FT CONFLICT 312 313 MR -> NA (in Ref. 1; AAF18267).
FT HELIX 28 43
FT HELIX 51 53
FT HELIX 64 87
FT TURN 88 90
FT STRAND 92 97
FT HELIX 104 110
FT STRAND 116 122
FT HELIX 124 136
FT HELIX 138 147
FT STRAND 148 152
FT STRAND 159 161
FT STRAND 163 169
FT HELIX 175 184
FT STRAND 193 199
FT HELIX 201 203
FT HELIX 206 219
FT STRAND 221 230
FT HELIX 236 246
FT TURN 247 249
FT HELIX 255 259
FT HELIX 261 269
FT TURN 270 272
FT STRAND 274 280
FT HELIX 281 286
FT HELIX 290 299
FT HELIX 305 312
FT STRAND 315 323
FT TURN 325 328
FT HELIX 329 331
SQ SEQUENCE 334 AA; 38379 MW; C8D200118E6F353D CRC64;
MATRQRESSI TSCCSTSSCD ADDEGVRGTC EDASLCKRFA VSIGYWHDPY IQHFVRLSKE
RKAPEINRGY FARVHGVSQL IKAFLRKTEC HCQIVNLGAG MDTTFWRLKD EDLLPSKYFE
VDFPMIVTRK LHSIKCKPPL SSPILELHSE DTLQMDGHIL DSKRYAVIGA DLRDLSELEE
KLKKCNMNTQ LPTLLIAECV LVYMTPEQSA NLLKWAANSF ERAMFINYEQ VNMGDRFGQI
MIENLRRRQC DLAGVETCKS LESQKERLLS NGWETASAVD MMELYNRLPR AEVSRIESLE
FLDEMELLEQ LMRHYCLCWA TKGGNELGLK EITY
//
MIM
610286
*RECORD*
*FIELD* NO
610286
*FIELD* TI
*610286 LEUCINE CARBOXYL METHYLTRANSFERASE 1; LCMT1
*FIELD* TX
DESCRIPTION
LCMT1 catalyzes the methylation of the carboxyl group of the C-terminal
read moreleucine residue (leu309) of the catalytic subunit of protein
phosphatase-2A (PPP2CA; 176915) (De Baere et al., 1999).
CLONING
By database analysis with partial peptide sequences of a leucine
carboxyl methyltransferase purified from porcine brain as probe, De
Baere et al. (1999) identified overlapping EST clones and used PCR
techniques to generate the complete human LCMT1 open reading frame. The
deduced 334-amino acid LCMT1 protein has a predicted molecular mass of
38.305 kD and shares high sequence similarity in the methyltransferase
domain with other leucine carboxyl methyltransferases across diverse
species.
GENE FUNCTION
Using a variety of techniques including HPLC analysis of radiolabeled,
methylated peptides, multiple inhibitors, and recognition by antibodies
sensitive to substrate methylation, De Baere et al. (1999) determined
that recombinant LCMT1 expressed in bacterial cells catalyzes the
specific methylation of the C-terminal leu309 of the catalytic subunit
of protein phosphatase-2A, and that methylation does not affect
phosphatase activity. De Baere et al. (1999) determined that the
specific activities, Km, and other properties of the recombinant LCMT1
enzyme corresponded well with those of the native porcine brain leucine
carboxyl methyltransferase.
Lee and Pallas (2007) found that knockdown of LCMT1 by small hairpin RNA
substantially reduced PP2A methylation in HeLa cells, indicating that
LCMT1 is the major PP2A-methylating enzyme. LCMT1 knockdown also
decreased association of the PP2A regulatory subunit B-alpha (PPP2R2A;
604941) with the PP2A catalytic subunit, induced apoptosis, and
sensitized HeLa and colon carcinoma cells to the microtubule
spindle-targeting drug nocodazole. Lee and Pallas (2007) concluded that
LCMT1 is important for normal progression through mitosis and for cell
survival.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the LCMT1
gene to chromosome 16 (TMAP RH64916).
ANIMAL MODEL
Lee and Pallas (2007) found that Lcmt1 knockout in mice was embryonic
lethal.
*FIELD* RF
1. De Baere, I.; Derua, R.; Janssens, V.; Van Hoof, C.; Waelkens,
E.; Merlevede, W.; Goris, J.: Purification of porcine brain protein
phosphatase 2A leucine carboxyl methyltransferase and cloning of the
human homologue. Biochemistry 38: 16539-16547, 1999.
2. Lee, J. A.; Pallas, D. C.: Leucine carboxyl methyltransferase-1
is necessary for normal progression through mitosis in mammalian cells. J.
Biol. Chem. 282: 30974-30984, 2007.
*FIELD* CN
Patricia A. Hartz - updated: 11/30/2007
*FIELD* CD
Dorothy S. Reilly: 7/28/2006
*FIELD* ED
mgross: 11/30/2007
terry: 11/30/2007
carol: 7/28/2006
*RECORD*
*FIELD* NO
610286
*FIELD* TI
*610286 LEUCINE CARBOXYL METHYLTRANSFERASE 1; LCMT1
*FIELD* TX
DESCRIPTION
LCMT1 catalyzes the methylation of the carboxyl group of the C-terminal
read moreleucine residue (leu309) of the catalytic subunit of protein
phosphatase-2A (PPP2CA; 176915) (De Baere et al., 1999).
CLONING
By database analysis with partial peptide sequences of a leucine
carboxyl methyltransferase purified from porcine brain as probe, De
Baere et al. (1999) identified overlapping EST clones and used PCR
techniques to generate the complete human LCMT1 open reading frame. The
deduced 334-amino acid LCMT1 protein has a predicted molecular mass of
38.305 kD and shares high sequence similarity in the methyltransferase
domain with other leucine carboxyl methyltransferases across diverse
species.
GENE FUNCTION
Using a variety of techniques including HPLC analysis of radiolabeled,
methylated peptides, multiple inhibitors, and recognition by antibodies
sensitive to substrate methylation, De Baere et al. (1999) determined
that recombinant LCMT1 expressed in bacterial cells catalyzes the
specific methylation of the C-terminal leu309 of the catalytic subunit
of protein phosphatase-2A, and that methylation does not affect
phosphatase activity. De Baere et al. (1999) determined that the
specific activities, Km, and other properties of the recombinant LCMT1
enzyme corresponded well with those of the native porcine brain leucine
carboxyl methyltransferase.
Lee and Pallas (2007) found that knockdown of LCMT1 by small hairpin RNA
substantially reduced PP2A methylation in HeLa cells, indicating that
LCMT1 is the major PP2A-methylating enzyme. LCMT1 knockdown also
decreased association of the PP2A regulatory subunit B-alpha (PPP2R2A;
604941) with the PP2A catalytic subunit, induced apoptosis, and
sensitized HeLa and colon carcinoma cells to the microtubule
spindle-targeting drug nocodazole. Lee and Pallas (2007) concluded that
LCMT1 is important for normal progression through mitosis and for cell
survival.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the LCMT1
gene to chromosome 16 (TMAP RH64916).
ANIMAL MODEL
Lee and Pallas (2007) found that Lcmt1 knockout in mice was embryonic
lethal.
*FIELD* RF
1. De Baere, I.; Derua, R.; Janssens, V.; Van Hoof, C.; Waelkens,
E.; Merlevede, W.; Goris, J.: Purification of porcine brain protein
phosphatase 2A leucine carboxyl methyltransferase and cloning of the
human homologue. Biochemistry 38: 16539-16547, 1999.
2. Lee, J. A.; Pallas, D. C.: Leucine carboxyl methyltransferase-1
is necessary for normal progression through mitosis in mammalian cells. J.
Biol. Chem. 282: 30974-30984, 2007.
*FIELD* CN
Patricia A. Hartz - updated: 11/30/2007
*FIELD* CD
Dorothy S. Reilly: 7/28/2006
*FIELD* ED
mgross: 11/30/2007
terry: 11/30/2007
carol: 7/28/2006