Full text data of PPME1
PPME1
(PME1)
[Confidence: low (only semi-automatic identification from reviews)]
Protein phosphatase methylesterase 1; PME-1; 3.1.1.89
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Protein phosphatase methylesterase 1; PME-1; 3.1.1.89
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q9Y570
ID PPME1_HUMAN Reviewed; 386 AA.
AC Q9Y570; B3KMU6; B5MEE7; Q8WYG8; Q9NVT5; Q9UI18;
DT 24-MAY-2004, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 3.
DT 22-JAN-2014, entry version 116.
DE RecName: Full=Protein phosphatase methylesterase 1;
DE Short=PME-1;
DE EC=3.1.1.89;
GN Name=PPME1; Synonyms=PME1; ORFNames=PP2593, PRO0750;
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 INTERACTION WITH PPP2CB.
RC TISSUE=Cervix carcinoma;
RX PubMed=10318862; DOI=10.1074/jbc.274.20.14382;
RA Ogris E., Du X., Nelson K.C., Mak E.K., Yu X.X., Lane W.S.,
RA Pallas D.C.;
RT "A protein phosphatase methylesterase (PME-1) is one of several novel
RT proteins stably associating with two inactive mutants of protein
RT phosphatase 2A.";
RL J. Biol. Chem. 274:14382-14391(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Fetal liver;
RA Zhang C., Yu Y., Zhang S., Ouyang S., Luo L., Wei H., Zhou G.,
RA Zhang Y., Liu M., He F.;
RT "Functional prediction of the coding sequences of 9 new genes deduced
RT by analysis of cDNA clones from human fetal liver.";
RL Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=Amygdala;
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 GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F.,
RA Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E.,
RA FitzGerald M.G., Jaffe D.B., LaButti K., Nicol R., Park H.-S.,
RA Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W.,
RA Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S.,
RA Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lung, 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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP PROTEIN SEQUENCE OF 2-12.
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A.,
RA Thomas G.R., Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass
RT spectrometric identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 257-386 (ISOFORM 1).
RX PubMed=15498874; DOI=10.1073/pnas.0404089101;
RA Wan D., Gong Y., Qin W., Zhang P., Li J., Wei L., Zhou X., Li H.,
RA Qiu X., Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y.,
RA Shu H., Chen X., Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S.,
RA Gu J.;
RT "Large-scale cDNA transfection screening for genes related to cancer
RT development and progression.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:15724-15729(2004).
RN [9]
RP IDENTIFICATION BY 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 [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-42, AND MASS
RP SPECTROMETRY.
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 IDENTIFICATION BY 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.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation 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.,
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 [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 39-386 ALONE AND IN COMPLEX
RP WITH PPP2CA AND PPP2R1A, ACTIVE SITE, AND CATALYTIC ACTIVITY.
RX PubMed=18394995; DOI=10.1016/j.cell.2008.02.041;
RA Xing Y., Li Z., Chen Y., Stock J.B., Jeffrey P.D., Shi Y.;
RT "Structural mechanism of demethylation and inactivation of protein
RT phosphatase 2A.";
RL Cell 133:154-163(2008).
CC -!- FUNCTION: Demethylates proteins that have been reversibly
CC carboxymethylated. Demethylates PPP2CB (in vitro) and PPP2CA.
CC Binding to PPP2CA displaces the manganese ion and inactivates the
CC enzyme.
CC -!- CATALYTIC ACTIVITY: [Phosphatase 2A protein]-leucine methyl ester
CC + H(2)O = [phosphatase 2A protein]-leucine + methanol.
CC -!- SUBUNIT: Binds PPP2CA and PPP2CB.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9Y570-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9Y570-2; Sequence=VSP_010336;
CC Note=No experimental confirmation available;
CC Name=3;
CC IsoId=Q9Y570-3; Sequence=VSP_010335, VSP_010337;
CC Note=No experimental confirmation available;
CC -!- PTM: Phosphorylated by SIK1 following increases in intracellular
CC sodium, leading to dissociation from the protein phosphatase 2A
CC (PP2A) complex and subsequent dephosphorylation of
CC sodium/potassium-transporting ATPase ATP1A1 (By similarity).
CC -!- SIMILARITY: Belongs to the AB hydrolase superfamily.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAG22477.1; Type=Erroneous translation; Note=Wrong choice of CDS;
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DR EMBL; AF157028; AAD44976.1; -; mRNA.
DR EMBL; AF111853; AAF16692.1; -; mRNA.
DR EMBL; AK001381; BAA91661.1; -; mRNA.
DR EMBL; AK022725; BAG51108.1; -; mRNA.
DR EMBL; AK123288; BAC85574.1; -; mRNA.
DR EMBL; AP000577; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP002392; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471076; EAW74932.1; -; Genomic_DNA.
DR EMBL; BC003046; AAH03046.1; -; mRNA.
DR EMBL; BC050705; AAH50705.1; -; mRNA.
DR EMBL; AF193049; AAG22477.1; ALT_SEQ; mRNA.
DR RefSeq; NP_001258522.1; NM_001271593.1.
DR RefSeq; NP_057231.1; NM_016147.2.
DR UniGene; Hs.503251; -.
DR PDB; 3C5V; X-ray; 2.00 A; A=39-386.
DR PDB; 3C5W; X-ray; 2.80 A; P=39-386.
DR PDBsum; 3C5V; -.
DR PDBsum; 3C5W; -.
DR ProteinModelPortal; Q9Y570; -.
DR SMR; Q9Y570; 39-376.
DR IntAct; Q9Y570; 6.
DR STRING; 9606.ENSP00000381461; -.
DR BindingDB; Q9Y570; -.
DR ChEMBL; CHEMBL1293320; -.
DR MEROPS; S33.984; -.
DR PhosphoSite; Q9Y570; -.
DR DMDM; 47606055; -.
DR REPRODUCTION-2DPAGE; IPI00007694; -.
DR PaxDb; Q9Y570; -.
DR PRIDE; Q9Y570; -.
DR DNASU; 51400; -.
DR Ensembl; ENST00000328257; ENSP00000329867; ENSG00000214517.
DR Ensembl; ENST00000543525; ENSP00000441498; ENSG00000214517.
DR GeneID; 51400; -.
DR KEGG; hsa:51400; -.
DR UCSC; uc001ouw.4; human.
DR CTD; 51400; -.
DR GeneCards; GC11P073882; -.
DR HGNC; HGNC:30178; PPME1.
DR HPA; CAB004541; -.
DR MIM; 611117; gene.
DR neXtProt; NX_Q9Y570; -.
DR PharmGKB; PA142671152; -.
DR eggNOG; COG0596; -.
DR HOGENOM; HOG000116699; -.
DR HOVERGEN; HBG053622; -.
DR KO; K13617; -.
DR OrthoDB; EOG741Z2K; -.
DR BioCyc; MetaCyc:MONOMER-16514; -.
DR EvolutionaryTrace; Q9Y570; -.
DR GenomeRNAi; 51400; -.
DR NextBio; 54941; -.
DR PRO; PR:Q9Y570; -.
DR ArrayExpress; Q9Y570; -.
DR Bgee; Q9Y570; -.
DR CleanEx; HS_PPME1; -.
DR Genevestigator; Q9Y570; -.
DR GO; GO:0051722; F:protein C-terminal methylesterase activity; IDA:HGNC.
DR GO; GO:0051721; F:protein phosphatase 2A binding; IDA:HGNC.
DR GO; GO:0004864; F:protein phosphatase inhibitor activity; TAS:ProtInc.
DR GO; GO:0008601; F:protein phosphatase type 2A regulator activity; TAS:HGNC.
DR GO; GO:0006482; P:protein demethylation; IDA:HGNC.
DR InterPro; IPR016812; PPase_methylesterase_euk.
DR PANTHER; PTHR14189; PTHR14189; 1.
DR PIRSF; PIRSF022950; PPase_methylesterase_euk; 1.
DR PROSITE; PS00120; LIPASE_SER; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Complete proteome;
KW Direct protein sequencing; Hydrolase; Phosphoprotein;
KW Reference proteome; Serine esterase.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 386 Protein phosphatase methylesterase 1.
FT /FTId=PRO_0000090390.
FT COMPBIAS 256 263 Poly-Glu.
FT ACT_SITE 156 156
FT ACT_SITE 181 181
FT ACT_SITE 349 349
FT MOD_RES 42 42 Phosphoserine.
FT VAR_SEQ 1 276 Missing (in isoform 3).
FT /FTId=VSP_010335.
FT VAR_SEQ 1 187 Missing (in isoform 2).
FT /FTId=VSP_010336.
FT VAR_SEQ 360 386 AEAVATFLIRHRFAEPIGGFQCVFPGC -> SLVLSDCKRT
FT TVRITLDVTEDKSLSLSLHCLQQLLWSLCRCSSTSSPTSPW
FT QLLMVLVLCICAEELLTLCYFIPGPCG (in isoform
FT 3).
FT /FTId=VSP_010337.
FT CONFLICT 309 309 F -> S (in Ref. 3; BAA91661).
FT HELIX 46 48
FT STRAND 51 60
FT STRAND 63 72
FT STRAND 74 76
FT STRAND 78 82
FT HELIX 89 92
FT HELIX 93 100
FT STRAND 106 110
FT HELIX 128 143
FT STRAND 144 146
FT STRAND 150 155
FT HELIX 157 167
FT STRAND 174 181
FT HELIX 184 200
FT STRAND 205 207
FT HELIX 208 217
FT HELIX 224 234
FT STRAND 235 237
FT STRAND 285 288
FT HELIX 291 294
FT HELIX 295 302
FT HELIX 305 311
FT STRAND 312 314
FT STRAND 316 322
FT HELIX 323 325
FT HELIX 328 335
FT STRAND 339 343
FT HELIX 351 354
FT HELIX 356 369
FT STRAND 372 375
SQ SEQUENCE 386 AA; 42315 MW; 37B25324583E8578 CRC64;
MSALEKSMHL GRLPSRPPLP GSGGSQSGAK MRMGPGRKRD FSPVPWSQYF ESMEDVEVEN
ETGKDTFRVY KSGSEGPVLL LLHGGGHSAL SWAVFTAAII SRVQCRIVAL DLRSHGETKV
KNPEDLSAET MAKDVGNVVE AMYGDLPPPI MLIGHSMGGA IAVHTASSNL VPSLLGLCMI
DVVEGTAMDA LNSMQNFLRG RPKTFKSLEN AIEWSVKSGQ IRNLESARVS MVGQVKQCEG
ITSPEGSKSI VEGIIEEEEE DEEGSESISK RKKEDDMETK KDHPYTWRIE LAKTEKYWDG
WFRGLSNLFL SCPIPKLLLL AGVDRLDKDL TIGQMQGKFQ MQVLPQCGHA VHEDAPDKVA
EAVATFLIRH RFAEPIGGFQ CVFPGC
//
ID PPME1_HUMAN Reviewed; 386 AA.
AC Q9Y570; B3KMU6; B5MEE7; Q8WYG8; Q9NVT5; Q9UI18;
DT 24-MAY-2004, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 3.
DT 22-JAN-2014, entry version 116.
DE RecName: Full=Protein phosphatase methylesterase 1;
DE Short=PME-1;
DE EC=3.1.1.89;
GN Name=PPME1; Synonyms=PME1; ORFNames=PP2593, PRO0750;
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 INTERACTION WITH PPP2CB.
RC TISSUE=Cervix carcinoma;
RX PubMed=10318862; DOI=10.1074/jbc.274.20.14382;
RA Ogris E., Du X., Nelson K.C., Mak E.K., Yu X.X., Lane W.S.,
RA Pallas D.C.;
RT "A protein phosphatase methylesterase (PME-1) is one of several novel
RT proteins stably associating with two inactive mutants of protein
RT phosphatase 2A.";
RL J. Biol. Chem. 274:14382-14391(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Fetal liver;
RA Zhang C., Yu Y., Zhang S., Ouyang S., Luo L., Wei H., Zhou G.,
RA Zhang Y., Liu M., He F.;
RT "Functional prediction of the coding sequences of 9 new genes deduced
RT by analysis of cDNA clones from human fetal liver.";
RL Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=Amygdala;
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 GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F.,
RA Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E.,
RA FitzGerald M.G., Jaffe D.B., LaButti K., Nicol R., Park H.-S.,
RA Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W.,
RA Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S.,
RA Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lung, 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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP PROTEIN SEQUENCE OF 2-12.
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A.,
RA Thomas G.R., Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass
RT spectrometric identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 257-386 (ISOFORM 1).
RX PubMed=15498874; DOI=10.1073/pnas.0404089101;
RA Wan D., Gong Y., Qin W., Zhang P., Li J., Wei L., Zhou X., Li H.,
RA Qiu X., Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y.,
RA Shu H., Chen X., Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S.,
RA Gu J.;
RT "Large-scale cDNA transfection screening for genes related to cancer
RT development and progression.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:15724-15729(2004).
RN [9]
RP IDENTIFICATION BY 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 [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-42, AND MASS
RP SPECTROMETRY.
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 IDENTIFICATION BY 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.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation 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.,
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 [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 39-386 ALONE AND IN COMPLEX
RP WITH PPP2CA AND PPP2R1A, ACTIVE SITE, AND CATALYTIC ACTIVITY.
RX PubMed=18394995; DOI=10.1016/j.cell.2008.02.041;
RA Xing Y., Li Z., Chen Y., Stock J.B., Jeffrey P.D., Shi Y.;
RT "Structural mechanism of demethylation and inactivation of protein
RT phosphatase 2A.";
RL Cell 133:154-163(2008).
CC -!- FUNCTION: Demethylates proteins that have been reversibly
CC carboxymethylated. Demethylates PPP2CB (in vitro) and PPP2CA.
CC Binding to PPP2CA displaces the manganese ion and inactivates the
CC enzyme.
CC -!- CATALYTIC ACTIVITY: [Phosphatase 2A protein]-leucine methyl ester
CC + H(2)O = [phosphatase 2A protein]-leucine + methanol.
CC -!- SUBUNIT: Binds PPP2CA and PPP2CB.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9Y570-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9Y570-2; Sequence=VSP_010336;
CC Note=No experimental confirmation available;
CC Name=3;
CC IsoId=Q9Y570-3; Sequence=VSP_010335, VSP_010337;
CC Note=No experimental confirmation available;
CC -!- PTM: Phosphorylated by SIK1 following increases in intracellular
CC sodium, leading to dissociation from the protein phosphatase 2A
CC (PP2A) complex and subsequent dephosphorylation of
CC sodium/potassium-transporting ATPase ATP1A1 (By similarity).
CC -!- SIMILARITY: Belongs to the AB hydrolase superfamily.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAG22477.1; Type=Erroneous translation; Note=Wrong choice of CDS;
CC -----------------------------------------------------------------------
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DR EMBL; AF157028; AAD44976.1; -; mRNA.
DR EMBL; AF111853; AAF16692.1; -; mRNA.
DR EMBL; AK001381; BAA91661.1; -; mRNA.
DR EMBL; AK022725; BAG51108.1; -; mRNA.
DR EMBL; AK123288; BAC85574.1; -; mRNA.
DR EMBL; AP000577; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP002392; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471076; EAW74932.1; -; Genomic_DNA.
DR EMBL; BC003046; AAH03046.1; -; mRNA.
DR EMBL; BC050705; AAH50705.1; -; mRNA.
DR EMBL; AF193049; AAG22477.1; ALT_SEQ; mRNA.
DR RefSeq; NP_001258522.1; NM_001271593.1.
DR RefSeq; NP_057231.1; NM_016147.2.
DR UniGene; Hs.503251; -.
DR PDB; 3C5V; X-ray; 2.00 A; A=39-386.
DR PDB; 3C5W; X-ray; 2.80 A; P=39-386.
DR PDBsum; 3C5V; -.
DR PDBsum; 3C5W; -.
DR ProteinModelPortal; Q9Y570; -.
DR SMR; Q9Y570; 39-376.
DR IntAct; Q9Y570; 6.
DR STRING; 9606.ENSP00000381461; -.
DR BindingDB; Q9Y570; -.
DR ChEMBL; CHEMBL1293320; -.
DR MEROPS; S33.984; -.
DR PhosphoSite; Q9Y570; -.
DR DMDM; 47606055; -.
DR REPRODUCTION-2DPAGE; IPI00007694; -.
DR PaxDb; Q9Y570; -.
DR PRIDE; Q9Y570; -.
DR DNASU; 51400; -.
DR Ensembl; ENST00000328257; ENSP00000329867; ENSG00000214517.
DR Ensembl; ENST00000543525; ENSP00000441498; ENSG00000214517.
DR GeneID; 51400; -.
DR KEGG; hsa:51400; -.
DR UCSC; uc001ouw.4; human.
DR CTD; 51400; -.
DR GeneCards; GC11P073882; -.
DR HGNC; HGNC:30178; PPME1.
DR HPA; CAB004541; -.
DR MIM; 611117; gene.
DR neXtProt; NX_Q9Y570; -.
DR PharmGKB; PA142671152; -.
DR eggNOG; COG0596; -.
DR HOGENOM; HOG000116699; -.
DR HOVERGEN; HBG053622; -.
DR KO; K13617; -.
DR OrthoDB; EOG741Z2K; -.
DR BioCyc; MetaCyc:MONOMER-16514; -.
DR EvolutionaryTrace; Q9Y570; -.
DR GenomeRNAi; 51400; -.
DR NextBio; 54941; -.
DR PRO; PR:Q9Y570; -.
DR ArrayExpress; Q9Y570; -.
DR Bgee; Q9Y570; -.
DR CleanEx; HS_PPME1; -.
DR Genevestigator; Q9Y570; -.
DR GO; GO:0051722; F:protein C-terminal methylesterase activity; IDA:HGNC.
DR GO; GO:0051721; F:protein phosphatase 2A binding; IDA:HGNC.
DR GO; GO:0004864; F:protein phosphatase inhibitor activity; TAS:ProtInc.
DR GO; GO:0008601; F:protein phosphatase type 2A regulator activity; TAS:HGNC.
DR GO; GO:0006482; P:protein demethylation; IDA:HGNC.
DR InterPro; IPR016812; PPase_methylesterase_euk.
DR PANTHER; PTHR14189; PTHR14189; 1.
DR PIRSF; PIRSF022950; PPase_methylesterase_euk; 1.
DR PROSITE; PS00120; LIPASE_SER; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Complete proteome;
KW Direct protein sequencing; Hydrolase; Phosphoprotein;
KW Reference proteome; Serine esterase.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 386 Protein phosphatase methylesterase 1.
FT /FTId=PRO_0000090390.
FT COMPBIAS 256 263 Poly-Glu.
FT ACT_SITE 156 156
FT ACT_SITE 181 181
FT ACT_SITE 349 349
FT MOD_RES 42 42 Phosphoserine.
FT VAR_SEQ 1 276 Missing (in isoform 3).
FT /FTId=VSP_010335.
FT VAR_SEQ 1 187 Missing (in isoform 2).
FT /FTId=VSP_010336.
FT VAR_SEQ 360 386 AEAVATFLIRHRFAEPIGGFQCVFPGC -> SLVLSDCKRT
FT TVRITLDVTEDKSLSLSLHCLQQLLWSLCRCSSTSSPTSPW
FT QLLMVLVLCICAEELLTLCYFIPGPCG (in isoform
FT 3).
FT /FTId=VSP_010337.
FT CONFLICT 309 309 F -> S (in Ref. 3; BAA91661).
FT HELIX 46 48
FT STRAND 51 60
FT STRAND 63 72
FT STRAND 74 76
FT STRAND 78 82
FT HELIX 89 92
FT HELIX 93 100
FT STRAND 106 110
FT HELIX 128 143
FT STRAND 144 146
FT STRAND 150 155
FT HELIX 157 167
FT STRAND 174 181
FT HELIX 184 200
FT STRAND 205 207
FT HELIX 208 217
FT HELIX 224 234
FT STRAND 235 237
FT STRAND 285 288
FT HELIX 291 294
FT HELIX 295 302
FT HELIX 305 311
FT STRAND 312 314
FT STRAND 316 322
FT HELIX 323 325
FT HELIX 328 335
FT STRAND 339 343
FT HELIX 351 354
FT HELIX 356 369
FT STRAND 372 375
SQ SEQUENCE 386 AA; 42315 MW; 37B25324583E8578 CRC64;
MSALEKSMHL GRLPSRPPLP GSGGSQSGAK MRMGPGRKRD FSPVPWSQYF ESMEDVEVEN
ETGKDTFRVY KSGSEGPVLL LLHGGGHSAL SWAVFTAAII SRVQCRIVAL DLRSHGETKV
KNPEDLSAET MAKDVGNVVE AMYGDLPPPI MLIGHSMGGA IAVHTASSNL VPSLLGLCMI
DVVEGTAMDA LNSMQNFLRG RPKTFKSLEN AIEWSVKSGQ IRNLESARVS MVGQVKQCEG
ITSPEGSKSI VEGIIEEEEE DEEGSESISK RKKEDDMETK KDHPYTWRIE LAKTEKYWDG
WFRGLSNLFL SCPIPKLLLL AGVDRLDKDL TIGQMQGKFQ MQVLPQCGHA VHEDAPDKVA
EAVATFLIRH RFAEPIGGFQ CVFPGC
//
MIM
611117
*RECORD*
*FIELD* NO
611117
*FIELD* TI
*611117 PROTEIN PHOSPHATASE METHYLESTERASE 1; PPME1
;;PME1
*FIELD* TX
DESCRIPTION
read more
Protein phosphatase methylesterase-1 catalyzes the demethylation of the
protein phosphatase-2A catalytic subunit (PPP2CA; 176915) (Ogris et al.,
1999).
CLONING
Using immunoprecipitation and characterization of stable protein
complexes formed with catalytically inactive PPP2CA mutants H59Q and
H118Q, Ogris et al. (1999) identified an approximately 44-kD
PPP2CA-associated protein and cloned the cDNA, designated PPME1, from
HeLa cell mRNA by RT-PCR. The deduced 386-amino acid protein shares 40%
and 26% sequence identity with the C. elegans and S. cerevisiae
homologs, respectively. Human PPME1 contains a highly charged stretch of
amino acids, and all 3 PPME1 homologs contain a consensus sequence for
lipases that use an active site serine.
GENE FUNCTION
By immunoprecipitation analysis with wildtype and H59Q and H118Q mutant
PPP2CA, Ogris et al. (1999) showed that PPME1 forms a stable complex
with the catalytically inactive mutant subunits but not with the
wildtype subunit. Expression of PPME1 in bacteria demonstrated that
PPME1 has PPP2CA methylesterase activity that is inhibited by the PPP2CA
inhibitor okadaic acid but not by the serine protease inhibitor PMSF. By
coimmunoprecipitation experiments, Ogris et al. (1999) showed that the
PPP2CA inhibitors okadaic acid, sodium fluoride, and sodium
pyrophosphate decreased the association of PPME1 with the H59Q mutant.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the PPME1
gene to chromosome 11 (TMAP RH11842).
BIOCHEMICAL FEATURES
- Crystal Structure
Xing et al. (2008) reported the crystal structure at 2.1-angstrom
resolution of human PME1 by itself and in complex with a PP2A
heterodimeric core enzyme, which consists of PPP2CA and PPP2R1A
(605983). The structures revealed that PME1 directly binds to the active
site of PP2A and that this interaction results in the activation of PME1
by rearranging its catalytic triad residues into an active conformation.
This interaction also leads to inactivation of PP2A by evicting the
manganese ions required for the phosphatase activity of PP2A.
*FIELD* RF
1. Ogris, E.; Du, X.; Nelson, K. C.; Mak, E. K.; Yu, X. X.; Lane,
W. S.; Pallas, D. C.: A protein phosphatase methylesterase (PME-1)
is one of several novel proteins stably associating with two inactive
mutants of protein phosphatase 2A. J. Biol. Chem. 274: 14382-14391,
1999.
2. Xing,Y.; Li, Z.; Chen, Y.; Stock, J. B.; Jeffrey, P. D.; Shi, Y.
: Structural mechanism of demethylation and inactivation of protein
phosphatase 2A. Cell 133: 154-163, 2008.
*FIELD* CN
Patricia A. Hartz - updated: 5/27/2008
*FIELD* CD
Dorothy S. Reilly: 6/18/2007
*FIELD* ED
wwang: 05/30/2008
terry: 5/27/2008
carol: 6/18/2007
*RECORD*
*FIELD* NO
611117
*FIELD* TI
*611117 PROTEIN PHOSPHATASE METHYLESTERASE 1; PPME1
;;PME1
*FIELD* TX
DESCRIPTION
read more
Protein phosphatase methylesterase-1 catalyzes the demethylation of the
protein phosphatase-2A catalytic subunit (PPP2CA; 176915) (Ogris et al.,
1999).
CLONING
Using immunoprecipitation and characterization of stable protein
complexes formed with catalytically inactive PPP2CA mutants H59Q and
H118Q, Ogris et al. (1999) identified an approximately 44-kD
PPP2CA-associated protein and cloned the cDNA, designated PPME1, from
HeLa cell mRNA by RT-PCR. The deduced 386-amino acid protein shares 40%
and 26% sequence identity with the C. elegans and S. cerevisiae
homologs, respectively. Human PPME1 contains a highly charged stretch of
amino acids, and all 3 PPME1 homologs contain a consensus sequence for
lipases that use an active site serine.
GENE FUNCTION
By immunoprecipitation analysis with wildtype and H59Q and H118Q mutant
PPP2CA, Ogris et al. (1999) showed that PPME1 forms a stable complex
with the catalytically inactive mutant subunits but not with the
wildtype subunit. Expression of PPME1 in bacteria demonstrated that
PPME1 has PPP2CA methylesterase activity that is inhibited by the PPP2CA
inhibitor okadaic acid but not by the serine protease inhibitor PMSF. By
coimmunoprecipitation experiments, Ogris et al. (1999) showed that the
PPP2CA inhibitors okadaic acid, sodium fluoride, and sodium
pyrophosphate decreased the association of PPME1 with the H59Q mutant.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the PPME1
gene to chromosome 11 (TMAP RH11842).
BIOCHEMICAL FEATURES
- Crystal Structure
Xing et al. (2008) reported the crystal structure at 2.1-angstrom
resolution of human PME1 by itself and in complex with a PP2A
heterodimeric core enzyme, which consists of PPP2CA and PPP2R1A
(605983). The structures revealed that PME1 directly binds to the active
site of PP2A and that this interaction results in the activation of PME1
by rearranging its catalytic triad residues into an active conformation.
This interaction also leads to inactivation of PP2A by evicting the
manganese ions required for the phosphatase activity of PP2A.
*FIELD* RF
1. Ogris, E.; Du, X.; Nelson, K. C.; Mak, E. K.; Yu, X. X.; Lane,
W. S.; Pallas, D. C.: A protein phosphatase methylesterase (PME-1)
is one of several novel proteins stably associating with two inactive
mutants of protein phosphatase 2A. J. Biol. Chem. 274: 14382-14391,
1999.
2. Xing,Y.; Li, Z.; Chen, Y.; Stock, J. B.; Jeffrey, P. D.; Shi, Y.
: Structural mechanism of demethylation and inactivation of protein
phosphatase 2A. Cell 133: 154-163, 2008.
*FIELD* CN
Patricia A. Hartz - updated: 5/27/2008
*FIELD* CD
Dorothy S. Reilly: 6/18/2007
*FIELD* ED
wwang: 05/30/2008
terry: 5/27/2008
carol: 6/18/2007