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Protein

Protein phosphatase methylesterase 1

Gene

PPME1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Demethylates proteins that have been reversibly carboxymethylated. Demethylates PPP2CB (in vitro) and PPP2CA. Binding to PPP2CA displaces the manganese ion and inactivates the enzyme.1 Publication

Catalytic activityi

[Phosphatase 2A protein]-leucine methyl ester + H2O = [phosphatase 2A protein]-leucine + methanol.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei1561 Publication1
Active sitei1811 Publication1
Active sitei3491 Publication1

GO - Molecular functioni

  • cadherin binding Source: BHF-UCL
  • protein C-terminal methylesterase activity Source: HGNC
  • protein kinase binding Source: Ensembl
  • protein phosphatase 2A binding Source: HGNC
  • protein phosphatase binding Source: HGNC
  • protein phosphatase inhibitor activity Source: ProtInc
  • protein phosphatase regulator activity Source: HGNC

GO - Biological processi

  • G2/M transition of mitotic cell cycle Source: Reactome
  • protein demethylation Source: HGNC

Keywordsi

Molecular functionHydrolase, Serine esterase

Enzyme and pathway databases

BioCyciMetaCyc:MONOMER-16514
BRENDAi3.1.1.89 2681
ReactomeiR-HSA-69273 Cyclin A/B1/B2 associated events during G2/M transition

Protein family/group databases

ESTHERihuman-PPME1 PPase_methylesterase_euk
MEROPSiS33.984

Names & Taxonomyi

Protein namesi
Recommended name:
Protein phosphatase methylesterase 1 (EC:3.1.1.89)
Short name:
PME-1
Gene namesi
Name:PPME1
Synonyms:PME1
ORF Names:PP2593, PRO0750
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

EuPathDBiHostDB:ENSG00000214517.8
HGNCiHGNC:30178 PPME1
MIMi611117 gene
neXtProtiNX_Q9Y570

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Pathology & Biotechi

Organism-specific databases

DisGeNETi51400
OpenTargetsiENSG00000214517
PharmGKBiPA142671152

Chemistry databases

ChEMBLiCHEMBL1293320
GuidetoPHARMACOLOGYi2875

Polymorphism and mutation databases

DMDMi47606055

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved1 Publication
ChainiPRO_00000903902 – 386Protein phosphatase methylesterase 1Add BLAST385

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei15PhosphoserineCombined sources1
Modified residuei16Asymmetric dimethylarginine; alternateBy similarity1
Modified residuei16Omega-N-methylarginine; alternateCombined sources1
Modified residuei42PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylated by SIK1 following increases in intracellular sodium, leading to dissociation from the protein phosphatase 2A (PP2A) complex and subsequent dephosphorylation of sodium/potassium-transporting ATPase ATP1A1.By similarity

Keywords - PTMi

Methylation, Phosphoprotein

Proteomic databases

EPDiQ9Y570
PaxDbiQ9Y570
PeptideAtlasiQ9Y570
PRIDEiQ9Y570

2D gel databases

REPRODUCTION-2DPAGEiIPI00007694

PTM databases

iPTMnetiQ9Y570
PhosphoSitePlusiQ9Y570
SwissPalmiQ9Y570

Expressioni

Gene expression databases

BgeeiENSG00000214517
CleanExiHS_PPME1
ExpressionAtlasiQ9Y570 baseline and differential
GenevisibleiQ9Y570 HS

Organism-specific databases

HPAiCAB004541
HPA043900
HPA064396

Interactioni

Subunit structurei

Binds PPP2CA and PPP2CB.1 Publication

GO - Molecular functioni

  • cadherin binding Source: BHF-UCL
  • protein kinase binding Source: Ensembl
  • protein phosphatase 2A binding Source: HGNC
  • protein phosphatase binding Source: HGNC

Protein-protein interaction databases

BioGridi119524, 101 interactors
CORUMiQ9Y570
IntActiQ9Y570, 22 interactors
MINTiQ9Y570
STRINGi9606.ENSP00000329867

Chemistry databases

BindingDBiQ9Y570

Structurei

Secondary structure

1386
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi46 – 48Combined sources3
Beta strandi51 – 60Combined sources10
Beta strandi63 – 72Combined sources10
Beta strandi74 – 76Combined sources3
Beta strandi78 – 82Combined sources5
Helixi89 – 92Combined sources4
Helixi93 – 100Combined sources8
Beta strandi106 – 110Combined sources5
Helixi128 – 143Combined sources16
Beta strandi144 – 146Combined sources3
Beta strandi150 – 155Combined sources6
Helixi157 – 167Combined sources11
Beta strandi174 – 181Combined sources8
Helixi184 – 200Combined sources17
Beta strandi205 – 207Combined sources3
Helixi208 – 217Combined sources10
Helixi224 – 234Combined sources11
Beta strandi235 – 237Combined sources3
Beta strandi285 – 288Combined sources4
Helixi291 – 294Combined sources4
Helixi295 – 302Combined sources8
Helixi305 – 311Combined sources7
Beta strandi312 – 314Combined sources3
Beta strandi316 – 322Combined sources7
Helixi323 – 325Combined sources3
Helixi328 – 335Combined sources8
Beta strandi339 – 343Combined sources5
Helixi351 – 354Combined sources4
Helixi356 – 369Combined sources14
Beta strandi372 – 375Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3C5VX-ray2.00A39-386[»]
3C5WX-ray2.80P284-386[»]
P39-238[»]
ProteinModelPortaliQ9Y570
SMRiQ9Y570
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9Y570

Family & Domainsi

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi256 – 263Poly-Glu8

Sequence similaritiesi

Belongs to the AB hydrolase superfamily.Curated

Phylogenomic databases

eggNOGiKOG2564 Eukaryota
COG0596 LUCA
GeneTreeiENSGT00390000004396
HOGENOMiHOG000116699
HOVERGENiHBG053622
InParanoidiQ9Y570
KOiK13617
OMAiRIQCRIV
OrthoDBiEOG091G0D0P
PhylomeDBiQ9Y570
TreeFamiTF314697

Family and domain databases

InterProiView protein in InterPro
IPR029058 AB_hydrolase
IPR000073 AB_hydrolase_1
IPR016812 PPase_methylesterase_euk
PANTHERiPTHR14189 PTHR14189, 1 hit
PfamiView protein in Pfam
PF12697 Abhydrolase_6, 1 hit
PIRSFiPIRSF022950 PPase_methylesterase_euk, 1 hit
SUPFAMiSSF53474 SSF53474, 2 hits
PROSITEiView protein in PROSITE
PS00120 LIPASE_SER, 1 hit

Sequences (4)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9Y570-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSALEKSMHL GRLPSRPPLP GSGGSQSGAK MRMGPGRKRD FSPVPWSQYF
60 70 80 90 100
ESMEDVEVEN ETGKDTFRVY KSGSEGPVLL LLHGGGHSAL SWAVFTAAII
110 120 130 140 150
SRVQCRIVAL DLRSHGETKV KNPEDLSAET MAKDVGNVVE AMYGDLPPPI
160 170 180 190 200
MLIGHSMGGA IAVHTASSNL VPSLLGLCMI DVVEGTAMDA LNSMQNFLRG
210 220 230 240 250
RPKTFKSLEN AIEWSVKSGQ IRNLESARVS MVGQVKQCEG ITSPEGSKSI
260 270 280 290 300
VEGIIEEEEE DEEGSESISK RKKEDDMETK KDHPYTWRIE LAKTEKYWDG
310 320 330 340 350
WFRGLSNLFL SCPIPKLLLL AGVDRLDKDL TIGQMQGKFQ MQVLPQCGHA
360 370 380
VHEDAPDKVA EAVATFLIRH RFAEPIGGFQ CVFPGC
Length:386
Mass (Da):42,315
Last modified:January 23, 2007 - v3
Checksum:i37B25324583E8578
GO
Isoform 2 (identifier: Q9Y570-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-187: Missing.

Note: No experimental confirmation available.
Show »
Length:199
Mass (Da):22,462
Checksum:iF39B21A7AD5C5115
GO
Isoform 3 (identifier: Q9Y570-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-276: Missing.
     360-386: AEAVATFLIRHRFAEPIGGFQCVFPGC → SLVLSDCKRT...LCYFIPGPCG

Note: No experimental confirmation available.
Show »
Length:161
Mass (Da):18,214
Checksum:i53E51B3B7916DBFB
GO
Isoform 4 (identifier: Q9Y570-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     278-278: E → EGLPSETQNLLLFLQ

Note: Gene prediction based on EST data.
Show »
Length:400
Mass (Da):43,870
Checksum:i0F9F02DDFABA6C3B
GO

Sequence cautioni

The sequence AAG22477 differs from that shown. Reason: Erroneous translation. Wrong choice of CDS.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti309F → S in BAA91661 (PubMed:14702039).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0103351 – 276Missing in isoform 3. 1 PublicationAdd BLAST276
Alternative sequenceiVSP_0103361 – 187Missing in isoform 2. 1 PublicationAdd BLAST187
Alternative sequenceiVSP_054818278E → EGLPSETQNLLLFLQ in isoform 4. Curated1
Alternative sequenceiVSP_010337360 – 386AEAVA…VFPGC → SLVLSDCKRTTVRITLDVTE DKSLSLSLHCLQQLLWSLCR CSSTSSPTSPWQLLMVLVLC ICAEELLTLCYFIPGPCG in isoform 3. 1 PublicationAdd BLAST27

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF157028 mRNA Translation: AAD44976.1
AF111853 mRNA Translation: AAF16692.1
AK001381 mRNA Translation: BAA91661.1
AK022725 mRNA Translation: BAG51108.1
AK123288 mRNA Translation: BAC85574.1
AP000577 Genomic DNA No translation available.
AP002392 Genomic DNA No translation available.
CH471076 Genomic DNA Translation: EAW74932.1
BC003046 mRNA Translation: AAH03046.1
BC050705 mRNA Translation: AAH50705.1
AF193049 mRNA Translation: AAG22477.1 Sequence problems.
CCDSiCCDS44678.1 [Q9Y570-1]
CCDS60891.1 [Q9Y570-4]
RefSeqiNP_001258522.1, NM_001271593.1 [Q9Y570-4]
NP_057231.1, NM_016147.2 [Q9Y570-1]
UniGeneiHs.503251

Genome annotation databases

EnsembliENST00000328257; ENSP00000329867; ENSG00000214517 [Q9Y570-1]
ENST00000398427; ENSP00000381461; ENSG00000214517 [Q9Y570-4]
GeneIDi51400
KEGGihsa:51400
UCSCiuc001ouw.5 human [Q9Y570-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiPPME1_HUMAN
AccessioniPrimary (citable) accession number: Q9Y570
Secondary accession number(s): B3KMU6
, B5MEE7, J3QT22, Q8WYG8, Q9NVT5, Q9UI18
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 24, 2004
Last sequence update: January 23, 2007
Last modified: March 28, 2018
This is version 157 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome
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Main funding by: National Institutes of Health