Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Protein phosphatase 1A

Gene

PPM1A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Enzyme with a broad specificity. Negatively regulates TGF-beta signaling through dephosphorylating SMAD2 and SMAD3, resulting in their dissociation from SMAD4, nuclear export of the SMADs and termination of the TGF-beta-mediated signaling. Dephosphorylates PRKAA1 and PRKAA2. Plays an important role in the termination of TNF-alpha-mediated NF-kappa-B activation through dephosphorylating and inactivating IKBKB/IKKB.2 Publications

Catalytic activityi

[a protein]-serine/threonine phosphate + H2O = [a protein]-serine/threonine + phosphate.

Cofactori

Mg2+, Mn2+Note: Binds 2 magnesium or manganese ions per subunit.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi60Manganese 11
Metal bindingi60Manganese 21
Metal bindingi61Manganese 1; via carbonyl oxygen1
Metal bindingi239Manganese 21
Metal bindingi282Manganese 21

GO - Molecular functioni

  • calmodulin-dependent protein phosphatase activity Source: UniProtKB
  • magnesium ion binding Source: InterPro
  • manganese ion binding Source: InterPro
  • protein serine/threonine phosphatase activity Source: UniProtKB
  • R-SMAD binding Source: UniProtKB
  • signal transducer activity Source: UniProtKB

GO - Biological processi

  • cell cycle arrest Source: Reactome
  • cellular response to transforming growth factor beta stimulus Source: Ensembl
  • dephosphorylation Source: BHF-UCL
  • negative regulation of BMP signaling pathway Source: Ensembl
  • negative regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
  • negative regulation of NF-kappaB import into nucleus Source: UniProtKB
  • negative regulation of SMAD protein complex assembly Source: UniProtKB
  • negative regulation of transcription from RNA polymerase II promoter Source: Reactome
  • negative regulation of transforming growth factor beta receptor signaling pathway Source: UniProtKB
  • N-terminal protein myristoylation Source: UniProtKB
  • peptidyl-threonine dephosphorylation Source: UniProtKB
  • positive regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
  • positive regulation of protein export from nucleus Source: Ensembl
  • positive regulation of transcription, DNA-templated Source: BHF-UCL
  • positive regulation of Wnt signaling pathway Source: BHF-UCL
  • protein dephosphorylation Source: UniProtKB
  • Wnt signaling pathway Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protein phosphatase

Keywords - Ligandi

Magnesium, Manganese, Metal-binding

Enzyme and pathway databases

BioCyciZFISH:HS02125-MONOMER.
BRENDAi3.1.3.16. 2681.
ReactomeiR-HSA-2173795. Downregulation of SMAD2/3:SMAD4 transcriptional activity.
R-HSA-380972. Energy dependent regulation of mTOR by LKB1-AMPK.
SignaLinkiP35813.
SIGNORiP35813.

Names & Taxonomyi

Protein namesi
Recommended name:
Protein phosphatase 1A (EC:3.1.3.16)
Alternative name(s):
Protein phosphatase 2C isoform alpha
Short name:
PP2C-alpha
Protein phosphatase IA
Gene namesi
Name:PPM1A
Synonyms:PPPM1A
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 14

Organism-specific databases

HGNCiHGNC:9275. PPM1A.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: UniProtKB
  • membrane Source: UniProtKB
  • nucleoplasm Source: Reactome
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi239D → N: No effect on binding SMAD2. 1 Publication1

Organism-specific databases

DisGeNETi5494.
OpenTargetsiENSG00000100614.
PharmGKBiPA33603.

Chemistry databases

ChEMBLiCHEMBL2437.

Polymorphism and mutation databases

BioMutaiPPM1A.
DMDMi548442.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved1 Publication
ChainiPRO_00000577412 – 382Protein phosphatase 1AAdd BLAST381

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi2N-myristoyl glycine2 Publications1
Modified residuei375PhosphoserineCombined sources1
Modified residuei377PhosphoserineBy similarity1

Post-translational modificationi

N-myristoylation is essential for the recognition of its substrates for dephosphorylation.By similarity

Keywords - PTMi

Lipoprotein, Myristate, Phosphoprotein

Proteomic databases

EPDiP35813.
MaxQBiP35813.
PaxDbiP35813.
PeptideAtlasiP35813.
PRIDEiP35813.

PTM databases

DEPODiP35813.
iPTMnetiP35813.
PhosphoSitePlusiP35813.

Expressioni

Gene expression databases

BgeeiENSG00000100614.
CleanExiHS_PPM1A.
ExpressionAtlasiP35813. baseline and differential.
GenevisibleiP35813. HS.

Organism-specific databases

HPAiHPA029209.

Interactioni

Subunit structurei

Monomer. Interacts with SMAD2; the interaction dephosphorylates SMAD2 in its C-terminal SXS motif resulting in disruption of the SMAD2/SMAD4 complex, SMAD2 nuclear export and termination of the TGF-beta-mediated signaling. Interacts with SMAD2; the interaction dephosphorylates SMAD2 in its C-terminal SXS motif resulting in disruption of the SMAD2/SMAD4 complex, SMAD2 nuclear export and termination of the TGF-beta-mediated signaling. Interacts with the phosphorylated form of IKBKB/IKKB.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ARRB1P494074EBI-989143,EBI-743313
ARRB2P321213EBI-989143,EBI-714559
AXIN1O151692EBI-989143,EBI-710484
MAPK1P2848219EBI-989143,EBI-959949
MAPK14Q165392EBI-989143,EBI-73946
RANBP3Q9H6Z44EBI-989143,EBI-992681
SMAD2Q157962EBI-989143,EBI-1040141

GO - Molecular functioni

  • R-SMAD binding Source: UniProtKB

Protein-protein interaction databases

BioGridi111489. 53 interactors.
IntActiP35813. 33 interactors.
MINTiMINT-2802996.
STRINGi9606.ENSP00000327255.

Chemistry databases

BindingDBiP35813.

Structurei

Secondary structure

1382
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi4 – 9Combined sources6
Beta strandi13 – 19Combined sources7
Beta strandi22 – 29Combined sources8
Beta strandi31 – 35Combined sources5
Beta strandi38 – 45Combined sources8
Turni47 – 49Combined sources3
Beta strandi54 – 63Combined sources10
Helixi66 – 80Combined sources15
Helixi83 – 86Combined sources4
Beta strandi88 – 91Combined sources4
Helixi94 – 119Combined sources26
Beta strandi129 – 134Combined sources6
Beta strandi136 – 146Combined sources11
Beta strandi148 – 153Combined sources6
Beta strandi156 – 160Combined sources5
Helixi169 – 177Combined sources9
Turni188 – 190Combined sources3
Helixi200 – 202Combined sources3
Beta strandi212 – 216Combined sources5
Beta strandi220 – 225Combined sources6
Turni228 – 230Combined sources3
Beta strandi231 – 237Combined sources7
Helixi239 – 242Combined sources4
Helixi247 – 258Combined sources12
Helixi264 – 277Combined sources14
Beta strandi284 – 290Combined sources7
Helixi299 – 320Combined sources22
Helixi330 – 339Combined sources10
Turni347 – 350Combined sources4
Helixi351 – 354Combined sources4
Helixi355 – 365Combined sources11

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1A6QX-ray2.00A1-382[»]
3FXJX-ray2.50A1-382[»]
3FXKX-ray2.10A1-382[»]
3FXLX-ray2.30A1-382[»]
3FXMX-ray2.50A1-382[»]
3FXOX-ray2.50A1-382[»]
4RA2X-ray1.94A2-368[»]
4RAFX-ray2.00A2-368[»]
4RAGX-ray1.85A2-368[»]
ProteinModelPortaliP35813.
SMRiP35813.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP35813.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini23 – 291PPM-type phosphatasePROSITE-ProRule annotationAdd BLAST269

Sequence similaritiesi

Belongs to the PP2C family.Curated
Contains 1 PPM-type phosphatase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0697. Eukaryota.
COG0631. LUCA.
GeneTreeiENSGT00740000115384.
HOGENOMiHOG000233895.
HOVERGENiHBG053647.
InParanoidiP35813.
KOiK04457.
OMAiEPEVYAI.
OrthoDBiEOG091G0AJQ.
PhylomeDBiP35813.
TreeFamiTF313590.

Family and domain databases

Gene3Di1.10.10.430. 1 hit.
3.60.40.10. 1 hit.
InterProiIPR015655. PP2C.
IPR000222. PP2C_BS.
IPR012911. PP2C_C.
IPR001932. PPM-type_phosphatase_dom.
[Graphical view]
PANTHERiPTHR13832. PTHR13832. 1 hit.
PfamiPF00481. PP2C. 1 hit.
PF07830. PP2C_C. 1 hit.
[Graphical view]
SMARTiSM00332. PP2Cc. 1 hit.
[Graphical view]
SUPFAMiSSF81601. SSF81601. 1 hit.
SSF81606. SSF81606. 1 hit.
PROSITEiPS01032. PPM_1. 1 hit.
PS51746. PPM_2. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

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

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform Alpha-1 (identifier: P35813-1) [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
MGAFLDKPKM EKHNAQGQGN GLRYGLSSMQ GWRVEMEDAH TAVIGLPSGL
60 70 80 90 100
ESWSFFAVYD GHAGSQVAKY CCEHLLDHIT NNQDFKGSAG APSVENVKNG
110 120 130 140 150
IRTGFLEIDE HMRVMSEKKH GADRSGSTAV GVLISPQHTY FINCGDSRGL
160 170 180 190 200
LCRNRKVHFF TQDHKPSNPL EKERIQNAGG SVMIQRVNGS LAVSRALGDF
210 220 230 240 250
DYKCVHGKGP TEQLVSPEPE VHDIERSEED DQFIILACDG IWDVMGNEEL
260 270 280 290 300
CDFVRSRLEV TDDLEKVCNE VVDTCLYKGS RDNMSVILIC FPNAPKVSPE
310 320 330 340 350
AVKKEAELDK YLECRVEEII KKQGEGVPDL VHVMRTLASE NIPSLPPGGE
360 370 380
LASKRNVIEA VYNRLNPYKN DDTDSTSTDD MW
Length:382
Mass (Da):42,448
Last modified:June 1, 1994 - v1
Checksum:iD48EF508B4A76687
GO
Isoform Alpha-2 (identifier: P35813-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     318-324: EIIKKQG → GGSFNKK
     325-382: Missing.

Show »
Length:324
Mass (Da):35,958
Checksum:iED58E203BB26CE00
GO
Isoform 3 (identifier: P35813-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MFCSGRKWVAEATICTKLMKREKRRMGKRRAKKAKREEKKKGGERRRNEKRGNQMKRMCERKKYETDLEDQDIM

Note: No experimental confirmation available.Curated
Show »
Length:455
Mass (Da):51,366
Checksum:iCBC6E3F350D6FDBD
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti342I → T in AK097843 (PubMed:14702039).Curated1
Isoform 3 (identifier: P35813-3)
Sequence conflicti54Q → R in AK097843 (PubMed:14702039).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0456871M → MFCSGRKWVAEATICTKLMK REKRRMGKRRAKKAKREEKK KGGERRRNEKRGNQMKRMCE RKKYETDLEDQDIM in isoform 3. 1 Publication1
Alternative sequenceiVSP_005085318 – 324EIIKKQG → GGSFNKK in isoform Alpha-2. 1 Publication7
Alternative sequenceiVSP_005086325 – 382Missing in isoform Alpha-2. 1 PublicationAdd BLAST58

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S87759 mRNA. Translation: AAB21784.1.
AF070670 mRNA. Translation: AAC28354.1.
AK097843 mRNA. No translation available.
AB451247 mRNA. Translation: BAG70061.1.
AL132778 Genomic DNA. No translation available.
AL157756 Genomic DNA. No translation available.
CH471061 Genomic DNA. Translation: EAW80774.1.
BC026691 mRNA. Translation: AAH26691.1.
BC063243 mRNA. Translation: AAH63243.1.
CCDSiCCDS45120.1. [P35813-3]
CCDS9744.1. [P35813-1]
CCDS9745.1. [P35813-2]
PIRiS22423.
RefSeqiNP_066283.1. NM_021003.4. [P35813-1]
NP_808820.1. NM_177951.2. [P35813-2]
NP_808821.2. NM_177952.2. [P35813-3]
XP_005267836.1. XM_005267779.1. [P35813-1]
XP_005267838.1. XM_005267781.1. [P35813-1]
XP_011535180.1. XM_011536878.1. [P35813-1]
XP_011535181.1. XM_011536879.2. [P35813-1]
XP_011535182.1. XM_011536880.2. [P35813-1]
XP_011535183.1. XM_011536881.2. [P35813-1]
XP_011535184.1. XM_011536882.2. [P35813-1]
XP_011535185.1. XM_011536883.1. [P35813-1]
XP_011535186.1. XM_011536884.1. [P35813-1]
XP_016876873.1. XM_017021384.1. [P35813-1]
XP_016876874.1. XM_017021385.1. [P35813-1]
XP_016876875.1. XM_017021386.1. [P35813-1]
XP_016876876.1. XM_017021387.1. [P35813-1]
UniGeneiHs.130036.

Genome annotation databases

EnsembliENST00000325642; ENSP00000327255; ENSG00000100614. [P35813-3]
ENST00000325658; ENSP00000314850; ENSG00000100614. [P35813-2]
ENST00000395076; ENSP00000378514; ENSG00000100614. [P35813-1]
GeneIDi5494.
KEGGihsa:5494.
UCSCiuc001xew.5. human. [P35813-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S87759 mRNA. Translation: AAB21784.1.
AF070670 mRNA. Translation: AAC28354.1.
AK097843 mRNA. No translation available.
AB451247 mRNA. Translation: BAG70061.1.
AL132778 Genomic DNA. No translation available.
AL157756 Genomic DNA. No translation available.
CH471061 Genomic DNA. Translation: EAW80774.1.
BC026691 mRNA. Translation: AAH26691.1.
BC063243 mRNA. Translation: AAH63243.1.
CCDSiCCDS45120.1. [P35813-3]
CCDS9744.1. [P35813-1]
CCDS9745.1. [P35813-2]
PIRiS22423.
RefSeqiNP_066283.1. NM_021003.4. [P35813-1]
NP_808820.1. NM_177951.2. [P35813-2]
NP_808821.2. NM_177952.2. [P35813-3]
XP_005267836.1. XM_005267779.1. [P35813-1]
XP_005267838.1. XM_005267781.1. [P35813-1]
XP_011535180.1. XM_011536878.1. [P35813-1]
XP_011535181.1. XM_011536879.2. [P35813-1]
XP_011535182.1. XM_011536880.2. [P35813-1]
XP_011535183.1. XM_011536881.2. [P35813-1]
XP_011535184.1. XM_011536882.2. [P35813-1]
XP_011535185.1. XM_011536883.1. [P35813-1]
XP_011535186.1. XM_011536884.1. [P35813-1]
XP_016876873.1. XM_017021384.1. [P35813-1]
XP_016876874.1. XM_017021385.1. [P35813-1]
XP_016876875.1. XM_017021386.1. [P35813-1]
XP_016876876.1. XM_017021387.1. [P35813-1]
UniGeneiHs.130036.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1A6QX-ray2.00A1-382[»]
3FXJX-ray2.50A1-382[»]
3FXKX-ray2.10A1-382[»]
3FXLX-ray2.30A1-382[»]
3FXMX-ray2.50A1-382[»]
3FXOX-ray2.50A1-382[»]
4RA2X-ray1.94A2-368[»]
4RAFX-ray2.00A2-368[»]
4RAGX-ray1.85A2-368[»]
ProteinModelPortaliP35813.
SMRiP35813.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111489. 53 interactors.
IntActiP35813. 33 interactors.
MINTiMINT-2802996.
STRINGi9606.ENSP00000327255.

Chemistry databases

BindingDBiP35813.
ChEMBLiCHEMBL2437.

PTM databases

DEPODiP35813.
iPTMnetiP35813.
PhosphoSitePlusiP35813.

Polymorphism and mutation databases

BioMutaiPPM1A.
DMDMi548442.

Proteomic databases

EPDiP35813.
MaxQBiP35813.
PaxDbiP35813.
PeptideAtlasiP35813.
PRIDEiP35813.

Protocols and materials databases

DNASUi5494.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000325642; ENSP00000327255; ENSG00000100614. [P35813-3]
ENST00000325658; ENSP00000314850; ENSG00000100614. [P35813-2]
ENST00000395076; ENSP00000378514; ENSG00000100614. [P35813-1]
GeneIDi5494.
KEGGihsa:5494.
UCSCiuc001xew.5. human. [P35813-1]

Organism-specific databases

CTDi5494.
DisGeNETi5494.
GeneCardsiPPM1A.
HGNCiHGNC:9275. PPM1A.
HPAiHPA029209.
MIMi606108. gene.
neXtProtiNX_P35813.
OpenTargetsiENSG00000100614.
PharmGKBiPA33603.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0697. Eukaryota.
COG0631. LUCA.
GeneTreeiENSGT00740000115384.
HOGENOMiHOG000233895.
HOVERGENiHBG053647.
InParanoidiP35813.
KOiK04457.
OMAiEPEVYAI.
OrthoDBiEOG091G0AJQ.
PhylomeDBiP35813.
TreeFamiTF313590.

Enzyme and pathway databases

BioCyciZFISH:HS02125-MONOMER.
BRENDAi3.1.3.16. 2681.
ReactomeiR-HSA-2173795. Downregulation of SMAD2/3:SMAD4 transcriptional activity.
R-HSA-380972. Energy dependent regulation of mTOR by LKB1-AMPK.
SignaLinkiP35813.
SIGNORiP35813.

Miscellaneous databases

ChiTaRSiPPM1A. human.
EvolutionaryTraceiP35813.
GeneWikiiPPM1A.
GenomeRNAii5494.
PROiP35813.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000100614.
CleanExiHS_PPM1A.
ExpressionAtlasiP35813. baseline and differential.
GenevisibleiP35813. HS.

Family and domain databases

Gene3Di1.10.10.430. 1 hit.
3.60.40.10. 1 hit.
InterProiIPR015655. PP2C.
IPR000222. PP2C_BS.
IPR012911. PP2C_C.
IPR001932. PPM-type_phosphatase_dom.
[Graphical view]
PANTHERiPTHR13832. PTHR13832. 1 hit.
PfamiPF00481. PP2C. 1 hit.
PF07830. PP2C_C. 1 hit.
[Graphical view]
SMARTiSM00332. PP2Cc. 1 hit.
[Graphical view]
SUPFAMiSSF81601. SSF81601. 1 hit.
SSF81606. SSF81606. 1 hit.
PROSITEiPS01032. PPM_1. 1 hit.
PS51746. PPM_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPPM1A_HUMAN
AccessioniPrimary (citable) accession number: P35813
Secondary accession number(s): B5BU11, J3KNM0, O75551
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: June 1, 1994
Last modified: November 2, 2016
This is version 175 of the entry and version 1 of the sequence. [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, Reference proteome

Documents

  1. Human chromosome 14
    Human chromosome 14: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.