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Protein

Protein phosphatase 1A

Gene

PPM1A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

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 NIK/NF-kappaB signaling Source: UniProtKB
  • negative regulation of SMAD protein complex assembly Source: UniProtKB
  • negative regulation of transcription by RNA polymerase II 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

Keywordsi

Molecular functionHydrolase, Protein phosphatase
LigandMagnesium, Manganese, Metal-binding

Enzyme and pathway databases

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
SABIO-RKiP35813
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

EuPathDBiHostDB:ENSG00000100614.17
HGNCiHGNC:9275 PPM1A
MIMi606108 gene
neXtProtiNX_P35813

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

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
ProteomicsDBi55156
55157 [P35813-2]

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

Show more details

GO - Molecular functioni

  • R-SMAD binding Source: UniProtKB

Protein-protein interaction databases

BioGridi111489, 94 interactors
IntActiP35813, 34 interactors
MINTiP35813
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

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

Phylogenomic databases

eggNOGiKOG0697 Eukaryota
COG0631 LUCA
GeneTreeiENSGT00880000137909
HOGENOMiHOG000233895
HOVERGENiHBG053647
InParanoidiP35813
KOiK04457
OMAiVMSGRVN
OrthoDBiEOG091G0AJQ
PhylomeDBiP35813
TreeFamiTF313590

Family and domain databases

CDDicd00143 PP2Cc, 1 hit
Gene3Di1.10.10.430, 1 hit
3.60.40.10, 1 hit
InterProiView protein in InterPro
IPR015655 PP2C
IPR000222 PP2C_BS
IPR012911 PP2C_C
IPR036580 PP2C_C_sf
IPR036457 PPM-type_dom_sf
IPR001932 PPM-type_phosphatase_dom
PANTHERiPTHR13832 PTHR13832, 1 hit
PfamiView protein in Pfam
PF00481 PP2C, 1 hit
PF07830 PP2C_C, 1 hit
SMARTiView protein in SMART
SM00332 PP2Cc, 1 hit
SUPFAMiSSF81601 SSF81601, 1 hit
SSF81606 SSF81606, 1 hit
PROSITEiView protein in PROSITE
PS01032 PPM_1, 1 hit
PS51746 PPM_2, 1 hit

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

Similar proteinsi

Entry informationi

Entry nameiPPM1A_HUMAN
AccessioniPrimary (citable) accession number: P35813
Secondary accession number(s): B5BU11, J3KNM0, O75551
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: June 1, 1994
Last modified: July 18, 2018
This is version 188 of the entry and version 1 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, 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

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