UniProtKB - P35813 (PPM1A_HUMAN)
Protein phosphatase 1A
PPM1A
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 PublicationsCatalytic activityi
Cofactori
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 60 | Manganese 1Combined sources1 Publication | 1 | |
Metal bindingi | 60 | Manganese 2Combined sources1 Publication | 1 | |
Metal bindingi | 61 | Manganese 1; via carbonyl oxygenCombined sources1 Publication | 1 | |
Metal bindingi | 239 | Manganese 2Combined sources1 Publication | 1 | |
Metal bindingi | 282 | Manganese 2Combined sources1 Publication | 1 |
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
- protein serine phosphatase activity Source: UniProtKB-EC
- protein threonine phosphatase activity Source: UniProtKB-EC
- R-SMAD binding Source: UniProtKB
GO - Biological processi
- 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 canonical Wnt signaling pathway Source: BHF-UCL
- 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
- protein dephosphorylation Source: UniProtKB
- regulation of cell cycle Source: Reactome
Keywordsi
Molecular function | Hydrolase, Protein phosphatase |
Ligand | Magnesium, Manganese, Metal-binding |
Enzyme and pathway databases
BRENDAi | 3.1.3.16, 2681 |
PathwayCommonsi | P35813 |
Reactomei | R-HSA-2173795, Downregulation of SMAD2/3:SMAD4 transcriptional activity R-HSA-380972, Energy dependent regulation of mTOR by LKB1-AMPK |
SABIO-RKi | P35813 |
SignaLinki | P35813 |
SIGNORi | P35813 |
Names & Taxonomyi
Protein namesi | Recommended name: Protein phosphatase 1A (EC:3.1.3.16PROSITE-ProRule annotation1 Publication)Alternative name(s): Protein phosphatase 2C isoform alpha Short name: PP2C-alpha Protein phosphatase IA |
Gene namesi | Name:PPM1A Synonyms:PPPM1A |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:9275, PPM1A |
MIMi | 606108, gene |
neXtProti | NX_P35813 |
VEuPathDBi | HostDB:ENSG00000100614 |
Subcellular locationi
Cytoplasm and Cytosol
- cytosol 1 Publication
Nucleus
- Nucleus 1 Publication
Other locations
- Membrane 2 Publications; Lipid-anchor 2 Publications
Note: Weakly associates at the membrane and N-myristoylation mediates the membrane localization.By similarity
Cytosol
- cytosol Source: HPA
Nucleus
- nucleoplasm Source: Reactome
- nucleus Source: UniProtKB
Plasma Membrane
- plasma membrane Source: HPA
Other locations
- membrane Source: UniProtKB
Keywords - Cellular componenti
Cytoplasm, Membrane, NucleusPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 239 | D → N: No effect on binding SMAD2. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 5494 |
OpenTargetsi | ENSG00000100614 |
PharmGKBi | PA33603 |
Miscellaneous databases
Pharosi | P35813, Tchem |
Chemistry databases
ChEMBLi | CHEMBL2437 |
Genetic variation databases
BioMutai | PPM1A |
DMDMi | 548442 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Initiator methioninei | Removed1 Publication | |||
ChainiPRO_0000057741 | 2 – 382 | Protein phosphatase 1AAdd BLAST | 381 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Lipidationi | 2 | N-myristoyl glycine2 Publications | 1 | |
Modified residuei | 375 | PhosphoserineCombined sources | 1 | |
Modified residuei | 377 | PhosphoserineBy similarity | 1 |
Post-translational modificationi
Keywords - PTMi
Lipoprotein, Myristate, PhosphoproteinProteomic databases
EPDi | P35813 |
jPOSTi | P35813 |
MassIVEi | P35813 |
MaxQBi | P35813 |
PaxDbi | P35813 |
PeptideAtlasi | P35813 |
PRIDEi | P35813 |
ProteomicsDBi | 55156 [P35813-1] 55157 [P35813-2] |
PTM databases
DEPODi | PPM1A |
GlyGeni | P35813, 1 site, 2 O-linked glycans (1 site) |
iPTMneti | P35813 |
MetOSitei | P35813 |
PhosphoSitePlusi | P35813 |
Expressioni
Gene expression databases
Bgeei | ENSG00000100614, Expressed in blood and 250 other tissues |
ExpressionAtlasi | P35813, baseline and differential |
Genevisiblei | P35813, HS |
Organism-specific databases
HPAi | ENSG00000100614, Tissue enhanced (bone) |
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 PublicationsBinary interactionsi
P35813
GO - Molecular functioni
- R-SMAD binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 111489, 119 interactors |
IntActi | P35813, 77 interactors |
MINTi | P35813 |
STRINGi | 9606.ENSP00000327255 |
Chemistry databases
BindingDBi | P35813 |
Miscellaneous databases
RNActi | P35813, protein |
Structurei
Secondary structure
3D structure databases
SMRi | P35813 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P35813 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 23 – 291 | PPM-type phosphatasePROSITE-ProRule annotationAdd BLAST | 269 |
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG0697, Eukaryota |
GeneTreei | ENSGT00940000154832 |
HOGENOMi | CLU_013173_4_0_1 |
InParanoidi | P35813 |
OrthoDBi | 957254at2759 |
PhylomeDBi | P35813 |
TreeFami | TF313590 |
Family and domain databases
CDDi | cd00143, PP2Cc, 1 hit |
Gene3Di | 1.10.10.430, 1 hit 3.60.40.10, 1 hit |
InterProi | View protein in InterPro IPR000222, PP2C_BS IPR012911, PP2C_C IPR036580, PP2C_C_sf IPR036457, PPM-type_dom_sf IPR001932, PPM-type_phosphatase_dom |
Pfami | View protein in Pfam PF00481, PP2C, 1 hit PF07830, PP2C_C, 1 hit |
SMARTi | View protein in SMART SM00332, PP2Cc, 1 hit |
SUPFAMi | SSF81601, SSF81601, 1 hit SSF81606, SSF81606, 1 hit |
PROSITEi | View protein in PROSITE PS01032, PPM_1, 1 hit PS51746, PPM_2, 1 hit |
s (3+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 3 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 3 described isoforms and 5 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
The sequence of this isoform differs from the canonical sequence as follows:
318-324: EIIKKQG → GGSFNKK
325-382: Missing.
Computationally mapped potential isoform sequencesi
There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketE9PKB5 | E9PKB5_HUMAN | Protein phosphatase 1A | PPM1A | 187 | Annotation score: | ||
E9PJN3 | E9PJN3_HUMAN | Protein phosphatase 1A | PPM1A | 148 | Annotation score: | ||
E9PL75 | E9PL75_HUMAN | Protein phosphatase 1A | PPM1A | 128 | Annotation score: | ||
E9PP44 | E9PP44_HUMAN | Protein phosphatase 1A | PPM1A | 164 | Annotation score: | ||
E9PNE1 | E9PNE1_HUMAN | Protein phosphatase 1A | PPM1A | 93 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length | |
---|---|---|---|---|---|
Sequence conflicti | 342 | I → T in AK097843 (PubMed:14702039).Curated | 1 | ||
Isoform 3 (identifier: P35813-3) | |||||
Sequence conflicti | 54 | Q → R in AK097843 (PubMed:14702039).Curated | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_045687 | 1 | M → MFCSGRKWVAEATICTKLMK REKRRMGKRRAKKAKREEKK KGGERRRNEKRGNQMKRMCE RKKYETDLEDQDIM in isoform 3. 1 Publication | 1 | |
Alternative sequenceiVSP_005085 | 318 – 324 | EIIKKQG → GGSFNKK in isoform Alpha-2. 1 Publication | 7 | |
Alternative sequenceiVSP_005086 | 325 – 382 | Missing in isoform Alpha-2. 1 PublicationAdd BLAST | 58 |
Sequence databases
Genome annotation databases
Ensembli | ENST00000325642; ENSP00000327255; ENSG00000100614 [P35813-3] ENST00000325658; ENSP00000314850; ENSG00000100614 [P35813-2] ENST00000395076; ENSP00000378514; ENSG00000100614 |
GeneIDi | 5494 |
KEGGi | hsa:5494 |
MANE-Selecti | ENST00000395076.9; ENSP00000378514.4; NM_021003.5; NP_066283.1 |
UCSCi | uc001xew.5, human [P35813-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1A6Q | X-ray | 2.00 | A | 1-382 | [»] | |
3FXJ | X-ray | 2.50 | A | 1-382 | [»] | |
3FXK | X-ray | 2.10 | A | 1-382 | [»] | |
3FXL | X-ray | 2.30 | A | 1-382 | [»] | |
3FXM | X-ray | 2.50 | A | 1-382 | [»] | |
3FXO | X-ray | 2.50 | A | 1-382 | [»] | |
4RA2 | X-ray | 1.94 | A | 2-368 | [»] | |
4RAF | X-ray | 2.00 | A | 2-368 | [»] | |
4RAG | X-ray | 1.85 | A | 2-368 | [»] | |
6B67 | X-ray | 2.20 | A/B/C | 2-297 | [»] | |
SMRi | P35813 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 111489, 119 interactors |
IntActi | P35813, 77 interactors |
MINTi | P35813 |
STRINGi | 9606.ENSP00000327255 |
Chemistry databases
BindingDBi | P35813 |
ChEMBLi | CHEMBL2437 |
PTM databases
DEPODi | PPM1A |
GlyGeni | P35813, 1 site, 2 O-linked glycans (1 site) |
iPTMneti | P35813 |
MetOSitei | P35813 |
PhosphoSitePlusi | P35813 |
Genetic variation databases
BioMutai | PPM1A |
DMDMi | 548442 |
Proteomic databases
EPDi | P35813 |
jPOSTi | P35813 |
MassIVEi | P35813 |
MaxQBi | P35813 |
PaxDbi | P35813 |
PeptideAtlasi | P35813 |
PRIDEi | P35813 |
ProteomicsDBi | 55156 [P35813-1] 55157 [P35813-2] |
Protocols and materials databases
Antibodypediai | 11485, 472 antibodies from 38 providers |
DNASUi | 5494 |
Genome annotation databases
Ensembli | ENST00000325642; ENSP00000327255; ENSG00000100614 [P35813-3] ENST00000325658; ENSP00000314850; ENSG00000100614 [P35813-2] ENST00000395076; ENSP00000378514; ENSG00000100614 |
GeneIDi | 5494 |
KEGGi | hsa:5494 |
MANE-Selecti | ENST00000395076.9; ENSP00000378514.4; NM_021003.5; NP_066283.1 |
UCSCi | uc001xew.5, human [P35813-1] |
Organism-specific databases
CTDi | 5494 |
DisGeNETi | 5494 |
GeneCardsi | PPM1A |
HGNCi | HGNC:9275, PPM1A |
HPAi | ENSG00000100614, Tissue enhanced (bone) |
MIMi | 606108, gene |
neXtProti | NX_P35813 |
OpenTargetsi | ENSG00000100614 |
PharmGKBi | PA33603 |
VEuPathDBi | HostDB:ENSG00000100614 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG0697, Eukaryota |
GeneTreei | ENSGT00940000154832 |
HOGENOMi | CLU_013173_4_0_1 |
InParanoidi | P35813 |
OrthoDBi | 957254at2759 |
PhylomeDBi | P35813 |
TreeFami | TF313590 |
Enzyme and pathway databases
BRENDAi | 3.1.3.16, 2681 |
PathwayCommonsi | P35813 |
Reactomei | R-HSA-2173795, Downregulation of SMAD2/3:SMAD4 transcriptional activity R-HSA-380972, Energy dependent regulation of mTOR by LKB1-AMPK |
SABIO-RKi | P35813 |
SignaLinki | P35813 |
SIGNORi | P35813 |
Miscellaneous databases
BioGRID-ORCSi | 5494, 9 hits in 1054 CRISPR screens |
ChiTaRSi | PPM1A, human |
EvolutionaryTracei | P35813 |
GeneWikii | PPM1A |
GenomeRNAii | 5494 |
Pharosi | P35813, Tchem |
PROi | PR:P35813 |
RNActi | P35813, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000100614, Expressed in blood and 250 other tissues |
ExpressionAtlasi | P35813, baseline and differential |
Genevisiblei | P35813, HS |
Family and domain databases
CDDi | cd00143, PP2Cc, 1 hit |
Gene3Di | 1.10.10.430, 1 hit 3.60.40.10, 1 hit |
InterProi | View protein in InterPro IPR000222, PP2C_BS IPR012911, PP2C_C IPR036580, PP2C_C_sf IPR036457, PPM-type_dom_sf IPR001932, PPM-type_phosphatase_dom |
Pfami | View protein in Pfam PF00481, PP2C, 1 hit PF07830, PP2C_C, 1 hit |
SMARTi | View protein in SMART SM00332, PP2Cc, 1 hit |
SUPFAMi | SSF81601, SSF81601, 1 hit SSF81606, SSF81606, 1 hit |
PROSITEi | View protein in PROSITE PS01032, PPM_1, 1 hit PS51746, PPM_2, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | PPM1A_HUMAN | |
Accessioni | P35813Primary (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: | February 23, 2022 | |
This is version 210 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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, Reference proteomeDocuments
- Human chromosome 14
Human chromosome 14: entries, gene names and cross-references to MIM - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families