P62140 · PP1B_HUMAN
- ProteinSerine/threonine-protein phosphatase PP1-beta catalytic subunit
- GenePPP1CB
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids327 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Protein phosphatase that associates with over 200 regulatory proteins to form highly specific holoenzymes which dephosphorylate hundreds of biological targets. Protein phosphatase (PP1) is essential for cell division, it participates in the regulation of glycogen metabolism, muscle contractility and protein synthesis. Involved in regulation of ionic conductances and long-term synaptic plasticity. Component of the PTW/PP1 phosphatase complex, which plays a role in the control of chromatin structure and cell cycle progression during the transition from mitosis into interphase. In balance with CSNK1D and CSNK1E, determines the circadian period length, through the regulation of the speed and rhythmicity of PER1 and PER2 phosphorylation. May dephosphorylate CSNK1D and CSNK1E. Dephosphorylates the 'Ser-418' residue of FOXP3 in regulatory T-cells (Treg) from patients with rheumatoid arthritis, thereby inactivating FOXP3 and rendering Treg cells functionally defective (PubMed:23396208).
Catalytic activity
- H2O + O-phospho-L-seryl-[protein] = L-seryl-[protein] + phosphate
Cofactor
Note: Binds 2 manganese ions per subunit.
Activity regulation
Inhibited by the toxins okadaic acid, tautomycin and microcystin Leu-Arg (By similarity).
The phosphatase activity of the PPP1R15A-PP1 complex toward EIF2S1 is specifically inhibited by Salubrinal, a drug that protects cells from endoplasmic reticulum stress
The phosphatase activity of the PPP1R15A-PP1 complex toward EIF2S1 is specifically inhibited by Salubrinal, a drug that protects cells from endoplasmic reticulum stress
Features
Showing features for binding site, active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 63 | Mn2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 65 | Mn2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 91 | Mn2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 91 | Mn2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 123 | Mn2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: N | ||||||
Active site | 124 | Proton donor | ||||
Sequence: H | ||||||
Binding site | 172 | Mn2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 247 | Mn2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: H |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Cellular Component | cytosol | |
Cellular Component | extracellular exosome | |
Cellular Component | focal adhesion | |
Cellular Component | nucleolus | |
Cellular Component | nucleoplasm | |
Cellular Component | nucleus | |
Cellular Component | PTW/PP1 phosphatase complex | |
Molecular Function | metal ion binding | |
Molecular Function | myosin phosphatase activity | |
Molecular Function | myosin-light-chain-phosphatase activity | |
Molecular Function | phosphatase activity | |
Molecular Function | protein kinase binding | |
Molecular Function | protein serine/threonine phosphatase activity | |
Biological Process | cell division | |
Biological Process | circadian regulation of gene expression | |
Biological Process | entrainment of circadian clock by photoperiod | |
Biological Process | glycogen metabolic process | |
Biological Process | MAPK cascade | |
Biological Process | protein dephosphorylation | |
Biological Process | regulation of cell adhesion | |
Biological Process | regulation of circadian rhythm |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameSerine/threonine-protein phosphatase PP1-beta catalytic subunit
- EC number
- Short namesPP-1B; PPP1CD
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP62140
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Highly mobile in cells and can be relocalized through interaction with targeting subunits. In the presence of PPP1R8 relocalizes from the nucleus to nuclear speckles.
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Noonan syndrome-like disorder with loose anagen hair 2 (NSLH2)
- Note
- DescriptionA syndrome characterized by Noonan dysmorphic features such as macrocephaly, high forehead, hypertelorism, palpebral ptosis, low-set and posteriorly rotated ears, short and webbed neck, pectus anomalies, in association with pluckable, sparse, thin and slow-growing hair.
- See alsoMIM:617506
Natural variants in NSLH2
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_076839 | 49 | P>R | in NSLH2; dbSNP:rs886037952 | |
VAR_076840 | 56 | A>P | in NSLH2; dbSNP:rs1114167429 | |
VAR_079189 | 183 | E>A | in NSLH2; dbSNP:rs886037954 | |
VAR_079190 | 183 | E>V | in NSLH2; dbSNP:rs886037954 | |
VAR_079191 | 252 | D>Y | in NSLH2; dbSNP:rs886037953 | |
VAR_079192 | 274 | E>K | in NSLH2; uncertain significance; dbSNP:rs886037955 |
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_076839 | 49 | in NSLH2; dbSNP:rs886037952 | |||
Sequence: P → R | ||||||
Natural variant | VAR_076840 | 56 | in NSLH2; dbSNP:rs1114167429 | |||
Sequence: A → P | ||||||
Natural variant | VAR_079189 | 183 | in NSLH2; dbSNP:rs886037954 | |||
Sequence: E → A | ||||||
Natural variant | VAR_079190 | 183 | in NSLH2; dbSNP:rs886037954 | |||
Sequence: E → V | ||||||
Natural variant | VAR_079191 | 252 | in NSLH2; dbSNP:rs886037953 | |||
Sequence: D → Y | ||||||
Natural variant | VAR_079192 | 274 | in NSLH2; uncertain significance; dbSNP:rs886037955 | |||
Sequence: E → K |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 206 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for initiator methionine, modified residue, chain, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Initiator methionine | 1 | UniProt | Removed | ||||
Sequence: M | |||||||
Modified residue | 2 | UniProt | N-acetylalanine | ||||
Sequence: A | |||||||
Chain | PRO_0000058779 | 2-327 | UniProt | Serine/threonine-protein phosphatase PP1-beta catalytic subunit | |||
Sequence: ADGELNVDSLITRLLEVRGCRPGKIVQMTEAEVRGLCIKSREIFLSQPILLELEAPLKICGDIHGQYTDLLRLFEYGGFPPEANYLFLGDYVDRGKQSLETICLLLAYKIKYPENFFLLRGNHECASINRIYGFYDECKRRFNIKLWKTFTDCFNCLPIAAIVDEKIFCCHGGLSPDLQSMEQIRRIMRPTDVPDTGLLCDLLWSDPDKDVQGWGENDRGVSFTFGADVVSKFLNRHDLDLICRAHQVVEDGYEFFAKRQLVTLFSAPNYCGEFDNAGGMMSVDETLMCSFQILKPSEKKAKYQYGGLNSGRPVTPPRTANPPKKR | |||||||
Modified residue (large scale data) | 47 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 128 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 176 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 181 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 304 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 306 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 311 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 316 | UniProt | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 316 | PRIDE | Phosphothreonine | ||||
Sequence: T |
Keywords
- PTM
Proteomic databases
2D gel databases
PTM databases
Expression
Induction
Up-regulated in synovial fluid mononuclear cells and peripheral blood mononuclear cells from patients with rheumatoid arthritis.
Gene expression databases
Organism-specific databases
Interaction
Subunit
PP1 comprises a catalytic subunit, PPP1CA, PPP1CB or PPP1CC, which is folded into its native form by inhibitor 2 and glycogen synthetase kinase 3, and then complexed to one or several targeting or regulatory subunits. The targeting or regulatory subunits determine the substrate specificity of PP1. PPP1R12A, PPP1R12B and PPP1R12C mediate binding to myosin. PPP1R3A (in skeletal muscle), PPP1R3B (in liver), PPP1R3C, PPP1R3D and PPP1R3F (in brain) mediate binding to glycogen. Part of a complex containing PPP1R15B, PP1 and NCK1/2 (By similarity).
Interacts with PPP1R7 and PPP1R12C. PPP1R15A and PPP1R15B mediate binding to EIF2S1. Interacts with PPP1R16B. Component of the PTW/PP1 phosphatase complex, composed of PPP1R10/PNUTS, TOX4, WDR82, and PPP1CA or PPP1CB or PPP1CC. Interacts with PPP1R8. Interacts with TRIM28; the interaction is weak. Interacts with PPP1R12A and NUAK1; the interaction is direct. Interacts with FOXP3. Interacts with RRP1B (PubMed:20926688).
Interacts with SERPINE1 (PubMed:28296156).
Interacts with LZTR1 (PubMed:30368668).
Interacts with PPP1R7 and PPP1R12C. PPP1R15A and PPP1R15B mediate binding to EIF2S1. Interacts with PPP1R16B. Component of the PTW/PP1 phosphatase complex, composed of PPP1R10/PNUTS, TOX4, WDR82, and PPP1CA or PPP1CB or PPP1CC. Interacts with PPP1R8. Interacts with TRIM28; the interaction is weak. Interacts with PPP1R12A and NUAK1; the interaction is direct. Interacts with FOXP3. Interacts with RRP1B (PubMed:20926688).
Interacts with SERPINE1 (PubMed:28296156).
Interacts with LZTR1 (PubMed:30368668).
Binary interactions
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 305-327 | Disordered | ||||
Sequence: QYGGLNSGRPVTPPRTANPPKKR |
Sequence similarities
Belongs to the PPP phosphatase family. PP-1 subfamily.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length327
- Mass (Da)37,187
- Last updated2007-01-23 v3
- ChecksumE8356022E9B94ECD
Computationally mapped potential isoform sequences
There are 8 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
C9J9S3 | C9J9S3_HUMAN | PPP1CB | 125 | ||
F8WE71 | F8WE71_HUMAN | PPP1CB | 64 | ||
C9JP48 | C9JP48_HUMAN | PPP1CB | 138 | ||
B4DJ75 | B4DJ75_HUMAN | PPP1CB | 299 | ||
H0Y3Y6 | H0Y3Y6_HUMAN | PPP1CB | 207 | ||
A0A8V8TRH9 | A0A8V8TRH9_HUMAN | PPP1CB | 368 | ||
A0A8V8TR83 | A0A8V8TR83_HUMAN | PPP1CB | 92 | ||
A0A8V8TQ71 | A0A8V8TQ71_HUMAN | PPP1CB | 316 |
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 51 | in Ref. 5; AAV38549 | ||||
Sequence: L → P |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
X80910 EMBL· GenBank· DDBJ | CAA56870.1 EMBL· GenBank· DDBJ | mRNA | ||
U11005 EMBL· GenBank· DDBJ | AAA85093.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U10998 EMBL· GenBank· DDBJ | AAA85093.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U10999 EMBL· GenBank· DDBJ | AAA85093.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U11000 EMBL· GenBank· DDBJ | AAA85093.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U11001 EMBL· GenBank· DDBJ | AAA85093.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U11002 EMBL· GenBank· DDBJ | AAA85093.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U11003 EMBL· GenBank· DDBJ | AAA85093.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U11004 EMBL· GenBank· DDBJ | AAA85093.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF092905 EMBL· GenBank· DDBJ | AAF01137.1 EMBL· GenBank· DDBJ | mRNA | ||
CR542263 EMBL· GenBank· DDBJ | CAG47059.1 EMBL· GenBank· DDBJ | mRNA | ||
CR542285 EMBL· GenBank· DDBJ | CAG47080.1 EMBL· GenBank· DDBJ | mRNA | ||
BT019744 EMBL· GenBank· DDBJ | AAV38549.1 EMBL· GenBank· DDBJ | mRNA | ||
AK312329 EMBL· GenBank· DDBJ | BAG35251.1 EMBL· GenBank· DDBJ | mRNA | ||
BX647970 EMBL· GenBank· DDBJ | - | mRNA | No translation available. | |
AC097724 EMBL· GenBank· DDBJ | AAY24124.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471053 EMBL· GenBank· DDBJ | EAX00527.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471053 EMBL· GenBank· DDBJ | EAX00528.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471053 EMBL· GenBank· DDBJ | EAX00529.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471053 EMBL· GenBank· DDBJ | EAX00530.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC002697 EMBL· GenBank· DDBJ | AAH02697.1 EMBL· GenBank· DDBJ | mRNA | ||
BC012045 EMBL· GenBank· DDBJ | AAH12045.1 EMBL· GenBank· DDBJ | mRNA |