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Protein

Serine/threonine-protein phosphatase PP1-beta catalytic subunit

Gene

PPP1CB

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

Functioni

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).3 Publications

Caution

Was originally thought to be part of the MLL5-L complex, at least composed of KMT2E, STK38, PPP1CA, PPP1CB, PPP1CC, HCFC1, ACTB and OGT (PubMed:19377461). However, the corresponding article has been retracted (PubMed:24336203).2 Publications

Catalytic activityi

[a protein]-serine/threonine phosphate + H2O = [a protein]-serine/threonine + phosphate.
[Myosin light-chain] phosphate + H2O = [myosin light-chain] + phosphate.

Cofactori

Mn2+By similarityNote: Binds 2 manganese ions per subunit.By similarity

Activity regulationi

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.By similarity1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi63Manganese 1By similarity1
Metal bindingi65Manganese 1By similarity1
Metal bindingi91Manganese 1By similarity1
Metal bindingi91Manganese 2By similarity1
Metal bindingi123Manganese 2By similarity1
Active sitei124Proton donorBy similarity1
Metal bindingi172Manganese 2By similarity1
Metal bindingi247Manganese 2By similarity1

GO - Molecular functioni

  • metal ion binding Source: UniProtKB-KW
  • myosin-light-chain-phosphatase activity Source: UniProtKB
  • myosin phosphatase activity Source: UniProtKB
  • phosphatase activity Source: UniProtKB
  • protein kinase binding Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Protein phosphatase
Biological processBiological rhythms, Carbohydrate metabolism, Cell cycle, Cell division, Glycogen metabolism
LigandManganese, Metal-binding

Enzyme and pathway databases

ReactomeiR-HSA-163560 Triglyceride catabolism
R-HSA-2173788 Downregulation of TGF-beta receptor signaling
R-HSA-2565942 Regulation of PLK1 Activity at G2/M Transition
R-HSA-400253 Circadian Clock
R-HSA-5625740 RHO GTPases activate PKNs
R-HSA-5625900 RHO GTPases activate CIT
R-HSA-5627117 RHO GTPases Activate ROCKs
R-HSA-5627123 RHO GTPases activate PAKs
SIGNORiP62140

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein phosphatase PP1-beta catalytic subunit (EC:3.1.3.16, EC:3.1.3.53)
Short name:
PP-1B
Short name:
PPP1CD
Gene namesi
Name:PPP1CB
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000213639.9
HGNCiHGNC:9282 PPP1CB
MIMi600590 gene
neXtProtiNX_P62140

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, Nucleus

Pathology & Biotechi

Involvement in diseasei

Noonan syndrome-like disorder with loose anagen hair 2 (NSLH2)4 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease 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 also OMIM:617506
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07683949P → R in NSLH2. 4 PublicationsCorresponds to variant dbSNP:rs886037952EnsemblClinVar.1
Natural variantiVAR_07684056A → P in NSLH2. 1 PublicationCorresponds to variant dbSNP:rs1114167429Ensembl.1
Natural variantiVAR_079189183E → A in NSLH2. 1 PublicationCorresponds to variant dbSNP:rs886037954EnsemblClinVar.1
Natural variantiVAR_079190183E → V in NSLH2. 1 PublicationCorresponds to variant dbSNP:rs886037954EnsemblClinVar.1
Natural variantiVAR_079191252D → Y in NSLH2. 1 PublicationCorresponds to variant dbSNP:rs886037953EnsemblClinVar.1
Natural variantiVAR_079192274E → K in NSLH2; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs886037955EnsemblClinVar.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi5500
MalaCardsiPPP1CB
MIMi617506 phenotype
OpenTargetsiENSG00000213639
PharmGKBiPA33610

Polymorphism and mutation databases

BioMutaiPPP1CB
DMDMi49065814

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources1 Publication
ChainiPRO_00000587792 – 327Serine/threonine-protein phosphatase PP1-beta catalytic subunitAdd BLAST326

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1 Publication1
Modified residuei316PhosphothreonineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP62140
PaxDbiP62140
PeptideAtlasiP62140
PRIDEiP62140
ProteomicsDBi57367
TopDownProteomicsiP62140

2D gel databases

OGPiP37140

PTM databases

DEPODiP62140
iPTMnetiP62140
PhosphoSitePlusiP62140
SwissPalmiP62140

Expressioni

Inductioni

Up-regulated in synovial fluid mononuclear cells and peripheral blood mononuclear cells from patients with rheumatoid arthritis.1 Publication

Gene expression databases

BgeeiENSG00000213639 Expressed in 235 organ(s), highest expression level in lower esophagus
CleanExiHS_PPP1CB
ExpressionAtlasiP62140 baseline and differential
GenevisibleiP62140 HS

Organism-specific databases

HPAiCAB022558
CAB069426
HPA065425

Interactioni

Subunit structurei

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).By similarity10 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi111494, 269 interactors
DIPiDIP-33220N
IntActiP62140, 240 interactors
MINTiP62140
STRINGi9606.ENSP00000296122

Structurei

3D structure databases

ProteinModelPortaliP62140
SMRiP62140
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the PPP phosphatase family. PP-1 subfamily.Curated

Phylogenomic databases

eggNOGiENOG410IN85 Eukaryota
ENOG410XPVF LUCA
GeneTreeiENSGT00530000062911
HOGENOMiHOG000172697
HOVERGENiHBG000216
InParanoidiP62140
KOiK06269
OMAiEEHEIRY
OrthoDBiEOG091G0EKF
PhylomeDBiP62140
TreeFamiTF354243

Family and domain databases

Gene3Di3.60.21.10, 1 hit
InterProiView protein in InterPro
IPR004843 Calcineurin-like_PHP_ApaH
IPR029052 Metallo-depent_PP-like
IPR037979 PPP1CA/PPP1CB
IPR006186 Ser/Thr-sp_prot-phosphatase
IPR031675 STPPase_N
PANTHERiPTHR11668:SF377 PTHR11668:SF377, 1 hit
PfamiView protein in Pfam
PF00149 Metallophos, 1 hit
PF16891 STPPase_N, 1 hit
PRINTSiPR00114 STPHPHTASE
SMARTiView protein in SMART
SM00156 PP2Ac, 1 hit
PROSITEiView protein in PROSITE
PS00125 SER_THR_PHOSPHATASE, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

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

This entry has 1 described isoform and 5 potential isoforms that are computationally mapped.Show allAlign All

P62140-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MADGELNVDS LITRLLEVRG CRPGKIVQMT EAEVRGLCIK SREIFLSQPI
60 70 80 90 100
LLELEAPLKI CGDIHGQYTD LLRLFEYGGF PPEANYLFLG DYVDRGKQSL
110 120 130 140 150
ETICLLLAYK IKYPENFFLL RGNHECASIN RIYGFYDECK RRFNIKLWKT
160 170 180 190 200
FTDCFNCLPI AAIVDEKIFC CHGGLSPDLQ SMEQIRRIMR PTDVPDTGLL
210 220 230 240 250
CDLLWSDPDK DVQGWGENDR GVSFTFGADV VSKFLNRHDL DLICRAHQVV
260 270 280 290 300
EDGYEFFAKR QLVTLFSAPN YCGEFDNAGG MMSVDETLMC SFQILKPSEK
310 320
KAKYQYGGLN SGRPVTPPRT ANPPKKR
Length:327
Mass (Da):37,187
Last modified:January 23, 2007 - v3
Checksum:iE8356022E9B94ECD
GO

Computationally mapped potential isoform sequencesi

There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E7ETD8E7ETD8_HUMAN
Serine/threonine-protein phosphatas...
PPP1CB
169Annotation score:
C9JP48C9JP48_HUMAN
Serine/threonine-protein phosphatas...
PPP1CB
138Annotation score:
C9J9S3C9J9S3_HUMAN
Serine/threonine-protein phosphatas...
PPP1CB
125Annotation score:
H0Y3Y6H0Y3Y6_HUMAN
Serine/threonine-protein phosphatas...
PPP1CB
82Annotation score:
F8WE71F8WE71_HUMAN
Serine/threonine-protein phosphatas...
PPP1CB
64Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti51L → P in AAV38549 (Ref. 5) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07683949P → R in NSLH2. 4 PublicationsCorresponds to variant dbSNP:rs886037952EnsemblClinVar.1
Natural variantiVAR_07684056A → P in NSLH2. 1 PublicationCorresponds to variant dbSNP:rs1114167429Ensembl.1
Natural variantiVAR_079189183E → A in NSLH2. 1 PublicationCorresponds to variant dbSNP:rs886037954EnsemblClinVar.1
Natural variantiVAR_079190183E → V in NSLH2. 1 PublicationCorresponds to variant dbSNP:rs886037954EnsemblClinVar.1
Natural variantiVAR_079191252D → Y in NSLH2. 1 PublicationCorresponds to variant dbSNP:rs886037953EnsemblClinVar.1
Natural variantiVAR_079192274E → K in NSLH2; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs886037955EnsemblClinVar.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X80910 mRNA Translation: CAA56870.1
U11005
, U10998, U10999, U11000, U11001, U11002, U11003, U11004 Genomic DNA Translation: AAA85093.1
AF092905 mRNA Translation: AAF01137.1
CR542263 mRNA Translation: CAG47059.1
CR542285 mRNA Translation: CAG47080.1
BT019744 mRNA Translation: AAV38549.1
AK312329 mRNA Translation: BAG35251.1
BX647970 mRNA No translation available.
AC097724 Genomic DNA Translation: AAY24124.1
CH471053 Genomic DNA Translation: EAX00527.1
CH471053 Genomic DNA Translation: EAX00528.1
CH471053 Genomic DNA Translation: EAX00529.1
CH471053 Genomic DNA Translation: EAX00530.1
BC002697 mRNA Translation: AAH02697.1
BC012045 mRNA Translation: AAH12045.1
CCDSiCCDS33169.1
PIRiS41052
RefSeqiNP_002700.1, NM_002709.2
NP_996759.1, NM_206876.1
UniGeneiHs.702907

Genome annotation databases

EnsembliENST00000296122; ENSP00000296122; ENSG00000213639
ENST00000358506; ENSP00000351298; ENSG00000213639
ENST00000395366; ENSP00000378769; ENSG00000213639
GeneIDi5500
KEGGihsa:5500

Similar proteinsi

Cross-referencesi

Web resourcesi

Protein Spotlight

The things we forget - Issue 32 of March 2003

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X80910 mRNA Translation: CAA56870.1
U11005
, U10998, U10999, U11000, U11001, U11002, U11003, U11004 Genomic DNA Translation: AAA85093.1
AF092905 mRNA Translation: AAF01137.1
CR542263 mRNA Translation: CAG47059.1
CR542285 mRNA Translation: CAG47080.1
BT019744 mRNA Translation: AAV38549.1
AK312329 mRNA Translation: BAG35251.1
BX647970 mRNA No translation available.
AC097724 Genomic DNA Translation: AAY24124.1
CH471053 Genomic DNA Translation: EAX00527.1
CH471053 Genomic DNA Translation: EAX00528.1
CH471053 Genomic DNA Translation: EAX00529.1
CH471053 Genomic DNA Translation: EAX00530.1
BC002697 mRNA Translation: AAH02697.1
BC012045 mRNA Translation: AAH12045.1
CCDSiCCDS33169.1
PIRiS41052
RefSeqiNP_002700.1, NM_002709.2
NP_996759.1, NM_206876.1
UniGeneiHs.702907

3D structure databases

ProteinModelPortaliP62140
SMRiP62140
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111494, 269 interactors
DIPiDIP-33220N
IntActiP62140, 240 interactors
MINTiP62140
STRINGi9606.ENSP00000296122

PTM databases

DEPODiP62140
iPTMnetiP62140
PhosphoSitePlusiP62140
SwissPalmiP62140

Polymorphism and mutation databases

BioMutaiPPP1CB
DMDMi49065814

2D gel databases

OGPiP37140

Proteomic databases

EPDiP62140
PaxDbiP62140
PeptideAtlasiP62140
PRIDEiP62140
ProteomicsDBi57367
TopDownProteomicsiP62140

Protocols and materials databases

DNASUi5500
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000296122; ENSP00000296122; ENSG00000213639
ENST00000358506; ENSP00000351298; ENSG00000213639
ENST00000395366; ENSP00000378769; ENSG00000213639
GeneIDi5500
KEGGihsa:5500

Organism-specific databases

CTDi5500
DisGeNETi5500
EuPathDBiHostDB:ENSG00000213639.9
GeneCardsiPPP1CB
HGNCiHGNC:9282 PPP1CB
HPAiCAB022558
CAB069426
HPA065425
MalaCardsiPPP1CB
MIMi600590 gene
617506 phenotype
neXtProtiNX_P62140
OpenTargetsiENSG00000213639
PharmGKBiPA33610
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IN85 Eukaryota
ENOG410XPVF LUCA
GeneTreeiENSGT00530000062911
HOGENOMiHOG000172697
HOVERGENiHBG000216
InParanoidiP62140
KOiK06269
OMAiEEHEIRY
OrthoDBiEOG091G0EKF
PhylomeDBiP62140
TreeFamiTF354243

Enzyme and pathway databases

ReactomeiR-HSA-163560 Triglyceride catabolism
R-HSA-2173788 Downregulation of TGF-beta receptor signaling
R-HSA-2565942 Regulation of PLK1 Activity at G2/M Transition
R-HSA-400253 Circadian Clock
R-HSA-5625740 RHO GTPases activate PKNs
R-HSA-5625900 RHO GTPases activate CIT
R-HSA-5627117 RHO GTPases Activate ROCKs
R-HSA-5627123 RHO GTPases activate PAKs
SIGNORiP62140

Miscellaneous databases

ChiTaRSiPPP1CB human
GeneWikiiPPP1CB
GenomeRNAii5500
PROiPR:P62140
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000213639 Expressed in 235 organ(s), highest expression level in lower esophagus
CleanExiHS_PPP1CB
ExpressionAtlasiP62140 baseline and differential
GenevisibleiP62140 HS

Family and domain databases

Gene3Di3.60.21.10, 1 hit
InterProiView protein in InterPro
IPR004843 Calcineurin-like_PHP_ApaH
IPR029052 Metallo-depent_PP-like
IPR037979 PPP1CA/PPP1CB
IPR006186 Ser/Thr-sp_prot-phosphatase
IPR031675 STPPase_N
PANTHERiPTHR11668:SF377 PTHR11668:SF377, 1 hit
PfamiView protein in Pfam
PF00149 Metallophos, 1 hit
PF16891 STPPase_N, 1 hit
PRINTSiPR00114 STPHPHTASE
SMARTiView protein in SMART
SM00156 PP2Ac, 1 hit
PROSITEiView protein in PROSITE
PS00125 SER_THR_PHOSPHATASE, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiPP1B_HUMAN
AccessioniPrimary (citable) accession number: P62140
Secondary accession number(s): B2R5V4
, D6W565, P37140, Q5U087, Q6FG45
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 21, 2004
Last sequence update: January 23, 2007
Last modified: November 7, 2018
This is version 169 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

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. Protein Spotlight
    Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries
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