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Protein

Serine/threonine-protein phosphatase 2B catalytic subunit beta isoform

Gene

Ppp3cb

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Calcium-dependent, calmodulin-stimulated protein phosphatase which plays an essential role in the transduction of intracellular Ca2+-mediated signals. Dephosphorylates and activates transcription factor NFATC1. Dephosphorylates and inactivates transcription factor ELK1. Dephosphorylates DARPP32.By similarity

Miscellaneous

Unlike for protein substrates, PPP3CB activity towards synthetic phosphatase substrate p-nitrophenyl phosphate (pNPP) is increased in presence of the immunosuppressant complex FKBP12-FK506.By similarity

Catalytic activityi

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

Cofactori

Protein has several cofactor binding sites:
  • Fe3+By similarityNote: Binds 1 Fe3+ ion per subunit.By similarity
  • Zn2+By similarityNote: Binds 1 zinc ion per subunit.By similarity

Enzyme regulationi

Activated by Ca2+-bound calmodulin following an increase in intracellular Ca2+. At low Ca2+ concentrations, the catalytic subunit (also known as calcineurin A) is inactive and is bound to the regulatory subunit (also known as calcineurin B) in which only two high-affinity binding sites are occupied by Ca2+. In response to elevated calcium levels, the occupancy of the low-affinity sites on calcineurin B by Ca2+ causes a conformational change of the C-terminal regulatory domain of calcineurin A, resulting in the exposure of the calmodulin-binding domain and in the partial activation of calcineurin A. The subsequent binding of Ca2+-bound calmodulin leads to the displacement of the autoinhibitory domain from the active site and possibly of the autoinhibitory segment from the substrate binding site which fully activates calcineurin A.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi99IronBy similarity1
Metal bindingi101Iron; via tele nitrogenBy similarity1
Metal bindingi127IronBy similarity1
Metal bindingi127ZincBy similarity1
Metal bindingi159ZincBy similarity1
Active sitei160Proton donorBy similarity1
Metal bindingi208Zinc; via tele nitrogenBy similarity1
Metal bindingi290Zinc; via pros nitrogenBy similarity1

GO - Molecular functioni

GO - Biological processi

  • calcineurin-NFAT signaling cascade Source: MGI
  • calcium ion regulated exocytosis Source: UniProtKB
  • cellular response to drug Source: UniProtKB
  • heart development Source: MGI
  • locomotion involved in locomotory behavior Source: MGI
  • lymphangiogenesis Source: MGI
  • negative regulation of T cell mediated cytotoxicity Source: MGI
  • positive regulation of insulin secretion involved in cellular response to glucose stimulus Source: UniProtKB
  • positive regulation of transcription by RNA polymerase II Source: MGI
  • protein dephosphorylation Source: UniProtKB
  • protein phosphorylation Source: UniProtKB
  • regulation of gene expression Source: MGI
  • regulation of insulin secretion Source: UniProtKB
  • response to cytokine Source: MGI
  • social behavior Source: Ensembl
  • T cell differentiation Source: MGI
  • T cell homeostasis Source: MGI

Keywordsi

Molecular functionCalmodulin-binding, Hydrolase, Protein phosphatase
LigandIron, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-MMU-2025928 Calcineurin activates NFAT
R-MMU-2871809 FCERI mediated Ca+2 mobilization
R-MMU-4086398 Ca2+ pathway
R-MMU-5607763 CLEC7A (Dectin-1) induces NFAT activation

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein phosphatase 2B catalytic subunit beta isoform (EC:3.1.3.16By similarity)
Alternative name(s):
CAM-PRP catalytic subunit
Calmodulin-dependent calcineurin A subunit beta isoform
Short name:
CNA betaBy similarity
Gene namesi
Name:Ppp3cb
Synonyms:Calnb
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 14

Organism-specific databases

MGIiMGI:107163 Ppp3cb

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00000588262 – 525Serine/threonine-protein phosphatase 2B catalytic subunit beta isoformAdd BLAST524

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineBy similarity1
Modified residuei479PhosphoserineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

MaxQBiP48453
PaxDbiP48453
PRIDEiP48453

PTM databases

iPTMnetiP48453
PhosphoSitePlusiP48453

Expressioni

Tissue specificityi

Two isoforms in Ehrlich ascites tumor (EAT) is demonstrated by polymerase chain reaction specific primers to the catalytic and calmodulin-binding domain, respectively. Isoform 1 is of medium abundance in EAT cells.1 Publication

Gene expression databases

BgeeiENSMUSG00000021816
ExpressionAtlasiP48453 baseline and differential
GenevisibleiP48453 MM

Interactioni

Subunit structurei

Forms a complex composed of a calmodulin-dependent catalytic subunit (also known as calcineurin A) and a regulatory Ca2+-binding subunit (also known as calcineurin B). There are three catalytic subunits, each encoded by a separate gene (PPP3CA, PPP3CB, and PPP3CC) and two regulatory subunits which are also encoded by separate genes (PPP3R1 and PPP3R2). In response to an increase in Ca2+ intracellular levels, forms a complex composed of PPP3CB/calcineurin A, calcineurin B and calmodulin. Interacts (via calcineurin B binding domain) with regulatory subunit PPP3R1/calcineurin B. Interacts (via calmodulin-binding domain) with calmodulin; the interaction depends on calmodulin binding to Ca2+.By similarity

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi2023457 interactors.
IntActiP48453 13 interactors.
MINTiP48453
STRINGi10090.ENSMUSP00000125722

Structurei

3D structure databases

ProteinModelPortaliP48453
SMRiP48453
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni65 – 356CatalyticBy similarityAdd BLAST292
Regioni357 – 379Calcineurin B bindingBy similarityAdd BLAST23
Regioni402 – 416Calmodulin-bindingBy similarityAdd BLAST15
Regioni417 – 424Autoinhibitory segmentBy similarity8
Regioni475 – 497Autoinhibitory domainBy similarityAdd BLAST23

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi11 – 20Poly-ProSequence analysis10

Domaini

The poly-Pro domain may confer substrate specificity.By similarity
The autoinhibitory domain prevents access to the catalytic site.By similarity
The autoinhibitory segment prevents access to the substrate binding site.By similarity

Sequence similaritiesi

Belongs to the PPP phosphatase family. PP-2B subfamily.Curated

Phylogenomic databases

eggNOGiKOG0375 Eukaryota
COG0639 LUCA
GeneTreeiENSGT00530000063087
HOGENOMiHOG000172699
HOVERGENiHBG002819
InParanoidiP48453
KOiK04348
OMAiQFDVKVG
OrthoDBiEOG091G094R
TreeFamiTF105557

Family and domain databases

Gene3Di3.60.21.101 hit
InterProiView protein in InterPro
IPR004843 Calcineurin-like_PHP_ApaH
IPR029052 Metallo-depent_PP-like
IPR006186 Ser/Thr-sp_prot-phosphatase
PfamiView protein in Pfam
PF00149 Metallophos, 1 hit
PRINTSiPR00114 STPHPHTASE
SMARTiView protein in SMART
SM00156 PP2Ac, 1 hit
PROSITEiView protein in PROSITE
PS00125 SER_THR_PHOSPHATASE, 1 hit

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 2 (identifier: P48453-1) [UniParc]FASTAAdd to basket
Also known as: 2B2

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
MAAPEPARAA PPPPPPPPPP LGADRVVKAV PFPPTHRLTS EEVFDMDGIP
60 70 80 90 100
RVDVLKNHLV KEGRVDEEIA LRIINEGAAI LRREKTMIEV EAPITVCGDI
110 120 130 140 150
HGQFFDLMKL FEVGGSPANT RYLFLGDYVD RGYFSIECVL YLWVLKILYP
160 170 180 190 200
STLFLLRGNH ECRHLTEYFT FKQECKIKYS ERVYEACMEA FDSLPLAALL
210 220 230 240 250
NQQFLCVHGG LSPEIHTLDD IRRLDRFKEP PAFGPMCDLL WSDPSEDFGN
260 270 280 290 300
EKSQEHFSHN TVRGCSYFYN YPAVCEFLQN NNLLSIIRAH EAQDAGYRMY
310 320 330 340 350
RKSQTTGFPS LITIFSAPNY LDVYNNKAAV LKYENNVMNI RQFNCSPHPY
360 370 380 390 400
WLPNFMDVFT WSLPFVGEKV TEMLVNVLSI CSDDELMTEG EDQFDVGSAA
410 420 430 440 450
ARKEIIRNKI RAIGKMARVF SVLREESESV LTLKGLTPTG MLPSGVLAGG
460 470 480 490 500
RQTLQSATVE AIEAEKAIRG FSPPHRICSF EEAKGLDRIN ERMPPRKDAV
510 520
QQDGFNSLNT AHTTENHGTG NHSAQ
Length:525
Mass (Da):59,173
Last modified:November 9, 2004 - v2
Checksum:i5E73BA3100BE2337
GO
Isoform 1 (identifier: P48453-2) [UniParc]FASTAAdd to basket
Also known as: 2B1

The sequence of this isoform differs from the canonical sequence as follows:
     387-406: MTEGEDQFDVGSAAARKEII → GSEEDGFDGATAAARKEVI

Show »
Length:524
Mass (Da):58,929
Checksum:iD5348F544E5ACB35
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti481E → G in AAA37411 (PubMed:1659808).Curated1
Sequence conflicti523 – 524SA → TP in AAA37411 (PubMed:1659808).Curated2

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_011856387 – 406MTEGE…RKEII → GSEEDGFDGATAAARKEVI in isoform 1. 1 PublicationAdd BLAST20

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC066000 mRNA Translation: AAH66000.1
M81483 mRNA Translation: AAA37411.1
CCDSiCCDS26846.1 [P48453-1]
PIRiJT0976
RefSeqiNP_001297355.1, NM_001310426.1
NP_001297356.1, NM_001310427.1
NP_032940.1, NM_008914.3 [P48453-1]
UniGeneiMm.274432

Genome annotation databases

EnsembliENSMUST00000159027; ENSMUSP00000125722; ENSMUSG00000021816 [P48453-1]
GeneIDi19056
KEGGimmu:19056
UCSCiuc007sjx.2 mouse [P48453-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiPP2BB_MOUSE
AccessioniPrimary (citable) accession number: P48453
Secondary accession number(s): Q6NZR4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: November 9, 2004
Last modified: April 25, 2018
This is version 163 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome