P48453

SS
Gene name
Ppp3cb (Calnb)
Protein name
Serine/threonine-protein phosphatase 2B catalytic subunit beta isoform
Names
EC 3.1.3.16 , CAM-PRP catalytic subunit , Calmodulin-dependent calcineurin A subunit beta isoform , CNA beta
Species
Mus musculus (Mouse)
KEGG Pathway
mmu:19056
EC number
3.1.3.16: Phosphoric monoester hydrolases
Protein Class

Descriptions

Calcium-dependent, calmodulin-stimulated protein phosphatase calcineurin (CN) plays a role in the transduction of intracellular Ca2+-dependent signals. CN is a heterodimer composed of a catalytic subunit A (CNA) and an essential regulatory subunit B (CNB). <br>CNA contains two autoinhibitory regions, which interfere with the function of the catalytic domain: autoinhibitory segment (AIS) and autoinhibitory domain (AID). The AIS interacts with a hydrophobic intersubunit groove formed at the junction of CNA and CNB, and disruption of the AIS interaction results in partial stimulation of CN activity. In addition, the binding partner calmodulin regulates the orientation of AID with respect to the catalytic core, resulting in incomplete activation of CN.

Autoinhibitory domains (AIDs)

475-497 (Autoinhibitory Domain) SS

Target domain

102-302 (Calcineurin-like phosphoesterase domain)

Relief mechanism

Partner binding

Assay

Accessory elements

No accessory elements

References

Autoinhibited structure

Activated structure

1 structures for P48453

Entry ID Method Resolution Chain Position Source
AF-P48453-F1 Predicted AlphaFoldDB

22 variants for P48453

Variant ID(s) Position Change Description Diseaes Association Provenance
rs3389293995 42 E>A No EVA
rs3389303134 42 E>D No EVA
rs3389266189 203 Q>R No EVA
rs1134266962 234 G>R No EVA
rs1134989160 238 D>E No EVA
rs1131843856 238 D>N No EVA
rs1133036588 244 P>A No EVA
rs1132006749 245 S>F No EVA
rs1135142592 246 E>K No EVA
rs1132729693 300 Y>D No EVA
rs3389305871 357 D>V No EVA
rs3389266129 359 F>L No EVA
rs3389326520 382 S>P No EVA
rs3389282964 408 N>K No EVA
rs3389316747 440 G>R No EVA
rs3389311556 444 S>E* No EVA
rs3389236316 446 V>E No EVA
rs3389236316 446 V>G No EVA
rs3389316800 448 A>S No EVA
rs3389301701 448 A>V No EVA
rs3389266138 469 R>L No EVA
rs3389311519 512 H>Y No EVA

No associated diseases with P48453

3 regional properties for P48453

Type Name Position InterPro Accession
domain Calcineurin-like phosphoesterase domain, ApaH type 93 - 292 IPR004843
domain Serine/threonine-specific protein phosphatase/bis(5-nucleosyl)-tetraphosphatase 65 - 356 IPR006186
domain PP2B, metallophosphatase domain 50 - 354 IPR041751

Functions

Description
EC Number 3.1.3.16 Phosphoric monoester hydrolases
Subcellular Localization
  • Cytoplasm
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

10 GO annotations of cellular component

Name Definition
calcineurin complex A heterodimeric calcium ion and calmodulin dependent protein phosphatase composed of catalytic and regulatory subunits; the regulatory subunit is very similar in sequence to calmodulin.
cytoplasm The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
cytosol The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
glutamatergic synapse A synapse that uses glutamate as a neurotransmitter.
plasma membrane The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.
protein serine/threonine phosphatase complex A complex, normally consisting of a catalytic and a regulatory subunit, which catalyzes the removal of a phosphate group from a serine or threonine residue of a protein.
protein-containing complex A stable assembly of two or more macromolecules, i.e. proteins, nucleic acids, carbohydrates or lipids, in which at least one component is a protein and the constituent parts function together.
synapse The junction between an axon of one neuron and a dendrite of another neuron, a muscle fiber or a glial cell. As the axon approaches the synapse it enlarges into a specialized structure, the presynaptic terminal bouton, which contains mitochondria and synaptic vesicles. At the tip of the terminal bouton is the presynaptic membrane; facing it, and separated from it by a minute cleft (the synaptic cleft) is a specialized area of membrane on the receiving cell, known as the postsynaptic membrane. In response to the arrival of nerve impulses, the presynaptic terminal bouton secretes molecules of neurotransmitters into the synaptic cleft. These diffuse across the cleft and transmit the signal to the postsynaptic membrane.
T-tubule Invagination of the plasma membrane of a muscle cell that extends inward from the cell surface around each myofibril. The ends of T-tubules make contact with the sarcoplasmic reticulum membrane.
Z disc Platelike region of a muscle sarcomere to which the plus ends of actin filaments are attached.

10 GO annotations of molecular function

Name Definition
calcium ion binding Binding to a calcium ion (Ca2+).
calcium-dependent protein serine/threonine phosphatase activity Catalysis of the reactions
calmodulin binding Binding to calmodulin, a calcium-binding protein with many roles, both in the calcium-bound and calcium-free states.
calmodulin-dependent protein phosphatase activity Catalysis of the reaction
enzyme binding Binding to an enzyme, a protein with catalytic activity.
myosin phosphatase activity Catalysis of the reaction
protein dimerization activity The formation of a protein dimer, a macromolecular structure consists of two noncovalently associated identical or nonidentical subunits.
protein phosphatase 2B binding Binding to a protein phosphatase 2B.
protein serine/threonine phosphatase activity Catalysis of the reaction
protein-containing complex binding Binding to a macromolecular complex.

25 GO annotations of biological process

Name Definition
calcineurin-mediated signaling Any intracellular signal transduction in which the signal is passed on within the cell by activation of a transcription factor as a consequence of dephosphorylation by Ca(2+)-activated calcineurin. The process begins with calcium-dependent activation of the phosphatase calcineurin. Calcineurin is a calcium- and calmodulin-dependent serine/threonine protein phosphatase with a conserved function in eukaryotic species from yeast to humans. In yeast and fungi, calcineurin regulates stress signaling and cell cycle, and sporulation and virulence in pathogenic fungi. In metazoans, calcineurin is involved in cell commitment, organogenesis and organ development and immune function of T-lymphocytes. By a conserved mechanism, calcineurin phosphatase activates fungal Crz1 and mammalian NFATc by dephosphorylation and translocation of these transcription factors to the nucleus to regulate gene expression.
calcineurin-NFAT signaling cascade Any intracellular signal transduction in which the signal is passed on within the cell by activation of a member of the NFAT protein family as a consequence of NFAT dephosphorylation by Ca(2+)-activated calcineurin. The cascade begins with calcium-dependent activation of the phosphatase calcineurin. Calcineurin dephosphorylates multiple phosphoserine residues on NFAT, resulting in the translocation of NFAT to the nucleus. The cascade ends with regulation of transcription by NFAT. The calcineurin-NFAT cascade lies downstream of many cell surface receptors, including G protein-coupled receptors (GPCRs) and receptor tyrosine kinases (RTKs) that signal to mobilize calcium ions (Ca2+).
calcium-ion regulated exocytosis The release of intracellular molecules (e.g. hormones, matrix proteins) contained within a membrane-bounded vesicle by fusion of the vesicle with the plasma membrane of a cell, induced by a rise in cytosolic calcium-ion levels.
heart development The process whose specific outcome is the progression of the heart over time, from its formation to the mature structure. The heart is a hollow, muscular organ, which, by contracting rhythmically, keeps up the circulation of the blood.
locomotion involved in locomotory behavior Self-propelled movement of a cell or organism from one location to another in a behavioral context; the aspect of locomotory behavior having to do with movement.
lymphangiogenesis Lymph vessel formation when new vessels emerge from the proliferation of pre-existing vessels.
negative regulation of calcium ion import across plasma membrane Any process that stops, prevents or reduces the frequency, rate or extent of calcium ion import across plasma membrane.
negative regulation of signaling Any process that stops, prevents, or reduces the frequency, rate or extent of a signaling process.
negative regulation of T cell mediated cytotoxicity Any process that stops, prevents, or reduces the rate of T cell mediated cytotoxicity.
positive regulation of calcineurin-NFAT signaling cascade Any process that activates or increases the frequency, rate or extent of signaling via the calcineurin-NFAT signaling cascade.
positive regulation of calcium ion import across plasma membrane Any process that activates or increases the frequency, rate or extent of calcium ion import across plasma membrane.
positive regulation of insulin secretion involved in cellular response to glucose stimulus Any process that increases the frequency, rate or extent of the regulated release of insulin that contributes to the response of a cell to glucose.
positive regulation of lysosome organization Any process that activates or increases the frequency, rate or extent of lysosome organization.
positive regulation of protein localization to nucleus Any process that activates or increases the frequency, rate or extent of protein localization to nucleus.
positive regulation of transcription by RNA polymerase II Any process that activates or increases the frequency, rate or extent of transcription from an RNA polymerase II promoter.
protein dephosphorylation The process of removing one or more phosphoric residues from a protein.
protein phosphorylation The process of introducing a phosphate group on to a protein.
regulation of gene expression Any process that modulates the frequency, rate or extent of gene expression. Gene expression is the process in which a gene's coding sequence is converted into a mature gene product (protein or RNA).
regulation of insulin secretion Any process that modulates the frequency, rate or extent of the regulated release of insulin.
regulation of synaptic vesicle endocytosis Any process that modulates the frequency, rate or extent of synaptic vesicle endocytosis.
response to cytokine Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a cytokine stimulus.
skeletal muscle fiber development The process whose specific outcome is the progression of the skeletal muscle fiber over time, from its formation to the mature structure. Muscle fibers are formed by the maturation of myotubes. They can be classed as slow, intermediate/fast or fast.
T cell differentiation The process in which a precursor cell type acquires characteristics of a more mature T-cell. A T cell is a type of lymphocyte whose definin characteristic is the expression of a T cell receptor complex.
T cell homeostasis The process of regulating the proliferation and elimination of T cells such that the total number of T cells within a whole or part of an organism is stable over time in the absence of an outside stimulus.
T cell mediated cytotoxicity The directed killing of a target cell by a T cell through the release of granules containing cytotoxic mediators or through the engagement of death receptors.

13 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
P23287 CNA1 Serine/threonine-protein phosphatase 2B catalytic subunit A1 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) PR
P48452 PPP3CA Protein phosphatase 3 catalytic subunit alpha Bos taurus (Bovine) SS
Q27889 Pp2B-14D Serine/threonine-protein phosphatase 2B catalytic subunit 2 Drosophila melanogaster (Fruit fly) SS
P48456 CanA1 Serine/threonine-protein phosphatase 2B catalytic subunit 1 Drosophila melanogaster (Fruit fly) SS
Q9VXF1 CanA-14F Serine/threonine-protein phosphatase 2B catalytic subunit 3 Drosophila melanogaster (Fruit fly) SS
P48454 PPP3CC Serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform Homo sapiens (Human) SS
Q08209 PPP3CA Serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform Homo sapiens (Human) EV
P16298 PPP3CB Serine/threonine-protein phosphatase 2B catalytic subunit beta isoform Homo sapiens (Human) EV
P48455 Ppp3cc Serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform Mus musculus (Mouse) PR
P63328 Ppp3ca Serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform Mus musculus (Mouse) EV
P63329 Ppp3ca Serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform Rattus norvegicus (Rat) SS
P20651 Ppp3cb Serine/threonine-protein phosphatase 2B catalytic subunit beta isoform Rattus norvegicus (Rat) SS
Q0G819 tax-6 Serine/threonine-protein phosphatase 2B catalytic subunit Caenorhabditis elegans SS
10 20 30 40 50 60
MAAPEPARAA PPPPPPPPPP LGADRVVKAV PFPPTHRLTS EEVFDMDGIP RVDVLKNHLV
70 80 90 100 110 120
KEGRVDEEIA LRIINEGAAI LRREKTMIEV EAPITVCGDI HGQFFDLMKL FEVGGSPANT
130 140 150 160 170 180
RYLFLGDYVD RGYFSIECVL YLWVLKILYP STLFLLRGNH ECRHLTEYFT FKQECKIKYS
190 200 210 220 230 240
ERVYEACMEA FDSLPLAALL NQQFLCVHGG LSPEIHTLDD IRRLDRFKEP PAFGPMCDLL
250 260 270 280 290 300
WSDPSEDFGN EKSQEHFSHN TVRGCSYFYN YPAVCEFLQN NNLLSIIRAH EAQDAGYRMY
310 320 330 340 350 360
RKSQTTGFPS LITIFSAPNY LDVYNNKAAV LKYENNVMNI RQFNCSPHPY WLPNFMDVFT
370 380 390 400 410 420
WSLPFVGEKV TEMLVNVLSI CSDDELMTEG EDQFDVGSAA ARKEIIRNKI RAIGKMARVF
430 440 450 460 470 480
SVLREESESV LTLKGLTPTG MLPSGVLAGG RQTLQSATVE AIEAEKAIRG FSPPHRICSF
490 500 510 520
EEAKGLDRIN ERMPPRKDAV QQDGFNSLNT AHTTENHGTG NHSAQ