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Protein

Serine/threonine-protein phosphatase 2B catalytic subunit

Gene

tax-6

Organism
Caenorhabditis elegans
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Calcium-dependent, calmodulin-stimulated protein phosphatase (PubMed:12221132, PubMed:16481400, PubMed:22300764, PubMed:23805378). Dephosphorylates arrd-17 (PubMed:22300764). Dephosphorylates daf-16 at 'Ser-319' which regulates daf-16 nuclear translocation (PubMed:23805378). Dephosphorylates calcium permeable cation channel pkd-2 at 'Ser-534' (PubMed:16481400). Regulates male mating behavior including response to hermaphrodite contact and vulva location and localization of pkd-2 to neuronal cilium (PubMed:16481400). Negatively regulates several sensory behaviors including thermotaxis in ADF neurons, osmosensation in ASH neurons, olfaction adaptation in AWC neurons and sensitivity to CO2 levels (PubMed:18524955, PubMed:11879652). Plays a role in modulating temperature-dependent calcium responses in AFD neurons and together with tax-6 inhibitor rcan-1 regulates thermotaxis in AFD neurons (PubMed:26232604). Regulates expression of rcan-1 (PubMed:12684004). In response to changes in intracellular calcium levels may also regulate nuclear translocation of transcriptional regulators such as crtc-1 (PubMed:26232604). Plays a role in egg-laying, body-size, fertility, growth, movement and cuticle development (PubMed:12684004, PubMed:15522306, PubMed:17113567, PubMed:22300764, PubMed:27871170). Negatively regulates lifespan (PubMed:19279398). Promotes transcription activator crtc-1 nuclear localization, probably by dephosphorylating crtc-1 and thereby negatively regulates lifespan (PubMed:21331044). Regulates expression of chemoreceptor srt-2 in AWC neurons probably downstream of Ser/Thr kinase kin-29 (PubMed:17113567). Negatively regulates nicotinic acetylcholine receptor (nAChR) sensitivity to nicotine (PubMed:15990870). Plays a role in several endocytic processes including in coelomocyte endocytosis, intestine apical endocytosis and synaptic vesicle recycling (PubMed:20803083, PubMed:21345307). May negatively regulate excitatory GABA receptor exp-1 during enteric muscle contraction (PubMed:16084527). May negatively regulate autophagy (PubMed:19279398).17 Publications

Catalytic activityi

[a protein]-serine/threonine phosphate + H2O = [a protein]-serine/threonine + phosphate.UniRule annotation4 Publications

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+ (By similarity). 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+ (PubMed:12221132). 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 (PubMed:12221132). 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). Inhibited by immunosuppressant cyclosporin A (CsA) (PubMed:12221132).By similarity1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi115IronBy similarity1
Metal bindingi117Iron; via tele nitrogenBy similarity1
Metal bindingi143IronBy similarity1
Metal bindingi143ZincBy similarity1
Metal bindingi175ZincBy similarity1
Active sitei176Proton donorBy similarity1
Metal bindingi224Zinc; via tele nitrogenBy similarity1
Metal bindingi306Zinc; via pros nitrogenBy similarity1

GO - Molecular functioni

  • calcium ion binding Source: WormBase
  • calmodulin binding Source: UniProtKB-KW
  • calmodulin-dependent protein phosphatase activity Source: WormBase
  • phosphoprotein phosphatase activity Source: WormBase

GO - Biological processi

  • calcium-mediated signaling Source: UniProtKB
  • chemosensory behavior Source: UniProtKB
  • chemotaxis Source: UniProtKB
  • dauer larval development Source: WormBase
  • determination of adult lifespan Source: WormBase
  • endocytosis Source: UniProtKB-KW
  • hyperosmotic response Source: WormBase
  • olfactory behavior Source: WormBase
  • olfactory learning Source: WormBase
  • peptidyl-serine dephosphorylation Source: WormBase
  • positive regulation of growth rate Source: WormBase
  • positive regulation of multicellular organism growth Source: WormBase
  • protein dephosphorylation Source: WormBase
  • protein localization to non-motile cilium Source: WormBase
  • regulation of gene expression Source: WormBase
  • response to alkaline pH Source: UniProtKB
  • response to hermaphrodite contact Source: WormBase
  • thermosensory behavior Source: WormBase
  • thermotaxis Source: WormBase
  • vulval location Source: WormBase

Keywordsi

Molecular functionCalmodulin-binding, Hydrolase, Protein phosphatase
Biological processBehavior, Chemotaxis, Endocytosis
LigandIron, Metal-binding, Zinc

Enzyme and pathway databases

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

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein phosphatase 2B catalytic subunitCurated (EC:3.1.3.16UniRule annotation4 Publications)
Alternative name(s):
Abnormal chemotaxis protein 6Imported
Calmodulin-dependent calcineurin subunit A1 Publication
Gene namesi
Name:tax-6Imported
Synonyms:cna-1Imported
ORF Names:C02F4.2Imported
OrganismiCaenorhabditis elegansImported
Taxonomic identifieri6239 [NCBI]
Taxonomic lineageiEukaryotaMetazoaEcdysozoaNematodaChromadoreaRhabditidaRhabditoideaRhabditidaePeloderinaeCaenorhabditis
Proteomesi
  • UP000001940 Componenti: Chromosome IV

Organism-specific databases

WormBaseiC02F4.2a ; CE07853 ; WBGene00006527 ; tax-6
C02F4.2b ; CE52450 ; WBGene00006527 ; tax-6
C02F4.2c ; CE46586 ; WBGene00006527 ; tax-6

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

Cell projection, Cytoplasm

Pathology & Biotechi

Disruption phenotypei

Shorter body length and reduced serotinin-induced egg laying as compared to wild-type (PubMed:27871170). Reduced calcium responses in AFD neurons upon a temperature increase from 16 to 20 degrees Celsius as compared to wild-type. At 17 degrees Celsius displays thermophilic behavior, preferentialy migrating towards hotter regions (PubMed:26232604). RNAi-mediated knockdown results in an increase in lifespan (PubMed:21331044, PubMed:23805378). Also causes nuclear exclusion of crtc-1 (PubMed:21331044).4 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi259D → N in p675; impaired thermotaxis and chemotaxis towards NaCl, hypersensitivity to low osmotic conditions, enhanced olfactory adaptation to isoamyl alcohol. Slow growth rate and body is smaller and slender with a transparent appearance resulting from a thinner cuticle. Reduced brood size associated with egg retention. Partially resistant to serotonin-induced egg laying. Increased susceptibility to nicotine-mediated paralysis. Impaired mating behavior and reduced localization of pkd-2 to neuronal cilium. Impaired CO2 avoidance. Impaired coelomocyte endocytosis, apical endocytosis in intestine and recycling of synaptic vesicles at synapses. 7 Publications1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00004369041 – 542Serine/threonine-protein phosphatase 2B catalytic subunitCuratedAdd BLAST542

Proteomic databases

EPDiQ0G819
PaxDbiQ0G819
PeptideAtlasiQ0G819

Expressioni

Tissue specificityi

Expressed in head and tail neurons, ventral nerve cord, body wall and vulva muscles, sperm and spermatheca (PubMed:12221132). Expressed in hypodermal seam cells (PubMed:15522306). Expressed in intestinal and anal depressor muscles (PubMed:16084527). In male, expressed in CEM, HOB and ray RnB neurons (PubMed:16481400). Isoform a: Expressed in thermosensory ADF neurons, chemosensory ASE, AWA and AWC neurons, osmosensory ASH neurons and AIY and AIZ interneurons (PubMed:11879652). Expressed in body wall, vulva and pharyngeal muscles (PubMed:11879652).5 Publications

Developmental stagei

Expressed in embryos and at all larval stages.1 Publication

Gene expression databases

BgeeiWBGene00006527

Interactioni

Subunit structurei

Forms a complex composed of a calmodulin-dependent catalytic subunit tax-6 (also known as calcineurin A) and a regulatory Ca2+-binding subunit cnb-1 (also known as calcineurin B) (PubMed:12221132). Interacts (via catalytic domain) with rcan-1; the interaction is calcium-dependent and inhibits tax-6 catalytic activity (PubMed:12684004, PubMed:26232604). Interacts with exp-1; the interaction is calcium and cnb-1-independent (PubMed:16084527). Interacts with arrd-17 (PubMed:22300764). Interacts with kin-29 (PubMed:17113567). Interacts with cnp-2 (PubMed:18593529). Interacts with daf-16 (PubMed:23805378). Interacts with dyn-1 (PubMed:20803083).9 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei377Interaction with PxVP motif in substrateBy similarity1

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

ComplexPortaliCPX-1128 Calcineurin-Calmodulin complex
DIPiDIP-25135N
IntActiQ0G819, 6 interactors
MINTiQ0G819
STRINGi6239.C02F4.2c

Structurei

3D structure databases

ProteinModelPortaliQ0G819
SMRiQ0G819
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni81 – 365CatalyticCuratedAdd BLAST285
Regioni352 – 361Interaction with PxIxIF motif in substrateBy similarity10
Regioni366 – 394Calcineurin B bindingBy similarityAdd BLAST29
Regioni418 – 432Calmodulin-bindingBy similarityAdd BLAST15
Regioni433 – 440Autoinhibitory segmentBy similarity8
Regioni490 – 512Autoinhibitory domainBy similarityAdd BLAST23

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi332 – 336SAPNY motifBy similarity5

Domaini

The autoinhibitory domain prevents access to the catalytic site.By similarity
The autoinhibitory segment prevents access to the substrate binding site.By similarity
Possible isomerization of Pro-334 within the SAPNY motif triggers a conformation switch which affects the organization and thus accessibility of the active site and the substrate binding region (PxIxIF motif). The trans- to cis-transition may favor calcineurin A activation and substrate binding. The reverse cis- to trans-transition may be enhanced by peptidyl-prolyl isomerases such as PPIA.By similarity

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiKOG0375 Eukaryota
COG0639 LUCA
GeneTreeiENSGT00530000063087
HOGENOMiHOG000172699
InParanoidiQ0G819
KOiK04348
OMAiQFDVKVG
OrthoDBiEOG091G094R

Family and domain databases

Gene3Di3.60.21.10, 1 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 (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform cImported (identifier: Q0G819-1) [UniParc]FASTAAdd to basket

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
MASTSAGQNS AAKPDTTNTT TTASNNNRER ERDLKQFTER FVKTVQFPVS
60 70 80 90 100
ERLTVDQVYD RRTGKPRHEV LRDHFIKEGR IEEEAAIRVI QECSSLFRNE
110 120 130 140 150
KTMLEIEAPV TVCGDIHGQF YDLMKLFEVG GSPATTKYLF LGDYVDRGYF
160 170 180 190 200
SIECVLYLWA LKICYPTTLF LLRGNHECRH LTEYFTFKQE CKIKYSERVY
210 220 230 240 250
DVCMESFDAL PLAALMNQQF LCVHGGLSPE IHTLEDIRRI DRFKEPPAFG
260 270 280 290 300
PMCDLLWSDP LEDFGNERNS EQFSHNSVRG CSYFYSYAAC CDFLQHNNLL
310 320 330 340 350
SIIRAHEAQD AGYRMYRKSQ ATGFPSLITI FSAPNYLDVY NNKAAILKYE
360 370 380 390 400
NNVMNIRQFN CSPHPYWLPN FMDVFTWSLP FVGEKVTEML VHILNICSDD
410 420 430 440 450
ELMAECDDTF EGGVGSARKE VIRHKIRAIG KMARAFSVLR HESESVLQLK
460 470 480 490 500
GLNAGGKLPQ GALSEGRTGL NAAYRIEQSV AAESGCDSGH LIQSFEEARR
510 520 530 540
LDKINERMPP TMATPPAQSP SQSPIPSRQT TPQPPQNGPS NS
Note: No experimental confirmation available.Curated
Length:542
Mass (Da):61,505
Last modified:January 25, 2012 - v2
Checksum:i60983B8A0C504883
GO
Isoform aImported (identifier: Q0G819-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     441-441: H → E
     448-479: QLKGLNAGGKLPQGALSEGRTGLNAAYRIEQS → ALKGLTPTGALPMGTLQGGSRGVRE

Show »
Length:535
Mass (Da):60,666
Checksum:iFC0363809D04103E
GO
Isoform bImported (identifier: Q0G819-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     413-450: GVGSARKEVI...HESESVLQLK → ADGKWIFPYP...IFYQTFFGTP
     451-542: Missing.

Note: No experimental confirmation available.Curated
Show »
Length:450
Mass (Da):52,057
Checksum:iEC01B58E6C8F3E43
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_058441413 – 450GVGSA…VLQLK → ADGKWIFPYPPHTGDVCLTI RFSFIFSLIFYQTFFGTP in isoform b. Add BLAST38
Alternative sequenceiVSP_058442441H → E in isoform a. Curated1
Alternative sequenceiVSP_058443448 – 479QLKGL…RIEQS → ALKGLTPTGALPMGTLQGGS RGVRE in isoform a. Add BLAST32
Alternative sequenceiVSP_058444451 – 542Missing in isoform b. CuratedAdd BLAST92

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BX284604 Genomic DNA Translation: CAB02719.1
BX284604 Genomic DNA Translation: CAD88213.2
BX284604 Genomic DNA Translation: CAL36491.2
PIRiT18864
RefSeqiNP_001021292.1, NM_001026121.1
NP_001021293.2, NM_001026122.3
NP_001076658.2, NM_001083189.4 [Q0G819-1]
UniGeneiCel.13613

Genome annotation databases

EnsemblMetazoaiC02F4.2c; C02F4.2c; WBGene00006527 [Q0G819-1]
GeneIDi177943
KEGGicel:CELE_C02F4.2
UCSCiC02F4.2c c. elegans [Q0G819-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiPP2B_CAEEL
AccessioniPrimary (citable) accession number: Q0G819
Secondary accession number(s): Q86MD4, Q95002
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 6, 2016
Last sequence update: January 25, 2012
Last modified: July 18, 2018
This is version 113 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programCaenorhabditis annotation project

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Caenorhabditis elegans
    Caenorhabditis elegans: entries, gene names and cross-references to WormBase
  2. SIMILARITY comments
    Index of protein domains and families

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