PP2BA_DICDI
ID PP2BA_DICDI Reviewed; 623 AA.
AC Q7YSW8; Q27558; Q27560; Q550X1;
DT 29-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2003, sequence version 1.
DT 03-AUG-2022, entry version 119.
DE RecName: Full=Serine/threonine-protein phosphatase 2B catalytic subunit;
DE EC=3.1.3.16 {ECO:0000269|PubMed:10608845, ECO:0000269|PubMed:11352578, ECO:0000269|PubMed:8681950, ECO:0000269|PubMed:9765812};
DE AltName: Full=Calcineurin subunit A;
GN Name=canA; ORFNames=DDB_G0276883;
OS Dictyostelium discoideum (Slime mold).
OC Eukaryota; Amoebozoa; Evosea; Eumycetozoa; Dictyostelia; Dictyosteliales;
OC Dictyosteliaceae; Dictyostelium.
OX NCBI_TaxID=44689;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, ACTIVITY
RP REGULATION, AND DEVELOPMENTAL STAGE.
RX PubMed=8681950; DOI=10.1111/j.1432-1033.1996.0391z.x;
RA Dammann H., Hellstern S., Husain Q., Mutzel R.;
RT "Primary structure, expression and developmental regulation of a
RT Dictyostelium calcineurin A homologue.";
RL Eur. J. Biochem. 238:391-399(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=AX3-1;
RA Lydan M.A., O'Day D.H., Cotter D.A.;
RT "Cloning and characterization of calcineurin from Dictyostelium
RT discoideum.";
RL Submitted (OCT-1997) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=AX4;
RX PubMed=12097910; DOI=10.1038/nature00847;
RA Gloeckner G., Eichinger L., Szafranski K., Pachebat J.A., Bankier A.T.,
RA Dear P.H., Lehmann R., Baumgart C., Parra G., Abril J.F., Guigo R.,
RA Kumpf K., Tunggal B., Cox E.C., Quail M.A., Platzer M., Rosenthal A.,
RA Noegel A.A.;
RT "Sequence and analysis of chromosome 2 of Dictyostelium discoideum.";
RL Nature 418:79-85(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=AX4;
RX PubMed=15875012; DOI=10.1038/nature03481;
RA Eichinger L., Pachebat J.A., Gloeckner G., Rajandream M.A., Sucgang R.,
RA Berriman M., Song J., Olsen R., Szafranski K., Xu Q., Tunggal B.,
RA Kummerfeld S., Madera M., Konfortov B.A., Rivero F., Bankier A.T.,
RA Lehmann R., Hamlin N., Davies R., Gaudet P., Fey P., Pilcher K., Chen G.,
RA Saunders D., Sodergren E.J., Davis P., Kerhornou A., Nie X., Hall N.,
RA Anjard C., Hemphill L., Bason N., Farbrother P., Desany B., Just E.,
RA Morio T., Rost R., Churcher C.M., Cooper J., Haydock S., van Driessche N.,
RA Cronin A., Goodhead I., Muzny D.M., Mourier T., Pain A., Lu M., Harper D.,
RA Lindsay R., Hauser H., James K.D., Quiles M., Madan Babu M., Saito T.,
RA Buchrieser C., Wardroper A., Felder M., Thangavelu M., Johnson D.,
RA Knights A., Loulseged H., Mungall K.L., Oliver K., Price C., Quail M.A.,
RA Urushihara H., Hernandez J., Rabbinowitsch E., Steffen D., Sanders M.,
RA Ma J., Kohara Y., Sharp S., Simmonds M.N., Spiegler S., Tivey A.,
RA Sugano S., White B., Walker D., Woodward J.R., Winckler T., Tanaka Y.,
RA Shaulsky G., Schleicher M., Weinstock G.M., Rosenthal A., Cox E.C.,
RA Chisholm R.L., Gibbs R.A., Loomis W.F., Platzer M., Kay R.R.,
RA Williams J.G., Dear P.H., Noegel A.A., Barrell B.G., Kuspa A.;
RT "The genome of the social amoeba Dictyostelium discoideum.";
RL Nature 435:43-57(2005).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RX PubMed=9765812; DOI=10.1016/s0923-2508(97)81589-6;
RA Hellstern S., Dammann H., Husain Q., Mutzel R.;
RT "Overexpression, purification and characterization of Dictyostelium
RT calcineurin A.";
RL Res. Microbiol. 148:335-343(1997).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND INTERACTION WITH
RP CALMODULIN.
RX PubMed=10608845; DOI=10.1074/jbc.274.53.37821;
RA Kessen U., Schaloske R., Aichem A., Mutzel R.;
RT "Ca(2+)/calmodulin-independent activation of calcineurin from Dictyostelium
RT by unsaturated long chain fatty acids.";
RL J. Biol. Chem. 274:37821-37826(1999).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND INTERACTION WITH
RP CNBA AND CALMODULIN.
RX PubMed=11352578; DOI=10.1006/jmbi.2001.4645;
RA Aichem A., Mutzel R.;
RT "Unconventional mRNA processing in the expression of two calcineurin B
RT isoforms in Dictyostelium.";
RL J. Mol. Biol. 308:873-882(2001).
CC -!- FUNCTION: Catalytic subunit of calcineurin, a calcium-dependent,
CC calmodulin stimulated protein phosphatase which plays an essential role
CC in the transduction of intracellular Ca(2+)-mediated signals.
CC {ECO:0000269|PubMed:10608845, ECO:0000269|PubMed:11352578,
CC ECO:0000269|PubMed:8681950, ECO:0000269|PubMed:9765812}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + O-phospho-L-seryl-[protein] = L-seryl-[protein] +
CC phosphate; Xref=Rhea:RHEA:20629, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15377, ChEBI:CHEBI:29999, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:83421; EC=3.1.3.16;
CC Evidence={ECO:0000269|PubMed:10608845, ECO:0000269|PubMed:11352578,
CC ECO:0000269|PubMed:8681950, ECO:0000269|PubMed:9765812};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + O-phospho-L-threonyl-[protein] = L-threonyl-[protein] +
CC phosphate; Xref=Rhea:RHEA:47004, Rhea:RHEA-COMP:11060, Rhea:RHEA-
CC COMP:11605, ChEBI:CHEBI:15377, ChEBI:CHEBI:30013, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:61977; EC=3.1.3.16;
CC Evidence={ECO:0000269|PubMed:10608845, ECO:0000269|PubMed:11352578,
CC ECO:0000269|PubMed:8681950, ECO:0000269|PubMed:9765812};
CC -!- COFACTOR:
CC Name=Fe(3+); Xref=ChEBI:CHEBI:29034;
CC Evidence={ECO:0000250|UniProtKB:Q08209};
CC Note=Binds 1 Fe(3+) ion per subunit. {ECO:0000250|UniProtKB:Q08209};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:Q08209};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:Q08209};
CC -!- ACTIVITY REGULATION: Activated by Ca(2+)-bound calmodulin following an
CC increase in intracellular Ca(2+) (PubMed:11352578, PubMed:10608845,
CC PubMed:9765812, PubMed:8681950). At low Ca(2+) concentrations, the
CC catalytic subunit (also known as calcineurin A) is inactive and is
CC bound to the regulatory subunit (also known as calcineurin B) in which
CC only two high-affinity binding sites are occupied by Ca(2+)
CC (PubMed:11352578). In response to elevated calcium levels, the
CC occupancy of the low-affinity sites on calcineurin B by Ca(2+) causes a
CC conformational change of the C-terminal regulatory domain of
CC calcineurin A, resulting in the exposure of the calmodulin-binding
CC domain and in the partial activation of calcineurin A
CC (PubMed:11352578). The subsequent binding of Ca(2+)-bound calmodulin
CC leads to the displacement of the autoinhibitory domain from the active
CC site and possibly of the autoinhibitory segment from the substrate
CC binding site which fully activates calcineurin A (PubMed:11352578,
CC PubMed:10608845, PubMed:9765812, PubMed:8681950). Activated by
CC arachidonic acid, linoleic acid and oleic acid to the same extent as
CC calmodulin (PubMed:10608845). {ECO:0000269|PubMed:10608845,
CC ECO:0000269|PubMed:11352578, ECO:0000269|PubMed:8681950,
CC ECO:0000269|PubMed:9765812}.
CC -!- SUBUNIT: Forms a complex composed of a catalytic and calmodulin-
CC dependent subunit, calcineurin A, and a regulatory Ca(2+)-binding
CC subunit, calcineurin B (PubMed:11352578). In response to an increase in
CC Ca(2+) intracellular levels, forms a complex composed of
CC canA/calcineurin A, cnbA/calcineurin B and calA/calmodulin
CC (PubMed:11352578). Interacts (via calcineurin B binding domain) with
CC regulatory subunit cnbA/calcineurin B (PubMed:11352578). Interacts (via
CC calmodulin-binding domain) with calmodulin; the interaction depends on
CC calmodulin binding to Ca(2+) (PubMed:10608845, PubMed:11352578).
CC {ECO:0000269|PubMed:10608845, ECO:0000269|PubMed:11352578}.
CC -!- DEVELOPMENTAL STAGE: Highest levels are found after 10 hours of
CC development. Levels decrease during multicellular development (at
CC protein level). {ECO:0000269|PubMed:8681950}.
CC -!- DOMAIN: The autoinhibitory domain prevents access to the catalytic
CC site. {ECO:0000250|UniProtKB:P63328}.
CC -!- DOMAIN: The autoinhibitory segment prevents access to the substrate
CC binding site. {ECO:0000250|UniProtKB:P63328}.
CC -!- DOMAIN: Possible isomerization of Pro-358 within the SAPNY motif
CC triggers a conformation switch which affects the organization and thus
CC accessibility of the active site and the substrate binding region
CC (PxIxIF motif). The trans- to cis-transition may favor calcineurin A
CC activation and substrate binding. The reverse cis- to trans-transition
CC may be enhanced by peptidyl-prolyl isomerases such as PPIA.
CC {ECO:0000250|UniProtKB:Q08209}.
CC -!- PTM: The N-terminus is blocked.
CC -!- SIMILARITY: Belongs to the PPP phosphatase family. PP-2B subfamily.
CC {ECO:0000305}.
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DR EMBL; X97280; CAA65935.1; -; mRNA.
DR EMBL; U22397; AAB82063.1; -; mRNA.
DR EMBL; AAFI02000019; EAL68943.1; -; Genomic_DNA.
DR RefSeq; XP_642811.1; XM_637719.1.
DR AlphaFoldDB; Q7YSW8; -.
DR SMR; Q7YSW8; -.
DR IntAct; Q7YSW8; 1.
DR STRING; 44689.DDB0185021; -.
DR PaxDb; Q7YSW8; -.
DR EnsemblProtists; EAL68943; EAL68943; DDB_G0276883.
DR GeneID; 8620674; -.
DR KEGG; ddi:DDB_G0276883; -.
DR dictyBase; DDB_G0276883; canA.
DR eggNOG; KOG0375; Eukaryota.
DR HOGENOM; CLU_004962_6_3_1; -.
DR InParanoid; Q7YSW8; -.
DR OMA; MESFCCL; -.
DR PhylomeDB; Q7YSW8; -.
DR Reactome; R-DDI-2871809; FCERI mediated Ca+2 mobilization.
DR Reactome; R-DDI-4086398; Ca2+ pathway.
DR Reactome; R-DDI-5607763; CLEC7A (Dectin-1) induces NFAT activation.
DR PRO; PR:Q7YSW8; -.
DR Proteomes; UP000002195; Chromosome 2.
DR GO; GO:0005955; C:calcineurin complex; IDA:dictyBase.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005516; F:calmodulin binding; IDA:dictyBase.
DR GO; GO:0033192; F:calmodulin-dependent protein phosphatase activity; IDA:dictyBase.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0017018; F:myosin phosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0004722; F:protein serine/threonine phosphatase activity; IDA:dictyBase.
DR GO; GO:0097720; P:calcineurin-mediated signaling; IMP:dictyBase.
DR GO; GO:0006470; P:protein dephosphorylation; IDA:dictyBase.
DR GO; GO:0031156; P:regulation of sorocarp development; IMP:dictyBase.
DR GO; GO:0043157; P:response to cation stress; IMP:dictyBase.
DR GO; GO:1903013; P:response to differentiation-inducing factor 1; HDA:dictyBase.
DR GO; GO:0044671; P:sorocarp spore cell differentiation; IMP:dictyBase.
DR GO; GO:0031149; P:sorocarp stalk cell differentiation; IMP:dictyBase.
DR CDD; cd07416; MPP_PP2B; 1.
DR Gene3D; 3.60.21.10; -; 1.
DR InterPro; IPR004843; Calcineurin-like_PHP_ApaH.
DR InterPro; IPR029052; Metallo-depent_PP-like.
DR InterPro; IPR041751; MPP_PP2B.
DR InterPro; IPR043360; PP2B.
DR InterPro; IPR006186; Ser/Thr-sp_prot-phosphatase.
DR PANTHER; PTHR45673; PTHR45673; 1.
DR Pfam; PF00149; Metallophos; 1.
DR PRINTS; PR00114; STPHPHTASE.
DR SMART; SM00156; PP2Ac; 1.
DR SUPFAM; SSF56300; SSF56300; 1.
DR PROSITE; PS00125; SER_THR_PHOSPHATASE; 1.
PE 1: Evidence at protein level;
KW Calmodulin-binding; Coiled coil; Hydrolase; Iron; Metal-binding;
KW Protein phosphatase; Reference proteome; Zinc.
FT CHAIN 1..623
FT /note="Serine/threonine-protein phosphatase 2B catalytic
FT subunit"
FT /id="PRO_0000331279"
FT REGION 1..53
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 104..389
FT /note="Catalytic"
FT /evidence="ECO:0000305"
FT REGION 376..385
FT /note="Interaction with PxIxIF motif in substrate"
FT /evidence="ECO:0000250|UniProtKB:Q08209"
FT REGION 390..418
FT /note="Calcineurin B binding"
FT /evidence="ECO:0000250|UniProtKB:Q08209"
FT REGION 444..458
FT /note="Calmodulin-binding"
FT /evidence="ECO:0000250|UniProtKB:Q08209"
FT REGION 459..466
FT /note="Autoinhibitory segment"
FT /evidence="ECO:0000250|UniProtKB:P16298"
FT REGION 500..520
FT /note="Autoinhibitory domain"
FT /evidence="ECO:0000250|UniProtKB:P16298"
FT REGION 577..623
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 422..460
FT /evidence="ECO:0000255"
FT MOTIF 356..360
FT /note="SAPNY motif"
FT /evidence="ECO:0000250|UniProtKB:Q08209"
FT COMPBIAS 1..25
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 26..49
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 201
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:Q08209"
FT BINDING 138
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:Q08209"
FT BINDING 140
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:Q08209"
FT BINDING 168
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:Q08209"
FT BINDING 168
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q08209"
FT BINDING 200
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q08209"
FT BINDING 249
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q08209"
FT BINDING 330
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q08209"
FT SITE 401
FT /note="Interaction with PxVP motif in substrate"
FT /evidence="ECO:0000250|UniProtKB:Q08209"
FT CONFLICT 77
FT /note="L -> I (in Ref. 1; CAA65935)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 623 AA; 71393 MW; EB9E46E18795FA6C CRC64;
MSTNNNKAPT SQSSDKSATT ESKLNDNENT ETETKTDENN EEKPKMTLKP PQPKIENKVS
TIDRVVPSVK YPKSLPLPHD VLFNEDKTIN LPKLQEHFFA EGRLNHDDVI EIVKMAAEIL
EKEPTLIQVE APITVCGDTH GQFYDLIKIF ENDIGGNPAN TNYLFLGDYV DRGYFSMEVI
IYLYACKINY PNTFFLLRGN HECRHLTEYF TFKEECLHKY SEEVYDFITE SFNALPLAAL
MNGKFLCIHG GLSPDIKTLD DIANIDRFKE PPSSGPMCDL LWSDPMEEFS PEIREHFVPN
DVRGCSYLYS YRAVCSFLQK NKLLSVIRAH EAQNAGYKMH LQNDATGFPS VITLFSAPNY
LDAYNNKGAV LRYENNVMNI RQFTCSPHPY WLPNFMDVFT WSMPFVSEKV AEMLLVLLNL
CNDEEAEKNE NAQTVKDTSE EEKRRQMLRA KVKSVSKMMR MFSLLRQERE TIMMIKSFSP
SRKIPQGLLT EGKDALKKAL GDFAQARKMD LINEKRPPIL DRVNSRGELL RMNSRGELFR
INSKGDLFRS NSYADLKPPQ GPQETIKITE CHEQNITTNN INPNSITTNE NNSNEQLQQQ
QQQQQQQQPP TTTSTTTQTE VAK
