PPP5_RAT
ID PPP5_RAT Reviewed; 499 AA.
AC P53042;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 173.
DE RecName: Full=Serine/threonine-protein phosphatase 5;
DE Short=PP5;
DE EC=3.1.3.16 {ECO:0000269|PubMed:11523989, ECO:0000269|PubMed:11969423};
DE AltName: Full=Protein phosphatase T;
DE Short=PPT;
GN Name=Ppp5c;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Testis;
RX PubMed=8077208; DOI=10.1016/s0021-9258(17)31686-1;
RA Becker W., Kentrup H., Klumpp S., Schultz J.E., Joost H.G.;
RT "Molecular cloning of a protein serine/threonine phosphatase containing a
RT putative regulatory tetratricopeptide repeat domain.";
RL J. Biol. Chem. 269:22586-22592(1994).
RN [2]
RP FUNCTION AS PHOSPHATASE, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND
RP MUTAGENESIS OF GLU-29; LYS-32; GLU-56; ILE-63; ARG-74; GLU-76; CYS-77;
RP TYR-80; LYS-97 AND ARG-101.
RX PubMed=11523989; DOI=10.1021/bi010999i;
RA Kang H., Sayner S.L., Gross K.L., Russell L.C., Chinkers M.;
RT "Identification of amino acids in the tetratricopeptide repeat and C-
RT terminal domains of protein phosphatase 5 involved in autoinhibition and
RT lipid activation.";
RL Biochemistry 40:10485-10490(2001).
RN [3]
RP COFACTOR, ACTIVITY REGULATION, AND CATALYTIC ACTIVITY.
RX PubMed=11969423; DOI=10.1021/bi016090h;
RA Ramsey A.J., Chinkers M.;
RT "Identification of potential physiological activators of protein
RT phosphatase 5.";
RL Biochemistry 41:5625-5632(2002).
RN [4]
RP FUNCTION AS PHOSPHATASE, INTERACTION WITH GNA12 AND GNA13, AND SUBCELLULAR
RP LOCATION.
RX PubMed=12176367; DOI=10.1016/s0960-9822(02)01034-5;
RA Yamaguchi Y., Katoh H., Mori K., Negishi M.;
RT "Galpha(12) and Galpha(13) interact with Ser/Thr protein phosphatase type 5
RT and stimulate its phosphatase activity.";
RL Curr. Biol. 12:1353-1358(2002).
RN [5]
RP FUNCTION IN DEPHOSPHORYLATING MAPT, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP TISSUE SPECIFICITY.
RX PubMed=15546861; DOI=10.1074/jbc.m410775200;
RA Liu F., Iqbal K., Grundke-Iqbal I., Rossie S., Gong C.X.;
RT "Dephosphorylation of tau by protein phosphatase 5: impairment in
RT Alzheimer's disease.";
RL J. Biol. Chem. 280:1790-1796(2005).
RN [6]
RP FUNCTION IN MAPK SIGNALING.
RX PubMed=16892053; DOI=10.1038/ncb1465;
RA von Kriegsheim A., Pitt A., Grindlay G.J., Kolch W., Dhillon A.S.;
RT "Regulation of the Raf-MEK-ERK pathway by protein phosphatase 5.";
RL Nat. Cell Biol. 8:1011-1016(2006).
RN [7]
RP FUNCTION IN RAC1 SIGNALING, ACTIVITY REGULATION, INTERACTION WITH RAC1, AND
RP MUTAGENESIS OF LYS-93; LYS-126 AND TYR-451.
RX PubMed=16549782; DOI=10.1073/pnas.0600080103;
RA Gentile S., Darden T., Erxleben C., Romeo C., Russo A., Martin N.,
RA Rossie S., Armstrong D.L.;
RT "Rac GTPase signaling through the PP5 protein phosphatase.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:5202-5206(2006).
RN [8]
RP INTERACTION WITH CRY1 AND CRY2.
RX PubMed=16790549; DOI=10.1073/pnas.0604138103;
RA Partch C.L., Shields K.F., Thompson C.L., Selby C.P., Sancar A.;
RT "Posttranslational regulation of the mammalian circadian clock by
RT cryptochrome and protein phosphatase 5.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:10467-10472(2006).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 16-499 IN COMPLEX WITH MAGNESIUM,
RP COFACTOR, AND INTERACTION WITH HSP90AA1.
RX PubMed=26182372; DOI=10.1042/bsr20150042;
RA Haslbeck V., Drazic A., Eckl J.M., Alte F., Helmuth M., Popowicz G.,
RA Schmidt W., Braun F., Weiwad M., Fischer G., Gemmecker G., Sattler M.,
RA Striggow F., Groll M., Richter K.;
RT "Selective activators of protein phosphatase 5 target the autoinhibitory
RT mechanism.";
RL Biosci. Rep. 35:E00210-E00210(2015).
CC -!- FUNCTION: Serine/threonine-protein phosphatase that dephosphorylates a
CC myriad of proteins involved in different signaling pathways including
CC the kinases CSNK1E, ASK1/MAP3K5, PRKDC and RAF1, the nuclear receptors
CC NR3C1, PPARG, ESR1 and ESR2, SMAD proteins and TAU/MAPT
CC (PubMed:11523989, PubMed:12176367, PubMed:15546861, PubMed:16892053,
CC PubMed:16549782). Implicated in wide ranging cellular processes,
CC including apoptosis, differentiation, DNA damage response, cell
CC survival, regulation of ion channels or circadian rhythms, in response
CC to steroid and thyroid hormones, calcium, fatty acids, TGF-beta as well
CC as oxidative and genotoxic stresses (By similarity). Participates in
CC the control of DNA damage response mechanisms such as checkpoint
CC activation and DNA damage repair through, for instance, the regulation
CC ATM/ATR-signaling and dephosphorylation of PRKDC and TP53BP1 (By
CC similarity). Inhibits ASK1/MAP3K5-mediated apoptosis induced by
CC oxidative stress (By similarity). Plays a positive role in
CC adipogenesis, mainly through the dephosphorylation and activation of
CC PPARG transactivation function. Also dephosphorylates and inhibits the
CC anti-adipogenic effect of NR3C1 (By similarity). Regulates the
CC circadian rhythms, through the dephosphorylation and activation of
CC CSNK1E (By similarity). May modulate TGF-beta signaling pathway by the
CC regulation of SMAD3 phosphorylation and protein expression levels (By
CC similarity). Dephosphorylates and may play a role in the regulation of
CC TAU/MAPT (PubMed:15546861). Through their dephosphorylation, may play a
CC role in the regulation of ions channels such as KCNH2
CC (PubMed:16549782). Dephosphorylate FNIP1, disrupting interaction with
CC HSP90AA1/Hsp90 (By similarity). {ECO:0000250|UniProtKB:P53041,
CC ECO:0000250|UniProtKB:Q60676, ECO:0000269|PubMed:11523989,
CC ECO:0000269|PubMed:12176367, ECO:0000269|PubMed:15546861,
CC ECO:0000269|PubMed:16549782, ECO:0000269|PubMed:16892053}.
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:11523989, ECO:0000269|PubMed:11969423};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20630;
CC Evidence={ECO:0000269|PubMed:11523989, ECO:0000269|PubMed:11969423};
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:11523989, ECO:0000269|PubMed:11969423};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47005;
CC Evidence={ECO:0000269|PubMed:11523989, ECO:0000269|PubMed:11969423};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:11969423, ECO:0000269|PubMed:26182372};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:11969423, ECO:0000269|PubMed:26182372};
CC Note=Binds 2 magnesium or manganese ions per subunit.
CC {ECO:0000269|PubMed:11969423, ECO:0000269|PubMed:26182372};
CC -!- ACTIVITY REGULATION: Autoinhibited. In the autoinhibited state, the TPR
CC domain interacts with the catalytic region and prevents substrate
CC access to the catalytic pocket. Allosterically activated by various
CC polyunsaturated fatty acids, free long-chain fatty-acids and long-chain
CC fatty acyl-CoA esters, arachidonic acid being the most effective
CC activator. HSP90A and probably RAC1, GNA12 and GNA13 can also release
CC the autoinhibition by the TPR repeat. Activation by RAC1, GNA12 and
CC GNA13 is synergistic with the one produced by fatty acids binding.
CC Inhibited by okadaic acid. {ECO:0000269|PubMed:11523989,
CC ECO:0000269|PubMed:11969423, ECO:0000269|PubMed:16549782}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=12.1 uM for MAPT/TAU (at pH 7.4 and 30 degrees Celsius)
CC {ECO:0000269|PubMed:15546861};
CC -!- SUBUNIT: Probably forms a complex composed of chaperones HSP90 and
CC HSP70, co-chaperones STIP1/HOP, CDC37, PPP5C, PTGES3/p23, TSC1 and
CC client protein TSC2 (By similarity). Probably forms a complex composed
CC of chaperones HSP90 and HSP70, co-chaperones CDC37, PPP5C, TSC1 and
CC client protein TSC2, CDK4, AKT, RAF1 and NR3C1; this complex does not
CC contain co-chaperones STIP1/HOP and PTGES3/p23 (By similarity). Part of
CC a complex with HSP90/HSP90AA1 and steroid receptors (By similarity).
CC Interacts (via TPR repeats) with HSP90AA1 (via TPR repeat-binding
CC motif) or HSPA1A/HSPA1B; the interaction is direct and activates the
CC phosphatase activity (PubMed:26182372). Dissociates from HSPA1A/HSPA1B
CC and HSP90AA1 in response to arachidonic acid (By similarity). Interacts
CC with CPNE1 (via VWFA domain) (By similarity). Interacts with CDC16,
CC CDC27 (By similarity). Interacts with KLHDC10 (via the 6 Kelch
CC repeats); inhibits the phosphatase activity on MAP3K5 (By similarity).
CC Interacts with ATM and ATR; both interactions are induced by DNA damage
CC and enhance ATM and ATR kinase activity (By similarity). Interacts with
CC RAD17; reduced by DNA damage (By similarity). Interacts with nuclear
CC receptors such as NR3C1/GCR and PPARG (activated by agonist); regulates
CC their transactivation activities (By similarity). Interacts (via TPR
CC repeats) with S100 proteins S100A1, S100A2, S100A6, S100B and S100P;
CC the interactions are calcium-dependent, strongly activate PPP5C
CC phosphatase activity and compete with HSP90AA1 and MAP3K5 interactions
CC (By similarity). Interacts with SMAD2 and SMAD3 but not with SMAD1;
CC decreases SMAD3 phosphorylation and protein levels (By similarity).
CC Interacts (via TPR repeats) with CRY1 and CRY2; the interaction with
CC CRY2 down-regulates the phosphatase activity on CSNK1E
CC (PubMed:16790549). Interacts (via TPR repeats) with the active form of
CC RAC1, GNA12 or GNA13; these interactions activate the phosphatase
CC activity and translocate PPP5C to the cell membrane (PubMed:12176367,
CC PubMed:16549782). Interacts with FLCN (By similarity).
CC {ECO:0000250|UniProtKB:P53041, ECO:0000250|UniProtKB:Q60676,
CC ECO:0000269|PubMed:12176367, ECO:0000269|PubMed:16549782,
CC ECO:0000269|PubMed:16790549, ECO:0000269|PubMed:26182372}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:12176367}. Cytoplasm
CC {ECO:0000269|PubMed:12176367}. Cell membrane
CC {ECO:0000250|UniProtKB:P53041}. Note=Predominantly nuclear. But also
CC present in the cytoplasm. Translocates from the cytoplasm to the plasma
CC membrane in a RAC1-dependent manner. {ECO:0000250|UniProtKB:P53041}.
CC -!- TISSUE SPECIFICITY: Predominantly found in brain and, in lower levels,
CC in testis, but was nearly undetectable in spleen, lung, skeletal
CC muscle, kidney and liver. {ECO:0000269|PubMed:15546861}.
CC -!- PTM: Activated by at least two different proteolytic cleavages
CC producing a 56 kDa and a 50 kDa form. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the PPP phosphatase family. PP-5 (PP-T)
CC subfamily. {ECO:0000305}.
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DR EMBL; X77237; CAA54454.1; -; mRNA.
DR PIR; A55346; A55346.
DR RefSeq; NP_113917.1; NM_031729.1.
DR PDB; 4JA7; X-ray; 2.00 A; A=16-499.
DR PDB; 4JA9; X-ray; 2.30 A; A=16-499.
DR PDBsum; 4JA7; -.
DR PDBsum; 4JA9; -.
DR AlphaFoldDB; P53042; -.
DR SMR; P53042; -.
DR BioGRID; 249291; 3.
DR DIP; DIP-61212N; -.
DR IntAct; P53042; 2.
DR STRING; 10116.ENSRNOP00000023078; -.
DR iPTMnet; P53042; -.
DR PhosphoSitePlus; P53042; -.
DR SwissPalm; P53042; -.
DR jPOST; P53042; -.
DR PaxDb; P53042; -.
DR PRIDE; P53042; -.
DR Ensembl; ENSRNOT00000023078; ENSRNOP00000023078; ENSRNOG00000016907.
DR GeneID; 65179; -.
DR KEGG; rno:65179; -.
DR UCSC; RGD:68415; rat.
DR CTD; 5536; -.
DR RGD; 68415; Ppp5c.
DR eggNOG; KOG0376; Eukaryota.
DR GeneTree; ENSGT00940000158785; -.
DR HOGENOM; CLU_004962_5_2_1; -.
DR InParanoid; P53042; -.
DR OMA; NHFFMSR; -.
DR OrthoDB; 671536at2759; -.
DR PhylomeDB; P53042; -.
DR TreeFam; TF105562; -.
DR BRENDA; 3.1.3.16; 5301.
DR Reactome; R-RNO-5675221; Negative regulation of MAPK pathway.
DR Reactome; R-RNO-5693565; Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks.
DR Reactome; R-RNO-8939211; ESR-mediated signaling.
DR SABIO-RK; P53042; -.
DR PRO; PR:P53042; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Bgee; ENSRNOG00000016907; Expressed in cerebellum and 20 other tissues.
DR Genevisible; P53042; RN.
DR GO; GO:0071944; C:cell periphery; IDA:RGD.
DR GO; GO:0101031; C:chaperone complex; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0043005; C:neuron projection; IDA:RGD.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0043204; C:perikaryon; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0032991; C:protein-containing complex; ISO:RGD.
DR GO; GO:1990635; C:proximal dendrite; IDA:RGD.
DR GO; GO:0043531; F:ADP binding; ISO:RGD.
DR GO; GO:0005524; F:ATP binding; ISO:RGD.
DR GO; GO:0001965; F:G-protein alpha-subunit binding; IDA:RGD.
DR GO; GO:0031072; F:heat shock protein binding; IPI:RGD.
DR GO; GO:0051879; F:Hsp90 protein binding; ISO:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008017; F:microtubule binding; IDA:RGD.
DR GO; GO:0017018; F:myosin phosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0016791; F:phosphatase activity; ISO:RGD.
DR GO; GO:0004721; F:phosphoprotein phosphatase activity; IDA:UniProtKB.
DR GO; GO:0004722; F:protein serine/threonine phosphatase activity; IDA:ARUK-UCL.
DR GO; GO:0044877; F:protein-containing complex binding; IDA:RGD.
DR GO; GO:0003723; F:RNA binding; ISO:RGD.
DR GO; GO:0071276; P:cellular response to cadmium ion; IEP:RGD.
DR GO; GO:0070301; P:cellular response to hydrogen peroxide; IEP:RGD.
DR GO; GO:0060548; P:negative regulation of cell death; IMP:RGD.
DR GO; GO:1901215; P:negative regulation of neuron death; IMP:RGD.
DR GO; GO:0001933; P:negative regulation of protein phosphorylation; IMP:RGD.
DR GO; GO:0070262; P:peptidyl-serine dephosphorylation; ISS:UniProtKB.
DR GO; GO:2000324; P:positive regulation of glucocorticoid receptor signaling pathway; IMP:RGD.
DR GO; GO:0006470; P:protein dephosphorylation; IDA:RGD.
DR GO; GO:1904550; P:response to arachidonic acid; IDA:ARUK-UCL.
DR GO; GO:0010288; P:response to lead ion; IDA:ARUK-UCL.
DR GO; GO:0043278; P:response to morphine; ISO:RGD.
DR CDD; cd07417; MPP_PP5_C; 1.
DR Gene3D; 1.25.40.10; -; 1.
DR Gene3D; 3.60.21.10; -; 1.
DR InterPro; IPR004843; Calcineurin-like_PHP_ApaH.
DR InterPro; IPR029052; Metallo-depent_PP-like.
DR InterPro; IPR041753; PP5_C.
DR InterPro; IPR013235; PPP_dom.
DR InterPro; IPR006186; Ser/Thr-sp_prot-phosphatase.
DR InterPro; IPR011236; Ser/Thr_PPase_5.
DR InterPro; IPR011990; TPR-like_helical_dom_sf.
DR InterPro; IPR001440; TPR_1.
DR InterPro; IPR019734; TPR_repeat.
DR PANTHER; PTHR45668:SF5; PTHR45668:SF5; 1.
DR Pfam; PF00149; Metallophos; 1.
DR Pfam; PF08321; PPP5; 1.
DR Pfam; PF00515; TPR_1; 1.
DR PRINTS; PR00114; STPHPHTASE.
DR SMART; SM00156; PP2Ac; 1.
DR SMART; SM00028; TPR; 3.
DR SUPFAM; SSF48452; SSF48452; 1.
DR SUPFAM; SSF56300; SSF56300; 1.
DR PROSITE; PS00125; SER_THR_PHOSPHATASE; 1.
DR PROSITE; PS50005; TPR; 3.
DR PROSITE; PS50293; TPR_REGION; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Cell membrane; Cytoplasm; Hydrolase; Magnesium;
KW Manganese; Membrane; Metal-binding; Nucleus; Protein phosphatase;
KW Reference proteome; Repeat; TPR repeat.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P53041"
FT CHAIN 2..499
FT /note="Serine/threonine-protein phosphatase 5"
FT /id="PRO_0000058897"
FT REPEAT 28..61
FT /note="TPR 1"
FT REPEAT 62..95
FT /note="TPR 2"
FT REPEAT 96..129
FT /note="TPR 3"
FT REGION 1..23
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 200..499
FT /note="Catalytic"
FT REGION 495..499
FT /note="Required for autoinhibition"
FT /evidence="ECO:0000269|PubMed:11523989"
FT COMPBIAS 9..23
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 304
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250|UniProtKB:P53041"
FT BINDING 242
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:26182372,
FT ECO:0007744|PDB:4JA7"
FT BINDING 244
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:26182372,
FT ECO:0007744|PDB:4JA7"
FT BINDING 244
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P53041"
FT BINDING 271
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:26182372,
FT ECO:0007744|PDB:4JA7"
FT BINDING 271
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:26182372,
FT ECO:0007744|PDB:4JA7, ECO:0007744|PDB:4JA9"
FT BINDING 275
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P53041"
FT BINDING 303..304
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P53041"
FT BINDING 303
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:26182372,
FT ECO:0007744|PDB:4JA7, ECO:0007744|PDB:4JA9"
FT BINDING 352
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:26182372,
FT ECO:0007744|PDB:4JA7, ECO:0007744|PDB:4JA9"
FT BINDING 400
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P53041"
FT BINDING 427
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:26182372,
FT ECO:0007744|PDB:4JA7, ECO:0007744|PDB:4JA9"
FT BINDING 427
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P53041"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:P53041"
FT MUTAGEN 29
FT /note="E->A: No effect on phosphatase activity."
FT /evidence="ECO:0000269|PubMed:11523989"
FT MUTAGEN 32
FT /note="K->A: No effect on phosphatase activity."
FT /evidence="ECO:0000269|PubMed:11523989"
FT MUTAGEN 40
FT /note="K->A: Slightly reduces activation by arachidonic
FT acid."
FT MUTAGEN 56
FT /note="E->A: No effect on phosphatase activity."
FT /evidence="ECO:0000269|PubMed:11523989"
FT MUTAGEN 63
FT /note="I->A: No effect on phosphatase activity."
FT /evidence="ECO:0000269|PubMed:11523989"
FT MUTAGEN 74
FT /note="R->A: No effect on phosphatase activity."
FT /evidence="ECO:0000269|PubMed:11523989"
FT MUTAGEN 76
FT /note="E->A: Increases basal phosphatase activity."
FT /evidence="ECO:0000269|PubMed:11523989"
FT MUTAGEN 77
FT /note="C->A: No effect on phosphatase activity."
FT /evidence="ECO:0000269|PubMed:11523989"
FT MUTAGEN 80
FT /note="Y->A: No effect on phosphatase activity."
FT /evidence="ECO:0000269|PubMed:11523989"
FT MUTAGEN 93
FT /note="K->E: Loss of inhibition of KCNH2 channel
FT stimulation."
FT /evidence="ECO:0000269|PubMed:16549782"
FT MUTAGEN 97
FT /note="K->A: No effect on phosphatase activity."
FT /evidence="ECO:0000269|PubMed:11523989"
FT MUTAGEN 101
FT /note="R->A: No effect on phosphatase activity."
FT /evidence="ECO:0000269|PubMed:11523989"
FT MUTAGEN 126
FT /note="K->A: Loss of inhibition of KCNH2 channel
FT stimulation."
FT /evidence="ECO:0000269|PubMed:16549782"
FT MUTAGEN 451
FT /note="Y->A: Insensitive to okadaic acid."
FT /evidence="ECO:0000269|PubMed:16549782"
FT HELIX 24..40
FT /evidence="ECO:0007829|PDB:4JA7"
FT HELIX 44..57
FT /evidence="ECO:0007829|PDB:4JA7"
FT HELIX 62..74
FT /evidence="ECO:0007829|PDB:4JA7"
FT HELIX 78..91
FT /evidence="ECO:0007829|PDB:4JA7"
FT HELIX 96..108
FT /evidence="ECO:0007829|PDB:4JA7"
FT HELIX 112..125
FT /evidence="ECO:0007829|PDB:4JA7"
FT HELIX 130..148
FT /evidence="ECO:0007829|PDB:4JA7"
FT HELIX 161..164
FT /evidence="ECO:0007829|PDB:4JA7"
FT HELIX 167..169
FT /evidence="ECO:0007829|PDB:4JA7"
FT HELIX 188..199
FT /evidence="ECO:0007829|PDB:4JA7"
FT HELIX 206..221
FT /evidence="ECO:0007829|PDB:4JA7"
FT STRAND 225..229
FT /evidence="ECO:0007829|PDB:4JA7"
FT STRAND 236..240
FT /evidence="ECO:0007829|PDB:4JA7"
FT HELIX 247..257
FT /evidence="ECO:0007829|PDB:4JA7"
FT STRAND 262..264
FT /evidence="ECO:0007829|PDB:4JA9"
FT STRAND 266..270
FT /evidence="ECO:0007829|PDB:4JA7"
FT STRAND 273..276
FT /evidence="ECO:0007829|PDB:4JA7"
FT HELIX 279..292
FT /evidence="ECO:0007829|PDB:4JA7"
FT TURN 294..296
FT /evidence="ECO:0007829|PDB:4JA7"
FT STRAND 297..300
FT /evidence="ECO:0007829|PDB:4JA7"
FT HELIX 307..313
FT /evidence="ECO:0007829|PDB:4JA7"
FT HELIX 315..322
FT /evidence="ECO:0007829|PDB:4JA7"
FT HELIX 325..335
FT /evidence="ECO:0007829|PDB:4JA7"
FT STRAND 340..344
FT /evidence="ECO:0007829|PDB:4JA7"
FT TURN 345..347
FT /evidence="ECO:0007829|PDB:4JA7"
FT STRAND 348..353
FT /evidence="ECO:0007829|PDB:4JA7"
FT STRAND 357..359
FT /evidence="ECO:0007829|PDB:4JA9"
FT HELIX 363..367
FT /evidence="ECO:0007829|PDB:4JA7"
FT STRAND 372..374
FT /evidence="ECO:0007829|PDB:4JA7"
FT STRAND 377..379
FT /evidence="ECO:0007829|PDB:4JA7"
FT HELIX 380..386
FT /evidence="ECO:0007829|PDB:4JA7"
FT STRAND 391..397
FT /evidence="ECO:0007829|PDB:4JA7"
FT STRAND 401..406
FT /evidence="ECO:0007829|PDB:4JA7"
FT HELIX 408..418
FT /evidence="ECO:0007829|PDB:4JA7"
FT STRAND 422..425
FT /evidence="ECO:0007829|PDB:4JA7"
FT STRAND 433..437
FT /evidence="ECO:0007829|PDB:4JA7"
FT HELIX 438..440
FT /evidence="ECO:0007829|PDB:4JA7"
FT STRAND 442..445
FT /evidence="ECO:0007829|PDB:4JA7"
FT HELIX 451..453
FT /evidence="ECO:0007829|PDB:4JA7"
FT STRAND 459..465
FT /evidence="ECO:0007829|PDB:4JA7"
FT STRAND 468..476
FT /evidence="ECO:0007829|PDB:4JA7"
FT TURN 486..489
FT /evidence="ECO:0007829|PDB:4JA7"
FT HELIX 492..494
FT /evidence="ECO:0007829|PDB:4JA9"
SQ SEQUENCE 499 AA; 56917 MW; 720A7FB7AFC701D2 CRC64;
MAMAEGERTE CAEPPRDEPP AEGTLKRAEE LKTQANDYFK AKDYENAIKF YSQAIELNPS
NAIYYGNRSL AYLRTECYGY ALGDATRAIE LDKKYIKGYY RRAASNMALG KFRAALRDYE
TVVKVKPNDK DAKMKYQECS KIVKQKAFER AIAGDEHRRS VVDSLDIESM TIEDEYSGPK
LEDGKVTITF MKDLMQWYKD QKKLHRKCAY QILVQVKEVL CKLSTLVETT LKETEKITVC
GDTHGQFYDL LNIFELNGLP SETNPYIFNG DFVDRGSFSV EVILTLFGFK LLYPDHFHLL
RGNHETDNMN QIYGFEGEVK AKYTAQMYEL FSEVFEWLPL AQCINGKVLI MHGGLFSEDG
VTLDDIRKIE RNRQPPDSGP MCDLLWSDPQ PQNGRSVSKR GVSCQFGPDV TKAFLEENQL
DYIIRSHEVK AEGYEVAHGG RCVTVFSAPN YCDQMGNKAS YIHLQGSDLR PQFHQFTAVP
HPNVKPMAYA NTLLQLGMM
