ID   PDE4A_RAT               Reviewed;         844 AA.
AC   P54748; P14645; Q9EQR7;
DT   01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1996, sequence version 1.
DT   24-JAN-2024, entry version 164.
DE   RecName: Full=3',5'-cyclic-AMP phosphodiesterase 4A {ECO:0000305};
DE            EC=3.1.4.53 {ECO:0000269|PubMed:8557632};
DE   AltName: Full=DPDE2;
DE   AltName: Full=cAMP-specific phosphodiesterase 4A {ECO:0000305};
GN   Name=Pde4a;
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] (ISOFORMS 3; 4 AND 5).
RX   PubMed=2542942; DOI=10.1073/pnas.86.10.3604;
RA   Davis R.L., Takayasu H., Eberwine M., Myres J.;
RT   "Cloning and characterization of mammalian homologs of the Drosophila
RT   dunce+ gene.";
RL   Proc. Natl. Acad. Sci. U.S.A. 86:3604-3608(1989).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 3; 4 AND 5).
RC   TISSUE=Brain;
RX   PubMed=7958996; DOI=10.1016/0378-1119(94)90155-4;
RA   Bolger G.B., Rodgers L., Riggs M.;
RT   "Differential CNS expression of alternative mRNA isoforms of the mammalian
RT   genes encoding cAMP-specific phosphodiesterases.";
RL   Gene 149:237-244(1994).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION (ISOFORM 2), CATALYTIC
RP   ACTIVITY (ISOFORM 2), BIOPHYSICOCHEMICAL PROPERTIES (ISOFORM 2), ACTIVITY
RP   REGULATION (ISOFORM 2), SUBCELLULAR LOCATION (ISOFORM 2), AND TISSUE
RP   SPECIFICITY (ISOFORM 2).
RC   STRAIN=Sprague-Dawley; TISSUE=Testis;
RX   PubMed=8557632; DOI=10.1074/jbc.271.2.1065;
RA   Bolger G.B., McPhee I., Houslay M.D.;
RT   "Alternative splicing of cAMP-specific phosphodiesterase mRNA transcripts.
RT   Characterization of a novel tissue-specific isoform, RNPDE4A8.";
RL   J. Biol. Chem. 271:1065-1071(1996).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 319-677 (ISOFORMS 3/4).
RC   TISSUE=Testis;
RX   PubMed=2546153; DOI=10.1073/pnas.86.14.5325;
RA   Swinnen J.V., Joseph D.R., Conti M.;
RT   "Molecular cloning of rat homologues of the Drosophila melanogaster dunce
RT   cAMP phosphodiesterase: evidence for a family of genes.";
RL   Proc. Natl. Acad. Sci. U.S.A. 86:5325-5329(1989).
RN   [5]
RP   PARTIAL NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 6).
RX   PubMed=11306681; DOI=10.1124/mol.59.5.996;
RA   Rena G., Begg F., Ross A., MacKenzie C., McPhee I., Campbell L., Huston E.,
RA   Sullivan M., Houslay M.D.;
RT   "Molecular cloning, genomic positioning, promoter identification, and
RT   characterization of the novel cyclic AMP-specific phosphodiesterase
RT   PDE4A10.";
RL   Mol. Pharmacol. 59:996-1011(2001).
RN   [6]
RP   FUNCTION (ISOFORM 1), CATALYTIC ACTIVITY (ISOFORM 1), PATHWAY,
RP   PHOSPHORYLATION AT SER-147 (ISOFORM 1), AND MUTAGENESIS OF SER-147 AND
RP   SER-161.
RX   PubMed=21323643; DOI=10.1042/bj20101184;
RA   MacKenzie K.F., Wallace D.A., Hill E.V., Anthony D.F., Henderson D.J.,
RA   Houslay D.M., Arthur J.S., Baillie G.S., Houslay M.D.;
RT   "Phosphorylation of cAMP-specific PDE4A5 (phosphodiesterase-4A5) by MK2
RT   (MAPKAPK2) attenuates its activation through protein kinase A
RT   phosphorylation.";
RL   Biochem. J. 435:755-769(2011).
RN   [7]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-147; SER-152; SER-672 AND
RP   SER-674, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=22673903; DOI=10.1038/ncomms1871;
RA   Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA   Olsen J.V.;
RT   "Quantitative maps of protein phosphorylation sites across 14 different rat
RT   organs and tissues.";
RL   Nat. Commun. 3:876-876(2012).
RN   [8]
RP   STRUCTURE BY NMR OF 1-26 OF ISOFORM 3.
RX   PubMed=8663181; DOI=10.1074/jbc.271.28.16703;
RA   Smith K.J., Scotland G., Beattie J., Trayer I.P., Houslay M.D.;
RT   "Determination of the structure of the N-terminal splice region of the
RT   cyclic AMP-specific phosphodiesterase RD1 (RNPDE4A1) by 1H NMR and
RT   identification of the membrane association domain using chimeric
RT   constructs.";
RL   J. Biol. Chem. 271:16703-16711(1996).
CC   -!- FUNCTION: Hydrolyzes the second messenger 3',5'-cyclic AMP (cAMP),
CC       which is a key regulator of many important physiological processes.
CC       {ECO:0000269|PubMed:21323643, ECO:0000269|PubMed:8557632}.
CC   -!- FUNCTION: [Isoform 1]: Efficiently hydrolyzes cAMP.
CC       {ECO:0000269|PubMed:21323643}.
CC   -!- FUNCTION: [Isoform 2]: Efficiently hydrolyzes cAMP.
CC       {ECO:0000269|PubMed:8557632}.
CC   -!- CATALYTIC ACTIVITY: [Isoform 1]:
CC       Reaction=3',5'-cyclic AMP + H2O = AMP + H(+); Xref=Rhea:RHEA:25277,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:58165,
CC         ChEBI:CHEBI:456215; EC=3.1.4.53;
CC         Evidence={ECO:0000269|PubMed:21323643};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25278;
CC         Evidence={ECO:0000305|PubMed:21323643};
CC   -!- CATALYTIC ACTIVITY: [Isoform 2]:
CC       Reaction=3',5'-cyclic AMP + H2O = AMP + H(+); Xref=Rhea:RHEA:25277,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:58165,
CC         ChEBI:CHEBI:456215; EC=3.1.4.53;
CC         Evidence={ECO:0000269|PubMed:8557632};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25278;
CC         Evidence={ECO:0000305|PubMed:8557632};
CC   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC         Evidence={ECO:0000250|UniProtKB:P27815};
CC       Note=Binds 2 divalent metal cations per subunit. Site 1 may
CC       preferentially bind zinc ions. {ECO:0000250|UniProtKB:P27815};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000250|UniProtKB:P27815};
CC       Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC         Evidence={ECO:0000250|UniProtKB:Q07343};
CC       Note=Binds 2 divalent metal cations per subunit (By similarity). Site 2
CC       has a preference for magnesium and/or manganese ions (By similarity).
CC       {ECO:0000250|UniProtKB:P27815, ECO:0000250|UniProtKB:Q07343};
CC   -!- ACTIVITY REGULATION: [Isoform 2]: Inhibited by rolipram.
CC       {ECO:0000269|PubMed:8557632}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES: [Isoform 2]:
CC       Kinetic parameters:
CC         KM=5.4 uM for cAMP {ECO:0000269|PubMed:8557632};
CC   -!- PATHWAY: Purine metabolism; 3',5'-cyclic AMP degradation; AMP from
CC       3',5'-cyclic AMP: step 1/1. {ECO:0000305|PubMed:21323643}.
CC   -!- SUBUNIT: Interacts with LYN (via SH3 domain). Interacts with ARRB2.
CC       {ECO:0000250|UniProtKB:P27815}.
CC   -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm, cytosol
CC       {ECO:0000269|PubMed:8557632}. Membrane; Peripheral membrane protein
CC       {ECO:0000269|PubMed:8557632}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=6;
CC       Name=1; Synonyms=PDE4A5 {ECO:0000303|PubMed:21323643};
CC         IsoId=P54748-1; Sequence=Displayed;
CC       Name=2; Synonyms=PDE4A8;
CC         IsoId=P54748-2; Sequence=VSP_004565;
CC       Name=3;
CC         IsoId=P54748-3; Sequence=VSP_004566, VSP_004567;
CC       Name=4; Synonyms=Medium;
CC         IsoId=P54748-4; Sequence=VSP_004568;
CC       Name=5; Synonyms=Short;
CC         IsoId=P54748-5; Sequence=VSP_004569, VSP_004570;
CC       Name=6; Synonyms=PDE4A10;
CC         IsoId=P54748-6; Sequence=VSP_038187;
CC   -!- TISSUE SPECIFICITY: [Isoform 2]: Isoform 2 is testis specific.
CC       {ECO:0000269|PubMed:8557632}.
CC   -!- PTM: [Isoform 1]: Phosphorylated by MAPKAPK2 at Ser-147; it counteracts
CC       PKA-induced activation of PDE4A and modulates intracellular cAMP
CC       levels. Likely involved in cellular desensitization to cAMP signaling.
CC       {ECO:0000269|PubMed:21323643}.
CC   -!- PTM: Proteolytically cleaved by CASP3. {ECO:0000250|UniProtKB:P27815}.
CC   -!- MISCELLANEOUS: [Isoform 6]: Incomplete sequence. {ECO:0000305}.
CC   -!- SIMILARITY: Belongs to the cyclic nucleotide phosphodiesterase family.
CC       PDE4 subfamily. {ECO:0000305}.
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DR   EMBL; L27057; AAC27098.1; -; mRNA.
DR   EMBL; L36467; AAB00357.1; -; mRNA.
DR   EMBL; L27062; AAA56859.1; -; mRNA.
DR   EMBL; M25348; AAA41848.1; -; mRNA.
DR   EMBL; M28411; AAA41823.1; -; mRNA.
DR   EMBL; M26715; AAC37699.1; -; mRNA.
DR   EMBL; M26716; AAA41101.1; -; mRNA.
DR   EMBL; M26717; AAA41102.1; -; mRNA.
DR   EMBL; AF110461; AAF14352.2; -; mRNA.
DR   PIR; I53865; I53865.
DR   PIR; I67946; I67946.
DR   RefSeq; NP_037233.3; NM_013101.3.
DR   PDB; 1LOI; NMR; -; A=1-25.
DR   PDBsum; 1LOI; -.
DR   AlphaFoldDB; P54748; -.
DR   SMR; P54748; -.
DR   BioGRID; 247667; 4.
DR   IntAct; P54748; 1.
DR   STRING; 10116.ENSRNOP00000057815; -.
DR   BindingDB; P54748; -.
DR   ChEMBL; CHEMBL4964; -.
DR   DrugCentral; P54748; -.
DR   iPTMnet; P54748; -.
DR   PhosphoSitePlus; P54748; -.
DR   PaxDb; 10116-ENSRNOP00000057815; -.
DR   GeneID; 25638; -.
DR   KEGG; rno:25638; -.
DR   UCSC; RGD:3279; rat. [P54748-1]
DR   AGR; RGD:3279; -.
DR   CTD; 5141; -.
DR   RGD; 3279; Pde4a.
DR   eggNOG; KOG3689; Eukaryota.
DR   InParanoid; P54748; -.
DR   OrthoDB; 240889at2759; -.
DR   PhylomeDB; P54748; -.
DR   BRENDA; 3.1.4.53; 5301.
DR   Reactome; R-RNO-180024; DARPP-32 events.
DR   Reactome; R-RNO-418555; G alpha (s) signalling events.
DR   UniPathway; UPA00762; UER00747.
DR   EvolutionaryTrace; P54748; -.
DR   PRO; PR:P54748; -.
DR   Proteomes; UP000002494; Unplaced.
DR   GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR   GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR   GO; GO:0016020; C:membrane; ISO:RGD.
DR   GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR   GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:RGD.
DR   GO; GO:0098685; C:Schaffer collateral - CA1 synapse; IDA:SynGO.
DR   GO; GO:0004115; F:3',5'-cyclic-AMP phosphodiesterase activity; IDA:UniProtKB.
DR   GO; GO:0030552; F:cAMP binding; ISO:RGD.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0006198; P:cAMP catabolic process; IDA:UniProtKB.
DR   GO; GO:0071466; P:cellular response to xenobiotic stimulus; ISO:RGD.
DR   GO; GO:0050804; P:modulation of chemical synaptic transmission; IDA:SynGO.
DR   GO; GO:0106070; P:regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway; ISO:RGD.
DR   GO; GO:0010738; P:regulation of protein kinase A signaling; ISO:RGD.
DR   GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR   GO; GO:0007608; P:sensory perception of smell; ISO:RGD.
DR   GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR   CDD; cd00077; HDc; 1.
DR   Gene3D; 1.10.1300.10; 3'5'-cyclic nucleotide phosphodiesterase, catalytic domain; 1.
DR   InterPro; IPR003607; HD/PDEase_dom.
DR   InterPro; IPR040844; PDE4_UCR.
DR   InterPro; IPR023088; PDEase.
DR   InterPro; IPR002073; PDEase_catalytic_dom.
DR   InterPro; IPR036971; PDEase_catalytic_dom_sf.
DR   InterPro; IPR023174; PDEase_CS.
DR   PANTHER; PTHR11347:SF74; CAMP-SPECIFIC 3',5'-CYCLIC PHOSPHODIESTERASE 4A; 1.
DR   PANTHER; PTHR11347; CYCLIC NUCLEOTIDE PHOSPHODIESTERASE; 1.
DR   Pfam; PF18100; PDE4_UCR; 1.
DR   Pfam; PF00233; PDEase_I; 1.
DR   PRINTS; PR00387; PDIESTERASE1.
DR   SMART; SM00471; HDc; 1.
DR   SUPFAM; SSF109604; HD-domain/PDEase-like; 1.
DR   PROSITE; PS00126; PDEASE_I_1; 1.
DR   PROSITE; PS51845; PDEASE_I_2; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; cAMP; Cytoplasm; Hydrolase;
KW   Isopeptide bond; Magnesium; Manganese; Membrane; Metal-binding;
KW   Phosphoprotein; Reference proteome; Ubl conjugation; Zinc.
FT   CHAIN           1..844
FT                   /note="3',5'-cyclic-AMP phosphodiesterase 4A"
FT                   /id="PRO_0000198808"
FT   DOMAIN          343..672
FT                   /note="PDEase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01192"
FT   REGION          1..124
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          296..317
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          668..690
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          818..844
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        49..76
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        82..96
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        419
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000250|UniProtKB:Q07343"
FT   BINDING         419
FT                   /ligand="3',5'-cyclic AMP"
FT                   /ligand_id="ChEBI:CHEBI:58165"
FT                   /evidence="ECO:0000250|UniProtKB:Q08499"
FT   BINDING         419
FT                   /ligand="AMP"
FT                   /ligand_id="ChEBI:CHEBI:456215"
FT                   /evidence="ECO:0000250|UniProtKB:Q07343"
FT   BINDING         423
FT                   /ligand="AMP"
FT                   /ligand_id="ChEBI:CHEBI:456215"
FT                   /evidence="ECO:0000250|UniProtKB:Q07343"
FT   BINDING         423
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:P27815"
FT   BINDING         459
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:P27815"
FT   BINDING         460
FT                   /ligand="AMP"
FT                   /ligand_id="ChEBI:CHEBI:456215"
FT                   /evidence="ECO:0000250|UniProtKB:Q07343"
FT   BINDING         460
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250|UniProtKB:P27815"
FT   BINDING         460
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /evidence="ECO:0000250|UniProtKB:Q07343"
FT   BINDING         460
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:P27815"
FT   BINDING         460
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:Q07343"
FT   BINDING         577
FT                   /ligand="AMP"
FT                   /ligand_id="ChEBI:CHEBI:456215"
FT                   /evidence="ECO:0000250|UniProtKB:Q07343"
FT   BINDING         577
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:P27815"
FT   BINDING         628
FT                   /ligand="3',5'-cyclic AMP"
FT                   /ligand_id="ChEBI:CHEBI:58165"
FT                   /evidence="ECO:0000250|UniProtKB:Q08499"
FT   BINDING         628
FT                   /ligand="AMP"
FT                   /ligand_id="ChEBI:CHEBI:456215"
FT                   /evidence="ECO:0000250|UniProtKB:Q07343"
FT   BINDING         631
FT                   /ligand="3',5'-cyclic AMP"
FT                   /ligand_id="ChEBI:CHEBI:58165"
FT                   /evidence="ECO:0000250|UniProtKB:Q08499"
FT   BINDING         631
FT                   /ligand="AMP"
FT                   /ligand_id="ChEBI:CHEBI:456215"
FT                   /evidence="ECO:0000250|UniProtKB:Q07343"
FT   SITE            69..70
FT                   /note="Cleavage; by caspase-3"
FT                   /evidence="ECO:0000250|UniProtKB:P27815"
FT   MOD_RES         13
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P27815"
FT   MOD_RES         147
FT                   /note="Phosphoserine; by MAPKAPK2"
FT                   /evidence="ECO:0000269|PubMed:21323643,
FT                   ECO:0007744|PubMed:22673903"
FT   MOD_RES         152
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:22673903"
FT   MOD_RES         160
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P27815"
FT   MOD_RES         204
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P27815"
FT   MOD_RES         333
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P27815"
FT   MOD_RES         672
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:22673903"
FT   MOD_RES         674
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:22673903"
FT   CROSSLNK        344
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO)"
FT                   /evidence="ECO:0000250"
FT   VAR_SEQ         1..318
FT                   /note="Missing (in isoform 5)"
FT                   /evidence="ECO:0000303|PubMed:2542942,
FT                   ECO:0000303|PubMed:7958996"
FT                   /id="VSP_004569"
FT   VAR_SEQ         1..259
FT                   /note="Missing (in isoform 4)"
FT                   /evidence="ECO:0000303|PubMed:2542942,
FT                   ECO:0000303|PubMed:7958996"
FT                   /id="VSP_004568"
FT   VAR_SEQ         1..234
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:2542942,
FT                   ECO:0000303|PubMed:7958996"
FT                   /id="VSP_004566"
FT   VAR_SEQ         1..102
FT                   /note="MEPPAAPSERSLSLSLPGPREGQATLKPPPQHLWRQPRTPIRIQQRGYPDSA
FT                   ERSETERSPHRPIERADAVDTGDRPGLRTTRMSWPSSFHGTGTGGGSSRR -> MPSRK
FT                   RLTLPRIFIVRKNGNS (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:8557632"
FT                   /id="VSP_004565"
FT   VAR_SEQ         1..102
FT                   /note="MEPPAAPSERSLSLSLPGPREGQATLKPPPQHLWRQPRTPIRIQQRGYPDSA
FT                   ERSETERSPHRPIERADAVDTGDRPGLRTTRMSWPSSFHGTGTGGGSSRR -> ALPLG
FT                   PESLTHFSFSEEDTLRHPPGRCVS (in isoform 6)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_038187"
FT   VAR_SEQ         235..256
FT                   /note="WCLEQLETMQTYRSVSEMASHK -> MPLVDFFCETCSKPWLVGWWDQ (in
FT                   isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:2542942,
FT                   ECO:0000303|PubMed:7958996"
FT                   /id="VSP_004567"
FT   VAR_SEQ         354..386
FT                   /note="Missing (in isoform 5)"
FT                   /evidence="ECO:0000303|PubMed:2542942,
FT                   ECO:0000303|PubMed:7958996"
FT                   /id="VSP_004570"
FT   MUTAGEN         147
FT                   /note="S->A: Abolishes phosphorylation by MAPKAPK2."
FT                   /evidence="ECO:0000269|PubMed:21323643"
FT   MUTAGEN         161
FT                   /note="S->A: Does not affect phosphorylation by MAPKAPK2."
FT                   /evidence="ECO:0000269|PubMed:21323643"
FT   CONFLICT        130
FT                   /note="A -> R (in Ref. 5; AAF14352)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        465..466
FT                   /note="GV -> AL (in Ref. 4; AAA41848/AAA41823)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        603..604
FT                   /note="GD -> AH (in Ref. 4; AAA41848/AAA41823)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        833
FT                   /note="A -> T (in Ref. 1; AAC37699/AAA41101/AAA41102 and 5;
FT                   AAF14352)"
FT                   /evidence="ECO:0000305"
FT   HELIX           3..9
FT                   /evidence="ECO:0007829|PDB:1LOI"
FT   HELIX           16..19
FT                   /evidence="ECO:0007829|PDB:1LOI"
FT   HELIX           20..23
FT                   /evidence="ECO:0007829|PDB:1LOI"
SQ   SEQUENCE   844 AA;  93439 MW;  1A5F5101E4DBF1B6 CRC64;
     MEPPAAPSER SLSLSLPGPR EGQATLKPPP QHLWRQPRTP IRIQQRGYPD SAERSETERS
     PHRPIERADA VDTGDRPGLR TTRMSWPSSF HGTGTGGGSS RRLEAENGPT PSPGRSPLDS
     QASPGLVLHA GATTSQRRES FLYRSDSDYD MSPKAVSRSS SVASEAHAED LIVTPFAQVL
     ASLRSVRSNF SLLTNVPIPS NKRSPLGGPP SVCKATLSEE TCQQLARETL EELDWCLEQL
     ETMQTYRSVS EMASHKFKRM LNRELTHLSE MSRSGNQVSE YISNTFLDKQ NEVEIPSPTP
     RQRAFQQPPP SVLRQSQPMS QITGLKKLVH TGSLNTNVPR FGVKTDQEDL LAQELENLSK
     WGLNIFCVSE YAGGRSLSCI MYTIFQERDL LKKFHIPVDT MMMYMLTLED HYHADVAYHN
     SLHAADVLQS THVLLATPAL DAVFTDLEIL AALFAAAIHD VDHPGVSNQF LINTNSELAL
     MYNDESVLEN HHLAVGFKLL QEENCDIFQN LSKRQRQSLR KMVIDMVLAT DMSKHMTLLA
     DLKTMVETKK VTSSGVLLLD NYSDRIQVLR NMVHCADLSN PTKPLELYRQ WTDRIMAEFF
     QQGDRERERG MEISPMCDKH TASVEKSQVG FIDYIVHPLW ETWADLVHPD AQDILDTLED
     NRDWYHSAIR QSPSPPLEEE PGGLGHPSLP DKFQFELTLE EEEEEDSLEV PGLPTTEETF
     LAAEDARAQA VDWSKVKGPS TTVVEVAERL KQETASAYGA PQESMEAVGC SFSPGTPILP
     DVRTLSSSEE APGLLGLPST AAEVEAPRDH LAATRACSAC SGTSGDNSAI ISAPGRWGSG
     GDPA
//