PDE4A_HUMAN
ID PDE4A_HUMAN Reviewed; 886 AA.
AC P27815; O75522; O76092; Q16255; Q16691; Q5DM53; Q6PMT2; Q8IVA7; Q8WUQ3;
AC Q9H3H2;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 3.
DT 03-AUG-2022, entry version 201.
DE RecName: Full=cAMP-specific 3',5'-cyclic phosphodiesterase 4A;
DE EC=3.1.4.53 {ECO:0000269|PubMed:11566027, ECO:0000269|PubMed:15738310, ECO:0000269|PubMed:18095939, ECO:0000269|PubMed:7888306, ECO:0000269|PubMed:9677330};
DE AltName: Full=DPDE2;
DE AltName: Full=PDE46;
GN Name=PDE4A; Synonyms=DPDE2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=8413254; DOI=10.1128/mcb.13.10.6558-6571.1993;
RA Bolger G., Michaeli T., Martins T., St John T., Steiner B., Rodgers L.,
RA Riggs M., Wigler M., Ferguson K.;
RT "A family of human phosphodiesterases homologous to the dunce learning and
RT memory gene product of Drosophila melanogaster are potential targets for
RT antidepressant drugs.";
RL Mol. Cell. Biol. 13:6558-6571(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), FUNCTION (ISOFORM 3), CATALYTIC
RP ACTIVITY (ISOFORM 3), ACTIVITY REGULATION (ISOFORM 3), BIOPHYSICOCHEMICAL
RP PROPERTIES (ISOFORM 3), AND SUBCELLULAR LOCATION (ISOFORM 3).
RX PubMed=7888306; DOI=10.1016/0898-6568(94)00039-5;
RA Sullivan M., Egerton M., Shakur Y., Marquardsen A., Houslay M.D.;
RT "Molecular cloning and expression, in both COS-1 cells and S. cerevisiae,
RT of a human cytosolic type-IVA, cyclic AMP specific phosphodiesterase (hPDE-
RT IVA-h6.1).";
RL Cell. Signal. 6:793-812(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3 AND 5), AND VARIANT GLU-736.
RX PubMed=7772058; DOI=10.1042/bj3080683;
RA Horton Y.M., Sullivan M., Houslay M.D.;
RT "Molecular cloning of a novel splice variant of human type IVA (PDE-IVA)
RT cyclic AMP phosphodiesterase and localization of the gene to the p13.2-q12
RT region of human chromosome 19.";
RL Biochem. J. 308:683-691(1995).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1; 2; 3; 4 AND 5),
RP FUNCTION (ISOFORM 4), CATALYTIC ACTIVITY (ISOFORM 4), ACTIVITY REGULATION
RP (ISOFORM 4), AND SUBCELLULAR LOCATION (ISOFORM 4).
RC TISSUE=Brain;
RX PubMed=9677330; DOI=10.1042/bj3330693;
RA Sullivan M., Rena G., Begg F., Gordon L., Olsen A.S., Houslay M.D.;
RT "Identification and characterization of the human homologue of the short
RT PDE4A cAMP-specific phosphodiesterase 4A variant RD1 (PDE4A1) by analysis
RT of the human HSPDE4A gene locus located at chromosome 19p13.2.";
RL Biochem. J. 333:693-703(1998).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 6), FUNCTION (ISOFORMS 1 AND 6),
RP CATALYTIC ACTIVITY (ISOFORMS 1 AND 6), SUBCELLULAR LOCATION (ISOFORM 6),
RP BIOPHYSICOCHEMICAL PROPERTIES (ISOFORM 6), ACTIVITY REGULATION (ISOFORM 6),
RP TISSUE SPECIFICITY (ISOFORM 6), AND INTERACTION WITH LYN (ISOFORMS 1 AND
RP 6).
RC TISSUE=Brain;
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 NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION (ISOFORMS 1; 2 AND 6),
RP CATALYTIC ACTIVITY (ISOFORMS 1; 2 AND 6), ACTIVITY REGULATION (ISOFORMS 1;
RP 2 AND 6), BIOPHYSICOCHEMICAL PROPERTIES (ISOFORM 2), PATHWAY, SUBCELLULAR
RP LOCATION (ISOFORMS 1; 2 AND 6), PHOSPHORYLATION AT SER-119 (ISOFORM 2),
RP CLEAVAGE BY CASPASE-3 (ISOFORM 1), INTERACTION WITH LYN AND ARRB2 (ISOFORMS
RP 1; 2 AND 6), TISSUE SPECIFICITY (ISOFORMS 1 AND 2), AND DEVELOPMENTAL STAGE
RP (ISOFORM 2).
RX PubMed=15738310; DOI=10.1124/mol.104.009423;
RA Wallace D.A., Johnston L.A., Huston E., Macmaster D., Houslay T.M.,
RA Cheung Y.-F., Campbell L., Millen J.E., Smith R.A., Gall I., Knowles R.G.,
RA Sullivan M., Houslay M.D.;
RT "Identification and characterization of PDE4A11, a novel, widely expressed
RT long isoform encoded by the human PDE4A cAMP phosphodiesterase gene.";
RL Mol. Pharmacol. 67:1920-1934(2005).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 7), FUNCTION (ISOFORM 7), CATALYTIC
RP ACTIVITY (ISOFORM 7), ACTIVITY REGULATION (ISOFORM 7), SUBCELLULAR LOCATION
RP (ISOFORM 7), TISSUE SPECIFICITY (ISOFORM 7), AND PHOSPHORYLATION AT SER-123
RP (ISOFORM 7).
RX PubMed=18095939; DOI=10.1042/bj20071251;
RA Mackenzie K.F., Topping E.C., Bugaj-Gaweda B., Deng C., Cheung Y.-F.,
RA Olsen A.E., Stockard C.R., High Mitchell L., Baillie G.S., Grizzle W.E.,
RA De Vivo M., Houslay M.D., Wang D., Bolger G.B.;
RT "Human PDE4A8, a novel brain-expressed PDE4 cAMP-specific phosphodiesterase
RT that has undergone rapid evolutionary change.";
RL Biochem. J. 411:361-369(2008).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [11]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 112-886, VARIANT GLU-736, FUNCTION, AND
RP CATALYTIC ACTIVITY.
RC TISSUE=Monocyte;
RX PubMed=2160582; DOI=10.1128/mcb.10.6.2678-2686.1990;
RA Livi G.P., Kmetz P., McHale M.M., Cieslinski L.B., Sathe G.M., Taylor D.P.,
RA Davis R.L., Torphy T.J., Balcarek J.M.;
RT "Cloning and expression of cDNA for a human low-Km, rolipram-sensitive
RT cyclic AMP phosphodiesterase.";
RL Mol. Cell. Biol. 10:2678-2686(1990).
RN [12]
RP SEQUENCE REVISION.
RA McLaughlin M.M.;
RL Submitted (JAN-1991) to the EMBL/GenBank/DDBJ databases.
RN [13]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, COFACTOR,
RP PHOSPHORYLATION AT SER-686 AND SER-688, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RX PubMed=11566027; DOI=10.1006/abbi.2001.2513;
RA Lario P.I., Bobechko B., Bateman K., Kelly J., Vrielink A., Huang Z.;
RT "Purification and characterization of the human pde4a catalytic domain
RT (pde4a(330-723)) expressed in sf9 cells.";
RL Arch. Biochem. Biophys. 394:54-60(2001).
RN [14]
RP SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
RX PubMed=14759258; DOI=10.1186/gb-2004-5-2-r8;
RA Hillman R.T., Green R.E., Brenner S.E.;
RT "An unappreciated role for RNA surveillance.";
RL Genome Biol. 5:R8.1-R8.16(2004).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-165, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [17]
RP SUMOYLATION AT LYS-358 BY PIAS4.
RX PubMed=20196770; DOI=10.1042/bj20091672;
RA Li X., Vadrevu S., Dunlop A., Day J., Advant N., Troeger J., Klussmann E.,
RA Jaffrey E., Hay R.T., Adams D.R., Houslay M.D., Baillie G.S.;
RT "Selective SUMO modification of cAMP-specific phosphodiesterase-4D5
RT (PDE4D5) regulates the functional consequences of phosphorylation by PKA
RT and ERK.";
RL Biochem. J. 428:55-65(2010).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-13; SER-209 AND SER-346, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [19] {ECO:0007744|PDB:2QYK}
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 351-683 IN COMPLEX WITH ZINC;
RP MAGNESIUM AND THE INHIBITOR NVP, FUNCTION (ISOFORM 6), CATALYTIC ACTIVITY
RP (ISOFORM 6), AND COFACTOR.
RX PubMed=17727341; DOI=10.1042/bj20070970;
RA Wang H., Peng M.-S., Chen Y., Geng J., Robinson H., Houslay M.D., Cai J.,
RA Ke H.;
RT "Structures of the four subfamilies of phosphodiesterase-4 provide insight
RT into the selectivity of their inhibitors.";
RL Biochem. J. 408:193-201(2007).
RN [20] {ECO:0007744|PDB:3I8V}
RP X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 351-683 IN COMPLEX WITH ZINC;
RP MAGNESIUM AND INHIBITOR, AND COFACTOR.
RA Cheng R.K.Y., Crawley L., Barker J., Wood M., Felicetti B., Whittaker M.;
RT "Crystal structure of human PDE4a with 4-(3-butoxy-4-methoxyphenyl)methyl-
RT 2-imidazolidone.";
RL Submitted (JUL-2009) to the PDB data bank.
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:11566027, ECO:0000269|PubMed:2160582}.
CC -!- FUNCTION: [Isoform 1]: Efficiently hydrolyzes cAMP.
CC {ECO:0000269|PubMed:11306681, ECO:0000269|PubMed:15738310}.
CC -!- FUNCTION: [Isoform 2]: Efficiently hydrolyzes cAMP.
CC {ECO:0000269|PubMed:15738310}.
CC -!- FUNCTION: [Isoform 3]: Efficiently hydrolyzes cAMP. The
CC phosphodiesterase activity is not affected by calcium, calmodulin or
CC cyclic GMP (cGMP) levels. Does not hydrolyze cGMP.
CC {ECO:0000269|PubMed:7888306}.
CC -!- FUNCTION: [Isoform 4]: Efficiently hydrolyzes cAMP.
CC {ECO:0000269|PubMed:9677330}.
CC -!- FUNCTION: [Isoform 6]: Efficiently hydrolyzes cAMP.
CC {ECO:0000269|PubMed:11306681, ECO:0000269|PubMed:15738310,
CC ECO:0000269|PubMed:17727341}.
CC -!- FUNCTION: [Isoform 7]: Efficiently hydrolyzes cAMP.
CC {ECO:0000269|PubMed:18095939}.
CC -!- CATALYTIC ACTIVITY:
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:11566027, ECO:0000269|PubMed:2160582};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25278;
CC Evidence={ECO:0000305|PubMed:11566027, ECO:0000305|PubMed:2160582};
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:11306681, ECO:0000269|PubMed:15738310};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25278;
CC Evidence={ECO:0000305|PubMed:11306681, ECO:0000305|PubMed:15738310};
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:15738310};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25278;
CC Evidence={ECO:0000305|PubMed:15738310};
CC -!- CATALYTIC ACTIVITY: [Isoform 3]:
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:7888306};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25278;
CC Evidence={ECO:0000305|PubMed:7888306};
CC -!- CATALYTIC ACTIVITY: [Isoform 4]:
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:9677330};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25278;
CC Evidence={ECO:0000305|PubMed:9677330};
CC -!- CATALYTIC ACTIVITY: [Isoform 6]:
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:11306681, ECO:0000269|PubMed:15738310,
CC ECO:0000269|PubMed:17727341};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25278;
CC Evidence={ECO:0000305|PubMed:11306681, ECO:0000305|PubMed:15738310,
CC ECO:0000305|PubMed:17727341};
CC -!- CATALYTIC ACTIVITY: [Isoform 7]:
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:18095939};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25278;
CC Evidence={ECO:0000305|PubMed:18095939};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:17727341, ECO:0000269|Ref.20};
CC Note=Binds 2 divalent metal cations per subunit. Site 1 may
CC preferentially bind zinc ions. {ECO:0000269|PubMed:17727341,
CC ECO:0000269|Ref.20};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:17727341, ECO:0000269|Ref.20};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:Q07343};
CC Note=Binds 2 divalent metal cations per subunit (PubMed:17727341,
CC Ref.20). Site 2 has a preference for magnesium and/or manganese ions
CC (By similarity). {ECO:0000250|UniProtKB:Q07343,
CC ECO:0000269|PubMed:17727341, ECO:0000269|Ref.20};
CC -!- ACTIVITY REGULATION: [Isoform 1]: Inhibited by rolipram, cilomilast, Ro
CC 20-1724, roflumilast and denbufylline. {ECO:0000269|PubMed:15738310}.
CC -!- ACTIVITY REGULATION: [Isoform 2]: Inhibited by rolipram, cilomilast, Ro
CC 20-1724, roflumilast and denbufylline. {ECO:0000269|PubMed:15738310}.
CC -!- ACTIVITY REGULATION: [Isoform 3]: Inhibited by rolipram.
CC {ECO:0000269|PubMed:7888306}.
CC -!- ACTIVITY REGULATION: [Isoform 4]: Inhibited by rolipram.
CC {ECO:0000269|PubMed:9677330}.
CC -!- ACTIVITY REGULATION: [Isoform 6]: Inhibited by rolipram, cilomilast, Ro
CC 20-1724, roflumilast and denbufylline. {ECO:0000269|PubMed:11306681,
CC ECO:0000269|PubMed:15738310}.
CC -!- ACTIVITY REGULATION: [Isoform 7]: Inhibited by rolipram and cilomilast.
CC {ECO:0000269|PubMed:18095939}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=2 uM for cAMP {ECO:0000269|PubMed:11566027};
CC Vmax=8.8 umol/min/mg enzyme towards cAMP
CC {ECO:0000269|PubMed:11566027};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES: [Isoform 2]:
CC Kinetic parameters:
CC KM=4.2 uM for cAMP {ECO:0000269|PubMed:15738310};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES: [Isoform 3]:
CC Kinetic parameters:
CC KM=6 uM for cAMP {ECO:0000269|PubMed:7888306};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES: [Isoform 6]:
CC Kinetic parameters:
CC KM=3 uM for cAMP {ECO:0000269|PubMed:11306681};
CC KM=5.1 uM for cAMP {ECO:0000269|PubMed:17727341};
CC -!- PATHWAY: Purine metabolism; 3',5'-cyclic AMP degradation; AMP from
CC 3',5'-cyclic AMP: step 1/1. {ECO:0000305|PubMed:15738310}.
CC -!- SUBUNIT: [Isoform 1]: Interacts with LYN (via SH3 domain). Interacts
CC with ARRB2. {ECO:0000269|PubMed:11306681, ECO:0000269|PubMed:15738310}.
CC -!- SUBUNIT: [Isoform 2]: Interacts with LYN (via SH3 domain). Interacts
CC with ARRB2. {ECO:0000269|PubMed:15738310}.
CC -!- SUBUNIT: [Isoform 6]: Interacts with LYN (via SH3 domain). Interacts
CC with ARRB2. {ECO:0000269|PubMed:11306681, ECO:0000269|PubMed:15738310}.
CC -!- INTERACTION:
CC P27815-4; P55212: CASP6; NbExp=3; IntAct=EBI-12080840, EBI-718729;
CC P27815-4; O14569: CYB561D2; NbExp=3; IntAct=EBI-12080840, EBI-717654;
CC P27815-4; P13473-2: LAMP2; NbExp=3; IntAct=EBI-12080840, EBI-21591415;
CC P27815-4; Q9UJX0: OSGIN1; NbExp=3; IntAct=EBI-12080840, EBI-9057006;
CC P27815-4; P16118: PFKFB1; NbExp=3; IntAct=EBI-12080840, EBI-709807;
CC P27815-4; O75400-2: PRPF40A; NbExp=3; IntAct=EBI-12080840, EBI-5280197;
CC P27815-4; Q9Y371: SH3GLB1; NbExp=3; IntAct=EBI-12080840, EBI-2623095;
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm, perinuclear region
CC {ECO:0000269|PubMed:15738310}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm, perinuclear region
CC {ECO:0000269|PubMed:15738310}. Cell projection, ruffle membrane
CC {ECO:0000269|PubMed:15738310}.
CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Cytoplasm, cytosol
CC {ECO:0000269|PubMed:7888306}.
CC -!- SUBCELLULAR LOCATION: [Isoform 4]: Membrane; Peripheral membrane
CC protein {ECO:0000269|PubMed:9677330}. Note=Isoform 4 has propensity for
CC association with membranes. {ECO:0000269|PubMed:9677330}.
CC -!- SUBCELLULAR LOCATION: [Isoform 6]: Cytoplasm, perinuclear region
CC {ECO:0000269|PubMed:11306681, ECO:0000269|PubMed:15738310}.
CC -!- SUBCELLULAR LOCATION: [Isoform 7]: Cytoplasm, cytosol. Membrane;
CC Peripheral membrane protein {ECO:0000269|PubMed:18095939}.
CC Note=Predominantly cytosolic. {ECO:0000269|PubMed:18095939}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=7;
CC Comment=Additional isoforms seem to exist.;
CC Name=1; Synonyms=PDE4A4 {ECO:0000303|PubMed:11306681}, PDE4A4B
CC {ECO:0000303|PubMed:11306681}, PDE46;
CC IsoId=P27815-1; Sequence=Displayed;
CC Name=2; Synonyms=TM3, PDE4A11 {ECO:0000303|PubMed:15738310};
CC IsoId=P27815-2; Sequence=VSP_004556;
CC Name=3; Synonyms=PDE4A7, PDE4A6;
CC IsoId=P27815-3; Sequence=VSP_004557;
CC Name=4; Synonyms=PDE4A1, RD1;
CC IsoId=P27815-4; Sequence=VSP_004558;
CC Name=5; Synonyms=PDE4A8A, 2EL;
CC IsoId=P27815-5; Sequence=VSP_004559, VSP_004560, VSP_004561;
CC Name=6; Synonyms=PDE4A10 {ECO:0000303|PubMed:11306681};
CC IsoId=P27815-6; Sequence=VSP_038185;
CC Name=7; Synonyms=PDE4A8 {ECO:0000303|PubMed:18095939};
CC IsoId=P27815-7; Sequence=VSP_038186;
CC -!- TISSUE SPECIFICITY: [Isoform 1]: Expressed in lymphoid cell subsets
CC including CD8-positive T cells and T-helper 2 cells. Expressed in
CC dendritic cells. {ECO:0000269|PubMed:15738310}.
CC -!- TISSUE SPECIFICITY: [Isoform 2]: Highly expressed in liver, stomach,
CC testis, thyroid and adrenal glands and at a lower extent in placenta,
CC kidney, pancreas, ovary, uterus and skin. Expressed in myeloid cell
CC subsets including dendritic cells, monocytes, macrophages, eosinophils
CC and mast cells. Expressed in natural killer cells. Expressed in
CC bronchial smooth muscle. {ECO:0000269|PubMed:15738310}.
CC -!- TISSUE SPECIFICITY: [Isoform 6]: Expressed at high levels in the heart
CC and small intestine. It is also found in the brain, kidney, spleen,
CC colon, salivary gland, ovary and peripheral blood lymphocytes.
CC {ECO:0000269|PubMed:11306681}.
CC -!- TISSUE SPECIFICITY: [Isoform 7]: Expressed predominantly in skeletal
CC muscle and brain and at lower levels in the testis. Found in specific
CC neuronal subpopulations including cortical pyramidal neurons, horn
CC neurons in the spinal cord and Purkinje cells in cerebellum (at protein
CC level). {ECO:0000269|PubMed:18095939}.
CC -!- DEVELOPMENTAL STAGE: [Isoform 2]: Expressed in fetal brain.
CC {ECO:0000269|PubMed:15738310}.
CC -!- PTM: [Isoform 1]: Proteolytically cleaved by CASP3.
CC {ECO:0000269|PubMed:15738310}.
CC -!- PTM: [Isoform 2]: Phosphorylated at Ser-119 by PKA.
CC {ECO:0000269|PubMed:15738310}.
CC -!- MISCELLANEOUS: [Isoform 5]: May be produced at very low levels due to a
CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC decay. Probably represents a non-functional splice isoform.
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the cyclic nucleotide phosphodiesterase family.
CC PDE4 subfamily. {ECO:0000305}.
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DR EMBL; L20965; AAA03588.1; -; mRNA.
DR EMBL; S75213; AAB33798.1; -; mRNA.
DR EMBL; U18087; AAC50458.1; -; mRNA.
DR EMBL; U18088; AAA98540.1; -; mRNA.
DR EMBL; AF069491; AAC35012.1; -; Genomic_DNA.
DR EMBL; AF069487; AAC35012.1; JOINED; Genomic_DNA.
DR EMBL; AF069489; AAC35012.1; JOINED; Genomic_DNA.
DR EMBL; AF069490; AAC35012.1; JOINED; Genomic_DNA.
DR EMBL; AF069491; AAC35013.1; -; Genomic_DNA.
DR EMBL; AF069489; AAC35013.1; JOINED; Genomic_DNA.
DR EMBL; AF069490; AAC35013.1; JOINED; Genomic_DNA.
DR EMBL; AF069491; AAC35014.1; -; Genomic_DNA.
DR EMBL; AF069489; AAC35014.1; JOINED; Genomic_DNA.
DR EMBL; AF069490; AAC35014.1; JOINED; Genomic_DNA.
DR EMBL; AF069491; AAC35015.1; -; Genomic_DNA.
DR EMBL; AF069488; AAC35015.1; JOINED; Genomic_DNA.
DR EMBL; AF069489; AAC35015.1; JOINED; Genomic_DNA.
DR EMBL; AF069490; AAC35015.1; JOINED; Genomic_DNA.
DR EMBL; U68532; AAC63832.1; -; mRNA.
DR EMBL; U97584; AAC25679.1; -; mRNA.
DR EMBL; AF073745; AAD34217.2; -; mRNA.
DR EMBL; AY618547; AAU82096.1; -; mRNA.
DR EMBL; AY593872; AAT00628.1; -; mRNA.
DR EMBL; AC011548; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC011529; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC011461; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471106; EAW84104.1; -; Genomic_DNA.
DR EMBL; CH471106; EAW84105.1; -; Genomic_DNA.
DR EMBL; CH471106; EAW84108.1; -; Genomic_DNA.
DR EMBL; BC019864; AAH19864.1; -; mRNA.
DR EMBL; BC038234; AAH38234.1; -; mRNA.
DR EMBL; M37744; AAA69697.1; -; mRNA.
DR CCDS; CCDS12238.1; -. [P27815-4]
DR CCDS; CCDS45961.1; -. [P27815-1]
DR CCDS; CCDS45962.1; -. [P27815-2]
DR CCDS; CCDS45963.1; -. [P27815-6]
DR CCDS; CCDS58649.1; -. [P27815-7]
DR PIR; A54442; A54442.
DR PIR; S55348; S55348.
DR RefSeq; NP_001104777.1; NM_001111307.1. [P27815-1]
DR RefSeq; NP_001104778.1; NM_001111308.1. [P27815-2]
DR RefSeq; NP_001104779.1; NM_001111309.1. [P27815-6]
DR RefSeq; NP_001230050.1; NM_001243121.1. [P27815-7]
DR RefSeq; NP_006193.1; NM_006202.2. [P27815-4]
DR RefSeq; XP_011526356.1; XM_011528054.1. [P27815-7]
DR PDB; 2QYK; X-ray; 2.10 A; A/B=351-683.
DR PDB; 3I8V; X-ray; 2.25 A; A/B=351-683.
DR PDB; 3TVX; X-ray; 2.84 A; A/B=351-683.
DR PDBsum; 2QYK; -.
DR PDBsum; 3I8V; -.
DR PDBsum; 3TVX; -.
DR AlphaFoldDB; P27815; -.
DR SMR; P27815; -.
DR BioGRID; 111167; 21.
DR IntAct; P27815; 16.
DR MINT; P27815; -.
DR STRING; 9606.ENSP00000370078; -.
DR BindingDB; P27815; -.
DR ChEMBL; CHEMBL254; -.
DR DrugBank; DB06842; (4R)-4-(3-butoxy-4-methoxybenzyl)imidazolidin-2-one.
DR DrugBank; DB08299; 4-[8-(3-nitrophenyl)-1,7-naphthyridin-6-yl]benzoic acid.
DR DrugBank; DB01427; Amrinone.
DR DrugBank; DB00201; Caffeine.
DR DrugBank; DB05219; Crisaborole.
DR DrugBank; DB00975; Dipyridamole.
DR DrugBank; DB06751; Drotaverine.
DR DrugBank; DB00651; Dyphylline.
DR DrugBank; DB00824; Enprofylline.
DR DrugBank; DB05266; Ibudilast.
DR DrugBank; DB01088; Iloprost.
DR DrugBank; DB01303; Oxtriphylline.
DR DrugBank; DB01791; Piclamilast.
DR DrugBank; DB06479; Propentofylline.
DR DrugBank; DB01656; Roflumilast.
DR DrugBank; DB00277; Theophylline.
DR DrugBank; DB08811; Tofisopam.
DR DrugBank; DB09283; Trapidil.
DR DrugCentral; P27815; -.
DR GuidetoPHARMACOLOGY; 1300; -.
DR iPTMnet; P27815; -.
DR PhosphoSitePlus; P27815; -.
DR BioMuta; PDE4A; -.
DR DMDM; 116242706; -.
DR EPD; P27815; -.
DR jPOST; P27815; -.
DR MassIVE; P27815; -.
DR MaxQB; P27815; -.
DR PaxDb; P27815; -.
DR PeptideAtlas; P27815; -.
DR PRIDE; P27815; -.
DR ProteomicsDB; 54411; -. [P27815-1]
DR ProteomicsDB; 54412; -. [P27815-2]
DR ProteomicsDB; 54413; -. [P27815-3]
DR ProteomicsDB; 54414; -. [P27815-4]
DR ProteomicsDB; 54415; -. [P27815-5]
DR ProteomicsDB; 54416; -. [P27815-6]
DR ProteomicsDB; 54417; -. [P27815-7]
DR Antibodypedia; 4321; 492 antibodies from 26 providers.
DR DNASU; 5141; -.
DR Ensembl; ENST00000293683.9; ENSP00000293683.4; ENSG00000065989.16. [P27815-2]
DR Ensembl; ENST00000344979.7; ENSP00000341007.2; ENSG00000065989.16. [P27815-4]
DR Ensembl; ENST00000380702.7; ENSP00000370078.3; ENSG00000065989.16. [P27815-1]
DR Ensembl; ENST00000440014.6; ENSP00000394754.1; ENSG00000065989.16. [P27815-6]
DR Ensembl; ENST00000592685.5; ENSP00000468507.1; ENSG00000065989.16. [P27815-7]
DR GeneID; 5141; -.
DR KEGG; hsa:5141; -.
DR MANE-Select; ENST00000380702.7; ENSP00000370078.3; NM_001111307.2; NP_001104777.1.
DR UCSC; uc002moj.3; human. [P27815-1]
DR CTD; 5141; -.
DR DisGeNET; 5141; -.
DR GeneCards; PDE4A; -.
DR HGNC; HGNC:8780; PDE4A.
DR HPA; ENSG00000065989; Low tissue specificity.
DR MIM; 600126; gene.
DR neXtProt; NX_P27815; -.
DR OpenTargets; ENSG00000065989; -.
DR PharmGKB; PA33128; -.
DR VEuPathDB; HostDB:ENSG00000065989; -.
DR eggNOG; KOG3689; Eukaryota.
DR GeneTree; ENSGT00940000159788; -.
DR HOGENOM; CLU_005940_5_0_1; -.
DR OMA; SHCICSF; -.
DR OrthoDB; 904682at2759; -.
DR PhylomeDB; P27815; -.
DR TreeFam; TF314638; -.
DR BRENDA; 3.1.4.17; 2681.
DR BRENDA; 3.1.4.53; 2681.
DR PathwayCommons; P27815; -.
DR Reactome; R-HSA-180024; DARPP-32 events.
DR Reactome; R-HSA-418555; G alpha (s) signalling events.
DR SABIO-RK; P27815; -.
DR SignaLink; P27815; -.
DR SIGNOR; P27815; -.
DR UniPathway; UPA00762; UER00747.
DR BioGRID-ORCS; 5141; 20 hits in 1081 CRISPR screens.
DR ChiTaRS; PDE4A; human.
DR EvolutionaryTrace; P27815; -.
DR GeneWiki; PDE4A; -.
DR GenomeRNAi; 5141; -.
DR Pharos; P27815; Tclin.
DR PRO; PR:P27815; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; P27815; protein.
DR Bgee; ENSG00000065989; Expressed in pancreatic ductal cell and 184 other tissues.
DR ExpressionAtlas; P27815; baseline and differential.
DR Genevisible; P27815; HS.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0019898; C:extrinsic component of membrane; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; TAS:ProtInc.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0032587; C:ruffle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0004115; F:3',5'-cyclic-AMP phosphodiesterase activity; IDA:BHF-UCL.
DR GO; GO:0004114; F:3',5'-cyclic-nucleotide phosphodiesterase activity; IBA:GO_Central.
DR GO; GO:0030552; F:cAMP binding; IGI:BHF-UCL.
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; IEA:Ensembl.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; TAS:Reactome.
DR GO; GO:0106070; P:regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0010738; P:regulation of protein kinase A signaling; IEA:Ensembl.
DR GO; GO:0007608; P:sensory perception of smell; IEA:Ensembl.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR CDD; cd00077; HDc; 1.
DR Gene3D; 1.10.1300.10; -; 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 Pfam; PF18100; PDE4_UCR; 1.
DR Pfam; PF00233; PDEase_I; 1.
DR PRINTS; PR00387; PDIESTERASE1.
DR SMART; SM00471; HDc; 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; Cell membrane; Cell projection;
KW Cytoplasm; Hydrolase; Isopeptide bond; Manganese; Membrane; Metal-binding;
KW Phosphoprotein; Reference proteome; Ubl conjugation; Zinc.
FT CHAIN 1..886
FT /note="cAMP-specific 3',5'-cyclic phosphodiesterase 4A"
FT /id="PRO_0000198806"
FT DOMAIN 357..686
FT /note="PDEase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01192"
FT REGION 1..128
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 294..331
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 682..705
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 866..886
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 78..100
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 300..314
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 315..330
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 433
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:Q07343"
FT BINDING 433
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /evidence="ECO:0000250|UniProtKB:Q08499"
FT BINDING 433
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000250|UniProtKB:Q07343"
FT BINDING 437
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000250|UniProtKB:Q07343"
FT BINDING 437
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:17727341, ECO:0000269|Ref.20,
FT ECO:0007744|PDB:2QYK, ECO:0007744|PDB:3I8V"
FT BINDING 473
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:17727341, ECO:0000269|Ref.20,
FT ECO:0007744|PDB:2QYK, ECO:0007744|PDB:3I8V"
FT BINDING 474
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000250|UniProtKB:Q07343"
FT BINDING 474
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:17727341, ECO:0000269|Ref.20,
FT ECO:0007744|PDB:2QYK, ECO:0007744|PDB:3I8V"
FT BINDING 474
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000250|UniProtKB:Q07343"
FT BINDING 474
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:17727341, ECO:0000269|Ref.20,
FT ECO:0007744|PDB:2QYK, ECO:0007744|PDB:3I8V"
FT BINDING 474
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q07343"
FT BINDING 591
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000250|UniProtKB:Q07343"
FT BINDING 591
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:17727341, ECO:0000269|Ref.20,
FT ECO:0007744|PDB:2QYK, ECO:0007744|PDB:3I8V"
FT BINDING 642
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /evidence="ECO:0000250|UniProtKB:Q08499"
FT BINDING 642
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000250|UniProtKB:Q07343"
FT BINDING 645
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /evidence="ECO:0000250|UniProtKB:Q08499"
FT BINDING 645
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:0000269|PubMed:15738310"
FT MOD_RES 13
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 152
FT /note="Phosphoserine; by MAPKAPK2"
FT /evidence="ECO:0000250|UniProtKB:P54748"
FT MOD_RES 157
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P54748"
FT MOD_RES 165
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 209
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 346
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 686
FT /note="Phosphoserine"
FT /evidence="ECO:0000305|PubMed:11566027"
FT MOD_RES 688
FT /note="Phosphoserine"
FT /evidence="ECO:0000305|PubMed:11566027"
FT CROSSLNK 358
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000269|PubMed:20196770"
FT VAR_SEQ 1..367
FT /note="MEPPTVPSERSLSLSLPGPREGQATLKPPPQHLWRQPRTPIRIQQRGYSDSA
FT ERAERERQPHRPIERADAMDTSDRPGLRTTRMSWPSSFHGTGTGSGGAGGGSSRRFEAE
FT NGPTPSPGRSPLDSQASPGLVLHAGAATSQRRESFLYRSDSDYDMSPKTMSRNSSVTSE
FT AHAEDLIVTPFAQVLASLRSVRSNFSLLTNVPVPSNKRSPLGGPTPVCKATLSEETCQQ
FT LARETLEELDWCLEQLETMQTYRSVSEMASHKFKRMLNRELTHLSEMSRSGNQVSEYIS
FT TTFLDKQNEVEIPSPTMKEREKQQAPRPRPSQPPPPPVPHLQPMSQITGLKKLMHSNSL
FT NNSNIPRFGVKTDQEELLAQ -> MVLPSDQGFKLLGNVLQGPEPYRLLTSGLRLHQ
FT (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:7772058,
FT ECO:0000303|PubMed:9677330"
FT /id="VSP_004559"
FT VAR_SEQ 1..261
FT /note="MEPPTVPSERSLSLSLPGPREGQATLKPPPQHLWRQPRTPIRIQQRGYSDSA
FT ERAERERQPHRPIERADAMDTSDRPGLRTTRMSWPSSFHGTGTGSGGAGGGSSRRFEAE
FT NGPTPSPGRSPLDSQASPGLVLHAGAATSQRRESFLYRSDSDYDMSPKTMSRNSSVTSE
FT AHAEDLIVTPFAQVLASLRSVRSNFSLLTNVPVPSNKRSPLGGPTPVCKATLSEETCQQ
FT LARETLEELDWCLEQLETMQTYRSVSEMASHK -> MPLVDFFCETCSKPWLVGWWDQ
FT (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:9677330"
FT /id="VSP_004558"
FT VAR_SEQ 1..209
FT /note="MEPPTVPSERSLSLSLPGPREGQATLKPPPQHLWRQPRTPIRIQQRGYSDSA
FT ERAERERQPHRPIERADAMDTSDRPGLRTTRMSWPSSFHGTGTGSGGAGGGSSRRFEAE
FT NGPTPSPGRSPLDSQASPGLVLHAGAATSQRRESFLYRSDSDYDMSPKTMSRNSSVTSE
FT AHAEDLIVTPFAQVLASLRSVRSNFSLLTNVPVPSNKRS -> MCPFPVTTV (in
FT isoform 3)"
FT /evidence="ECO:0000303|PubMed:7772058,
FT ECO:0000303|PubMed:7888306, ECO:0000303|PubMed:9677330"
FT /id="VSP_004557"
FT VAR_SEQ 1..107
FT /note="MEPPTVPSERSLSLSLPGPREGQATLKPPPQHLWRQPRTPIRIQQRGYSDSA
FT ERAERERQPHRPIERADAMDTSDRPGLRTTRMSWPSSFHGTGTGSGGAGGGSSRR ->
FT MARPRGLGRIPELQLVAFPVAVAAEDEAFLPEPLAPRAPRRPRSPPSSPVFFASPSPTF
FT RRRLRLLRSCQDLGRQAWAGAG (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15738310,
FT ECO:0000303|PubMed:9677330"
FT /id="VSP_004556"
FT VAR_SEQ 1..107
FT /note="MEPPTVPSERSLSLSLPGPREGQATLKPPPQHLWRQPRTPIRIQQRGYSDSA
FT ERAERERQPHRPIERADAMDTSDRPGLRTTRMSWPSSFHGTGTGSGGAGGGSSRR ->
FT MRSGAAPRARPRPPALALPPTGPESLTHFPFSDEDTRRHPPGRSVS (in isoform
FT 6)"
FT /evidence="ECO:0000303|PubMed:11306681"
FT /id="VSP_038185"
FT VAR_SEQ 1..107
FT /note="MEPPTVPSERSLSLSLPGPREGQATLKPPPQHLWRQPRTPIRIQQRGYSDSA
FT ERAERERQPHRPIERADAMDTSDRPGLRTTRMSWPSSFHGTGTGSGGAGGGSSRR ->
FT MKRSRSALSVAGTGDERSRETPESDRANMLGADLRRPRRRLSSGPGLGWAQPEPSDPGV
FT PLPPRPTTLPLLIPPRISITRAENDS (in isoform 7)"
FT /evidence="ECO:0000303|PubMed:18095939"
FT /id="VSP_038186"
FT VAR_SEQ 644..657
FT /note="GFIDYIVHPLWETW -> QARGIDGRAQGGFY (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:7772058,
FT ECO:0000303|PubMed:9677330"
FT /id="VSP_004560"
FT VAR_SEQ 658..886
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:7772058,
FT ECO:0000303|PubMed:9677330"
FT /id="VSP_004561"
FT VARIANT 736
FT /note="A -> E (in dbSNP:rs1051738)"
FT /evidence="ECO:0000269|PubMed:2160582,
FT ECO:0000269|PubMed:7772058"
FT /id="VAR_059544"
FT VARIANT 808
FT /note="H -> Y (in dbSNP:rs2230190)"
FT /id="VAR_059545"
FT HELIX 362..368
FT /evidence="ECO:0007829|PDB:2QYK"
FT HELIX 369..371
FT /evidence="ECO:0007829|PDB:2QYK"
FT HELIX 379..385
FT /evidence="ECO:0007829|PDB:2QYK"
FT TURN 386..388
FT /evidence="ECO:0007829|PDB:2QYK"
FT HELIX 390..401
FT /evidence="ECO:0007829|PDB:2QYK"
FT HELIX 404..407
FT /evidence="ECO:0007829|PDB:2QYK"
FT HELIX 412..424
FT /evidence="ECO:0007829|PDB:2QYK"
FT STRAND 430..434
FT /evidence="ECO:0007829|PDB:2QYK"
FT HELIX 435..449
FT /evidence="ECO:0007829|PDB:2QYK"
FT HELIX 452..454
FT /evidence="ECO:0007829|PDB:2QYK"
FT TURN 455..457
FT /evidence="ECO:0007829|PDB:2QYK"
FT HELIX 460..472
FT /evidence="ECO:0007829|PDB:2QYK"
FT TURN 473..476
FT /evidence="ECO:0007829|PDB:2QYK"
FT HELIX 482..487
FT /evidence="ECO:0007829|PDB:2QYK"
FT HELIX 491..495
FT /evidence="ECO:0007829|PDB:2QYK"
FT TURN 496..498
FT /evidence="ECO:0007829|PDB:2QYK"
FT HELIX 501..512
FT /evidence="ECO:0007829|PDB:2QYK"
FT HELIX 513..515
FT /evidence="ECO:0007829|PDB:2QYK"
FT TURN 521..524
FT /evidence="ECO:0007829|PDB:2QYK"
FT HELIX 527..542
FT /evidence="ECO:0007829|PDB:2QYK"
FT HELIX 546..548
FT /evidence="ECO:0007829|PDB:2QYK"
FT HELIX 549..561
FT /evidence="ECO:0007829|PDB:2QYK"
FT STRAND 567..569
FT /evidence="ECO:0007829|PDB:2QYK"
FT HELIX 576..591
FT /evidence="ECO:0007829|PDB:2QYK"
FT HELIX 594..596
FT /evidence="ECO:0007829|PDB:2QYK"
FT HELIX 599..622
FT /evidence="ECO:0007829|PDB:2QYK"
FT TURN 633..635
FT /evidence="ECO:0007829|PDB:2QYK"
FT HELIX 638..648
FT /evidence="ECO:0007829|PDB:2QYK"
FT HELIX 650..660
FT /evidence="ECO:0007829|PDB:2QYK"
FT TURN 661..665
FT /evidence="ECO:0007829|PDB:2QYK"
FT HELIX 666..682
FT /evidence="ECO:0007829|PDB:2QYK"
FT MOD_RES P27815-2:119
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:11566027"
FT MOD_RES P27815-7:123
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:11566027"
SQ SEQUENCE 886 AA; 98143 MW; 92BB9B98BED711E7 CRC64;
MEPPTVPSER SLSLSLPGPR EGQATLKPPP QHLWRQPRTP IRIQQRGYSD SAERAERERQ
PHRPIERADA MDTSDRPGLR TTRMSWPSSF HGTGTGSGGA GGGSSRRFEA ENGPTPSPGR
SPLDSQASPG LVLHAGAATS QRRESFLYRS DSDYDMSPKT MSRNSSVTSE AHAEDLIVTP
FAQVLASLRS VRSNFSLLTN VPVPSNKRSP LGGPTPVCKA TLSEETCQQL ARETLEELDW
CLEQLETMQT YRSVSEMASH KFKRMLNREL THLSEMSRSG NQVSEYISTT FLDKQNEVEI
PSPTMKEREK QQAPRPRPSQ PPPPPVPHLQ PMSQITGLKK LMHSNSLNNS NIPRFGVKTD
QEELLAQELE NLNKWGLNIF CVSDYAGGRS LTCIMYMIFQ ERDLLKKFRI PVDTMVTYML
TLEDHYHADV AYHNSLHAAD VLQSTHVLLA TPALDAVFTD LEILAALFAA AIHDVDHPGV
SNQFLINTNS ELALMYNDES VLENHHLAVG FKLLQEDNCD IFQNLSKRQR QSLRKMVIDM
VLATDMSKHM TLLADLKTMV ETKKVTSSGV LLLDNYSDRI QVLRNMVHCA DLSNPTKPLE
LYRQWTDRIM AEFFQQGDRE RERGMEISPM CDKHTASVEK SQVGFIDYIV HPLWETWADL
VHPDAQEILD TLEDNRDWYY SAIRQSPSPP PEEESRGPGH PPLPDKFQFE LTLEEEEEEE
ISMAQIPCTA QEALTAQGLS GVEEALDATI AWEASPAQES LEVMAQEASL EAELEAVYLT
QQAQSTGSAP VAPDEFSSRE EFVVAVSHSS PSALALQSPL LPAWRTLSVS EHAPGLPGLP
STAAEVEAQR EHQAAKRACS ACAGTFGEDT SALPAPGGGG SGGDPT
