TY3H_RAT
ID TY3H_RAT Reviewed; 498 AA.
AC P04177;
DT 20-MAR-1987, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 183.
DE RecName: Full=Tyrosine 3-monooxygenase;
DE EC=1.14.16.2 {ECO:0000269|PubMed:10933781, ECO:0000269|PubMed:11922614};
DE AltName: Full=Tyrosine 3-hydroxylase;
DE Short=TH;
GN Name=Th;
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].
RX PubMed=2857492; DOI=10.1073/pnas.82.2.617;
RA Grima B., Lamouroux A., Blanot F., Faucon Biguet N., Mallet J.;
RT "Complete coding sequence of rat tyrosine hydroxylase mRNA.";
RL Proc. Natl. Acad. Sci. U.S.A. 82:617-621(1985).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Anton X.X., Manaster J.S., Kordower X.X., Markham X.X., Bredesen D.E.;
RL Submitted (JUL-1993) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP PROTEIN SEQUENCE OF 2-12; 284-298 AND 452-459, CLEAVAGE OF INITIATOR
RP METHIONINE, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Pheochromocytoma;
RA Bienvenut W.V., von Kriegsheim A.F., Kolch W.;
RL Submitted (AUG-2006) to UniProtKB.
RN [4]
RP PHOSPHORYLATION AT SER-19; SER-31 AND SER-40.
RX PubMed=1672315; DOI=10.1016/s0021-9258(19)67644-1;
RA Haycock J.W., Haycock D.A.;
RT "Tyrosine hydroxylase in rat brain dopaminergic nerve terminals. Multiple-
RT site phosphorylation in vivo and in synaptosomes.";
RL J. Biol. Chem. 266:5650-5657(1991).
RN [5]
RP PHOSPHORYLATION AT SER-19 AND SER-40, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RX PubMed=11502746; DOI=10.1074/jbc.m105280200;
RA Bevilaqua L.R., Graham M.E., Dunkley P.R., von Nagy-Felsobuki E.I.,
RA Dickson P.W.;
RT "Phosphorylation of Ser(19) alters the conformation of tyrosine hydroxylase
RT to increase the rate of phosphorylation of Ser(40).";
RL J. Biol. Chem. 276:40411-40416(2001).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 156-498 IN COMPLEX WITH IRON, AND
RP SUBUNIT.
RX PubMed=9228951; DOI=10.1038/nsb0797-578;
RA Goodwill K.E., Sabatier C., Marks C., Raag R., Fitzpatrick P.F.,
RA Stevens R.C.;
RT "Crystal structure of tyrosine hydroxylase at 2.3 A and its implications
RT for inherited neurodegenerative diseases.";
RL Nat. Struct. Biol. 4:578-585(1997).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF
RP GLN-310; HIS-323 AND ASP-425, AND SUBSTRATE SPECIFICITY.
RX PubMed=10933781; DOI=10.1021/bi000493k;
RA Daubner S.C., Melendez J., Fitzpatrick P.F.;
RT "Reversing the substrate specificities of phenylalanine and tyrosine
RT hydroxylase: aspartate 425 of tyrosine hydroxylase is essential for L-DOPA
RT formation.";
RL Biochemistry 39:9652-9661(2000).
RN [8]
RP CATALYTIC ACTIVITY, FUNCTION, MUTAGENESIS OF TRP-372, AND
RP BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=11922614; DOI=10.1006/bbrc.2002.6719;
RA Daubner S.C., Moran G.R., Fitzpatrick P.F.;
RT "Role of tryptophan hydroxylase phe313 in determining substrate
RT specificity.";
RL Biochem. Biophys. Res. Commun. 292:639-641(2002).
RN [9]
RP SUBCELLULAR LOCATION.
RX PubMed=15496595; DOI=10.1093/jb/mvh113;
RA Tsudzuki T., Tsujita M.;
RT "Isoosmotic isolation of rat brain synaptic vesicles, some of which contain
RT tyrosine hydroxylase.";
RL J. Biochem. 136:239-243(2004).
RN [10]
RP SUBCELLULAR LOCATION, AND PHOSPHORYLATION AT SER-19; SER-31 AND SER-40.
RX PubMed=21392500; DOI=10.1016/j.bbrc.2011.03.020;
RA Nakashima A., Mori K., Kaneko Y.S., Hayashi N., Nagatsu T., Ota A.;
RT "Phosphorylation of the N-terminal portion of tyrosine hydroxylase triggers
RT proteasomal digestion of the enzyme.";
RL Biochem. Biophys. Res. Commun. 407:343-347(2011).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 156-498 IN COMPLEX WITH IRON.
RX PubMed=9753429; DOI=10.1021/bi981462g;
RA Goodwill K.E., Sabatier C., Stevens R.C.;
RT "Crystal structure of tyrosine hydroxylase with bound cofactor analogue and
RT iron at 2.3 A resolution: self-hydroxylation of Phe300 and the pterin-
RT binding site.";
RL Biochemistry 37:13437-13445(1998).
RN [12] {ECO:0007744|PDB:2MDA}
RP STRUCTURE BY NMR OF 65-159.
RX PubMed=24361276; DOI=10.1016/j.jmb.2013.12.015;
RA Zhang S., Huang T., Ilangovan U., Hinck A.P., Fitzpatrick P.F.;
RT "The solution structure of the regulatory domain of tyrosine hydroxylase.";
RL J. Mol. Biol. 426:1483-1497(2014).
CC -!- FUNCTION: Catalyzes the conversion of L-tyrosine to L-
CC dihydroxyphenylalanine (L-Dopa), the rate-limiting step in the
CC biosynthesis of cathecolamines, dopamine, noradrenaline, and
CC adrenaline. Uses tetrahydrobiopterin and molecular oxygen to convert
CC tyrosine to L-Dopa (By similarity). In addition to tyrosine, is able to
CC catalyze the hydroxylation of phenylalanine and tryptophan but with
CC lower specificity (PubMed:11922614, PubMed:10933781). Positively
CC regulates the regression of retinal hyaloid vessels during postnatal
CC development (By similarity). {ECO:0000250|UniProtKB:P07101,
CC ECO:0000250|UniProtKB:P24529, ECO:0000269|PubMed:10933781,
CC ECO:0000269|PubMed:11922614}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin + L-tyrosine + O2 =
CC (4aS,6R)-4a-hydroxy-L-erythro-5,6,7,8-tetrahydrobiopterin + L-dopa;
CC Xref=Rhea:RHEA:18201, ChEBI:CHEBI:15379, ChEBI:CHEBI:15642,
CC ChEBI:CHEBI:57504, ChEBI:CHEBI:58315, ChEBI:CHEBI:59560;
CC EC=1.14.16.2; Evidence={ECO:0000269|PubMed:10933781,
CC ECO:0000269|PubMed:11922614};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:18202;
CC Evidence={ECO:0000305|PubMed:11922614};
CC -!- COFACTOR:
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC Evidence={ECO:0000269|PubMed:9228951};
CC -!- ACTIVITY REGULATION: Inhibited in feedback fashion by the catecholamine
CC neurotransmitters, especially by dopamine in competition with
CC tetrahydrobiopterin. Phosphorylation of several Ser/Thr residues in the
CC N-terminus regulates the catalytic activity. Ser-31 and Ser-40 are
CC readily phosphorylated to activate the catalytic activity. A cysteine
CC modification induced by N-ethylmaleimide (NEM), inhibits tyrosine 3-
CC monooxygenase activity through the modification of the Cys-177.
CC {ECO:0000250|UniProtKB:P07101}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=96 uM for phenylalanine {ECO:0000269|PubMed:10933781};
CC KM=210 uM for tryptophan {ECO:0000269|PubMed:11922614};
CC KM=16 uM for tyrosine {ECO:0000269|PubMed:10933781};
CC -!- PATHWAY: Catecholamine biosynthesis; dopamine biosynthesis; dopamine
CC from L-tyrosine: step 1/2. {ECO:0000250|UniProtKB:P07101}.
CC -!- SUBUNIT: Homotetramer (PubMed:9228951). Interacts (when phosphorylated
CC at Ser-19) with YWHAG; one YWHAG dimer bounds to one TH tetramer this
CC interaction may influence the phosphorylation and dephosphorylation of
CC other sites (By similarity). {ECO:0000250|UniProtKB:P07101,
CC ECO:0000269|PubMed:9228951}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, perinuclear region
CC {ECO:0000250|UniProtKB:P24529}. Nucleus {ECO:0000269|PubMed:21392500}.
CC Cell projection, axon {ECO:0000250|UniProtKB:P24529}. Cytoplasm
CC {ECO:0000269|PubMed:15496595, ECO:0000269|PubMed:21392500}. Cytoplasmic
CC vesicle, secretory vesicle, synaptic vesicle
CC {ECO:0000269|PubMed:15496595}. Note=When phosphorylated at Ser-19 shows
CC a nuclear distribution and when phsphorylated at Ser-31 as well at Ser-
CC 40 shows a cytosolic distribution (PubMed:21392500). Expressed in
CC dopaminergic axons and axon terminals (By similarity).
CC {ECO:0000250|UniProtKB:P07101, ECO:0000269|PubMed:21392500}.
CC -!- PTM: Phosphorylated on Ser-19, Ser-31 and Ser-40 by several protein
CC kinases with different site specificities. Phosphorylation at Ser-31
CC and Ser-40 leads to an increase of TH activity. Phosphorylation at Ser-
CC 40 activates the enzyme and also counteracts the feedback inhibition of
CC TH by catecholamines (By similarity). Phosphorylation of Ser-19 and
CC Ser-31 triggers the proteasomal degradation of TH through the
CC ubiquitin-proteasome pathway (PubMed:21392500). Phosphorylation at Ser-
CC 31 facilitates transport of TH from the soma to the nerve terminals via
CC the microtubule network (By similarity). Phosphorylation at Ser-19
CC induces the high-affinity binding to the 14-3-3 protein YWHAG; this
CC interaction may influence the phosphorylation and dephosphorylation of
CC other sites (By similarity). Ser-19 increases the phosphorylation at
CC Ser-40 in a hierarchical manner, leading to increased activity
CC (PubMed:1672315, PubMed:11502746). {ECO:0000250|UniProtKB:P07101,
CC ECO:0000269|PubMed:11502746, ECO:0000269|PubMed:1672315,
CC ECO:0000269|PubMed:21392500}.
CC -!- SIMILARITY: Belongs to the biopterin-dependent aromatic amino acid
CC hydroxylase family. {ECO:0000305}.
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DR EMBL; M10244; AAA42257.1; -; mRNA.
DR EMBL; L22651; AAA42258.1; -; mRNA.
DR PIR; A00510; WHRTY.
DR RefSeq; NP_036872.1; NM_012740.3.
DR PDB; 1TOH; X-ray; 2.30 A; A=156-498.
DR PDB; 2MDA; NMR; -; A/B=65-159.
DR PDB; 2TOH; X-ray; 2.30 A; A=156-498.
DR PDBsum; 1TOH; -.
DR PDBsum; 2MDA; -.
DR PDBsum; 2TOH; -.
DR AlphaFoldDB; P04177; -.
DR BMRB; P04177; -.
DR SMR; P04177; -.
DR BioGRID; 247158; 2.
DR CORUM; P04177; -.
DR IntAct; P04177; 3.
DR MINT; P04177; -.
DR STRING; 10116.ENSRNOP00000027682; -.
DR BindingDB; P04177; -.
DR ChEMBL; CHEMBL2462; -.
DR iPTMnet; P04177; -.
DR PhosphoSitePlus; P04177; -.
DR jPOST; P04177; -.
DR PaxDb; P04177; -.
DR PRIDE; P04177; -.
DR Ensembl; ENSRNOT00000027682; ENSRNOP00000027682; ENSRNOG00000020410.
DR GeneID; 25085; -.
DR KEGG; rno:25085; -.
DR UCSC; RGD:3853; rat.
DR CTD; 7054; -.
DR RGD; 3853; Th.
DR eggNOG; KOG3820; Eukaryota.
DR GeneTree; ENSGT00950000182885; -.
DR HOGENOM; CLU_023198_0_1_1; -.
DR InParanoid; P04177; -.
DR OMA; PELDMNH; -.
DR OrthoDB; 614557at2759; -.
DR PhylomeDB; P04177; -.
DR TreeFam; TF313327; -.
DR BRENDA; 1.14.16.2; 5301.
DR Reactome; R-RNO-209905; Catecholamine biosynthesis.
DR SABIO-RK; P04177; -.
DR UniPathway; UPA00747; UER00733.
DR EvolutionaryTrace; P04177; -.
DR PRO; PR:P04177; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Bgee; ENSRNOG00000020410; Expressed in brain and 3 other tissues.
DR Genevisible; P04177; RN.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0030424; C:axon; IDA:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0009898; C:cytoplasmic side of plasma membrane; ISO:RGD.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISO:RGD.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; IDA:BHF-UCL.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0030425; C:dendrite; IDA:RGD.
DR GO; GO:0033162; C:melanosome membrane; ISO:RGD.
DR GO; GO:0005739; C:mitochondrion; IDA:BHF-UCL.
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; ISS:UniProtKB.
DR GO; GO:0043204; C:perikaryon; IDA:RGD.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB.
DR GO; GO:0005790; C:smooth endoplasmic reticulum; ISO:RGD.
DR GO; GO:0008021; C:synaptic vesicle; IDA:RGD.
DR GO; GO:0043195; C:terminal bouton; IDA:RGD.
DR GO; GO:0016597; F:amino acid binding; IDA:RGD.
DR GO; GO:0035240; F:dopamine binding; IPI:RGD.
DR GO; GO:0019899; F:enzyme binding; ISO:RGD.
DR GO; GO:0008199; F:ferric iron binding; IDA:RGD.
DR GO; GO:0008198; F:ferrous iron binding; IDA:RGD.
DR GO; GO:0042802; F:identical protein binding; TAS:RGD.
DR GO; GO:0004497; F:monooxygenase activity; IDA:BHF-UCL.
DR GO; GO:0019825; F:oxygen binding; IDA:RGD.
DR GO; GO:0019904; F:protein domain specific binding; IPI:RGD.
DR GO; GO:0034617; F:tetrahydrobiopterin binding; IDA:RGD.
DR GO; GO:0004511; F:tyrosine 3-monooxygenase activity; IDA:RGD.
DR GO; GO:0015842; P:aminergic neurotransmitter loading into synaptic vesicle; IDA:RGD.
DR GO; GO:0009887; P:animal organ morphogenesis; ISO:RGD.
DR GO; GO:0042423; P:catecholamine biosynthetic process; IDA:RGD.
DR GO; GO:0071312; P:cellular response to alkaloid; IEP:RGD.
DR GO; GO:0071333; P:cellular response to glucose stimulus; IEP:RGD.
DR GO; GO:0071363; P:cellular response to growth factor stimulus; IEP:RGD.
DR GO; GO:0071287; P:cellular response to manganese ion; IEP:RGD.
DR GO; GO:0071316; P:cellular response to nicotine; IEP:RGD.
DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0021987; P:cerebral cortex development; IEP:RGD.
DR GO; GO:0042745; P:circadian sleep/wake cycle; IEP:RGD.
DR GO; GO:0050890; P:cognition; IEP:RGD.
DR GO; GO:0042416; P:dopamine biosynthetic process; ISO:RGD.
DR GO; GO:0006585; P:dopamine biosynthetic process from tyrosine; IDA:RGD.
DR GO; GO:0042755; P:eating behavior; ISO:RGD.
DR GO; GO:0048596; P:embryonic camera-type eye morphogenesis; ISO:RGD.
DR GO; GO:0042418; P:epinephrine biosynthetic process; ISO:RGD.
DR GO; GO:0042462; P:eye photoreceptor cell development; ISO:RGD.
DR GO; GO:0006631; P:fatty acid metabolic process; IEP:RGD.
DR GO; GO:0016137; P:glycoside metabolic process; IEP:RGD.
DR GO; GO:0007507; P:heart development; IDA:RGD.
DR GO; GO:1990384; P:hyaloid vascular plexus regression; ISS:UniProtKB.
DR GO; GO:0033076; P:isoquinoline alkaloid metabolic process; IEP:RGD.
DR GO; GO:0007612; P:learning; ISO:RGD.
DR GO; GO:0007626; P:locomotory behavior; ISO:RGD.
DR GO; GO:0007617; P:mating behavior; ISO:RGD.
DR GO; GO:0007613; P:memory; ISO:RGD.
DR GO; GO:0010259; P:multicellular organism aging; IEP:RGD.
DR GO; GO:0042136; P:neurotransmitter biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0042421; P:norepinephrine biosynthetic process; ISO:RGD.
DR GO; GO:0018963; P:phthalate metabolic process; IEP:RGD.
DR GO; GO:0052314; P:phytoalexin metabolic process; IEP:RGD.
DR GO; GO:0008016; P:regulation of heart contraction; ISO:RGD.
DR GO; GO:0014823; P:response to activity; IEP:RGD.
DR GO; GO:0001975; P:response to amphetamine; IEP:RGD.
DR GO; GO:0051412; P:response to corticosterone; IEP:RGD.
DR GO; GO:0051602; P:response to electrical stimulus; IEP:RGD.
DR GO; GO:0032355; P:response to estradiol; IEP:RGD.
DR GO; GO:0045471; P:response to ethanol; IEP:RGD.
DR GO; GO:0045472; P:response to ether; IEP:RGD.
DR GO; GO:0070848; P:response to growth factor; IEP:RGD.
DR GO; GO:0009635; P:response to herbicide; IEP:RGD.
DR GO; GO:0001666; P:response to hypoxia; IDA:RGD.
DR GO; GO:0035902; P:response to immobilization stress; IEP:RGD.
DR GO; GO:0017085; P:response to insecticide; IEP:RGD.
DR GO; GO:0035900; P:response to isolation stress; IEP:RGD.
DR GO; GO:0009416; P:response to light stimulus; IEP:RGD.
DR GO; GO:0032496; P:response to lipopolysaccharide; IEP:RGD.
DR GO; GO:0010038; P:response to metal ion; IEP:RGD.
DR GO; GO:0035094; P:response to nicotine; IEP:RGD.
DR GO; GO:0031667; P:response to nutrient levels; IEP:RGD.
DR GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD.
DR GO; GO:0043434; P:response to peptide hormone; IEP:RGD.
DR GO; GO:0046684; P:response to pyrethroid; IEP:RGD.
DR GO; GO:0009651; P:response to salt stress; IEP:RGD.
DR GO; GO:0048545; P:response to steroid hormone; IEP:RGD.
DR GO; GO:0009414; P:response to water deprivation; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0010043; P:response to zinc ion; IEP:RGD.
DR GO; GO:0007605; P:sensory perception of sound; IEP:RGD.
DR GO; GO:0035176; P:social behavior; IEP:RGD.
DR GO; GO:0006665; P:sphingolipid metabolic process; IEP:RGD.
DR GO; GO:0001963; P:synaptic transmission, dopaminergic; ISO:RGD.
DR GO; GO:0042214; P:terpene metabolic process; IEP:RGD.
DR GO; GO:0007601; P:visual perception; ISO:RGD.
DR CDD; cd03345; eu_TyrOH; 1.
DR DisProt; DP00094; -.
DR Gene3D; 1.10.800.10; -; 1.
DR InterPro; IPR045865; ACT-like_dom_sf.
DR InterPro; IPR001273; ArAA_hydroxylase.
DR InterPro; IPR018301; ArAA_hydroxylase_Fe/CU_BS.
DR InterPro; IPR036951; ArAA_hydroxylase_sf.
DR InterPro; IPR036329; Aro-AA_hydroxylase_C_sf.
DR InterPro; IPR019774; Aromatic-AA_hydroxylase_C.
DR InterPro; IPR041903; Eu_TyrOH_cat.
DR InterPro; IPR005962; Tyr_3_mOase.
DR InterPro; IPR019773; Tyrosine_3-monooxygenase-like.
DR InterPro; IPR021164; Tyrosine_hydroxylase_CS.
DR PANTHER; PTHR11473; PTHR11473; 1.
DR Pfam; PF00351; Biopterin_H; 1.
DR Pfam; PF12549; TOH_N; 2.
DR PIRSF; PIRSF000336; TH; 1.
DR PRINTS; PR00372; FYWHYDRXLASE.
DR SUPFAM; SSF55021; SSF55021; 1.
DR SUPFAM; SSF56534; SSF56534; 1.
DR TIGRFAMs; TIGR01269; Tyr_3_monoox; 1.
DR PROSITE; PS00367; BH4_AAA_HYDROXYL_1; 1.
DR PROSITE; PS51410; BH4_AAA_HYDROXYL_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Catecholamine biosynthesis; Cell projection; Cytoplasm;
KW Cytoplasmic vesicle; Direct protein sequencing; Iron; Metal-binding;
KW Monooxygenase; Neurotransmitter biosynthesis; Nucleus; Oxidoreductase;
KW Phosphoprotein; Reference proteome; Synapse.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|Ref.3"
FT CHAIN 2..498
FT /note="Tyrosine 3-monooxygenase"
FT /id="PRO_0000205564"
FT REGION 1..31
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 331
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000269|PubMed:9228951,
FT ECO:0000269|PubMed:9753429, ECO:0007744|PDB:1TOH,
FT ECO:0007744|PDB:2TOH"
FT BINDING 336
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000269|PubMed:9228951,
FT ECO:0000269|PubMed:9753429, ECO:0007744|PDB:1TOH,
FT ECO:0007744|PDB:2TOH"
FT BINDING 376
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000269|PubMed:9228951,
FT ECO:0000269|PubMed:9753429, ECO:0007744|PDB:1TOH,
FT ECO:0007744|PDB:2TOH"
FT SITE 425
FT /note="Important for substrate specificity"
FT /evidence="ECO:0000269|PubMed:10933781"
FT MOD_RES 19
FT /note="Phosphoserine; by CaMK2"
FT /evidence="ECO:0000269|PubMed:11502746,
FT ECO:0000269|PubMed:1672315, ECO:0000269|PubMed:21392500"
FT MOD_RES 31
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:1672315,
FT ECO:0000269|PubMed:21392500"
FT MOD_RES 40
FT /note="Phosphoserine; by CaMK2 and PKA"
FT /evidence="ECO:0000269|PubMed:11502746,
FT ECO:0000269|PubMed:1672315, ECO:0000269|PubMed:21392500"
FT MOD_RES 472
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P24529"
FT MUTAGEN 310
FT /note="Q->H: Does not affect Vmax for phenylalanine.
FT Increases KM for phenylalanine."
FT /evidence="ECO:0000269|PubMed:10933781"
FT MUTAGEN 323
FT /note="H->Y: Does not affect Vmax for phenylalaninet.
FT Increases KM for phenylalanine."
FT /evidence="ECO:0000269|PubMed:10933781"
FT MUTAGEN 372
FT /note="W->F: Does not affect substrate specificity."
FT /evidence="ECO:0000269|PubMed:11922614"
FT MUTAGEN 425
FT /note="D->V: Shifts substrate specificity from tyrosine to
FT phenylalanine."
FT /evidence="ECO:0000269|PubMed:10933781"
FT STRAND 75..77
FT /evidence="ECO:0007829|PDB:2MDA"
FT STRAND 80..85
FT /evidence="ECO:0007829|PDB:2MDA"
FT STRAND 91..93
FT /evidence="ECO:0007829|PDB:2MDA"
FT HELIX 98..106
FT /evidence="ECO:0007829|PDB:2MDA"
FT STRAND 110..116
FT /evidence="ECO:0007829|PDB:2MDA"
FT STRAND 119..122
FT /evidence="ECO:0007829|PDB:2MDA"
FT STRAND 133..138
FT /evidence="ECO:0007829|PDB:2MDA"
FT HELIX 141..150
FT /evidence="ECO:0007829|PDB:2MDA"
FT STRAND 162..164
FT /evidence="ECO:0007829|PDB:2TOH"
FT HELIX 171..176
FT /evidence="ECO:0007829|PDB:1TOH"
FT STRAND 177..179
FT /evidence="ECO:0007829|PDB:2TOH"
FT TURN 193..196
FT /evidence="ECO:0007829|PDB:1TOH"
FT HELIX 198..213
FT /evidence="ECO:0007829|PDB:1TOH"
FT HELIX 227..247
FT /evidence="ECO:0007829|PDB:1TOH"
FT HELIX 250..262
FT /evidence="ECO:0007829|PDB:1TOH"
FT HELIX 273..283
FT /evidence="ECO:0007829|PDB:1TOH"
FT STRAND 287..290
FT /evidence="ECO:0007829|PDB:1TOH"
FT HELIX 297..304
FT /evidence="ECO:0007829|PDB:1TOH"
FT TURN 305..307
FT /evidence="ECO:0007829|PDB:1TOH"
FT STRAND 308..311
FT /evidence="ECO:0007829|PDB:1TOH"
FT HELIX 329..335
FT /evidence="ECO:0007829|PDB:1TOH"
FT HELIX 337..340
FT /evidence="ECO:0007829|PDB:1TOH"
FT HELIX 343..356
FT /evidence="ECO:0007829|PDB:1TOH"
FT HELIX 361..372
FT /evidence="ECO:0007829|PDB:1TOH"
FT TURN 373..377
FT /evidence="ECO:0007829|PDB:1TOH"
FT STRAND 379..382
FT /evidence="ECO:0007829|PDB:1TOH"
FT STRAND 385..388
FT /evidence="ECO:0007829|PDB:1TOH"
FT HELIX 391..394
FT /evidence="ECO:0007829|PDB:1TOH"
FT HELIX 397..403
FT /evidence="ECO:0007829|PDB:1TOH"
FT STRAND 405..412
FT /evidence="ECO:0007829|PDB:1TOH"
FT HELIX 415..419
FT /evidence="ECO:0007829|PDB:1TOH"
FT STRAND 425..427
FT /evidence="ECO:0007829|PDB:1TOH"
FT STRAND 430..436
FT /evidence="ECO:0007829|PDB:1TOH"
FT HELIX 438..450
FT /evidence="ECO:0007829|PDB:1TOH"
FT STRAND 457..461
FT /evidence="ECO:0007829|PDB:1TOH"
FT TURN 462..465
FT /evidence="ECO:0007829|PDB:1TOH"
FT STRAND 466..470
FT /evidence="ECO:0007829|PDB:1TOH"
FT HELIX 473..496
FT /evidence="ECO:0007829|PDB:1TOH"
SQ SEQUENCE 498 AA; 55966 MW; 17F7E003D29218C5 CRC64;
MPTPSAPSPQ PKGFRRAVSE QDAKQAEAVT SPRFIGRRQS LIEDARKERE AAAAAAAAAV
ASSEPGNPLE AVVFEERDGN AVLNLLFSLR GTKPSSLSRA VKVFETFEAK IHHLETRPAQ
RPLAGSPHLE YFVRFEVPSG DLAALLSSVR RVSDDVRSAR EDKVPWFPRK VSELDKCHHL
VTKFDPDLDL DHPGFSDQVY RQRRKLIAEI AFQYKHGEPI PHVEYTAEEI ATWKEVYVTL
KGLYATHACR EHLEGFQLLE RYCGYREDSI PQLEDVSRFL KERTGFQLRP VAGLLSARDF
LASLAFRVFQ CTQYIRHASS PMHSPEPDCC HELLGHVPML ADRTFAQFSQ DIGLASLGAS
DEEIEKLSTV YWFTVEFGLC KQNGELKAYG AGLLSSYGEL LHSLSEEPEV RAFDPDTAAV
QPYQDQTYQP VYFVSESFND AKDKLRNYAS RIQRPFSVKF DPYTLAIDVL DSPHTIQRSL
EGVQDELHTL AHALSAIS
