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 27-MAR-2024, entry version 192. 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 phosphorylated at Ser-31 as well as at CC Ser-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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 GlyGen; P04177; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P04177; -. DR PhosphoSitePlus; P04177; -. DR jPOST; P04177; -. DR PaxDb; 10116-ENSRNOP00000027682; -. DR Ensembl; ENSRNOT00000027682.6; ENSRNOP00000027682.3; ENSRNOG00000020410.6. DR Ensembl; ENSRNOT00055053621; ENSRNOP00055044346; ENSRNOG00055030903. DR Ensembl; ENSRNOT00060054459; ENSRNOP00060045080; ENSRNOG00060031396. DR Ensembl; ENSRNOT00065055278; ENSRNOP00065045469; ENSRNOG00065032083. DR GeneID; 25085; -. DR KEGG; rno:25085; -. DR UCSC; RGD:3853; rat. DR AGR; RGD:3853; -. 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; VRYNPHT; -. DR OrthoDB; 275463at2759; -. 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 cell types or tissues. DR GO; GO:0030424; C:axon; IDA:RGD. DR GO; GO:0005737; C:cytoplasm; ISO: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: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; ISO: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:0036094; F:small molecule binding; IDA:DisProt. 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: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:0009410; P:response to xenobiotic stimulus; IEP:RGD. DR GO; GO:0010043; P:response to zinc ion; 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; cd04930; ACT_TH; 1. DR CDD; cd03345; eu_TyrOH; 1. DR DisProt; DP00094; -. DR Gene3D; 3.30.70.260; -; 1. DR Gene3D; 1.10.800.10; Aromatic amino acid hydroxylase; 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; IPR049321; TH_ACT. DR InterPro; IPR005962; Tyr_3_mOase. DR InterPro; IPR019773; Tyrosine_3-monooxygenase-like. DR InterPro; IPR021164; Tyrosine_hydroxylase_CS. DR NCBIfam; TIGR01269; Tyr_3_monoox; 1. DR PANTHER; PTHR11473; AROMATIC AMINO ACID HYDROXYLASE; 1. DR PANTHER; PTHR11473:SF18; TYROSINE 3-MONOOXYGENASE; 1. DR Pfam; PF00351; Biopterin_H; 1. DR Pfam; PF21417; TH_ACT; 1. DR Pfam; PF12549; TOH_N; 2. DR PIRSF; PIRSF000336; TH; 1. DR PRINTS; PR00372; FYWHYDRXLASE. DR SUPFAM; SSF55021; ACT-like; 1. DR SUPFAM; SSF56534; Aromatic aminoacid monoxygenases, catalytic and oligomerization domains; 1. DR PROSITE; PS00367; BH4_AAA_HYDROXYL_1; 1. DR PROSITE; PS51410; BH4_AAA_HYDROXYL_2; 1. DR Genevisible; P04177; RN. 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 //