Reviewed, UniProtKB/Swiss-Prot P18459 (TY3H_DROME)

Names and origin

Protein names

Recommended name:
    Tyrosine 3-monooxygenase
    EC=1.14.16.2
Alternative name(s):
    Tyrosine 3-hydroxylase
      Short name=TH
    Protein Pale

Gene names

Name:	ple
Synonyms:	TH
ORF Names:	CG10118

Organism

Drosophila melanogaster (Fruit fly) [Complete proteome]

Taxonomic identifier

7227 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Arthropoda › Hexapoda › Insecta › Pterygota › Neoptera › Endopterygota › Diptera › Brachycera › Muscomorpha › Ephydroidea › Drosophilidae › Drosophila › Sophophora

Protein attributes

Sequence length	579 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Plays an important role in the physiology of adrenergic neurons.
Catalytic activity	L-tyrosine + tetrahydrobiopterin + O2 = 3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin.
Cofactor	Fe2+ ion.
Pathway	Catecholamine biosynthesis; dopamine biosynthesis; dopamine from L-tyrosine: step 1/2.
Sequence similarities	Belongs to the biopterin-dependent aromatic amino acid hydroxylase family.

Ontologies

Keywords
Biological process	Catecholamine biosynthesis Neurotransmitter biosynthesis
Coding sequence diversity	Alternative splicing
Ligand	Iron Metal-binding
Molecular function	Monooxygenase Oxidoreductase
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	adult locomotory behavior Inferred from mutant phenotype. Source: FlyBase aromatic amino acid family metabolic process Inferred from electronic annotation. Source: InterPro catecholamine biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW courtship behavior Non-traceable author statement. Source: FlyBase neurotransmitter biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW pigmentation during development Traceable author statement. Source: FlyBase
Molecular function	iron ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Inferred from physical interaction. Source: IntAct tyrosine 3-monooxygenase activity Ref.1 Non-traceable author statement. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
MED19	Q9VVL6	1	EBI-198251,EBI-125442
Sdc	P49415	1	EBI-198251,EBI-198254

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform Neuronal (identifier: P18459-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform Hypodermal (identifier: P18459-2)

The sequence of this isoform differs from the canonical sequence as follows:
     60-130: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 579	579	Tyrosine 3-monooxygenase		PRO_0000205566
Sites
	Metal binding	409	1	Iron By similarity
	Metal binding	414	1	Iron By similarity
	Metal binding	454	1	Iron By similarity
Natural variations
	Alternative sequence	60 – 130	71	Missing in isoform Hypodermal.		VSP_000545
Experimental info
	Sequence conflict	264	1	P → L in AAL49320. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform Neuronal [UniParc]. Last modified February 28, 2003. Version 2. Checksum: 416CF26E04087E85	FASTA	579	65,996
	10 20 30 40 50 60 MMAVAAAQKN REMFAIKKSY SIENGYPSRR RSLVDDARFE TLVVKQTKQT VLEEARSKAN 70 80 90 100 110 120 DDSLEDCIVQ AQEHIPSEQD VELQDEHANL ENLPLEEYVP VEEDVEFESV EQEQSESQSQ 130 140 150 160 170 180 EPEGNQQPTK NDYGLTEDEI LLANAASESS DAEAAMQSAA LVVRLKEGIS SLGRILKAIE 190 200 210 220 230 240 TFHGTVQHVE SRQSRVEGVD HDVLIKLDMT RGNLLQLIRS LRQSGSFSSM NLMADNNLNV 250 260 270 280 290 300 KAPWFPKHAS ELDNCNHLMT KYEPDLDMNH PGFADKVYRQ RRKEIAEIAF AYKYGDPIPF 310 320 330 340 350 360 IDYSDVEVKT WRSVFKTVQD LAPKHACAEY RAAFQKLQDE QIFVETRLPQ LQEMSDFLRK 370 380 390 400 410 420 NTGFSLRPAA GLLTARDFLA SLAFRIFQST QYVRHVNSPY HTPEPDSIHE LLGHMPLLAD 430 440 450 460 470 480 PSFAQFSQEI GLASLGASDE EIEKLSTVYW FTVEFGLCKE HGQIKAYGAG LLSSYGELLH 490 500 510 520 530 540 AISDKCEHRA FEPASTAVQP YQDQEYQPIY YVAESFEDAK DKFRRWVSTM SRPFEVRFNP 550 560 570 HTERVEVLDS VDKLETLVHQ MNTEILHLTN AISKLRRPF
	Isoform Hypodermal. Checksum: 2D194E0E8495E66F	FASTA	508	57,862
	10 20 30 40 50 60 MMAVAAAQKN REMFAIKKSY SIENGYPSRR RSLVDDARFE TLVVKQTKQT VLEEARSKAN 70 80 90 100 110 120 DYGLTEDEIL LANAASESSD AEAAMQSAAL VVRLKEGISS LGRILKAIET FHGTVQHVES 130 140 150 160 170 180 RQSRVEGVDH DVLIKLDMTR GNLLQLIRSL RQSGSFSSMN LMADNNLNVK APWFPKHASE 190 200 210 220 230 240 LDNCNHLMTK YEPDLDMNHP GFADKVYRQR RKEIAEIAFA YKYGDPIPFI DYSDVEVKTW 250 260 270 280 290 300 RSVFKTVQDL APKHACAEYR AAFQKLQDEQ IFVETRLPQL QEMSDFLRKN TGFSLRPAAG 310 320 330 340 350 360 LLTARDFLAS LAFRIFQSTQ YVRHVNSPYH TPEPDSIHEL LGHMPLLADP SFAQFSQEIG 370 380 390 400 410 420 LASLGASDEE IEKLSTVYWF TVEFGLCKEH GQIKAYGAGL LSSYGELLHA ISDKCEHRAF 430 440 450 460 470 480 EPASTAVQPY QDQEYQPIYY VAESFEDAKD KFRRWVSTMS RPFEVRFNPH TERVEVLDSV 490 500 DKLETLVHQM NTEILHLTNA ISKLRRPF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation and characterization of the gene for Drosophila tyrosine hydroxylase." Neckameyer W.S., Quinn W.G. Neuron 2:1167-1175(1989) [PubMed: 2483109] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS NEURONAL AND HYPODERMAL).
[2]	"The genome sequence of Drosophila melanogaster." Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D., Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F., George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N., Sutton G.G., Wortman J.R., Yandell M.D. , Zhang Q., Chen L.X., Brandon R.C., Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C., Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A., An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A., Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V., Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J., Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E., Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B., Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I., Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C., Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S., Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M., Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M., Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D., Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F., Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D., Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A., Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C., McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C., Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L., Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R., Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V., Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F., Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J., Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R., Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y., Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T., Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S., Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W., Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M., Venter J.C. Science 287:2185-2195(2000) [PubMed: 10731132] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: Berkeley.
[3]	"Annotation of the Drosophila melanogaster euchromatic genome: a systematic review." Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S., Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E., Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P., Bettencourt B.R., Celniker S.E., de Grey A.D.N.J. , Drysdale R.A., Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M., Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E. Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002) [PubMed: 12537572] [Abstract] Cited for: GENOME REANNOTATION, ALTERNATIVE SPLICING.
[4]	"A Drosophila full-length cDNA resource." Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A., Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M., Celniker S.E. Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002) [PubMed: 12537569] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM NEURONAL). Strain: Berkeley. Tissue: Head.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	U14395 Genomic DNA. Translation: AAA62876.1. U14395 Genomic DNA. Translation: AAA62877.1. X76209 mRNA. Translation: CAA53802.1. AE014296 Genomic DNA. Translation: AAN12080.1. AE014296 Genomic DNA. Translation: AAF50648.1. AY071698 mRNA. Translation: AAL49320.1.
PIR	A55369.
RefSeq	NP_476897.1. NP_476898.1.
UniGene	Dm.3463
3D structure databases
HSSP	HSSP built from PDB template 2TOH based on UniProtKB P04177.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP:17399N.
IntAct	P18459. 22 interactions.
Genome annotation databases
Ensembl	FBgn0005626. Drosophila melanogaster. [Contig view]
GeneID	38746.
KEGG	dme:Dmel_CG10118.
NMPDR	fig|7227.3.peg.8571.
Organism-specific databases
FlyBase	FBgn0005626. ple.
Phylogenomic databases
HOGENOM	P18459.
OMA	P18459. YSIENGY.
Enzyme and pathway databases
BioCyc	DMEL-XXX-02:DMEL-XXX-02-015478-MON.
BRENDA	1.14.16.2. 48.
Gene expression databases
ArrayExpress	P18459.
GermOnline	CG10118. Drosophila melanogaster.
Family and domain databases
InterPro	IPR001273. ArAA_hydroxylase. IPR018301. ArAA_hydroxylase_Fe/CU_BS. IPR019774. Aromatic-AA_hydroxylase_C. IPR005962. Tyr_3_mOase. [Graphical view]
Gene3D	G3DSA:1.10.800.10. Aaa_hydroxylase. 1 hit.
PANTHER	PTHR11473. Aaa_hydroxylase. 1 hit.
Pfam	PF00351. Biopterin_H. 1 hit. [Graphical view]
PRINTS	PR00372. FYWHYDRXLASE.
ProDom	PD002559. Aaa_hydroxylase. 1 hit. [Graphical view] [Entries sharing at least one domain]
TIGRFAMs	TIGR01269. Tyr_3_monoox. 1 hit.
PROSITE	PS00367. BIOPTERIN_HYDROXYL. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	810172.

Entry information

Entry name

TY3H_DROME

Accession

Primary (citable) accession number: P18459
Secondary accession number(s): Q24000, Q8SY95

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1990
Last sequence update:	February 28, 2003
Last modified:	June 16, 2009
This is version 93 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

Drosophila annotation project