P17276 (PH4H_DROME) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Protein henna
EC=1.14.16.1
EC=1.14.16.4

Alternative name(s):
Phe-4-monooxygenase
Phenylalanine-4-hydroxylase
Short name=PAH
Tryptophan 5-hydroxylase
Short name=TRH
Tryptophan 5-monooxygenase

Gene names

Name:	Hn
Synonyms:	pah, Tph
ORF Names:	CG7399

Organism

Drosophila melanogaster (Fruit fly)

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	452 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

General annotation (Comments)

Catalytic activity	L-phenylalanine + tetrahydrobiopterin + O2 = L-tyrosine + 4a-hydroxytetrahydrobiopterin. L-tryptophan + tetrahydrobiopterin + O2 = 5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin.
Cofactor	Fe2+ ion.
Enzyme regulation	N-terminal region of PAH is thought to contain allosteric binding sites for phenylalanine and to constitute an "inhibitory" domain that regulates the activity of a catalytic domain in the C-terminal portion of the molecule.
Pathway	Amino-acid degradation; L-phenylalanine degradation; acetoacetate and fumarate from L-phenylalanine: step 1/6.
Tissue specificity	Phenylalanine hydrolase activity is found in yolk granules of embryos, and female abdomen and fat body tissues. Tryptophan hydroxylase is expressed in serotonergic neurons. Both enzymes are present in cuticular tissues.
Miscellaneous	In Drosophila, the 2 enzymes, PAH and TRH are found to be encoded by the same gene. Preference for the substrate is probably due to post-translational modifications such as phosphorylation, or by changes in the N-terminal regulatory domain.
Sequence similarities	Belongs to the biopterin-dependent aromatic amino acid hydroxylase family. Contains 1 ACT domain.

Ontologies

Keywords
Biological process	Phenylalanine catabolism Serotonin biosynthesis
Ligand	Iron Metal-binding
Molecular function	Monooxygenase Oxidoreductase
PTM	Phosphoprotein
Technical term	Allosteric enzyme Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	L-phenylalanine catabolic process Inferred from mutant phenotype. Source: FlyBase phagocytosis, engulfment Inferred from mutant phenotype. Source: FlyBase serotonin biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	iron ion binding Inferred from electronic annotation. Source: InterPro phenylalanine 4-monooxygenase activity Inferred from mutant phenotype. Source: FlyBase tryptophan 5-monooxygenase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 452	452	Protein henna		PRO_0000205552
Regions
	Domain	32 – 108	77	ACT
Sites
	Metal binding	284	1	Iron By similarity
	Metal binding	289	1	Iron By similarity
	Metal binding	329	1	Iron By similarity
Amino acid modifications
	Modified residue	272	1	Phosphoserine; by CaMK2 By similarity
Experimental info
	Sequence conflict	28	1	E → A in AAA69513. Ref.2
	Sequence conflict	39 – 47	9	KDSSLSSGA → RIRRCPAEL in AAA69513. Ref.2
	Sequence conflict	55 – 56	2	FK → LR in AAA69513. Ref.2
	Sequence conflict	63 – 71	9	VHIESRSSL → CILSRILAPWF in AAA69513. Ref.2
	Sequence conflict	74 – 114	41	PGYEF…YKDNA → SSCFWRRMENRSLGKSHRGC EGAMLATLTSSCRELQGVMP in AAA69513. Ref.2
	Sequence conflict	154	1	R → A in AAA69513. Ref.2
	Sequence conflict	164	1	A → G in AAA69513. Ref.2
	Sequence conflict	171	1	E → Q in AAA69513. Ref.2
	Sequence conflict	264	1	S → C in AAA69513. Ref.2
	Sequence conflict	297	1	A → S in AAA69513. Ref.2
	Sequence conflict	332	1	V → L in M81833. Ref.1
	Sequence conflict	332	1	V → L in AAA69513. Ref.2
	Sequence conflict	333 – 335	3	CRQ → LAK in AAA69513. Ref.2
	Sequence conflict	370	1	V → S in AAA69513. Ref.2
	Sequence conflict	449 – 452	4	KLRV → NCASE in M81833. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P17276 [UniParc]. Last modified December 1, 2000. Version 3. Checksum: 990F554150056867	FASTA	452	51,660
	10 20 30 40 50 60 MYQRQVSFDK PTRVEDSAYI VEGVDIKEAR NTCLLFSPKD SSLSSGALAN ILAIFKKHDI 70 80 90 100 110 120 NLVHIESRSS LRVPGYEFFV EADGKSGALG KAIEDVKEQC SYFNIISRDY KDNATAVPWF 130 140 150 160 170 180 PRRIRDLDRF ANQILSYGSE LDADHPGFTD PEYRKRRKYF ADIAYNYKHG EPLPHVDYTK 190 200 210 220 230 240 EEIETWGIIF RNLTKLYKTH ACREYNHVFP LLVDNCGFRE DNIPQLEDVS NFLRDCTGFT 250 260 270 280 290 300 LRPVAGLLSS RDFLAGLAFR VFHSTQYIRH PSKPMYTPEP DVCHELMGHV PLFADPAFAQ 310 320 330 340 350 360 FSQEIGLASL GAPDDYIEKL STIFWFTVEY GVCRQEGELK AYGAGLLSSY GELEYCLTDK 370 380 390 400 410 420 PQLKDFEPEV TGVTKYPITQ FQPLYYVADS FETAKEKTIK FANSIPRPFG VRYNAYTQSV 430 440 450 EVLDSKPQIS NLMDNINSEF QILQNAVAKL RV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A single locus encodes both phenylalanine hydroxylase and tryptophan hydroxylase activities in Drosophila." Neckameyer W.S., White K. J. Biol. Chem. 267:4199-4206(1992) [PubMed: 1371286] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA]. Strain: Canton-S and Oregon-R. Tissue: Embryo and Head.
[2]	"Sequence and expression of the Drosophila phenylalanine hydroxylase mRNA." Morales G., Requena J.M., Jimenez-Ruiz A., Lopez M.C., Ugarte M., Alonso C. Gene 93:213-219(1990) [PubMed: 2121612] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Structure of the phenylalanine hydroxylase gene in Drosophila melanogaster and evidence of alternative promoter usage." Ruiz-Vazquez P., Moulard M., Silva F.J. Biochem. Biophys. Res. Commun. 225:238-242(1996) [PubMed: 8769124] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: Canton-S.
[4]	"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.
[5]	"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. Strain: Berkeley.
[6]	"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]. Strain: Berkeley. Tissue: Head.
[7]	"Aberrant splicing of the Drosophila melanogaster phenylalanine hydroxylase pre-mRNA caused by the insertion of a B104/roo transposable element in the Henna locus." Ruiz-Vazquez P., Silva F.J. Insect Biochem. Mol. Biol. 29:311-318(1999) [PubMed: 10333570] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] OF 5-93 AND 161-412 (MUTANT HN-R3).
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	M81833 Genomic RNA. No translation available. M32802 mRNA. Translation: AAA69513.1. X98116 Genomic DNA. Translation: CAA66797.1. X98116 Genomic DNA. Translation: CAA66798.1. AE014296 Genomic DNA. Translation: AAF50517.1. AY069306 mRNA. Translation: AAL39451.1. AJ001718 Genomic DNA. Translation: CAA04950.1. AJ001719, AJ001720 Genomic DNA. Translation: CAB51601.1. AJ001722 mRNA. Translation: CAB51599.1. AJ001723 mRNA. Translation: CAB51597.1.
PIR	A42271. JC4888. JQ0766.
RefSeq	NP_001014573.1. NM_001014573.1. NP_523963.2. NM_079239.3.
UniGene	Dm.7375.
3D structure databases
ProteinModelPortal	P17276.
SMR	P17276. Positions 34-451.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-20514N.
IntAct	P17276. 14 interactions.
MINT	MINT-321332.
STRING	P17276.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
EnsemblMetazoa	FBtr0076811; FBpp0076523; FBgn0001208.
GeneID	38871.
KEGG	dme:Dmel_CG7399.
NMPDR	fig|7227.3.peg.8736.
Organism-specific databases
CTD	38871.
FlyBase	FBgn0001208. Hn.
Phylogenomic databases
eggNOG	inNOG09135.
GeneTree	EMGT00050000016900.
InParanoid	P17276.
OMA	QETSYIE.
OrthoDB	EOG48GTJP.
PhylomeDB	P17276.
Gene expression databases
ArrayExpress	P17276.
Bgee	P17276.
GermOnline	CG7399. Drosophila melanogaster.
Family and domain databases
InterPro	IPR001273. ArAA_hydroxylase. IPR018301. ArAA_hydroxylase_Fe/CU_BS. IPR019774. Aromatic-AA_hydroxylase_C. IPR005961. Phe-4-hydroxylase_tetra. IPR019773. Tyrosine_3-monooxygenase-like. [Graphical view]
Gene3D	G3DSA:1.10.800.10. Aaa_hydroxylase. 1 hit.
KO	K00500.
PANTHER	PTHR11473. Aaa_hydroxylase. 1 hit.
Pfam	PF00351. Biopterin_H. 1 hit. [Graphical view]
PIRSF	PIRSF000336. TH. 1 hit.
PRINTS	PR00372. FYWHYDRXLASE.
SUPFAM	SSF56534. Aaa_hydroxylase. 1 hit.
TIGRFAMs	TIGR01268. Phe4hydrox_tetr. 1 hit.
PROSITE	PS00367. BH4_AAA_HYDROXYL_1. 1 hit. PS51410. BH4_AAA_HYDROXYL_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	810779.

Entry information

Entry name

PH4H_DROME

Accession

Primary (citable) accession number: P17276
Secondary accession number(s): O46110, Q27599, Q27600

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1990
Last sequence update:	December 1, 2000
Last modified:	January 25, 2012
This is version 131 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Drosophila annotation project