Reviewed, UniProtKB/Swiss-Prot O01404 (PHM_DROME)

Names and origin

Protein names

Recommended name:
    Peptidylglycine alpha-hydroxylating monooxygenase
      Short name=dPHM
    EC=1.14.17.3

Gene names

Name:	Phm
ORF Names:	CG3832

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	365 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Monooxygenase that catalyzes an essential reaction in C-terminal alpha-amidation of peptides. Produces an unstable peptidyl(2-hydroxyglycine) intermediate. C-terminal amidation of peptides is required for normal developmental transitions and for biosynthesis of secretory peptides throughout the life. Ref.5 Ref.6
Catalytic activity	Peptidylglycine + ascorbate + O2 = peptidyl(2-hydroxyglycine) + dehydroascorbate + H2O. Ref.1
Cofactor	Binds 2 copper ions per subunit Probable.
Subcellular location	Secreted Probable.
Tissue specificity	Expressed in the central nervous system (CNS) in a small number of CNS neurons (approximately a few hundred). Expression is present both in cell bodies and within neuropil regions. It is strongly expressed in neuroendocrine neurons (at protein level). Ref.1
Induction	Transcriptionally regulated by DIMM. Ref.7
Disruption phenotype	Death as late embryos with morphological defects that resemble those of animals with mutations in genes of the ecdysone-inducible regulatory circuit. Amidated peptides are largely absent but peptide precursors, a nonamidated neuropeptide, nonpeptide transmitters, and other peptide biosynthetic enzymes are detected. Ref.5
Sequence similarities	Belongs to the copper type II ascorbate-dependent monooxygenase family.
Biophysicochemical properties	Kinetic parameters: KM=2.2 µM for alpha-N-acetyl-Tyr-Val-Gly pH dependence: Optimum pH is 5.0.

Ontologies

Keywords
Cellular component	Secreted
Domain	Signal
Ligand	Copper Metal-binding
Molecular function	Monooxygenase Oxidoreductase
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	catecholamine metabolic process Inferred from electronic annotation. Source: InterPro oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW peptide metabolic process Inferred from electronic annotation. Source: InterPro
Cellular component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell membrane Inferred from electronic annotation. Source: InterPro
Molecular function	copper ion binding Inferred from electronic annotation. Source: UniProtKB-KW dopamine beta-monooxygenase activity Inferred from electronic annotation. Source: InterPro peptidylglycine monooxygenase activity Inferred from electronic annotation. Source: EC protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
	Q9VP96	1	EBI-149384,EBI-142310

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 24	24	Potential
	Chain	25 – 365	341	Peptidylglycine alpha-hydroxylating monooxygenase		PRO_0000248571
Sites
	Metal binding	95	1	Copper A By similarity
	Metal binding	96	1	Copper A By similarity
	Metal binding	172	1	Copper A By similarity
	Metal binding	241	1	Copper B By similarity
	Metal binding	243	1	Copper B By similarity
	Metal binding	317	1	Copper B By similarity
Amino acid modifications
	Glycosylation	88	1	N-linked (GlcNAc...) Potential
	Glycosylation	280	1	N-linked (GlcNAc...) Potential
	Disulfide bond	69 ↔ 114		By similarity
	Disulfide bond	102 ↔ 129		By similarity
	Disulfide bond	297 ↔ 318		By similarity

Sequences

	Sequence		Length	Mass (Da)
	O01404-1 [UniParc]. Last modified November 1, 1998. Version 2. Checksum: 9368D9D92018C178	FASTA	365	40,564
	10 20 30 40 50 60 MPRISEIAAS VGLLLLIGVI SVDGLVKEGD YQNSLYQQNL ESNSATGATA SFPFLMPNVS 70 80 90 100 110 120 PQTPDLYLCT PIKVDPTTTY YIVGFNPNAT MNTAHHMLLY GCGEPGTSKT TWNCGEMNRA 130 140 150 160 170 180 SQEESASPCG PHSNSQIVYA WARDAQKLNL PEGVGFKVGK NSPIKYLVLQ VHYAHIDKFK 190 200 210 220 230 240 DGSTDDSGVF LDYTEEPRKK LAGTLLLGTD GQIPAMKTEH LETACEVNEQ KVLHPFAYRV 250 260 270 280 290 300 HTHGLGKVVS GYRVRTNSDG EQEWLQLGKR DPLTPQMFYN TSNTDPIIEG DKIAVRCTMQ 310 320 330 340 350 360 STRHRTTKIG PTNEDEMCNF YLMYYVDHGE TLNMKFCFSQ GAPYYFWSNP DSGLHNIPHI EASTL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Neuropeptide amidation in Drosophila: separate genes encode the two enzymes catalyzing amidation." Kolhekar A.S., Roberts M.S., Jiang N., Johnson R.C., Mains R.E., Eipper B.A., Taghert P.H. J. Neurosci. 17:1363-1376(1997) [PubMed: 9006979] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 43-201 AND 291-324, ENZYME ACTIVITY, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY.
[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.
[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]. Strain: Berkeley. Tissue: Head.
[5]	"PHM is required for normal developmental transitions and for biosynthesis of secretory peptides in Drosophila." Jiang N., Kolhekar A.S., Jacobs P.S., Mains R.E., Eipper B.A., Taghert P.H. Dev. Biol. 226:118-136(2000) [PubMed: 10993678] [Abstract] Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[6]	"Multiple amidated neuropeptides are required for normal circadian locomotor rhythms in Drosophila." Taghert P.H., Hewes R.S., Park J.H., O'Brien M.A., Han M., Peck M.E. J. Neurosci. 21:6673-6686(2001) [PubMed: 11517257] [Abstract] Cited for: FUNCTION.
[7]	"Regulation of secretory protein expression in mature cells by DIMM, a basic helix-loop-helix neuroendocrine differentiation factor." Hewes R.S., Gu T., Brewster J.A., Qu C., Zhao T. J. Neurosci. 26:7860-7869(2006) [PubMed: 16870731] [Abstract] Cited for: INDUCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF006663 mRNA. Translation: AAB61676.1. U77426 Genomic DNA. Translation: AAB52566.1. U77427 Genomic DNA. Translation: AAB52567.1. U77428 Genomic DNA. Translation: AAB52568.2. U77429 Genomic DNA. Translation: AAB52569.1. U77430 Genomic DNA. Translation: AAB52570.1. U77431 Genomic DNA. Translation: AAB52571.1. U77432 Genomic DNA. Translation: AAB52572.1. AE013599 Genomic DNA. Translation: AAF47127.1. AY069103 mRNA. Translation: AAL39248.1.
RefSeq	NP_477225.1. NP_726394.1.
UniGene	Dm.2282
3D structure databases
HSSP	HSSP built from PDB template 1PHM based on UniProtKB P14925.
ModBase	Search...
Protein-protein interaction databases
IntAct	O01404. 5 interactions.
Genome annotation databases
Ensembl	FBtr0072203; FBpp0072112; FBgn0019948; Drosophila melanogaster. [Genome view]
GeneID	37823.
KEGG	dme:Dmel_CG3832.
Organism-specific databases
FlyBase	FBgn0019948. Phm.
Phylogenomic databases
OMA	AYRTHTH.
Enzyme and pathway databases
BRENDA	1.14.17.3. 48.
Gene expression databases
ArrayExpress	O01404.
Bgee	O01404.
GermOnline	CG3832. Drosophila melanogaster.
Family and domain databases
InterPro	IPR014784. Cu2_ascorb_mOase-like_C. IPR014783. Cu2_ascorb_mOase_C. IPR000323. Cu2_ascorb_mOase_N. IPR000945. Dopamine_b_mOase. IPR000720. Pep_amidat_mOase. [Graphical view]
Gene3D	G3DSA:2.60.120.230. Cu2_ascorb_mOase_core. 1 hit. G3DSA:2.60.120.310. Cu2_ascorb_mOase_core. 1 hit.
PANTHER	PTHR10157. Dopamine_b_mOase. 1 hit.
Pfam	PF03712. Cu2_monoox_C. 1 hit. PF01082. Cu2_monooxygen. 1 hit. [Graphical view]
PRINTS	PR00790. PAMONOXGNASE.
PROSITE	PS00084. CU2_MONOOXYGENASE_1. False negative. PS00085. CU2_MONOOXYGENASE_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	805568.

Entry information

Entry name

PHM_DROME

Accession

Primary (citable) accession number: O01404
Secondary accession number(s): O01402 , O01403, O01405, O01406, O01407, O01408, Q7JNH8, Q7JNH9, Q7JNI0, Q7JNI1, Q7JNI2, Q7JNI3, Q7JNI4

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 5, 2006
Last sequence update:	November 1, 1998
Last modified:	November 3, 2009
This is version 71 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

Drosophila annotation project