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UniProtKB/Swiss-Prot entry O01404


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name PHM_DROME
Primary accession number O01404
Secondary accession numbers O01402 O01403 O01405 O01406 O01407 O01408 Q7JNH8 Q7JNH9 Q7JNI0 Q7JNI1 Q7JNI2 Q7JNI3 Q7JNI4
Integrated into Swiss-Prot on September 5, 2006
Sequence was last modified on November 1, 1998 (Sequence version 2)
Annotations were last modified on    December 16, 2008 (Entry version 64)
Name and origin of the protein
Protein name Peptidylglycine alpha-hydroxylating monooxygenase [Precursor]
Synonyms dPHM
EC 1.14.17.3
Gene name
Name: Phm
ORFNames: CG3832
From
Drosophila melanogaster (Fruit fly) [TaxID: 7227] 
Taxonomy Eukaryota; Metazoa; Arthropoda; Hexapoda; Insecta; Pterygota; Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea; Drosophilidae; Drosophila; Sophophora.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [MRNA], NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 43-201 AND 291-324, ENZYME ACTIVITY, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, AND TISSUE SPECIFICITY.
PubMed=9006979 [NCBI, ExPASy, EBI, Israel, Japan]
Kolhekar A.S., Roberts M.S., Jiang N., Johnson R.C., Mains R.E., Eipper B.A., Taghert P.H.;
"Neuropeptide amidation in Drosophila: separate genes encode the two enzymes catalyzing amidation.";
J. Neurosci. 17:1363-1376(1997).
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
STRAIN=Berkeley;
DOI=10.1126/science.287.5461.2185; PubMed=10731132 [NCBI, ExPASy, EBI, Israel, Japan]
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.;
"The genome sequence of Drosophila melanogaster.";
Science 287:2185-2195(2000).
[3]
GENOME REANNOTATION.
PubMed=12537572 [NCBI, ExPASy, EBI, Israel, Japan]
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.;
"Annotation of the Drosophila melanogaster euchromatic genome: a systematic review.";
Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
STRAIN=Berkeley;
TISSUE=Head;
PubMed=12537569 [NCBI, ExPASy, EBI, Israel, Japan]
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.;
"A Drosophila full-length cDNA resource.";
Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
[5]
FUNCTION.
DOI=10.1006/dbio.2000.9832; PubMed=10993678 [NCBI, ExPASy, EBI, Israel, Japan]
Jiang N., Kolhekar A.S., Jacobs P.S., Mains R.E., Eipper B.A., Taghert P.H.;
"PHM is required for normal developmental transitions and for biosynthesis of secretory peptides in Drosophila.";
Dev. Biol. 226:118-136(2000).
[6]
FUNCTION.
PubMed=11517257 [NCBI, ExPASy, EBI, Israel, Japan]
Taghert P.H., Hewes R.S., Park J.H., O'Brien M.A., Han M., Peck M.E.;
"Multiple amidated neuropeptides are required for normal circadian locomotor rhythms in Drosophila.";
J. Neurosci. 21:6673-6686(2001).
[7]
INDUCTION.
DOI=10.1523/JNEUROSCI.1759-06.2006; PubMed=16870731 [NCBI, ExPASy, EBI, Israel, Japan]
Hewes R.S., Gu T., Brewster J.A., Qu C., Zhao T.;
"Regulation of secretory protein expression in mature cells by DIMM, a basic helix-loop-helix neuroendocrine differentiation factor.";
J. Neurosci. 26:7860-7869(2006).
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.
  • CATALYTIC ACTIVITY: Peptidylglycine + ascorbate + O2 = peptidyl(2-hydroxyglycine) + dehydroascorbate + H2O.
  • COFACTOR: Binds 2 copper ions per subunit (Probable).
  • BIOPHYSICOCHEMICAL PROPERTIES:
    Kinetic parameters:   KM=2.2 µM for alpha-N-acetyl-Tyr-Val-Gly;
    pH dependence:   Optimum pH is 5.0;
  • INTERACTION:
    Q9VP96:-; NbExp=1; IntAct=EBI-149384, EBI-142310;
  • 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).
  • INDUCTION: Transcriptionally regulated by DIMM.
  • MISCELLANEOUS: Flies lacking Phm die 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.
  • SIMILARITY: Belongs to the copper type II ascorbate-dependent monooxygenase family.
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
AF006663; AAB61676.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
U77426; AAB52566.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
U77427; AAB52567.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
U77428; AAB52568.2; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
U77429; AAB52569.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
U77430; AAB52570.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
U77431; AAB52571.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
U77432; AAB52572.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AE013599; AAF47127.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AY069103; AAL39248.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
RefSeq NP_477225.1; -.
NP_726394.1; -.
UniGene Dm.2282
3D structure databases
HSSP P14925; 1PHM. [HSSP ENTRY / PDB]
ModBase O01404.
Protein-protein interaction databases
IntAct O01404; 5.
Organism-specific databases
FlyBase FBgn0019948; Phm.
Gene expression databases
ArrayExpress O01404; -.
GermOnline CG3832; Drosophila melanogaster.
Ontologies
GO
GO:0005576; Cellular component: extracellular region (inferred from electronic annotation from UniProtKB-KW).
GO:0016020; Cellular component: membrane (inferred from electronic annotation from InterPro).
GO:0005507; Molecular function: copper ion binding (inferred from electronic annotation from InterPro).
GO:0004500; Molecular function: dopamine beta-monooxygenase activity (inferred from electronic annotation from InterPro).
GO:0004504; Molecular function: peptidylglycine monooxygenase activity (inferred from electronic annotation from InterPro).
GO:0005515; Molecular function: protein binding (inferred from physical interaction from IntAct).
GO:0006584; Biological process: catecholamine metabolic process (inferred from electronic annotation from InterPro).
GO:0055114; Biological process: oxidation reduction (inferred from electronic annotation from UniProtKB-KW).
GO:0006518; Biological process: peptide metabolic process (inferred from electronic annotation from InterPro).
QuickGo view.
Family and domain databases
InterPro IPR014783; Cu2_ascorb_mOase_C.
IPR014784; Cu2_ascorb_mOase_like_C.
IPR000323; Cu2_ascorb_mOase_N.
IPR000945; Dopamine_b_mOase.
IPR000720; Pep_amidat_mOase.
Graphical view of domain structure.
Gene3D G3DSA:2.60.120.230; Cu2_ascorb_mOase_core; 1.
G3DSA:2.60.120.310; Cu2_ascorb_mOase_core; 1.
PANTHER PTHR10157; Dopamine_b_mOase; 1.
Pfam PF03712; Cu2_monoox_C; 1.
PF01082; Cu2_monooxygen; 1.
Pfam graphical view of domain structure.
PRINTS PR00790; PAMONOXGNASE.
PROSITE PS00084; CU2_MONOOXYGENASE_1; FALSE_NEG.
PS00085; CU2_MONOOXYGENASE_2; 1.
Genome annotation databases
Ensembl CG3832; Drosophila melanogaster. [Contig view]
GeneID 37823; -.
KEGG dme:Dmel_CG3832; -.
Other
NextBio 805568; -.
ProtoNet O01404.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
Complete proteome; Copper; Glycoprotein; Metal-binding; Monooxygenase; Oxidoreductase; Secreted; Signal.
Features
SEVIEWER logo Feature table viewer
KeyFrom   To Length Description FTId
SIGNAL   1    24  24     Potential. 
CHAIN   25   365  341     Peptidylglycine alpha-hydroxylating monooxygenase. PRO_0000248571
METAL   95    95        Copper A (By similarity). 
METAL   96    96        Copper A (By similarity). 
METAL   172   172        Copper A (By similarity). 
METAL   241   241        Copper B (By similarity). 
METAL   243   243        Copper B (By similarity). 
METAL   317   317        Copper B (By similarity). 
CARBOHYD   88    88        N-linked (GlcNAc...) (Potential). 
CARBOHYD   280   280        N-linked (GlcNAc...) (Potential). 
DISULFID   69   114        By similarity. 
DISULFID   102   129        By similarity. 
DISULFID   297   318        By similarity. 
Sequence information
Length: 365 AA [This is the length of the unprocessed precursor] Molecular weight: 40564 Da [This is the MW of the unprocessed precursor] CRC64: 9368D9D92018C178 [This is a checksum on the sequence]
        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 

O01404 in FASTA format

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