PHM_DROME
ID PHM_DROME Reviewed; 365 AA.
AC O01404; O01402; O01403; O01405; O01406; O01407; O01408; Q7JNH8; Q7JNH9;
AC Q7JNI0; Q7JNI1; Q7JNI2; Q7JNI3; Q7JNI4;
DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 2.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Peptidylglycine alpha-hydroxylating monooxygenase;
DE Short=dPHM;
DE EC=1.14.17.3;
DE Flags: Precursor;
GN Name=Phm; ORFNames=CG3832;
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 43-201 AND
RP 291-324, ENZYME ACTIVITY, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP TISSUE SPECIFICITY.
RX PubMed=9006979; DOI=10.1523/jneurosci.17-04-01363.1997;
RA Kolhekar A.S., Roberts M.S., Jiang N., Johnson R.C., Mains R.E.,
RA Eipper B.A., Taghert P.H.;
RT "Neuropeptide amidation in Drosophila: separate genes encode the two
RT enzymes catalyzing amidation.";
RL J. Neurosci. 17:1363-1376(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Head;
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=10993678; DOI=10.1006/dbio.2000.9832;
RA Jiang N., Kolhekar A.S., Jacobs P.S., Mains R.E., Eipper B.A.,
RA Taghert P.H.;
RT "PHM is required for normal developmental transitions and for biosynthesis
RT of secretory peptides in Drosophila.";
RL Dev. Biol. 226:118-136(2000).
RN [6]
RP FUNCTION.
RX PubMed=11517257; DOI=10.1523/jneurosci.21-17-06673.2001;
RA Taghert P.H., Hewes R.S., Park J.H., O'Brien M.A., Han M., Peck M.E.;
RT "Multiple amidated neuropeptides are required for normal circadian
RT locomotor rhythms in Drosophila.";
RL J. Neurosci. 21:6673-6686(2001).
RN [7]
RP INDUCTION.
RX PubMed=16870731; DOI=10.1523/jneurosci.1759-06.2006;
RA Hewes R.S., Gu T., Brewster J.A., Qu C., Zhao T.;
RT "Regulation of secretory protein expression in mature cells by DIMM, a
RT basic helix-loop-helix neuroendocrine differentiation factor.";
RL J. Neurosci. 26:7860-7869(2006).
CC -!- FUNCTION: Monooxygenase that catalyzes an essential reaction in C-
CC terminal alpha-amidation of peptides. Produces an unstable peptidyl(2-
CC hydroxyglycine) intermediate. C-terminal amidation of peptides is
CC required for normal developmental transitions and for biosynthesis of
CC secretory peptides throughout the life. {ECO:0000269|PubMed:10993678,
CC ECO:0000269|PubMed:11517257}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a [peptide]-C-terminal glycine + 2 L-ascorbate + O2 = a
CC [peptide]-C-terminal (2S)-2-hydroxyglycine + H2O + 2 monodehydro-L-
CC ascorbate radical; Xref=Rhea:RHEA:21452, Rhea:RHEA-COMP:13486,
CC Rhea:RHEA-COMP:15321, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:38290, ChEBI:CHEBI:59513, ChEBI:CHEBI:137000,
CC ChEBI:CHEBI:142768; EC=1.14.17.3;
CC Evidence={ECO:0000269|PubMed:9006979};
CC -!- COFACTOR:
CC Name=Cu(2+); Xref=ChEBI:CHEBI:29036;
CC Evidence={ECO:0000305|PubMed:9006979};
CC Note=Binds 2 copper ions per subunit. {ECO:0000305|PubMed:9006979};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=2.2 uM for alpha-N-acetyl-Tyr-Val-Gly
CC {ECO:0000269|PubMed:9006979};
CC pH dependence:
CC Optimum pH is 5.0. {ECO:0000269|PubMed:9006979};
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Expressed in the central nervous system (CNS) in a
CC small number of CNS neurons (approximately a few hundred). Expression
CC is present both in cell bodies and within neuropil regions. It is
CC strongly expressed in neuroendocrine neurons (at protein level).
CC {ECO:0000269|PubMed:9006979}.
CC -!- INDUCTION: Transcriptionally regulated by DIMM.
CC {ECO:0000269|PubMed:16870731}.
CC -!- DISRUPTION PHENOTYPE: Death as late embryos with morphological defects
CC that resemble those of animals with mutations in genes of the ecdysone-
CC inducible regulatory circuit. Amidated peptides are largely absent but
CC peptide precursors, a nonamidated neuropeptide, nonpeptide
CC transmitters, and other peptide biosynthetic enzymes are detected.
CC {ECO:0000269|PubMed:10993678}.
CC -!- SIMILARITY: Belongs to the copper type II ascorbate-dependent
CC monooxygenase family. {ECO:0000305}.
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DR EMBL; AF006663; AAB61676.1; -; mRNA.
DR EMBL; U77426; AAB52566.1; -; Genomic_DNA.
DR EMBL; U77427; AAB52567.1; -; Genomic_DNA.
DR EMBL; U77428; AAB52568.2; -; Genomic_DNA.
DR EMBL; U77429; AAB52569.1; -; Genomic_DNA.
DR EMBL; U77430; AAB52570.1; -; Genomic_DNA.
DR EMBL; U77431; AAB52571.1; -; Genomic_DNA.
DR EMBL; U77432; AAB52572.1; -; Genomic_DNA.
DR EMBL; AE013599; AAF47127.1; -; Genomic_DNA.
DR EMBL; AY069103; AAL39248.1; -; mRNA.
DR RefSeq; NP_477225.1; NM_057877.4.
DR RefSeq; NP_726394.1; NM_166644.2.
DR AlphaFoldDB; O01404; -.
DR SMR; O01404; -.
DR BioGRID; 63409; 6.
DR IntAct; O01404; 2.
DR STRING; 7227.FBpp0072112; -.
DR GlyGen; O01404; 2 sites.
DR PaxDb; O01404; -.
DR DNASU; 37823; -.
DR EnsemblMetazoa; FBtr0072202; FBpp0072111; FBgn0283509.
DR EnsemblMetazoa; FBtr0072203; FBpp0072112; FBgn0283509.
DR GeneID; 37823; -.
DR KEGG; dme:Dmel_CG3832; -.
DR FlyBase; FBgn0283509; Phm.
DR VEuPathDB; VectorBase:FBgn0283509; -.
DR eggNOG; KOG3567; Eukaryota.
DR GeneTree; ENSGT00940000173843; -.
DR HOGENOM; CLU_051564_0_0_1; -.
DR InParanoid; O01404; -.
DR OMA; PELYLCT; -.
DR OrthoDB; 1156284at2759; -.
DR PhylomeDB; O01404; -.
DR BRENDA; 1.14.17.3; 1994.
DR BioGRID-ORCS; 37823; 0 hits in 1 CRISPR screen.
DR ChiTaRS; phm; fly.
DR GenomeRNAi; 37823; -.
DR PRO; PR:O01404; -.
DR Proteomes; UP000000803; Chromosome 2R.
DR Bgee; FBgn0283509; Expressed in oviduct (Drosophila) and 30 other tissues.
DR ExpressionAtlas; O01404; baseline and differential.
DR Genevisible; O01404; DM.
DR GO; GO:0005576; C:extracellular region; IBA:GO_Central.
DR GO; GO:0005615; C:extracellular space; HDA:FlyBase.
DR GO; GO:0016020; C:membrane; IEA:InterPro.
DR GO; GO:0005507; F:copper ion binding; IEA:InterPro.
DR GO; GO:0004504; F:peptidylglycine monooxygenase activity; IEA:UniProtKB-EC.
DR GO; GO:0007613; P:memory; IMP:FlyBase.
DR GO; GO:0006518; P:peptide metabolic process; IEA:InterPro.
DR GO; GO:0044719; P:regulation of imaginal disc-derived wing size; IMP:FlyBase.
DR GO; GO:0009620; P:response to fungus; HEP:FlyBase.
DR GO; GO:0019953; P:sexual reproduction; HEP:FlyBase.
DR Gene3D; 2.60.120.230; -; 1.
DR Gene3D; 2.60.120.310; -; 1.
DR InterPro; IPR014784; Cu2_ascorb_mOase-like_C.
DR InterPro; IPR014783; Cu2_ascorb_mOase_CS-2.
DR InterPro; IPR000323; Cu2_ascorb_mOase_N.
DR InterPro; IPR036939; Cu2_ascorb_mOase_N_sf.
DR InterPro; IPR024548; Cu2_monoox_C.
DR InterPro; IPR000720; PHM/PAL.
DR InterPro; IPR008977; PHM/PNGase_F_dom_sf.
DR Pfam; PF03712; Cu2_monoox_C; 1.
DR Pfam; PF01082; Cu2_monooxygen; 1.
DR PRINTS; PR00790; PAMONOXGNASE.
DR SUPFAM; SSF49742; SSF49742; 2.
DR PROSITE; PS00085; CU2_MONOOXYGENASE_2; 1.
PE 1: Evidence at protein level;
KW Copper; Disulfide bond; Glycoprotein; Metal-binding; Monooxygenase;
KW Oxidoreductase; Reference proteome; Secreted; Signal.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT CHAIN 25..365
FT /note="Peptidylglycine alpha-hydroxylating monooxygenase"
FT /id="PRO_0000248571"
FT BINDING 95
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="A"
FT /evidence="ECO:0000250"
FT BINDING 96
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="A"
FT /evidence="ECO:0000250"
FT BINDING 172
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="A"
FT /evidence="ECO:0000250"
FT BINDING 241
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="B"
FT /evidence="ECO:0000250"
FT BINDING 243
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="B"
FT /evidence="ECO:0000250"
FT BINDING 317
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="B"
FT /evidence="ECO:0000250"
FT CARBOHYD 88
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 280
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 69..114
FT /evidence="ECO:0000250"
FT DISULFID 102..129
FT /evidence="ECO:0000250"
FT DISULFID 297..318
FT /evidence="ECO:0000250"
SQ SEQUENCE 365 AA; 40564 MW; 9368D9D92018C178 CRC64;
MPRISEIAAS VGLLLLIGVI SVDGLVKEGD YQNSLYQQNL ESNSATGATA SFPFLMPNVS
PQTPDLYLCT PIKVDPTTTY YIVGFNPNAT MNTAHHMLLY GCGEPGTSKT TWNCGEMNRA
SQEESASPCG PHSNSQIVYA WARDAQKLNL PEGVGFKVGK NSPIKYLVLQ VHYAHIDKFK
DGSTDDSGVF LDYTEEPRKK LAGTLLLGTD GQIPAMKTEH LETACEVNEQ KVLHPFAYRV
HTHGLGKVVS GYRVRTNSDG EQEWLQLGKR DPLTPQMFYN TSNTDPIIEG DKIAVRCTMQ
STRHRTTKIG PTNEDEMCNF YLMYYVDHGE TLNMKFCFSQ GAPYYFWSNP DSGLHNIPHI
EASTL
