PAL2_DROME
ID PAL2_DROME Reviewed; 406 AA.
AC Q9W1L5; A4UZT8; Q7KVI0; Q9GPF3;
DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 2.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=Peptidyl-alpha-hydroxyglycine alpha-amidating lyase 2;
DE EC=4.3.2.5;
DE AltName: Full=Peptidylamidoglycolate lyase 2;
DE Short=dPAL2 {ECO:0000303|PubMed:15198673};
DE Flags: Precursor;
GN Name=Pal2; Synonyms=Pal; ORFNames=CG5472;
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].
RA Williamson M., Grimmelikhuijzen C.J.P.;
RT "Molecular cloning of a peptidyl-alpha-hydroxyglycine alpha-amidating lyase
RT from Drosophila melanogaster.";
RL Submitted (AUG-2000) to the EMBL/GenBank/DDBJ databases.
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, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR
RP LOCATION, GLYCOSYLATION, AND TISSUE SPECIFICITY.
RX PubMed=15198673; DOI=10.1111/j.1471-4159.2004.02464.x;
RA Han M., Park D., Vanderzalm P.J., Mains R.E., Eipper B.A., Taghert P.H.;
RT "Drosophila uses two distinct neuropeptide amidating enzymes, dPAL1 and
RT dPAL2.";
RL J. Neurochem. 90:129-141(2004).
CC -!- FUNCTION: Peptidyl-alpha-hydroxylglycine alpha-amidating lyase that
CC catalyzes an essential reaction in C-terminal alpha-amidation of
CC peptides. Mediates the dismutation of the unstable peptidyl(2-
CC hydroxyglycine) intermediate to glyoxylate and the corresponding
CC desglycine peptide amide. C-terminal amidation of peptides such as
CC neuropeptides is essential for full biological activity.
CC {ECO:0000269|PubMed:15198673}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a [peptide]-C-terminal (2S)-2-hydroxyglycine = a [peptide]-C-
CC terminal amide + glyoxylate; Xref=Rhea:RHEA:20924, Rhea:RHEA-
CC COMP:13485, Rhea:RHEA-COMP:15321, ChEBI:CHEBI:36655,
CC ChEBI:CHEBI:137001, ChEBI:CHEBI:142768; EC=4.3.2.5;
CC Evidence={ECO:0000269|PubMed:15198673};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20925;
CC Evidence={ECO:0000269|PubMed:15198673};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=70 uM for peptidyl-alpha-hydroxyglycine
CC {ECO:0000269|PubMed:15198673};
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305|PubMed:15198673}.
CC -!- TISSUE SPECIFICITY: Only found in a subset of neurons distributed
CC throughout all levels of the central nervous system (CNS). Present in
CC at least some neuroendocrine cells. In adult brains, it is only present
CC in a small handful of cells, the majority of which being distributed in
CC distal parts of the medulla, with a higher expression in the posterior
CC surface of the brain (at protein level). {ECO:0000269|PubMed:15198673}.
CC -!- PTM: N-glycosylated. {ECO:0000305|PubMed:15198673}.
CC -!- SIMILARITY: Belongs to the peptidyl-alpha-hydroxyglycine alpha-
CC amidating lyase family. {ECO:0000305}.
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DR EMBL; AY007228; AAG01895.1; -; mRNA.
DR EMBL; AE013599; AAF47043.2; -; Genomic_DNA.
DR EMBL; AE013599; AAS64763.2; -; Genomic_DNA.
DR EMBL; AY119165; AAM51025.1; -; mRNA.
DR RefSeq; NP_001286776.1; NM_001299847.1.
DR RefSeq; NP_525118.2; NM_080379.5.
DR RefSeq; NP_995929.2; NM_206207.3.
DR AlphaFoldDB; Q9W1L5; -.
DR SMR; Q9W1L5; -.
DR BioGRID; 63345; 2.
DR STRING; 7227.FBpp0088497; -.
DR PaxDb; Q9W1L5; -.
DR PRIDE; Q9W1L5; -.
DR DNASU; 37746; -.
DR EnsemblMetazoa; FBtr0089500; FBpp0088497; FBgn0262728.
DR EnsemblMetazoa; FBtr0301509; FBpp0290724; FBgn0262728.
DR EnsemblMetazoa; FBtr0346652; FBpp0312237; FBgn0262728.
DR GeneID; 37746; -.
DR KEGG; dme:Dmel_CG5472; -.
DR UCSC; CG5472-RC; d. melanogaster.
DR CTD; 37746; -.
DR FlyBase; FBgn0262728; Pal2.
DR VEuPathDB; VectorBase:FBgn0262728; -.
DR eggNOG; KOG3567; Eukaryota.
DR GeneTree; ENSGT00940000156369; -.
DR HOGENOM; CLU_037899_6_0_1; -.
DR InParanoid; Q9W1L5; -.
DR OMA; NERFFDQ; -.
DR OrthoDB; 476471at2759; -.
DR PhylomeDB; Q9W1L5; -.
DR BRENDA; 4.3.2.5; 1994.
DR SABIO-RK; Q9W1L5; -.
DR BioGRID-ORCS; 37746; 0 hits in 1 CRISPR screen.
DR GenomeRNAi; 37746; -.
DR PRO; PR:Q9W1L5; -.
DR Proteomes; UP000000803; Chromosome 2R.
DR Bgee; FBgn0262728; Expressed in brain and 15 other tissues.
DR ExpressionAtlas; Q9W1L5; baseline and differential.
DR Genevisible; Q9W1L5; DM.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004598; F:peptidylamidoglycolate lyase activity; IDA:UniProtKB.
DR GO; GO:0004504; F:peptidylglycine monooxygenase activity; ISS:FlyBase.
DR Gene3D; 2.120.10.30; -; 1.
DR InterPro; IPR011042; 6-blade_b-propeller_TolB-like.
DR InterPro; IPR001258; NHL_repeat.
DR Pfam; PF01436; NHL; 1.
DR PROSITE; PS51125; NHL; 4.
PE 1: Evidence at protein level;
KW Disulfide bond; Glycoprotein; Lyase; Metal-binding; Reference proteome;
KW Repeat; Secreted; Signal; Zinc.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..406
FT /note="Peptidyl-alpha-hydroxyglycine alpha-amidating lyase
FT 2"
FT /id="PRO_0000248574"
FT REPEAT 168..209
FT /note="NHL 1"
FT REPEAT 218..261
FT /note="NHL 2"
FT REPEAT 264..308
FT /note="NHL 3"
FT REPEAT 358..402
FT /note="NHL 4"
FT DISULFID 231..251
FT /evidence="ECO:0000250"
FT DISULFID 293..304
FT /evidence="ECO:0000250"
FT CONFLICT 13
FT /note="S -> T (in Ref. 1; AAG01895)"
FT /evidence="ECO:0000305"
FT CONFLICT 16
FT /note="Y -> C (in Ref. 1; AAG01895)"
FT /evidence="ECO:0000305"
FT CONFLICT 40
FT /note="N -> S (in Ref. 1; AAG01895)"
FT /evidence="ECO:0000305"
FT CONFLICT 382
FT /note="N -> S (in Ref. 1; AAG01895)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 406 AA; 44712 MW; 47E6037A41071DF9 CRC64;
MSRLLFVALL AISLGYVASS SSNHLPAGLA MDLGPGVNLN ERFFDQVRAL IKRRLQEKGL
AKPEQPELAM PLTDDDAVAL QNQRSYDNVP LPAASVPTPV LVENWPTEQH SFGQVTAVAV
DPQGSPVVFH RAERYWDVNT FNESNIYYLI EYGPIKENTI YVLDAKTGAI KSGWGSNMFY
MPHGLTIDLH GNYWITDVAM HQAFKFKPFS NKPLLTIGKR FRPGSSVKHL CKPTSIAVAT
TGEFFIADGY CNSRILKFNA AGKLLRTIPQ PPEFLSLQVP HAITLLEHLD LLCIADRENM
RVVCPKAGLI SSHGEGEPAA TIQEPDLGRV FGVASFGDIV FAVNGPTSML PVRGFTIDPR
SETIIGHWGE FKNPHSMAVS VNGSALYVTE IGTNHQTNRV WKYVLA
