AMDA_XENLA
ID AMDA_XENLA Reviewed; 935 AA.
AC P08478; B7ZR22; Q5D0B6; Q91697;
DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
DT 23-MAR-2010, sequence version 3.
DT 03-AUG-2022, entry version 130.
DE RecName: Full=Peptidyl-glycine alpha-amidating monooxygenase A;
DE Short=PAM-A;
DE AltName: Full=Peptide C-terminal alpha-amidating enzyme I;
DE Short=AE-I;
DE AltName: Full=Peptidyl-glycine alpha-amidating monooxygenase I;
DE Includes:
DE RecName: Full=Peptidylglycine alpha-hydroxylating monooxygenase A;
DE Short=PHM-A;
DE EC=1.14.17.3;
DE Includes:
DE RecName: Full=Peptidyl-alpha-hydroxyglycine alpha-amidating lyase A;
DE EC=4.3.2.5;
DE AltName: Full=Peptidylamidoglycolate lyase-A;
DE Short=PAL-A;
DE Flags: Precursor;
GN Name=pam-a;
OS Xenopus laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND PARTIAL PROTEIN SEQUENCE.
RX PubMed=3689360; DOI=10.1016/0006-291x(87)90911-9;
RA Mizuno K., Ohsuye K., Wada Y., Fuchimura K., Tanaka S., Matsuo H.;
RT "Cloning and sequence of cDNA encoding a peptide C-terminal alpha-amidating
RT enzyme from Xenopus laevis.";
RL Biochem. Biophys. Res. Commun. 148:546-552(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE, AND
RP FUNCTION.
RC TISSUE=Skin;
RX PubMed=1935950; DOI=10.1111/j.1432-1033.1991.tb16314.x;
RA Iwasaki Y., Kawahara T., Shimoi H., Suzuki K., Ghisalba O., Kangawa K.,
RA Matsuo H., Nishikawa Y.;
RT "Purification and cDNA cloning of Xenopus laevis skin
RT peptidylhydroxyglycine N-C lyase, catalyzing the second reaction of C-
RT terminal alpha-amidation.";
RL Eur. J. Biochem. 201:551-559(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Gastrula, and Tail bud;
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (NOV-2008) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Bifunctional enzyme that catalyzes 2 sequential steps in C-
CC terminal alpha-amidation of peptides. The monooxygenase part produces
CC an unstable peptidyl(2-hydroxyglycine) intermediate that is dismutated
CC to glyoxylate and the corresponding desglycine peptide amide by the
CC lyase part. C-terminal amidation of peptides such as neuropeptides is
CC essential for full biological activity. {ECO:0000269|PubMed:1935950}.
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 -!- 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 -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Zn(2+) is required for the lyase reaction. {ECO:0000250};
CC -!- COFACTOR:
CC Name=Cu(2+); Xref=ChEBI:CHEBI:29036; Evidence={ECO:0000250};
CC Note=Binds 2 copper ions per subunit for the monooxygenase reaction.
CC {ECO:0000250};
CC -!- SUBUNIT: Monomer. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle membrane
CC {ECO:0000250}; Single-pass membrane protein {ECO:0000250}.
CC Note=Secretory granules.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=AE-III;
CC IsoId=P08478-1; Sequence=Displayed;
CC Name=2; Synonyms=AE-I;
CC IsoId=P08478-2; Sequence=VSP_020312, VSP_020313;
CC -!- SIMILARITY: In the C-terminal section; belongs to the peptidyl-alpha-
CC hydroxyglycine alpha-amidating lyase family. {ECO:0000305}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the copper type II
CC ascorbate-dependent monooxygenase family. {ECO:0000305}.
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DR EMBL; M18134; AAA49640.1; -; mRNA.
DR EMBL; X62771; CAA44615.1; -; mRNA.
DR EMBL; BC043987; AAH43987.1; -; mRNA.
DR EMBL; BC170012; AAI70012.1; -; mRNA.
DR EMBL; BC170016; AAI70016.1; -; mRNA.
DR PIR; A29726; URXLA1.
DR PIR; S17855; S17855.
DR RefSeq; NP_001079520.2; NM_001086051.2.
DR AlphaFoldDB; P08478; -.
DR SMR; P08478; -.
DR PRIDE; P08478; -.
DR GeneID; 379207; -.
DR KEGG; xla:379207; -.
DR CTD; 379207; -.
DR Xenbase; XB-GENE-950939; pam.L.
DR Proteomes; UP000186698; Chromosome 1L.
DR Bgee; 379207; Expressed in brain and 20 other tissues.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0030658; C:transport vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005507; F:copper ion binding; IEA:InterPro.
DR GO; GO:0004598; F:peptidylamidoglycolate lyase activity; IEA:UniProtKB-EC.
DR GO; GO:0004504; F:peptidylglycine monooxygenase activity; IEA:UniProtKB-EC.
DR GO; GO:0006518; P:peptide metabolic process; IEA:InterPro.
DR Gene3D; 2.120.10.30; -; 1.
DR Gene3D; 2.60.120.230; -; 1.
DR Gene3D; 2.60.120.310; -; 1.
DR InterPro; IPR011042; 6-blade_b-propeller_TolB-like.
DR InterPro; IPR014784; Cu2_ascorb_mOase-like_C.
DR InterPro; IPR020611; Cu2_ascorb_mOase_CS-1.
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; IPR001258; NHL_repeat.
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 Pfam; PF01436; NHL; 3.
DR PRINTS; PR00790; PAMONOXGNASE.
DR SUPFAM; SSF49742; SSF49742; 2.
DR PROSITE; PS00084; CU2_MONOOXYGENASE_1; 1.
DR PROSITE; PS00085; CU2_MONOOXYGENASE_2; 1.
DR PROSITE; PS51125; NHL; 4.
PE 1: Evidence at protein level;
KW Alternative splicing; Copper; Cytoplasmic vesicle;
KW Direct protein sequencing; Disulfide bond; Glycoprotein; Lyase; Membrane;
KW Metal-binding; Monooxygenase; Multifunctional enzyme; Oxidoreductase;
KW Reference proteome; Repeat; Signal; Transmembrane; Transmembrane helix;
KW Zinc.
FT SIGNAL 1..36
FT /evidence="ECO:0000255"
FT CHAIN 37..935
FT /note="Peptidyl-glycine alpha-amidating monooxygenase A"
FT /id="PRO_0000006367"
FT TOPO_DOM 37..825
FT /note="Intragranular"
FT /evidence="ECO:0000255"
FT TRANSMEM 826..846
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 847..935
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REPEAT 463..504
FT /note="NHL 1"
FT REPEAT 512..557
FT /note="NHL 2"
FT REPEAT 565..609
FT /note="NHL 3"
FT REPEAT 662..705
FT /note="NHL 4"
FT REGION 1..390
FT /note="Peptidylglycine alpha-hydroxylating monooxygenase"
FT /evidence="ECO:0000250"
FT REGION 362..385
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 391..712
FT /note="Peptidyl-alpha-hydroxyglycine alpha-amidating lyase"
FT /evidence="ECO:0000250"
FT REGION 728..764
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 778..812
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 896..935
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 728..750
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 103
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="A"
FT /evidence="ECO:0000250"
FT BINDING 104
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="A"
FT /evidence="ECO:0000250"
FT BINDING 168
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="A"
FT /evidence="ECO:0000250"
FT BINDING 238
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="B"
FT /evidence="ECO:0000250"
FT BINDING 240
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="B"
FT /evidence="ECO:0000250"
FT BINDING 310
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="B"
FT /evidence="ECO:0000250"
FT CARBOHYD 658
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 739
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 43..182
FT /evidence="ECO:0000250"
FT DISULFID 77..122
FT /evidence="ECO:0000250"
FT DISULFID 110..127
FT /evidence="ECO:0000250"
FT DISULFID 223..330
FT /evidence="ECO:0000250"
FT DISULFID 289..311
FT /evidence="ECO:0000250"
FT DISULFID 526..547
FT /evidence="ECO:0000250"
FT DISULFID 594..605
FT /evidence="ECO:0000250"
FT VAR_SEQ 391..400
FT /note="DVHLEEDTDW -> GLITLGDSAV (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:3689360, ECO:0000303|Ref.3"
FT /id="VSP_020312"
FT VAR_SEQ 401..935
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:3689360, ECO:0000303|Ref.3"
FT /id="VSP_020313"
FT CONFLICT 792
FT /note="P -> S (in Ref. 2; CAA44615)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 935 AA; 103389 MW; E9C2BF75733AB83C CRC64;
MASLSSSFLV LFLLFQNSCY CFRSPLSVFK RYEESTRSLS NDCLGTTRPV MSPGSSDYTL
DIRMPGVTPT ESDTYLCKSY RLPVDDEAYV VDFRPHANMD TAHHMLLFGC NIPSSTDDYW
DCSAGTCMDK SSIMYAWAKN APPTKLPEGV GFRVGGKSGS RYFVLQVHYG NVKAFQDKHK
DCTGVTVRVT PEKQPQIAGI YLSMSVDTVI PPGEEAVNSD IACLYNRPTI HPFAYRVHTH
QLGQVVSGFR VRHGKWSLIG RQSPQLPQAF YPVEHPVEIS PGDIIATRCL FTGKGRTSAT
YIGGTSNDEM CNLYIMYYMD AAHATSYMTC VQTGEPKLFQ NIPEIANVPI PVSPDMMMMM
GHGHHHTEAE PEKNTGLQQP KREEEEVLDQ DVHLEEDTDW PGVNLKVGQV SGLALDPKNN
LAIFHRGDHV WDENSFDRNF VYQQRGIGPI QESTILVVDP SSSKVLKSTG KNLFFLPHGL
TIDRDGNYWV TDVALHQVFK LGAGKETPLL VLGRAFQPGS DRKHFCQPTD VAVDPITGNF
FVADGYCNSR IMQFSPNGMF IMQWGEETSS NVPRPGQFRI PHSLTMVPDQ GQLCVADREN
GRIQCFHAET GNFVKQIKHQ EFGREVFAVS YAPGGVLYAV NGKPYYGYSA PVQGFMLNFS
NGDILDTFIP ARKNFDMPHD IAAADDGTVY VGDAHANAVW KFSPSKAEHR SVKKAGIEVE
EITETEIFET HIRSRPKTNE SVEKQTQEKQ QKQKNSAGVS TQEKQNVVQE INAGVPTQEK
QNVVQESSAG VPTQEKQSVV QESSAGVSTQ EKQSVVQESS AGVSFVLIIT LLIIPIAVLI
AIAIFIRWRK VRMYGGDIDH KSESSSVGIL GKLRGKGSGG LNLGTFFATH KGYSRKGFDR
LSTEGSDQEK DDDDGSDSEE EYSAPPIPPA PVSSS
