ID AMD_BOVIN Reviewed; 972 AA. AC P10731; DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot. DT 01-APR-1993, sequence version 2. DT 23-FEB-2022, entry version 169. DE RecName: Full=Peptidyl-glycine alpha-amidating monooxygenase {ECO:0000250|UniProtKB:P19021}; DE Short=PAM {ECO:0000303|PubMed:2059626}; DE Includes: DE RecName: Full=Peptidylglycine alpha-hydroxylating monooxygenase {ECO:0000250|UniProtKB:P19021}; DE Short=PHM {ECO:0000250|UniProtKB:P19021}; DE EC=1.14.17.3 {ECO:0000269|PubMed:2059626}; DE Includes: DE RecName: Full=Peptidyl-alpha-hydroxyglycine alpha-amidating lyase; DE EC=4.3.2.5 {ECO:0000269|PubMed:2059626}; DE AltName: Full=Peptidylamidoglycolate lyase {ECO:0000250|UniProtKB:P19021}; DE Short=PAL {ECO:0000250|UniProtKB:P19021}; DE Flags: Precursor; GN Name=PAM; OS Bos taurus (Bovine). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae; OC Bovinae; Bos. OX NCBI_TaxID=9913; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE. RC TISSUE=Pituitary; RX PubMed=3153462; DOI=10.1210/mend-1-11-777; RA Eipper B.A., Park L.P., Dickerson I.M., Keutmann H.T., Thiele E.A., RA Rodriguez H., Schofield P.R., Mains R.E.; RT "Structure of the precursor to an enzyme mediating COOH-terminal amidation RT in peptide biosynthesis."; RL Mol. Endocrinol. 1:777-790(1987). RN [2] RP PROTEIN SEQUENCE OF 478-499; 544-575; 611-630 AND 665-695, FUNCTION, RP SUBCELLULAR LOCATION, CATALYTIC ACTIVITY, COFACTOR, AND BIOPHYSICOCHEMICAL RP PROPERTIES. RX PubMed=2059626; DOI=10.1021/bi00239a016; RA Katopodis A.G., Ping D.S., Smith C.E., May S.W.; RT "Functional and structural characterization of peptidylamidoglycolate RT lyase, the enzyme catalyzing the second step in peptide amidation."; RL Biochemistry 30:6189-6194(1991). CC -!- FUNCTION: Bifunctional enzyme that catalyzes the post-translational CC modification of inactive peptidylglycine precursors to the CC corresponding bioactive alpha-amidated peptides, a terminal CC modification in biosynthesis of many neural and endocrine peptides CC (PubMed:2059626). Alpha-amidation involves two sequential reactions, CC both of which are catalyzed by separate catalytic domains of the CC enzyme. The first step, catalyzed by peptidyl alpha-hydroxylating CC monooxygenase (PHM) domain, is the copper-, ascorbate-, and CC O2- dependent stereospecific hydroxylation (with S stereochemistry) at CC the alpha-carbon (C-alpha) of the C-terminal glycine of the CC peptidylglycine substrate (PubMed:2059626). The second step, catalyzed CC by the peptidylglycine amidoglycolate lyase (PAL) domain, is the zinc- CC dependent cleavage of the N-C-alpha bond, producing the alpha-amidated CC peptide and glyoxylate (PubMed:2059626). Similarly, catalyzes the two- CC step conversion of an N-fatty acylglycine to a primary fatty acid amide CC and glyoxylate (By similarity). {ECO:0000250|UniProtKB:P14925, CC ECO:0000269|PubMed:2059626}. 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:2059626}; 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:2059626}; CC -!- CATALYTIC ACTIVITY: CC Reaction=2 L-ascorbate + N-dodecanoylglycine + O2 = H2O + 2 CC monodehydro-L-ascorbate radical + N-dodecanoyl-(2S)-hydroxyglycine; CC Xref=Rhea:RHEA:58540, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:38290, ChEBI:CHEBI:59513, ChEBI:CHEBI:142678, CC ChEBI:CHEBI:142693; Evidence={ECO:0000250|UniProtKB:P14925}; CC -!- CATALYTIC ACTIVITY: CC Reaction=N-dodecanoyl-(2S)-hydroxyglycine = dodecanamide + glyoxylate; CC Xref=Rhea:RHEA:58624, ChEBI:CHEBI:34726, ChEBI:CHEBI:36655, CC ChEBI:CHEBI:142693; Evidence={ECO:0000250|UniProtKB:P14925}; CC -!- CATALYTIC ACTIVITY: CC Reaction=2 L-ascorbate + N-(9Z,12Z,15Z)-octadecatrienoylglycine + O2 = CC H2O + 2 monodehydro-L-ascorbate radical + N-(9Z,12Z,15Z)- CC octadecatrienoyl-(2S)-hydroxyglycine; Xref=Rhea:RHEA:58548, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:38290, CC ChEBI:CHEBI:59513, ChEBI:CHEBI:142679, ChEBI:CHEBI:142697; CC Evidence={ECO:0000250|UniProtKB:P14925}; CC -!- CATALYTIC ACTIVITY: CC Reaction=N-(9Z,12Z,15Z)-octadecatrienoyl-(2S)-hydroxyglycine = CC (9Z,12Z,15Z)-octadecatrienamide + glyoxylate; Xref=Rhea:RHEA:58644, CC ChEBI:CHEBI:36655, ChEBI:CHEBI:142684, ChEBI:CHEBI:142697; CC Evidence={ECO:0000250|UniProtKB:P14925}; CC -!- CATALYTIC ACTIVITY: CC Reaction=2 L-ascorbate + N-(9Z-octadecenoyl)glycine + O2 = H2O + 2 CC monodehydro-L-ascorbate radical + N-(9Z-octadecenoyl)-(2S)- CC hydroxyglycine; Xref=Rhea:RHEA:58600, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15379, ChEBI:CHEBI:38290, ChEBI:CHEBI:59513, CC ChEBI:CHEBI:133992, ChEBI:CHEBI:142696; CC Evidence={ECO:0000250|UniProtKB:P14925}; CC -!- CATALYTIC ACTIVITY: CC Reaction=N-(9Z-octadecenoyl)-(2S)-hydroxyglycine = (9Z)-octadecenamide CC + glyoxylate; Xref=Rhea:RHEA:58636, ChEBI:CHEBI:36655, CC ChEBI:CHEBI:116314, ChEBI:CHEBI:142696; CC Evidence={ECO:0000250|UniProtKB:P14925}; CC -!- CATALYTIC ACTIVITY: CC Reaction=2 L-ascorbate + N-tetradecanoylglycine + O2 = H2O + 2 CC monodehydro-L-ascorbate radical + N-tetradecanoyl-(2S)- CC hydroxyglycine; Xref=Rhea:RHEA:58544, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15379, ChEBI:CHEBI:38290, ChEBI:CHEBI:59513, CC ChEBI:CHEBI:86500, ChEBI:CHEBI:142694; CC Evidence={ECO:0000250|UniProtKB:P14925}; CC -!- CATALYTIC ACTIVITY: CC Reaction=N-tetradecanoyl-(2S)-hydroxyglycine = glyoxylate + CC tetradecamide; Xref=Rhea:RHEA:58632, ChEBI:CHEBI:36655, CC ChEBI:CHEBI:137125, ChEBI:CHEBI:142694; CC Evidence={ECO:0000250|UniProtKB:P14925}; CC -!- CATALYTIC ACTIVITY: CC Reaction=2 L-ascorbate + N-decanoylglycine + O2 = H2O + 2 monodehydro- CC L-ascorbate radical + N-decanoyl-(2S)-hydroxyglycine; CC Xref=Rhea:RHEA:58608, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:38290, ChEBI:CHEBI:59513, ChEBI:CHEBI:142680, CC ChEBI:CHEBI:142692; Evidence={ECO:0000250|UniProtKB:P14925}; CC -!- CATALYTIC ACTIVITY: CC Reaction=N-decanoyl-(2S)-hydroxyglycine = decanamide + glyoxylate; CC Xref=Rhea:RHEA:58620, ChEBI:CHEBI:36655, ChEBI:CHEBI:38833, CC ChEBI:CHEBI:142692; Evidence={ECO:0000250|UniProtKB:P14925}; CC -!- CATALYTIC ACTIVITY: CC Reaction=2 L-ascorbate + N-octanoylglycine + O2 = H2O + 2 monodehydro- CC L-ascorbate radical + N-octanoyl-(2S)-hydroxyglycine; CC Xref=Rhea:RHEA:58612, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:38290, ChEBI:CHEBI:59513, ChEBI:CHEBI:142681, CC ChEBI:CHEBI:142691; Evidence={ECO:0000250|UniProtKB:P14925}; CC -!- CATALYTIC ACTIVITY: CC Reaction=N-octanoyl-(2S)-hydroxyglycine = glyoxylate + octanamide; CC Xref=Rhea:RHEA:58616, ChEBI:CHEBI:36655, ChEBI:CHEBI:142682, CC ChEBI:CHEBI:142691; Evidence={ECO:0000250|UniProtKB:P14925}; CC -!- COFACTOR: CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; CC Evidence={ECO:0000250|UniProtKB:P14925}; CC Note=Binds one Zn(2+) ion per subunit. {ECO:0000250|UniProtKB:P14925}; CC -!- COFACTOR: CC Name=Cu(2+); Xref=ChEBI:CHEBI:29036; CC Evidence={ECO:0000269|PubMed:2059626}; CC Note=Binds 2 Cu(2+) ions per subunit. {ECO:0000250|UniProtKB:P14925}; CC -!- ACTIVITY REGULATION: PAM activity is inhibited by EDTA, phenylglyoxal CC and diethyl pyrocarbonate (By similarity). PAL activity is stimulated CC by cadmium and inhibited by mercury (By similarity). CC {ECO:0000250|UniProtKB:P14925, ECO:0000250|UniProtKB:P19021}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC pH dependence: CC Optimally active at acidic pHs. {ECO:0000269|PubMed:2059626}; CC -!- SUBUNIT: Monomer. Interacts with RASSF9. CC {ECO:0000250|UniProtKB:P14925}. CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle membrane CC {ECO:0000269|PubMed:2059626}; Single-pass membrane protein CC {ECO:0000269|PubMed:2059626}. Note=Secretory granules. CC {ECO:0000269|PubMed:2059626}. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M18683; AAA30683.1; -; mRNA. DR PIR; A40063; URBOAP. DR RefSeq; NP_776373.1; NM_173948.2. DR SMR; P10731; -. DR MINT; P10731; -. DR STRING; 9913.ENSBTAP00000016466; -. DR PaxDb; P10731; -. DR PRIDE; P10731; -. DR GeneID; 280890; -. DR KEGG; bta:280890; -. DR CTD; 5066; -. DR eggNOG; KOG3567; Eukaryota. DR InParanoid; P10731; -. DR OrthoDB; 476471at2759; -. DR Proteomes; UP000009136; Unplaced. DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW. DR GO; GO:0030667; C:secretory granule membrane; IDA:UniProtKB. DR GO; GO:0030658; C:transport vesicle membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB. DR GO; GO:0005507; F:copper ion binding; ISS:UniProtKB. DR GO; GO:0031418; F:L-ascorbic acid binding; IEA:UniProtKB-KW. DR GO; GO:0004598; F:peptidylamidoglycolate lyase activity; IDA:UniProtKB. DR GO; GO:0004504; F:peptidylglycine monooxygenase activity; IDA:UniProtKB. DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB. DR GO; GO:0062112; P:fatty acid primary amide biosynthetic process; ISS:UniProtKB. DR GO; GO:0001519; P:peptide amidation; IDA:UniProtKB. 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; IPR013017; NHL_repeat_subgr. 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; 5. PE 1: Evidence at protein level; KW Calcium; Cleavage on pair of basic residues; Copper; Cytoplasmic vesicle; KW Direct protein sequencing; Disulfide bond; Glycoprotein; Lipid metabolism; KW Lyase; Membrane; Metal-binding; Monooxygenase; Multifunctional enzyme; KW Oxidoreductase; Phosphoprotein; Reference proteome; Repeat; Signal; KW Transmembrane; Transmembrane helix; Vitamin C; Zinc. FT SIGNAL 1..20 FT /evidence="ECO:0000255" FT PROPEP 21..30 FT /evidence="ECO:0000255" FT /id="PRO_0000006359" FT CHAIN 31..972 FT /note="Peptidyl-glycine alpha-amidating monooxygenase" FT /id="PRO_0000006360" FT TOPO_DOM 31..873 FT /note="Intragranular" FT /evidence="ECO:0000255" FT TRANSMEM 874..897 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 898..972 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT REPEAT 498..541 FT /note="NHL 1" FT REPEAT 567..608 FT /note="NHL 2" FT REPEAT 617..662 FT /note="NHL 3" FT REPEAT 670..714 FT /note="NHL 4" FT REPEAT 766..809 FT /note="NHL 5" FT REGION 1..494 FT /note="Peptidylglycine alpha-hydroxylating monooxygenase" FT /evidence="ECO:0000250" FT REGION 495..817 FT /note="Peptidyl-alpha-hydroxyglycine alpha-amidating lyase" FT /evidence="ECO:0000250" FT REGION 925..942 FT /note="Interaction with RASSF9" FT /evidence="ECO:0000250|UniProtKB:P14925" FT REGION 937..972 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT METAL 102 FT /note="Copper 1; via pros nitrogen; catalytic" FT /evidence="ECO:0000250|UniProtKB:P14925" FT METAL 103 FT /note="Copper 1; via pros nitrogen; catalytic" FT /evidence="ECO:0000250|UniProtKB:P14925" FT METAL 167 FT /note="Copper 1; via pros nitrogen; catalytic" FT /evidence="ECO:0000250|UniProtKB:P14925" FT METAL 237 FT /note="Copper 2; via tele nitrogen; catalytic" FT /evidence="ECO:0000250|UniProtKB:P14925" FT METAL 239 FT /note="Copper 2; via tele nitrogen; catalytic" FT /evidence="ECO:0000250|UniProtKB:P14925" FT METAL 309 FT /note="Copper 2" FT /evidence="ECO:0000250|UniProtKB:P14925" FT METAL 517 FT /note="Calcium; via carbonyl oxygen; structural" FT /evidence="ECO:0000250|UniProtKB:P14925" FT METAL 582 FT /note="Zinc; via tele nitrogen; catalytic" FT /evidence="ECO:0000250|UniProtKB:P14925" FT METAL 584 FT /note="Calcium; via carbonyl oxygen; structural" FT /evidence="ECO:0000250|UniProtKB:P14925" FT METAL 687 FT /note="Zinc; via tele nitrogen; catalytic" FT /evidence="ECO:0000250|UniProtKB:P14925" FT METAL 783 FT /note="Zinc; via tele nitrogen; catalytic" FT /evidence="ECO:0000250|UniProtKB:P14925" FT METAL 784 FT /note="Calcium; structural" FT /evidence="ECO:0000250|UniProtKB:P14925" FT BINDING 530 FT /note="Substrate" FT /evidence="ECO:0000250|UniProtKB:P14925" FT BINDING 651 FT /note="Substrate" FT /evidence="ECO:0000250|UniProtKB:P14925" FT BINDING 703 FT /note="Substrate" FT /evidence="ECO:0000250|UniProtKB:P14925" FT MOD_RES 929 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P19021" FT MOD_RES 942 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P19021" FT MOD_RES 943 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P19021" FT MOD_RES 946 FT /note="Phosphoserine; by UHMK1" FT /evidence="ECO:0000250|UniProtKB:P19021" FT MOD_RES 957 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P14925" FT CARBOHYD 762 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 42..181 FT /evidence="ECO:0000250|UniProtKB:P14925" FT DISULFID 76..121 FT /evidence="ECO:0000250|UniProtKB:P14925" FT DISULFID 109..126 FT /evidence="ECO:0000250|UniProtKB:P14925" FT DISULFID 222..329 FT /evidence="ECO:0000250|UniProtKB:P14925" FT DISULFID 288..310 FT /evidence="ECO:0000250|UniProtKB:P14925" FT DISULFID 631..652 FT /evidence="ECO:0000250|UniProtKB:P14925" FT DISULFID 699..710 FT /evidence="ECO:0000250|UniProtKB:P14925" SQ SEQUENCE 972 AA; 108177 MW; EBD41F83E341BAF1 CRC64; MAGFRSLLVL LLVFPSGCVG FRSPLSVFKR FKETTRSFSN ECLGTTRPVI PIDSSDFALD IRMPGVTPKQ SDTYFCMSVR LPMDEEAFVI DFKPRASMDT VHHMLLFGCN MPASTGNYWF CDEGTCTDKA NILYAWARNA PPTRLPKGVG FRVGGETGSK YFVLQVHYGD ISAFRDNHKD CSGVSLHLTR LPQPLIAGMY LMMSVDTVIP PGGKVVNSDI SCHYKKYPMH VFAYRVHTHH LGKVVSGYRV RNGQWTLIGR QSPQLPQAFY PVEHPVDVSF GDILAARCVF TGEGRTEVTH IGGTSSDEMC NLYIMYYMEA KHAVSFMTCT QNVAPDIFRT IPPEANIPIP VKSDMVMMHG HHKETENKDK TSLLQQPKRE EEGVLEQGDF YSLLSKLLGE REDVVHVHKY NPTEKAESES DLVAEIANVV QKKDLGRSDT RESAEQERGN AILVRDRIHK FHRLVSTLRP AESRVLSLQQ PLPGEGTWEP EHTGDFHVEE ALDWPGVYLL PGQVSGVALD PQNNLVIFHR GDHVWDGNSF DSKFVYQQRG LGPIEEDTIL VIDPNNAAVL QSSGKNLFYL PHGLSIDKDG NYWVTDVALH QVFKLDPKSK EGPLLTLGRS MQPGSDQNHF CQPTDVAVDP DTGTIYVSDG YCNSRLVQFS PSGKFITQWG EASLESSPKP GQFRVPHSLA LVPPLGQLCV ADRENGRIQC FKTDTKEFVR EIKHPSFGRN VFAISYIPGL LFAVNGKPYF EDQEPVQGFV MNFSSGEIID VFKPVRKHFD MPHDIAASED GTVYVGDAHT NTVWKFTSTE KMEHRSVKKA GIEVQEIKES EAVVETKMEN KPASSELQKI QEKQKLVKEP GSGVPAVLIT TLLVIPVVVL LAIALFIRWK KSRAFGDSER KLEASSGRVL GRLRGKGGGG LNLGNFFASR KGYSRKGFDR LSTEGSDQEK DEDASESEEE YSAPPPAPAP SS //