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 08-MAY-2019, entry version 159. 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; OC Mammalia; Eutheria; Laurasiatheria; Cetartiodactyla; Ruminantia; OC Pecora; Bovidae; 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 RT amidation 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 RP BIOPHYSICOCHEMICAL 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- CC translational modification of inactive peptidylglycine precursors CC to the 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 CC reactions, both of which are catalyzed by separate catalytic CC domains of the enzyme. The first step, catalyzed by peptidyl CC alpha-hydroxylating monoxygenase (PHM) domain, is the copper-, CC ascorbate-, and O2- dependent stereospecific hydroxylation (with S CC stereochemistry) at the alpha-carbon (C-alpha) of the C-terminal CC glycine of the peptidylglycine substrate (PubMed:2059626). The CC second step, catalyzed by the peptidylglycine amidoglycolate lyase CC (PAL) domain, is the zinc-dependent cleavage of the N-C-alpha CC bond, producing the alpha-amidated peptide and glyoxylate CC (PubMed:2059626). Similarly, catalyzes the two-step conversion of CC an N-fatty acylglycine to a primary fatty acid amide and CC 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 CC monodehydro-L-ascorbate radical; Xref=Rhea:RHEA:21452, CC Rhea:RHEA-COMP:13486, Rhea:RHEA-COMP:15321, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15379, ChEBI:CHEBI:38290, ChEBI:CHEBI:59513, CC ChEBI:CHEBI:137000, 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 CC [peptide]-C-terminal amide + glyoxylate; Xref=Rhea:RHEA:20924, CC Rhea:RHEA-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)- CC hydroxyglycine; Xref=Rhea:RHEA:58540, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15379, ChEBI:CHEBI:38290, ChEBI:CHEBI:59513, CC ChEBI:CHEBI:142678, ChEBI:CHEBI:142693; CC Evidence={ECO:0000250|UniProtKB:P14925}; CC -!- CATALYTIC ACTIVITY: CC Reaction=N-dodecanoyl-(2S)-hydroxyglycine = dodecanamide + CC glyoxylate; Xref=Rhea:RHEA:58624, ChEBI:CHEBI:34726, CC ChEBI:CHEBI:36655, ChEBI:CHEBI:142693; CC Evidence={ECO:0000250|UniProtKB:P14925}; CC -!- CATALYTIC ACTIVITY: CC Reaction=2 L-ascorbate + N-(9Z,12Z,15Z)-octadecatrienoylglycine + CC O2 = 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; CC Xref=Rhea:RHEA:58644, ChEBI:CHEBI:36655, ChEBI:CHEBI:142684, CC ChEBI:CHEBI:142697; 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)- CC octadecenamide + glyoxylate; Xref=Rhea:RHEA:58636, CC ChEBI:CHEBI:36655, 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 CC monodehydro-L-ascorbate radical + N-decanoyl-(2S)- CC hydroxyglycine; Xref=Rhea:RHEA:58608, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15379, ChEBI:CHEBI:38290, ChEBI:CHEBI:59513, CC ChEBI:CHEBI:142680, ChEBI:CHEBI:142692; CC 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 CC monodehydro-L-ascorbate radical + N-octanoyl-(2S)- CC hydroxyglycine; Xref=Rhea:RHEA:58612, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15379, ChEBI:CHEBI:38290, ChEBI:CHEBI:59513, CC ChEBI:CHEBI:142681, ChEBI:CHEBI:142691; CC 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. CC {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. CC {ECO:0000250|UniProtKB:P14925}; CC -!- ACTIVITY REGULATION: PAM activity is inhibited by EDTA, CC phenylglyoxal and diethyl pyrocarbonate (By similarity). PAL CC activity is stimulated by cadmium and inhibited by mercury (By CC similarity). {ECO:0000250|UniProtKB:P14925, CC 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 CC membrane {ECO:0000269|PubMed:2059626}; Single-pass membrane CC protein {ECO:0000269|PubMed:2059626}. Note=Secretory granules. CC {ECO:0000269|PubMed:2059626}. CC -!- SIMILARITY: In the C-terminal section; belongs to the peptidyl- CC alpha-hydroxyglycine alpha-amidating lyase family. {ECO:0000305}. CC -!- SIMILARITY: In the N-terminal section; belongs to the copper type CC II 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 eggNOG; ENOG410XS0X; LUCA. DR HOGENOM; HOG000293368; -. DR InParanoid; P10731; -. DR KO; K00504; -. DR KO; K18200; -. DR OrthoDB; 476471at2759; -. DR Proteomes; UP000009136; Unplaced. DR GO; GO:0005576; C:extracellular region; IBA:GO_Central. DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW. DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central. 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; Complete proteome; KW Copper; Cytoplasmic vesicle; Direct protein sequencing; KW Disulfide bond; Glycoprotein; Lyase; Membrane; Metal-binding; KW Monooxygenase; Multifunctional enzyme; Oxidoreductase; Phosphoprotein; KW Reference proteome; Repeat; Signal; Transmembrane; KW Transmembrane helix; Vitamin C; Zinc. FT SIGNAL 1 20 {ECO:0000255}. FT PROPEP 21 30 {ECO:0000255}. FT /FTId=PRO_0000006359. FT CHAIN 31 972 Peptidyl-glycine alpha-amidating FT monooxygenase. FT /FTId=PRO_0000006360. FT TOPO_DOM 31 873 Intragranular. {ECO:0000255}. FT TRANSMEM 874 897 Helical. {ECO:0000255}. FT TOPO_DOM 898 972 Cytoplasmic. {ECO:0000255}. FT REPEAT 498 541 NHL 1. FT REPEAT 567 608 NHL 2. FT REPEAT 617 662 NHL 3. FT REPEAT 670 714 NHL 4. FT REPEAT 766 809 NHL 5. FT REGION 1 494 Peptidylglycine alpha-hydroxylating FT monooxygenase. {ECO:0000250}. FT REGION 495 817 Peptidyl-alpha-hydroxyglycine alpha- FT amidating lyase. {ECO:0000250}. FT REGION 925 942 Interaction with RASSF9. FT {ECO:0000250|UniProtKB:P14925}. FT METAL 102 102 Copper 1; via pros nitrogen; catalytic. FT {ECO:0000250|UniProtKB:P14925}. FT METAL 103 103 Copper 1; via pros nitrogen; catalytic. FT {ECO:0000250|UniProtKB:P14925}. FT METAL 167 167 Copper 1; via pros nitrogen; catalytic. FT {ECO:0000250|UniProtKB:P14925}. FT METAL 237 237 Copper 2; via tele nitrogen; catalytic. FT {ECO:0000250|UniProtKB:P14925}. FT METAL 239 239 Copper 2; via tele nitrogen; catalytic. FT {ECO:0000250|UniProtKB:P14925}. FT METAL 309 309 Copper 2. {ECO:0000250|UniProtKB:P14925}. FT METAL 517 517 Calcium; via carbonyl oxygen; structural. FT {ECO:0000250|UniProtKB:P14925}. FT METAL 582 582 Zinc; via tele nitrogen; catalytic. FT {ECO:0000250|UniProtKB:P14925}. FT METAL 584 584 Calcium; via carbonyl oxygen; structural. FT {ECO:0000250|UniProtKB:P14925}. FT METAL 687 687 Zinc; via tele nitrogen; catalytic. FT {ECO:0000250|UniProtKB:P14925}. FT METAL 783 783 Zinc; via tele nitrogen; catalytic. FT {ECO:0000250|UniProtKB:P14925}. FT METAL 784 784 Calcium; structural. FT {ECO:0000250|UniProtKB:P14925}. FT BINDING 530 530 Substrate. FT {ECO:0000250|UniProtKB:P14925}. FT BINDING 651 651 Substrate. FT {ECO:0000250|UniProtKB:P14925}. FT BINDING 703 703 Substrate. FT {ECO:0000250|UniProtKB:P14925}. FT MOD_RES 929 929 Phosphoserine. FT {ECO:0000250|UniProtKB:P19021}. FT MOD_RES 942 942 Phosphoserine. FT {ECO:0000250|UniProtKB:P19021}. FT MOD_RES 943 943 Phosphothreonine. FT {ECO:0000250|UniProtKB:P19021}. FT MOD_RES 946 946 Phosphoserine; by UHMK1. FT {ECO:0000250|UniProtKB:P19021}. FT MOD_RES 957 957 Phosphoserine. FT {ECO:0000250|UniProtKB:P14925}. FT CARBOHYD 762 762 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT DISULFID 42 181 {ECO:0000250|UniProtKB:P14925}. FT DISULFID 76 121 {ECO:0000250|UniProtKB:P14925}. FT DISULFID 109 126 {ECO:0000250|UniProtKB:P14925}. FT DISULFID 222 329 {ECO:0000250|UniProtKB:P14925}. FT DISULFID 288 310 {ECO:0000250|UniProtKB:P14925}. FT DISULFID 631 652 {ECO:0000250|UniProtKB:P14925}. FT DISULFID 699 710 {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 //