ID   AMDB_XENLA              Reviewed;         875 AA.
AC   P12890;
DT   01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1989, sequence version 1.
DT   02-SEP-2026, entry version 140.
DE   RecName: Full=Peptidyl-glycine alpha-amidating monooxygenase B;
DE            Short=PAM-B;
DE   AltName: Full=Peptide C-terminal alpha-amidating enzyme II;
DE            Short=AE-II;
DE   AltName: Full=Peptidyl-glycine alpha-amidating monooxygenase II;
DE   Includes:
DE     RecName: Full=Peptidylglycine alpha-hydroxylating monooxygenase B;
DE              Short=PHM-B;
DE              EC=1.14.17.3 {ECO:0000250|UniProtKB:P14925};
DE   Includes:
DE     RecName: Full=Peptidyl-alpha-hydroxyglycine alpha-amidating lyase B;
DE              EC=4.3.2.5;
DE     AltName: Full=Peptidylamidoglycolate lyase-B;
DE              Short=PAL-B {ECO:0000250|UniProtKB:P14925};
DE   Flags: Precursor;
GN   Name=pam-b;
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].
RC   TISSUE=Skin;
RX   PubMed=2829895; DOI=10.1016/0006-291x(88)90767-x;
RA   Ohsuye K., Kitano K., Wada Y., Fuchimura K., Tanaka S., Mizuno K.,
RA   Matsuo H.;
RT   "Cloning of cDNA encoding a new peptide C-terminal alpha-amidating enzyme
RT   having a putative membrane-spanning domain from Xenopus laevis skin.";
RL   Biochem. Biophys. Res. Commun. 150:1275-1281(1988).
CC   -!- FUNCTION: Bifunctional enzyme that catalyzes amidation of the C-
CC       terminus of proteins (By similarity). Alpha-amidation is present at the
CC       C-terminus of many endocrine hormones and neuropeptides and is required
CC       for their activity (By similarity). C-terminal amidation also takes
CC       place in response to protein fragmentation triggered by oxidative
CC       stress, promoting degradation of amidated protein fragments by the
CC       proteasome (By similarity). Alpha-amidation involves two sequential
CC       reactions, both of which are catalyzed by separate catalytic domains of
CC       the enzyme (By similarity). The first step, catalyzed by peptidyl
CC       alpha-hydroxylating monooxygenase (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 (By similarity). The second
CC       step, catalyzed by the peptidylglycine amidoglycolate lyase (PAL)
CC       domain, is the zinc-dependent cleavage of the N-C-alpha bond, producing
CC       the alpha-amidated peptide and glyoxylate (By similarity).
CC       {ECO:0000250|UniProtKB:P14925, ECO:0000250|UniProtKB:P19021}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a [peptide]-C-terminal glycine + 2 L-ascorbate + O2 = a
CC         [peptide]-C-terminal (2S)-2-hydroxyglycine + 2 monodehydro-L-
CC         ascorbate radical + H2O; 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:0000250|UniProtKB:P14925};
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: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:0000250|UniProtKB:P14925};
CC       Note=Binds 2 Cu(2+) ions per subunit. {ECO:0000250|UniProtKB:P14925};
CC   -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:P14925}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle membrane
CC       {ECO:0000250|UniProtKB:P10731}; Single-pass membrane protein
CC       {ECO:0000250|UniProtKB:P10731}. Note=Secretory granules.
CC       {ECO:0000250|UniProtKB:P10731}.
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; M19032; AAA49667.1; -; mRNA.
DR   PIR; A27715; URXLA2.
DR   RefSeq; NP_001081254.1; NM_001087785.1.
DR   AlphaFoldDB; P12890; -.
DR   SMR; P12890; -.
DR   GlyCosmos; P12890; 3 sites, No reported glycans.
DR   GeneID; 397736; -.
DR   KEGG; xla:397736; -.
DR   AGR; Xenbase:XB-GENE-6252615; -.
DR   CTD; 397736; -.
DR   Xenbase; XB-GENE-6252615; pam.S.
DR   OrthoDB; 10018185at2759; -.
DR   Proteomes; UP000186698; Chromosome 1S.
DR   Bgee; 397736; Expressed in heart and 19 other cell types or tissues.
DR   GO; GO:0005576; C:extracellular region; IBA:GO_Central.
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; ISS:UniProtKB.
DR   GO; GO:0004504; F:peptidylglycine monooxygenase activity; ISS:UniProtKB.
DR   GO; GO:0001519; P:peptide amidation; IEA:UniProtKB-ARBA.
DR   CDD; cd14958; NHL_PAL_like; 1.
DR   FunFam; 2.60.120.230:FF:000002; Peptidyl-glycine alpha-amidating monooxygenase B; 1.
DR   FunFam; 2.120.10.30:FF:000016; peptidyl-glycine alpha-amidating monooxygenase isoform X1; 1.
DR   FunFam; 2.60.120.310:FF:000001; peptidyl-glycine alpha-amidating monooxygenase isoform X1; 1.
DR   Gene3D; 2.60.120.230; -; 1.
DR   Gene3D; 2.60.120.310; Copper type II, ascorbate-dependent monooxygenase, N-terminal domain; 1.
DR   Gene3D; 2.120.10.30; TolB, C-terminal domain; 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   PANTHER; PTHR10680; PEPTIDYL-GLYCINE ALPHA-AMIDATING MONOOXYGENASE; 1.
DR   PANTHER; PTHR10680:SF14; PEPTIDYL-GLYCINE ALPHA-AMIDATING MONOOXYGENASE; 1.
DR   Pfam; PF03712; Cu2_monoox_C; 1.
DR   Pfam; PF01082; Cu2_monooxygen; 1.
DR   Pfam; PF01436; NHL; 3.
DR   PRINTS; PR00790; PAMONOXGNASE.
DR   SUPFAM; SSF101898; NHL repeat; 1.
DR   SUPFAM; SSF49742; PHM/PNGase F; 2.
DR   PROSITE; PS00084; CU2_MONOOXYGENASE_1; 1.
DR   PROSITE; PS00085; CU2_MONOOXYGENASE_2; 1.
DR   PROSITE; PS51125; NHL; 4.
PE   2: Evidence at transcript level;
KW   Copper; Cytoplasmic vesicle; 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..39
FT                   /evidence="ECO:0000255"
FT   CHAIN           40..875
FT                   /note="Peptidyl-glycine alpha-amidating monooxygenase B"
FT                   /id="PRO_0000006368"
FT   TOPO_DOM        40..763
FT                   /note="Intragranular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        764..787
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        788..875
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   REPEAT          467..508
FT                   /note="NHL 1"
FT   REPEAT          516..561
FT                   /note="NHL 2"
FT   REPEAT          569..613
FT                   /note="NHL 3"
FT   REPEAT          666..709
FT                   /note="NHL 4"
FT   REGION          3..394
FT                   /note="Peptidylglycine alpha-hydroxylating monooxygenase"
FT                   /evidence="ECO:0000250|UniProtKB:P14925"
FT   REGION          395..716
FT                   /note="Peptidyl-alpha-hydroxyglycine alpha-amidating lyase"
FT                   /evidence="ECO:0000250|UniProtKB:P14925"
FT   REGION          735..755
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          837..875
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        743..755
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        850..864
FT                   /note="Acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         105
FT                   /ligand="Cu(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29036"
FT                   /ligand_label="A"
FT                   /evidence="ECO:0000250|UniProtKB:P14925"
FT   BINDING         106
FT                   /ligand="Cu(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29036"
FT                   /ligand_label="A"
FT                   /evidence="ECO:0000250|UniProtKB:P14925"
FT   BINDING         170
FT                   /ligand="Cu(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29036"
FT                   /ligand_label="A"
FT                   /evidence="ECO:0000250|UniProtKB:P14925"
FT   BINDING         240
FT                   /ligand="Cu(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29036"
FT                   /ligand_label="B"
FT                   /evidence="ECO:0000250|UniProtKB:P14925"
FT   BINDING         242
FT                   /ligand="Cu(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29036"
FT                   /ligand_label="B"
FT                   /evidence="ECO:0000250|UniProtKB:P14925"
FT   BINDING         312
FT                   /ligand="Cu(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29036"
FT                   /ligand_label="B"
FT                   /evidence="ECO:0000250|UniProtKB:P14925"
FT   BINDING         430
FT                   /ligand="a protein"
FT                   /ligand_id="ChEBI:CHEBI:16541"
FT                   /ligand_part="C-terminal Xaa-(2S)-2-hydroxyglycine residue"
FT                   /ligand_part_id="ChEBI:CHEBI:142768"
FT                   /evidence="ECO:0000250|UniProtKB:P14925"
FT   BINDING         550
FT                   /ligand="a protein"
FT                   /ligand_id="ChEBI:CHEBI:16541"
FT                   /ligand_part="C-terminal Xaa-(2S)-2-hydroxyglycine residue"
FT                   /ligand_part_id="ChEBI:CHEBI:142768"
FT                   /evidence="ECO:0000250|UniProtKB:P14925"
FT   BINDING         602
FT                   /ligand="a protein"
FT                   /ligand_id="ChEBI:CHEBI:16541"
FT                   /ligand_part="C-terminal Xaa-(2S)-2-hydroxyglycine residue"
FT                   /ligand_part_id="ChEBI:CHEBI:142768"
FT                   /evidence="ECO:0000250|UniProtKB:P14925"
FT   CARBOHYD        465
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        662
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        743
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        45..184
FT                   /evidence="ECO:0000250|UniProtKB:P14925"
FT   DISULFID        79..124
FT                   /evidence="ECO:0000250|UniProtKB:P14925"
FT   DISULFID        112..129
FT                   /evidence="ECO:0000250|UniProtKB:P14925"
FT   DISULFID        225..332
FT                   /evidence="ECO:0000250|UniProtKB:P14925"
FT   DISULFID        291..313
FT                   /evidence="ECO:0000250|UniProtKB:P14925"
FT   DISULFID        530..551
FT                   /evidence="ECO:0000250|UniProtKB:P14925"
FT   DISULFID        598..609
FT                   /evidence="ECO:0000250|UniProtKB:P14925"
SQ   SEQUENCE   875 AA;  97085 MW;  C07373AF6BF13450 CRC64;
     MDMASLISSL LVLFLIFQNS CYCFRSPLSV FKRYEESTRS LSNDCLGTTR PVMSPGSSDY
     TLDIRMPGVT PTESDTYLCK SYRLPVDDEA YVVDYRPHAN MDTAHHMLLF GCNVPSSTDD
     YWDCSAGTCN DKSSIMYAWA KNAPPTKLPE GVGFQVGGKS GSRYFVLQVH YGDVKAFQDK
     HKDCTGVTVR ITPEKQPLIA GIYLSMSLNT VVPPGQEVVN SDIACLYNRP TIHPFAYRVH
     THQLGQVVSG FRVRHGKWTL IGRQSPQLPQ AFYPVEHPLE ISPGDIIATR CLFTGKGRMS
     ATYIGGTAKD EMCNLYIMYY MDAAHATSYM TCVQTGNPKL FENIPEIANV PIPVSPDMMM
     MMMMGHGHHH TEAEAETNTA LQQPKREEEE VLNQDVHLEE DTDWPGVNLK VGQVSGLALD
     PKNNLVIFHR GDHVWDENSF DRNFVYQQRG IGPIQESTIL VVDPNTSKVL KSTGQNLFFL
     PHGLTIDRDG NYWVTDVALH QVFKVGAEKE TPLLVLGRAF QPGSDRKHFC QPTDVAVDPI
     TGNFFVADGY CNSRIMQFSP NGMFIMQWGE ETSSNLPRPG QFRIPHSLTM ISDQGQLCVA
     DRENGRIQCF HAKTGEFVKQ IKHQEFGREV FAVSYAPGGV LYAVNGKPYY GDSTPVQGFM
     LNFSNGDILD TFIPARKNFE MPHDIAAGDD GTVYVGDAHA NAVWKFSPSK AEHRSVKKAG
     IEVEEITETE IFETHMRSRP KTNESVGQQT QEKPSVVQES SAGVSFVLII TLLIIPVVVL
     IAIAIFIRWR KVRMYGGDIG HKSESSSGGI LGKLRGKGSG GLNLGTFFAT HKGYSRKGFD
     RLSTEGSDQE KDDDDDGSDS EEEYSAPPIP PVSSS
//