UniProt functional annotation for P14925



	UniProt functional annotation for P14925

UniProt code: P14925.

Organism: Rattus norvegicus (Rat).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus.

Function: Bifunctional enzyme that catalyzes the post-translational modification of inactive peptidylglycine precursors to the corresponding bioactive alpha-amidated peptides, a terminal modification in biosynthesis of many neural and endocrine peptides (By similarity). Alpha-amidation involves two sequential reactions, both of which are catalyzed by separate catalytic domains of the enzyme. The first step, catalyzed by peptidyl alpha-hydroxylating monoxygenase (PHM) domain, is the copper-, ascorbate-, and O2- dependent stereospecific hydroxylation (with S stereochemistry) at the alpha- carbon (C-alpha) of the C-terminal glycine of the peptidylglycine substrate (PubMed:10079066). The second step, catalyzed by the peptidylglycine amidoglycolate lyase (PAL) domain, is the zinc- dependent cleavage of the N-C-alpha bond, producing the alpha-amidated peptide and glyoxylate (PubMed:10079066). Similarly, catalyzes the two- step conversion of an N-fatty acylglycine to a primary fatty acid amide and glyoxylate (PubMed:10079066). {ECO:0000250|UniProtKB:P10731, ECO:0000250|UniProtKB:P19021, ECO:0000269|PubMed:10079066}.

Catalytic activity: Reaction=a [peptide]-C-terminal glycine + 2 L-ascorbate + O2 = a [peptide]-C-terminal (2S)-2-hydroxyglycine + H2O + 2 monodehydro-L- ascorbate radical; Xref=Rhea:RHEA:21452, Rhea:RHEA-COMP:13486, Rhea:RHEA-COMP:15321, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:38290, ChEBI:CHEBI:59513, ChEBI:CHEBI:137000, ChEBI:CHEBI:142768; EC=1.14.17.3; Evidence={ECO:0000269|PubMed:10079066};

Catalytic activity: Reaction=a [peptide]-C-terminal (2S)-2-hydroxyglycine = a [peptide]-C- terminal amide + glyoxylate; Xref=Rhea:RHEA:20924, Rhea:RHEA- COMP:13485, Rhea:RHEA-COMP:15321, ChEBI:CHEBI:36655, ChEBI:CHEBI:137001, ChEBI:CHEBI:142768; EC=4.3.2.5; Evidence={ECO:0000269|PubMed:10079066};

Catalytic activity: Reaction=2 L-ascorbate + N-dodecanoylglycine + O2 = H2O + 2 monodehydro-L-ascorbate radical + N-dodecanoyl-(2S)-hydroxyglycine; Xref=Rhea:RHEA:58540, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:38290, ChEBI:CHEBI:59513, ChEBI:CHEBI:142678, ChEBI:CHEBI:142693; Evidence={ECO:0000269|PubMed:10079066};

Catalytic activity: Reaction=N-dodecanoyl-(2S)-hydroxyglycine = dodecanamide + glyoxylate; Xref=Rhea:RHEA:58624, ChEBI:CHEBI:34726, ChEBI:CHEBI:36655, ChEBI:CHEBI:142693; Evidence={ECO:0000269|PubMed:10079066};

Catalytic activity: Reaction=2 L-ascorbate + N-(9Z,12Z,15Z)-octadecatrienoylglycine + O2 = H2O + 2 monodehydro-L-ascorbate radical + N-(9Z,12Z,15Z)- octadecatrienoyl-(2S)-hydroxyglycine; Xref=Rhea:RHEA:58548, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:38290, ChEBI:CHEBI:59513, ChEBI:CHEBI:142679, ChEBI:CHEBI:142697; Evidence={ECO:0000269|PubMed:10079066};

Catalytic activity: Reaction=N-(9Z,12Z,15Z)-octadecatrienoyl-(2S)-hydroxyglycine = (9Z,12Z,15Z)-octadecatrienamide + glyoxylate; Xref=Rhea:RHEA:58644, ChEBI:CHEBI:36655, ChEBI:CHEBI:142684, ChEBI:CHEBI:142697; Evidence={ECO:0000269|PubMed:10079066};

Catalytic activity: Reaction=2 L-ascorbate + N-(9Z-octadecenoyl)glycine + O2 = H2O + 2 monodehydro-L-ascorbate radical + N-(9Z-octadecenoyl)-(2S)- hydroxyglycine; Xref=Rhea:RHEA:58600, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:38290, ChEBI:CHEBI:59513, ChEBI:CHEBI:133992, ChEBI:CHEBI:142696; Evidence={ECO:0000269|PubMed:10079066};

Catalytic activity: Reaction=N-(9Z-octadecenoyl)-(2S)-hydroxyglycine = (9Z)-octadecenamide + glyoxylate; Xref=Rhea:RHEA:58636, ChEBI:CHEBI:36655, ChEBI:CHEBI:116314, ChEBI:CHEBI:142696; Evidence={ECO:0000269|PubMed:10079066};

Catalytic activity: Reaction=2 L-ascorbate + N-tetradecanoylglycine + O2 = H2O + 2 monodehydro-L-ascorbate radical + N-tetradecanoyl-(2S)- hydroxyglycine; Xref=Rhea:RHEA:58544, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:38290, ChEBI:CHEBI:59513, ChEBI:CHEBI:86500, ChEBI:CHEBI:142694; Evidence={ECO:0000269|PubMed:10079066};

Catalytic activity: Reaction=N-tetradecanoyl-(2S)-hydroxyglycine = glyoxylate + tetradecamide; Xref=Rhea:RHEA:58632, ChEBI:CHEBI:36655, ChEBI:CHEBI:137125, ChEBI:CHEBI:142694; Evidence={ECO:0000269|PubMed:10079066};

Catalytic activity: Reaction=2 L-ascorbate + N-decanoylglycine + O2 = H2O + 2 monodehydro- L-ascorbate radical + N-decanoyl-(2S)-hydroxyglycine; Xref=Rhea:RHEA:58608, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:38290, ChEBI:CHEBI:59513, ChEBI:CHEBI:142680, ChEBI:CHEBI:142692; Evidence={ECO:0000269|PubMed:10079066};

Catalytic activity: Reaction=N-decanoyl-(2S)-hydroxyglycine = decanamide + glyoxylate; Xref=Rhea:RHEA:58620, ChEBI:CHEBI:36655, ChEBI:CHEBI:38833, ChEBI:CHEBI:142692; Evidence={ECO:0000269|PubMed:10079066};

Catalytic activity: Reaction=2 L-ascorbate + N-octanoylglycine + O2 = H2O + 2 monodehydro- L-ascorbate radical + N-octanoyl-(2S)-hydroxyglycine; Xref=Rhea:RHEA:58612, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:38290, ChEBI:CHEBI:59513, ChEBI:CHEBI:142681, ChEBI:CHEBI:142691; Evidence={ECO:0000269|PubMed:10079066};

Catalytic activity: Reaction=N-octanoyl-(2S)-hydroxyglycine = glyoxylate + octanamide; Xref=Rhea:RHEA:58616, ChEBI:CHEBI:36655, ChEBI:CHEBI:142682, ChEBI:CHEBI:142691; Evidence={ECO:0000269|PubMed:10079066};

Cofactor: Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Note=Binds one Zn(2+) ion per subunit. {ECO:0000269|PubMed:19604476};

Cofactor: Name=Cu(2+); Xref=ChEBI:CHEBI:29036; Note=Binds 2 Cu(2+) ions per subunit. {ECO:0000269|PubMed:10504734};

Activity regulation: PAM activity is inhibited by EDTA, phenylglyoxal and diethyl pyrocarbonate (By similarity). PAL activity is stimulated by cadmium and inhibited by mercury (PubMed:19604476). {ECO:0000250|UniProtKB:P19021, ECO:0000269|PubMed:19604476}.

Biophysicochemical properties: Kinetic parameters: KM=13.8 uM for [peptide]-C-terminal (2S)-2-hydroxyglycine {ECO:0000269|PubMed:19604476};

Subunit: Monomer. Interacts with RASSF9. {ECO:0000269|PubMed:9837933}.

Subcellular location: Cytoplasmic vesicle, secretory vesicle membrane {ECO:0000250|UniProtKB:P10731}; Single-pass membrane protein {ECO:0000250|UniProtKB:P10731}. Note=Secretory granules. {ECO:0000250|UniProtKB:P10731}.

Miscellaneous: [Isoform PAM-1]: Membrane-bound.

Miscellaneous: [Isoform PAM-2]: Membrane-bound. {ECO:0000305}.

Miscellaneous: [Isoform PAM-3]: Soluble. {ECO:0000305}.

Miscellaneous: [Isoform PAM-3A]: Soluble. {ECO:0000305}.

Miscellaneous: [Isoform PAM-3B]: Membrane-bound. {ECO:0000305}.

Miscellaneous: [Isoform PAM-4]: Soluble. {ECO:0000305}.

Miscellaneous: [Isoform PAM-5]: Soluble. {ECO:0000305}.

Similarity: In the C-terminal section; belongs to the peptidyl-alpha- hydroxyglycine alpha-amidating lyase family. {ECO:0000305}.

Similarity: In the N-terminal section; belongs to the copper type II ascorbate-dependent monooxygenase family. {ECO:0000305}.

Sequence caution: Sequence=AAA42068.1; Type=Miscellaneous discrepancy; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Rattus norvegicus (Rat).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus.



Function:		Bifunctional enzyme that catalyzes the post-translational modification of inactive peptidylglycine precursors to the corresponding bioactive alpha-amidated peptides, a terminal modification in biosynthesis of many neural and endocrine peptides (By similarity). Alpha-amidation involves two sequential reactions, both of which are catalyzed by separate catalytic domains of the enzyme. The first step, catalyzed by peptidyl alpha-hydroxylating monoxygenase (PHM) domain, is the copper-, ascorbate-, and O2- dependent stereospecific hydroxylation (with S stereochemistry) at the alpha- carbon (C-alpha) of the C-terminal glycine of the peptidylglycine substrate (PubMed:10079066). The second step, catalyzed by the peptidylglycine amidoglycolate lyase (PAL) domain, is the zinc- dependent cleavage of the N-C-alpha bond, producing the alpha-amidated peptide and glyoxylate (PubMed:10079066). Similarly, catalyzes the two- step conversion of an N-fatty acylglycine to a primary fatty acid amide and glyoxylate (PubMed:10079066). {ECO:0000250\|UniProtKB:P10731, ECO:0000250\|UniProtKB:P19021, ECO:0000269\|PubMed:10079066}.


Catalytic activity:		Reaction=a [peptide]-C-terminal glycine + 2 L-ascorbate + O2 = a [peptide]-C-terminal (2S)-2-hydroxyglycine + H2O + 2 monodehydro-L- ascorbate radical; Xref=Rhea:RHEA:21452, Rhea:RHEA-COMP:13486, Rhea:RHEA-COMP:15321, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:38290, ChEBI:CHEBI:59513, ChEBI:CHEBI:137000, ChEBI:CHEBI:142768; EC=1.14.17.3; Evidence={ECO:0000269\|PubMed:10079066};
Catalytic activity:		Reaction=a [peptide]-C-terminal (2S)-2-hydroxyglycine = a [peptide]-C- terminal amide + glyoxylate; Xref=Rhea:RHEA:20924, Rhea:RHEA- COMP:13485, Rhea:RHEA-COMP:15321, ChEBI:CHEBI:36655, ChEBI:CHEBI:137001, ChEBI:CHEBI:142768; EC=4.3.2.5; Evidence={ECO:0000269\|PubMed:10079066};
Catalytic activity:		Reaction=2 L-ascorbate + N-dodecanoylglycine + O2 = H2O + 2 monodehydro-L-ascorbate radical + N-dodecanoyl-(2S)-hydroxyglycine; Xref=Rhea:RHEA:58540, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:38290, ChEBI:CHEBI:59513, ChEBI:CHEBI:142678, ChEBI:CHEBI:142693; Evidence={ECO:0000269\|PubMed:10079066};
Catalytic activity:		Reaction=N-dodecanoyl-(2S)-hydroxyglycine = dodecanamide + glyoxylate; Xref=Rhea:RHEA:58624, ChEBI:CHEBI:34726, ChEBI:CHEBI:36655, ChEBI:CHEBI:142693; Evidence={ECO:0000269\|PubMed:10079066};
Catalytic activity:		Reaction=2 L-ascorbate + N-(9Z,12Z,15Z)-octadecatrienoylglycine + O2 = H2O + 2 monodehydro-L-ascorbate radical + N-(9Z,12Z,15Z)- octadecatrienoyl-(2S)-hydroxyglycine; Xref=Rhea:RHEA:58548, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:38290, ChEBI:CHEBI:59513, ChEBI:CHEBI:142679, ChEBI:CHEBI:142697; Evidence={ECO:0000269\|PubMed:10079066};
Catalytic activity:		Reaction=N-(9Z,12Z,15Z)-octadecatrienoyl-(2S)-hydroxyglycine = (9Z,12Z,15Z)-octadecatrienamide + glyoxylate; Xref=Rhea:RHEA:58644, ChEBI:CHEBI:36655, ChEBI:CHEBI:142684, ChEBI:CHEBI:142697; Evidence={ECO:0000269\|PubMed:10079066};
Catalytic activity:		Reaction=2 L-ascorbate + N-(9Z-octadecenoyl)glycine + O2 = H2O + 2 monodehydro-L-ascorbate radical + N-(9Z-octadecenoyl)-(2S)- hydroxyglycine; Xref=Rhea:RHEA:58600, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:38290, ChEBI:CHEBI:59513, ChEBI:CHEBI:133992, ChEBI:CHEBI:142696; Evidence={ECO:0000269\|PubMed:10079066};
Catalytic activity:		Reaction=N-(9Z-octadecenoyl)-(2S)-hydroxyglycine = (9Z)-octadecenamide + glyoxylate; Xref=Rhea:RHEA:58636, ChEBI:CHEBI:36655, ChEBI:CHEBI:116314, ChEBI:CHEBI:142696; Evidence={ECO:0000269\|PubMed:10079066};
Catalytic activity:		Reaction=2 L-ascorbate + N-tetradecanoylglycine + O2 = H2O + 2 monodehydro-L-ascorbate radical + N-tetradecanoyl-(2S)- hydroxyglycine; Xref=Rhea:RHEA:58544, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:38290, ChEBI:CHEBI:59513, ChEBI:CHEBI:86500, ChEBI:CHEBI:142694; Evidence={ECO:0000269\|PubMed:10079066};
Catalytic activity:		Reaction=N-tetradecanoyl-(2S)-hydroxyglycine = glyoxylate + tetradecamide; Xref=Rhea:RHEA:58632, ChEBI:CHEBI:36655, ChEBI:CHEBI:137125, ChEBI:CHEBI:142694; Evidence={ECO:0000269\|PubMed:10079066};
Catalytic activity:		Reaction=2 L-ascorbate + N-decanoylglycine + O2 = H2O + 2 monodehydro- L-ascorbate radical + N-decanoyl-(2S)-hydroxyglycine; Xref=Rhea:RHEA:58608, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:38290, ChEBI:CHEBI:59513, ChEBI:CHEBI:142680, ChEBI:CHEBI:142692; Evidence={ECO:0000269\|PubMed:10079066};
Catalytic activity:		Reaction=N-decanoyl-(2S)-hydroxyglycine = decanamide + glyoxylate; Xref=Rhea:RHEA:58620, ChEBI:CHEBI:36655, ChEBI:CHEBI:38833, ChEBI:CHEBI:142692; Evidence={ECO:0000269\|PubMed:10079066};
Catalytic activity:		Reaction=2 L-ascorbate + N-octanoylglycine + O2 = H2O + 2 monodehydro- L-ascorbate radical + N-octanoyl-(2S)-hydroxyglycine; Xref=Rhea:RHEA:58612, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:38290, ChEBI:CHEBI:59513, ChEBI:CHEBI:142681, ChEBI:CHEBI:142691; Evidence={ECO:0000269\|PubMed:10079066};
Catalytic activity:		Reaction=N-octanoyl-(2S)-hydroxyglycine = glyoxylate + octanamide; Xref=Rhea:RHEA:58616, ChEBI:CHEBI:36655, ChEBI:CHEBI:142682, ChEBI:CHEBI:142691; Evidence={ECO:0000269\|PubMed:10079066};
Cofactor:		Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Note=Binds one Zn(2+) ion per subunit. {ECO:0000269\|PubMed:19604476};
Cofactor:		Name=Cu(2+); Xref=ChEBI:CHEBI:29036; Note=Binds 2 Cu(2+) ions per subunit. {ECO:0000269\|PubMed:10504734};
Activity regulation:		PAM activity is inhibited by EDTA, phenylglyoxal and diethyl pyrocarbonate (By similarity). PAL activity is stimulated by cadmium and inhibited by mercury (PubMed:19604476). {ECO:0000250\|UniProtKB:P19021, ECO:0000269\|PubMed:19604476}.
Biophysicochemical properties:		Kinetic parameters: KM=13.8 uM for [peptide]-C-terminal (2S)-2-hydroxyglycine {ECO:0000269\|PubMed:19604476};
Subunit:		Monomer. Interacts with RASSF9. {ECO:0000269\|PubMed:9837933}.
Subcellular location:		Cytoplasmic vesicle, secretory vesicle membrane {ECO:0000250\|UniProtKB:P10731}; Single-pass membrane protein {ECO:0000250\|UniProtKB:P10731}. Note=Secretory granules. {ECO:0000250\|UniProtKB:P10731}.
Miscellaneous:		[Isoform PAM-1]: Membrane-bound.
Miscellaneous:		[Isoform PAM-2]: Membrane-bound. {ECO:0000305}.
Miscellaneous:		[Isoform PAM-3]: Soluble. {ECO:0000305}.
Miscellaneous:		[Isoform PAM-3A]: Soluble. {ECO:0000305}.
Miscellaneous:		[Isoform PAM-3B]: Membrane-bound. {ECO:0000305}.
Miscellaneous:		[Isoform PAM-4]: Soluble. {ECO:0000305}.
Miscellaneous:		[Isoform PAM-5]: Soluble. {ECO:0000305}.
Similarity:		In the C-terminal section; belongs to the peptidyl-alpha- hydroxyglycine alpha-amidating lyase family. {ECO:0000305}.
Similarity:		In the N-terminal section; belongs to the copper type II ascorbate-dependent monooxygenase family. {ECO:0000305}.
Sequence caution:		Sequence=AAA42068.1; Type=Miscellaneous discrepancy; Evidence={ECO:0000305};