AMD_HUMAN
ID AMD_HUMAN Reviewed; 973 AA.
AC P19021; A6NMR0; A8K293; O43211; O95080; Q16252; Q16253; Q54A45; Q86U53;
AC Q8WVC7; Q9UCG0;
DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
DT 19-SEP-2002, sequence version 2.
DT 03-AUG-2022, entry version 230.
DE RecName: Full=Peptidyl-glycine alpha-amidating monooxygenase {ECO:0000303|PubMed:12699694};
DE Short=PAM {ECO:0000303|PubMed:12699694};
DE Includes:
DE RecName: Full=Peptidylglycine alpha-hydroxylating monooxygenase {ECO:0000303|PubMed:12699694};
DE Short=PHM {ECO:0000303|PubMed:12699694};
DE EC=1.14.17.3 {ECO:0000269|PubMed:12699694};
DE Includes:
DE RecName: Full=Peptidyl-alpha-hydroxyglycine alpha-amidating lyase;
DE EC=4.3.2.5 {ECO:0000269|PubMed:12699694};
DE AltName: Full=Peptidylamidoglycolate lyase {ECO:0000303|PubMed:12699694};
DE Short=PAL {ECO:0000303|PubMed:12699694};
DE Flags: Precursor;
GN Name=PAM {ECO:0000303|PubMed:12699694, ECO:0000312|HGNC:HGNC:8596};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5).
RC TISSUE=Thyroid carcinoma;
RX PubMed=2357221; DOI=10.1016/0006-291x(90)90366-u;
RA Glauder J., Ragg H., Rauch J., Engels J.W.;
RT "Human peptidylglycine alpha-amidating monooxygenase: cDNA, cloning and
RT functional expression of a truncated form in COS cells.";
RL Biochem. Biophys. Res. Commun. 169:551-558(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 3).
RX PubMed=7999037; DOI=10.1006/bbrc.1994.2662;
RA Tateishi K., Arakawa F., Misumi Y., Treston A.M., Vos M., Matsuoka Y.;
RT "Isolation and functional expression of human pancreatic peptidylglycine
RT alpha-amidating monooxygenase.";
RL Biochem. Biophys. Res. Commun. 205:282-290(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), COFACTOR, ACTIVITY REGULATION,
RP FUNCTION, AND CATALYTIC ACTIVITY.
RC TISSUE=Heart;
RX PubMed=12699694; DOI=10.1016/s1046-5928(02)00684-8;
RA Satani M., Takahashi K., Sakamoto H., Harada S., Kaida Y., Noguchi M.;
RT "Expression and characterization of human bifunctional peptidylglycine
RT alpha-amidating monooxygenase.";
RL Protein Expr. Purif. 28:293-302(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Thalamus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 29-973 (ISOFORM 4).
RC TISSUE=Kidney;
RA Chung B.H., Oh G.H., Choi E.S.;
RT "The alpha-amidating monooxygenase gene of human kidney.";
RL Submitted (JUN-1997) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 707-973 (ISOFORM 6).
RC TISSUE=Brain;
RX PubMed=9110174; DOI=10.1101/gr.7.4.353;
RA Yu W., Andersson B., Worley K.C., Muzny D.M., Ding Y., Liu W.,
RA Ricafrente J.Y., Wentland M.A., Lennon G., Gibbs R.A.;
RT "Large-scale concatenation cDNA sequencing.";
RL Genome Res. 7:353-358(1997).
RN [11]
RP SULFATION AT TYR-875 (ISOFORM 4), AND SULFATION AT TYR-893 (ISOFORM 3).
RX PubMed=8144680; DOI=10.1016/s0021-9258(17)34149-2;
RA Yun H.Y., Keutmann H.T., Eipper B.A.;
RT "Alternative splicing governs sulfation of tyrosine or oligosaccharide on
RT peptidylglycine alpha-amidating monooxygenase.";
RL J. Biol. Chem. 269:10946-10955(1994).
RN [12]
RP PHOSPHORYLATION AT THR-943 AND SER-946 BY UHMK1.
RX PubMed=10574929; DOI=10.1074/jbc.274.49.34646;
RA Caldwell B.D., Darlington D.N., Penzes P., Johnson R.C., Eipper B.A.,
RA Mains R.E.;
RT "The novel kinase peptidylglycine alpha-amidating monooxygenase cytosolic
RT interactor protein 2 interacts with the cytosolic routing determinants of
RT the peptide processing enzyme peptidylglycine alpha-amidating
RT monooxygenase.";
RL J. Biol. Chem. 274:34646-34656(1999).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-946, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-929, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-942 AND SER-946, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-918 AND SER-929, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
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:12699694). 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:12699694). 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:12699694). 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:12699694}.
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:12699694};
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:12699694};
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:0000269|PubMed:12699694};
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:12699694};
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 (PubMed:12699694). PAL activity is stimulated
CC by cadmium and inhibited by mercury (By similarity).
CC {ECO:0000250|UniProtKB:P14925, ECO:0000269|PubMed:12699694}.
CC -!- SUBUNIT: Monomer. Interacts with RASSF9.
CC {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 -!- SUBCELLULAR LOCATION: [Isoform 1]: Membrane; Single-pass type I
CC membrane protein.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Membrane; Single-pass type I
CC membrane protein.
CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Secreted. Note=Secreted from
CC secretory granules.
CC -!- SUBCELLULAR LOCATION: [Isoform 4]: Secreted. Note=Secreted from
CC secretory granules.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=6;
CC Comment=Additional isoforms seem to exist.;
CC Name=1;
CC IsoId=P19021-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P19021-2; Sequence=VSP_001227;
CC Name=3;
CC IsoId=P19021-3; Sequence=VSP_001228;
CC Name=4;
CC IsoId=P19021-4; Sequence=VSP_001229;
CC Name=5;
CC IsoId=P19021-5; Sequence=VSP_038691;
CC Name=6;
CC IsoId=P19021-6; Sequence=VSP_042209;
CC -!- MISCELLANEOUS: [Isoform 3]: Soluble. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 4]: Soluble. {ECO:0000305}.
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 -!- SEQUENCE CAUTION:
CC Sequence=AAD01439.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; M37721; AAA36414.1; -; mRNA.
DR EMBL; S75037; AAB32775.1; -; mRNA.
DR EMBL; S75038; AAB32776.1; -; mRNA.
DR EMBL; AB095007; BAC22594.1; -; mRNA.
DR EMBL; AK290158; BAF82847.1; -; mRNA.
DR EMBL; BT007419; AAP36087.1; -; mRNA.
DR EMBL; AC008779; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC010250; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC113373; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471086; EAW49085.1; -; Genomic_DNA.
DR EMBL; BC018127; AAH18127.1; -; mRNA.
DR EMBL; AF010472; AAD01439.1; ALT_INIT; mRNA.
DR EMBL; AF035320; AAB88190.1; -; mRNA.
DR CCDS; CCDS4092.1; -. [P19021-3]
DR CCDS; CCDS4093.1; -. [P19021-2]
DR CCDS; CCDS4094.1; -. [P19021-4]
DR CCDS; CCDS43348.1; -. [P19021-5]
DR CCDS; CCDS54885.1; -. [P19021-1]
DR PIR; A35477; URHUAP.
DR RefSeq; NP_000910.2; NM_000919.3. [P19021-5]
DR RefSeq; NP_001170777.1; NM_001177306.1. [P19021-1]
DR RefSeq; NP_001306872.1; NM_001319943.1.
DR RefSeq; NP_620121.1; NM_138766.2. [P19021-3]
DR RefSeq; NP_620176.1; NM_138821.2. [P19021-2]
DR RefSeq; NP_620177.1; NM_138822.2. [P19021-4]
DR RefSeq; XP_016864986.1; XM_017009497.1. [P19021-5]
DR RefSeq; XP_016864990.1; XM_017009501.1.
DR RefSeq; XP_016864994.1; XM_017009505.1. [P19021-3]
DR AlphaFoldDB; P19021; -.
DR SMR; P19021; -.
DR BioGRID; 111101; 92.
DR CORUM; P19021; -.
DR IntAct; P19021; 13.
DR STRING; 9606.ENSP00000306100; -.
DR BindingDB; P19021; -.
DR ChEMBL; CHEMBL2544; -.
DR DrugBank; DB00126; Ascorbic acid.
DR DrugBank; DB09130; Copper.
DR DrugBank; DB04150; N-alpha-Acetyl-3,5-diiodotyrosyl-D-threonine.
DR DrugBank; DB02598; N-Alpha-Acetyl-3,5-Diiodotyrosylglycine.
DR GlyGen; P19021; 4 sites, 3 O-linked glycans (3 sites).
DR iPTMnet; P19021; -.
DR PhosphoSitePlus; P19021; -.
DR BioMuta; PAM; -.
DR DMDM; 23503036; -.
DR EPD; P19021; -.
DR jPOST; P19021; -.
DR MassIVE; P19021; -.
DR MaxQB; P19021; -.
DR PaxDb; P19021; -.
DR PeptideAtlas; P19021; -.
DR PRIDE; P19021; -.
DR ProteomicsDB; 53622; -. [P19021-1]
DR ProteomicsDB; 53623; -. [P19021-2]
DR ProteomicsDB; 53624; -. [P19021-3]
DR ProteomicsDB; 53625; -. [P19021-4]
DR ProteomicsDB; 53626; -. [P19021-5]
DR ProteomicsDB; 53627; -. [P19021-6]
DR Antibodypedia; 25194; 154 antibodies from 33 providers.
DR DNASU; 5066; -.
DR Ensembl; ENST00000346918.7; ENSP00000282992.3; ENSG00000145730.21. [P19021-4]
DR Ensembl; ENST00000348126.7; ENSP00000314638.3; ENSG00000145730.21. [P19021-2]
DR Ensembl; ENST00000438793.8; ENSP00000396493.3; ENSG00000145730.21. [P19021-1]
DR Ensembl; ENST00000455264.7; ENSP00000403461.2; ENSG00000145730.21. [P19021-3]
DR Ensembl; ENST00000682407.1; ENSP00000506966.1; ENSG00000145730.21. [P19021-6]
DR Ensembl; ENST00000684529.1; ENSP00000507038.1; ENSG00000145730.21. [P19021-5]
DR GeneID; 5066; -.
DR KEGG; hsa:5066; -.
DR MANE-Select; ENST00000438793.8; ENSP00000396493.3; NM_001177306.2; NP_001170777.1.
DR UCSC; uc003kns.4; human. [P19021-1]
DR CTD; 5066; -.
DR DisGeNET; 5066; -.
DR GeneCards; PAM; -.
DR HGNC; HGNC:8596; PAM.
DR HPA; ENSG00000145730; Tissue enhanced (heart).
DR MIM; 170270; gene.
DR neXtProt; NX_P19021; -.
DR OpenTargets; ENSG00000145730; -.
DR PharmGKB; PA32926; -.
DR VEuPathDB; HostDB:ENSG00000145730; -.
DR eggNOG; KOG3567; Eukaryota.
DR GeneTree; ENSGT00940000156369; -.
DR HOGENOM; CLU_012293_0_0_1; -.
DR InParanoid; P19021; -.
DR OMA; KRNPQWP; -.
DR OrthoDB; 476471at2759; -.
DR PhylomeDB; P19021; -.
DR TreeFam; TF320698; -.
DR BRENDA; 1.14.17.3; 2681.
DR BRENDA; 4.3.2.5; 2681.
DR PathwayCommons; P19021; -.
DR SignaLink; P19021; -.
DR SIGNOR; P19021; -.
DR BioGRID-ORCS; 5066; 14 hits in 1071 CRISPR screens.
DR ChiTaRS; PAM; human.
DR GeneWiki; Peptidylglycine_alpha-amidating_monooxygenase; -.
DR GenomeRNAi; 5066; -.
DR Pharos; P19021; Tchem.
DR PRO; PR:P19021; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; P19021; protein.
DR Bgee; ENSG00000145730; Expressed in cardiac muscle of right atrium and 205 other tissues.
DR ExpressionAtlas; P19021; baseline and differential.
DR Genevisible; P19021; HS.
DR GO; GO:0009986; C:cell surface; IEA:Ensembl.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
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:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0043005; C:neuron projection; IEA:Ensembl.
DR GO; GO:0043204; C:perikaryon; IEA:Ensembl.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IEA:Ensembl.
DR GO; GO:0030667; C:secretory granule membrane; ISS:UniProtKB.
DR GO; GO:0005802; C:trans-Golgi network; IEA:Ensembl.
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:0042802; F:identical protein binding; IEA:Ensembl.
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:0019901; F:protein kinase binding; IEA:Ensembl.
DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR GO; GO:0007417; P:central nervous system development; IEA:Ensembl.
DR GO; GO:0062112; P:fatty acid primary amide biosynthetic process; ISS:UniProtKB.
DR GO; GO:0007507; P:heart development; IEA:Ensembl.
DR GO; GO:0007595; P:lactation; IEA:Ensembl.
DR GO; GO:0060173; P:limb development; IEA:Ensembl.
DR GO; GO:0001676; P:long-chain fatty acid metabolic process; IEA:Ensembl.
DR GO; GO:0060135; P:maternal process involved in female pregnancy; IEA:Ensembl.
DR GO; GO:0042476; P:odontogenesis; IEA:Ensembl.
DR GO; GO:0022602; P:ovulation cycle process; IEA:Ensembl.
DR GO; GO:0001519; P:peptide amidation; IDA:UniProtKB.
DR GO; GO:0018032; P:protein amidation; IEA:Ensembl.
DR GO; GO:0032956; P:regulation of actin cytoskeleton organization; IEA:Ensembl.
DR GO; GO:0050708; P:regulation of protein secretion; IEA:Ensembl.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0046688; P:response to copper ion; IEA:Ensembl.
DR GO; GO:0032355; P:response to estradiol; IEA:Ensembl.
DR GO; GO:0051384; P:response to glucocorticoid; IEA:Ensembl.
DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl.
DR GO; GO:0009268; P:response to pH; IEA:Ensembl.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0010043; P:response to zinc ion; IDA:UniProtKB.
DR GO; GO:0009404; P:toxin metabolic process; IEA:Ensembl.
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; 5.
PE 1: Evidence at protein level;
KW Alternative splicing; Calcium; Cleavage on pair of basic residues; Copper;
KW Cytoplasmic vesicle; Disulfide bond; Glycoprotein; Lipid metabolism; Lyase;
KW Membrane; Metal-binding; Monooxygenase; Multifunctional enzyme;
KW Oxidoreductase; Phosphoprotein; Reference proteome; Repeat; Secreted;
KW Signal; Sulfation; Transmembrane; Transmembrane helix; Vitamin C; Zinc.
FT SIGNAL 1..20
FT /evidence="ECO:0000305"
FT PROPEP 21..30
FT /evidence="ECO:0000305"
FT /id="PRO_0000006361"
FT CHAIN 31..973
FT /note="Peptidyl-glycine alpha-amidating monooxygenase"
FT /id="PRO_0000006362"
FT TOPO_DOM 31..863
FT /note="Intragranular"
FT /evidence="ECO:0000255"
FT TRANSMEM 864..887
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 888..973
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..973
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 102
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P14925"
FT BINDING 103
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P14925"
FT BINDING 167
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P14925"
FT BINDING 237
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P14925"
FT BINDING 239
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P14925"
FT BINDING 309
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P14925"
FT BINDING 517
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_note="structural"
FT /evidence="ECO:0000250|UniProtKB:P14925"
FT BINDING 530
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P14925"
FT BINDING 582
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P14925"
FT BINDING 584
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_note="structural"
FT /evidence="ECO:0000250|UniProtKB:P14925"
FT BINDING 651
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P14925"
FT BINDING 687
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P14925"
FT BINDING 703
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P14925"
FT BINDING 783
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P14925"
FT BINDING 784
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_note="structural"
FT /evidence="ECO:0000250|UniProtKB:P14925"
FT MOD_RES 918
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 929
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 942
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 943
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:10574929"
FT MOD_RES 946
FT /note="Phosphoserine; by UHMK1; in vitro"
FT /evidence="ECO:0000269|PubMed:10574929,
FT ECO:0007744|PubMed:17081983, ECO:0007744|PubMed:21406692"
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"
FT VAR_SEQ 388..494
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334, ECO:0000303|Ref.5"
FT /id="VSP_001227"
FT VAR_SEQ 829..914
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|Ref.9"
FT /id="VSP_001229"
FT VAR_SEQ 829..896
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:7999037"
FT /id="VSP_001228"
FT VAR_SEQ 896
FT /note="G -> GA (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:2357221"
FT /id="VSP_038691"
FT VAR_SEQ 897..914
FT /note="Missing (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:9110174"
FT /id="VSP_042209"
FT VARIANT 49
FT /note="V -> L (in dbSNP:rs2230458)"
FT /id="VAR_055694"
FT CONFLICT 26
FT /note="S -> P (in Ref. 4; BAF82847)"
FT /evidence="ECO:0000305"
FT CONFLICT 574
FT /note="G -> E (in Ref. 1; AAA36414)"
FT /evidence="ECO:0000305"
FT CONFLICT 774
FT /note="P -> L (in Ref. 4; BAF82847)"
FT /evidence="ECO:0000305"
FT CONFLICT 830..831
FT /note="Missing (in Ref. 2; AAB32775)"
FT /evidence="ECO:0000305"
FT MOD_RES P19021-3:893
FT /note="Sulfotyrosine"
FT /evidence="ECO:0000269|PubMed:8144680"
FT MOD_RES P19021-4:875
FT /note="Sulfotyrosine"
FT /evidence="ECO:0000269|PubMed:8144680"
SQ SEQUENCE 973 AA; 108332 MW; 8A089B657F56EE39 CRC64;
MAGRVPSLLV LLVFPSSCLA FRSPLSVFKR FKETTRPFSN ECLGTTRPVV PIDSSDFALD
IRMPGVTPKQ SDTYFCMSMR IPVDEEAFVI DFKPRASMDT VHHMLLFGCN MPSSTGSYWF
CDEGTCTDKA NILYAWARNA PPTRLPKGVG FRVGGETGSK YFVLQVHYGD ISAFRDNNKD
CSGVSLHLTR LPQPLIAGMY LMMSVDTVIP AGEKVVNSDI SCHYKNYPMH VFAYRVHTHH
LGKVVSGYRV RNGQWTLIGR QSPQLPQAFY PVGHPVDVSF GDLLAARCVF TGEGRTEATH
IGGTSSDEMC NLYIMYYMEA KHAVSFMTCT QNVAPDMFRT IPPEANIPIP VKSDMVMMHE
HHKETEYKDK IPLLQQPKRE EEEVLDQGDF YSLLSKLLGE REDVVHVHKY NPTEKAESES
DLVAEIANVV QKKDLGRSDA REGAEHERGN AILVRDRIHK FHRLVSTLRP PESRVFSLQQ
PPPGEGTWEP EHTGDFHMEE ALDWPGVYLL PGQVSGVALD PKNNLVIFHR GDHVWDGNSF
DSKFVYQQIG LGPIEEDTIL VIDPNNAAVL QSSGKNLFYL PHGLSIDKDG NYWVTDVALH
QVFKLDPNNK EGPVLILGRS MQPGSDQNHF CQPTDVAVDP GTGAIYVSDG YCNSRIVQFS
PSGKFITQWG EESSGSSPLP GQFTVPHSLA LVPLLGQLCV ADRENGRIQC FKTDTKEFVR
EIKHSSFGRN VFAISYIPGL LFAVNGKPHF GDQEPVQGFV MNFSNGEIID IFKPVRKHFD
MPHDIVASED GTVYIGDAHT NTVWKFTLTE KLEHRSVKKA GIEVQEIKEA EAVVETKMEN
KPTSSELQKM QEKQKLIKEP GSGVPVVLIT TLLVIPVVVL LAIAIFIRWK KSRAFGDSEH
KLETSSGRVL GRFRGKGSGG LNLGNFFASR KGYSRKGFDR LSTEGSDQEK EDDGSESEEE
YSAPLPALAP SSS
