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 27-MAR-2024, entry version 239. 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}; 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; 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 CCDS; CCDS93753.1; -. [P19021-6] 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; 95. 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 GlyCosmos; P19021; 4 sites, 3 glycans. DR GlyGen; P19021; 9 sites, 4 O-linked glycans (8 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; 9606-ENSP00000306100; -. DR PeptideAtlas; 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 Pumba; P19021; -. DR Antibodypedia; 25194; 169 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 AGR; HGNC:8596; -. 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; 2908431at2759; -. 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 1151 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 207 other cell types or tissues. DR ExpressionAtlas; P19021; baseline and differential. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; IBA:GO_Central. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:0030667; C:secretory granule membrane; ISS: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; IDA:UniProtKB. DR GO; GO:0062112; P:fatty acid primary amide biosynthetic process; ISS:UniProtKB. DR GO; GO:0001519; P:peptide amidation; IDA:UniProtKB. DR GO; GO:0010043; P:response to zinc ion; IDA:UniProtKB. DR CDD; cd14958; NHL_PAL_like; 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; 5. DR Genevisible; P19021; HS. 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(2+)" FT /ligand_id="ChEBI:CHEBI:29036" FT /ligand_label="1" FT /ligand_note="catalytic" FT /evidence="ECO:0000250|UniProtKB:P14925" FT BINDING 103 FT /ligand="Cu(2+)" FT /ligand_id="ChEBI:CHEBI:29036" FT /ligand_label="1" FT /ligand_note="catalytic" FT /evidence="ECO:0000250|UniProtKB:P14925" FT BINDING 167 FT /ligand="Cu(2+)" FT /ligand_id="ChEBI:CHEBI:29036" FT /ligand_label="1" FT /ligand_note="catalytic" FT /evidence="ECO:0000250|UniProtKB:P14925" FT BINDING 237 FT /ligand="Cu(2+)" FT /ligand_id="ChEBI:CHEBI:29036" FT /ligand_label="2" FT /ligand_note="catalytic" FT /evidence="ECO:0000250|UniProtKB:P14925" FT BINDING 239 FT /ligand="Cu(2+)" FT /ligand_id="ChEBI:CHEBI:29036" FT /ligand_label="2" FT /ligand_note="catalytic" FT /evidence="ECO:0000250|UniProtKB:P14925" FT BINDING 309 FT /ligand="Cu(2+)" FT /ligand_id="ChEBI:CHEBI:29036" 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="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 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="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 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="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 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 //