ID   CERU_HUMAN              Reviewed;        1065 AA.
AC   P00450; Q14063; Q2PP18; Q9UKS4;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   24-JAN-2024, sequence version 2.
DT   04-NOV-2026, entry version 252.
DE   RecName: Full=Ceruloplasmin {ECO:0000305};
DE   AltName: Full=Cuproxidase ceruloplasmin {ECO:0000305|PubMed:14623105};
DE            EC=1.16.3.4 {ECO:0000269|PubMed:14623105};
DE   AltName: Full=Ferroxidase ceruloplasmin;
DE            EC=1.16.3.1 {ECO:0000269|PubMed:10481051, ECO:0000269|PubMed:16150804};
DE   AltName: Full=Glutathione peroxidase ceruloplasmin {ECO:0000305|PubMed:10481051};
DE            EC=1.11.1.9 {ECO:0000269|PubMed:10481051, ECO:0000269|PubMed:10508415};
DE   AltName: Full=Glutathione-dependent peroxiredoxin ceruloplasmin {ECO:0000305|PubMed:10481051};
DE            EC=1.11.1.27 {ECO:0000269|PubMed:10481051, ECO:0000269|PubMed:10508415};
DE   Flags: Precursor;
GN   Name=CP {ECO:0000312|HGNC:HGNC:2295};
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], AND VARIANT ASP-544.
RX   PubMed=2873574; DOI=10.1073/pnas.83.14.5086;
RA   Koschinsky M.L., Funk W.D., van Oost B.A., McGillivray R.T.A.;
RT   "Complete cDNA sequence of human preceruloplasmin.";
RL   Proc. Natl. Acad. Sci. U.S.A. 83:5086-5090(1986).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ASP-544.
RG   NHLBI resequencing and genotyping service (RS&G);
RL   Submitted (DEC-2005) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-1006.
RX   PubMed=7702601; DOI=10.1006/bbrc.1995.1437;
RA   Daimon M., Yamatani K., Igarashi M., Fukase N., Kawanami T., Kato T.,
RA   Tominaga M., Sasaki H.;
RT   "Fine structure of the human ceruloplasmin gene.";
RL   Biochem. Biophys. Res. Commun. 208:1028-1035(1995).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 1-40; 549-599; 784-829 AND 919-952.
RX   PubMed=3755405; DOI=10.1016/0014-5793(86)80739-6;
RA   Mercer J.F.B., Grimes A.;
RT   "Isolation of a human ceruloplasmin cDNA clone that includes the N-terminal
RT   leader sequence.";
RL   FEBS Lett. 203:185-190(1986).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-22.
RA   Bingle C.D.;
RT   "Cloning and functional analysis of the human ceruloplasmin gene minimal
RT   promoter.";
RL   Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 218-1065, AND VARIANT ASP-544.
RX   PubMed=3486416; DOI=10.1073/pnas.83.10.3257;
RA   Yang F., Naylor S.L., Lum J.B., Cutshaw S., McCombs J.L., Naberhaus K.H.,
RA   McGill J.R., Adrian G.S., Moore C.M., Barnett D.R., Bowman B.H.;
RT   "Characterization, mapping, and expression of the human ceruloplasmin
RT   gene.";
RL   Proc. Natl. Acad. Sci. U.S.A. 83:3257-3261(1986).
RN   [7]
RP   PROTEIN SEQUENCE OF 20-1065.
RX   PubMed=6582496; DOI=10.1073/pnas.81.2.390;
RA   Takahashi N., Ortel T.L., Putnam F.W.;
RT   "Single-chain structure of human ceruloplasmin: the complete amino acid
RT   sequence of the whole molecule.";
RL   Proc. Natl. Acad. Sci. U.S.A. 81:390-394(1984).
RN   [8]
RP   PROTEIN SEQUENCE OF 158-333; 518-724 AND 858-1065.
RX   PubMed=6571985; DOI=10.1073/pnas.80.1.115;
RA   Takahashi N., Bauman R.A., Ortel T.L., Dwulet F.E., Wang C.-C.,
RA   Putnam F.W.;
RT   "Internal triplication in the structure of human ceruloplasmin.";
RL   Proc. Natl. Acad. Sci. U.S.A. 80:115-119(1983).
RN   [9]
RP   PROTEIN SEQUENCE OF 501-905.
RX   PubMed=6940148; DOI=10.1073/pnas.78.2.790;
RA   Dwulet F.E., Putnam F.W.;
RT   "Complete amino acid sequence of a 50,000-dalton fragment of human
RT   ceruloplasmin.";
RL   Proc. Natl. Acad. Sci. U.S.A. 78:790-794(1981).
RN   [10]
RP   PROTEIN SEQUENCE OF 907-1065.
RX   PubMed=6987229; DOI=10.1016/s0021-9258(19)85822-2;
RA   Kingston I.B., Kingston B.L., Putnam F.W.;
RT   "Primary structure of a histidine-rich proteolytic fragment of human
RT   ceruloplasmin. I. Amino acid sequence of the cyanogen bromide peptides.";
RL   J. Biol. Chem. 255:2878-2885(1980).
RN   [11]
RP   PROTEIN SEQUENCE OF 907-1065.
RX   PubMed=6987230; DOI=10.1016/s0021-9258(19)85823-4;
RA   Kingston I.B., Kingston B.L., Putnam F.W.;
RT   "Primary structure of a histidine-rich proteolytic fragment of human
RT   ceruloplasmin. II. Amino acid sequence of the tryptic peptides.";
RL   J. Biol. Chem. 255:2886-2896(1980).
RN   [12]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1007-1061.
RX   PubMed=2355023; DOI=10.1016/s0021-9258(18)87015-6;
RA   Yang F.M., Friedrichs W.E., Cupples R.L., Banifacio M.J., Sanford J.A.,
RA   Horton W.A., Bowman B.H.;
RT   "Human ceruloplasmin. Tissue-specific expression of transcripts produced by
RT   alternative splicing.";
RL   J. Biol. Chem. 265:10780-10785(1990).
RN   [13]
RP   FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=5912351; DOI=10.1016/s0021-9258(18)96527-0;
RA   Osaki S., Johnson D.A., Frieden E.;
RT   "The possible significance of the ferrous oxidase activity of ceruloplasmin
RT   in normal human serum.";
RL   J. Biol. Chem. 241:2746-2751(1966).
RN   [14]
RP   FUNCTION.
RX   PubMed=4643313; DOI=10.1042/bj1290273;
RA   Young S.N., Curzon G.;
RT   "A method for obtaining linear reciprocal plots with caeruloplasmin and its
RT   application in a study of the kinetic parameters of caeruloplasmin
RT   substrates.";
RL   Biochem. J. 129:273-283(1972).
RN   [15]
RP   FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND ACTIVE
RP   SITE.
RX   PubMed=10508415; DOI=10.1021/bi990444b;
RA   Cha M.K., Kim I.H.;
RT   "Ceruloplasmin has a distinct active site for the catalyzing glutathione-
RT   dependent reduction of alkyl hydroperoxide.";
RL   Biochemistry 38:12104-12110(1999).
RN   [16]
RP   FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=10481051; DOI=10.1016/s0014-5793(99)01142-4;
RA   Park Y.S., Suzuki K., Taniguchi N., Gutteridge J.M.;
RT   "Glutathione peroxidase-like activity of caeruloplasmin as an important
RT   lung antioxidant.";
RL   FEBS Lett. 458:133-136(1999).
RN   [17]
RP   REVIEW.
RX   PubMed=12055353; DOI=10.1146/annurev.nutr.22.012502.114457;
RA   Hellman N.E., Gitlin J.D.;
RT   "Ceruloplasmin metabolism and function.";
RL   Annu. Rev. Nutr. 22:439-458(2002).
RN   [18]
RP   FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX   PubMed=14623105; DOI=10.1016/s0014-5793(03)01218-3;
RA   Stoj C., Kosman D.J.;
RT   "Cuprous oxidase activity of yeast Fet3p and human ceruloplasmin:
RT   implication for function.";
RL   FEBS Lett. 554:422-426(2003).
RN   [19]
RP   GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-138.
RC   TISSUE=Bile;
RX   PubMed=15084671; DOI=10.1074/mcp.m400015-mcp200;
RA   Kristiansen T.Z., Bunkenborg J., Gronborg M., Molina H., Thuluvath P.J.,
RA   Argani P., Goggins M.G., Maitra A., Pandey A.;
RT   "A proteomic analysis of human bile.";
RL   Mol. Cell. Proteomics 3:715-728(2004).
RN   [20]
RP   GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-138; ASN-397 AND ASN-762.
RC   TISSUE=Plasma;
RX   PubMed=14760718; DOI=10.1002/pmic.200300556;
RA   Bunkenborg J., Pilch B.J., Podtelejnikov A.V., Wisniewski J.R.;
RT   "Screening for N-glycosylated proteins by liquid chromatography mass
RT   spectrometry.";
RL   Proteomics 4:454-465(2004).
RN   [21]
RP   GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-138; ASN-358; ASN-397; ASN-588;
RP   ASN-762 AND ASN-926.
RC   TISSUE=Plasma;
RX   PubMed=16335952; DOI=10.1021/pr0502065;
RA   Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J.,
RA   Smith R.D.;
RT   "Human plasma N-glycoproteome analysis by immunoaffinity subtraction,
RT   hydrazide chemistry, and mass spectrometry.";
RL   J. Proteome Res. 4:2070-2080(2005).
RN   [22]
RP   FUNCTION.
RX   PubMed=16906150; DOI=10.1038/nchembio813;
RA   Shiva S., Wang X., Ringwood L.A., Xu X., Yuditskaya S., Annavajjhala V.,
RA   Miyajima H., Hogg N., Harris Z.L., Gladwin M.T.;
RT   "Ceruloplasmin is a NO oxidase and nitrite synthase that determines
RT   endocrine NO homeostasis.";
RL   Nat. Chem. Biol. 2:486-493(2006).
RN   [23]
RP   GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-138; ASN-358; ASN-397 AND
RP   ASN-762.
RC   TISSUE=Liver;
RX   PubMed=19159218; DOI=10.1021/pr8008012;
RA   Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT   "Glycoproteomics analysis of human liver tissue by combination of multiple
RT   enzyme digestion and hydrazide chemistry.";
RL   J. Proteome Res. 8:651-661(2009).
RN   [24]
RP   GLYCOSYLATION AT ASN-138; ASN-358; ASN-397 AND ASN-762.
RX   PubMed=19139490; DOI=10.1074/mcp.m800504-mcp200;
RA   Jia W., Lu Z., Fu Y., Wang H.P., Wang L.H., Chi H., Yuan Z.F., Zheng Z.B.,
RA   Song L.N., Han H.H., Liang Y.M., Wang J.L., Cai Y., Zhang Y.K., Deng Y.L.,
RA   Ying W.T., He S.M., Qian X.H.;
RT   "A strategy for precise and large scale identification of core fucosylated
RT   glycoproteins.";
RL   Mol. Cell. Proteomics 8:913-923(2009).
RN   [25]
RP   GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-138; ASN-358 AND ASN-397, AND
RP   STRUCTURE OF CARBOHYDRATES.
RC   TISSUE=Cerebrospinal fluid;
RX   PubMed=19838169; DOI=10.1038/nmeth.1392;
RA   Nilsson J., Rueetschi U., Halim A., Hesse C., Carlsohn E., Brinkmalm G.,
RA   Larson G.;
RT   "Enrichment of glycopeptides for glycan structure and attachment site
RT   identification.";
RL   Nat. Methods 6:809-811(2009).
RN   [26]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA   Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA   Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT   phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
RN   [27]
RP   PHOSPHORYLATION AT SER-722.
RX   PubMed=26091039; DOI=10.1016/j.cell.2015.05.028;
RA   Tagliabracci V.S., Wiley S.E., Guo X., Kinch L.N., Durrant E., Wen J.,
RA   Xiao J., Cui J., Nguyen K.B., Engel J.L., Coon J.J., Grishin N.,
RA   Pinna L.A., Pagliarini D.J., Dixon J.E.;
RT   "A single kinase generates the majority of the secreted phosphoproteome.";
RL   Cell 161:1619-1632(2015).
RN   [28]
RP   CATALYTIC ACTIVITY.
RX   PubMed=29183916; DOI=10.15252/emmm.201708361;
RA   Zanardi A., Conti A., Cremonesi M., D'Adamo P., Gilberti E., Apostoli P.,
RA   Cannistraci C.V., Piperno A., David S., Alessio M.;
RT   "Ceruloplasmin replacement therapy ameliorates neurological symptoms in a
RT   preclinical model of aceruloplasminemia.";
RL   EMBO Mol. Med. 10:91-106(2018).
RN   [29] {ECO:0007744|PDB:1KCW}
RP   X-RAY CRYSTALLOGRAPHY IN COMPLEX WITH CU(2+), GLYCOSYLATION AT ASN-138 AND
RP   ASN-762, DOMAIN, AND DISULFIDE BOND.
RA   Zaitseva I., Zaitsev V., Card G., Moshkov K., Bax B., Ralph A., Lindley P.;
RT   "The X-ray structure of human serum ceruloplasmin at 3.1 A: nature of the
RT   copper centres.";
RL   J. Biol. Inorg. Chem. 1:15-23(1996).
RN   [30] {ECO:0007744|PDB:2J5W}
RP   X-RAY CRYSTALLOGRAPHY IN COMPLEX WITH O2; CA(2+); CU(2+) AND NA(+),
RP   GLYCOSYLATION AT ASN-138 AND ASN-397, AND DISULFIDE BOND.
RX   PubMed=17242517; DOI=10.1107/s090744490604947x;
RA   Bento I., Peixoto C., Zaitsev V.N., Lindley P.F.;
RT   "Ceruloplasmin revisited: structural and functional roles of various metal
RT   cation-binding sites.";
RL   Acta Crystallogr. D 63:240-248(2007).
RN   [31] {ECO:0007744|PDB:4EJX, ECO:0007744|PDB:4ENZ}
RP   X-RAY CRYSTALLOGRAPHY IN COMPLEX WITH MPO; CA(2+); CU(2+) AND NA(+),
RP   GLYCOSYLATION AT ASN-138 AND ASN-397, AND INTERACTION WITH MPO AND LTF.
RX   PubMed=23843990; DOI=10.1371/journal.pone.0067145;
RA   Samygina V.R., Sokolov A.V., Bourenkov G., Petoukhov M.V., Pulina M.O.,
RA   Zakharova E.T., Vasilyev V.B., Bartunik H., Svergun D.I.;
RT   "Ceruloplasmin: macromolecular assemblies with iron-containing acute phase
RT   proteins.";
RL   PLoS ONE 8:e67145-e67145(2013).
RN   [32]
RP   INVOLVEMENT IN ACEP.
RX   PubMed=7708681; DOI=10.1073/pnas.92.7.2539;
RA   Harris Z.L., Takahashi Y., Miyajima H., Serizawa M., MacGillivray R.T.,
RA   Gitlin J.D.;
RT   "Aceruloplasminemia: molecular characterization of this disorder of iron
RT   metabolism.";
RL   Proc. Natl. Acad. Sci. U.S.A. 92:2539-2543(1995).
RN   [33]
RP   VARIANTS THR-63; LEU-477; ILE-551; HIS-793 AND ARG-841.
RX   PubMed=15557511; DOI=10.1212/01.wnl.0000144276.29988.c3;
RA   Hochstrasser H., Bauer P., Walter U., Behnke S., Spiegel J., Csoti I.,
RA   Zeiler B., Bornemann A., Pahnke J., Becker G., Riess O., Berg D.;
RT   "Ceruloplasmin gene variations and substantia nigra hyperechogenicity in
RT   Parkinson disease.";
RL   Neurology 63:1912-1917(2004).
RN   [34]
RP   CHARACTERIZATION OF VARIANTS THR-63 AND HIS-793, FUNCTION, CATALYTIC
RP   ACTIVITY, AND SUBCELLULAR LOCATION.
RX   PubMed=16150804; DOI=10.1096/fj.04-3486fje;
RA   Hochstrasser H., Tomiuk J., Walter U., Behnke S., Spiegel J., Krueger R.,
RA   Becker G., Riess O., Berg D.;
RT   "Functional relevance of ceruloplasmin mutations in Parkinson's disease.";
RL   FASEB J. 19:1851-1853(2005).
CC   -!- FUNCTION: Multifunctional blue, copper-binding (6-7 atoms per molecule)
CC       glycoprotein. It has ferroxidase activity oxidizing Fe(2+) to Fe(3+)
CC       without releasing radical oxygen species. It is involved in iron
CC       transport across the cell membrane (PubMed:16150804). Copper ions
CC       provide a large number of enzymatic activities. Oxidizes highly toxic
CC       ferrous ions to the ferric state for further incorporation onto apo-
CC       transferrins, catalyzes Cu(+) oxidation and promotes the oxidation of
CC       biogenic amines such as norepinephrin and serotonin (PubMed:14623105,
CC       PubMed:4643313, PubMed:5912351). Provides Cu(2+) ions for the
CC       ascorbate-mediated deaminase degradation of the heparan sulfate chains
CC       of GPC1 (By similarity). Has glutathione peroxidase-like activity, can
CC       remove both hydrogen peroxide and lipid hydroperoxide in the presence
CC       of thiols (PubMed:10481051). Acts as an inhibitor of the peroxidase
CC       activity of MPO (By similarity). Also shows NO-oxidase and NO2 synthase
CC       activities that determine endocrine NO homeostasis (PubMed:16906150).
CC       {ECO:0000250|UniProtKB:P13635, ECO:0000250|UniProtKB:Q61147,
CC       ECO:0000269|PubMed:10481051, ECO:0000269|PubMed:14623105,
CC       ECO:0000269|PubMed:16150804, ECO:0000269|PubMed:16906150,
CC       ECO:0000269|PubMed:4643313, ECO:0000269|PubMed:5912351}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=4 Fe(2+) + O2 + 4 H(+) = 4 Fe(3+) + 2 H2O;
CC         Xref=Rhea:RHEA:11148, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:15379, ChEBI:CHEBI:29033, ChEBI:CHEBI:29034; EC=1.16.3.1;
CC         Evidence={ECO:0000269|PubMed:10481051, ECO:0000269|PubMed:16150804,
CC         ECO:0000269|PubMed:29183916, ECO:0000269|PubMed:5912351};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:11150;
CC         Evidence={ECO:0000269|PubMed:16150804, ECO:0000269|PubMed:29183916};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=4 Cu(+) + O2 + 4 H(+) = 4 Cu(2+) + 2 H2O;
CC         Xref=Rhea:RHEA:30083, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:15379, ChEBI:CHEBI:29036, ChEBI:CHEBI:49552; EC=1.16.3.4;
CC         Evidence={ECO:0000269|PubMed:14623105};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:30084;
CC         Evidence={ECO:0000305|PubMed:14623105};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a hydroperoxide + 2 glutathione = an alcohol + glutathione
CC         disulfide + H2O; Xref=Rhea:RHEA:62632, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:30879, ChEBI:CHEBI:35924, ChEBI:CHEBI:57925,
CC         ChEBI:CHEBI:58297; EC=1.11.1.27;
CC         Evidence={ECO:0000269|PubMed:10481051, ECO:0000269|PubMed:10508415};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62633;
CC         Evidence={ECO:0000305|PubMed:10508415};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=4 nitric oxide + O2 + 2 H2O = 4 nitrite + 4 H(+);
CC         Xref=Rhea:RHEA:78539, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:15379, ChEBI:CHEBI:16301, ChEBI:CHEBI:16480;
CC         Evidence={ECO:0000269|PubMed:29183916};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:78540;
CC         Evidence={ECO:0000305|PubMed:29183916};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=2 glutathione + H2O2 = glutathione disulfide + 2 H2O;
CC         Xref=Rhea:RHEA:16833, ChEBI:CHEBI:15377, ChEBI:CHEBI:16240,
CC         ChEBI:CHEBI:57925, ChEBI:CHEBI:58297; EC=1.11.1.9;
CC         Evidence={ECO:0000269|PubMed:10481051, ECO:0000269|PubMed:10508415};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16834;
CC         Evidence={ECO:0000305|PubMed:10508415};
CC   -!- COFACTOR:
CC       Name=Cu(2+); Xref=ChEBI:CHEBI:29036;
CC         Evidence={ECO:0000269|PubMed:17242517, ECO:0000269|PubMed:23843990,
CC         ECO:0000269|Ref.29};
CC       Note=Binds 6 Cu(2+) cations per monomer. {ECO:0000269|PubMed:17242517,
CC       ECO:0000269|PubMed:23843990, ECO:0000269|Ref.29};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=36.8 uM for Cu(+) {ECO:0000269|PubMed:14623105};
CC         KM=8.3 uM for Fe(2+) {ECO:0000269|PubMed:14623105};
CC         KM=1.57 mM for glutathione {ECO:0000269|PubMed:10508415};
CC         KM=0.63 mM for tert-butyl hydroperoxide
CC         {ECO:0000269|PubMed:10508415};
CC         KM=0.87 mM for glutathione {ECO:0000269|PubMed:10508415};
CC         Vmax=156 nmol/min/mg enzyme (in presence of 5 mM tert-butyl
CC         hydroperoxide) {ECO:0000269|PubMed:10508415};
CC         Vmax=49 nmol/min/mg enzyme (in presence of 5 mM H2O2)
CC         {ECO:0000269|PubMed:10508415};
CC         Note=kcat is 22.5 min(-1) and 30.3 min(-1) with Cu(+) and Fe(2+) as
CC         substrates, respectively. {ECO:0000269|PubMed:14623105};
CC   -!- SUBUNIT: Found in a complex with MPO and LTF; interacts directly with
CC       MPO and LTF, which allows Fe(3+) incorporation into LTF, activation of
CC       CP ferroxidase activity and protection of CP antioxidant properties by
CC       MPO. {ECO:0000269|PubMed:23843990}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16150804}.
CC       Note=Colocalizes with GCP1 in secretory intracellular compartments.
CC       {ECO:0000250|UniProtKB:P13635}.
CC   -!- TISSUE SPECIFICITY: Expressed by the liver and secreted in plasma.
CC       {ECO:0000305|PubMed:12055353}.
CC   -!- DISEASE: Aceruloplasminemia (ACEP) [MIM:604290]: An autosomal recessive
CC       disorder of iron metabolism characterized by iron accumulation in the
CC       brain as well as visceral organs. Clinical features consist of the
CC       triad of retinal degeneration, diabetes mellitus and neurological
CC       disturbances. {ECO:0000269|PubMed:7708681}. Note=The disease is caused
CC       by variants affecting the gene represented in this entry.
CC   -!- SIMILARITY: Belongs to the multicopper oxidase family. {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=Wikipedia; Note=Ceruloplasmin entry;
CC       URL="https://en.wikipedia.org/wiki/Ceruloplasmin";
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DR   EMBL; M13699; AAA51976.1; -; mRNA.
DR   EMBL; DQ314867; ABC40726.1; -; Genomic_DNA.
DR   EMBL; D45045; BAA08085.1; -; Genomic_DNA.
DR   EMBL; D00025; BAA00019.1; -; mRNA.
DR   EMBL; X04135; CAA27752.1; -; mRNA.
DR   EMBL; X04136; CAA27753.1; -; mRNA.
DR   EMBL; X04137; CAA27754.1; -; mRNA.
DR   EMBL; X04138; CAA27755.1; -; mRNA.
DR   EMBL; AF132978; AAF02483.1; -; Genomic_DNA.
DR   EMBL; M13536; AAA51975.1; -; mRNA.
DR   EMBL; J05506; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   CCDS; CCDS3141.1; -.
DR   PIR; A25443; KUHU.
DR   RefSeq; NP_000087.2; NM_000096.4.
DR   PDB; 1KCW; X-ray; 3.00 A; A=20-1065.
DR   PDB; 2J5W; X-ray; 2.80 A; A=1-1065.
DR   PDB; 4EJX; X-ray; 4.69 A; A=1-1065.
DR   PDB; 4ENZ; X-ray; 2.60 A; A=1-1065.
DR   AlphaFoldDB; P00450; -.
DR   SASBDB; P00450; -.
DR   SMR; P00450; -.
DR   BioGRID; 107748; 73.
DR   CORUM; P00450; -.
DR   FunCoup; P00450; 262.
DR   IntAct; P00450; 39.
DR   NDEx; IQUERY-CP-CP; 4 NDEx IQuery Curated Pathways.
DR   STRING; 9606.ENSP00000264613; -.
DR   DrugBank; DB01373; Calcium.
DR   DrugBank; DB09130; Copper.
DR   DrugBank; DB11134; Cupric oxide.
DR   DrugBank; DB06778; Cupric sulfate.
DR   DrugBank; DB14490; Ferrous ascorbate.
DR   DrugBank; DB14491; Ferrous fumarate.
DR   DrugBank; DB14488; Ferrous gluconate.
DR   DrugBank; DB14501; Ferrous glycine sulfate.
DR   DrugBank; DB14489; Ferrous succinate.
DR   DrugBank; DB13257; Ferrous sulfate anhydrous.
DR   DrugBank; DB01592; Iron.
DR   DrugBank; DB06757; Manganese cation.
DR   DrugBank; DB12965; Silver.
DR   DrugBank; DB01593; Zinc.
DR   DrugBank; DB14487; Zinc acetate.
DR   DrugBank; DB14533; Zinc chloride.
DR   DrugBank; DB14548; Zinc sulfate, unspecified form.
DR   TCDB; 8.A.105.1.2; the multi-copper-containing ferroxidase (mcfo) family.
DR   CarbonylDB; P00450; -.
DR   GlyConnect; P00450; 80 N-Linked glycans (5 sites), 1 O-Linked glycan (1 site).
DR   GlyCosmos; P00450; 15 sites, 228 glycans.
DR   GlyGen; P00450; 14 sites, 225 N-linked glycans (6 sites), 4 O-linked glycans (6 sites).
DR   iPTMnet; P00450; -.
DR   PhosphoSitePlus; P00450; -.
DR   SwissPalm; P00450; -.
DR   BioMuta; CP; -.
DR   DMDM; 116117; -.
DR   CPTAC; CPTAC-660; -.
DR   CPTAC; non-CPTAC-1093; -.
DR   CPTAC; non-CPTAC-1094; -.
DR   CPTAC; non-CPTAC-1095; -.
DR   jPOST; P00450; -.
DR   MassIVE; P00450; -.
DR   PaxDb; 9606-ENSP00000264613; -.
DR   PeptideAtlas; P00450; -.
DR   PRIDE; P00450; -.
DR   ProteomicsDB; 51251; -.
DR   Pumba; P00450; -.
DR   Antibodypedia; 861; 447 antibodies from 39 providers.
DR   DNASU; 1356; -.
DR   Ensembl; ENST00000264613.11; ENSP00000264613.6; ENSG00000047457.15.
DR   GeneID; 1356; -.
DR   KEGG; hsa:1356; -.
DR   MANE-Select; ENST00000264613.11; ENSP00000264613.6; NM_000096.4; NP_000087.2.
DR   UCSC; uc003ewy.6; human.
DR   AGR; HGNC:2295; -.
DR   ClinPGx; PA26815; -.
DR   CTD; 1356; -.
DR   DisGeNET; 1356; -.
DR   GeneCards; CP; -.
DR   GeneReviews; CP; -.
DR   HGNC; HGNC:2295; CP.
DR   HPA; ENSG00000047457; Tissue enriched (liver).
DR   MalaCards; CP; -.
DR   MIM; 117700; gene.
DR   MIM; 604290; phenotype.
DR   OpenTargets; ENSG00000047457; -.
DR   Orphanet; 48818; Aceruloplasminemia.
DR   VEuPathDB; HostDB:ENSG00000047457; -.
DR   eggNOG; KOG1263; Eukaryota.
DR   GeneTree; ENSGT00940000155866; -.
DR   InParanoid; P00450; -.
DR   OMA; AACDWNK; -.
DR   OrthoDB; 2121828at2759; -.
DR   PAN-GO; P00450; 2 GO annotations based on evolutionary models.
DR   PhylomeDB; P00450; -.
DR   BioCyc; MetaCyc:HS00590-MONOMER; -.
DR   BRENDA; 1.16.3.1; 2681.
DR   BRENDA; 1.16.3.4; 2681.
DR   PathwayCommons; P00450; -.
DR   Reactome; R-HSA-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR   Reactome; R-HSA-425410; Metal ion SLC transporters.
DR   Reactome; R-HSA-5619049; Defective SLC40A1 causes hemochromatosis 4 (HFE4) (macrophages).
DR   Reactome; R-HSA-5619060; Defective CP causes aceruloplasminemia (ACERULOP).
DR   Reactome; R-HSA-8957275; Post-translational protein phosphorylation.
DR   Reactome; R-HSA-917937; Iron uptake and transport.
DR   SABIO-RK; P00450; -.
DR   SignaLink; P00450; -.
DR   SIGNOR; P00450; -.
DR   Agora; ENSG00000047457; -.
DR   BioGRID-ORCS; 1356; 9 hits in 1151 CRISPR screens.
DR   CD-CODE; 91857CE7; Nucleolus.
DR   ChiTaRS; CP; human.
DR   EvolutionaryTrace; P00450; -.
DR   GeneWiki; Ceruloplasmin; -.
DR   GenomeRNAi; 1356; -.
DR   Pharos; P00450; Tbio.
DR   PRO; PR:P00450; -.
DR   Proteomes; UP000005640; Chromosome 3.
DR   RNAct; P00450; protein.
DR   Bgee; ENSG00000047457; Expressed in right lobe of liver and 156 other cell types or tissues.
DR   ExpressionAtlas; P00450; baseline and differential.
DR   GO; GO:0072562; C:blood microparticle; HDA:UniProtKB.
DR   GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR   GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR   GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR   GO; GO:0005765; C:lysosomal membrane; HDA:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR   GO; GO:0005507; F:copper ion binding; IEA:InterPro.
DR   GO; GO:0004322; F:ferroxidase activity; IDA:UniProtKB.
DR   GO; GO:0004602; F:glutathione peroxidase activity; IDA:UniProtKB.
DR   GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR   GO; GO:0016724; F:oxidoreductase activity, acting on metal ions, oxygen as acceptor; IDA:UniProtKB.
DR   GO; GO:0036479; F:peroxidase inhibitor activity; ISS:UniProtKB.
DR   GO; GO:0047066; F:phospholipid-hydroperoxide glutathione peroxidase activity; IDA:UniProtKB.
DR   GO; GO:0051087; F:protein-folding chaperone binding; IPI:BHF-UCL.
DR   GO; GO:0098869; P:cellular oxidant detoxification; ISS:UniProt.
DR   GO; GO:0006878; P:intracellular copper ion homeostasis; IDA:UniProtKB.
DR   GO; GO:0006879; P:intracellular iron ion homeostasis; IDA:UniProtKB.
DR   CDD; cd04222; CuRO_1_ceruloplasmin; 1.
DR   CDD; cd11021; CuRO_2_ceruloplasmin; 1.
DR   CDD; cd04224; CuRO_3_ceruloplasmin; 1.
DR   CDD; cd11022; CuRO_4_ceruloplasmin; 1.
DR   CDD; cd04225; CuRO_5_ceruloplasmin; 1.
DR   CDD; cd11012; CuRO_6_ceruloplasmin; 1.
DR   FunFam; 2.60.40.420:FF:000009; Ceruloplasmin; 1.
DR   FunFam; 2.60.40.420:FF:000015; Ceruloplasmin; 1.
DR   FunFam; 2.60.40.420:FF:000028; Ceruloplasmin; 1.
DR   FunFam; 2.60.40.420:FF:000033; Ceruloplasmin; 1.
DR   FunFam; 2.60.40.420:FF:000037; Ceruloplasmin; 1.
DR   Gene3D; 2.60.40.420; Cupredoxins - blue copper proteins; 5.
DR   InterPro; IPR048236; Ceruloplasmin-like_CuRO_5.
DR   InterPro; IPR011707; Cu-oxidase-like_N.
DR   InterPro; IPR001117; Cu-oxidase_2nd.
DR   InterPro; IPR011706; Cu-oxidase_C.
DR   InterPro; IPR045087; Cu-oxidase_fam.
DR   InterPro; IPR033138; Cu_oxidase_CS.
DR   InterPro; IPR002355; Cu_oxidase_Cu_BS.
DR   InterPro; IPR008972; Cupredoxin.
DR   PANTHER; PTHR11709:SF226; CERULOPLASMIN; 1.
DR   PANTHER; PTHR11709; MULTI-COPPER OXIDASE; 1.
DR   Pfam; PF00394; Cu-oxidase; 1.
DR   Pfam; PF07731; Cu-oxidase_2; 1.
DR   Pfam; PF07732; Cu-oxidase_3; 2.
DR   SUPFAM; SSF49503; Cupredoxins; 6.
DR   PROSITE; PS00079; MULTICOPPER_OXIDASE1; 3.
DR   PROSITE; PS00080; MULTICOPPER_OXIDASE2; 1.
DR   PCDDB; P00450; -.
PE   1: Evidence at protein level;
KW   3D-structure; Direct protein sequencing; Disulfide bond; Glycoprotein;
KW   Metal-binding; Neurodegeneration; Oxidoreductase; Phosphoprotein;
KW   Proteomics identification; Reference proteome; Repeat; Secreted; Signal.
FT   SIGNAL          1..19
FT                   /evidence="ECO:0000269|PubMed:6582496"
FT   CHAIN           20..1065
FT                   /note="Ceruloplasmin"
FT                   /id="PRO_0000002912"
FT   DOMAIN          20..200
FT                   /note="Plastocyanin-like 1"
FT                   /evidence="ECO:0000269|Ref.29, ECO:0007744|PDB:1KCW"
FT   DOMAIN          209..357
FT                   /note="Plastocyanin-like 2"
FT                   /evidence="ECO:0000269|Ref.29, ECO:0007744|PDB:1KCW"
FT   DOMAIN          370..560
FT                   /note="Plastocyanin-like 3"
FT                   /evidence="ECO:0000269|Ref.29, ECO:0007744|PDB:1KCW"
FT   DOMAIN          570..718
FT                   /note="Plastocyanin-like 4"
FT                   /evidence="ECO:0000269|Ref.29, ECO:0007744|PDB:1KCW"
FT   DOMAIN          730..900
FT                   /note="Plastocyanin-like 5"
FT                   /evidence="ECO:0000269|Ref.29, ECO:0007744|PDB:1KCW"
FT   DOMAIN          908..1061
FT                   /note="Plastocyanin-like 6"
FT                   /evidence="ECO:0000269|Ref.29, ECO:0007744|PDB:1KCW"
FT   ACT_SITE        699
FT                   /note="Nucleophile; for glutathione peroxidase activity"
FT                   /evidence="ECO:0000269|PubMed:10508415"
FT   BINDING         55
FT                   /ligand="Na(+)"
FT                   /ligand_id="ChEBI:CHEBI:29101"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000269|PubMed:17242517,
FT                   ECO:0000269|PubMed:23843990, ECO:0007744|PDB:2J5W,
FT                   ECO:0007744|PDB:4ENZ"
FT   BINDING         64
FT                   /ligand="Na(+)"
FT                   /ligand_id="ChEBI:CHEBI:29101"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000269|PubMed:17242517,
FT                   ECO:0000269|PubMed:23843990, ECO:0007744|PDB:2J5W,
FT                   ECO:0007744|PDB:4ENZ"
FT   BINDING         67
FT                   /ligand="Na(+)"
FT                   /ligand_id="ChEBI:CHEBI:29101"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000269|PubMed:17242517,
FT                   ECO:0000269|PubMed:23843990, ECO:0007744|PDB:2J5W,
FT                   ECO:0007744|PDB:4ENZ"
FT   BINDING         120
FT                   /ligand="Cu(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29036"
FT                   /ligand_label="1"
FT                   /note="type 2 copper site"
FT                   /evidence="ECO:0000269|PubMed:17242517,
FT                   ECO:0000269|PubMed:23843990, ECO:0000269|Ref.29,
FT                   ECO:0007744|PDB:1KCW, ECO:0007744|PDB:2J5W,
FT                   ECO:0007744|PDB:4EJX, ECO:0007744|PDB:4ENZ"
FT   BINDING         120
FT                   /ligand="O2"
FT                   /ligand_id="ChEBI:CHEBI:15379"
FT                   /evidence="ECO:0000269|PubMed:17242517,
FT                   ECO:0000269|PubMed:23843990, ECO:0007744|PDB:2J5W,
FT                   ECO:0007744|PDB:4ENZ"
FT   BINDING         122
FT                   /ligand="Cu(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29036"
FT                   /ligand_label="2"
FT                   /note="type 3 copper site"
FT                   /evidence="ECO:0000269|PubMed:17242517,
FT                   ECO:0000269|PubMed:23843990, ECO:0000269|Ref.29,
FT                   ECO:0007744|PDB:1KCW, ECO:0007744|PDB:2J5W,
FT                   ECO:0007744|PDB:4EJX, ECO:0007744|PDB:4ENZ"
FT   BINDING         128
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000269|PubMed:17242517,
FT                   ECO:0000269|PubMed:23843990, ECO:0007744|PDB:2J5W,
FT                   ECO:0007744|PDB:4ENZ"
FT   BINDING         143
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000269|PubMed:17242517,
FT                   ECO:0000269|PubMed:23843990, ECO:0007744|PDB:2J5W,
FT                   ECO:0007744|PDB:4ENZ"
FT   BINDING         146
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000269|PubMed:17242517,
FT                   ECO:0000269|PubMed:23843990, ECO:0007744|PDB:2J5W,
FT                   ECO:0007744|PDB:4ENZ"
FT   BINDING         147
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000269|PubMed:17242517,
FT                   ECO:0000269|PubMed:23843990, ECO:0007744|PDB:2J5W,
FT                   ECO:0007744|PDB:4ENZ"
FT   BINDING         180
FT                   /ligand="Cu(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29036"
FT                   /ligand_label="2"
FT                   /note="type 3 copper site"
FT                   /evidence="ECO:0000269|PubMed:17242517,
FT                   ECO:0000269|PubMed:23843990, ECO:0000269|Ref.29,
FT                   ECO:0007744|PDB:1KCW, ECO:0007744|PDB:2J5W,
FT                   ECO:0007744|PDB:4EJX, ECO:0007744|PDB:4ENZ"
FT   BINDING         180
FT                   /ligand="O2"
FT                   /ligand_id="ChEBI:CHEBI:15379"
FT                   /evidence="ECO:0000269|PubMed:17242517,
FT                   ECO:0000269|PubMed:23843990, ECO:0007744|PDB:2J5W,
FT                   ECO:0007744|PDB:4ENZ"
FT   BINDING         182
FT                   /ligand="Cu(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29036"
FT                   /ligand_label="3"
FT                   /note="type 3 copper site"
FT                   /evidence="ECO:0000269|PubMed:17242517,
FT                   ECO:0000269|PubMed:23843990, ECO:0000269|Ref.29,
FT                   ECO:0007744|PDB:1KCW, ECO:0007744|PDB:2J5W,
FT                   ECO:0007744|PDB:4EJX, ECO:0007744|PDB:4ENZ"
FT   BINDING         256
FT                   /ligand="Na(+)"
FT                   /ligand_id="ChEBI:CHEBI:29101"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000269|PubMed:17242517,
FT                   ECO:0000269|PubMed:23843990, ECO:0007744|PDB:2J5W,
FT                   ECO:0007744|PDB:4ENZ"
FT   BINDING         295
FT                   /ligand="Cu(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29036"
FT                   /ligand_label="4"
FT                   /note="type 1 copper site"
FT                   /evidence="ECO:0000269|PubMed:17242517,
FT                   ECO:0000269|PubMed:23843990, ECO:0000269|Ref.29,
FT                   ECO:0007744|PDB:1KCW, ECO:0007744|PDB:2J5W,
FT                   ECO:0007744|PDB:4ENZ"
FT   BINDING         338
FT                   /ligand="Cu(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29036"
FT                   /ligand_label="4"
FT                   /note="type 1 copper site"
FT                   /evidence="ECO:0000269|PubMed:17242517,
FT                   ECO:0000269|PubMed:23843990, ECO:0000269|Ref.29,
FT                   ECO:0007744|PDB:1KCW, ECO:0007744|PDB:2J5W,
FT                   ECO:0007744|PDB:4ENZ"
FT   BINDING         343
FT                   /ligand="Cu(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29036"
FT                   /ligand_label="4"
FT                   /note="type 1 copper site"
FT                   /evidence="ECO:0000269|PubMed:17242517,
FT                   ECO:0000269|PubMed:23843990, ECO:0000269|Ref.29,
FT                   ECO:0007744|PDB:1KCW, ECO:0007744|PDB:2J5W,
FT                   ECO:0007744|PDB:4ENZ"
FT   BINDING         408
FT                   /ligand="Na(+)"
FT                   /ligand_id="ChEBI:CHEBI:29101"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000269|PubMed:17242517,
FT                   ECO:0007744|PDB:2J5W"
FT   BINDING         417
FT                   /ligand="Na(+)"
FT                   /ligand_id="ChEBI:CHEBI:29101"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000269|PubMed:17242517,
FT                   ECO:0007744|PDB:2J5W"
FT   BINDING         420
FT                   /ligand="Na(+)"
FT                   /ligand_id="ChEBI:CHEBI:29101"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000269|PubMed:17242517,
FT                   ECO:0007744|PDB:2J5W"
FT   BINDING         617
FT                   /ligand="Na(+)"
FT                   /ligand_id="ChEBI:CHEBI:29101"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000269|PubMed:17242517,
FT                   ECO:0007744|PDB:2J5W"
FT   BINDING         656
FT                   /ligand="Cu(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29036"
FT                   /ligand_label="5"
FT                   /note="type 1 copper site"
FT                   /evidence="ECO:0000269|PubMed:17242517,
FT                   ECO:0000269|PubMed:23843990, ECO:0000269|Ref.29,
FT                   ECO:0007744|PDB:1KCW, ECO:0007744|PDB:2J5W,
FT                   ECO:0007744|PDB:4ENZ"
FT   BINDING         699
FT                   /ligand="Cu(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29036"
FT                   /ligand_label="5"
FT                   /note="type 1 copper site"
FT                   /evidence="ECO:0000269|PubMed:17242517,
FT                   ECO:0000269|PubMed:23843990, ECO:0000269|Ref.29,
FT                   ECO:0007744|PDB:1KCW, ECO:0007744|PDB:2J5W,
FT                   ECO:0007744|PDB:4ENZ"
FT   BINDING         704
FT                   /ligand="Cu(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29036"
FT                   /ligand_label="5"
FT                   /note="type 1 copper site"
FT                   /evidence="ECO:0000269|PubMed:17242517,
FT                   ECO:0000269|PubMed:23843990, ECO:0000269|Ref.29,
FT                   ECO:0007744|PDB:1KCW, ECO:0007744|PDB:2J5W,
FT                   ECO:0007744|PDB:4ENZ"
FT   BINDING         709
FT                   /ligand="Cu(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29036"
FT                   /ligand_label="5"
FT                   /note="type 1 copper site"
FT                   /evidence="ECO:0000269|PubMed:17242517,
FT                   ECO:0000269|PubMed:23843990, ECO:0000269|Ref.29,
FT                   ECO:0007744|PDB:1KCW, ECO:0007744|PDB:2J5W,
FT                   ECO:0007744|PDB:4ENZ"
FT   BINDING         767
FT                   /ligand="Na(+)"
FT                   /ligand_id="ChEBI:CHEBI:29101"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000269|PubMed:17242517,
FT                   ECO:0007744|PDB:2J5W"
FT   BINDING         776
FT                   /ligand="Na(+)"
FT                   /ligand_id="ChEBI:CHEBI:29101"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000269|PubMed:17242517,
FT                   ECO:0007744|PDB:2J5W"
FT   BINDING         779
FT                   /ligand="Na(+)"
FT                   /ligand_id="ChEBI:CHEBI:29101"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000269|PubMed:17242517,
FT                   ECO:0007744|PDB:2J5W"
FT   BINDING         955
FT                   /ligand="Na(+)"
FT                   /ligand_id="ChEBI:CHEBI:29101"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000269|PubMed:17242517,
FT                   ECO:0007744|PDB:2J5W"
FT   BINDING         994
FT                   /ligand="Cu(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29036"
FT                   /ligand_label="6"
FT                   /note="type 1 copper site"
FT                   /evidence="ECO:0000269|PubMed:17242517,
FT                   ECO:0000269|PubMed:23843990, ECO:0000269|Ref.29,
FT                   ECO:0007744|PDB:1KCW, ECO:0007744|PDB:2J5W,
FT                   ECO:0007744|PDB:4EJX, ECO:0007744|PDB:4ENZ"
FT   BINDING         997
FT                   /ligand="Cu(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29036"
FT                   /ligand_label="1"
FT                   /note="type 2 copper site"
FT                   /evidence="ECO:0000269|PubMed:17242517,
FT                   ECO:0000269|PubMed:23843990, ECO:0000269|Ref.29,
FT                   ECO:0007744|PDB:1KCW, ECO:0007744|PDB:2J5W,
FT                   ECO:0007744|PDB:4EJX, ECO:0007744|PDB:4ENZ"
FT   BINDING         997
FT                   /ligand="O2"
FT                   /ligand_id="ChEBI:CHEBI:15379"
FT                   /evidence="ECO:0000269|PubMed:17242517,
FT                   ECO:0000269|PubMed:23843990, ECO:0007744|PDB:2J5W,
FT                   ECO:0007744|PDB:4ENZ"
FT   BINDING         999
FT                   /ligand="Cu(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29036"
FT                   /ligand_label="3"
FT                   /note="type 3 copper site"
FT                   /evidence="ECO:0000269|PubMed:17242517,
FT                   ECO:0000269|PubMed:23843990, ECO:0000269|Ref.29,
FT                   ECO:0007744|PDB:1KCW, ECO:0007744|PDB:2J5W,
FT                   ECO:0007744|PDB:4EJX, ECO:0007744|PDB:4ENZ"
FT   BINDING         999
FT                   /ligand="O2"
FT                   /ligand_id="ChEBI:CHEBI:15379"
FT                   /evidence="ECO:0000269|PubMed:23843990,
FT                   ECO:0007744|PDB:4ENZ"
FT   BINDING         1039
FT                   /ligand="Cu(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29036"
FT                   /ligand_label="3"
FT                   /note="type 3 copper site"
FT                   /evidence="ECO:0000269|PubMed:17242517,
FT                   ECO:0000269|PubMed:23843990, ECO:0000269|Ref.29,
FT                   ECO:0007744|PDB:1KCW, ECO:0007744|PDB:2J5W,
FT                   ECO:0007744|PDB:4EJX, ECO:0007744|PDB:4ENZ"
FT   BINDING         1040
FT                   /ligand="Cu(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29036"
FT                   /ligand_label="6"
FT                   /note="type 1 copper site"
FT                   /evidence="ECO:0000269|PubMed:17242517,
FT                   ECO:0000269|PubMed:23843990, ECO:0000269|Ref.29,
FT                   ECO:0007744|PDB:1KCW, ECO:0007744|PDB:2J5W,
FT                   ECO:0007744|PDB:4EJX, ECO:0007744|PDB:4ENZ"
FT   BINDING         1041
FT                   /ligand="Cu(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29036"
FT                   /ligand_label="2"
FT                   /note="type 3 copper site"
FT                   /evidence="ECO:0000269|PubMed:17242517,
FT                   ECO:0000269|PubMed:23843990, ECO:0000269|Ref.29,
FT                   ECO:0007744|PDB:1KCW, ECO:0007744|PDB:2J5W,
FT                   ECO:0007744|PDB:4EJX, ECO:0007744|PDB:4ENZ"
FT   BINDING         1041
FT                   /ligand="O2"
FT                   /ligand_id="ChEBI:CHEBI:15379"
FT                   /evidence="ECO:0000269|PubMed:17242517,
FT                   ECO:0000269|PubMed:23843990, ECO:0007744|PDB:2J5W,
FT                   ECO:0007744|PDB:4ENZ"
FT   BINDING         1045
FT                   /ligand="Cu(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29036"
FT                   /ligand_label="6"
FT                   /note="type 1 copper site"
FT                   /evidence="ECO:0000269|PubMed:17242517,
FT                   ECO:0000269|PubMed:23843990, ECO:0000269|Ref.29,
FT                   ECO:0007744|PDB:1KCW, ECO:0007744|PDB:2J5W,
FT                   ECO:0007744|PDB:4ENZ"
FT   BINDING         1050
FT                   /ligand="Cu(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29036"
FT                   /ligand_label="6"
FT                   /note="type 1 copper site"
FT                   /evidence="ECO:0000269|PubMed:17242517,
FT                   ECO:0000269|PubMed:23843990, ECO:0000269|Ref.29,
FT                   ECO:0007744|PDB:1KCW, ECO:0007744|PDB:2J5W,
FT                   ECO:0007744|PDB:4ENZ"
FT   MOD_RES         722
FT                   /note="Phosphoserine; by FAM20C"
FT                   /evidence="ECO:0000269|PubMed:26091039"
FT   CARBOHYD        138
FT                   /note="N-linked (GlcNAc...) (complex) asparagine"
FT                   /evidence="ECO:0000269|PubMed:14760718,
FT                   ECO:0000269|PubMed:15084671, ECO:0000269|PubMed:16335952,
FT                   ECO:0000269|PubMed:17242517, ECO:0000269|PubMed:19139490,
FT                   ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:19838169,
FT                   ECO:0000269|PubMed:23843990, ECO:0000269|Ref.29,
FT                   ECO:0007744|PDB:1KCW, ECO:0007744|PDB:2J5W,
FT                   ECO:0007744|PDB:4EJX, ECO:0007744|PDB:4ENZ"
FT   CARBOHYD        358
FT                   /note="N-linked (GlcNAc...) (complex) asparagine"
FT                   /evidence="ECO:0000269|PubMed:16335952,
FT                   ECO:0000269|PubMed:19139490, ECO:0000269|PubMed:19159218,
FT                   ECO:0000269|PubMed:19838169"
FT   CARBOHYD        397
FT                   /note="N-linked (GlcNAc...) (complex) asparagine"
FT                   /evidence="ECO:0000269|PubMed:14760718,
FT                   ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:17242517,
FT                   ECO:0000269|PubMed:19139490, ECO:0000269|PubMed:19159218,
FT                   ECO:0000269|PubMed:19838169, ECO:0000269|PubMed:23843990,
FT                   ECO:0007744|PDB:2J5W, ECO:0007744|PDB:4EJX,
FT                   ECO:0007744|PDB:4ENZ"
FT   CARBOHYD        588
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:16335952"
FT   CARBOHYD        762
FT                   /note="N-linked (GlcNAc...) (complex) asparagine"
FT                   /evidence="ECO:0000269|PubMed:14760718,
FT                   ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:19139490,
FT                   ECO:0000269|PubMed:19159218, ECO:0000269|Ref.29,
FT                   ECO:0007744|PDB:1KCW"
FT   CARBOHYD        926
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:16335952"
FT   DISULFID        174..200
FT                   /evidence="ECO:0000269|PubMed:17242517, ECO:0000269|Ref.29,
FT                   ECO:0007744|PDB:1KCW, ECO:0007744|PDB:2J5W"
FT   DISULFID        276..357
FT                   /evidence="ECO:0000269|PubMed:17242517, ECO:0000269|Ref.29,
FT                   ECO:0007744|PDB:1KCW, ECO:0007744|PDB:2J5W"
FT   DISULFID        534..560
FT                   /evidence="ECO:0000269|PubMed:17242517, ECO:0000269|Ref.29,
FT                   ECO:0007744|PDB:1KCW, ECO:0007744|PDB:2J5W"
FT   DISULFID        637..718
FT                   /evidence="ECO:0000269|PubMed:17242517, ECO:0000269|Ref.29,
FT                   ECO:0007744|PDB:1KCW, ECO:0007744|PDB:2J5W"
FT   DISULFID        874..900
FT                   /evidence="ECO:0000269|PubMed:17242517, ECO:0000269|Ref.29,
FT                   ECO:0007744|PDB:1KCW, ECO:0007744|PDB:2J5W"
FT   VARIANT         63
FT                   /note="I -> T (retained in the endoplasmic reticulum;
FT                   dbSNP:rs759185877)"
FT                   /evidence="ECO:0000269|PubMed:15557511,
FT                   ECO:0000269|PubMed:16150804"
FT                   /id="VAR_025655"
FT   VARIANT         367
FT                   /note="R -> C (in dbSNP:rs34624984)"
FT                   /id="VAR_032815"
FT   VARIANT         477
FT                   /note="P -> L (in dbSNP:rs35331711)"
FT                   /evidence="ECO:0000269|PubMed:15557511"
FT                   /id="VAR_025656"
FT   VARIANT         544
FT                   /note="E -> D (no effect on the localization at the plasma
FT                   membrane; dbSNP:rs701753)"
FT                   /evidence="ECO:0000269|PubMed:15557511,
FT                   ECO:0000269|PubMed:16150804, ECO:0000269|PubMed:2873574"
FT                   /id="VAR_025657"
FT   VARIANT         551
FT                   /note="T -> I (in dbSNP:rs61733458)"
FT                   /evidence="ECO:0000269|PubMed:15557511"
FT                   /id="VAR_025658"
FT   VARIANT         793
FT                   /note="R -> H (no effect on the localization at the plasma
FT                   membrane; dbSNP:rs115552500)"
FT                   /evidence="ECO:0000269|PubMed:15557511,
FT                   ECO:0000269|PubMed:16150804"
FT                   /id="VAR_025659"
FT   VARIANT         841
FT                   /note="T -> R (in dbSNP:rs56033670)"
FT                   /evidence="ECO:0000269|PubMed:15557511"
FT                   /id="VAR_025660"
FT   CONFLICT        1060
FT                   /note="E -> EGEYP (in Ref. 6; AAA51975)"
FT                   /evidence="ECO:0000305"
FT   STRAND          21..36
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   TURN            49..52
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   HELIX           53..56
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   STRAND          58..61
FT                   /evidence="ECO:0007829|PDB:1KCW"
FT   STRAND          65..79
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   STRAND          82..84
FT                   /evidence="ECO:0007829|PDB:1KCW"
FT   HELIX           88..90
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   STRAND          97..100
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   STRAND          104..111
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   STRAND          113..115
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   STRAND          120..125
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   HELIX           128..130
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   HELIX           141..144
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   HELIX           145..147
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   STRAND          154..160
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   STRAND          173..180
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   HELIX           185..190
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   STRAND          194..200
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   STRAND          205..210
FT                   /evidence="ECO:0007829|PDB:2J5W"
FT   STRAND          214..225
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   HELIX           226..228
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   HELIX           232..239
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   HELIX           243..245
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   HELIX           251..257
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   STRAND          258..262
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   STRAND          274..276
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   STRAND          280..287
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   STRAND          295..301
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   STRAND          304..306
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   STRAND          309..312
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   STRAND          321..327
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   STRAND          332..338
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   HELIX           341..344
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   TURN            345..347
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   STRAND          349..355
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   STRAND          367..385
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   STRAND          389..391
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   TURN            392..395
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   STRAND          401..403
FT                   /evidence="ECO:0007829|PDB:1KCW"
FT   HELIX           406..409
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   STRAND          412..414
FT                   /evidence="ECO:0007829|PDB:1KCW"
FT   STRAND          418..427
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   STRAND          429..435
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   HELIX           444..446
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   STRAND          453..456
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   STRAND          459..471
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   STRAND          476..481
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   HELIX           484..486
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   STRAND          514..520
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   TURN            523..525
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   STRAND          529..531
FT                   /evidence="ECO:0007829|PDB:2J5W"
FT   STRAND          533..540
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   STRAND          542..544
FT                   /evidence="ECO:0007829|PDB:2J5W"
FT   HELIX           545..551
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   STRAND          554..560
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   STRAND          575..580
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   STRAND          582..586
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   HELIX           587..589
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   HELIX           593..600
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   HELIX           604..606
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   HELIX           612..617
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   STRAND          619..623
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   STRAND          635..637
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   STRAND          642..647
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   STRAND          656..660
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   STRAND          665..667
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   STRAND          670..677
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   STRAND          682..687
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   STRAND          693..699
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   HELIX           702..706
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   STRAND          710..716
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   STRAND          729..745
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   HELIX           750..759
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   TURN            766..768
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   TURN            771..773
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   STRAND          777..789
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   HELIX           800..805
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   STRAND          812..815
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   STRAND          818..826
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   STRAND          828..830
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   STRAND          835..838
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   STRAND          842..844
FT                   /evidence="ECO:0007829|PDB:1KCW"
FT   STRAND          854..860
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   HELIX           863..865
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   STRAND          869..871
FT                   /evidence="ECO:0007829|PDB:1KCW"
FT   STRAND          873..880
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   HELIX           885..890
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   STRAND          894..900
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   STRAND          913..924
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   HELIX           925..927
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   HELIX           931..938
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   HELIX           942..944
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   HELIX           950..955
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   STRAND          957..961
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   STRAND          973..975
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   STRAND          979..986
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   STRAND          994..998
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   STRAND          1003..1006
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   HELIX           1007..1009
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   STRAND          1011..1018
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   STRAND          1023..1028
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   STRAND          1034..1040
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   HELIX           1043..1047
FT                   /evidence="ECO:0007829|PDB:4ENZ"
FT   STRAND          1051..1057
FT                   /evidence="ECO:0007829|PDB:4ENZ"
SQ   SEQUENCE   1065 AA;  122219 MW;  2F2F76BB47D30F58 CRC64;
     MKILILGIFL FLCSTPAWAK EKHYYIGIIE TTWDYASDHG EKKLISVDTE HSNIYLQNGP
     DRIGRLYKKA LYLQYTDETF RTTIEKPVWL GFLGPIIKAE TGDKVYVHLK NLASRPYTFH
     SHGITYYKEH EGAIYPDNTT DFQRADDKVY PGEQYTYMLL ATEEQSPGEG DGNCVTRIYH
     SHIDAPKDIA SGLIGPLIIC KKDSLDKEKE KHIDREFVVM FSVVDENFSW YLEDNIKTYC
     SEPEKVDKDN EDFQESNRMY SVNGYTFGSL PGLSMCAEDR VKWYLFGMGN EVDVHAAFFH
     GQALTNKNYR IDTINLFPAT LFDAYMVAQN PGEWMLSCQN LNHLKAGLQA FFQVQECNKS
     SSKDNIRGKH VRHYYIAAEE IIWNYAPSGI DIFTKENLTA PGSDSAVFFE QGTTRIGGSY
     KKLVYREYTD ASFTNRKERG PEEEHLGILG PVIWAEVGDT IRVTFHNKGA YPLSIEPIGV
     RFNKNNEGTY YSPNYNPQSR SVPPSASHVA PTETFTYEWT VPKEVGPTNA DPVCLAKMYY
     SAVEPTKDIF TGLIGPMKIC KKGSLHANGR QKDVDKEFYL FPTVFDENES LLLEDNIRMF
     TTAPDQVDKE DEDFQESNKM HSMNGFMYGN QPGLTMCKGD SVVWYLFSAG NEADVHGIYF
     SGNTYLWRGE RRDTANLFPQ TSLTLHMWPD TEGTFNVECL TTDHYTGGMK QKYTVNQCRR
     QSEDSTFYLG ERTYYIAAVE VEWDYSPQRE WEKELHHLQE QNVSNAFLDK GEFYIGSKYK
     KVVYRQYTDS TFRVPVERKA EEEHLGILGP QLHADVGDKV KIIFKNMATR PYSIHAHGVQ
     TESSTVTPTL PGETLTYVWK IPERSGAGTE DSACIPWAYY STVDQVKDLY SGLIGPLIVC
     RRPYLKVFNP RRKLEFALLF LVFDENESWY LDDNIKTYSD HPEKVNKDDE EFIESNKMHA
     INGRMFGNLQ GLTMHVGDEV NWYLMGMGNE IDLHTVHFHG HSFQYKHRGV YSSDVFDIFP
     GTYQTLEMFP RTPGIWLLHC HVTDHIHAGM ETTYTVLQNE DTKSG
//