ID   A5PL27_HUMAN            Unreviewed;      1065 AA.
AC   A5PL27;
DT   10-JUL-2007, integrated into UniProtKB/TrEMBL.
DT   10-JUL-2007, sequence version 1.
DT   02-SEP-2026, entry version 144.
DE   RecName: Full=Ceruloplasmin {ECO:0000256|ARBA:ARBA00072777};
DE            EC=1.11.1.27 {ECO:0000256|ARBA:ARBA00026115};
DE            EC=1.11.1.9 {ECO:0000256|ARBA:ARBA00012310};
DE            EC=1.16.3.1 {ECO:0000256|ARBA:ARBA00013107};
DE            EC=1.16.3.4 {ECO:0000256|ARBA:ARBA00038978};
DE   AltName: Full=Cuproxidase ceruloplasmin {ECO:0000256|ARBA:ARBA00082571};
DE   AltName: Full=Ferroxidase ceruloplasmin {ECO:0000256|ARBA:ARBA00080685};
DE   AltName: Full=Glutathione peroxidase ceruloplasmin {ECO:0000256|ARBA:ARBA00077782};
DE   AltName: Full=Glutathione-dependent peroxiredoxin ceruloplasmin {ECO:0000256|ARBA:ARBA00078105};
GN   Name=CP {ECO:0000313|EMBL:AAI42715.1};
GN   ORFNames=hCG_1781201 {ECO:0000313|EMBL:EAW78882.1};
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 {ECO:0000313|EMBL:AAI42715.1};
RN   [1] {ECO:0000313|EMBL:EAW78882.1}
RP   NUCLEOTIDE SEQUENCE.
RX   PubMed=11181995; DOI=10.1126/science.1058040;
RA   Venter J.C., Adams M.D., Myers E.W., Li P.W., Mural R.J., Sutton G.G.,
RA   Smith H.O., Yandell M., Evans C.A., Holt R.A., Gocayne J.D., Amanatides P.,
RA   Ballew R.M., Huson D.H., Wortman J.R., Zhang Q., Kodira C.D., Zheng X.H.,
RA   Chen L., Skupski M., Subramanian G., Thomas P.D., Zhang J.,
RA   Gabor Miklos G.L., Nelson C., Broder S., Clark A.G., Nadeau J.,
RA   McKusick V.A., Zinder N., Levine A.J., Roberts R.J., Simon M., Slayman C.,
RA   Hunkapiller M., Bolanos R., Delcher A., Dew I., Fasulo D., Flanigan M.,
RA   Florea L., Halpern A., Hannenhalli S., Kravitz S., Levy S., Mobarry C.,
RA   Reinert K., Remington K., Abu-Threideh J., Beasley E., Biddick K.,
RA   Bonazzi V., Brandon R., Cargill M., Chandramouliswaran I., Charlab R.,
RA   Chaturvedi K., Deng Z., Di Francesco V., Dunn P., Eilbeck K.,
RA   Evangelista C., Gabrielian A.E., Gan W., Ge W., Gong F., Gu Z., Guan P.,
RA   Heiman T.J., Higgins M.E., Ji R.R., Ke Z., Ketchum K.A., Lai Z., Lei Y.,
RA   Li Z., Li J., Liang Y., Lin X., Lu F., Merkulov G.V., Milshina N.,
RA   Moore H.M., Naik A.K., Narayan V.A., Neelam B., Nusskern D., Rusch D.B.,
RA   Salzberg S., Shao W., Shue B., Sun J., Wang Z., Wang A., Wang X., Wang J.,
RA   Wei M., Wides R., Xiao C., Yan C., Yao A., Ye J., Zhan M., Zhang W.,
RA   Zhang H., Zhao Q., Zheng L., Zhong F., Zhong W., Zhu S., Zhao S.,
RA   Gilbert D., Baumhueter S., Spier G., Carter C., Cravchik A., Woodage T.,
RA   Ali F., An H., Awe A., Baldwin D., Baden H., Barnstead M., Barrow I.,
RA   Beeson K., Busam D., Carver A., Center A., Cheng M.L., Curry L.,
RA   Danaher S., Davenport L., Desilets R., Dietz S., Dodson K., Doup L.,
RA   Ferriera S., Garg N., Gluecksmann A., Hart B., Haynes J., Haynes C.,
RA   Heiner C., Hladun S., Hostin D., Houck J., Howland T., Ibegwam C.,
RA   Johnson J., Kalush F., Kline L., Koduru S., Love A., Mann F., May D.,
RA   McCawley S., McIntosh T., McMullen I., Moy M., Moy L., Murphy B.,
RA   Nelson K., Pfannkoch C., Pratts E., Puri V., Qureshi H., Reardon M.,
RA   Rodriguez R., Rogers Y.H., Romblad D., Ruhfel B., Scott R., Sitter C.,
RA   Smallwood M., Stewart E., Strong R., Suh E., Thomas R., Tint N.N., Tse S.,
RA   Vech C., Wang G., Wetter J., Williams S., Williams M., Windsor S.,
RA   Winn-Deen E., Wolfe K., Zaveri J., Zaveri K., Abril J.F., Guigo R.,
RA   Campbell M.J., Sjolander K.V., Karlak B., Kejariwal A., Mi H., Lazareva B.,
RA   Hatton T., Narechania A., Diemer K., Muruganujan A., Guo N., Sato S.,
RA   Bafna V., Istrail S., Lippert R., Schwartz R., Walenz B., Yooseph S.,
RA   Allen D., Basu A., Baxendale J., Blick L., Caminha M., Carnes-Stine J.,
RA   Caulk P., Chiang Y.H., Coyne M., Dahlke C., Mays A., Dombroski M.,
RA   Donnelly M., Ely D., Esparham S., Fosler C., Gire H., Glanowski S.,
RA   Glasser K., Glodek A., Gorokhov M., Graham K., Gropman B., Harris M.,
RA   Heil J., Henderson S., Hoover J., Jennings D., Jordan C., Jordan J.,
RA   Kasha J., Kagan L., Kraft C., Levitsky A., Lewis M., Liu X., Lopez J.,
RA   Ma D., Majoros W., McDaniel J., Murphy S., Newman M., Nguyen T., Nguyen N.,
RA   Nodell M., Pan S., Peck J., Peterson M., Rowe W., Sanders R., Scott J.,
RA   Simpson M., Smith T., Sprague A., Stockwell T., Turner R., Venter E.,
RA   Wang M., Wen M., Wu D., Wu M., Xia A., Zandieh A., Zhu X.;
RT   "The sequence of the human genome.";
RL   Science 291:1304-1351(2001).
RN   [2] {ECO:0000313|EMBL:AAI42715.1}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RA   Gerhard D.S., Wagner L., Feingold E.A., Shenmen C.M., Grouse L.H.,
RA   Schuler G., Klein S.L., Old S., Rasooly R., Good P., Guyer M., Peck A.M.,
RA   Derge J.G., Lipman D., Collins F.S., Jang W., Sherry S., Feolo M.,
RA   Misquitta L., Lee E., Rotmistrovsky K., Greenhut S.F., Schaefer C.F.,
RA   Buetow K., Bonner T.I., Haussler D., Kent J., Kiekhaus M., Furey T.,
RA   Brent M., Prange C., Schreiber K., Shapiro N., Bhat N.K., Hopkins R.F.,
RA   Hsie F., Driscoll T., Soares M.B., Casavant T.L., Scheetz T.E.,
RA   Brown-stein M.J., Usdin T.B., Toshiyuki S., Carninci P., Piao Y.,
RA   Dudekula D.B., Ko M.S., Kawakami K., Suzuki Y., Sugano S., Gruber C.E.,
RA   Smith M.R., Simmons B., Moore T., Waterman R., Johnson S.L., Ruan Y.,
RA   Wei C.L., Mathavan S., Gunaratne P.H., Wu J., Garcia A.M., Hulyk S.W.,
RA   Fuh E., Yuan Y., Sneed A., Kowis C., Hodgson A., Muzny D.M., McPherson J.,
RA   Gibbs R.A., Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S.,
RA   Sanchez A., Whiting M., Madari A., Young A.C., Wetherby K.D., Granite S.J.,
RA   Kwong P.N., Brinkley C.P., Pearson R.L., Bouffard G.G., Blakesly R.W.,
RA   Green E.D., Dickson M.C., Rodriguez A.C., Grimwood J., Schmutz J.,
RA   Myers R.M., Butterfield Y.S., Griffith M., Griffith O.L., Krzywinski M.I.,
RA   Liao N., Morin R., Morrin R., Palmquist D., Petrescu A.S., Skalska U.,
RA   Smailus D.E., Stott J.M., Schnerch A., Schein J.E., Jones S.J., Holt R.A.,
RA   Baross A., Marra M.A., Clifton S., Makowski K.A., Bosak S., Malek J.;
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   [3] {ECO:0000313|EMBL:EAW78882.1}
RP   NUCLEOTIDE SEQUENCE.
RA   Mural R.J., Istrail S., Sutton 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.
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. Copper ions provide a large number
CC       of enzymatic activites. Oxidizes highly toxic ferrous ions to the
CC       ferric state for further incorporation onto apo-transferrins, catalyzes
CC       Cu(+) oxidation and promotes the oxidation of biogenic amines such as
CC       norepinephrin and serotonin. Provides Cu(2+) ions for the ascorbate-
CC       mediated deaminase degradation of the heparan sulfate chains of GPC1.
CC       Has glutathione peroxidase-like activity, can remove both hydrogen
CC       peroxide and lipid hydroperoxide in the presence of thiols. Acts as an
CC       inhibitor of the peroxidase activity of MPO. Also shows NO-oxidase and
CC       NO2 synthase activities that determine endocrine NO homeostasis.
CC       {ECO:0000256|ARBA:ARBA00096239}.
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:0000256|ARBA:ARBA00036108};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16834;
CC         Evidence={ECO:0000256|ARBA:ARBA00036108};
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:0000256|ARBA:ARBA00048092};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:30084;
CC         Evidence={ECO:0000256|ARBA:ARBA00048092};
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:0000256|ARBA:ARBA00052510};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:11150;
CC         Evidence={ECO:0000256|ARBA:ARBA00052510};
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:0000256|ARBA:ARBA00050279};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:78540;
CC         Evidence={ECO:0000256|ARBA:ARBA00050279};
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:0000256|ARBA:ARBA00050220};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62633;
CC         Evidence={ECO:0000256|ARBA:ARBA00050220};
CC   -!- COFACTOR:
CC       Name=Cu(2+); Xref=ChEBI:CHEBI:29036;
CC         Evidence={ECO:0000256|ARBA:ARBA00001973};
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:0000256|ARBA:ARBA00062165}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000256|ARBA:ARBA00004613}.
CC   -!- SIMILARITY: Belongs to the multicopper oxidase family.
CC       {ECO:0000256|ARBA:ARBA00010609}.
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DR   EMBL; BC142714; AAI42715.1; -; mRNA.
DR   EMBL; BC146663; AAI46664.1; -; mRNA.
DR   EMBL; CH471052; EAW78882.1; -; Genomic_DNA.
DR   RefSeq; NP_000087.2; NM_000096.4.
DR   AlphaFoldDB; A5PL27; -.
DR   SMR; A5PL27; -.
DR   PeptideAtlas; A5PL27; -.
DR   DNASU; 1356; -.
DR   GeneID; 1356; -.
DR   KEGG; hsa:1356; -.
DR   ClinPGx; PA26815; -.
DR   CTD; 1356; -.
DR   DisGeNET; 1356; -.
DR   OrthoDB; 2121828at2759; -.
DR   BioGRID-ORCS; 1356; 9 hits in 1151 CRISPR screens.
DR   ChiTaRS; CP; human.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0005765; C:lysosomal membrane; HDA:UniProtKB.
DR   GO; GO:0005507; F:copper ion binding; IEA:InterPro.
DR   GO; GO:0004322; F:ferroxidase activity; IEA:UniProtKB-EC.
DR   GO; GO:0004602; F:glutathione peroxidase activity; IEA:UniProtKB-EC.
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.
PE   2: Evidence at transcript level;
KW   Disulfide bond {ECO:0000256|ARBA:ARBA00023157};
KW   Glycoprotein {ECO:0000256|ARBA:ARBA00023180};
KW   Metal-binding {ECO:0000256|ARBA:ARBA00022723};
KW   Oxidoreductase {ECO:0000256|ARBA:ARBA00023002};
KW   Repeat {ECO:0000256|ARBA:ARBA00022737};
KW   Secreted {ECO:0000256|ARBA:ARBA00022525};
KW   Signal {ECO:0000256|ARBA:ARBA00022729, ECO:0000256|SAM:SignalP}.
FT   SIGNAL          1..19
FT                   /evidence="ECO:0000256|SAM:SignalP"
FT   CHAIN           20..1065
FT                   /note="Ceruloplasmin"
FT                   /evidence="ECO:0000256|SAM:SignalP"
FT                   /id="PRO_5014296989"
FT   DOMAIN          92..202
FT                   /note="Plastocyanin-like"
FT                   /evidence="ECO:0000259|Pfam:PF07732"
FT   DOMAIN          222..357
FT                   /note="Plastocyanin-like"
FT                   /evidence="ECO:0000259|Pfam:PF00394"
FT   DOMAIN          807..867
FT                   /note="Plastocyanin-like"
FT                   /evidence="ECO:0000259|Pfam:PF07732"
FT   DOMAIN          956..1057
FT                   /note="Plastocyanin-like"
FT                   /evidence="ECO:0000259|Pfam:PF07731"
SQ   SEQUENCE   1065 AA;  122205 MW;  2F2F1294E2D30F58 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
     SAVDPTKDIF 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
//