CP

Protein identityUniProt · HPA

UniProt accession

P00450

Gene

CP

Ensembl

ENSG00000047457

Chromosome

3

Canonical length

1065 aa

Protein class

Cancer-related genes, Candidate cardiovascular disease genes, Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Plasma proteins, Potential drug targets, Predicted intracellular proteins, Predicted secreted proteins, Transporters

Secretome location

Secreted to blood

OverviewNCBI Gene

The protein encoded by this gene is a metalloprotein that binds most of the copper in plasma and is involved in the peroxidation of Fe(II)transferrin to Fe(III) transferrin. Mutations in this gene cause aceruloplasminemia, which results in iron accumulation and tissue damage, and is associated with diabetes and neurologic abnormalities. Two transcript variants, one protein-coding and the other not protein-coding, have been found for this gene. [provided by RefSeq, Feb 2012]

Canonical amino-acid sequenceUniProt

1065 residues, UniProt reviewed canonical sequence.

>P00450|CP
     1  MKILILGIFL FLCSTPAWAK EKHYYIGIIE TTWDYASDHG EKKLISVDTE HSNIYLQNGP
    61  DRIGRLYKKA LYLQYTDETF RTTIEKPVWL GFLGPIIKAE TGDKVYVHLK NLASRPYTFH
   121  SHGITYYKEH EGAIYPDNTT DFQRADDKVY PGEQYTYMLL ATEEQSPGEG DGNCVTRIYH
   181  SHIDAPKDIA SGLIGPLIIC KKDSLDKEKE KHIDREFVVM FSVVDENFSW YLEDNIKTYC
   241  SEPEKVDKDN EDFQESNRMY SVNGYTFGSL PGLSMCAEDR VKWYLFGMGN EVDVHAAFFH
   301  GQALTNKNYR IDTINLFPAT LFDAYMVAQN PGEWMLSCQN LNHLKAGLQA FFQVQECNKS
   361  SSKDNIRGKH VRHYYIAAEE IIWNYAPSGI DIFTKENLTA PGSDSAVFFE QGTTRIGGSY
   421  KKLVYREYTD ASFTNRKERG PEEEHLGILG PVIWAEVGDT IRVTFHNKGA YPLSIEPIGV
   481  RFNKNNEGTY YSPNYNPQSR SVPPSASHVA PTETFTYEWT VPKEVGPTNA DPVCLAKMYY
   541  SAVEPTKDIF TGLIGPMKIC KKGSLHANGR QKDVDKEFYL FPTVFDENES LLLEDNIRMF
   601  TTAPDQVDKE DEDFQESNKM HSMNGFMYGN QPGLTMCKGD SVVWYLFSAG NEADVHGIYF
   661  SGNTYLWRGE RRDTANLFPQ TSLTLHMWPD TEGTFNVECL TTDHYTGGMK QKYTVNQCRR
   721  QSEDSTFYLG ERTYYIAAVE VEWDYSPQRE WEKELHHLQE QNVSNAFLDK GEFYIGSKYK
   781  KVVYRQYTDS TFRVPVERKA EEEHLGILGP QLHADVGDKV KIIFKNMATR PYSIHAHGVQ
   841  TESSTVTPTL PGETLTYVWK IPERSGAGTE DSACIPWAYY STVDQVKDLY SGLIGPLIVC
   901  RRPYLKVFNP RRKLEFALLF LVFDENESWY LDDNIKTYSD HPEKVNKDDE EFIESNKMHA
   961  INGRMFGNLQ GLTMHVGDEV NWYLMGMGNE IDLHTVHFHG HSFQYKHRGV YSSDVFDIFP
  1021  GTYQTLEMFP RTPGIWLLHC HVTDHIHAGM ETTYTVLQNE DTKSG

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against CP can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Secreted

Secreted

Yes

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.2

Highest tissue expression

1,750 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about CP.

Disease | AllUniProt

Conditions CP is implicated in, by any mechanism.

• Aceruloplasminemia (ACEP) MIM:604290

Disease | GeneticClinVar

99 pathogenic / likely-pathogenic of 784 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Deficiency of ferroxidase
• Neurodegeneration with brain iron accumulation
• CP-related disorder
• Inborn genetic diseases
• Thyroid cancer, nonmedullary, 1

Disease | ImmuneIEDB

Conditions an epitope on CP was assayed in.

• rheumatoid arthritis B cell

ReferencesPubMed · IEDB

Publications for CP from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.65

gnomAD pLI

0

gnomAD missense Z

0.22

DepMap mean gene effect

0.06

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• intracellular copper ion homeostasis
• intracellular iron ion homeostasis

Molecular functions

• copper ion binding
• ferroxidase activity
• glutathione peroxidase activity
• oxidoreductase activity
• phospholipid-hydroperoxide glutathione peroxidase activity
• protein-folding chaperone binding
• oxidoreductase activity, acting on metal ions, oxygen as acceptor

Cellular components

• blood microparticle
• endoplasmic reticulum lumen
• extracellular exosome
• extracellular region
• extracellular space
• lysosomal membrane
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• Multicopper oxidase, copper-binding site
• Cupredoxin
• Multicopper oxidase, C-terminal
• Multicopper oxidase-like, N-terminal
• Multicopper oxidases, conserved site
• Multicopper oxidase
• Ceruloplasmin-like, fifth cupredoxin domain
• Multicopper oxidase
• Multicopper oxidase
• Multicopper oxidase, second cupredoxin domain
• Multicopper oxidase

KeywordsUniProt

• Disulfide bond
• Glycoprotein
• Metal-binding
• Oxidoreductase
• Phosphoprotein
• Repeat
• Secreted
• Signal

InteractionsUniProt · HPA

Protein binding partners of CP in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• LTF
• MPO