Copine-1 (CPNE1)

The protein contains 537 amino acids for an estimated molecular weight of 59059 Da.

 

Calcium-dependent phospholipid-binding protein that plays a role in calcium-mediated intracellular processes (PubMed:14674885). Involved in the TNF-alpha receptor signaling pathway in a calcium-dependent manner (PubMed:14674885). Exhibits calcium-dependent phospholipid binding properties (PubMed:9430674, PubMed:19539605). Plays a role in neuronal progenitor cell differentiation; induces neurite outgrowth via a AKT-dependent signaling cascade and calcium-independent manner (PubMed:23263657, PubMed:25450385). May recruit target proteins to the cell membrane in a calcium-dependent manner (PubMed:12522145). May function in membrane trafficking (PubMed:9430674). Involved in TNF-alpha-induced NF-kappa-B transcriptional repression by inducing endoprotease processing of the transcription factor NF-kappa-B p65/RELA subunit (PubMed:18212740). Also induces endoprotease processing of NF-kappa-B p50/NFKB1, p52/NFKB2, RELB and REL (PubMed:18212740). (updated: Nov. 22, 2017)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
  3. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  4. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  5. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.

This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.


Interpro domains
Total structural coverage: 0%
Model score: 0
No model available.

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VariantDescription
dbSNP:rs6579255
dbSNP:rs12481228
dbSNP:rs11543239

The reference OMIM entry for this protein is 604205

Copine i; cpne1
Cpn1

DESCRIPTION

Copines are a family of calcium-dependent lipid-binding proteins that are evolutionarily conserved from Arabidopsis to Homo sapiens. Copines are comprised of 2 N-terminal C2 domains (C2Ds) and a C-terminal A domain (AD). The C2Ds contain aspartate residues important for calcium and phospholipid binding (summary by Ramsey et al., 2008).

CLONING

To identify proteins that may underlie membrane trafficking processes in ciliates, Creutz et al. (1998) isolated calcium-dependent phospholipid-binding proteins from Paramecium. They named the major protein that they obtained 'copine' (pronounced 'ko-peen'), the French feminine noun meaning 'friend,' because it associates like a 'companion' with lipid membranes. Creutz et al. (1998) found that the 55-kD copine protein bound phosphatidylserine in a calcium- but not magnesium-dependent manner, but it did not bind phosphatidylcholine. Copine promoted calcium-dependent aggregation of lipid vesicles. Creutz et al. (1998) cloned partial cDNAs representing 2 distinct Paramecium copine genes. By searching sequence databases for genes with sequence similarity to the Paramecium copine genes, Creutz et al. (1998) identified human ESTs corresponding to 5 copine genes, named copine I to V. Two overlapping ESTs contained the complete copine I (CPNE1) coding sequence. The deduced 537-amino acid CPNE1 protein contains 2 type II C2 domains in its N-terminal half and a domain similar to the A domain, which is present in a number of extracellular proteins or the extracellular portions of membrane proteins, in its C-terminal half; it does not have a predicted signal sequence or transmembrane domains. C2 domains mediate calcium-dependent interactions with phospholipids, and the A domain of integrins appears to mediate the binding of the integrin to extracellular ligands. CPNE1 has a broad tissue distribution. Tomsig and Creutz (2000) cloned bovine Cpne1, and by EST database analysis, they identified human CPNE1. The deduced 537-amino acid human protein has a calculated molecular mass of 58.9 kD. Western blot analysis detected Cpne1 at an apparent molecular mass of 58 kD in all rat and bovine tissues examined. Purified bovine Cpne1 existed as a monomer in calcium-free solution.

GENE FUNCTION

Creutz et al (1998) found that recombinant CPNE1 expressed in bacteria exhibited calcium-dependent binding to phosphatidylserine vesicles. Antibody against CPNE1 reacted with bovine chromobindin-17, which is a 55-kD calcium-dependent chromaffin vesicle-binding protein, and the authors concluded that chromobindin-17 is a copine. They suggested that copines function in membrane trafficking.

MAPPING

Gross (2014) mapped the CPNE1 gene to chromosome 20q11.22 based on an alignment of the CPNE1 sequence (GenBank GENBANK BC001142) with the genomic sequence (GRCh37). ... More on the omim web site

Subscribe to this protein entry history

Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 604205 was added.