2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNP)

The protein contains 421 amino acids for an estimated molecular weight of 47579 Da.

 

May participate in RNA metabolism in the myelinating cell, CNP is the third most abundant protein in central nervous system myelin. (updated: Sept. 12, 2018)

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. Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
  5. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  6. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
  7. Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.

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.
Protein sequence (FASTA)
Protein coevolution profile (FreeContact)
Multiple Sequence Alignment (Muscle)

This protein is annotated as membranous in Gene Ontology.


Interpro domains
Total structural coverage: 63%
Model score: 0
No model available.

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VariantDescription
dbSNP:rs34353668

No binding partner found

The reference OMIM entry for this protein is 123830

Cyclic nucleotide phosphodiesterase; cnp
Cnp1
2-prime,3-prime @cyclic nucleotide 3-prime phosphohydrolase

CLONING

Cyclic nucleotide phosphodiesterase is a useful marker of myelin. CNPase is a membrane-bound enzyme found at high concentrations in central nervous system myelin and in the outer segments of photoreceptors in the retina (Vogel and Thompson, 1988). Two proteins with CNP activity are known to exist in brain and lymphoid tissues. They appear to be the products of distinct but related mRNA species. Kurihara et al. (1990) showed that the 2 gene products can arise by translation of 2 mRNAs alternatively spliced from a single transcript. In bovine and human brain, there appears to be a single species of mRNA (Vogel and Thompson, 1988), and the bovine brain and retinal forms of the enzyme appear to be identical in sequence. By Northern blot analysis, Miyoshi et al. (2001) determined that mouse Cnp1 was expressed as a major 2.5-kb transcript and a minor 2.3-kb transcript. Highest expression was in brain, followed by liver, lung, spleen, and heart, with little to no expression in the other tissues examined.

GENE FUNCTION

Bifulco et al. (2002) demonstrated that CNP is firmly associated with tubulin (602529) from brain tissue and thyroid cells. They showed that CNP acts as a microtubule-associated protein in promoting microtubule assembly. This activity was found to reside in the C terminus of the enzyme. The authors concluded that CNP is a membrane-bound microtubule-associated protein that can link tubulin to membranes and may regulate cytoplasmic microtubule distribution.

GENE STRUCTURE

Douglas et al. (1992) used human CNP cDNAs to isolate genomic clones containing the CNP gene which they found to be 9 kb long, with 4 exons separated by 3 introns. Using human CNP cDNA as probes, Monoh et al. (1993) isolated genomic DNA clones. Restriction mapping and sequence analysis demonstrated that the human CNP gene is about 8.5 kb long. There are 2 transcription start points and, in human brain, 2 forms of CNP mRNA are produced from a single gene by alternative splicing, similar to the mouse. Miyoshi et al. (2001) determined that the mouse Cnp1 gene contains 4 exons and spans 6.8 kb.

MAPPING

Using cDNA probes corresponding to CNP, Bernier et al. (1988) assigned CNP genes to chromosomes 3 and 11 in the mouse. The gene on chromosome 11 is closely linked to the GFAP locus (137780). Using a human partial cDNA to clone a genomic library, Douglas et al. (1991, 1992) isolated a clone containing the entire structural gene for human CNPase and constructed primers for polymerase chain reaction (PCR) analysis of a panel of somatic cell hybrids, which showed that only hybrids containing human chromosome 17 produced a PCR product. By fluorescence in situ hybridization, they showed that the gene is located at 17q21. Neither method showed evidence of a gene on human chromosome 1 in an area homologous to chromosome 3 of the mouse. Sprinkle et al. (1992) confirmed the assignment of CNP to chromosome 17 by PCR used with 2 somatic cell hybrid DNA panels. They identified an intron C-to-T polymorphism at nucleotide 1215 that might be useful in mapping the CNP gene more precisely within chromosome 17. Sprinkle et al. (1993) refined the assignment of CNP on chromosome 17 by a 2-step strategy. First, dot blots containing DNA from the parents of 10 three-generation families were screened to identify informative families. Second, 53 members of 4 selected families were typed at this locus. In these 4 families, 29 sibs carried a tota ... More on the omim web site

Subscribe to this protein entry history

Oct. 19, 2018: Protein entry updated
Automatic update: OMIM entry 123830 was added.

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).