Chronophin (PDXP)

The protein contains 296 amino acids for an estimated molecular weight of 31698 Da.

 

Functions as a pyridoxal phosphate (PLP) phosphatase, which also catalyzes the dephosphorylation of pyridoxine 5'-phosphate (PNP) and pyridoxamine 5'-phosphate (PMP), with order of substrate preference PLP > PNP > PMP and therefore plays a role in vitamin B6 metabolism (PubMed:14522954, PubMed:8132548). Also functions as a protein serine phosphatase that specifically dephosphorylates 'Ser-3' in proteins of the actin-depolymerizing factor (ADF)/cofilin family like CFL1 and DSTN. Thereby, regulates cofilin-dependent actin cytoskeleton reorganization, being required for normal progress through mitosis and normal cytokinesis. Does not dephosphorylate phosphothreonines in LIMK1. Does not dephosphorylate peptides containing phosphotyrosine (PubMed:15580268). (updated: June 2, 2021)

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.
  6. 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 UniProt.


Interpro domains
Total structural coverage: 100%
Model score: 100
No model available.

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The reference OMIM entry for this protein is 609246

Pyridoxal phosphatase; pdxp
Plp phosphatase
Chronophin; cin

DESCRIPTION

Pyridoxal 5-prime-phosphate (PLP) is the active form of vitamin B6 that acts as a coenzyme in maintaining biochemical homeostasis. The preferred degradation route from PLP to 4-pyridoxic acid involves the dephosphorylation of PLP by PDXP (Jang et al., 2003).

CLONING

By searching an EST database for sequences similar to tryptic fragments of purified erythrocyte PDXP, followed by PCR of a brain cDNA library, Jang et al. (2003) cloned PDXP, which they called PLP phosphatase. The deduced 296-amino acid protein has a calculated molecular mass of 31.7 kD. PDXP contains 2 N-glycosylation sites, 7 phosphorylation sites, and 4 N-myristoylation sites. Gel filtration analysis showed that recombinant PDXP expressed in E. coli formed dimers of about 60 kD. Northern blot analysis detected a 2.1-kb transcript expressed at variable levels in all adult tissues examined. RNA dot blot analysis detected ubiquitous expression, with highest levels in fetal brain and all adult brain regions examined. High expression was also detected in liver and testis. Jang et al. (2003) also cloned mouse Pdxp, which encodes a deduced 292-amino acid protein that shares 94% identity with human PDXP. Gohla et al. (2005) cloned human PDXP, which they called chronophin, by searching databases using the bovine sequence and RT-PCR of HeLa cell RNA. They derived the name chronophin from 'chronos,' the Greek word for time, because the protein seemed to regulate cofilin (see 601442)-dependent actin dynamics in a temporal and spatial manner. The deduced protein contains motifs characteristic of haloacid dehalogenases. Endogenous PDXP partially colocalized with F-actin and cofilin in membrane ruffles and lamellipodia. It showed a dynamic localization during the cell cycle, with strong colocalization with cofilin at constricting cleavage furrows during cytokinesis.

GENE FUNCTION

By expression in E. coli, Jang et al. (2003) obtained catalytically active PDXP that showed highest phosphatase activity toward PLP and required a divalent ion, preferably Mg(2+). PDXP had lower catalytic activity against pyridoxine 5-prime-phosphate and pyridoxamine 5-prime-phosphate, and very low activity against p-nitrophenyl phosphate. Gohla et al. (2005) demonstrated that recombinant PDXP hydrolyzed p-nitrophenyl phosphate in a concentration-dependent manner. Mutation of a conserved catalytic residue, asp25, inactivated the enzyme. PDXP dephosphorylated ser3 of cofilin in a concentration-dependent manner, but it was inactive against several other phosphorylated protein and peptide substrates. Overexpression of PDXP in HeLa cells decreased the steady-state levels of phosphorylated cofilin. Overexpression also caused dissolution of cortical actin cytoskeletons and reduced stress fiber content. Catalytically inactive PDXP functioned as a dominant-negative phosphatase when overexpressed, increasing phosphorylated cofilin levels and actin polymerization. Depletion of endogenous PDXP levels with RNA interference increased phosphorylated cofilin levels, elevated total cellular F-actin content, and stabilized membrane protrusions and stress fibers. Gohla et al. (2005) concluded that PDXP has a role in cofilin-mediated actin reorganization.

GENE STRUCTURE

Jang et al. (2003) determined that the coding region of the PDXP gene is contained within 2 exons.

MAPPING

By genomic sequence analysis, Jang et al. (2003) mapped the PDXP gene to chromosome 22q12. ... More on the omim web site

Subscribe to this protein entry history

July 1, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.

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

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 609246 was added.

Jan. 28, 2016: Protein entry updated
Automatic update: model status changed

Jan. 25, 2016: Protein entry updated
Automatic update: model status changed