Dihydropyrimidinase-related protein 2 (DPYSL2)

The protein contains 572 amino acids for an estimated molecular weight of 62294 Da.

 

Plays a role in neuronal development and polarity, as well as in axon growth and guidance, neuronal growth cone collapse and cell migration. Necessary for signaling by class 3 semaphorins and subsequent remodeling of the cytoskeleton. May play a role in endocytosis. (updated: April 1, 2015)

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.

This protein is annotated as membranous in Gene Ontology.


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

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VariantDescription
dbSNP:rs2228979
a colorectal cancer sample

The reference OMIM entry for this protein is 602463

Dihydropyrimidinase-like 2; dpysl2
Dihydropyrimidinase-related protein 2; drp2
Collapsin response mediator protein 2; crmp2

DESCRIPTION

The DPYSL2 gene encodes a cytosolic phosphoprotein that can act as a mediator of growth cone collapse as well as modify axon number, length, and neuronal polarity (summary by Brittain et al., 2011).

CLONING

Hamajima et al. (1996) isolated a human cDNA encoding dihydropyrimidinase-like 2 (DPYSL2), called DRP2 by them, from a fetal brain cDNA library (see 222748). The DPYSL2 protein has 572 amino acids. Northern blot analysis detected a 4.9-kb DPYSL2 transcript in all tissues examined except liver.

GENE FUNCTION

Using several mammalian cell lines and expression constructs, Fukata et al. (2002) found that Crmp2 preferentially bound tubulin (see 602529) dimers rather than microtubules. The binding property of Crmp2 with tubulin was distinct from that of Tau (157140). In neurons, overexpression of Crmp2 promoted axonal growth and branching. A Crmp2 mutant lacking the region responsible for microtubule assembly inhibited axonal growth and branching in a dominant-negative manner. Fukata et al. (2002) concluded that Crmp2 regulates axonal growth and branching as a partner of the tubulin heterodimer in a manner that differs from other microtubule-associated proteins. Yoshimura et al. (2005) showed that GSK3-beta (605004) phosphorylated CRMP2 at thr514 and inactivated it. Expression of the nonphosphorylated form of CRMP2 or inhibition of GSK3-beta induced the formation of multiple axon-like neurites in hippocampal neurons. Expression of constitutively active GSK3-beta impaired neuronal polarization, whereas the nonphosphorylated form of CRMP2 counteracted the inhibitory effects of GSK3-beta, indicating that GSK3-beta regulates neuronal polarity through phosphorylation of CRMP2. Treatment of hippocampal neurons with neurotrophin-3 (NT3; 162660) induced inactivation of GSK3-beta and dephosphorylation of CRMP2. Knockdown of CRMP2 inhibited NT3-induced axon outgrowth. These results suggested that NT3 decreases phosphorylated CRMP2 and increases nonphosphorylated active CRMP2, thereby promoting axon outgrowth. Using RT-PCR, flow cytometry, and Western blot analysis, Vincent et al. (2005) found that CRMP2 was expressed in neural and T-lymphocyte cell lines, CD4- and CD8-positive peripheral blood T cells, monocytes, and B cells. Immunofluorescence microscopy showed that CRMP2 expression redistributed to the uropod of IL2 (147680)-polarized T cells. Blockade of CRMP2 expression with short interfering RNA inhibited chemokine- but not semaphorin-directed lymphocyte transmigration. Patients affected with HTLV-1-associated myelopathy (HAM; 159580) had increased T-lymphocyte transmigration activity and increased expression of CRMP2. Vincent et al. (2005) proposed that CRMP2 has a role in pathogenesis of neuroinflammatory disease. CRMP2 interacts with and modulates the CaV2.2 calcium channel (CACNA1B; 601012). Overexpression of CRMP2 leads to increased surface expression of CaV2.2 on neurons, enhanced calcium currents, and an increase in stimulated release of the neuropeptide calcitonin gene-related peptide (CGRP; 114130) from dorsal root ganglia (summary by Brittain et al., 2011).

MAPPING

Hamajima et al. (1996) noted that 3 ESTs mapped to chromosome 8p21 by Koyama et al. (1995) correspond to a portion of the coding region of DPYSL2.

ANIMAL MODEL

In rats, Brittain et al. (2011) demonstrated that inflammatory and neuropathic hypersensitivity can be suppressed by a synthetic 15-mer peptide (CBD3) ... More on the omim web site

Subscribe to this protein entry history

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 602463 was added.

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

Jan. 24, 2016: Protein entry updated
Automatic update: model status changed