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Gene Review

DPYSL2  -  dihydropyrimidinase-like 2

Homo sapiens

Synonyms: CRMP-2, CRMP2, Collapsin response mediator protein 2, DHPRP2, DRP-2, ...
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Disease relevance of DPYSL2


Psychiatry related information on DPYSL2


High impact information on DPYSL2

  • GSK-3beta regulates phosphorylation of CRMP-2 and neuronal polarity [7].
  • We previously showed that collapsin response mediator protein-2 (CRMP-2) is critical for specifying axon/dendrite fate, possibly by promoting neurite elongation via microtubule assembly [7].
  • The expression of the nonphosphorylated form of CRMP-2 or inhibition of GSK-3beta induced the formation of multiple axon-like neurites in hippocampal neurons [7].
  • We found that Numb was associated with L1, a neuronal cell adhesion molecule that is endocytosed and recycled at the growth cone, where CRMP-2 and Numb were colocalized [8].
  • CRMP-2 regulates polarized Numb-mediated endocytosis for axon growth [8].

Chemical compound and disease context of DPYSL2


Biological context of DPYSL2


Anatomical context of DPYSL2

  • We suggest that CRMP-2 functions by regulating the dynamics of microtubules [1].
  • Furthermore, some cells exhibited intranuclear inclusions, which were labeled with antibodies to CRMP-2 and tubulin [1].
  • In the presence of Sema3A, these oligodendrocytes displayed a dramatic reduction in process extension, which was reversed by removal of Sema3A and prevented by anti-neuropilin-1, anti-Ulip6/CRMP5, anti-Ulip2/CRMP2 antibodies, or VEGF-165, another neuropilin-1 ligand [12].
  • The knockdown of CRMP-2 and kinesin-1 delocalized Sra-1 and WAVE1 from the growth cones of axons [13].
  • The phosphorylation of this particular portion carboxyl-terminal to the basic region of CRMP-2 may play an important role in regulating its activity, and may be involved in the formation of degenerating neurites in AD brain [14].

Associations of DPYSL2 with chemical compounds


Enzymatic interactions of DPYSL2

  • Using this antibody, we found that Rho-kinase phosphorylated CRMP-2 downstream of Rho in COS7 cells [2].

Regulatory relationships of DPYSL2

  • GDNF-mediated CRMP-2 expression was regulated mainly by the extracellular regulated kinase (ERK) pathway, but was independent of activation of phosphatidylinositol 3-kinase and Src family kinases [18].

Other interactions of DPYSL2

  • Collapsin response mediator protein-2 (CRMP-2) is a member of the CRMP/TOAD/Ulip/DRP family of cytosolic phosphoproteins involved in neuronal differentiation and axonal guidance [1].
  • The constructed evolutionary tree also implies that the vertebrate small and simple structured gene encoding a Dp71-like protein, called DRP2 , evolved from the dystrophin/utrophin ancestral large and complex gene by a duplication of only a small part of the gene [19].
  • As expected, the CRMP-2 protein accumulated in extended neurites of TGW cells treated with GDNF [18].
  • Serum IgG in all cases bound to recombinant CRMP-5 (predominantly N-terminal epitopes), but not to human CRMP-2 or CRMP-3 [20].
  • However, neuritogenesis of TGW cells was mostly dependent on Src family kinase activity and not ERK activity, indicating that the increased expression of CRMP-2 alone was not sufficient for neuritogenesis [18].

Analytical, diagnostic and therapeutic context of DPYSL2


  1. Evidence that collapsin response mediator protein-2 is involved in the dynamics of microtubules. Gu, Y., Ihara, Y. J. Biol. Chem. (2000) [Pubmed]
  2. Phosphorylation of collapsin response mediator protein-2 by Rho-kinase. Evidence for two separate signaling pathways for growth cone collapse. Arimura, N., Inagaki, N., Chihara, K., Ménager, C., Nakamura, N., Amano, M., Iwamatsu, A., Goshima, Y., Kaibuchi, K. J. Biol. Chem. (2000) [Pubmed]
  3. Expression of the dihydropyrimidinase related protein 2 (DRP-2) in Down syndrome and Alzheimer's disease brain is downregulated at the mRNA and dysregulated at the protein level. Lubec, G., Nonaka, M., Krapfenbauer, K., Gratzer, M., Cairns, N., Fountoulakis, M. J. Neural Transm. Suppl. (1999) [Pubmed]
  4. Identification of collapsin response mediator protein-2 as a potential marker of colorectal carcinoma by comparative analysis of cancer cell secretomes. Wu, C.C., Chen, H.C., Chen, S.J., Liu, H.P., Hsieh, Y.Y., Yu, C.J., Tang, R., Hsieh, L.L., Yu, J.S., Chang, Y.S. Proteomics (2008) [Pubmed]
  5. Proteomic identification of oxidatively modified proteins in Alzheimer's disease brain. Part II: dihydropyrimidinase-related protein 2, alpha-enolase and heat shock cognate 71. Castegna, A., Aksenov, M., Thongboonkerd, V., Klein, J.B., Pierce, W.M., Booze, R., Markesbery, W.R., Butterfield, D.A. J. Neurochem. (2002) [Pubmed]
  6. No association between the dihydropyrimidinase-related protein 2 (DRP-2) gene and bipolar disorder in humans. Nakata, K., Ujike, H., Tanaka, Y., Takaki, M., Sakai, A., Nomura, A., Katsu, T., Uchida, N., Imamura, T., Fujiwara, Y., Hamamura, T., Kuroda, S. Neurosci. Lett. (2003) [Pubmed]
  7. GSK-3beta regulates phosphorylation of CRMP-2 and neuronal polarity. Yoshimura, T., Kawano, Y., Arimura, N., Kawabata, S., Kikuchi, A., Kaibuchi, K. Cell (2005) [Pubmed]
  8. CRMP-2 regulates polarized Numb-mediated endocytosis for axon growth. Nishimura, T., Fukata, Y., Kato, K., Yamaguchi, T., Matsuura, Y., Kamiguchi, H., Kaibuchi, K. Nat. Cell Biol. (2003) [Pubmed]
  9. All-trans-retinoic acid inhibits collapsin response mediator protein-2 transcriptional activity during SH-SY5Y neuroblastoma cell differentiation. Fontán-Gabás, L., Oliemuller, E., Martínez-Irujo, J.J., de Miguel, C., Rouzaut, A. FEBS J. (2007) [Pubmed]
  10. The human dihydropyrimidinase-related protein 2 gene on chromosome 8p21 is associated with paranoid-type schizophrenia. Nakata, K., Ujike, H., Sakai, A., Takaki, M., Imamura, T., Tanaka, Y., Kuroda, S. Biol. Psychiatry (2003) [Pubmed]
  11. Dihydropyrimidinase-related protein 2 (DRP-2) gene and association to deficit and nondeficit schizophrenia. Hong, L.E., Wonodi, I., Avila, M.T., Buchanan, R.W., McMahon, R.P., Mitchell, B.D., Stine, O.C., Carpenter, W.T., Thaker, G.K. Am. J. Med. Genet. B Neuropsychiatr. Genet. (2005) [Pubmed]
  12. Isolation and expression pattern of human Unc-33-like phosphoprotein 6/collapsin response mediator protein 5 (Ulip6/CRMP5): coexistence with Ulip2/CRMP2 in Sema3a- sensitive oligodendrocytes. Ricard, D., Rogemond, V., Charrier, E., Aguera, M., Bagnard, D., Belin, M.F., Thomasset, N., Honnorat, J. J. Neurosci. (2001) [Pubmed]
  13. CRMP-2 is involved in kinesin-1-dependent transport of the Sra-1/WAVE1 complex and axon formation. Kawano, Y., Yoshimura, T., Tsuboi, D., Kawabata, S., Kaneko-Kawano, T., Shirataki, H., Takenawa, T., Kaibuchi, K. Mol. Cell. Biol. (2005) [Pubmed]
  14. Neurofibrillary tangle-associated collapsin response mediator protein-2 (CRMP-2) is highly phosphorylated on Thr-509, Ser-518, and Ser-522. Gu, Y., Hamajima, N., Ihara, Y. Biochemistry (2000) [Pubmed]
  15. Collapsin response mediator protein-2 inhibits neuronal phospholipase D(2) activity by direct interaction. Lee, S., Kim, J.H., Lee, C.S., Kim, J.H., Kim, Y., Heo, K., Ihara, Y., Goshima, Y., Suh, P.G., Ryu, S.H. J. Biol. Chem. (2002) [Pubmed]
  16. Comparative proteome analysis of the hippocampus implicates chromosome 6q in schizophrenia. Edgar, P.F., Douglas, J.E., Cooper, G.J., Dean, B., Kydd, R., Faull, R.L. Mol. Psychiatry (2000) [Pubmed]
  17. Disease-specific alterations in frontal cortex brain proteins in schizophrenia, bipolar disorder, and major depressive disorder. The Stanley Neuropathology Consortium. Johnston-Wilson, N.L., Sims, C.D., Hofmann, J.P., Anderson, L., Shore, A.D., Torrey, E.F., Yolken, R.H. Mol. Psychiatry (2000) [Pubmed]
  18. Induction of CRMP-2 by GDNF and analysis of the CRMP-2 promoter region. Kodama, Y., Murakumo, Y., Ichihara, M., Kawai, K., Shimono, Y., Takahashi, M. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  19. A sea urchin gene encoding dystrophin-related proteins. Wang, J., Pansky, A., Venuti, J.M., Yaffe, D., Nudel, U. Hum. Mol. Genet. (1998) [Pubmed]
  20. CRMP-5 neuronal autoantibody: marker of lung cancer and thymoma-related autoimmunity. Yu, Z., Kryzer, T.J., Griesmann, G.E., Kim, K., Benarroch, E.E., Lennon, V.A. Ann. Neurol. (2001) [Pubmed]
  21. An investigation of the dihydropyrimidinase-like 2 (DPYSL2) gene in schizophrenia: genetic association study and expression analysis. Zhao, X., Tang, R., Xiao, Z., Shi, Y., Feng, G., Gu, N., Shi, J., Xing, Y., Yan, L., Sang, H., Zhu, S., Liu, H., Chen, W., Liu, J., Tang, W., Zhang, J., He, L. Int. J. Neuropsychopharmacol. (2006) [Pubmed]
  22. Association of dystrophin-related protein 2 (DRP2) with postsynaptic densities in rat brain. Roberts, R.G., Sheng, M. Mol. Cell. Neurosci. (2000) [Pubmed]
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