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Gene Review

NPTX2  -  neuronal pentraxin II

Homo sapiens

Synonyms: NARP, NP-II, NP2, Neuronal pentraxin II, Neuronal pentraxin-2
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Disease relevance of NPTX2

  • The effects of irradiation on cytokine production in glioma cell lines, NP1, NP2 and NP3, were studied [1].
  • The increased permeability and edema observed during the secretory phase in the primate endometrium may be mediated in part by VEGF-NP-2 interaction [2].
  • Expression of NP1 and NP2 was significantly higher in carcinomas than in benign tumors (P < .0001 and .0002, respectively) [3].
  • Male B27(+)NP1(+) rats had a significantly reduced prevalence of arthritis, compared with B27(+)NP- males or B27(+) males with a control construct, NP2, whereas colitis was not significantly affected by the NP1 transgene [4].
  • The selective binding of mitochondria-specific ZFPs to mtDNA was exemplified by targeting the T8993G mutation, which causes two mitochondrial diseases, neurogenic muscle weakness, ataxia, and retinitis pigmentosa (NARP) and also maternally inherited Leigh's syndrome [5].

Psychiatry related information on NPTX2

  • Concomitant loss of dynorphin, NARP, and orexin in narcolepsy [6].

High impact information on NPTX2

  • There was a derangement of mitochondrial Ca2+ homeostasis in MERRF, but not in NARP cells, whereas cytosolic Ca2+ responses were normal in both cell types [7].
  • These studies support a model in which Narp can regulate the latent synaptogenic activity of NP1 by forming mixed pentraxin assemblies [8].
  • Narp is a neuronal immediate early gene that plays a role in excitatory synaptogenesis [8].
  • The AVP-NPII gene, locating on chromosome 20, consists of three exons that encode putative signal peptide, AVP, NPII, and glycoprotein [9].
  • It was a G----A transition at nucleotide position 1859 in the second exon, resulting in a substitution of Gly for Ser at amino acid position 57 in the NPII moiety [9].

Chemical compound and disease context of NPTX2


Biological context of NPTX2


Anatomical context of NPTX2

  • Northern blot analysis reveals that NPII message is present in brain, testis, pancreas, liver, heart, and skeletal muscle, so, unlike NPI, NPII is not exclusively localized to neurons [12].
  • Fifth instar nymphs contain, in their salivary glands, four nitrophorins which have already been described in the literature (NP1, NP2, NP3 and NP4) [15].
  • These are the first data to specify the hormonal regulation and cell-specific expression of NP-1 and NP-2 mRNA in the endometrium of both women and nonhuman primates [2].
  • NP-2 mRNA, unlike NP-1, was expressed only by the endothelium of veins, and in these cells, its expression was hormonally regulated in the converse manner: it was very low during the proliferative phase and high during the secretory phase [2].
  • In addition, it was shown that fibroblasts from NARP subjects have a tendency to undergo apoptotic cell death, perhaps as a result of increased free radical production [16].

Associations of NPTX2 with chemical compounds

  • All four Rhodnius nitrophorins transport NO and sequester histamine through heme binding, but only NP2 acts as an anticoagulant [17].
  • The premature termination eliminates part of the C-terminal domain of NPII, including a cysteine residue in position 85, which could be involved in the correct folding of the prohormone [18].
  • All affected individuals presented a missense mutation (G1757-->A) that replaces glycine at position 23 with arginine within the NPII domain [19].
  • Competitive elutions of radiolabeled bovine neurophysin II (NPII) from the affinity matrices Met-Tyr-Phe-omega-(amino-hexyl)- [and (aminobutyl)-] agarose were performed with increasing concentrations of either of the soluble ligands oxytocin or lysine-vasopressin [20].
  • The significantly slower Ca(2+) influx rates observed in 98% NARP and rho(0), in comparison to parental cells, indicates that proper actin cytoskeletal organization is important for CCE in these cells [21].

Physical interactions of NPTX2

  • Here, we report that native Narp in brain is part of a pentraxin complex that includes NP1 [8].

Other interactions of NPTX2

  • Other newly identified long pentraxins are constitutively expressed proteins associated with sperm-egg fusion (apexin/p50), may function at the neuronal synapse (neuronal pentraxin I, NPI), or may serve yet other, unknown functions (NPII and XL-PXN1) [22].
  • Identification of two distinct mutations at the same nucleotide position, concomitantly with a novel polymorphism in the vasopressin-neurophysin II gene (AVP-NP II) in two dutch families with familial neurohypophyseal diabetes insipidus [23].

Analytical, diagnostic and therapeutic context of NPTX2


  1. Effects of irradiation on cytokine production in glioma cell lines. Yamanaka, R., Tanaka, R., Yoshida, S. Neurol. Med. Chir. (Tokyo) (1993) [Pubmed]
  2. Cellular expression and hormonal regulation of neuropilin-1 and -2 messenger ribonucleic Acid in the human and rhesus macaque endometrium. Germeyer, A., Hamilton, A.E., Laughlin, L.S., Lasley, B.L., Brenner, R.M., Giudice, L.C., Nayak, N.R. J. Clin. Endocrinol. Metab. (2005) [Pubmed]
  3. Expression of semaphorins, vascular endothelial growth factor, and their common receptor neuropilins and alleic loss of semaphorin locus in epithelial ovarian neoplasms: increased ratio of vascular endothelial growth factor to semaphorin is a poor prognostic factor in ovarian carcinomas. Osada, R., Horiuchi, A., Kikuchi, N., Ohira, S., Ota, M., Katsuyama, Y., Konishi, I. Hum. Pathol. (2006) [Pubmed]
  4. The specificity of peptides bound to human histocompatibility leukocyte antigen (HLA)-B27 influences the prevalence of arthritis in HLA-B27 transgenic rats. Zhou, M., Sayad, A., Simmons, W.A., Jones, R.C., Maika, S.D., Satumtira, N., Dorris, M.L., Gaskell, S.J., Bordoli, R.S., Sartor, R.B., Slaughter, C.A., Richardson, J.A., Hammer, R.E., Taurog, J.D. J. Exp. Med. (1998) [Pubmed]
  5. Sequence-specific modification of mitochondrial DNA using a chimeric zinc finger methylase. Minczuk, M., Papworth, M.A., Kolasinska, P., Murphy, M.P., Klug, A. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  6. Concomitant loss of dynorphin, NARP, and orexin in narcolepsy. Crocker, A., España, R.A., Papadopoulou, M., Saper, C.B., Faraco, J., Sakurai, T., Honda, M., Mignot, E., Scammell, T.E. Neurology (2005) [Pubmed]
  7. A calcium signaling defect in the pathogenesis of a mitochondrial DNA inherited oxidative phosphorylation deficiency. Brini, M., Pinton, P., King, M.P., Davidson, M., Schon, E.A., Rizzuto, R. Nat. Med. (1999) [Pubmed]
  8. Narp and NP1 form heterocomplexes that function in developmental and activity-dependent synaptic plasticity. Xu, D., Hopf, C., Reddy, R., Cho, R.W., Guo, L., Lanahan, A., Petralia, R.S., Wenthold, R.J., O'Brien, R.J., Worley, P. Neuron (2003) [Pubmed]
  9. A single base substitution in the coding region for neurophysin II associated with familial central diabetes insipidus. Ito, M., Mori, Y., Oiso, Y., Saito, H. J. Clin. Invest. (1991) [Pubmed]
  10. A novel mutation in the preprovasopressin gene identified in a kindred with autosomal dominant neurohypophyseal diabetes insipidus. Wahlstrom, J.T., Fowler, M.J., Nicholson, W.E., Kovacs, W.J. J. Clin. Endocrinol. Metab. (2004) [Pubmed]
  11. The expanding clinical spectrum of mitochondrial diseases. De Vivo, D.C. Brain Dev. (1993) [Pubmed]
  12. Human neuronal pentraxin II (NPTX2): conservation, genomic structure, and chromosomal localization. Hsu, Y.C., Perin, M.S. Genomics (1995) [Pubmed]
  13. Mouse and human neuronal pentraxin 1 (NPTX1): conservation, genomic structure, and chromosomal localization. Omeis, I.A., Hsu, Y.C., Perin, M.S. Genomics (1996) [Pubmed]
  14. Characterization of a new alternatively spliced neuropilin-1 isoform. Tao, Q., Spring, S.C., Terman, B.I. Angiogenesis (2003) [Pubmed]
  15. Changes in salivary nitrophorin profile during the life cycle of the blood-sucking bug Rhodnius prolixus. Moreira, M.F., Coelho, H.S., Zingali, R.B., Oliveira, P.L., Masuda, H. Insect Biochem. Mol. Biol. (2003) [Pubmed]
  16. The mtDNA T8993G (NARP) mutation results in an impairment of oxidative phosphorylation that can be improved by antioxidants. Mattiazzi, M., Vijayvergiya, C., Gajewski, C.D., DeVivo, D.C., Lenaz, G., Wiedmann, M., Manfredi, G. Hum. Mol. Genet. (2004) [Pubmed]
  17. The crystal structure of nitrophorin 2. A trifunctional antihemostatic protein from the saliva of Rhodnius prolixus. Andersen, J.F., Montfort, W.R. J. Biol. Chem. (2000) [Pubmed]
  18. Identification of a novel nonsense mutation and a missense substitution in the vasopressin-neurophysin II gene in two Spanish kindreds with familial neurohypophyseal diabetes insipidus. Calvo, B., Bilbao, J.R., Urrutia, I., Eizaguirre, J., Gaztambide, S., Castaño, L. J. Clin. Endocrinol. Metab. (1998) [Pubmed]
  19. Molecular analysis in familial neurohypophyseal diabetes insipidus: early diagnosis of an asymptomatic carrier. Calvo, B., Bilbao, J.R., Rodríguez, A., Rodríguez-Arnao, M.D., Castaño, L. J. Clin. Endocrinol. Metab. (1999) [Pubmed]
  20. Interdependence of neurophysin self-association and neuropeptide hormone binding as expressed by quantitative affinity chromatography. Angal, S., Chaiken, I.M. Biochemistry (1982) [Pubmed]
  21. Influence of a mitochondrial genetic defect on capacitative calcium entry and mitochondrial organization in the osteosarcoma cells. Szczepanowska, J., Zabłocki, K., Duszyński, J. FEBS Lett. (2004) [Pubmed]
  22. Long pentraxins: an emerging group of proteins with diverse functions. Goodman, A.R., Cardozo, T., Abagyan, R., Altmeyer, A., Wisniewski, H.G., Vilcek, J. Cytokine Growth Factor Rev. (1996) [Pubmed]
  23. Identification of two distinct mutations at the same nucleotide position, concomitantly with a novel polymorphism in the vasopressin-neurophysin II gene (AVP-NP II) in two dutch families with familial neurohypophyseal diabetes insipidus. Abbes, A.P., Bruggeman, B., van Den Akker, E.L., de Groot, M.R., Franken, A.A., Drexhage, V.R., Engel, H. Clin. Chem. (2000) [Pubmed]
  24. Structural determinants of factor IX(a) binding in nitrophorin 2, a lipocalin inhibitor of the intrinsic coagulation pathway. Gudderra, N.P., Ribeiro, J.M., Andersen, J.F. J. Biol. Chem. (2005) [Pubmed]
  25. Impaired ATP synthase assembly associated with a mutation in the human ATP synthase subunit 6 gene. Nijtmans, L.G., Henderson, N.S., Attardi, G., Holt, I.J. J. Biol. Chem. (2001) [Pubmed]
  26. A novel point mutation in the translation initiation codon of the pre-pro-vasopressin-neurophysin II gene: cosegregation with morphological abnormalities and clinical symptoms in autosomal dominant neurohypophyseal diabetes insipidus. Rutishauser, J., Böni-Schnetzler, M., Böni, J., Wichmann, W., Huisman, T., Vallotton, M.B., Froesch, E.R. J. Clin. Endocrinol. Metab. (1996) [Pubmed]
  27. Autosomal dominant neurohypophyseal diabetes insipidus in a Swiss family, caused by a novel mutation (C59Delta/A60W) in the neurophysin moiety of prepro-vasopressin-neurophysin II (AVP-NP II). Flück, C.E., Deladoëy, J., Nayak, S., Zeller, O., Kopp, P., Mullis, P.E. Eur. J. Endocrinol. (2001) [Pubmed]
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