| Literature References | 1. HOFER, M., PAGLIUSI, S.R., HOHN, A., LEIBROCK, J. AND BARDE, Y.A.
Regional distribution of brain-derived neurotrophic factor messenger RNA in
the adult mouse brain.
EMBO J. 9(8) 2459-2464 (1990).
2. KOYAMA, J.I., INOUE, S., IKEDA, K. AND HAYASHI, K.
Purification and amino acid sequence of a nerve growth factor from the
venom of Vipera russelli russelli.
BIOCHIM.BIOPHYS.ACTA 1160 287-292 (1992).
3. INOUE, S., ODA, T., KOYAMA, J., IKEDA, K. AND HAYASHI, K.
Amino acid sequences of nerve growth factors derived from cobra venoms.
FEBS LETT. 279(1) 38-40 (1991).
4. KOSTIZA, T. AND MEIER, J.
Nerve growth factors from snake venoms: chemical properties, mode of action
and biological significance.
TOXICON 34 787-806 (1996).
5. KATZIR, I., SHANI, J., GOSHEN, G., SELA, J., NINARY, E., DOGNOVSKI, A.,
SHABASHOV, D., INOUE, S., IKEDA, K., HAYASHI, K., GORINSTEIN, S.,
DEUTSCH, J. AND LAZAROVICI, P.
Characterization of nerve growth factors (NGFs) from snake venoms by use of
a novel, quantitative bioassay utilizing pheochromocytoma (PC12) cells
overexpressing human trkA receptors.
TOXICON 42 481-490 (2003).
6. KUKHTINA, V., TSETLIN, V., UTKIN, Y., INOZEMTSEVA, L. AND GRIVENNIKOV, I.
Two forms of nerve growth factor from cobra venom prevent the death of PC12
cells in serum-free medium.
J.NAT.TOXINS 10 9-16 (2001).
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| Documentation | During the development of the vertebrate nervous system, many neurons
become redundant (because they have died, failed to connect to target
cells, etc.) and are eliminated. At the same time, developing neurons send
out axon outgrowths that contact their target cells [1]. Such cells control
their degree of innervation (the number of axon connections) by the
secretion of various specific neurotrophic factors that are essential for
neuron survival. One of these is nerve growth factor (NGF), which is
involved in the survival of some classes of embryonic neuron (e.g., peri-
pheral sympathetic neurons) [1]. NGF is mostly found outside the central
nervous system (CNS), but slight traces have been detected in adult CNS
tissues, although a physiological role for this is unknown [1]; it has also
been found in several snake venoms [2,3]. Proteins similar to NGF include
brain-derived neurotrophic factor (BDNF) and neurotrophins 3 to 7, all of
which demonstrate neuron survival and outgrowth activities.
In contrast to mammalian NGFs, which exist as multimeric complexes of
alpha, beta and gamma subunits, snake venom NGFs exist almost exclusively
as beta-chains [4]. They act as low-potency neurotrophic tyrosine kinase
receptor type 1 (NTRK1; also called TrkA) agonists [5], and have been shown
to promote survival and differentiation of cultured cells [6].
VENOMNGF is a 4-element fingerprint that provides a signature for the venom
nerve growth factors. The fingerprint was derived from an initial alignment
of 4 sequences: the motifs were drawn from conserved regions in the
N-terminal half of the alignment, focusing on those sections that
characterise the snake venom nerve growth factors but distinguish them from
other closely related NGF beta subunits. Two iterations on SPTR55_38f were
required to reach convergence, at which point a true set comprising 29
sequences was identified.
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