| 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. WLODAWER, A., HODGSON, K. AND SHOOTER, E.
Crystallization of nerve growth factor from mouse submaxillary glands.
PROC.NATL.ACAD.SCI.U.S.A. 72 777-779 (1975).
5. WIESMANN, C. AND DE VOS, A.
Nerve growth factor: structure and function.
CELL.MOL.LIFE SCI. 58 748-759 (2001).
6. KURUVILLA, R., ZWEIFEL, L., GLEBOVA, N., LONZE, B., VALDEZ, G., YE, H.
AND GINTY, D.
A neurotrophin signaling cascade coordinates sympathetic neuron development
through differential control of TrkA trafficking and retrograde signaling.
CELL 118 243-255 (2004).
7. 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).
8. EINARSDOTTIR, E., CARLSSON, A., MINDE, J., TOOLANEN, G., SVENSSON, O.,
SOLDERS, G., HOLMGREN, G., HOLMBERG, D. AND HOLMBERG, M.
A mutation in the nerve growth factor beta gene (NGFB) causes loss of pain
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HUM.MOL.GENET. 13 799-805 (2004).
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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.
Although NGF was originally identified in snake venom, its most abundant
and best studied source is the submaxillary gland of adult male mice [4].
Mouse NGF is a high molecular weight hexamer, composed of 2 subunits each
of alpha, beta and gamma polypeptides. The beta subunit (NGF-beta) is
responsible for the physiological activity of the complex [4].
NGF-beta induces its cell survival effects through activation of
neurotrophic tyrosine kinase receptor type 1 (NTRK1; also called TrkA), and
can induce cell death by binding to the low affinity nerve growth factor
receptor, p75NTR [5]. The neurotophin has been shown to be involved in
sympathetic axon growth and innervation of target fields [6].
Mammalian NGF-beta tend to be higher potency NTRK1 agonsits than their
snake venom counterparts [7]. In humans, NGF-beta gene mutations can cause
a loss of pain perception [8].
MAMLNGFBETA is a 3-element fingerprint that provides a signature for the
mammalian nerve growth factor beta subunit. The fingerprint was derived from
an initial alignment of 2 sequences: the motifs were drawn from conserved
regions in the N-terminal quarter of the alignment, within the propeptide,
focusing on those sections that characterise the mammalian 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 12 sequences was identified.
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