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PR01925

Identifier
MAMLNGFBETA  [View Relations]  [View Alignment]  
Accession
PR01925
No. of Motifs
3
Creation Date
03-APR-2008
Title
Mammalian nerve growth factor beta subunit signature
Database References
PRINTS; PR00268 NGF; PR01913 NGFBETA
PDB; 1BET; 1BTG; 1SGF; 1WWW; 1SG1; 2IFG
SCOP; 1BET; 1BTG; 1SGF; 1WWW; 1SG1; 2IFG
CATH; 1BET; 1BTG; 1SGF; 1WWW; 1SG1; 2IFG
MIM; 162030
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
perception.
HUM.MOL.GENET. 13 799-805 (2004).

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.
Summary Information
12 codes involving  3 elements
0 codes involving 2 elements
Composite Feature Index
3121212
2000
123
True Positives
A1A4E5_HUMAN  NGF_BOVIN     NGF_CAVPO     NGF_GORGO     
NGF_HUMAN NGF_MOUSE NGF_PANTR NGF_PONPY
NGF_PRANA NGF_RAT NGF_SAIBB Q6LDU8_MOUSE
Sequence Titles
A1A4E5_HUMAN Nerve growth factor, beta polypeptide - Homo sapiens (Human). 
NGF_BOVIN Beta-nerve growth factor precursor (Beta-NGF) - Bos taurus (Bovine).
NGF_CAVPO Beta-nerve growth factor precursor (Beta-NGF) - Cavia porcellus (Guinea pig).
NGF_GORGO Beta-nerve growth factor precursor (Beta-NGF) - Gorilla gorilla gorilla (Lowland gorilla).
NGF_HUMAN Beta-nerve growth factor precursor (Beta-NGF) - Homo sapiens (Human).
NGF_MOUSE Beta-nerve growth factor precursor (Beta-NGF) - Mus musculus (Mouse).
NGF_PANTR Beta-nerve growth factor precursor (Beta-NGF) - Pan troglodytes (Chimpanzee).
NGF_PONPY Beta-nerve growth factor precursor (Beta-NGF) - Pongo pygmaeus (Orangutan).
NGF_PRANA Beta-nerve growth factor precursor (Beta-NGF) - Praomys natalensis (African soft-furred rat) (Mastomys natalensis).
NGF_RAT Beta-nerve growth factor precursor (Beta-NGF) - Rattus norvegicus (Rat).
NGF_SAIBB Beta-nerve growth factor precursor (Beta-NGF) - Saimiri boliviensis boliviensis (Bolivian squirrel monkey).
Q6LDU8_MOUSE Nerve growth factor (Lung RCB-0558 LLC cDNA, RIKEN full-length enriched library, clone:G730006F04 product:nerve growth factor, beta, full insert sequence) - Mus musculus (Mouse).
Scan History
SPTR55_38f 2  300  NSINGLE    
Initial Motifs
Motif 1  width=10
Element Seqn Id St Int Rpt
QAEPHSESNV NGF_HUMAN 17 17 -
QAEPYSDSNV NGF_CAVPO 17 17 -

Motif 2 width=12
Element Seqn Id St Int Rpt
TIPQAHWTKLQH NGF_HUMAN 31 4 -
TIPQAHWTKLQH NGF_CAVPO 31 4 -

Motif 3 width=12
Element Seqn Id St Int Rpt
LDTALRRARSAP NGF_HUMAN 44 1 -
LDTALRRAHSAP NGF_CAVPO 44 1 -
Final Motifs
Motif 1  width=10
Element Seqn Id St Int Rpt
QAEPHSESNV A1A4E5_HUMAN 17 17 -
QAEPHSESNV NGF_SAIBB 17 17 -
QAEPHSESNV NGF_PANTR 17 17 -
QAEPHSESNV NGF_HUMAN 17 17 -
QAEPYSDSNV NGF_CAVPO 17 17 -
QAEPHSESNV NGF_PONPY 17 17 -
QAELHSESNV NGF_GORGO 17 17 -
QAEPYTDSNV NGF_MOUSE 17 17 -
QAEPYTDSNV Q6LDU8_MOUSE 83 83 -
QAEPYTDSNV NGF_RAT 17 17 -
QAEPYTDSNL NGF_PRANA 17 17 -
QAAPHTESNV NGF_BOVIN 17 17 -

Motif 2 width=12
Element Seqn Id St Int Rpt
TIPQVHWTKLQH A1A4E5_HUMAN 31 4 -
TIPQAHWTKLQH NGF_SAIBB 31 4 -
TIPQAHWTKLQH NGF_PANTR 31 4 -
TIPQAHWTKLQH NGF_HUMAN 31 4 -
TIPQAHWTKLQH NGF_CAVPO 31 4 -
TIPQAHWTKLQH NGF_PONPY 31 4 -
TIPQAHWTKLQH NGF_GORGO 31 4 -
SVPEAHWTKLQH NGF_MOUSE 31 4 -
SVPEAHWTKLQH Q6LDU8_MOUSE 97 4 -
SVPEAHWTKLQH NGF_RAT 31 4 -
SVPEAHWTKLQH NGF_PRANA 31 4 -
AIPQAHWIKLQH NGF_BOVIN 31 4 -

Motif 3 width=12
Element Seqn Id St Int Rpt
LDTALRRARSAP A1A4E5_HUMAN 44 1 -
LDTALRRARSAP NGF_SAIBB 44 1 -
LDTALRRARSAP NGF_PANTR 44 1 -
LDTALRRARSAP NGF_HUMAN 44 1 -
LDTALRRAHSAP NGF_CAVPO 44 1 -
LDTALRRARSTP NGF_PONPY 44 1 -
LDTALRRARSAP NGF_GORGO 44 1 -
LDTALRRARSAP NGF_MOUSE 44 1 -
LDTALRRARSAP Q6LDU8_MOUSE 110 1 -
LDTALRRARSAP NGF_RAT 44 1 -
LDTALRRARSAP NGF_PRANA 44 1 -
LDTVLRRAHSAP NGF_BOVIN 44 1 -