人とマウス共通自閉症の遺伝子 BDNF
人とマウス共通 自閉症の遺伝子
BDNF の異常
理研が発見 古市貞一チームリーダー研究 日経新聞朝刊平成 19 年 3 月 23 日
Usage of Human Famsbase for Brain-derived neurotrophic factor precursor (BDNF)
(Abrineurin)
3: P23560 Reports
BLink, Conserved Domains, Links
Brain-derived neurotrophic factor precursor (BDNF) (Abrineurin)
gi|114900|sp|P23560|BDNF_HUMAN[114900]
1:
P23560. Reports
Brain-derived neu...[gi:114900]
BLink, Conserved Domains,
Links
CommentFeaturesSequenceLOCUS
linear
P23560
247 aa
PRI 20-MAR-2007
DEFINITION Brain-derived neurotrophic factor precursor (BDNF) (Abrineurin).
ACCESSION
VERSION
DBSOURCE
P23560
P23560 GI:114900
swissprot: locus BDNF_HUMAN, accession P23560;
class: standard.
extra accessions:Q9BYY7,Q9UC24
created: Nov 1, 1991.
sequence updated: Nov 1, 1991.
annotation updated: Mar 20, 2007.
xrefs: M37762.1, AAA51820.1, M61176.1, AAA69805.2, M61181.1,
AAA96140.1, X60201.1, CAA42761.1, X91251.1, CAA62632.1, AF400438.1,
AAK92487.1,
BC029795.1,
AAH29795.1,
AY011481.1,
AAG47514.1,
A40304,
1B8MA, 1BNDA
COMMENT
On Mar 15, 2005 this sequence version replaced gi:418818.
[FUNCTION] Promotes the survival of neuronal populations that are
all located either in the central nervous system or directly
connected to it. Major regulator of synaptic transmission and
plasticity at adult synapses in many regions of the CNS. The
versatility of BDNF is emphasized by its contribution to a range of
adaptive neuronal responses including long-term potentiation (LTP),
long-term depression (LTD), certain forms of short-term synaptic
plasticity, as well as homeostatic regulation of intrinsic neuronal
excitability.
[SUBUNIT] Monomers and homodimers. Binds to NTRK2/TRKB.
[INTERACTION] P20783:NTF3; NbExp=1; IntAct=EBI-1026003,
EBI-1025994.
[SUBCELLULAR LOCATION] Secreted protein.
[PTM] The propeptide is N-glycosylated and glycosulfated.
[PTM] Converted into mature BDNF by plasmin (PLG) (By similarity).
[POLYMORPHISM] Variations in BDNF are associated with
susceptybility to bulimia nervosa 2 (BULN2) [MIM:610269]. Several
genes with an essential role in the regulation of eating behavior
and body weight are considered candidates involved in the etiology
of eating disorders (ED), but no relevant susceptibility genes with
a major effect on anorexia nervosa (AN) or bulimia nervosa (BN)
have been identified. BDNF has been implicated in the regulation of
food intake and body weight in rodents. A strong association has
been reported of the Met-66 allele of the Val-66-Met BDNF variant
with restricting AN (ANR) and low minimum body mass index in
Spanish patients. Met-66 variant is strongly associated to all ED
subtypes (AN, ANR, binge-eating/purging AN and BN) in European
patients. Another single nucleotide polymorphism located in the
promoter region of the BDNF gene showed an effect on BN and late
age at onset of weight loss. These are two variants associated with
the pathophysiology of ED in different populations. These variants
support a role for BDNF in the susceptibility to aberrant eating
behaviors.
[DISEASE] Defects in BDNF are a cause of congenital central
hypoventilation syndrome (CCHS) [MIM:209880]; also known as
congenital failure of autonomic control or Ondine curse. CCHS is a
rare disorder characterized by abnormal control of respiration in
the absence of neuromuscular or lung disease, or an identifiable
brain stem lesion. A deficiency in autonomic control of respiration
results in inadequate or negligible ventilatory and arousal
responses to hypercapnia and hypoxemia. CCHS is frequently
complicated with neurocristopathies such as Hirschsprung disease
that occurs in about 16% of CCHS cases.
[SIMILARITY] Belongs to the NGF-beta family.
FEATURES
source
Location/Qualifiers
1..247
/organism="Homo sapiens"
/db_xref="taxon:9606"
gene
1..247
/gene="BDNF"
Protein
1..247
/gene="BDNF"
/product="Brain-derived neurotrophic factor precursor"
Region
1..18
/gene="BDNF"
/region_name="Signal"
/inference="non-experimental evidence, no additional
details recorded"
/note="Potential."
Region
2
/gene="BDNF"
/region_name="Variant"
/experiment="experimental evidence, no additional details
recorded"
/note="T -> I (in CCHS; dbSNP:rs8192466).
/FTId=VAR_018260."
Region
19..128
/gene="BDNF"
/region_name="Propeptide"
/experiment="experimental evidence, no additional details
recorded"
/note="/FTId=PRO_0000019633."
Site
54
/gene="BDNF"
/site_type="mutagenized"
/experiment="experimental evidence, no additional details
recorded"
/note="R->A: Abolishes processing by S1P."
Site
57..58
/gene="BDNF"
/site_type="cleavage"
/experiment="experimental evidence, no additional details
recorded"
/note="Cleavage (by S1P)."
Region
66
/gene="BDNF"
/region_name="Variant"
/experiment="experimental evidence, no additional details
recorded"
/note="V -> M (polymorphism that impairs localization to
secretory granules or synapses; associated with poorer
episodic memory; may have a protective effect in
obsessive-compulsive disorder; dbSNP:rs6265).
/FTId=VAR_004626."
Region
75
/gene="BDNF"
/region_name="Variant"
/experiment="experimental evidence, no additional details
recorded"
/note="Q -> H (in dbSNP:rs1048218). /FTId=VAR_011797."
Site
121
/gene="BDNF"
/site_type="glycosylation"
/experiment="experimental evidence, no additional details
recorded"
/note="N-linked (GlcNAc...)."
Region
125
/gene="BDNF"
/region_name="Variant"
/experiment="experimental evidence, no additional details
recorded"
/note="R -> M (in dbSNP:rs1048220). /FTId=VAR_011798."
Region
127
/gene="BDNF"
/region_name="Variant"
/experiment="experimental evidence, no additional details
recorded"
/note="R -> L (in dbSNP:rs1048221). /FTId=VAR_011799."
Region
129..247
/gene="BDNF"
/region_name="Mature chain"
/experiment="experimental evidence, no additional details
recorded"
/note="Brain-derived neurotrophic factor.
/FTId=PRO_0000019634."
Region
133..240
/gene="BDNF"
/region_name="NGF"
/note="Nerve growth factor (NGF or beta-NGF); NGF is
important for the development and maintenance of the
sympathetic and sensory nervous systems; smart00140"
/db_xref="CDD:47479"
Bond
bond(141,208)
/gene="BDNF"
/bond_type="disulfide"
/experiment="experimental evidence, no additional details
recorded"
Region
147..149
/gene="BDNF"
/region_name="Beta-strand region"
/experiment="experimental evidence, no additional details
recorded"
Region
150..153
/gene="BDNF"
/region_name="Helical region"
/experiment="experimental evidence, no additional details
recorded"
Region
155..158
/gene="BDNF"
/region_name="Beta-strand region"
/experiment="experimental evidence, no additional details
recorded"
Region
163..166
/gene="BDNF"
/region_name="Beta-strand region"
/experiment="experimental evidence, no additional details
recorded"
Region
168..171
/gene="BDNF"
/region_name="Beta-strand region"
/experiment="experimental evidence, no additional details
recorded"
Region
176..178
/gene="BDNF"
/region_name="Beta-strand region"
/experiment="experimental evidence, no additional details
recorded"
Region
180..182
/gene="BDNF"
/region_name="Beta-strand region"
/experiment="experimental evidence, no additional details
recorded"
Bond
bond(186,237)
/gene="BDNF"
/bond_type="disulfide"
/experiment="experimental evidence, no additional details
recorded"
Region
188..189
/gene="BDNF"
/region_name="Hydrogen bonded turn"
/experiment="experimental evidence, no additional details
recorded"
Region
191..193
/gene="BDNF"
/region_name="Helical region"
/experiment="experimental evidence, no additional details
recorded"
Bond
bond(196,239)
/gene="BDNF"
/bond_type="disulfide"
/experiment="experimental evidence, no additional details
recorded"
Region
197..198
/gene="BDNF"
/region_name="Hydrogen bonded turn"
/experiment="experimental evidence, no additional details
recorded"
Region
201..203
/gene="BDNF"
/region_name="Hydrogen bonded turn"
/experiment="experimental evidence, no additional details
recorded"
Region
208..220
/gene="BDNF"
/region_name="Beta-strand region"
/experiment="experimental evidence, no additional details
recorded"
Region
226..239
/gene="BDNF"
/region_name="Beta-strand region"
/experiment="experimental evidence, no additional details
recorded"
1:
P23560. Reports
Brain-derived neu...[gi:114900]
BLink, Conserved Domains,
Links
>gi|114900|sp|P23560|BDNF_HUMAN Brain-derived neurotrophic factor precursor
(BDNF) (Abrineurin)
MTILFLTMVISYFGCMKAAPMKEANIRGQGGLAYPGVRTHGTLESVNGPKAGSRGL
TSLADTFEHVIEEL
LDEDQKVRPNEENNKDADLYTSRVMLSSQVPLEPPLLFLLEEYKNYLDAANMSMR
VRRHSDPARRGELSV
CDSISEWVTAADKKTAVDMSGGTVTVLEKVPVSKGQLKQYFYETKCNPMGYTKEG
CRGIDKRHWNSQCRT
TQSYVRALTMDSKKRIGWRFIRIDTSCVCTLTIKRGR
10: P21237 Reports
BLink, Conserved Domains, Links
Brain-derived neurotrophic factor precursor (BDNF)
gi|114901|sp|P21237|BDNF_MOUSE[114901]
1:
P21237. Reports
Brain-derived neu...[gi:114901]
BLink, Conserved Domains,
Links
CommentFeaturesSequenceLOCUS
linear
P21237
ROD 20-MAR-2007
DEFINITION Brain-derived neurotrophic factor precursor (BDNF).
ACCESSION
VERSION
DBSOURCE
P21237
P21237 GI:114901
swissprot: locus BDNF_MOUSE, accession P21237;
class: standard.
created: May 1, 1991.
sequence updated: May 1, 1991.
annotation updated: Mar 20, 2007.
249 aa
COMMENT
On Mar 15, 2005 this sequence version replaced gi:110749.
[FUNCTION] Promotes the survival of neuronal populations that are
all located either in the central nervous system or directly
connected to it. Major regulator of synaptic transmission and
plasticity at adult synapses in many regions of the CNS. The
versatility of BDNF is emphasized by its contribution to a range of
adaptive neuronal responses including long-term potentiation (LTP),
long-term depression (LTD), certain forms of short-term synaptic
plasticity, as well as homeostatic regulation of intrinsic neuronal
excitability.
[SUBUNIT] Monomers and homodimers. Binds to NTRK2/TRKB.
[SUBCELLULAR LOCATION] Secreted protein.
[PTM] Converted into mature BDNF by plasmin (PLG).
[SIMILARITY] Belongs to the NGF-beta family.
FEATURES
source
Location/Qualifiers
1..249
/organism="Mus musculus"
/db_xref="taxon:10090"
gene
1..249
/gene="Bdnf"
Protein
1..249
/gene="Bdnf"
/product="Brain-derived neurotrophic factor precursor"
Region
1..18
/gene="Bdnf"
/region_name="Signal"
/inference="non-experimental evidence, no additional
details recorded"
/note="Potential."
Region
19..130
/gene="Bdnf"
/region_name="Propeptide"
/experiment="experimental evidence, no additional details
recorded"
/note="/FTId=PRO_0000019635."
Site
57..58
/gene="Bdnf"
/site_type="cleavage"
/inference="non-experimental evidence, no additional
details recorded"
/note="Cleavage (by S1P) (By similarity)."
Site
68
/gene="Bdnf"
/site_type="mutagenized"
/experiment="experimental evidence, no additional details
recorded"
/note="V->M: Reduced hippocampal volume, dendritic
complexity and context- dependent memory. Increased
anxiety- related behaviors."
Site
123
/gene="Bdnf"
/site_type="glycosylation"
/inference="non-experimental evidence, no additional
details recorded"
/note="N-linked (GlcNAc...) (Potential)."
Site
130
/gene="Bdnf"
/site_type="mutagenized"
/experiment="experimental evidence, no additional details
recorded"
/note="R->K: Forms homodimers processed at L-112 that seem
more stable than the wild type."
Region
131..249
/gene="Bdnf"
/region_name="Mature chain"
/experiment="experimental evidence, no additional details
recorded"
/note="Brain-derived neurotrophic factor.
/FTId=PRO_0000019636."
Region
135..242
/gene="Bdnf"
/region_name="NGF"
/note="Nerve growth factor (NGF or beta-NGF); NGF is
important for the development and maintenance of the
sympathetic and sensory nervous systems; smart00140"
/db_xref="CDD:47479"
Bond
bond(143,210)
/gene="Bdnf"
/bond_type="disulfide"
/inference="non-experimental evidence, no additional
details recorded"
/note="By similarity."
Bond
bond(188,239)
/gene="Bdnf"
/bond_type="disulfide"
/inference="non-experimental evidence, no additional
details recorded"
/note="By similarity."
Bond
bond(198,241)
/gene="Bdnf"
/bond_type="disulfide"
/inference="non-experimental evidence, no additional
details recorded"
/note="By similarity."
1:
P21237. Reports
Brain-derived neu...[gi:114901]
BLink, Conserved Domains,
Links
>gi|114901|sp|P21237|BDNF_MOUSE Brain-derived neurotrophic factor precursor
(BDNF)
MTILFLTMVISYFGCMKAAPMKEVNVHGQGNLAYPGVRTHGTLESVNGPRAGSRG
LTTTSLADTFEHVIE
ELLDEDQKVRPNEENHKDADLYTSRVMLSSQVPLEPPLLFLLEEYKNYLDAANMS
MRVRRHSDPARRGEL
SVCDSISEWVTAADKKTAVDMSGGTVTVLEKVPVSKGQLKQYFYETKCNPMGYTKE
GCRGIDKRHWNSQC
RTTQSYVRALTMDSKKRIGWRFIRIDTSCVCTLTIKRGR