Human Gene BDNF (uc001mrv.1) Description and Page Index
  Description: brain-derived neurotrophic factor isoform a
RefSeq Summary (NM_170733): This gene encodes a member of the nerve growth factor family of proteins. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate the mature protein. Binding of this protein to its cognate receptor promotes neuronal survival in the adult brain. Expression of this gene is reduced in Alzheimer's, Parkinson's, and Huntington's disease patients. This gene may play a role in the regulation of the stress response and in the biology of mood disorders. [provided by RefSeq, Nov 2015].
Transcript (Including UTRs)
   Position: hg18 chr11:27,633,018-27,679,729 Size: 46,712 Total Exon Count: 2 Strand: -
Coding Region
   Position: hg18 chr11:27,635,944-27,636,687 Size: 744 Coding Exon Count: 1 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsCTDMicroarray Expression
RNA StructureProtein StructureOther SpeciesGO AnnotationsmRNA DescriptionsPathways
Other NamesGeneReviewsModel InformationMethods
Data last updated: 2009-03-03

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr11:27,633,018-27,679,729)mRNA (may differ from genome)Protein (247 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
GeneNetworkH-INVHGNCHPRDHuGEMGI
OMIMPubMedReactomeStanford SOURCEUniProtKB

-  Comments and Description Text from UniProtKB
  ID: BDNF_HUMAN
DESCRIPTION: RecName: Full=Brain-derived neurotrophic factor; Short=BDNF; AltName: Full=Abrineurin; Flags: Precursor;
FUNCTION: During development, promotes the survival and differentiation of selected neuronal populations of the peripheral and central nervous systems. Participates in axonal growth, pathfinding and in the modulation of dendritic growth and morphology. 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.
TISSUE SPECIFICITY: Brain. Highly expressed in hippocampus, amygdala, cerebral cortex and cerebellum. Also expressed in heart, lung, skeletal muscle, testis, prostate and placenta.
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 susceptibility 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.
WEB RESOURCE: Name=Wikipedia; Note=BDNF entry; URL="http://en.wikipedia.org/wiki/Brain-derived_neurotrophic_factor";

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): BDNF
CDC HuGE Published Literature: BDNF
Positive Disease Associations: affective psychoses , alcoholism , Alzheimer's Disease , Alzheimer's disease; Parkinson's disease; multiple system atrophy , anorexia nervosa , anorexia nervosa; bulimia , Bipolar disorder , body mass , brain activity , bulimia eating disorder , childhood-onset mood disorders , cognitive function , cognitive function schizophrenia , depression , depression stroke , depressive disorder, major hippocampal volume , eating disorders , eating disorders mood disorders schizophrenia substance abuse , epilepsy , hippocampal volume , methamphetamine abuse; substance abuse , mood disorder , obsessive-compulsive disorder , Parkinson's Disease , Parkinson's disease; cognition , Parkinsons disease , personality disorders , personality traits , reasoning skills , Schizophrenia , schizophrenia weight gain , schizophrenia; psychoses , smoking behavior
Related Studies:
  1. affective psychoses
    Hong, C. J. et al. 2003, Association study of a brain-derived neurotrophic-factor genetic polymorphism and mood disorders, age of onset and suicidal behavior., Neuropsychobiology. 2003 ;48(4):186-9. [PubMed 14673216]
    GiveY the fact that the positive associatioY betweeY BDYF geYe Val66Met polymorphism aYd bipolar disorder has oYly beeY demoYstrated for a CaucasiaY populatioY but Yot for a JapaYese aYalog or our ChiYese sample, it appears likely that this associatioY is ethYicity depeYdeYt.
  2. alcoholism
    Matsushita, S. et al. 2004, Association study of brain-derived neurotrophic factor gene polymorphism and alcoholism., Alcoholism, clinical and experimental research. 2004 Nov;28(11):1609-12. [PubMed 15547445]
    These results indicate that BDNF gene polymorphism might modify phenotypes of alcoholism.
  3. Alzheimer's Disease
    Riemenschneider M et al. 2002, A polymorphism of the brain-derived neurotrophic factor (BDNF) is associated with Alzheimer's disease in patients lacking the Apolipoprotein E epsilon4 allele., Molecular psychiatry. 2002 ;7(7):782-5. [PubMed 12192623]
    The results suggest that the BDNF C-270T polymorphism is a relevant risk factor for AD particularly in patients lacking the ApoE epsilon4 allele in this German sample.
           more ... click here to view the complete list

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  Microarray Expression Data
 
Expression ratio colors:

GNF Expression Atlas 2 Data from U133A and GNF1H Chips

      
      
      
     
    
     
Ratios
      
      
      
     
    
     
Absolute
      
       
      
      
     
    
Ratios
      
       
      
      
     
    
Absolute
   
     
     
Ratios
   
     
     
Absolute

Affymetrix All Exon Microarrays

           
Ratios

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -103.60331-0.313 Picture PostScript Text
3' UTR -794.252926-0.271 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR020430 - Brain-der_neurotrophic_factor
IPR020408 - Nerve_growth_factor-like
IPR002072 - Nerve_growth_factor-rel
IPR019846 - Nerve_growth_factor_CS

Pfam Domains:
PF00243 - Nerve growth factor family

SCOP Domains:
57501 - Cystine-knot cytokines

Protein Data Bank (PDB) 3-D Structure
MuPIT help

1B8M
- X-ray MuPIT

1BND
- X-ray MuPIT


ModBase Predicted Comparative 3D Structure on P23560
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserNo orthologNo orthologNo orthologNo orthologNo ortholog
Gene DetailsGene Details    
Gene SorterGene Sorter    
MGIRGD    
Protein Sequence     
Alignment     

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005102 receptor binding
GO:0005169 neurotrophin TRKB receptor binding
GO:0008083 growth factor activity

Biological Process:
GO:0007202 activation of phospholipase C activity
GO:0007267 cell-cell signaling
GO:0007399 nervous system development
GO:0007411 axon guidance
GO:0007416 synapse assembly
GO:0010469 regulation of receptor activity
GO:0010832 negative regulation of myotube differentiation
GO:0031547 brain-derived neurotrophic factor receptor signaling pathway
GO:0031550 positive regulation of brain-derived neurotrophic factor receptor signaling pathway
GO:0043524 negative regulation of neuron apoptotic process
GO:0048011 neurotrophin TRK receptor signaling pathway
GO:0048668 collateral sprouting
GO:0048672 positive regulation of collateral sprouting
GO:0051965 positive regulation of synapse assembly
GO:1900122 positive regulation of receptor binding
GO:1903997 positive regulation of non-membrane spanning protein tyrosine kinase activity
GO:2000008 regulation of protein localization to cell surface

Cellular Component:
GO:0005576 extracellular region
GO:0005737 cytoplasm
GO:0005739 mitochondrion
GO:0016607 nuclear speck
GO:0031410 cytoplasmic vesicle
GO:0048471 perinuclear region of cytoplasm


-  Descriptions from all associated GenBank mRNAs
  AY054399 - Homo sapiens brain-derived neurotrophic factor BDNF6A (BDNF) mRNA, complete cds, alternatively spliced.
AY054400 - Homo sapiens brain-derived neurotrophic factor BDNF6B (BDNF) mRNA, complete cds, alternatively spliced.
EF689017 - Homo sapiens brain derived neurotrophic factor variant (BDNF) mRNA, complete cds.
EF689018 - Homo sapiens brain derived neurotrophic factor variant (BDNF) mRNA, complete cds.
AY054398 - Homo sapiens brain-derived neurotrophic factor BDNF5 (BDNF) mRNA, complete cds, alternatively spliced.
EF689014 - Homo sapiens brain derived neurotrophic factor variant (BDNF) mRNA, complete cds.
EF689015 - Homo sapiens brain derived neurotrophic factor variant (BDNF) mRNA, complete cds.
EF689016 - Homo sapiens brain derived neurotrophic factor variant (BDNF) mRNA, complete cds.
EF689013 - Homo sapiens brain derived neurotrophic factor variant (BDNF) mRNA, complete cds.
EF689011 - Homo sapiens brain derived neurotrophic factor variant (BDNF) mRNA, complete cds.
EF689012 - Homo sapiens brain derived neurotrophic factor variant (BDNF) mRNA, complete cds.
EF689019 - Homo sapiens brain derived neurotrophic factor variant (BDNF) mRNA, complete cds.
EF689020 - Homo sapiens brain derived neurotrophic factor variant (BDNF) mRNA, complete cds.
AY054397 - Homo sapiens brain-derived neurotrophic factor BDNF4 (BDNF) mRNA, complete cds, alternatively spliced.
EF674521 - Homo sapiens brain derived neurotrophic factor transcript IV (BDNF) mRNA, complete cds, alternatively spliced.
AY054396 - Homo sapiens brain-derived neurotrophic factor BDNF3 (BDNF) mRNA, complete cds, alternatively spliced.
EF674520 - Homo sapiens brain derived neurotrophic factor transcript III (BDNF) mRNA, complete cds, alternatively spliced.
AY054393 - Homo sapiens brain-derived neurotrophic factor BDNF2A (BDNF) mRNA, complete cds, alternatively spliced.
AY054394 - Homo sapiens brain-derived neurotrophic factor BDNF2B (BDNF) mRNA, complete cds, alternatively spliced.
AY054395 - Homo sapiens brain-derived neurotrophic factor BDNF2C (BDNF) mRNA, complete cds, alternatively spliced.
EF674517 - Homo sapiens brain derived neurotrophic factor transcript IIa (BDNF) mRNA, complete cds, alternatively spliced.
EF674518 - Homo sapiens brain derived neurotrophic factor transcript IIb (BDNF) mRNA, complete cds, alternatively spliced.
EF674519 - Homo sapiens brain derived neurotrophic factor transcript IIc (BDNF) mRNA, complete cds, alternatively spliced.
AY054392 - Homo sapiens brain-derived neurotrophic factor BDNF1 (BDNF) mRNA, complete cds, alternatively spliced.
EF689021 - Homo sapiens brain derived neurotrophic factor variant (BDNF) mRNA, complete cds.
BC029795 - Homo sapiens brain-derived neurotrophic factor, mRNA (cDNA clone MGC:34632 IMAGE:5193877), complete cds.
X60201 - Human mRNA for brain-derived neurotrophic factor.
X91251 - H.sapiens mRNA for BDNF protein.
AK289853 - Homo sapiens cDNA FLJ77015 complete cds, highly similar to Homo sapiens brain-derived neurotrophic factor (BDNF), transcript variant 3, mRNA.
AK289763 - Homo sapiens cDNA FLJ77010 complete cds, highly similar to Homo sapiens brain-derived neurotrophic factor (BDNF), transcript variant 4, mRNA.
AB038674 - Homo sapiens BDNF 4I-5 mRNA for brain-derived neurotrophic factor, partial cds.
AB038673 - Homo sapiens BDNF 4-5 mRNA for brain-derived neurotrophic factor, partial cds.
AB038672 - Homo sapiens BDNF 3-5 mRNA for brain-derived neurotrophic factor, partial cds.
AB038670 - Homo sapiens BDNF 1-5 mRNA for brain-derived neurotrophic factor, partial cds.
DQ250642 - Homo sapiens brain-derived neurotrophic factor preproprotein isoform 2 (BDNF) mRNA, partial cds.
AB038671 - Homo sapiens BDNF 2-5 mRNA for brain-derived neurotrophic factor, partial cds.
AY442188 - Homo sapiens brain-derived neurotrophic factor isoform 1 (BDNF) mRNA, partial cds, alternatively spliced.
E05934 - Base sequence of human BDNF cDNA.
EF689009 - Homo sapiens brain derived neurotrophic factor variant (BDNF) mRNA, complete cds.
EF689010 - Homo sapiens brain derived neurotrophic factor variant (BDNF) mRNA, complete cds.
AY054406 - Homo sapiens brain-derived neurotrophic factor BDNF7 (BDNF) mRNA, complete cds, alternatively spliced.
M61176 - Homo sapiens brain-derived neurotrophic factor precursor (BDNF) mRNA, complete cds.
AF400438 - Homo sapiens brain-derived neurotrophic factor (BDNF) mRNA, complete cds.
AY656701 - Homo sapiens brain-derived neurotrophic factor transcript variant 5 mRNA, complete cds.
DQ890811 - Synthetic construct clone IMAGE:100003441; FLH166124.01X; RZPDo839D0286D brain-derived neurotrophic factor (BDNF) gene, encodes complete protein.
CU688744 - Synthetic construct Homo sapiens gateway clone IMAGE:100018605 5' read BDNF mRNA.
DQ893966 - Synthetic construct Homo sapiens clone IMAGE:100008426; FLH166120.01L; RZPDo839D0285D brain-derived neurotrophic factor (BDNF) gene, encodes complete protein.
AB464470 - Synthetic construct DNA, clone: pF1KB9810, Homo sapiens BDNF gene for brain-derived neurotrophic factor, without stop codon, in Flexi system.
KC855559 - Homo sapiens isolate EUN-5-9-12 brain-derived neurotrophic factor mRNA, partial cds.
JD347353 - Sequence 328377 from Patent EP1572962.
KP229412 - Homo sapiens brain-derived neurotrophic factor (BDNF) mRNA, complete cds.
KJ896492 - Synthetic construct Homo sapiens clone ccsbBroadEn_05886 BDNF gene, encodes complete protein.
KR710721 - Synthetic construct Homo sapiens clone CCSBHm_00016104 BDNF (BDNF) mRNA, encodes complete protein.
JD311341 - Sequence 292365 from Patent EP1572962.
JD214207 - Sequence 195231 from Patent EP1572962.
JD221517 - Sequence 202541 from Patent EP1572962.
KU177943 - Homo sapiens brain-derived neurotrophic factor isoform 1 (BDNF) mRNA, partial cds.
KU177944 - Homo sapiens brain-derived neurotrophic factor isoform 2 (BDNF) mRNA, partial cds, alternatively spliced.
KU177945 - Homo sapiens brain-derived neurotrophic factor isoform 3 (BDNF) mRNA, partial cds, alternatively spliced.
E05935 - Base sequence of human BDNF gene.
JD419384 - Sequence 400408 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04010 - MAPK signaling pathway
hsa04722 - Neurotrophin signaling pathway
hsa05016 - Huntington's disease

Reactome (by CSHL, EBI, and GO)

Protein P23560 (Reactome details) participates in the following event(s):

R-HSA-9024906 BDNF binds NTRK2 (TRKB)
R-NUL-9025041 BDNF binds Ntrk2
R-HSA-9024967 BDNF-bound NTRK2 dimerizes
R-NUL-9025035 BDNF-bound Ntrk2 dimerizes
R-HSA-9026464 BDNF-bound NTRK2 dimers trans-autophosphorylate
R-HSA-9032502 Activated NTRK2 binds FYN
R-HSA-9032841 Activated NTRK2 binds CDK5
R-NUL-9030372 BDNF-bound Ntrk2 dimers trans-autophosphorylate
R-NUL-9032399 Activated Ntrk2 binds FRS3
R-NUL-9032516 Activated Ntrk2 binds Fyn
R-NUL-9032908 Activated Ntrk2 binds Cdk5
R-HSA-9033276 NTRK2 binds TIAM1
R-HSA-9032863 CDK5 phosphorylates NTRK2
R-NUL-9032961 Cdk5 phosphorylates Ntrk2
R-NUL-9033304 Ntrk2 binds Tiam1
R-HSA-9032854 NTRK2 phosphorylates CDK5
R-HSA-9026493 p-Y516 of p-5Y-NTRK2 recruits SHC1
R-HSA-9026531 p-Y817 of p-5Y-NTRK2 recruits PLCG1
R-HSA-9028730 Activated NTRK2 binds FRS2
R-HSA-9032402 Activated NTRK2 binds FRS3
R-NUL-9032361 Ntrk2-phosphorylated Frs2 binds Ptpn11
R-NUL-9032423 Ntrk2 phosphorylates FRS3
R-NUL-9030433 BDNF- or NTF4-activated Ntrk2 recruits Plcg1
R-NUL-9030473 BDNF- or NTF4-activated Ntrk2 binds Shc1
R-HSA-9026890 NTRK2 phosphorylates SHC1
R-HSA-9026579 NTRK2 phosphorylates PLCG1
R-HSA-9028328 SHC1 bound to activated NTRK2 recruits GRB2:SOS1
R-HSA-9028728 NTRK2 phosphorylates FRS2
R-HSA-9031981 NTRK2-phosphorylated FRS2 binds PTPN11
R-HSA-9032426 NTRK2 phosphorylates FRS3
R-HSA-9033292 NTRK2 and CDK5 promote activation of RAC1 by TIAM1
R-NUL-9033341 Ntrk2 and Cdk5 promote activation of Rac1 by Tiam1
R-NUL-9030450 BDNF- or NTF4-activated Ntrk2 phosphorylates Plcg1
R-NUL-9031971 Ntrk2 phosphorylates Frs2
R-HSA-9026891 NTRK2 activates RAS signaling through SHC1
R-HSA-9024909 BDNF activates NTRK2 (TRKB) signaling
R-HSA-9006115 Signaling by NTRK2 (TRKB)
R-HSA-9032500 Activated NTRK2 signals through FYN
R-HSA-9032845 Activated NTRK2 signals through CDK5
R-HSA-166520 Signaling by NTRKs
R-HSA-9032759 NTRK2 activates RAC1
R-HSA-9026519 Activated NTRK2 signals through RAS
R-HSA-9026527 Activated NTRK2 signals through PLCG1
R-HSA-9028335 Activated NTRK2 signals through PI3K
R-HSA-9028731 Activated NTRK2 signals through FRS2 and FRS3
R-HSA-9006934 Signaling by Receptor Tyrosine Kinases
R-HSA-162582 Signal Transduction

-  Other Names for This Gene
  Alternate Gene Symbols: BDNF_HUMAN, NM_170733, NP_733931, P23560, Q9BYY7, Q9UC24
UCSC ID: uc001mrv.1
RefSeq Accession: NM_170733
Protein: P23560 (aka BDNF_HUMAN)
CCDS: CCDS7865.1, CCDS7866.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene BDNF:
hirschsprung-ov (Hirschsprung Disease Overview)

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_170733.2
exon count: 2CDS single in 3' UTR: no RNA size: 4016
ORF size: 744CDS single in intron: no Alignment % ID: 99.95
txCdsPredict score: 1495.00frame shift in genome: no % Coverage: 99.60
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.