Human Gene BDNF (ENST00000395980.6) Description and Page Index
  Description: Homo sapiens brain derived neurotrophic factor (BDNF), transcript variant 5, mRNA. (from RefSeq NM_170733)
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].
Gencode Transcript: ENST00000395980.6
Gencode Gene: ENSG00000176697.19
Transcript (Including UTRs)
   Position: hg38 chr11:27,654,893-27,701,633 Size: 46,741 Total Exon Count: 2 Strand: -
Coding Region
   Position: hg38 chr11:27,657,821-27,658,564 Size: 744 Coding Exon Count: 1 

Page IndexSequence and LinksUniProtKB CommentsMalaCardsCTDRNA-Seq Expression
Microarray ExpressionRNA StructureProtein StructureOther SpeciesGO AnnotationsmRNA Descriptions
PathwaysOther NamesMethods
Data last updated: 2019-09-04

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr11:27,654,893-27,701,633)mRNA (may differ from genome)Protein (247 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaBioGPS
CGAPEnsemblEntrez GeneExonPrimerGeneCardsHGNC
HPRDLynxMGIneXtProtOMIMPubMed
ReactomeStanford SOURCEUniProtKBWikipedia

-  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";

-  MalaCards Disease Associations
  MalaCards Gene Search: BDNF
Diseases sorted by gene-association score: bulimia nervosa, age of onset of weight loss in* (950), central hypoventilation syndrome, congenital* (767), anorexia nervosa* (606), obsessive-compulsive disorder* (335), bulimia nervosa (41), wagr syndrome* (32), bipolar disorder (28), mood disorder (26), huntington disease (24), bipolar i disorder (24), fetal alcohol spectrum disorder (23), cerebral artery occlusion (21), sydenham chorea (18), rett syndrome (16), transient global amnesia (15), psychotic disorder (14), status epilepticus (13), spinal cord injury (13), early-onset schizophrenia (13), wagro syndrome (13), eating disorder (12), postpartum depression (12), paranoid schizophrenia (12), cannabis abuse (11), relapsing-remitting multiple sclerosis (11), endogenous depression (10), temporal lobe epilepsy (10), segmental dystonia (10), anxiety disorder (10), substance abuse (10), mental depression (9), post-traumatic stress disorder (9), schizoaffective disorder (9), cervical dystonia (8), heroin dependence (8), traumatic brain injury (8), central nervous system disease (8), borderline personality disorder (8), disease of mental health (7), benign epilepsy with centrotemporal spikes (7), interstitial cystitis (7), generalized anxiety disorder (7), alcohol abuse (6), substance dependence (6), brain injury (6), dementia (6), childhood disintegrative disease (6), acute stress disorder (6), drug dependence (5), gilles de la tourette syndrome (5), toxic encephalopathy (5), neonatal hypoxic and ischemic brain injury (5), amnestic disorder (5), meningoencephalitis (5), nodular ganglioneuroblastoma (5), vertebral artery occlusion (4), tendinosis (4), pain disorder (4), attention deficit-hyperactivity disorder (4), motor neuron disease (4), sudden infant death syndrome (4), schizophrenia (3), brachial plexus lesion (3), valproate embryopathy, susceptibility to (3), alzheimer disease (3), fragile x syndrome (3), autism spectrum disorder (3), parkinson disease, late-onset (3), asthma (2), eye disease (2), multiple sclerosis, disease progression, modifier of (2), alcohol dependence (2), amyotrophic lateral sclerosis 1 (2), nervous system disease (2), autistic disorder (2), pervasive developmental disorder (1), neuroblastoma (1), autonomic nervous system neoplasm (1), peripheral nervous system neoplasm (1), specific developmental disorder (1), tetralogy of fallot (1)
* = Manually curated disease association

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

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 2.44 RPKM in Brain - Cerebellar Hemisphere
Total median expression: 23.76 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -111.60358-0.312 Picture PostScript Text
3' UTR -752.602928-0.257 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

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

1B8M
- X-ray MuPIT

1BND
- X-ray MuPIT


ModBase Predicted Comparative 3D Structure on P23560
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-  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 BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGD    
Protein SequenceProtein Sequence    
AlignmentAlignment    

-  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
  EF689009 - Homo sapiens brain derived neurotrophic factor variant (BDNF) mRNA, complete cds.
EF689010 - Homo sapiens brain derived neurotrophic factor variant (BDNF) mRNA, complete cds.
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.
E05934 - Base sequence of human BDNF cDNA.
X60201 - Human mRNA for brain-derived neurotrophic factor.
X91251 - H.sapiens mRNA for BDNF protein.
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.
JD311341 - Sequence 292365 from Patent EP1572962.
JD214207 - Sequence 195231 from Patent EP1572962.
JD347353 - Sequence 328377 from Patent EP1572962.
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.
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.
KP229412 - Homo sapiens brain-derived neurotrophic factor (BDNF) mRNA, complete cds.
CU688744 - Synthetic construct Homo sapiens gateway clone IMAGE:100018605 5' read BDNF mRNA.
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.
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.
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.
KC855559 - Homo sapiens isolate EUN-5-9-12 brain-derived neurotrophic factor mRNA, partial cds.
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.
JD221517 - Sequence 202541 from Patent EP1572962.
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: A7LA85, A7LA92, BDNF_HUMAN, D3DQZ2, NM_170733, P23560, Q598Q1, Q6DN19, Q6YNR2, Q6YNR3, Q9BYY7, Q9UC24, uc001mrv.1, uc001mrv.2, uc001mrv.3, uc001mrv.4
UCSC ID: uc001mrv.4
RefSeq Accession: NM_170733
Protein: P23560 (aka BDNF_HUMAN)
CCDS: CCDS7865.1, CCDS7866.1

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