UniProtKB - P23560 (BDNF_HUMAN)
Brain-derived neurotrophic factor
BDNF
Functioni
Important signaling molecule that activates signaling cascades downstream of NTRK2 (PubMed:11152678).
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.
3 PublicationsImportant signaling molecule that activates signaling cascades downstream of NTRK2. Activates signaling cascades via the heterodimeric receptor formed by NGFR and SORCS2 (PubMed:24908487, PubMed:29909994).
Signaling via NGFR and SORCS2 plays a role in synaptic plasticity and long-term depression (LTD). Binding to NGFR and SORCS2 promotes neuronal apoptosis. Promotes neuronal growth cone collapse (By similarity).
By similarity2 PublicationsGO - Molecular functioni
- growth factor activity Source: GO_Central
- nerve growth factor receptor binding Source: GO_Central
GO - Biological processi
- axon guidance Source: BHF-UCL
- brain-derived neurotrophic factor receptor signaling pathway Source: BHF-UCL
- collateral sprouting Source: BHF-UCL
- memory Source: GO_Central
- modulation of chemical synaptic transmission Source: GO_Central
- negative regulation of apoptotic signaling pathway Source: ARUK-UCL
- negative regulation of myotube differentiation Source: ParkinsonsUK-UCL
- negative regulation of neuron apoptotic process Source: GO_Central
- nerve development Source: GO_Central
- nerve growth factor signaling pathway Source: GO_Central
- nervous system development Source: ProtInc
- neuron projection morphogenesis Source: GO_Central
- peripheral nervous system development Source: GO_Central
- positive regulation of brain-derived neurotrophic factor receptor signaling pathway Source: BHF-UCL
- positive regulation of collateral sprouting Source: BHF-UCL
- positive regulation of neuron projection development Source: ARUK-UCL
- positive regulation of peptidyl-serine phosphorylation Source: GO_Central
- positive regulation of receptor binding Source: ParkinsonsUK-UCL
- positive regulation of synapse assembly Source: BHF-UCL
- regulation of neuron differentiation Source: GO_Central
- regulation of protein localization to cell surface Source: ParkinsonsUK-UCL
- synapse assembly Source: BHF-UCL
- transmembrane receptor protein tyrosine kinase signaling pathway Source: GO_Central
Keywordsi
Molecular function | Growth factor |
Enzyme and pathway databases
PathwayCommonsi | P23560 |
Reactomei | R-HSA-9022702, MECP2 regulates transcription of neuronal ligands R-HSA-9024909, BDNF activates NTRK2 (TRKB) signaling 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-9032500, Activated NTRK2 signals through FYN R-HSA-9032759, NTRK2 activates RAC1 R-HSA-9032845, Activated NTRK2 signals through CDK5 |
SignaLinki | P23560 |
SIGNORi | P23560 |
Names & Taxonomyi
Protein namesi | Recommended name: Brain-derived neurotrophic factorShort name: BDNF Alternative name(s): Abrineurin Cleaved into the following chain: |
Gene namesi | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:1033, BDNF |
MIMi | 113505, gene |
neXtProti | NX_P23560 |
VEuPathDBi | HostDB:ENSG00000176697 |
Subcellular locationi
Extracellular region or secreted
- Secreted 3 Publications
Extracellular region or secreted
- Secreted 2 Publications
Note: A proportion of BDNF is secreted as immature precursor (proBDNF).2 Publications
Extracellular region or secreted
- extracellular region Source: Reactome
- extracellular space Source: GO_Central
Mitochondrion
- mitochondrion Source: HPA
Nucleus
- nuclear speck Source: HPA
Other locations
- axon Source: GO_Central
- cytoplasm Source: UniProtKB
- dendrite Source: GO_Central
- perinuclear region of cytoplasm Source: UniProtKB
- synaptic vesicle Source: GO_Central
Keywords - Cellular componenti
SecretedPathology & Biotechi
Involvement in diseasei
Congenital central hypoventilation syndrome (CCHS)1 Publication
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_018260 | 2 | T → I in CCHS. 1 PublicationCorresponds to variant dbSNP:rs8192466EnsemblClinVar. | 1 |
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 54 | R → A: Abolishes processing by MBTPS1. 1 Publication | 1 |
Keywords - Diseasei
Disease variantOrganism-specific databases
DisGeNETi | 627 |
MalaCardsi | BDNF |
MIMi | 209880, phenotype |
OpenTargetsi | ENSG00000176697 |
Orphaneti | 661, Ondine syndrome 893, WAGR syndrome |
PharmGKBi | PA31891 |
Miscellaneous databases
Pharosi | P23560, Tbio |
Chemistry databases
ChEMBLi | CHEMBL4523205 |
DrugBanki | DB09301, Chondroitin sulfate DB09130, Copper DB05047, CX-717 DB11823, Esketamine |
Genetic variation databases
BioMutai | BDNF |
DMDMi | 114900 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 18 | Sequence analysisAdd BLAST | 18 | |
ChainiPRO_0000447533 | 19 – 247 | BDNF precursor formCuratedAdd BLAST | 229 | |
PropeptideiPRO_0000019633 | 19 – 128 | 1 PublicationAdd BLAST | 110 | |
ChainiPRO_0000019634 | 129 – 247 | Brain-derived neurotrophic factorAdd BLAST | 119 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 121 | N-linked (GlcNAc...) asparagine2 Publications | 1 | |
Disulfide bondi | 141 ↔ 208 | Combined sources2 Publications | ||
Disulfide bondi | 186 ↔ 237 | Combined sources2 Publications | ||
Disulfide bondi | 196 ↔ 239 | Combined sources2 Publications |
Post-translational modificationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 57 – 58 | Cleavage; by MBTPS11 Publication | 2 |
Keywords - PTMi
Cleavage on pair of basic residues, Disulfide bond, GlycoproteinProteomic databases
MassIVEi | P23560 |
PaxDbi | P23560 |
PeptideAtlasi | P23560 |
PRIDEi | P23560 |
ProteomicsDBi | 54129 [P23560-1] 54130 [P23560-2] 54131 [P23560-3] 54132 [P23560-4] 54133 [P23560-5] |
TopDownProteomicsi | P23560-2 [P23560-2] |
PTM databases
GlyGeni | P23560, 1 site |
iPTMneti | P23560 |
PhosphoSitePlusi | P23560 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000176697, Expressed in saphenous vein and 168 other tissues |
ExpressionAtlasi | P23560, baseline and differential |
Genevisiblei | P23560, HS |
Organism-specific databases
HPAi | ENSG00000176697, Tissue enhanced (brain) |
Interactioni
Subunit structurei
Monomers and homodimers. Binds to NTRK2/TRKB (PubMed:8527932, PubMed:11152678). Can form heterodimers with other neurotrophin family members, such as NTF3 and NTF4 (in vitro), but the physiological relevance of this is not clear (PubMed:7703225, PubMed:10631974). BDNF precursor form: interacts with the heterodimer formed by NGFR and SORCS2 (PubMed:24908487).
5 PublicationsBinary interactionsi
P23560
With | #Exp. | IntAct |
---|---|---|
NTF4 [P34130] | 6 | EBI-1026003,EBI-3907456 |
Isoform 2 [P23560-2]
GO - Molecular functioni
- growth factor activity Source: GO_Central
- nerve growth factor receptor binding Source: GO_Central
Protein-protein interaction databases
BioGRIDi | 107096, 41 interactors |
DIPi | DIP-5719N |
IntActi | P23560, 60 interactors |
STRINGi | 9606.ENSP00000414303 |
Chemistry databases
BindingDBi | P23560 |
Miscellaneous databases
RNActi | P23560, protein |
Structurei
Secondary structure
3D structure databases
BMRBi | P23560 |
SMRi | P23560 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P23560 |
Family & Domainsi
Sequence similaritiesi
Keywords - Domaini
SignalPhylogenomic databases
eggNOGi | ENOG502QRU8, Eukaryota |
GeneTreei | ENSGT00390000007725 |
HOGENOMi | CLU_059942_0_0_1 |
InParanoidi | P23560 |
OMAi | YPGMRTH |
OrthoDBi | 1156054at2759 |
PhylomeDBi | P23560 |
TreeFami | TF106463 |
Family and domain databases
Gene3Di | 2.10.90.10, 1 hit |
InterProi | View protein in InterPro IPR020430, Brain-der_neurotrophic_factor IPR029034, Cystine-knot_cytokine IPR020408, Nerve_growth_factor-like IPR002072, Nerve_growth_factor-rel IPR019846, Nerve_growth_factor_CS |
PANTHERi | PTHR11589, PTHR11589, 1 hit PTHR11589:SF3, PTHR11589:SF3, 1 hit |
Pfami | View protein in Pfam PF00243, NGF, 1 hit |
PIRSFi | PIRSF001789, NGF, 1 hit |
PRINTSi | PR01912, BDNFACTOR PR00268, NGF |
SMARTi | View protein in SMART SM00140, NGF, 1 hit |
SUPFAMi | SSF57501, SSF57501, 1 hit |
PROSITEi | View protein in PROSITE PS00248, NGF_1, 1 hit PS50270, NGF_2, 1 hit |
s (5+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 5 produced by isoformsialternative promoter usage and alternative splicing. AlignAdd to basketThis entry has 5 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MTILFLTMVI SYFGCMKAAP MKEANIRGQG GLAYPGVRTH GTLESVNGPK
60 70 80 90 100
AGSRGLTSLA DTFEHVIEEL LDEDQKVRPN EENNKDADLY TSRVMLSSQV
110 120 130 140 150
PLEPPLLFLL EEYKNYLDAA NMSMRVRRHS DPARRGELSV CDSISEWVTA
160 170 180 190 200
ADKKTAVDMS GGTVTVLEKV PVSKGQLKQY FYETKCNPMG YTKEGCRGID
210 220 230 240
KRHWNSQCRT TQSYVRALTM DSKKRIGWRF IRIDTSCVCT LTIKRGR
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketE9PMP3 | E9PMP3_HUMAN | Brain-derived neurotrophic factor | BDNF | 77 | Annotation score: |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_018260 | 2 | T → I in CCHS. 1 PublicationCorresponds to variant dbSNP:rs8192466EnsemblClinVar. | 1 | |
Natural variantiVAR_004626 | 66 | V → M Strongly associated with susceptibility to eating disorders such as anorexia nervosa and bulimia nervosa; associated with poorer episodic memory; may have a protective effect in obsessive-compulsive disorder; impairs localization to secretory granules or synapses; decreases density of dendritic mushroom spines and synapses. 8 PublicationsCorresponds to variant dbSNP:rs6265EnsemblClinVar. | 1 | |
Natural variantiVAR_011797 | 75 | Q → H. Corresponds to variant dbSNP:rs1048218Ensembl. | 1 | |
Natural variantiVAR_080766 | 122 | M → T Found in a small consanguineous family with intellectual disability; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs765594245Ensembl. | 1 | |
Natural variantiVAR_011798 | 125 | R → M. Corresponds to variant dbSNP:rs1048220Ensembl. | 1 | |
Natural variantiVAR_011799 | 127 | R → L. Corresponds to variant dbSNP:rs1048221Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_037948 | 1 | M → MFHQVRRVM in isoform 2. 3 Publications | 1 | |
Alternative sequenceiVSP_038099 | 1 | M → MQSREEEWFHQVRRVM in isoform 3. 2 Publications | 1 | |
Alternative sequenceiVSP_038100 | 1 | M → MCGATSFLHECTRLILVTTQ NAEFLQKGLQVHTCFGVYPH ASVWHDCASQKKGCAVYLHV SVEFNKLIPENGFIKFHQVR RVM in isoform 4. 1 Publication | 1 | |
Alternative sequenceiVSP_038101 | 1 | M → MLCAISLCARVRKLRSAGRC GKFHQVRRVM in isoform 5. 1 Publication | 1 |
Sequence databases
Genome annotation databases
Keywords - Coding sequence diversityi
Alternative promoter usage, Alternative splicingSimilar proteinsi
Cross-referencesi
Web resourcesi
Wikipedia BDNF entry |
Sequence databases
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1B8M | X-ray | 2.75 | A | 129-247 | [»] | |
1BND | X-ray | 2.30 | A | 129-247 | [»] | |
BMRBi | P23560 | |||||
SMRi | P23560 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 107096, 41 interactors |
DIPi | DIP-5719N |
IntActi | P23560, 60 interactors |
STRINGi | 9606.ENSP00000414303 |
Chemistry databases
BindingDBi | P23560 |
ChEMBLi | CHEMBL4523205 |
DrugBanki | DB09301, Chondroitin sulfate DB09130, Copper DB05047, CX-717 DB11823, Esketamine |
PTM databases
GlyGeni | P23560, 1 site |
iPTMneti | P23560 |
PhosphoSitePlusi | P23560 |
Genetic variation databases
BioMutai | BDNF |
DMDMi | 114900 |
Proteomic databases
MassIVEi | P23560 |
PaxDbi | P23560 |
PeptideAtlasi | P23560 |
PRIDEi | P23560 |
ProteomicsDBi | 54129 [P23560-1] 54130 [P23560-2] 54131 [P23560-3] 54132 [P23560-4] 54133 [P23560-5] |
TopDownProteomicsi | P23560-2 [P23560-2] |
Protocols and materials databases
ABCDi | P23560, 4 sequenced antibodies |
Antibodypediai | 4032, 1211 antibodies from 49 providers |
DNASUi | 627 |
Genome annotation databases
Organism-specific databases
CTDi | 627 |
DisGeNETi | 627 |
GeneCardsi | BDNF |
HGNCi | HGNC:1033, BDNF |
HPAi | ENSG00000176697, Tissue enhanced (brain) |
MalaCardsi | BDNF |
MIMi | 113505, gene 209880, phenotype |
neXtProti | NX_P23560 |
OpenTargetsi | ENSG00000176697 |
Orphaneti | 661, Ondine syndrome 893, WAGR syndrome |
PharmGKBi | PA31891 |
VEuPathDBi | HostDB:ENSG00000176697 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502QRU8, Eukaryota |
GeneTreei | ENSGT00390000007725 |
HOGENOMi | CLU_059942_0_0_1 |
InParanoidi | P23560 |
OMAi | YPGMRTH |
OrthoDBi | 1156054at2759 |
PhylomeDBi | P23560 |
TreeFami | TF106463 |
Enzyme and pathway databases
PathwayCommonsi | P23560 |
Reactomei | R-HSA-9022702, MECP2 regulates transcription of neuronal ligands R-HSA-9024909, BDNF activates NTRK2 (TRKB) signaling 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-9032500, Activated NTRK2 signals through FYN R-HSA-9032759, NTRK2 activates RAC1 R-HSA-9032845, Activated NTRK2 signals through CDK5 |
SignaLinki | P23560 |
SIGNORi | P23560 |
Miscellaneous databases
BioGRID-ORCSi | 627, 6 hits in 999 CRISPR screens |
ChiTaRSi | BDNF, human |
EvolutionaryTracei | P23560 |
GeneWikii | Brain-derived_neurotrophic_factor |
GenomeRNAii | 627 |
Pharosi | P23560, Tbio |
PROi | PR:P23560 |
RNActi | P23560, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000176697, Expressed in saphenous vein and 168 other tissues |
ExpressionAtlasi | P23560, baseline and differential |
Genevisiblei | P23560, HS |
Family and domain databases
Gene3Di | 2.10.90.10, 1 hit |
InterProi | View protein in InterPro IPR020430, Brain-der_neurotrophic_factor IPR029034, Cystine-knot_cytokine IPR020408, Nerve_growth_factor-like IPR002072, Nerve_growth_factor-rel IPR019846, Nerve_growth_factor_CS |
PANTHERi | PTHR11589, PTHR11589, 1 hit PTHR11589:SF3, PTHR11589:SF3, 1 hit |
Pfami | View protein in Pfam PF00243, NGF, 1 hit |
PIRSFi | PIRSF001789, NGF, 1 hit |
PRINTSi | PR01912, BDNFACTOR PR00268, NGF |
SMARTi | View protein in SMART SM00140, NGF, 1 hit |
SUPFAMi | SSF57501, SSF57501, 1 hit |
PROSITEi | View protein in PROSITE PS00248, NGF_1, 1 hit PS50270, NGF_2, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | BDNF_HUMAN | |
Accessioni | P23560Primary (citable) accession number: P23560 Secondary accession number(s): A7LA85 Q9UC24 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 1, 1991 |
Last sequence update: | November 1, 1991 | |
Last modified: | February 23, 2022 | |
This is version 214 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- Human chromosome 11
Human chromosome 11: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families