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UniProtKB - P23560 (BDNF_HUMAN)

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Protein

Brain-derived neurotrophic factor

Gene

BDNF

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.1 Publication

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

GO - Biological processi

  • activation of phospholipase C activity Source: Reactome
  • axon guidance Source: BHF-UCL
  • brain-derived neurotrophic factor receptor signaling pathway Source: BHF-UCL
  • cell-cell signaling Source: GO_Central
  • collateral sprouting Source: BHF-UCL
  • negative regulation of myotube differentiation Source: ParkinsonsUK-UCL
  • negative regulation of neuron apoptotic process Source: GO_Central
  • nervous system development Source: ProtInc
  • neurotrophin TRK receptor signaling pathway Source: Reactome
  • positive regulation of brain-derived neurotrophic factor receptor signaling pathway Source: BHF-UCL
  • positive regulation of collateral sprouting Source: BHF-UCL
  • positive regulation of non-membrane spanning protein tyrosine kinase activity Source: Reactome
  • positive regulation of receptor binding Source: ParkinsonsUK-UCL
  • positive regulation of synapse assembly Source: BHF-UCL
  • regulation of protein localization to cell surface Source: ParkinsonsUK-UCL
  • synapse assembly Source: BHF-UCL
View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionGrowth factor

Enzyme and pathway databases

ReactomeiR-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
SignaLinkiP23560
SIGNORiP23560

Names & Taxonomyi

Protein namesi
Recommended name:
Brain-derived neurotrophic factor
Short name:
BDNF
Alternative name(s):
Abrineurin
Gene namesi
Name:BDNF
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

EuPathDBiHostDB:ENSG00000176697.18
HGNCiHGNC:1033 BDNF
MIMi113505 gene
neXtProtiNX_P23560

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Involvement in diseasei

Bulimia nervosa 2 (BULN2)1 Publication
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA psychiatric disorder characterized by eating an unusually large amount of food in a short period of time, followed by inappropriate acts (purging) to avert weight gain. Compensatory behavior includes self-induced vomiting, laxative abuse, and excessive exercise.
See also OMIM:610269
Congenital central hypoventilation syndrome (CCHS)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionRare 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.
See also OMIM:209880
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0182602T → I in CCHS. 1 PublicationCorresponds to variant dbSNP:rs8192466Ensembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi54R → A: Abolishes processing by S1P. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi627
MalaCardsiBDNF
MIMi209880 phenotype
610269 phenotype
OpenTargetsiENSG00000176697
Orphaneti893 WAGR syndrome
PharmGKBiPA31891

Chemistry databases

DrugBankiDB05047 CX717

Polymorphism and mutation databases

BioMutaiBDNF
DMDMi114900

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 18Sequence analysisAdd BLAST18
PropeptideiPRO_000001963319 – 1281 PublicationAdd BLAST110
ChainiPRO_0000019634129 – 247Brain-derived neurotrophic factorAdd BLAST119

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi121N-linked (GlcNAc...) asparagine1
Disulfide bondi141 ↔ 208
Disulfide bondi186 ↔ 237
Disulfide bondi196 ↔ 239

Post-translational modificationi

The propeptide is N-glycosylated and glycosulfated.
Converted into mature BDNF by plasmin (PLG).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei57 – 58Cleavage; by S1P2

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP23560
PeptideAtlasiP23560
PRIDEiP23560
ProteomicsDBi54129
54130 [P23560-2]
54131 [P23560-3]
54132 [P23560-4]
54133 [P23560-5]
TopDownProteomicsiP23560-2 [P23560-2]

PTM databases

iPTMnetiP23560
PhosphoSitePlusiP23560

Miscellaneous databases

PMAP-CutDBiQ6YNR3

Expressioni

Tissue specificityi

Brain. Highly expressed in hippocampus, amygdala, cerebral cortex and cerebellum. Also expressed in heart, lung, skeletal muscle, testis, prostate and placenta.1 Publication

Gene expression databases

BgeeiENSG00000176697
CleanExiHS_BDNF
ExpressionAtlasiP23560 baseline and differential
GenevisibleiP23560 HS

Organism-specific databases

HPAiCAB009564
HPA031440
HPA056104

Interactioni

Subunit structurei

Monomers and homodimers. Binds to NTRK2/TRKB.

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi107096, 10 interactors
DIPiDIP-5719N
IntActiP23560, 9 interactors
STRINGi9606.ENSP00000414303

Structurei

Secondary structure

1247
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi138 – 141Combined sources4
Beta strandi143 – 149Combined sources7
Helixi150 – 153Combined sources4
Beta strandi155 – 158Combined sources4
Beta strandi163 – 166Combined sources4
Beta strandi168 – 171Combined sources4
Beta strandi173 – 178Combined sources6
Beta strandi180 – 186Combined sources7
Helixi191 – 193Combined sources3
Turni201 – 203Combined sources3
Beta strandi204 – 220Combined sources17
Beta strandi226 – 243Combined sources18

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1B8MX-ray2.75A129-247[»]
1BNDX-ray2.30A129-247[»]
ProteinModelPortaliP23560
SMRiP23560
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP23560

Family & Domainsi

Sequence similaritiesi

Belongs to the NGF-beta family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IH7X Eukaryota
ENOG410XRPH LUCA
GeneTreeiENSGT00390000007725
HOVERGENiHBG006494
InParanoidiP23560
KOiK04355
OMAiRVGWRFI
OrthoDBiEOG091G0GHL
PhylomeDBiP23560
TreeFamiTF106463

Family and domain databases

Gene3Di2.10.90.10, 1 hit
InterProiView 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
PANTHERiPTHR11589 PTHR11589, 1 hit
PTHR11589:SF3 PTHR11589:SF3, 1 hit
PfamiView protein in Pfam
PF00243 NGF, 1 hit
PIRSFiPIRSF001789 NGF, 1 hit
PRINTSiPR01912 BDNFACTOR
PR00268 NGF
ProDomiView protein in ProDom or Entries sharing at least one domain
PD002052 Nerve_growth_factor-rel, 1 hit
SMARTiView protein in SMART
SM00140 NGF, 1 hit
SUPFAMiSSF57501 SSF57501, 1 hit
PROSITEiView protein in PROSITE
PS00248 NGF_1, 1 hit
PS50270 NGF_2, 1 hit

Sequences (5)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 5 isoformsi produced by alternative promoter usage and alternative splicing. AlignAdd to basket

Note: 2 types of transcripts are produced: non-coding transcripts (antisense, opposite strand (OS), 8 exons) and coding transcripts (11 exons). Brain BDNF and anti-BDNF transcripts form dsRNA duplexes.
Isoform 1 (identifier: P23560-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        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
Length:247
Mass (Da):27,818
Last modified:November 1, 1991 - v1
Checksum:i0A60488254722A99
GO
Isoform 2 (identifier: P23560-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MFHQVRRVM

Show »
Length:255
Mass (Da):28,872
Checksum:i0E3881F4944CA23C
GO
Isoform 3 (identifier: P23560-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MQSREEEWFHQVRRVM

Show »
Length:262
Mass (Da):29,817
Checksum:i28DDC6F9E19BC727
GO
Isoform 4 (identifier: P23560-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MCGATSFLHE...IKFHQVRRVM

Show »
Length:329
Mass (Da):37,120
Checksum:i5D19D9F2F62588FA
GO
Isoform 5 (identifier: P23560-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MLCAISLCARVRKLRSAGRCGKFHQVRRVM

Show »
Length:276
Mass (Da):31,116
Checksum:iB7B42AA52E6C1A9C
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0182602T → I in CCHS. 1 PublicationCorresponds to variant dbSNP:rs8192466Ensembl.1
Natural variantiVAR_00462666V → M Polymorphism; 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. 7 PublicationsCorresponds to variant dbSNP:rs6265EnsemblClinVar.1
Natural variantiVAR_01179775Q → H. Corresponds to variant dbSNP:rs1048218Ensembl.1
Natural variantiVAR_011798125R → M. Corresponds to variant dbSNP:rs1048220Ensembl.1
Natural variantiVAR_011799127R → L. Corresponds to variant dbSNP:rs1048221Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0379481M → MFHQVRRVM in isoform 2. 3 Publications1
Alternative sequenceiVSP_0380991M → MQSREEEWFHQVRRVM in isoform 3. 2 Publications1
Alternative sequenceiVSP_0381001M → MCGATSFLHECTRLILVTTQ NAEFLQKGLQVHTCFGVYPH ASVWHDCASQKKGCAVYLHV SVEFNKLIPENGFIKFHQVR RVM in isoform 4. 1 Publication1
Alternative sequenceiVSP_0381011M → MLCAISLCARVRKLRSAGRC GKFHQVRRVM in isoform 5. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M37762 Genomic DNA Translation: AAA51820.1
M61176 mRNA Translation: AAA69805.2
M61181 Genomic DNA Translation: AAA96140.1
X60201 mRNA Translation: CAA42761.1
AY054392 mRNA Translation: AAL23557.2
AY054393 mRNA Translation: AAL23558.1
AY054394 mRNA Translation: AAL23559.1
AY054395 mRNA Translation: AAL23560.1
AY054396 mRNA Translation: AAL23561.1
AY054397 mRNA Translation: AAL23562.1
AY054398 mRNA Translation: AAL23563.1
AY054399 mRNA Translation: AAL23564.1
AY054400 mRNA Translation: AAL23565.2
AF411339 Genomic DNA Translation: AAO15434.1
EF674517 mRNA Translation: ABS29021.1
EF674518 mRNA Translation: ABS29022.1
EF674519 mRNA Translation: ABS29023.1
EF674520 mRNA Translation: ABS29024.1
EF674521 mRNA Translation: ABS29025.1
EF689009 mRNA Translation: ABS32249.1
EF689010 mRNA Translation: ABS32250.1
EF689011 mRNA Translation: ABS32251.1
EF689012 mRNA Translation: ABS32252.1
EF689013 mRNA Translation: ABS32253.1
EF689014 mRNA Translation: ABS32254.1
EF689015 mRNA Translation: ABS32255.1
EF689016 mRNA Translation: ABS32256.1
EF689017 mRNA Translation: ABS32257.1
EF689018 mRNA Translation: ABS32258.1
EF689019 mRNA Translation: ABS32259.1
EF689020 mRNA Translation: ABS32260.1
EF689021 mRNA Translation: ABS32261.1
X91251 mRNA Translation: CAA62632.1
AF400438 mRNA Translation: AAK92487.1
AY656701 mRNA Translation: AAT74399.1
AK289853 mRNA Translation: BAF82542.1
AK289763 mRNA Translation: BAF82452.1
AC104563 Genomic DNA No translation available.
CH471064 Genomic DNA Translation: EAW68274.1
CH471064 Genomic DNA Translation: EAW68278.1
CH471064 Genomic DNA Translation: EAW68279.1
CH471064 Genomic DNA Translation: EAW68275.1
CH471064 Genomic DNA Translation: EAW68276.1
CH471064 Genomic DNA Translation: EAW68277.1
BC029795 mRNA Translation: AAH29795.1
AY011481 Genomic DNA Translation: AAG47514.1
CCDSiCCDS41628.1 [P23560-3]
CCDS44558.1 [P23560-4]
CCDS7865.1 [P23560-2]
CCDS7866.1 [P23560-1]
PIRiB36208 A40304
RefSeqiNP_001137277.1, NM_001143805.1 [P23560-1]
NP_001137278.1, NM_001143806.1 [P23560-1]
NP_001137279.1, NM_001143807.1 [P23560-1]
NP_001137280.1, NM_001143808.1 [P23560-1]
NP_001137281.1, NM_001143809.1 [P23560-5]
NP_001137282.1, NM_001143810.1 [P23560-4]
NP_001137283.1, NM_001143811.1 [P23560-1]
NP_001137284.1, NM_001143812.1 [P23560-1]
NP_001137285.1, NM_001143813.1 [P23560-1]
NP_001137286.1, NM_001143814.1 [P23560-1]
NP_001137288.1, NM_001143816.1 [P23560-1]
NP_001700.2, NM_001709.4 [P23560-1]
NP_733927.1, NM_170731.4 [P23560-2]
NP_733928.1, NM_170732.4 [P23560-1]
NP_733929.1, NM_170733.3 [P23560-1]
NP_733930.1, NM_170734.3 [P23560-3]
NP_733931.1, NM_170735.5 [P23560-1]
XP_011518582.1, XM_011520280.2 [P23560-4]
UniGeneiHs.502182

Genome annotation databases

EnsembliENST00000314915; ENSP00000320002; ENSG00000176697 [P23560-2]
ENST00000356660; ENSP00000349084; ENSG00000176697 [P23560-1]
ENST00000395978; ENSP00000379302; ENSG00000176697 [P23560-1]
ENST00000395980; ENSP00000379304; ENSG00000176697 [P23560-1]
ENST00000395981; ENSP00000379305; ENSG00000176697 [P23560-1]
ENST00000395983; ENSP00000379307; ENSG00000176697 [P23560-1]
ENST00000395986; ENSP00000379309; ENSG00000176697 [P23560-3]
ENST00000418212; ENSP00000400502; ENSG00000176697 [P23560-1]
ENST00000420794; ENSP00000389564; ENSG00000176697 [P23560-1]
ENST00000438929; ENSP00000414303; ENSG00000176697 [P23560-4]
ENST00000439476; ENSP00000389345; ENSG00000176697 [P23560-1]
ENST00000525528; ENSP00000437138; ENSG00000176697 [P23560-1]
ENST00000525950; ENSP00000432035; ENSG00000176697 [P23560-1]
ENST00000530861; ENSP00000435564; ENSG00000176697 [P23560-1]
ENST00000532997; ENSP00000435805; ENSG00000176697 [P23560-1]
ENST00000533131; ENSP00000432727; ENSG00000176697 [P23560-1]
ENST00000533246; ENSP00000432376; ENSG00000176697 [P23560-1]
GeneIDi627
KEGGihsa:627
UCSCiuc001mrt.4 human [P23560-1]

Keywords - Coding sequence diversityi

Alternative promoter usage, Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiBDNF_HUMAN
AccessioniPrimary (citable) accession number: P23560
Secondary accession number(s): A7LA85
, A7LA92, D3DQZ2, Q598Q1, Q6DN19, Q6YNR2, Q6YNR3, Q9BYY7, Q9UC24
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1991
Last sequence update: November 1, 1991
Last modified: June 20, 2018
This is version 190 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

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