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UniProtKB/Swiss-Prot entry P23560


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name BDNF_HUMAN
Primary accession number P23560
Secondary accession numbers Q9BYY7 Q9UC24
Integrated into Swiss-Prot on November 1, 1991
Sequence was last modified on November 1, 1991 (Sequence version 1)
Annotations were last modified on    July 22, 2008 (Entry version 99)
Name and origin of the protein
Protein name Brain-derived neurotrophic factor [Precursor]
Synonyms BDNF
Abrineurin
Gene name
Name: BDNF
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
PubMed=2236018 [NCBI, ExPASy, EBI, Israel, Japan]
Jones K.R., Reichardt L.F.;
"Molecular cloning of a human gene that is a member of the nerve growth factor family.";
Proc. Natl. Acad. Sci. U.S.A. 87:8060-8064(1990).
[2]
NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
DOI=10.1016/0888-7543(91)90436-I; PubMed=1889806 [NCBI, ExPASy, EBI, Israel, Japan]
Maisonpierre P.C., le Beau M.M., Espinosa R. III, Ip N.Y., Belluscio L., de la Monte S.M., Squinto S., Furth M.E., Yancopoulos G.D.;
"Human and rat brain-derived neurotrophic factor and neurotrophin-3: gene structures, distributions, and chromosomal localizations.";
Genomics 10:558-568(1991).
[3]
NUCLEOTIDE SEQUENCE [MRNA].
DOI=10.1016/S0006-291X(05)80148-2; PubMed=1339267 [NCBI, ExPASy, EBI, Israel, Japan]
Shintani A., Ono Y., Kaisho Y., Igarashi K.;
"Characterization of the 5'-flanking region of the human brain-derived neurotrophic factor gene.";
Biochem. Biophys. Res. Commun. 182:325-332(1992).
[4]
NUCLEOTIDE SEQUENCE [MRNA].
Cheng Y., Gu J.;
"A cDNA clone of human brain-derived neurotrophic factor (HUMBDNFD).";
Submitted (MAY-1995) to the EMBL/GenBank/DDBJ databases.
[5]
NUCLEOTIDE SEQUENCE [MRNA].
Wu J., Zhang B., Zhou Y., Peng X., Yuan J., Qiang B.;
Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases.
[6]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Brain;
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[7]
NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 185-227.
TISSUE=Leukocyte;
DOI=10.1016/0896-6273(91)90180-8; PubMed=2025430 [NCBI, ExPASy, EBI, Israel, Japan]
Hallboeoek F., Ibanez C.F., Persson H.;
"Evolutionary studies of the nerve growth factor family reveal a novel member abundantly expressed in Xenopus ovary.";
Neuron 6:845-858(1991).
[8]
PROTEIN SEQUENCE OF 129-144.
TISSUE=Serum;
DOI=10.1006/prep.1995.1062; PubMed=8527932 [NCBI, ExPASy, EBI, Israel, Japan]
Rosenfeld R.D., Zeni L., Haniu M., Talvenheimo J., Radka S.F., Bennett L., Miller J.A., Welcher A.A.;
"Purification and identification of brain-derived neurotrophic factor from human serum.";
Protein Expr. Purif. 6:465-471(1995).
[9]
NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 12-197.
DOI=10.1038/35054550; PubMed=11214319 [NCBI, ExPASy, EBI, Israel, Japan]
Murphy W.J., Eizirik E., Johnson W.E., Zhang Y.-P., Ryder O.A., O'Brien S.J.;
"Molecular phylogenetics and the origins of placental mammals.";
Nature 409:614-618(2001).
[10]
X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS).
DOI=10.1021/bi00013a001; PubMed=7703225 [NCBI, ExPASy, EBI, Israel, Japan]
Robinson R.C., Radziejewski C., Stuart D.I., Jones E.Y.;
"Structure of the brain-derived neurotrophic factor/neurotrophin 3 heterodimer.";
Biochemistry 34:4139-4146(1995).
[11]
CHARACTERIZATION, AND MUTAGENESIS OF ARG-54.
DOI=10.1074/jbc.M008104200; PubMed=11152678 [NCBI, ExPASy, EBI, Israel, Japan]
Mowla S.J., Farhadi H.F., Pareek S., Atwal J.K., Morris S.J., Seidah N.G., Murphy R.A.;
"Biosynthesis and post-translational processing of the precursor to brain-derived neurotrophic factor.";
J. Biol. Chem. 276:12660-12666(2001).
[12]
VARIANT MET-66.
DOI=10.1038/10290; PubMed=10391209 [NCBI, ExPASy, EBI, Israel, Japan]
Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., Lander E.S.;
"Characterization of single-nucleotide polymorphisms in coding regions of human genes.";
Nat. Genet. 22:231-238(1999).
[13]
ERRATUM.
Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., Lander E.S.;
Nat. Genet. 23:373-373(1999).
[14]
VARIANT CCHS ILE-2.
DOI=10.1002/ajmg.10133; PubMed=11840487 [NCBI, ExPASy, EBI, Israel, Japan]
Weese-Mayer D.E., Bolk S., Silvestri J.M., Chakravarti A.;
"Idiopathic congenital central hypoventilation syndrome: evaluation of brain-derived neurotrophic factor genomic DNA sequence variation.";
Am. J. Med. Genet. 107:306-310(2002).
[15]
ROLE OF VARIANT MET-66 IN OBSESSIVE-COMPULSIVE DISORDER.
DOI=10.1086/377003; PubMed=12836135 [NCBI, ExPASy, EBI, Israel, Japan]
Hall D., Dhilla A., Charalambous A., Gogos J.A., Karayiorgou M.;
"Sequence variants of the brain-derived neurotrophic factor (BDNF) gene are strongly associated with obsessive-compulsive disorder.";
Am. J. Hum. Genet. 73:370-376(2003).
[16]
CHARACTERIZATION OF VARIANT MET-66, AND ROLE IN EPISODIC MEMORY.
DOI=10.1016/S0092-8674(03)00035-7; PubMed=12553913 [NCBI, ExPASy, EBI, Israel, Japan]
Egan M.F., Kojima M., Callicott J.H., Goldberg T.E., Kolachana B.S., Bertolino A., Zaitsev E., Gold B., Goldman D., Dean M., Lu B., Weinberger D.R.;
"The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function.";
Cell 112:257-269(2003).
[17]
VARIANT MET-66.
DOI=10.1007/s00439-003-1036-z; PubMed=14566559 [NCBI, ExPASy, EBI, Israel, Japan]
Sasaki A., Kanai M., Kijima K., Akaba K., Hashimoto M., Hasegawa H., Otaki S., Koizumi T., Kusuda S., Ogawa Y., Tuchiya K., Yamamoto W., Nakamura T., Hayasaka K.;
"Molecular analysis of congenital central hypoventilation syndrome.";
Hum. Genet. 114:22-26(2003).
[18]
ASSOCIATION OF VARIANT MET-66 WITH ANR.
DOI=10.1038/sj.mp.4001281; PubMed=12888803 [NCBI, ExPASy, EBI, Israel, Japan]
Ribases M., Gratacos M., Armengol L., de Cid R., Badia A., Jimenez L., Solano R., Vallejo J., Fernandez F., Estivill X.;
"Met66 in the brain-derived neurotrophic factor (BDNF) precursor is associated with anorexia nervosa restrictive type.";
Mol. Psychiatry 8:745-751(2003).
[19]
POLYMORPHISM, AND ASSOCIATION WITH BULIMIA NERVOSA.
DOI=10.1093/hmg/ddh137; PubMed=15115760 [NCBI, ExPASy, EBI, Israel, Japan]
Ribases M., Gratacos M., Fernandez-Aranda F., Bellodi L., Boni C., Anderluh M., Cavallini M.C., Cellini E., Di Bella D., Erzegovesi S., Foulon C., Gabrovsek M., Gorwood P., Hebebrand J., Hinney A., Holliday J., Hu X., Karwautz A., Kipman A., Komel R., Nacmias B., Remschmidt H., Ricca V., Sorbi S., Wagner G., Treasure J., Collier D.A., Estivill X.;
"Association of BDNF with anorexia, bulimia and age of onset of weight loss in six European populations.";
Hum. Mol. Genet. 13:1205-1212(2004).
Comments
  • 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.
  • 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.
  • WEB RESOURCE: Name=Wikipedia; Note=BDNF entry; URL="http://en.wikipedia.org/wiki/Brain-derived_neurotrophic_factor";.
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
M37762; AAA51820.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M61176; AAA69805.2; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M61181; AAA96140.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
X60201; CAA42761.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
X91251; CAA62632.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF400438; AAK92487.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC029795; AAH29795.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AY011481; AAG47514.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
PIR B36208; A40304.
RefSeq NP_001700.2; -.
NP_733928.1; -.
NP_733929.1; -.
NP_733931.1; -.
UniGene Hs.502182
3D structure databases
PDB
1B8M; X-ray; 2.75 A; A=129-247.[ExPASy / RCSB / EBI]
1BND; X-ray; 2.30 A; A=129-247.[ExPASy / RCSB / EBI]
Detailed list of linked structures.
PDBsum 1B8M; -.
1BND; -.
ModBase P23560.
Protein-protein interaction databases
DIP DIP:5719N; -.
IntAct P23560; -.
PTM databases
PhosphoSite P23560; -.
Organism-specific databases
H-InvDB HIX0009519; -.
HGNC HGNC:1033; BDNF.
GenAtlas BDNF.
HPA CAB009564; -.
MIM 113505; gene. [NCBI / EBI]
209880; phenotype. [NCBI / EBI]
610269; phenotype. [NCBI / EBI]
Orphanet 661; Ondine syndrome.
PharmGKB PA25335; -.
GeneCards P23560.
Gene expression databases
ArrayExpress P23560; -.
CleanEx HS_BDNF; -.
GermOnline ENSG00000176697; Homo sapiens.
Ontologies
GO
GO:0008083; Molecular function: growth factor activity (traceable author statement from ProtInc).
GO:0007399; Biological process: nervous system development (traceable author statement from ProtInc).
QuickGo view.
Family and domain databases
InterPro IPR002072; NGF.
Graphical view of domain structure.
PANTHER PTHR11589; NGF; 1.
Pfam PF00243; NGF; 1.
Pfam graphical view of domain structure.
PIRSF PIRSF001789; NGF; 1.
PRINTS PR00268; NGF.
ProDom PD002052; NGF; 1.
[Domain structure / List of seq. sharing at least 1 domain]
SMART SM00140; NGF; 1.
SMART graphical view of domain structure.
PROSITE PS00248; NGF_1; 1.
PS50270; NGF_2; 1.
PROSITE graphical view of domain structure (profiles).
BLOCKS P23560.
Genome annotation databases
Ensembl ENSG00000176697; Homo sapiens. [Contig view]
GeneID 627; -.
KEGG hsa:627; -.
Phylogenomic databases
HOVERGEN P23560; -.
Other
LinkHub P23560; -.
SOURCE BDNF; Homo sapiens.
ProtoNet P23560.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
3D-structure; Cleavage on pair of basic residues; Direct protein sequencing; Disease mutation; Glycoprotein; Growth factor; Polymorphism; Secreted; Signal.
Features
SEVIEWER logo Feature table viewer FT aligner logo Feature aligner
KeyFrom   To Length Description FTId
SIGNAL   1    18  18     Potential. 
PROPEP   19   128  110      PRO_0000019633
CHAIN   129   247  119     Brain-derived neurotrophic factor. PRO_0000019634
SITE   57    58  2     Cleavage; by S1P. 
CARBOHYD   121   121        N-linked (GlcNAc...). 
DISULFID   141   208         
DISULFID   186   237         
DISULFID   196   239         
VARIANT   2     2  1     T -> I (in CCHS; dbSNP:rs8192466 [NCBI]). VAR_018260 
VARIANT   66    66  1     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 [NCBI]). VAR_004626 
VARIANT   75    75  1     Q -> H (in dbSNP:rs1048218 [NCBI]). VAR_011797 
VARIANT   125   125  1     R -> M (in dbSNP:rs1048220 [NCBI]). VAR_011798 
VARIANT   127   127  1     R -> L (in dbSNP:rs1048221 [NCBI]). VAR_011799 
MUTAGEN   54    54        R->A: Abolishes processing by S1P. 
STRAND   138   141  4      
STRAND   143   149  7      
HELIX   150   153  4      
STRAND   155   158  4      
STRAND   163   166  4      
STRAND   168   171  4      
STRAND   173   178  6      
STRAND   180   186  7      
HELIX   191   193  3      
TURN   201   203  3      
STRAND   204   220  17      
STRAND   226   243  18      
Sequence information
Length: 247 AA [This is the length of the unprocessed precursor] Molecular weight: 27818 Da [This is the MW of the unprocessed precursor] CRC64: 0A60488254722A99 [This is a checksum on the sequence]
        10         20         30         40         50         60 
MTILFLTMVI SYFGCMKAAP MKEANIRGQG GLAYPGVRTH GTLESVNGPK AGSRGLTSLA 

        70         80         90        100        110        120 
DTFEHVIEEL LDEDQKVRPN EENNKDADLY TSRVMLSSQV PLEPPLLFLL EEYKNYLDAA 

       130        140        150        160        170        180 
NMSMRVRRHS DPARRGELSV CDSISEWVTA ADKKTAVDMS GGTVTVLEKV PVSKGQLKQY 

       190        200        210        220        230        240 
FYETKCNPMG YTKEGCRGID KRHWNSQCRT TQSYVRALTM DSKKRIGWRF IRIDTSCVCT 


LTIKRGR 

P23560 in FASTA format

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