BDNF_RAT
ID BDNF_RAT Reviewed; 249 AA.
AC P23363; Q53YL8;
DT 01-NOV-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1991, sequence version 1.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Brain-derived neurotrophic factor;
DE Short=BDNF;
DE Contains:
DE RecName: Full=BDNF precursor form {ECO:0000305};
DE Short=ProBDNF {ECO:0000305};
DE Flags: Precursor;
GN Name=Bdnf;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RX PubMed=1889806; DOI=10.1016/0888-7543(91)90436-i;
RA Maisonpierre P.C., le Beau M.M., Espinosa R. III, Ip N.Y., Belluscio L.,
RA de la Monte S.M., Squinto S., Furth M.E., Yancopoulos G.D.;
RT "Human and rat brain-derived neurotrophic factor and neurotrophin-3: gene
RT structures, distributions, and chromosomal localizations.";
RL Genomics 10:558-568(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1446835; DOI=10.1016/0378-1119(92)90148-i;
RA Ohara O., Gahara Y., Teraoka H., Kitamura T.;
RT "A rat brain-derived neurotrophic factor-encoding gene generates multiple
RT transcripts through alternative use of 5' exons and polyadenylation
RT sites.";
RL Gene 121:383-386(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1966766; DOI=10.1101/sqb.1990.055.01.038;
RA Yancopoulos G.D., Maisonpierre P.C., Ip N.Y., Aldrich T.H., Belluscio L.,
RA Boulton T.G., Cobb M.H., Squinto S.P., Furth M.E.;
RT "Neurotrophic factors, their receptors, and the signal transduction
RT pathways they activate.";
RL Cold Spring Harb. Symp. Quant. Biol. 55:371-379(1990).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley;
RX PubMed=16376315; DOI=10.1016/j.brainres.2005.10.004;
RA Liu Q.-R., Lu L., Zhu X.-G., Gong J.-P., Shaham Y., Uhl G.R.;
RT "Rodent BDNF genes, novel promoters, novel splice variants, and regulation
RT by cocaine.";
RL Brain Res. 1067:1-12(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley;
RX PubMed=17149751; DOI=10.1002/jnr.21139;
RA Aid T., Kazantseva A., Piirsoo M., Palm K., Timmusk T.;
RT "Mouse and rat BDNF gene structure and expression revisited.";
RL J. Neurosci. Res. 85:525-535(2007).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Wistar; TISSUE=Brain;
RA Zhao L.X., Zhang J., Wang D.M., Yu X.J., Yue W., Pei X.T., Xu X.H.;
RT "Reconstituting BDNF gene to bone marrow mesenchymal stem cells: serving as
RT portals in the therapy of Parkinson's disease.";
RL Submitted (NOV-2002) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 8-249.
RX PubMed=8461137; DOI=10.1016/0896-6273(93)90335-o;
RA Timmusk T., Palm K., Metsis M., Reintam T., Palme V., Saarma M.,
RA Persson H.;
RT "Multiple promoters direct tissue-specific expression of the rat BDNF
RT gene.";
RL Neuron 10:475-489(1993).
RN [9]
RP NUCLEOTIDE SEQUENCE OF 187-229.
RC STRAIN=Sprague-Dawley; TISSUE=Liver;
RX PubMed=2025430; DOI=10.1016/0896-6273(91)90180-8;
RA Hallboeoek F., Ibanez C.F., Persson H.;
RT "Evolutionary studies of the nerve growth factor family reveal a novel
RT member abundantly expressed in Xenopus ovary.";
RL Neuron 6:845-858(1991).
CC -!- FUNCTION: Important signaling molecule that activates signaling
CC cascades downstream of NTRK2 (By similarity). During development,
CC promotes the survival and differentiation of selected neuronal
CC populations of the peripheral and central nervous systems. Participates
CC in axonal growth, pathfinding and in the modulation of dendritic growth
CC and morphology. Major regulator of synaptic transmission and plasticity
CC at adult synapses in many regions of the CNS. The versatility of BDNF
CC is emphasized by its contribution to a range of adaptive neuronal
CC responses including long-term potentiation (LTP), long-term depression
CC (LTD), certain forms of short-term synaptic plasticity, as well as
CC homeostatic regulation of intrinsic neuronal excitability (By
CC similarity). {ECO:0000250|UniProtKB:P21237,
CC ECO:0000250|UniProtKB:P23560}.
CC -!- FUNCTION: [BDNF precursor form]: Important signaling molecule that
CC activates signaling cascades downstream of NTRK2. Activates signaling
CC cascades via the heterodimeric receptor formed by NGFR and SORCS2.
CC Signaling via NGFR and SORCS2 plays a role in synaptic plasticity and
CC long-term depression (LTD). Binding to NGFR and SORCS2 promotes
CC neuronal apoptosis. Promotes neuronal growth cone collapse.
CC {ECO:0000250|UniProtKB:P21237}.
CC -!- SUBUNIT: Monomers and homodimers (By similarity). Binds to NTRK2/TRKB.
CC Can form heterodimers with other neurotrophin family members, such as
CC NTF3 and NTF4 (in vitro), but the physiological relevance of this is
CC not clear (By similarity). BDNF precursor form: interacts with the
CC heterodimer formed by NGFR and SORCS2. Mature BDNF has much lower
CC affinity for the heterodimer formed by NGFR and SORCS2 (By similarity).
CC {ECO:0000250|UniProtKB:P21237, ECO:0000250|UniProtKB:P23560}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P23560}.
CC -!- SUBCELLULAR LOCATION: [BDNF precursor form]: Secreted
CC {ECO:0000250|UniProtKB:P23560}. Note=A proportion of BDNF is secreted
CC as immature precursor (proBDNF). {ECO:0000250|UniProtKB:P23560}.
CC -!- PTM: [BDNF precursor form]: N-glycosylated and glycosulfated, contrary
CC to mature BDNF. {ECO:0000250|UniProtKB:P23560}.
CC -!- PTM: Mature BDNF is produced by proteolytic removal of the propeptide,
CC catalyzed by a FURIN family member. In addition, the precursor form is
CC proteolytically cleaved within the propeptide, but this is not an
CC obligatory intermediate for the production of mature BDNF. Can be
CC converted into mature BDNF by plasmin (PLG).
CC {ECO:0000250|UniProtKB:P23560}.
CC -!- SIMILARITY: Belongs to the NGF-beta family. {ECO:0000305}.
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DR EMBL; M61175; AAA16841.1; -; mRNA.
DR EMBL; M61178; AAA63483.1; -; Genomic_DNA.
DR EMBL; D10938; BAA01732.1; -; Genomic_DNA.
DR EMBL; AY559248; AAS67380.1; -; mRNA.
DR EMBL; AY559249; AAS67381.1; -; mRNA.
DR EMBL; AY559250; AAS67382.1; -; mRNA.
DR EMBL; EF125675; ABM30161.1; -; mRNA.
DR EMBL; EF125676; ABM30162.1; -; mRNA.
DR EMBL; EF125677; ABM30163.1; -; mRNA.
DR EMBL; EF125678; ABM30164.1; -; mRNA.
DR EMBL; EF125679; ABM30165.1; -; mRNA.
DR EMBL; EF125680; ABM30166.1; -; mRNA.
DR EMBL; EF125686; ABM30172.1; -; mRNA.
DR EMBL; EF125687; ABM30173.1; -; mRNA.
DR EMBL; EF125688; ABM30174.1; -; mRNA.
DR EMBL; EF125689; ABM30175.1; -; mRNA.
DR EMBL; EF125690; ABM30176.1; -; mRNA.
DR EMBL; AY176065; AAO17828.1; -; mRNA.
DR EMBL; BC087634; AAH87634.1; -; mRNA.
DR EMBL; X67108; CAA47481.1; -; mRNA.
DR PIR; B60536; B40304.
DR RefSeq; NP_001257559.1; NM_001270630.1.
DR RefSeq; NP_001257560.1; NM_001270631.1.
DR RefSeq; NP_001257561.1; NM_001270632.1.
DR RefSeq; NP_001257562.1; NM_001270633.1.
DR RefSeq; NP_001257563.1; NM_001270634.1.
DR RefSeq; NP_001257564.1; NM_001270635.1.
DR RefSeq; NP_001257565.1; NM_001270636.1.
DR RefSeq; NP_001257566.1; NM_001270637.1.
DR RefSeq; NP_001257567.1; NM_001270638.1.
DR RefSeq; NP_036645.2; NM_012513.4.
DR AlphaFoldDB; P23363; -.
DR SMR; P23363; -.
DR BioGRID; 246413; 3.
DR IntAct; P23363; 3.
DR MINT; P23363; -.
DR STRING; 10116.ENSRNOP00000064356; -.
DR GlyGen; P23363; 1 site.
DR PaxDb; P23363; -.
DR ABCD; P23363; 2 sequenced antibodies.
DR Ensembl; ENSRNOT00000077703; ENSRNOP00000072849; ENSRNOG00000047466.
DR Ensembl; ENSRNOT00000078543; ENSRNOP00000072315; ENSRNOG00000047466.
DR Ensembl; ENSRNOT00000080190; ENSRNOP00000073265; ENSRNOG00000047466.
DR Ensembl; ENSRNOT00000083289; ENSRNOP00000074338; ENSRNOG00000047466.
DR Ensembl; ENSRNOT00000089233; ENSRNOP00000075479; ENSRNOG00000047466.
DR Ensembl; ENSRNOT00000090445; ENSRNOP00000073685; ENSRNOG00000047466.
DR GeneID; 24225; -.
DR KEGG; rno:24225; -.
DR CTD; 627; -.
DR RGD; 2202; Bdnf.
DR eggNOG; ENOG502QRU8; Eukaryota.
DR GeneTree; ENSGT00390000007725; -.
DR InParanoid; P23363; -.
DR OrthoDB; 1156054at2759; -.
DR PhylomeDB; P23363; -.
DR Reactome; R-RNO-9026527; Activated NTRK2 signals through PLCG1.
DR Reactome; R-RNO-9028731; Activated NTRK2 signals through FRS2 and FRS3.
DR Reactome; R-RNO-9032759; NTRK2 activates RAC1.
DR PRO; PR:P23363; -.
DR Proteomes; UP000002494; Chromosome 3.
DR Bgee; ENSRNOG00000047466; Expressed in heart and 7 other tissues.
DR ExpressionAtlas; P23363; baseline and differential.
DR Genevisible; P23363; RN.
DR GO; GO:0030424; C:axon; IDA:RGD.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISO:RGD.
DR GO; GO:0030425; C:dendrite; IDA:RGD.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IDA:RGD.
DR GO; GO:0030061; C:mitochondrial crista; IDA:RGD.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:0043204; C:perikaryon; IDA:RGD.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB.
DR GO; GO:0098794; C:postsynapse; IEA:GOC.
DR GO; GO:0030141; C:secretory granule; ISO:RGD.
DR GO; GO:0008021; C:synaptic vesicle; IDA:RGD.
DR GO; GO:0043195; C:terminal bouton; IDA:RGD.
DR GO; GO:0008083; F:growth factor activity; IBA:GO_Central.
DR GO; GO:0005163; F:nerve growth factor receptor binding; IBA:GO_Central.
DR GO; GO:0005169; F:neurotrophin TRKB receptor binding; IDA:RGD.
DR GO; GO:0007568; P:aging; IEP:RGD.
DR GO; GO:0048675; P:axon extension; ISO:RGD.
DR GO; GO:0007411; P:axon guidance; ISO:RGD.
DR GO; GO:0007412; P:axon target recognition; ISO:RGD.
DR GO; GO:0001662; P:behavioral fear response; ISO:RGD.
DR GO; GO:0048148; P:behavioral response to cocaine; IMP:RGD.
DR GO; GO:1990090; P:cellular response to nerve growth factor stimulus; IEP:RGD.
DR GO; GO:0071874; P:cellular response to norepinephrine stimulus; IEP:RGD.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IEP:RGD.
DR GO; GO:0002544; P:chronic inflammatory response; IEP:RGD.
DR GO; GO:0007623; P:circadian rhythm; ISO:RGD.
DR GO; GO:0050890; P:cognition; IEP:RGD.
DR GO; GO:0048668; P:collateral sprouting; ISO:RGD.
DR GO; GO:1990708; P:conditioned place preference; IMP:RGD.
DR GO; GO:0016358; P:dendrite development; ISO:RGD.
DR GO; GO:0097484; P:dendrite extension; ISO:RGD.
DR GO; GO:0060079; P:excitatory postsynaptic potential; IMP:RGD.
DR GO; GO:0042596; P:fear response; ISO:RGD.
DR GO; GO:0007631; P:feeding behavior; ISO:RGD.
DR GO; GO:0007214; P:gamma-aminobutyric acid signaling pathway; ISO:RGD.
DR GO; GO:0014047; P:glutamate secretion; ISO:RGD.
DR GO; GO:0060080; P:inhibitory postsynaptic potential; ISO:RGD.
DR GO; GO:0048839; P:inner ear development; ISO:RGD.
DR GO; GO:0007612; P:learning; IMP:RGD.
DR GO; GO:0007611; P:learning or memory; ISO:RGD.
DR GO; GO:0042490; P:mechanoreceptor differentiation; ISO:RGD.
DR GO; GO:0007613; P:memory; IBA:GO_Central.
DR GO; GO:0006120; P:mitochondrial electron transport, NADH to ubiquinone; IMP:RGD.
DR GO; GO:0050804; P:modulation of chemical synaptic transmission; IBA:GO_Central.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:RGD.
DR GO; GO:2001234; P:negative regulation of apoptotic signaling pathway; ISO:RGD.
DR GO; GO:0060548; P:negative regulation of cell death; ISO:RGD.
DR GO; GO:0010832; P:negative regulation of myotube differentiation; IMP:BHF-UCL.
DR GO; GO:0007406; P:negative regulation of neuroblast proliferation; ISO:RGD.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISO:RGD.
DR GO; GO:1901215; P:negative regulation of neuron death; IMP:RGD.
DR GO; GO:0045843; P:negative regulation of striated muscle tissue development; IMP:RGD.
DR GO; GO:0032229; P:negative regulation of synaptic transmission, GABAergic; ISO:RGD.
DR GO; GO:0021675; P:nerve development; ISO:RGD.
DR GO; GO:0038180; P:nerve growth factor signaling pathway; IBA:GO_Central.
DR GO; GO:0007399; P:nervous system development; IDA:RGD.
DR GO; GO:0030182; P:neuron differentiation; TAS:RGD.
DR GO; GO:1990138; P:neuron projection extension; IDA:RGD.
DR GO; GO:0048812; P:neuron projection morphogenesis; IBA:GO_Central.
DR GO; GO:0008038; P:neuron recognition; ISO:RGD.
DR GO; GO:0007422; P:peripheral nervous system development; IBA:GO_Central.
DR GO; GO:0048672; P:positive regulation of collateral sprouting; ISO:RGD.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; IDA:MGI.
DR GO; GO:2000324; P:positive regulation of glucocorticoid receptor signaling pathway; IDA:MGI.
DR GO; GO:0048170; P:positive regulation of long-term neuronal synaptic plasticity; IMP:RGD.
DR GO; GO:0045666; P:positive regulation of neuron differentiation; ISO:RGD.
DR GO; GO:0010976; P:positive regulation of neuron projection development; ISO:RGD.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IGI:MGI.
DR GO; GO:1900122; P:positive regulation of receptor binding; IDA:ParkinsonsUK-UCL.
DR GO; GO:0051965; P:positive regulation of synapse assembly; ISO:RGD.
DR GO; GO:0031099; P:regeneration; IDA:RGD.
DR GO; GO:0030516; P:regulation of axon extension; IMP:RGD.
DR GO; GO:0048670; P:regulation of collateral sprouting; ISO:RGD.
DR GO; GO:0048169; P:regulation of long-term neuronal synaptic plasticity; IDA:RGD.
DR GO; GO:0019222; P:regulation of metabolic process; ISO:RGD.
DR GO; GO:0043523; P:regulation of neuron apoptotic process; ISO:RGD.
DR GO; GO:0045664; P:regulation of neuron differentiation; IBA:GO_Central.
DR GO; GO:0046668; P:regulation of retinal cell programmed cell death; ISO:RGD.
DR GO; GO:0048172; P:regulation of short-term neuronal synaptic plasticity; IDA:RGD.
DR GO; GO:0048167; P:regulation of synaptic plasticity; ISO:RGD.
DR GO; GO:0014823; P:response to activity; IEP:RGD.
DR GO; GO:0072347; P:response to anesthetic; IEP:RGD.
DR GO; GO:0010996; P:response to auditory stimulus; IEP:RGD.
DR GO; GO:0051602; P:response to electrical stimulus; IEP:RGD.
DR GO; GO:0032094; P:response to food; IEP:RGD.
DR GO; GO:0009725; P:response to hormone; IEP:RGD.
DR GO; GO:0055093; P:response to hyperoxia; IEP:RGD.
DR GO; GO:0001666; P:response to hypoxia; IEP:RGD.
DR GO; GO:1902065; P:response to L-glutamate; IEP:RGD.
DR GO; GO:0009642; P:response to light intensity; IEP:RGD.
DR GO; GO:0009416; P:response to light stimulus; IEP:RGD.
DR GO; GO:1990089; P:response to nerve growth factor; IEP:RGD.
DR GO; GO:0031667; P:response to nutrient levels; IEP:RGD.
DR GO; GO:0035864; P:response to potassium ion; IEP:RGD.
DR GO; GO:0034612; P:response to tumor necrosis factor; IEP:RGD.
DR GO; GO:0033189; P:response to vitamin A; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0099083; P:retrograde trans-synaptic signaling by neuropeptide, modulating synaptic transmission; ISO:RGD.
DR GO; GO:0007416; P:synapse assembly; ISO:RGD.
DR GO; GO:0061193; P:taste bud development; ISO:RGD.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR GO; GO:0001657; P:ureteric bud development; ISO:RGD.
DR Gene3D; 2.10.90.10; -; 1.
DR InterPro; IPR020430; Brain-der_neurotrophic_factor.
DR InterPro; IPR029034; Cystine-knot_cytokine.
DR InterPro; IPR020408; Nerve_growth_factor-like.
DR InterPro; IPR002072; Nerve_growth_factor-rel.
DR InterPro; IPR019846; Nerve_growth_factor_CS.
DR PANTHER; PTHR11589; PTHR11589; 1.
DR PANTHER; PTHR11589:SF3; PTHR11589:SF3; 1.
DR Pfam; PF00243; NGF; 1.
DR PIRSF; PIRSF001789; NGF; 1.
DR PRINTS; PR01912; BDNFACTOR.
DR PRINTS; PR00268; NGF.
DR SMART; SM00140; NGF; 1.
DR SUPFAM; SSF57501; SSF57501; 1.
DR PROSITE; PS00248; NGF_1; 1.
DR PROSITE; PS50270; NGF_2; 1.
PE 2: Evidence at transcript level;
KW Cleavage on pair of basic residues; Disulfide bond; Glycoprotein;
KW Growth factor; Reference proteome; Secreted; Signal.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT CHAIN 19..249
FT /note="BDNF precursor form"
FT /evidence="ECO:0000305"
FT /id="PRO_0000447540"
FT PROPEP 19..130
FT /evidence="ECO:0000250|UniProtKB:P21237"
FT /id="PRO_0000019643"
FT CHAIN 131..249
FT /note="Brain-derived neurotrophic factor"
FT /id="PRO_0000019644"
FT SITE 59..60
FT /note="Cleavage; by MBTPS1"
FT /evidence="ECO:0000250|UniProtKB:P23560"
FT CARBOHYD 123
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 143..210
FT /evidence="ECO:0000250|UniProtKB:P23560"
FT DISULFID 188..239
FT /evidence="ECO:0000250|UniProtKB:P23560"
FT DISULFID 198..241
FT /evidence="ECO:0000250|UniProtKB:P23560"
SQ SEQUENCE 249 AA; 28109 MW; F9CAAA5DEF9A78B7 CRC64;
MTILFLTMVI SYFGCMKAAP MKEANVHGQG NLAYPAVRTH GTLESVNGPR AGSRGLTTTS
LADTFEHVIE ELLDEDQKVR PNEENHKDAD LYTSRVMLSS QVPLEPPLLF LLEEYKNYLD
AANMSMRVRR HSDPARRGEL SVCDSISEWV TAADKKTAVD MSGGTVTVLE KVPVSKGQLK
QYFYETKCNP MGYTKEGCRG IDKRHWNSQC RTTQSYVRAL TMDSKKRIGW RFIRIDTSCV
CTLTIKRGR
