BDNF_MOUSE
ID BDNF_MOUSE Reviewed; 249 AA.
AC P21237; A2AII2; Q8CCH9;
DT 01-MAY-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1991, sequence version 1.
DT 03-AUG-2022, entry version 177.
DE RecName: Full=Brain-derived neurotrophic factor {ECO:0000303|PubMed:2369898};
DE Short=BDNF {ECO:0000303|PubMed:2369898};
DE Contains:
DE RecName: Full=BDNF precursor form {ECO:0000305};
DE Short=ProBDNF {ECO:0000305};
DE Flags: Precursor;
GN Name=Bdnf;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RX PubMed=2369898; DOI=10.1002/j.1460-2075.1990.tb07423.x;
RA Hofer M., Pagliusi S.R., Hohn A., Leibrock J., Barde Y.-A.;
RT "Regional distribution of brain-derived neurotrophic factor mRNA in the
RT adult mouse brain.";
RL EMBO J. 9:2459-2464(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:BAC28164.1};
RC TISSUE=Testis {ECO:0000312|EMBL:BAC28164.1};
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Mammary gland;
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 [5]
RP PROTEIN SEQUENCE OF 112-121 AND 131-135, SUBUNIT, AND MUTAGENESIS OF
RP ARG-130.
RX PubMed=7957235; DOI=10.1111/j.1432-1033.1994.0995b.x;
RA Kolbeck R., Jungbluth S., Barde Y.-A.;
RT "Characterisation of neurotrophin dimers and monomers.";
RL Eur. J. Biochem. 225:995-1003(1994).
RN [6]
RP DISRUPTION PHENOTYPE, FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=8139657; DOI=10.1038/368147a0;
RA Ernfors P., Lee K.F., Jaenisch R.;
RT "Mice lacking brain-derived neurotrophic factor develop with sensory
RT deficits.";
RL Nature 368:147-150(1994).
RN [7]
RP FUNCTION, AND ACTIVATION BY PLG.
RX PubMed=15486301; DOI=10.1126/science.1100135;
RA Pang P.T., Teng H.K., Zaitsev E., Woo N.T., Sakata K., Zhen S., Teng K.K.,
RA Yung W.-H., Hempstead B.L., Lu B.;
RT "Cleavage of proBDNF by tPA/plasmin is essential for long-term hippocampal
RT plasticity.";
RL Science 306:487-491(2004).
RN [8]
RP FUNCTION (BDNF PRECURSOR FORM), AND MUTAGENESIS OF VAL-68.
RX PubMed=17023662; DOI=10.1126/science.1129663;
RA Chen Z.-Y., Jing D., Bath K.G., Ieraci A., Khan T., Siao C.-J.,
RA Herrera D.G., Toth M., Yang C., McEwen B.S., Hempstead B.L., Lee F.S.;
RT "Genetic variant BDNF (Val66Met) polymorphism alters anxiety-related
RT behavior.";
RL Science 314:140-143(2006).
RN [9]
RP INDUCTION.
RX PubMed=23785138; DOI=10.1523/jneurosci.2757-12.2013;
RA Baeza-Raja B., Eckel-Mahan K., Zhang L., Vagena E., Tsigelny I.F.,
RA Sassone-Corsi P., Ptacek L.J., Akassoglou K.;
RT "p75 neurotrophin receptor is a clock gene that regulates oscillatory
RT components of circadian and metabolic networks.";
RL J. Neurosci. 33:10221-10234(2013).
RN [10]
RP INTERACTION WITH SORCS2 AND NGFR, AND FUNCTION (BDNF PRECURSOR FORM).
RX PubMed=24908487; DOI=10.1016/j.neuron.2014.04.022;
RA Glerup S., Olsen D., Vaegter C.B., Gustafsen C., Sjoegaard S.S., Hermey G.,
RA Kjolby M., Molgaard S., Ulrichsen M., Boggild S., Skeldal S.,
RA Fjorback A.N., Nyengaard J.R., Jacobsen J., Bender D., Bjarkam C.R.,
RA Soerensen E.S., Fuechtbauer E.M., Eichele G., Madsen P., Willnow T.E.,
RA Petersen C.M., Nykjaer A.;
RT "SorCS2 regulates dopaminergic wiring and is processed into an apoptotic
RT two-chain receptor in peripheral glia.";
RL Neuron 82:1074-1087(2014).
RN [11]
RP FUNCTION (BDNF PRECURSOR FORM).
RX PubMed=27457814; DOI=10.1038/mp.2016.108;
RA Glerup S., Bolcho U., Moelgaard S., Boeggild S., Vaegter C.B., Smith A.H.,
RA Nieto-Gonzalez J.L., Ovesen P.L., Pedersen L.F., Fjorback A.N., Kjolby M.,
RA Login H., Holm M.M., Andersen O.M., Nyengaard J.R., Willnow T.E.,
RA Jensen K., Nykjaer A.;
RT "SorCS2 is required for BDNF-dependent plasticity in the hippocampus.";
RL Mol. Psychiatry 21:1740-1751(2016).
RN [12]
RP TISSUE SPECIFICITY, AND INDUCTION BY NERVE INJURY.
RX PubMed=28111162; DOI=10.1016/j.brainres.2017.01.019;
RA Sanna M.D., Ghelardini C., Galeotti N.;
RT "HuD-mediated distinct BDNF regulatory pathways promote regeneration after
RT nerve injury.";
RL Brain Res. 1659:55-63(2017).
RN [13]
RP FUNCTION (BDNF PRECURSOR FORM), AND MUTAGENESIS OF VAL-68.
RX PubMed=29909994; DOI=10.1016/j.neuron.2018.05.024;
RA Giza J.I., Kim J., Meyer H.C., Anastasia A., Dincheva I., Zheng C.I.,
RA Lopez K., Bains H., Yang J., Bracken C., Liston C., Jing D.,
RA Hempstead B.L., Lee F.S.;
RT "The BDNF Val66Met Prodomain Disassembles Dendritic Spines Altering Fear
RT Extinction Circuitry and Behavior.";
RL Neuron 99:163-178(2018).
CC -!- FUNCTION: Important signaling molecule that activates signaling
CC cascades downstream of NTRK2 (PubMed:27457814). 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
CC (PubMed:8139657, PubMed:15486301, PubMed:17023662, PubMed:27457814,
CC PubMed:29909994). {ECO:0000269|PubMed:15486301,
CC ECO:0000269|PubMed:17023662, ECO:0000269|PubMed:27457814,
CC ECO:0000269|PubMed:29909994, ECO:0000269|PubMed:8139657}.
CC -!- FUNCTION: [BDNF precursor form]: Important signaling molecule that
CC activates signaling cascades downstream of NTRK2 (PubMed:27457814).
CC Activates signaling cascades via the heterodimeric receptor formed by
CC NGFR and SORCS2 (PubMed:24908487, PubMed:29909994). Signaling via NGFR
CC and SORCS2 plays a role in synaptic plasticity and long-term depression
CC (LTD) (PubMed:27457814). Binding to NGFR and SORCS2 promotes neuronal
CC apoptosis (PubMed:24908487). Promotes neuronal growth cone collapse
CC (PubMed:24908487, PubMed:27457814). {ECO:0000269|PubMed:24908487,
CC ECO:0000269|PubMed:27457814, ECO:0000269|PubMed:29909994}.
CC -!- SUBUNIT: Monomers and homodimers (PubMed:7957235). Binds to NTRK2/TRKB
CC (By similarity). Can form heterodimers with other neurotrophin family
CC members, such as NTF3 and NTF4 (in vitro), but the physiological
CC relevance of this is not clear (By similarity). BDNF precursor form:
CC interacts with the heterodimer formed by NGFR and SORCS2. Mature BDNF
CC has much lower affinity for the heterodimer formed by NGFR and SORCS2
CC (PubMed:24908487). {ECO:0000250|UniProtKB:P23560,
CC ECO:0000269|PubMed:24908487, ECO:0000269|PubMed:7957235}.
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 -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P21237-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P21237-2; Sequence=VSP_060202;
CC -!- TISSUE SPECIFICITY: Expressed in the dorsal root ganglion and the
CC spinal cord (at protein level) (PubMed:28111162). Detected in brain,
CC especially in brain cortex, hippocampus, midbrain and cerebellum
CC (PubMed:2369898, PubMed:8139657). {ECO:0000269|PubMed:2369898,
CC ECO:0000269|PubMed:28111162, ECO:0000269|PubMed:8139657}.
CC -!- INDUCTION: Expression oscillates in a circadian manner in the
CC suprachiasmatic nucleus (SCN) of the brain (PubMed:23785138). Expressed
CC at higher levels during the dark period and at lower levels during the
CC light period (PubMed:23785138). Up-regulated after sciatic nerve injury
CC (PubMed:28111162). {ECO:0000269|PubMed:23785138,
CC ECO:0000269|PubMed:28111162}.
CC -!- PTM: Contrary to mature BDNF, the propeptide is N-glycosylated and
CC glycosulfated. {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 (By
CC similarity). Can be converted into mature BDNF by plasmin (PLG)
CC (PubMed:15486301). {ECO:0000250|UniProtKB:P23560,
CC ECO:0000269|PubMed:15486301}.
CC -!- DISRUPTION PHENOTYPE: Mutant mice are smaller than wild-type
CC littermates, and most die during the second week after birth. They
CC exhibit impaired motor coordination and balance, head bobbing and
CC tilting, and spinning during perionds of hyperactivity. Mutant mice
CC display a strongly reduced number of neurons in the dorsal root
CC ganglion, trigeminal ganglion, mesencephalic trigeminal nucleus,
CC vestibular ganglion and nodose ganglion. Cell death of vestibular
CC ganglion neurons is strongly increased 14 days after birth. The number
CC of facial motor neurons and sympathetic superior cervical ganglion
CC neurons are not decreased. Mutant mice display defects in the
CC innervation of the inner ear, but respond to auditory stimuli. Tne
CC inner ear from mutant mice has fewer nerve fibers that enter the
CC sacculus, utricle and ampulla of the semicircular ducts, and axons fail
CC to contact their target cells and terminate in the connective tissue
CC adjacent to the sensory epithelia of the sacculus.
CC {ECO:0000269|PubMed:8139657}.
CC -!- SIMILARITY: Belongs to the NGF-beta family. {ECO:0000305}.
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DR EMBL; X55573; CAA39159.1; -; mRNA.
DR EMBL; AK033127; BAC28164.1; -; mRNA.
DR EMBL; AL732477; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC034862; AAH34862.1; -; mRNA.
DR CCDS; CCDS38193.1; -. [P21237-2]
DR CCDS; CCDS38194.1; -. [P21237-1]
DR PIR; S12555; S12555.
DR RefSeq; NP_001041604.1; NM_001048139.1. [P21237-1]
DR RefSeq; NP_001041606.1; NM_001048141.1. [P21237-1]
DR RefSeq; NP_001041607.1; NM_001048142.1. [P21237-1]
DR RefSeq; NP_001272345.1; NM_001285416.1. [P21237-1]
DR RefSeq; NP_001272346.1; NM_001285417.1. [P21237-1]
DR RefSeq; NP_001272347.1; NM_001285418.1. [P21237-1]
DR RefSeq; NP_001272348.1; NM_001285419.1. [P21237-1]
DR RefSeq; NP_001272349.1; NM_001285420.1. [P21237-1]
DR RefSeq; NP_001272350.1; NM_001285421.1. [P21237-1]
DR RefSeq; NP_001272351.1; NM_001285422.1. [P21237-1]
DR RefSeq; NP_001303239.1; NM_001316310.1. [P21237-1]
DR AlphaFoldDB; P21237; -.
DR SMR; P21237; -.
DR BioGRID; 198334; 3.
DR DIP; DIP-5724N; -.
DR IntAct; P21237; 2.
DR STRING; 10090.ENSMUSP00000057989; -.
DR GlyGen; P21237; 1 site.
DR iPTMnet; P21237; -.
DR PhosphoSitePlus; P21237; -.
DR PaxDb; P21237; -.
DR PRIDE; P21237; -.
DR ProteomicsDB; 265206; -. [P21237-1]
DR ProteomicsDB; 328451; -.
DR ABCD; P21237; 2 sequenced antibodies.
DR Antibodypedia; 4032; 1196 antibodies from 50 providers.
DR DNASU; 12064; -.
DR Ensembl; ENSMUST00000053317; ENSMUSP00000057989; ENSMUSG00000048482. [P21237-2]
DR Ensembl; ENSMUST00000111043; ENSMUSP00000106672; ENSMUSG00000048482. [P21237-1]
DR Ensembl; ENSMUST00000111044; ENSMUSP00000106673; ENSMUSG00000048482. [P21237-1]
DR Ensembl; ENSMUST00000111045; ENSMUSP00000106674; ENSMUSG00000048482. [P21237-1]
DR Ensembl; ENSMUST00000111046; ENSMUSP00000106675; ENSMUSG00000048482. [P21237-1]
DR Ensembl; ENSMUST00000111047; ENSMUSP00000106676; ENSMUSG00000048482. [P21237-1]
DR Ensembl; ENSMUST00000111049; ENSMUSP00000106678; ENSMUSG00000048482. [P21237-1]
DR Ensembl; ENSMUST00000111050; ENSMUSP00000106679; ENSMUSG00000048482. [P21237-1]
DR Ensembl; ENSMUST00000111051; ENSMUSP00000106680; ENSMUSG00000048482. [P21237-1]
DR Ensembl; ENSMUST00000176893; ENSMUSP00000135762; ENSMUSG00000048482. [P21237-1]
DR GeneID; 12064; -.
DR KEGG; mmu:12064; -.
DR UCSC; uc008lme.1; mouse. [P21237-1]
DR CTD; 627; -.
DR MGI; MGI:88145; Bdnf.
DR VEuPathDB; HostDB:ENSMUSG00000048482; -.
DR eggNOG; ENOG502QRU8; Eukaryota.
DR GeneTree; ENSGT00390000007725; -.
DR HOGENOM; CLU_059942_0_0_1; -.
DR InParanoid; P21237; -.
DR OMA; YPGMRTH; -.
DR OrthoDB; 1156054at2759; -.
DR TreeFam; TF106463; -.
DR Reactome; R-MMU-9026527; Activated NTRK2 signals through PLCG1.
DR Reactome; R-MMU-9028731; Activated NTRK2 signals through FRS2 and FRS3.
DR Reactome; R-MMU-9032759; NTRK2 activates RAC1.
DR BioGRID-ORCS; 12064; 3 hits in 76 CRISPR screens.
DR PRO; PR:P21237; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; P21237; protein.
DR Bgee; ENSMUSG00000048482; Expressed in lumbar dorsal root ganglion and 160 other tissues.
DR ExpressionAtlas; P21237; baseline and differential.
DR Genevisible; P21237; MM.
DR GO; GO:0030424; C:axon; IDA:SynGO-UCL.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:MGI.
DR GO; GO:0030425; C:dendrite; IDA:SynGO-UCL.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; HDA:BHF-UCL.
DR GO; GO:0030061; C:mitochondrial crista; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; ISO:MGI.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0016607; C:nuclear speck; ISO:MGI.
DR GO; GO:0043204; C:perikaryon; ISO:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0098794; C:postsynapse; IEA:GOC.
DR GO; GO:0030141; C:secretory granule; IDA:MGI.
DR GO; GO:0008021; C:synaptic vesicle; ISO:MGI.
DR GO; GO:0043195; C:terminal bouton; ISO:MGI.
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; ISO:MGI.
DR GO; GO:0048675; P:axon extension; IDA:MGI.
DR GO; GO:0007411; P:axon guidance; IMP:MGI.
DR GO; GO:0007412; P:axon target recognition; IMP:MGI.
DR GO; GO:0001662; P:behavioral fear response; IMP:MGI.
DR GO; GO:0048148; P:behavioral response to cocaine; ISO:MGI.
DR GO; GO:0007623; P:circadian rhythm; IEP:UniProtKB.
DR GO; GO:0048668; P:collateral sprouting; ISO:MGI.
DR GO; GO:1990708; P:conditioned place preference; ISO:MGI.
DR GO; GO:0016358; P:dendrite development; IMP:MGI.
DR GO; GO:0097484; P:dendrite extension; IDA:MGI.
DR GO; GO:0060079; P:excitatory postsynaptic potential; ISO:MGI.
DR GO; GO:0042596; P:fear response; IMP:MGI.
DR GO; GO:0007631; P:feeding behavior; IMP:MGI.
DR GO; GO:0007214; P:gamma-aminobutyric acid signaling pathway; IDA:MGI.
DR GO; GO:0014047; P:glutamate secretion; IPI:MGI.
DR GO; GO:0060080; P:inhibitory postsynaptic potential; IMP:MGI.
DR GO; GO:0048839; P:inner ear development; IMP:MGI.
DR GO; GO:0007612; P:learning; ISO:MGI.
DR GO; GO:0007611; P:learning or memory; IMP:MGI.
DR GO; GO:0042490; P:mechanoreceptor differentiation; IGI:MGI.
DR GO; GO:0007613; P:memory; IBA:GO_Central.
DR GO; GO:0006120; P:mitochondrial electron transport, NADH to ubiquinone; ISO:MGI.
DR GO; GO:0050804; P:modulation of chemical synaptic transmission; IBA:GO_Central.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:MGI.
DR GO; GO:2001234; P:negative regulation of apoptotic signaling pathway; IGI:ARUK-UCL.
DR GO; GO:0060548; P:negative regulation of cell death; IMP:MGI.
DR GO; GO:0010832; P:negative regulation of myotube differentiation; ISO:MGI.
DR GO; GO:0007406; P:negative regulation of neuroblast proliferation; IDA:MGI.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IMP:MGI.
DR GO; GO:1901215; P:negative regulation of neuron death; ISO:MGI.
DR GO; GO:0045843; P:negative regulation of striated muscle tissue development; ISO:MGI.
DR GO; GO:0032229; P:negative regulation of synaptic transmission, GABAergic; IDA:MGI.
DR GO; GO:0021675; P:nerve development; IMP:MGI.
DR GO; GO:0038180; P:nerve growth factor signaling pathway; IBA:GO_Central.
DR GO; GO:0007399; P:nervous system development; ISO:MGI.
DR GO; GO:0051402; P:neuron apoptotic process; IMP:MGI.
DR GO; GO:1990138; P:neuron projection extension; ISO:MGI.
DR GO; GO:0048812; P:neuron projection morphogenesis; IBA:GO_Central.
DR GO; GO:0008038; P:neuron recognition; IMP:MGI.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IMP:MGI.
DR GO; GO:0007422; P:peripheral nervous system development; IBA:GO_Central.
DR GO; GO:0048672; P:positive regulation of collateral sprouting; IDA:MGI.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; ISO:MGI.
DR GO; GO:2000324; P:positive regulation of glucocorticoid receptor signaling pathway; ISO:MGI.
DR GO; GO:0048170; P:positive regulation of long-term neuronal synaptic plasticity; ISO:MGI.
DR GO; GO:0045666; P:positive regulation of neuron differentiation; IDA:MGI.
DR GO; GO:0010976; P:positive regulation of neuron projection development; IGI:ARUK-UCL.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IMP:MGI.
DR GO; GO:1900122; P:positive regulation of receptor binding; ISO:MGI.
DR GO; GO:0051965; P:positive regulation of synapse assembly; ISO:MGI.
DR GO; GO:0031099; P:regeneration; ISO:MGI.
DR GO; GO:0030516; P:regulation of axon extension; ISO:MGI.
DR GO; GO:0048670; P:regulation of collateral sprouting; IGI:MGI.
DR GO; GO:0048169; P:regulation of long-term neuronal synaptic plasticity; ISO:MGI.
DR GO; GO:0043523; P:regulation of neuron apoptotic process; IDA:MGI.
DR GO; GO:0045664; P:regulation of neuron differentiation; IBA:GO_Central.
DR GO; GO:0046668; P:regulation of retinal cell programmed cell death; IDA:MGI.
DR GO; GO:0048172; P:regulation of short-term neuronal synaptic plasticity; ISO:MGI.
DR GO; GO:0048167; P:regulation of synaptic plasticity; IDA:MGI.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IMP:MGI.
DR GO; GO:0099083; P:retrograde trans-synaptic signaling by neuropeptide, modulating synaptic transmission; IMP:SynGO.
DR GO; GO:0007416; P:synapse assembly; ISO:MGI.
DR GO; GO:0061193; P:taste bud development; IMP:MGI.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR GO; GO:0001657; P:ureteric bud development; IDA:MGI.
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 1: Evidence at protein level;
KW Alternative splicing; Cleavage on pair of basic residues;
KW Direct protein sequencing; Disulfide bond; Glycoprotein; Growth factor;
KW 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_0000447536"
FT PROPEP 19..130
FT /evidence="ECO:0000305|PubMed:7957235"
FT /id="PRO_0000019635"
FT CHAIN 131..249
FT /note="Brain-derived neurotrophic factor"
FT /evidence="ECO:0000305"
FT /id="PRO_0000019636"
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"
FT VAR_SEQ 1
FT /note="M -> MFHQVRRVM (in isoform 2)"
FT /id="VSP_060202"
FT MUTAGEN 68
FT /note="V->M: Reduced hippocampal volume, dendritic
FT complexity and context-dependent memory. Decreased density
FT of dendritic mushroom spines and synapses. Impaired fear
FT extinction. Increased anxiety-related behaviors."
FT /evidence="ECO:0000269|PubMed:17023662,
FT ECO:0000269|PubMed:29909994"
FT MUTAGEN 130
FT /note="R->K: Forms homodimers processed at L-112 that seem
FT more stable than the wild-type."
FT /evidence="ECO:0000269|PubMed:7957235"
FT CONFLICT 232
FT /note="F -> L (in Ref. 2; BAC28164)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 249 AA; 28123 MW; 90CE1F16BB235C97 CRC64;
MTILFLTMVI SYFGCMKAAP MKEVNVHGQG NLAYPGVRTH GTLESVNGPR AGSRGLTTTS
LADTFEHVIE ELLDEDQKVR PNEENHKDAD LYTSRVMLSS QVPLEPPLLF LLEEYKNYLD
AANMSMRVRR HSDPARRGEL SVCDSISEWV TAADKKTAVD MSGGTVTVLE KVPVSKGQLK
QYFYETKCNP MGYTKEGCRG IDKRHWNSQC RTTQSYVRAL TMDSKKRIGW RFIRIDTSCV
CTLTIKRGR