ID BDNF_HUMAN Reviewed; 247 AA. AC P23560; A7LA85; A7LA92; D3DQZ2; Q598Q1; Q6DN19; Q6YNR2; Q6YNR3; AC Q9BYY7; Q9UC24; DT 01-NOV-1991, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1991, sequence version 1. DT 11-NOV-2015, entry version 171. DE RecName: Full=Brain-derived neurotrophic factor; DE Short=BDNF; DE AltName: Full=Abrineurin; DE Flags: Precursor; GN Name=BDNF; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND ALTERNATIVE SPLICING (ISOFORM RP 1). RX PubMed=2236018; DOI=10.1073/pnas.87.20.8060; RA Jones K.R., Reichardt L.F.; RT "Molecular cloning of a human gene that is a member of the nerve RT growth factor family."; RL Proc. Natl. Acad. Sci. U.S.A. 87:8060-8064(1990). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1). 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., RA Belluscio L., de la Monte S.M., Squinto S., Furth M.E., RA Yancopoulos G.D.; RT "Human and rat brain-derived neurotrophic factor and neurotrophin-3: RT gene structures, distributions, and chromosomal localizations."; RL Genomics 10:558-568(1991). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=1339267; DOI=10.1016/S0006-291X(05)80148-2; RA Shintani A., Ono Y., Kaisho Y., Igarashi K.; RT "Characterization of the 5'-flanking region of the human brain-derived RT neurotrophic factor gene."; RL Biochem. Biophys. Res. Commun. 182:325-332(1992). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1; 2 AND 3), AND RP ALTERNATIVE SPLICING. RX PubMed=15666411; DOI=10.1002/ajmg.b.30109; RA Liu Q.-R., Walther D., Drgon T., Polesskaya O., Lesnick T.G., RA Strain K.J., de Andrade M., Bower J.H., Maraganore D.M., Uhl G.R.; RT "Human brain derived neurotrophic factor (BDNF) genes, splicing RT patterns, and assessments of associations with substance abuse and RT Parkinson's Disease."; RL Am. J. Med. Genet. B Neuropsychiatr. Genet. 134:93-103(2005). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3; 4 AND 5), ALTERNATIVE RP SPLICING, ALTERNATIVE PROMOTER USAGE, AND TISSUE SPECIFICITY. RC TISSUE=Brain; RX PubMed=17629449; DOI=10.1016/j.ygeno.2007.05.004; RA Pruunsild P., Kazantseva A., Aid T., Palm K., Timmusk T.; RT "Dissecting the human BDNF locus: bidirectional transcription, complex RT splicing, and multiple promoters."; RL Genomics 90:397-406(2007). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RA Cheng Y., Gu J.; RT "A cDNA clone of human brain-derived neurotrophic factor (HUMBDNFD)."; RL Submitted (MAY-1995) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RA Wu J., Zhang B., Zhou Y., Peng X., Yuan J., Qiang B.; RL Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT MET-66. RA Perez-Pinera P., Gonzalez-Martinez T., Garcia-Suarez O., RA Perez-Perez M., Esteban I., Monjil D., Vega J.A.; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Brain; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16554811; DOI=10.1038/nature04632; RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., RA Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., RA FitzGerald M.G., Jaffe D.B., LaButti K., Nicol R., Park H.-S., RA Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., RA Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., RA Sakaki Y.; RT "Human chromosome 11 DNA sequence and analysis including novel gene RT identification."; RL Nature 440:497-500(2006). RN [11] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [12] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [13] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [14] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 185-227. RC TISSUE=Leukocyte; 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). RN [15] RP PROTEIN SEQUENCE OF 129-144. RC TISSUE=Serum; RX PubMed=8527932; DOI=10.1006/prep.1995.1062; RA Rosenfeld R.D., Zeni L., Haniu M., Talvenheimo J., Radka S.F., RA Bennett L., Miller J.A., Welcher A.A.; RT "Purification and identification of brain-derived neurotrophic factor RT from human serum."; RL Protein Expr. Purif. 6:465-471(1995). RN [16] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 12-197. RX PubMed=11214319; DOI=10.1038/35054550; RA Murphy W.J., Eizirik E., Johnson W.E., Zhang Y.-P., Ryder O.A., RA O'Brien S.J.; RT "Molecular phylogenetics and the origins of placental mammals."; RL Nature 409:614-618(2001). RN [17] RP CHARACTERIZATION, AND MUTAGENESIS OF ARG-54. RX PubMed=11152678; DOI=10.1074/jbc.M008104200; RA Mowla S.J., Farhadi H.F., Pareek S., Atwal J.K., Morris S.J., RA Seidah N.G., Murphy R.A.; RT "Biosynthesis and post-translational processing of the precursor to RT brain-derived neurotrophic factor."; RL J. Biol. Chem. 276:12660-12666(2001). RN [18] RP POLYMORPHISM, AND ASSOCIATION WITH BULIMIA NERVOSA. RX PubMed=15115760; DOI=10.1093/hmg/ddh137; RA Ribases M., Gratacos M., Fernandez-Aranda F., Bellodi L., Boni C., RA Anderluh M., Cavallini M.C., Cellini E., Di Bella D., Erzegovesi S., RA Foulon C., Gabrovsek M., Gorwood P., Hebebrand J., Hinney A., RA Holliday J., Hu X., Karwautz A., Kipman A., Komel R., Nacmias B., RA Remschmidt H., Ricca V., Sorbi S., Wagner G., Treasure J., RA Collier D.A., Estivill X.; RT "Association of BDNF with anorexia, bulimia and age of onset of weight RT loss in six European populations."; RL Hum. Mol. Genet. 13:1205-1212(2004). RN [19] RP INVOLVEMENT IN WAGRO SYNDROME. RX PubMed=18753648; DOI=10.1056/NEJMoa0801119; RA Han J.C., Liu Q.-R., Jones M., Levinn R.L., Menzie C.M., RA Jefferson-George K.S., Adler-Wailes D.C., Sanford E.L., Lacbawan F.L., RA Uhl G.R., Rennert O.M., Yanovski J.A.; RT "Brain-derived neurotrophic factor and obesity in the WAGR syndrome."; RL N. Engl. J. Med. 359:918-927(2008). RN [20] RP ERRATUM. RA Han J.C., Liu Q.-R., Jones M., Levinn R.L., Menzie C.M., RA Jefferson-George K.S., Adler-Wailes D.C., Sanford E.L., Lacbawan F.L., RA Uhl G.R., Rennert O.M., Yanovski J.A.; RL N. Engl. J. Med. 359:1414-1414(2008). RN [21] RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS). RX PubMed=7703225; DOI=10.1021/bi00013a001; RA Robinson R.C., Radziejewski C., Stuart D.I., Jones E.Y.; RT "Structure of the brain-derived neurotrophic factor/neurotrophin 3 RT heterodimer."; RL Biochemistry 34:4139-4146(1995). RN [22] RP VARIANT MET-66. RX PubMed=10391209; DOI=10.1038/10290; RA Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., RA Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., RA Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., RA Lander E.S.; RT "Characterization of single-nucleotide polymorphisms in coding regions RT of human genes."; RL Nat. Genet. 22:231-238(1999). RN [23] RP ERRATUM. RA Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., RA Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., RA Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., RA Lander E.S.; RL Nat. Genet. 23:373-373(1999). RN [24] RP VARIANT CCHS ILE-2. RX PubMed=11840487; DOI=10.1002/ajmg.10133; RA Weese-Mayer D.E., Bolk S., Silvestri J.M., Chakravarti A.; RT "Idiopathic congenital central hypoventilation syndrome: evaluation of RT brain-derived neurotrophic factor genomic DNA sequence variation."; RL Am. J. Med. Genet. 107:306-310(2002). RN [25] RP VARIANT MET-66, AND ROLE OF VARIANT MET-66 IN OBSESSIVE-COMPULSIVE RP DISORDER. RX PubMed=12836135; DOI=10.1086/377003; RA Hall D., Dhilla A., Charalambous A., Gogos J.A., Karayiorgou M.; RT "Sequence variants of the brain-derived neurotrophic factor (BDNF) RT gene are strongly associated with obsessive-compulsive disorder."; RL Am. J. Hum. Genet. 73:370-376(2003). RN [26] RP VARIANT MET-66, CHARACTERIZATION OF VARIANT MET-66, AND ROLE IN RP EPISODIC MEMORY. RX PubMed=12553913; DOI=10.1016/S0092-8674(03)00035-7; RA Egan M.F., Kojima M., Callicott J.H., Goldberg T.E., Kolachana B.S., RA Bertolino A., Zaitsev E., Gold B., Goldman D., Dean M., Lu B., RA Weinberger D.R.; RT "The BDNF val66met polymorphism affects activity-dependent secretion RT of BDNF and human memory and hippocampal function."; RL Cell 112:257-269(2003). RN [27] RP VARIANT MET-66. RX PubMed=14566559; DOI=10.1007/s00439-003-1036-z; RA Sasaki A., Kanai M., Kijima K., Akaba K., Hashimoto M., Hasegawa H., RA Otaki S., Koizumi T., Kusuda S., Ogawa Y., Tuchiya K., Yamamoto W., RA Nakamura T., Hayasaka K.; RT "Molecular analysis of congenital central hypoventilation syndrome."; RL Hum. Genet. 114:22-26(2003). RN [28] RP VARIANT MET-66, AND ASSOCIATION OF VARIANT MET-66 WITH ANR. RX PubMed=12888803; DOI=10.1038/sj.mp.4001281; RA Ribases M., Gratacos M., Armengol L., de Cid R., Badia A., Jimenez L., RA Solano R., Vallejo J., Fernandez F., Estivill X.; RT "Met66 in the brain-derived neurotrophic factor (BDNF) precursor is RT associated with anorexia nervosa restrictive type."; RL Mol. Psychiatry 8:745-751(2003). CC -!- FUNCTION: During development, promotes the survival and CC differentiation of selected neuronal populations of the peripheral CC and central nervous systems. Participates in axonal growth, CC pathfinding and in the modulation of dendritic growth and CC morphology. Major regulator of synaptic transmission and CC plasticity at adult synapses in many regions of the CNS. The CC versatility of BDNF is emphasized by its contribution to a range CC of adaptive neuronal responses including long-term potentiation CC (LTP), long-term depression (LTD), certain forms of short-term CC synaptic plasticity, as well as homeostatic regulation of CC intrinsic neuronal excitability. {ECO:0000269|PubMed:12553913}. CC -!- SUBUNIT: Monomers and homodimers. Binds to NTRK2/TRKB. CC -!- SUBCELLULAR LOCATION: Secreted. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative promoter usage, Alternative splicing; Named isoforms=5; CC Comment=2 types of transcripts are produced: non-coding CC transcripts (antisense, opposite strand (OS), 8 exons) and CC coding transcripts (11 exons). Brain BDNF and anti-BDNF CC transcripts form dsRNA duplexes.; CC Name=1; CC IsoId=P23560-1; Sequence=Displayed; CC Name=2; CC IsoId=P23560-2; Sequence=VSP_037948; CC Name=3; CC IsoId=P23560-3; Sequence=VSP_038099; CC Name=4; CC IsoId=P23560-4; Sequence=VSP_038100; CC Name=5; CC IsoId=P23560-5; Sequence=VSP_038101; CC -!- TISSUE SPECIFICITY: Brain. Highly expressed in hippocampus, CC amygdala, cerebral cortex and cerebellum. Also expressed in heart, CC lung, skeletal muscle, testis, prostate and placenta. CC {ECO:0000269|PubMed:17629449}. CC -!- PTM: The propeptide is N-glycosylated and glycosulfated. CC -!- PTM: Converted into mature BDNF by plasmin (PLG). {ECO:0000250}. CC -!- POLYMORPHISM: Variations in BDNF are associated with CC susceptibility to bulimia nervosa 2 (BULN2) [MIM:610269]. Several CC genes with an essential role in the regulation of eating behavior CC and body weight are considered candidates involved in the etiology CC of eating disorders (ED), but no relevant susceptibility genes CC with a major effect on anorexia nervosa (AN) or bulimia nervosa CC (BN) have been identified. BDNF has been implicated in the CC regulation of food intake and body weight in rodents. A strong CC association has been reported of the Met-66 allele of the Val-66- CC Met BDNF variant with restricting AN (ANR) and low minimum body CC mass index in Spanish patients. Met-66 variant is strongly CC associated to all ED subtypes (AN, ANR, binge-eating/purging AN CC and BN) in European patients. Another single nucleotide CC polymorphism located in the promoter region of the BDNF gene CC showed an effect on BN and late age at onset of weight loss. These CC are two variants associated with the pathophysiology of ED in CC different populations. These variants support a role for BDNF in CC the susceptibility to aberrant eating behaviors. CC -!- DISEASE: Congenital central hypoventilation syndrome (CCHS) CC [MIM:209880]: Rare disorder characterized by abnormal control of CC respiration in the absence of neuromuscular or lung disease, or an CC identifiable brain stem lesion. A deficiency in autonomic control CC of respiration results in inadequate or negligible ventilatory and CC arousal responses to hypercapnia and hypoxemia. CC {ECO:0000269|PubMed:11840487}. Note=The disease is caused by CC mutations affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the NGF-beta family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Wikipedia; Note=BDNF entry; CC URL="https://en.wikipedia.org/wiki/Brain-derived_neurotrophic_factor"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M37762; AAA51820.1; -; Genomic_DNA. DR EMBL; M61176; AAA69805.2; -; mRNA. DR EMBL; M61181; AAA96140.1; -; Genomic_DNA. DR EMBL; X60201; CAA42761.1; -; mRNA. DR EMBL; AY054392; AAL23557.2; -; mRNA. DR EMBL; AY054393; AAL23558.1; -; mRNA. DR EMBL; AY054394; AAL23559.1; -; mRNA. DR EMBL; AY054395; AAL23560.1; -; mRNA. DR EMBL; AY054396; AAL23561.1; -; mRNA. DR EMBL; AY054397; AAL23562.1; -; mRNA. DR EMBL; AY054398; AAL23563.1; -; mRNA. DR EMBL; AY054399; AAL23564.1; -; mRNA. DR EMBL; AY054400; AAL23565.2; -; mRNA. DR EMBL; AF411339; AAO15434.1; -; Genomic_DNA. DR EMBL; EF674517; ABS29021.1; -; mRNA. DR EMBL; EF674518; ABS29022.1; -; mRNA. DR EMBL; EF674519; ABS29023.1; -; mRNA. DR EMBL; EF674520; ABS29024.1; -; mRNA. DR EMBL; EF674521; ABS29025.1; -; mRNA. DR EMBL; EF689009; ABS32249.1; -; mRNA. DR EMBL; EF689010; ABS32250.1; -; mRNA. DR EMBL; EF689011; ABS32251.1; -; mRNA. DR EMBL; EF689012; ABS32252.1; -; mRNA. DR EMBL; EF689013; ABS32253.1; -; mRNA. DR EMBL; EF689014; ABS32254.1; -; mRNA. DR EMBL; EF689015; ABS32255.1; -; mRNA. DR EMBL; EF689016; ABS32256.1; -; mRNA. DR EMBL; EF689017; ABS32257.1; -; mRNA. DR EMBL; EF689018; ABS32258.1; -; mRNA. DR EMBL; EF689019; ABS32259.1; -; mRNA. DR EMBL; EF689020; ABS32260.1; -; mRNA. DR EMBL; EF689021; ABS32261.1; -; mRNA. DR EMBL; X91251; CAA62632.1; -; mRNA. DR EMBL; AF400438; AAK92487.1; -; mRNA. DR EMBL; AY656701; AAT74399.1; -; mRNA. DR EMBL; AK289853; BAF82542.1; -; mRNA. DR EMBL; AK289763; BAF82452.1; -; mRNA. DR EMBL; AC104563; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471064; EAW68274.1; -; Genomic_DNA. DR EMBL; CH471064; EAW68278.1; -; Genomic_DNA. DR EMBL; CH471064; EAW68279.1; -; Genomic_DNA. DR EMBL; CH471064; EAW68275.1; -; Genomic_DNA. DR EMBL; CH471064; EAW68276.1; -; Genomic_DNA. DR EMBL; CH471064; EAW68277.1; -; Genomic_DNA. DR EMBL; BC029795; AAH29795.1; -; mRNA. DR EMBL; AY011481; AAG47514.1; -; Genomic_DNA. DR CCDS; CCDS41628.1; -. [P23560-3] DR CCDS; CCDS44558.1; -. [P23560-4] DR CCDS; CCDS7865.1; -. [P23560-2] DR CCDS; CCDS7866.1; -. [P23560-1] DR PIR; B36208; A40304. DR RefSeq; NP_001137277.1; NM_001143805.1. [P23560-1] DR RefSeq; NP_001137278.1; NM_001143806.1. [P23560-1] DR RefSeq; NP_001137279.1; NM_001143807.1. [P23560-1] DR RefSeq; NP_001137280.1; NM_001143808.1. [P23560-1] DR RefSeq; NP_001137281.1; NM_001143809.1. [P23560-5] DR RefSeq; NP_001137282.1; NM_001143810.1. [P23560-4] DR RefSeq; NP_001137283.1; NM_001143811.1. [P23560-1] DR RefSeq; NP_001137284.1; NM_001143812.1. [P23560-1] DR RefSeq; NP_001137285.1; NM_001143813.1. [P23560-1] DR RefSeq; NP_001137286.1; NM_001143814.1. [P23560-1] DR RefSeq; NP_001137288.1; NM_001143816.1. [P23560-1] DR RefSeq; NP_001700.2; NM_001709.4. [P23560-1] DR RefSeq; NP_733927.1; NM_170731.4. [P23560-2] DR RefSeq; NP_733928.1; NM_170732.4. [P23560-1] DR RefSeq; NP_733929.1; NM_170733.3. [P23560-1] DR RefSeq; NP_733930.1; NM_170734.3. [P23560-3] DR RefSeq; NP_733931.1; NM_170735.5. [P23560-1] DR RefSeq; XP_011518582.1; XM_011520280.1. [P23560-4] DR UniGene; Hs.502182; -. DR PDB; 1B8M; X-ray; 2.75 A; A=129-247. DR PDB; 1BND; X-ray; 2.30 A; A=129-247. DR PDBsum; 1B8M; -. DR PDBsum; 1BND; -. DR ProteinModelPortal; P23560; -. DR SMR; P23560; 136-244. DR BioGrid; 107096; 8. DR DIP; DIP-5719N; -. DR IntAct; P23560; 7. DR MINT; MINT-1508504; -. DR STRING; 9606.ENSP00000414303; -. DR PhosphoSite; P23560; -. DR BioMuta; BDNF; -. DR DMDM; 114900; -. DR PaxDb; P23560; -. DR PRIDE; P23560; -. DR DNASU; 627; -. DR Ensembl; ENST00000314915; ENSP00000320002; ENSG00000176697. [P23560-2] DR Ensembl; ENST00000356660; ENSP00000349084; ENSG00000176697. [P23560-1] DR Ensembl; ENST00000395978; ENSP00000379302; ENSG00000176697. [P23560-1] DR Ensembl; ENST00000395980; ENSP00000379304; ENSG00000176697. [P23560-1] DR Ensembl; ENST00000395981; ENSP00000379305; ENSG00000176697. [P23560-1] DR Ensembl; ENST00000395983; ENSP00000379307; ENSG00000176697. [P23560-1] DR Ensembl; ENST00000395986; ENSP00000379309; ENSG00000176697. [P23560-3] DR Ensembl; ENST00000418212; ENSP00000400502; ENSG00000176697. [P23560-1] DR Ensembl; ENST00000420794; ENSP00000389564; ENSG00000176697. [P23560-1] DR Ensembl; ENST00000438929; ENSP00000414303; ENSG00000176697. [P23560-4] DR Ensembl; ENST00000439476; ENSP00000389345; ENSG00000176697. [P23560-1] DR Ensembl; ENST00000525528; ENSP00000437138; ENSG00000176697. [P23560-1] DR Ensembl; ENST00000525950; ENSP00000432035; ENSG00000176697. [P23560-1] DR Ensembl; ENST00000530861; ENSP00000435564; ENSG00000176697. [P23560-1] DR Ensembl; ENST00000532997; ENSP00000435805; ENSG00000176697. [P23560-1] DR Ensembl; ENST00000533131; ENSP00000432727; ENSG00000176697. [P23560-1] DR Ensembl; ENST00000533246; ENSP00000432376; ENSG00000176697. [P23560-1] DR GeneID; 627; -. DR KEGG; hsa:627; -. DR UCSC; uc001mrt.3; human. [P23560-3] DR UCSC; uc001mru.3; human. [P23560-1] DR UCSC; uc001msa.3; human. [P23560-2] DR UCSC; uc009yje.3; human. [P23560-4] DR UCSC; uc009yjf.3; human. [P23560-5] DR CTD; 627; -. DR GeneCards; BDNF; -. DR H-InvDB; HIX0035926; -. DR HGNC; HGNC:1033; BDNF. DR HPA; CAB009564; -. DR MIM; 113505; gene. DR MIM; 209880; phenotype. DR MIM; 610269; phenotype. DR neXtProt; NX_P23560; -. DR Orphanet; 893; WAGR syndrome. DR PharmGKB; PA31891; -. DR eggNOG; ENOG410IH7X; Eukaryota. DR eggNOG; ENOG410XRPH; LUCA. DR GeneTree; ENSGT00390000007725; -. DR HOVERGEN; HBG006494; -. DR InParanoid; P23560; -. DR KO; K04355; -. DR OMA; RVGWRFI; -. DR OrthoDB; EOG7RBZ8Z; -. DR PhylomeDB; P23560; -. DR TreeFam; TF106463; -. DR SignaLink; P23560; -. DR EvolutionaryTrace; P23560; -. DR GeneWiki; Brain-derived_neurotrophic_factor; -. DR GenomeRNAi; 627; -. DR NextBio; 2530; -. DR PMAP-CutDB; Q6YNR3; -. DR PRO; PR:P23560; -. DR Proteomes; UP000005640; Chromosome 11. DR Bgee; P23560; -. DR CleanEx; HS_BDNF; -. DR ExpressionAtlas; P23560; baseline and differential. DR Genevisible; P23560; HS. DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB. DR GO; GO:0016023; C:cytoplasmic membrane-bounded vesicle; IBA:GO_Central. DR GO; GO:0030425; C:dendrite; IEA:Ensembl. DR GO; GO:0005615; C:extracellular space; IEA:Ensembl. DR GO; GO:0030061; C:mitochondrial crista; IEA:Ensembl. DR GO; GO:0043204; C:perikaryon; IEA:Ensembl. DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB. DR GO; GO:0008021; C:synaptic vesicle; IEA:Ensembl. DR GO; GO:0043195; C:terminal bouton; IEA:Ensembl. DR GO; GO:0008083; F:growth factor activity; TAS:ProtInc. DR GO; GO:0005169; F:neurotrophin TRKB receptor binding; IBA:GO_Central. DR GO; GO:0048675; P:axon extension; IEA:Ensembl. DR GO; GO:0007411; P:axon guidance; TAS:BHF-UCL. DR GO; GO:0007412; P:axon target recognition; IEA:Ensembl. DR GO; GO:0001662; P:behavioral fear response; IEA:Ensembl. DR GO; GO:0031547; P:brain-derived neurotrophic factor receptor signaling pathway; TAS:BHF-UCL. DR GO; GO:0007267; P:cell-cell signaling; IBA:GO_Central. DR GO; GO:1990090; P:cellular response to nerve growth factor stimulus; IEA:Ensembl. DR GO; GO:0071874; P:cellular response to norepinephrine stimulus; IEA:Ensembl. DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IEA:Ensembl. DR GO; GO:0002544; P:chronic inflammatory response; IEA:Ensembl. DR GO; GO:0048668; P:collateral sprouting; IDA:BHF-UCL. DR GO; GO:0016358; P:dendrite development; IEA:Ensembl. DR GO; GO:0097484; P:dendrite extension; IEA:Ensembl. DR GO; GO:0060079; P:excitatory postsynaptic potential; IEA:Ensembl. DR GO; GO:0007631; P:feeding behavior; IEA:Ensembl. DR GO; GO:0007214; P:gamma-aminobutyric acid signaling pathway; IEA:Ensembl. DR GO; GO:0014047; P:glutamate secretion; IEA:Ensembl. DR GO; GO:0060080; P:inhibitory postsynaptic potential; IEA:Ensembl. DR GO; GO:0048839; P:inner ear development; IEA:Ensembl. DR GO; GO:0007612; P:learning; IEA:Ensembl. DR GO; GO:0042490; P:mechanoreceptor differentiation; IEA:Ensembl. DR GO; GO:0006120; P:mitochondrial electron transport, NADH to ubiquinone; IEA:Ensembl. DR GO; GO:0007406; P:negative regulation of neuroblast proliferation; IEA:Ensembl. DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IBA:GO_Central. DR GO; GO:0045843; P:negative regulation of striated muscle tissue development; IEA:Ensembl. DR GO; GO:0032229; P:negative regulation of synaptic transmission, GABAergic; IEA:Ensembl. DR GO; GO:0021675; P:nerve development; IEA:Ensembl. DR GO; GO:0007399; P:nervous system development; TAS:ProtInc. DR GO; GO:0048812; P:neuron projection morphogenesis; IBA:GO_Central. DR GO; GO:0008038; P:neuron recognition; IEA:Ensembl. DR GO; GO:0031550; P:positive regulation of brain-derived neurotrophic factor receptor signaling pathway; TAS:BHF-UCL. DR GO; GO:0048672; P:positive regulation of collateral sprouting; IDA:BHF-UCL. DR GO; GO:2000324; P:positive regulation of glucocorticoid receptor signaling pathway; IEA:Ensembl. DR GO; GO:0048170; P:positive regulation of long-term neuronal synaptic plasticity; IEA:Ensembl. DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IEA:Ensembl. DR GO; GO:0051091; P:positive regulation of sequence-specific DNA binding transcription factor activity; IEA:Ensembl. DR GO; GO:0051965; P:positive regulation of synapse assembly; IDA:BHF-UCL. DR GO; GO:0030516; P:regulation of axon extension; IEA:Ensembl. DR GO; GO:0045664; P:regulation of neuron differentiation; IBA:GO_Central. DR GO; GO:0046668; P:regulation of retinal cell programmed cell death; IEA:Ensembl. DR GO; GO:0048172; P:regulation of short-term neuronal synaptic plasticity; IEA:Ensembl. DR GO; GO:0014823; P:response to activity; IEA:Ensembl. DR GO; GO:0072347; P:response to anesthetic; IEA:Ensembl. DR GO; GO:0010996; P:response to auditory stimulus; IEA:Ensembl. DR GO; GO:0051602; P:response to electrical stimulus; IEA:Ensembl. DR GO; GO:0014076; P:response to fluoxetine; IEA:Ensembl. DR GO; GO:0032094; P:response to food; IEA:Ensembl. DR GO; GO:0009725; P:response to hormone; IEA:Ensembl. DR GO; GO:0055093; P:response to hyperoxia; IEA:Ensembl. DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl. DR GO; GO:1902065; P:response to L-glutamate; IEA:Ensembl. DR GO; GO:0009642; P:response to light intensity; IEA:Ensembl. DR GO; GO:0035864; P:response to potassium ion; IEA:Ensembl. DR GO; GO:0033189; P:response to vitamin A; IEA:Ensembl. DR GO; GO:0007416; P:synapse assembly; IDA:BHF-UCL. DR GO; GO:0061193; P:taste bud development; IEA:Ensembl. DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central. DR GO; GO:0001657; P:ureteric bud development; IEA:Ensembl. 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 Pfam; PF00243; NGF; 1. DR PIRSF; PIRSF001789; NGF; 1. DR PRINTS; PR01912; BDNFACTOR. DR PRINTS; PR00268; NGF. DR ProDom; PD002052; Nerve_growth_factor-rel; 1. 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 3D-structure; Alternative promoter usage; Alternative splicing; KW Cleavage on pair of basic residues; Complete proteome; KW Direct protein sequencing; Disease mutation; Disulfide bond; KW Glycoprotein; Growth factor; Polymorphism; Reference proteome; KW Secreted; Signal. FT SIGNAL 1 18 {ECO:0000255}. FT PROPEP 19 128 {ECO:0000269|PubMed:8527932}. FT /FTId=PRO_0000019633. FT CHAIN 129 247 Brain-derived neurotrophic factor. FT /FTId=PRO_0000019634. FT SITE 57 58 Cleavage; by S1P. FT CARBOHYD 121 121 N-linked (GlcNAc...). FT DISULFID 141 208 FT DISULFID 186 237 FT DISULFID 196 239 FT VAR_SEQ 1 1 M -> MFHQVRRVM (in isoform 2). FT {ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15666411, FT ECO:0000303|PubMed:17629449}. FT /FTId=VSP_037948. FT VAR_SEQ 1 1 M -> MQSREEEWFHQVRRVM (in isoform 3). FT {ECO:0000303|PubMed:15666411, FT ECO:0000303|PubMed:17629449}. FT /FTId=VSP_038099. FT VAR_SEQ 1 1 M -> MCGATSFLHECTRLILVTTQNAEFLQKGLQVHTCFG FT VYPHASVWHDCASQKKGCAVYLHVSVEFNKLIPENGFIKFH FT QVRRVM (in isoform 4). FT {ECO:0000303|PubMed:17629449}. FT /FTId=VSP_038100. FT VAR_SEQ 1 1 M -> MLCAISLCARVRKLRSAGRCGKFHQVRRVM (in FT isoform 5). FT {ECO:0000303|PubMed:17629449}. FT /FTId=VSP_038101. FT VARIANT 2 2 T -> I (in CCHS; dbSNP:rs8192466). FT {ECO:0000269|PubMed:11840487}. FT /FTId=VAR_018260. FT VARIANT 66 66 V -> M (polymorphism; impairs FT localization to secretory granules or FT synapses; associated with poorer episodic FT memory; may have a protective effect in FT obsessive-compulsive disorder; FT dbSNP:rs6265). FT {ECO:0000269|PubMed:10391209, FT ECO:0000269|PubMed:12553913, FT ECO:0000269|PubMed:12836135, FT ECO:0000269|PubMed:12888803, FT ECO:0000269|PubMed:14566559, FT ECO:0000269|Ref.8}. FT /FTId=VAR_004626. FT VARIANT 75 75 Q -> H (in dbSNP:rs1048218). FT /FTId=VAR_011797. FT VARIANT 125 125 R -> M (in dbSNP:rs1048220). FT /FTId=VAR_011798. FT VARIANT 127 127 R -> L (in dbSNP:rs1048221). FT /FTId=VAR_011799. FT MUTAGEN 54 54 R->A: Abolishes processing by S1P. FT {ECO:0000269|PubMed:11152678}. FT STRAND 138 141 {ECO:0000244|PDB:1BND}. FT STRAND 143 149 {ECO:0000244|PDB:1BND}. FT HELIX 150 153 {ECO:0000244|PDB:1BND}. FT STRAND 155 158 {ECO:0000244|PDB:1BND}. FT STRAND 163 166 {ECO:0000244|PDB:1BND}. FT STRAND 168 171 {ECO:0000244|PDB:1BND}. FT STRAND 173 178 {ECO:0000244|PDB:1BND}. FT STRAND 180 186 {ECO:0000244|PDB:1BND}. FT HELIX 191 193 {ECO:0000244|PDB:1BND}. FT TURN 201 203 {ECO:0000244|PDB:1BND}. FT STRAND 204 220 {ECO:0000244|PDB:1BND}. FT STRAND 226 243 {ECO:0000244|PDB:1BND}. SQ SEQUENCE 247 AA; 27818 MW; 0A60488254722A99 CRC64; MTILFLTMVI SYFGCMKAAP MKEANIRGQG GLAYPGVRTH GTLESVNGPK AGSRGLTSLA DTFEHVIEEL LDEDQKVRPN EENNKDADLY TSRVMLSSQV PLEPPLLFLL EEYKNYLDAA NMSMRVRRHS DPARRGELSV CDSISEWVTA ADKKTAVDMS GGTVTVLEKV PVSKGQLKQY FYETKCNPMG YTKEGCRGID KRHWNSQCRT TQSYVRALTM DSKKRIGWRF IRIDTSCVCT LTIKRGR //