BDNF_HUMAN
ID BDNF_HUMAN Reviewed; 247 AA.
AC P23560; A7LA85; A7LA92; D3DQZ2; Q598Q1; Q6DN19; Q6YNR2; Q6YNR3; Q9BYY7;
AC Q9UC24;
DT 01-NOV-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1991, sequence version 1.
DT 03-AUG-2022, entry version 216.
DE RecName: Full=Brain-derived neurotrophic factor;
DE Short=BDNF;
DE AltName: Full=Abrineurin;
DE Contains:
DE RecName: Full=BDNF precursor form {ECO:0000305};
DE Short=ProBDNF {ECO:0000305};
DE Flags: Precursor;
GN Name=BDNF {ECO:0000303|PubMed:28397838, ECO:0000312|HGNC:HGNC:1033};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING (ISOFORM 1), AND
RP TISSUE SPECIFICITY.
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 growth
RT 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., 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 [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., Strain K.J.,
RA de Andrade M., Bower J.H., Maraganore D.M., Uhl G.R.;
RT "Human brain derived neurotrophic factor (BDNF) genes, splicing patterns,
RT and assessments of associations with substance abuse and Parkinson's
RT 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., Perez-Perez M.,
RA 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., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., 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., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA 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., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., 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., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., 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., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., 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 project:
RT 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, SUBCELLULAR LOCATION, AND INTERACTION WITH
RP NTRK2.
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., Bennett L.,
RA Miller J.A., Welcher A.A.;
RT "Purification and identification of brain-derived neurotrophic factor from
RT 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 FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH NTRK2, PROTEOLYTIC
RP CLEAVAGE, PARTIAL PROTEIN SEQUENCE, TISSUE SPECIFICITY, GLYCOSYLATION AT
RP ASN-121, 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., Seidah N.G.,
RA Murphy R.A.;
RT "Biosynthesis and post-translational processing of the precursor to brain-
RT derived neurotrophic factor.";
RL J. Biol. Chem. 276:12660-12666(2001).
RN [18]
RP SUBCELLULAR LOCATION, PROTEOLYTIC CLEAVAGE, VARIANT MET-66, GLYCOSYLATION
RP AT ASN-121, AND TISSUE SPECIFICITY.
RX PubMed=19467646; DOI=10.1016/j.archoralbio.2009.04.005;
RA Mandel A.L., Ozdener H., Utermohlen V.;
RT "Identification of pro- and mature brain-derived neurotrophic factor in
RT human saliva.";
RL Arch. Oral Biol. 54:689-695(2009).
RN [19]
RP INTERACTION WITH SORCS2 AND NGFR, AND FUNCTION.
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 [20] {ECO:0007744|PDB:1BND}
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 129-247 IN COMPLEX WITH NTF3, AND
RP DISULFIDE BONDS.
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 [21] {ECO:0007744|PDB:1B8M}
RP X-RAY CRYSTALLOGRAPHY (2.75 ANGSTROMS) OF 129-247 IN COMPLEX WITH NTF4, AND
RP DISULFIDE BONDS.
RX PubMed=10631974; DOI=10.1110/ps.8.12.2589;
RA Robinson R.C., Radziejewski C., Spraggon G., Greenwald J., Kostura M.R.,
RA Burtnick L.D., Stuart D.I., Choe S., Jones E.Y.;
RT "The structures of the neurotrophin 4 homodimer and the brain-derived
RT neurotrophic factor/neurotrophin 4 heterodimer reveal a common Trk-binding
RT site.";
RL Protein Sci. 8:2589-2597(1999).
RN [22]
RP VARIANT MET-66.
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., Holliday J.,
RA Hu X., Karwautz A., Kipman A., Komel R., Nacmias B., Remschmidt H.,
RA Ricca V., Sorbi S., Wagner G., Treasure J., Collier D.A., Estivill X.;
RT "Association of BDNF with anorexia, bulimia and age of onset of weight loss
RT in six European populations.";
RL Hum. Mol. Genet. 13:1205-1212(2004).
RN [23]
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 [24]
RP ERRATUM OF PUBMED:18753648.
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 [25]
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 of
RT human genes.";
RL Nat. Genet. 22:231-238(1999).
RN [26]
RP ERRATUM OF PUBMED:10391209.
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 [27]
RP VARIANT 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 [28]
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) gene are
RT strongly associated with obsessive-compulsive disorder.";
RL Am. J. Hum. Genet. 73:370-376(2003).
RN [29]
RP VARIANT MET-66, CHARACTERIZATION OF VARIANT MET-66, AND ROLE IN EPISODIC
RP 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 of
RT BDNF and human memory and hippocampal function.";
RL Cell 112:257-269(2003).
RN [30]
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 [31]
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).
RN [32]
RP VARIANT THR-122.
RX PubMed=28397838; DOI=10.1038/mp.2017.60;
RA Harripaul R., Vasli N., Mikhailov A., Rafiq M.A., Mittal K.,
RA Windpassinger C., Sheikh T.I., Noor A., Mahmood H., Downey S., Johnson M.,
RA Vleuten K., Bell L., Ilyas M., Khan F.S., Khan V., Moradi M., Ayaz M.,
RA Naeem F., Heidari A., Ahmed I., Ghadami S., Agha Z., Zeinali S., Qamar R.,
RA Mozhdehipanah H., John P., Mir A., Ansar M., French L., Ayub M.,
RA Vincent J.B.;
RT "Mapping autosomal recessive intellectual disability: combined microarray
RT and exome sequencing identifies 26 novel candidate genes in 192
RT consanguineous families.";
RL Mol. Psychiatry 23:973-984(2018).
RN [33]
RP FUNCTION, AND CHARACTERIZATION OF VARIANT MET-66.
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:11152678). 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 {ECO:0000269|PubMed:11152678, ECO:0000269|PubMed:12553913,
CC ECO:0000269|PubMed:29909994}.
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 (PubMed:24908487, PubMed:29909994). Signaling via NGFR and SORCS2 plays
CC a role in synaptic plasticity and long-term depression (LTD). Binding
CC to NGFR and SORCS2 promotes neuronal apoptosis. Promotes neuronal
CC growth cone collapse (By similarity). {ECO:0000250|UniProtKB:P21237,
CC ECO:0000269|PubMed:24908487, ECO:0000269|PubMed:29909994}.
CC -!- SUBUNIT: Monomers and homodimers. Binds to NTRK2/TRKB (PubMed:8527932,
CC PubMed:11152678). 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 (PubMed:7703225, PubMed:10631974). BDNF
CC precursor form: interacts with the heterodimer formed by NGFR and
CC SORCS2 (PubMed:24908487). {ECO:0000269|PubMed:10631974,
CC ECO:0000269|PubMed:11152678, ECO:0000269|PubMed:24908487,
CC ECO:0000269|PubMed:7703225, ECO:0000269|PubMed:8527932}.
CC -!- INTERACTION:
CC P23560; P34130: NTF4; NbExp=6; IntAct=EBI-1026003, EBI-3907456;
CC P23560-2; Q6UY14-3: ADAMTSL4; NbExp=3; IntAct=EBI-12275524, EBI-10173507;
CC P23560-2; Q15109: AGER; NbExp=3; IntAct=EBI-12275524, EBI-1646426;
CC P23560-2; Q9UIJ7: AK3; NbExp=3; IntAct=EBI-12275524, EBI-3916527;
CC P23560-2; Q8IWZ3-2: ANKHD1; NbExp=3; IntAct=EBI-12275524, EBI-9641396;
CC P23560-2; Q8IWZ3-3: ANKHD1; NbExp=3; IntAct=EBI-12275524, EBI-25833200;
CC P23560-2; Q6LES2: ANXA4; NbExp=3; IntAct=EBI-12275524, EBI-10250835;
CC P23560-2; Q8WW43: APH1B; NbExp=3; IntAct=EBI-12275524, EBI-2606497;
CC P23560-2; P05067: APP; NbExp=3; IntAct=EBI-12275524, EBI-77613;
CC P23560-2; Q9H0C5: BTBD1; NbExp=3; IntAct=EBI-12275524, EBI-935503;
CC P23560-2; Q9UQM7: CAMK2A; NbExp=3; IntAct=EBI-12275524, EBI-1383687;
CC P23560-2; Q8TAB7: CCDC26; NbExp=3; IntAct=EBI-12275524, EBI-10271580;
CC P23560-2; Q9BV29: CCDC32; NbExp=3; IntAct=EBI-12275524, EBI-2874058;
CC P23560-2; Q00535: CDK5; NbExp=3; IntAct=EBI-12275524, EBI-1041567;
CC P23560-2; Q6QEF8-4: CORO6; NbExp=3; IntAct=EBI-12275524, EBI-10699285;
CC P23560-2; Q14194: CRMP1; NbExp=3; IntAct=EBI-12275524, EBI-473101;
CC P23560-2; P35222: CTNNB1; NbExp=3; IntAct=EBI-12275524, EBI-491549;
CC P23560-2; Q15438: CYTH1; NbExp=3; IntAct=EBI-12275524, EBI-997830;
CC P23560-2; Q9BPW9-4: DHRS9; NbExp=3; IntAct=EBI-12275524, EBI-19157435;
CC P23560-2; P49184: DNASE1L1; NbExp=3; IntAct=EBI-12275524, EBI-20894690;
CC P23560-2; P07099: EPHX1; NbExp=3; IntAct=EBI-12275524, EBI-6138796;
CC P23560-2; O00471: EXOC5; NbExp=3; IntAct=EBI-12275524, EBI-949824;
CC P23560-2; Q5JX71: FAM209A; NbExp=3; IntAct=EBI-12275524, EBI-18304435;
CC P23560-2; O75344: FKBP6; NbExp=3; IntAct=EBI-12275524, EBI-744771;
CC P23560-2; Q10981: FUT2; NbExp=3; IntAct=EBI-12275524, EBI-9090702;
CC P23560-2; P06241: FYN; NbExp=3; IntAct=EBI-12275524, EBI-515315;
CC P23560-2; P22466: GAL; NbExp=3; IntAct=EBI-12275524, EBI-6624768;
CC P23560-2; Q8NEA9: GMCL2; NbExp=3; IntAct=EBI-12275524, EBI-745707;
CC P23560-2; Q8TDT2: GPR152; NbExp=3; IntAct=EBI-12275524, EBI-13345167;
CC P23560-2; Q9UBK5: HCST; NbExp=3; IntAct=EBI-12275524, EBI-2801937;
CC P23560-2; O43365: HOXA3; NbExp=3; IntAct=EBI-12275524, EBI-8643838;
CC P23560-2; Q96LI6-3: HSFY2; NbExp=3; IntAct=EBI-12275524, EBI-25830912;
CC P23560-2; Q92993-2: KAT5; NbExp=3; IntAct=EBI-12275524, EBI-20795332;
CC P23560-2; P18428: LBP; NbExp=3; IntAct=EBI-12275524, EBI-3927059;
CC P23560-2; Q96G30: MRAP2; NbExp=3; IntAct=EBI-12275524, EBI-9537218;
CC P23560-2; Q13405: MRPL49; NbExp=3; IntAct=EBI-12275524, EBI-5325200;
CC P23560-2; Q8TBJ4: PLPPR1; NbExp=3; IntAct=EBI-12275524, EBI-18063495;
CC P23560-2; P17612: PRKACA; NbExp=3; IntAct=EBI-12275524, EBI-476586;
CC P23560-2; P60891: PRPS1; NbExp=3; IntAct=EBI-12275524, EBI-749195;
CC P23560-2; A0A0C4DFM3: PRUNE2; NbExp=3; IntAct=EBI-12275524, EBI-25830870;
CC P23560-2; Q96GQ5: RUSF1; NbExp=3; IntAct=EBI-12275524, EBI-8636004;
CC P23560-2; Q96GZ6: SLC41A3; NbExp=3; IntAct=EBI-12275524, EBI-7225508;
CC P23560-2; Q8NCS7: SLC44A5; NbExp=3; IntAct=EBI-12275524, EBI-21504521;
CC P23560-2; Q7Z614-3: SNX20; NbExp=3; IntAct=EBI-12275524, EBI-12336127;
CC P23560-2; Q99523: SORT1; NbExp=3; IntAct=EBI-12275524, EBI-1057058;
CC P23560-2; Q9H808: TLE6; NbExp=3; IntAct=EBI-12275524, EBI-3921684;
CC P23560-2; P10599: TXN; NbExp=3; IntAct=EBI-12275524, EBI-594644;
CC P23560-2; Q15386-3: UBE3C; NbExp=3; IntAct=EBI-12275524, EBI-25833079;
CC P23560-2; Q9H6R7-2: WDCP; NbExp=3; IntAct=EBI-12275524, EBI-25833271;
CC P23560-2; O60293-2: ZFC3H1; NbExp=3; IntAct=EBI-12275524, EBI-25833374;
CC P23560-2; Q6P514: ZNF468; NbExp=3; IntAct=EBI-12275524, EBI-25833318;
CC P23560-2; A0A087WZY1; NbExp=3; IntAct=EBI-12275524, EBI-13387614;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:11152678,
CC ECO:0000269|PubMed:19467646, ECO:0000269|PubMed:8527932}.
CC -!- SUBCELLULAR LOCATION: [BDNF precursor form]: Secreted
CC {ECO:0000269|PubMed:11152678, ECO:0000269|PubMed:19467646}. Note=A
CC proportion of BDNF is secreted as immature precursor (proBDNF).
CC {ECO:0000269|PubMed:11152678, ECO:0000269|PubMed:19467646}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative promoter usage, Alternative splicing; Named isoforms=5;
CC Comment=2 types of transcripts are produced: non-coding transcripts
CC (antisense, opposite strand (OS), 8 exons) and coding transcripts (11
CC exons). Brain BDNF and anti-BDNF 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: Detected in blood plasma and in saliva (at protein
CC level) (PubMed:11152678, PubMed:19467646). Brain. Highly expressed in
CC hippocampus, amygdala, cerebral cortex and cerebellum. Also expressed
CC in heart, lung, skeletal muscle, testis, prostate and placenta.
CC {ECO:0000269|PubMed:11152678, ECO:0000269|PubMed:17629449,
CC ECO:0000269|PubMed:19467646, ECO:0000269|PubMed:2236018}.
CC -!- PTM: [BDNF precursor form]: N-glycosylated and glycosulfated, contrary
CC to mature BDNF. {ECO:0000269|PubMed:11152678,
CC ECO:0000269|PubMed:19467646}.
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
CC (PubMed:11152678). Can be converted into mature BDNF by plasmin (PLG)
CC (PubMed:19467646). {ECO:0000269|PubMed:11152678,
CC ECO:0000269|PubMed:19467646}.
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";
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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_011520280.2. [P23560-4]
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 AlphaFoldDB; P23560; -.
DR BMRB; P23560; -.
DR SMR; P23560; -.
DR BioGRID; 107096; 48.
DR DIP; DIP-5719N; -.
DR IntAct; P23560; 60.
DR STRING; 9606.ENSP00000414303; -.
DR BindingDB; P23560; -.
DR ChEMBL; CHEMBL4523205; -.
DR DrugBank; DB09301; Chondroitin sulfate.
DR DrugBank; DB09130; Copper.
DR DrugBank; DB05047; CX-717.
DR DrugBank; DB11823; Esketamine.
DR GlyGen; P23560; 1 site.
DR iPTMnet; P23560; -.
DR PhosphoSitePlus; P23560; -.
DR BioMuta; BDNF; -.
DR DMDM; 114900; -.
DR MassIVE; P23560; -.
DR PaxDb; P23560; -.
DR PeptideAtlas; P23560; -.
DR PRIDE; P23560; -.
DR ProteomicsDB; 54129; -. [P23560-1]
DR ProteomicsDB; 54130; -. [P23560-2]
DR ProteomicsDB; 54131; -. [P23560-3]
DR ProteomicsDB; 54132; -. [P23560-4]
DR ProteomicsDB; 54133; -. [P23560-5]
DR TopDownProteomics; P23560-2; -. [P23560-2]
DR ABCD; P23560; 4 sequenced antibodies.
DR Antibodypedia; 4032; 1196 antibodies from 50 providers.
DR DNASU; 627; -.
DR Ensembl; ENST00000314915.6; ENSP00000320002.6; ENSG00000176697.20. [P23560-2]
DR Ensembl; ENST00000356660.9; ENSP00000349084.4; ENSG00000176697.20. [P23560-1]
DR Ensembl; ENST00000395978.7; ENSP00000379302.3; ENSG00000176697.20. [P23560-1]
DR Ensembl; ENST00000395981.7; ENSP00000379305.3; ENSG00000176697.20. [P23560-1]
DR Ensembl; ENST00000395983.7; ENSP00000379307.3; ENSG00000176697.20. [P23560-1]
DR Ensembl; ENST00000395986.6; ENSP00000379309.2; ENSG00000176697.20. [P23560-3]
DR Ensembl; ENST00000418212.5; ENSP00000400502.1; ENSG00000176697.20. [P23560-1]
DR Ensembl; ENST00000438929.5; ENSP00000414303.1; ENSG00000176697.20. [P23560-4]
DR Ensembl; ENST00000439476.6; ENSP00000389345.2; ENSG00000176697.20. [P23560-1]
DR Ensembl; ENST00000525528.1; ENSP00000437138.1; ENSG00000176697.20. [P23560-1]
DR Ensembl; ENST00000525950.5; ENSP00000432035.1; ENSG00000176697.20. [P23560-1]
DR Ensembl; ENST00000530861.5; ENSP00000435564.1; ENSG00000176697.20. [P23560-1]
DR Ensembl; ENST00000532997.5; ENSP00000435805.1; ENSG00000176697.20. [P23560-1]
DR Ensembl; ENST00000533131.5; ENSP00000432727.1; ENSG00000176697.20. [P23560-1]
DR Ensembl; ENST00000533246.5; ENSP00000432376.1; ENSG00000176697.20. [P23560-1]
DR GeneID; 627; -.
DR KEGG; hsa:627; -.
DR MANE-Select; ENST00000356660.9; ENSP00000349084.4; NM_001709.5; NP_001700.2.
DR UCSC; uc001mrt.4; human. [P23560-1]
DR CTD; 627; -.
DR DisGeNET; 627; -.
DR GeneCards; BDNF; -.
DR HGNC; HGNC:1033; BDNF.
DR HPA; ENSG00000176697; Tissue enhanced (brain).
DR MalaCards; BDNF; -.
DR MIM; 113505; gene.
DR neXtProt; NX_P23560; -.
DR OpenTargets; ENSG00000176697; -.
DR Orphanet; 661; Congenital central hypoventilation syndrome.
DR Orphanet; 893; WAGR syndrome.
DR PharmGKB; PA31891; -.
DR VEuPathDB; HostDB:ENSG00000176697; -.
DR eggNOG; ENOG502QRU8; Eukaryota.
DR GeneTree; ENSGT00390000007725; -.
DR HOGENOM; CLU_059942_0_0_1; -.
DR InParanoid; P23560; -.
DR OMA; YPGMRTH; -.
DR OrthoDB; 1156054at2759; -.
DR PhylomeDB; P23560; -.
DR TreeFam; TF106463; -.
DR PathwayCommons; P23560; -.
DR Reactome; R-HSA-9022702; MECP2 regulates transcription of neuronal ligands.
DR Reactome; R-HSA-9024909; BDNF activates NTRK2 (TRKB) signaling.
DR Reactome; R-HSA-9026519; Activated NTRK2 signals through RAS.
DR Reactome; R-HSA-9026527; Activated NTRK2 signals through PLCG1.
DR Reactome; R-HSA-9028335; Activated NTRK2 signals through PI3K.
DR Reactome; R-HSA-9028731; Activated NTRK2 signals through FRS2 and FRS3.
DR Reactome; R-HSA-9032500; Activated NTRK2 signals through FYN.
DR Reactome; R-HSA-9032759; NTRK2 activates RAC1.
DR Reactome; R-HSA-9032845; Activated NTRK2 signals through CDK5.
DR SignaLink; P23560; -.
DR SIGNOR; P23560; -.
DR BioGRID-ORCS; 627; 14 hits in 1026 CRISPR screens.
DR ChiTaRS; BDNF; human.
DR EvolutionaryTrace; P23560; -.
DR GeneWiki; Brain-derived_neurotrophic_factor; -.
DR GenomeRNAi; 627; -.
DR Pharos; P23560; Tchem.
DR PRO; PR:P23560; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; P23560; protein.
DR Bgee; ENSG00000176697; Expressed in saphenous vein and 146 other tissues.
DR ExpressionAtlas; P23560; baseline and differential.
DR Genevisible; P23560; HS.
DR GO; GO:0030424; C:axon; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0030425; C:dendrite; IBA:GO_Central.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0016607; C:nuclear speck; IDA:HPA.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB.
DR GO; GO:0008021; C:synaptic vesicle; IBA:GO_Central.
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:0007411; P:axon guidance; TAS:BHF-UCL.
DR GO; GO:0031547; P:brain-derived neurotrophic factor receptor signaling pathway; TAS:BHF-UCL.
DR GO; GO:0048668; P:collateral sprouting; IDA:BHF-UCL.
DR GO; GO:0007613; P:memory; IBA:GO_Central.
DR GO; GO:0050804; P:modulation of chemical synaptic transmission; IBA:GO_Central.
DR GO; GO:2001234; P:negative regulation of apoptotic signaling pathway; ISS:ARUK-UCL.
DR GO; GO:0010832; P:negative regulation of myotube differentiation; ISS:ParkinsonsUK-UCL.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IBA:GO_Central.
DR GO; GO:0021675; P:nerve development; IBA:GO_Central.
DR GO; GO:0038180; P:nerve growth factor signaling pathway; IBA:GO_Central.
DR GO; GO:0007399; P:nervous system development; TAS:ProtInc.
DR GO; GO:0048812; P:neuron projection morphogenesis; IBA:GO_Central.
DR GO; GO:0007422; P:peripheral nervous system development; IBA:GO_Central.
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:0010976; P:positive regulation of neuron projection development; ISS:ARUK-UCL.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IBA:GO_Central.
DR GO; GO:1900122; P:positive regulation of receptor binding; IDA:ParkinsonsUK-UCL.
DR GO; GO:0051965; P:positive regulation of synapse assembly; IDA:BHF-UCL.
DR GO; GO:0045664; P:regulation of neuron differentiation; IBA:GO_Central.
DR GO; GO:2000008; P:regulation of protein localization to cell surface; TAS:ParkinsonsUK-UCL.
DR GO; GO:0007416; P:synapse assembly; IDA:BHF-UCL.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
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 3D-structure; Alternative promoter usage; Alternative splicing;
KW Cleavage on pair of basic residues; Direct protein sequencing;
KW Disease variant; Disulfide bond; Glycoprotein; Growth factor;
KW Reference proteome; Secreted; Signal.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT CHAIN 19..247
FT /note="BDNF precursor form"
FT /evidence="ECO:0000305"
FT /id="PRO_0000447533"
FT PROPEP 19..128
FT /evidence="ECO:0000305|PubMed:8527932"
FT /id="PRO_0000019633"
FT CHAIN 129..247
FT /note="Brain-derived neurotrophic factor"
FT /id="PRO_0000019634"
FT SITE 57..58
FT /note="Cleavage; by MBTPS1"
FT /evidence="ECO:0000269|PubMed:11152678"
FT CARBOHYD 121
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000305|PubMed:11152678,
FT ECO:0000305|PubMed:19467646"
FT DISULFID 141..208
FT /evidence="ECO:0000269|PubMed:10631974,
FT ECO:0000269|PubMed:7703225, ECO:0007744|PDB:1B8M,
FT ECO:0007744|PDB:1BND"
FT DISULFID 186..237
FT /evidence="ECO:0000269|PubMed:10631974,
FT ECO:0000269|PubMed:7703225, ECO:0007744|PDB:1B8M,
FT ECO:0007744|PDB:1BND"
FT DISULFID 196..239
FT /evidence="ECO:0000269|PubMed:10631974,
FT ECO:0000269|PubMed:7703225, ECO:0007744|PDB:1B8M,
FT ECO:0007744|PDB:1BND"
FT VAR_SEQ 1
FT /note="M -> MFHQVRRVM (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15666411, ECO:0000303|PubMed:17629449"
FT /id="VSP_037948"
FT VAR_SEQ 1
FT /note="M -> MQSREEEWFHQVRRVM (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15666411,
FT ECO:0000303|PubMed:17629449"
FT /id="VSP_038099"
FT VAR_SEQ 1
FT /note="M -> MCGATSFLHECTRLILVTTQNAEFLQKGLQVHTCFGVYPHASVWHDC
FT ASQKKGCAVYLHVSVEFNKLIPENGFIKFHQVRRVM (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:17629449"
FT /id="VSP_038100"
FT VAR_SEQ 1
FT /note="M -> MLCAISLCARVRKLRSAGRCGKFHQVRRVM (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:17629449"
FT /id="VSP_038101"
FT VARIANT 2
FT /note="T -> I (found in a patient with congenital central
FT hypoventilation syndrome; unknown pathological
FT significance; dbSNP:rs8192466)"
FT /evidence="ECO:0000269|PubMed:11840487"
FT /id="VAR_018260"
FT VARIANT 66
FT /note="V -> M (strongly associated with susceptibility to
FT eating disorders such as anorexia nervosa and bulimia
FT nervosa; associated with poorer episodic memory; may have a
FT protective effect in obsessive-compulsive disorder; impairs
FT localization to secretory granules or synapses; decreases
FT density of dendritic mushroom spines and synapses;
FT dbSNP:rs6265)"
FT /evidence="ECO:0000269|PubMed:10391209,
FT ECO:0000269|PubMed:12553913, ECO:0000269|PubMed:12836135,
FT ECO:0000269|PubMed:12888803, ECO:0000269|PubMed:14566559,
FT ECO:0000269|PubMed:15115760, ECO:0000269|PubMed:29909994,
FT ECO:0000269|Ref.8"
FT /id="VAR_004626"
FT VARIANT 75
FT /note="Q -> H (in dbSNP:rs1048218)"
FT /id="VAR_011797"
FT VARIANT 122
FT /note="M -> T (found in a small consanguineous family with
FT intellectual disability; unknown pathological significance;
FT dbSNP:rs765594245)"
FT /evidence="ECO:0000269|PubMed:28397838"
FT /id="VAR_080766"
FT VARIANT 125
FT /note="R -> M (in dbSNP:rs1048220)"
FT /id="VAR_011798"
FT VARIANT 127
FT /note="R -> L (in dbSNP:rs1048221)"
FT /id="VAR_011799"
FT MUTAGEN 54
FT /note="R->A: Abolishes processing by MBTPS1."
FT /evidence="ECO:0000269|PubMed:11152678"
FT STRAND 138..141
FT /evidence="ECO:0007829|PDB:1BND"
FT STRAND 143..149
FT /evidence="ECO:0007829|PDB:1BND"
FT HELIX 150..153
FT /evidence="ECO:0007829|PDB:1BND"
FT STRAND 155..158
FT /evidence="ECO:0007829|PDB:1BND"
FT STRAND 163..166
FT /evidence="ECO:0007829|PDB:1BND"
FT STRAND 168..171
FT /evidence="ECO:0007829|PDB:1BND"
FT STRAND 173..178
FT /evidence="ECO:0007829|PDB:1BND"
FT STRAND 180..186
FT /evidence="ECO:0007829|PDB:1BND"
FT HELIX 191..193
FT /evidence="ECO:0007829|PDB:1BND"
FT TURN 201..203
FT /evidence="ECO:0007829|PDB:1BND"
FT STRAND 204..220
FT /evidence="ECO:0007829|PDB:1BND"
FT STRAND 226..243
FT /evidence="ECO:0007829|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
