NTF3_HUMAN
ID NTF3_HUMAN Reviewed; 257 AA.
AC P20783; B7Z1T5; Q6FH50;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1991, sequence version 1.
DT 03-AUG-2022, entry version 205.
DE RecName: Full=Neurotrophin-3;
DE Short=NT-3;
DE AltName: Full=HDNF;
DE AltName: Full=Nerve growth factor 2;
DE Short=NGF-2;
DE AltName: Full=Neurotrophic factor;
DE Flags: Precursor;
GN Name=NTF3;
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 [MRNA] (ISOFORM 1).
RX PubMed=2365067; DOI=10.1016/0014-5793(90)81536-w;
RA Kaisho Y., Yoshimura K., Nakahama K.;
RT "Cloning and expression of a cDNA encoding a novel human neurotrophic
RT factor.";
RL FEBS Lett. 266:187-191(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
RX PubMed=2344409; DOI=10.1016/0896-6273(90)90203-r;
RA Rosenthal A., Goeddel D.V., Nguyen T., Lewis M., Shih A., Laramee G.R.,
RA Nikolics K., Winslow J.W.;
RT "Primary structure and biological activity of a novel human neurotrophic
RT factor.";
RL Neuron 4:767-773(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
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 [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Cerebellum;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P.,
RA Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y.,
RA LaBaer J.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [7]
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 [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [9]
RP NUCLEOTIDE SEQUENCE OF 194-236.
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 [10]
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 [11]
RP VARIANT GLU-76.
RX PubMed=7733919; DOI=10.1006/bbrc.1995.1531;
RA Hattori M., Nanko S.;
RT "Association of neurotrophin-3 gene variant with severe forms of
RT schizophrenia.";
RL Biochem. Biophys. Res. Commun. 209:513-518(1995).
RN [12]
RP VARIANT GLU-76.
RX PubMed=8925252; DOI=10.1097/00041444-199621000-00003;
RA Arinami T., Takekoshi K., Itokawa M., Hamaguchi H., Toru M.;
RT "Failure to find associations of the CA repeat polymorphism in the first
RT intron and the Gly-63/Glu-63 polymorphism of the neurotrophin-3 gene with
RT schizophrenia.";
RL Psychiatr. Genet. 6:13-15(1996).
CC -!- FUNCTION: Seems to promote the survival of visceral and proprioceptive
CC sensory neurons.
CC -!- INTERACTION:
CC P20783; P50222: MEOX2; NbExp=3; IntAct=EBI-1025994, EBI-748397;
CC P20783; P07174: Ngfr; Xeno; NbExp=4; IntAct=EBI-1025994, EBI-1038810;
CC P20783-2; Q14204: DYNC1H1; NbExp=3; IntAct=EBI-25844111, EBI-356015;
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P20783-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P20783-2; Sequence=VSP_043353;
CC -!- TISSUE SPECIFICITY: Brain and peripheral tissues.
CC -!- POLYMORPHISM: Variant Glu-76 (frequently reported as Glu-63) was
CC thought to be associated with severe forms of schizophrenia. This does
CC not seem to be the case. {ECO:0000269|PubMed:7733919,
CC ECO:0000269|PubMed:8925252}.
CC -!- SIMILARITY: Belongs to the NGF-beta family. {ECO:0000305}.
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DR EMBL; X53655; CAA37703.1; -; mRNA.
DR EMBL; M37763; AAA59953.1; -; Genomic_DNA.
DR EMBL; M61180; AAA63231.1; -; Genomic_DNA.
DR EMBL; AK293895; BAH11621.1; -; mRNA.
DR EMBL; CR541906; CAG46704.1; -; mRNA.
DR EMBL; CH471116; EAW88824.1; -; Genomic_DNA.
DR EMBL; CH471116; EAW88825.1; -; Genomic_DNA.
DR EMBL; BC069773; AAH69773.1; -; mRNA.
DR EMBL; BC107075; AAI07076.1; -; mRNA.
DR CCDS; CCDS44806.1; -. [P20783-2]
DR CCDS; CCDS8538.1; -. [P20783-1]
DR PIR; A36208; C40304.
DR RefSeq; NP_001096124.1; NM_001102654.1. [P20783-2]
DR RefSeq; NP_002518.1; NM_002527.4. [P20783-1]
DR RefSeq; XP_011519265.1; XM_011520963.2. [P20783-1]
DR PDB; 1B8K; X-ray; 2.15 A; A=139-257.
DR PDB; 1BND; X-ray; 2.30 A; B=139-257.
DR PDB; 1NT3; X-ray; 2.40 A; A=139-257.
DR PDB; 3BUK; X-ray; 2.60 A; A/B=139-257.
DR PDBsum; 1B8K; -.
DR PDBsum; 1BND; -.
DR PDBsum; 1NT3; -.
DR PDBsum; 3BUK; -.
DR AlphaFoldDB; P20783; -.
DR SMR; P20783; -.
DR BioGRID; 110963; 33.
DR CORUM; P20783; -.
DR DIP; DIP-346N; -.
DR IntAct; P20783; 10.
DR STRING; 9606.ENSP00000397297; -.
DR GlyGen; P20783; 1 site.
DR iPTMnet; P20783; -.
DR PhosphoSitePlus; P20783; -.
DR BioMuta; NTF3; -.
DR DMDM; 128581; -.
DR EPD; P20783; -.
DR jPOST; P20783; -.
DR MassIVE; P20783; -.
DR PaxDb; P20783; -.
DR PeptideAtlas; P20783; -.
DR PRIDE; P20783; -.
DR ProteomicsDB; 53785; -. [P20783-1]
DR ProteomicsDB; 53786; -. [P20783-2]
DR Antibodypedia; 22321; 653 antibodies from 41 providers.
DR DNASU; 4908; -.
DR Ensembl; ENST00000331010.7; ENSP00000328738.6; ENSG00000185652.12. [P20783-1]
DR Ensembl; ENST00000423158.4; ENSP00000397297.2; ENSG00000185652.12. [P20783-2]
DR GeneID; 4908; -.
DR KEGG; hsa:4908; -.
DR MANE-Select; ENST00000423158.4; ENSP00000397297.2; NM_001102654.2; NP_001096124.1. [P20783-2]
DR UCSC; uc001qnk.5; human. [P20783-1]
DR CTD; 4908; -.
DR DisGeNET; 4908; -.
DR GeneCards; NTF3; -.
DR HGNC; HGNC:8023; NTF3.
DR HPA; ENSG00000185652; Tissue enhanced (ovary).
DR MIM; 162660; gene.
DR neXtProt; NX_P20783; -.
DR OpenTargets; ENSG00000185652; -.
DR PharmGKB; PA31806; -.
DR VEuPathDB; HostDB:ENSG00000185652; -.
DR eggNOG; ENOG502R4FK; Eukaryota.
DR GeneTree; ENSGT00390000007725; -.
DR HOGENOM; CLU_059942_1_1_1; -.
DR InParanoid; P20783; -.
DR OMA; KQMVDIK; -.
DR OrthoDB; 1156054at2759; -.
DR PhylomeDB; P20783; -.
DR TreeFam; TF106463; -.
DR PathwayCommons; P20783; -.
DR Reactome; R-HSA-9025046; NTF3 activates NTRK2 (TRKB) signaling.
DR Reactome; R-HSA-9034013; NTF3 activates NTRK3 signaling.
DR Reactome; R-HSA-9034015; Signaling by NTRK3 (TRKC).
DR Reactome; R-HSA-9034793; Activated NTRK3 signals through PLCG1.
DR Reactome; R-HSA-9034864; Activated NTRK3 signals through RAS.
DR Reactome; R-HSA-9603381; Activated NTRK3 signals through PI3K.
DR SignaLink; P20783; -.
DR SIGNOR; P20783; -.
DR BioGRID-ORCS; 4908; 18 hits in 1071 CRISPR screens.
DR EvolutionaryTrace; P20783; -.
DR GeneWiki; Neurotrophin-3; -.
DR GenomeRNAi; 4908; -.
DR Pharos; P20783; Tbio.
DR PRO; PR:P20783; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; P20783; protein.
DR Bgee; ENSG00000185652; Expressed in popliteal artery and 117 other tissues.
DR Genevisible; P20783; HS.
DR GO; GO:0030424; C:axon; IBA:GO_Central.
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:0008021; C:synaptic vesicle; IBA:GO_Central.
DR GO; GO:0042056; F:chemoattractant activity; IDA:BHF-UCL.
DR GO; GO:0008083; F:growth factor activity; IDA:BHF-UCL.
DR GO; GO:0005163; F:nerve growth factor receptor binding; IBA:GO_Central.
DR GO; GO:0005102; F:signaling receptor binding; TAS:ProtInc.
DR GO; GO:0090630; P:activation of GTPase activity; IDA:BHF-UCL.
DR GO; GO:0032148; P:activation of protein kinase B activity; IDA:BHF-UCL.
DR GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc.
DR GO; GO:0050930; P:induction of positive chemotaxis; 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:0043524; P:negative regulation of neuron apoptotic process; IBA:GO_Central.
DR GO; GO:0050732; P:negative regulation of peptidyl-tyrosine phosphorylation; IDA:BHF-UCL.
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:2000251; P:positive regulation of actin cytoskeleton reorganization; IDA:BHF-UCL.
DR GO; GO:0030335; P:positive regulation of cell migration; IDA:BHF-UCL.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:BHF-UCL.
DR GO; GO:0043406; P:positive regulation of MAP kinase activity; IDA:BHF-UCL.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IDA:BHF-UCL.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IDA:BHF-UCL.
DR GO; GO:0002092; P:positive regulation of receptor internalization; IDA:BHF-UCL.
DR GO; GO:0042981; P:regulation of apoptotic process; IGI:MGI.
DR GO; GO:0045664; P:regulation of neuron differentiation; IBA:GO_Central.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IDA:BHF-UCL.
DR Gene3D; 2.10.90.10; -; 1.
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 InterPro; IPR015578; Neurotrophin-3.
DR InterPro; IPR045815; NTF3_N.
DR PANTHER; PTHR11589; PTHR11589; 1.
DR PANTHER; PTHR11589:SF4; PTHR11589:SF4; 1.
DR Pfam; PF00243; NGF; 1.
DR Pfam; PF19338; NTF3_N; 1.
DR PIRSF; PIRSF001789; NGF; 1.
DR PRINTS; PR01914; NEUROTROPHN3.
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 splicing; Cleavage on pair of basic residues;
KW Disulfide bond; Glycoprotein; Growth factor; Reference proteome; Secreted;
KW Signal.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT PROPEP 19..138
FT /id="PRO_0000019659"
FT CHAIN 139..257
FT /note="Neurotrophin-3"
FT /id="PRO_0000019660"
FT REGION 61..81
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 131
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 152..217
FT DISULFID 195..246
FT DISULFID 205..248
FT VAR_SEQ 1
FT /note="M -> MVTFATILQVNKVM (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_043353"
FT VARIANT 76
FT /note="G -> E (in dbSNP:rs1805149)"
FT /evidence="ECO:0000269|PubMed:7733919,
FT ECO:0000269|PubMed:8925252"
FT /id="VAR_012084"
FT STRAND 148..152
FT /evidence="ECO:0007829|PDB:1BND"
FT STRAND 154..159
FT /evidence="ECO:0007829|PDB:1B8K"
FT STRAND 164..167
FT /evidence="ECO:0007829|PDB:1B8K"
FT STRAND 172..175
FT /evidence="ECO:0007829|PDB:1B8K"
FT STRAND 177..179
FT /evidence="ECO:0007829|PDB:1BND"
FT TURN 181..183
FT /evidence="ECO:0007829|PDB:1BND"
FT STRAND 190..195
FT /evidence="ECO:0007829|PDB:1B8K"
FT STRAND 200..205
FT /evidence="ECO:0007829|PDB:1BND"
FT TURN 210..212
FT /evidence="ECO:0007829|PDB:3BUK"
FT STRAND 216..233
FT /evidence="ECO:0007829|PDB:1B8K"
FT STRAND 236..249
FT /evidence="ECO:0007829|PDB:1B8K"
SQ SEQUENCE 257 AA; 29355 MW; 39A5BB3B28E25E03 CRC64;
MSILFYVIFL AYLRGIQGNN MDQRSLPEDS LNSLIIKLIQ ADILKNKLSK QMVDVKENYQ
STLPKAEAPR EPERGGPAKS AFQPVIAMDT ELLRQQRRYN SPRVLLSDST PLEPPPLYLM
EDYVGSPVVA NRTSRRKRYA EHKSHRGEYS VCDSESLWVT DKSSAIDIRG HQVTVLGEIK
TGNSPVKQYF YETRCKEARP VKNGCRGIDD KHWNSQCKTS QTYVRALTSE NNKLVGWRWI
RIDTSCVCAL SRKIGRT
