NGF_HUMAN
ID NGF_HUMAN Reviewed; 241 AA.
AC P01138; A1A4E5; Q6FHA0; Q96P60; Q9P2Q8; Q9UKL8;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 21-MAR-2006, sequence version 3.
DT 03-AUG-2022, entry version 223.
DE RecName: Full=Beta-nerve growth factor {ECO:0000303|PubMed:6688123};
DE Short=Beta-NGF {ECO:0000303|PubMed:6327169};
DE Flags: Precursor;
GN Name=NGF; Synonyms=NGFB;
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], AND VARIANT VAL-35.
RX PubMed=6688123; DOI=10.1038/303821a0;
RA Ullrich A., Gray A., Berman C., Dull T.J.;
RT "Human beta-nerve growth factor gene sequence highly homologous to that of
RT mouse.";
RL Nature 303:821-825(1983).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT VAL-35.
RX PubMed=6327169; DOI=10.1101/sqb.1983.048.01.048;
RA Ullrich A., Gray A., Berman C., Coussens L., Dull T.J.;
RT "Sequence homology of human and mouse beta-NGF subunit genes.";
RL Cold Spring Harb. Symp. Quant. Biol. 48:435-442(1983).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT VAL-35.
RC TISSUE=Brain;
RX PubMed=2374737; DOI=10.1093/nar/18.13.4020;
RA Borsani G., Pizzuti A., Rugarli E.I., Falini A., Silani V., Sidoli A.,
RA Scarlato G., Barelle F.E.;
RT "cDNA sequence of human beta-NGF.";
RL Nucleic Acids Res. 18:4020-4020(1990).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10322959;
RA Tong Y., Wang H., Chen W.;
RT "Cloning and sequencing of the gene for premature beta nerve growth
RT factor.";
RL Zhongguo Ying Yong Sheng Li Xue Za Zhi 13:316-318(1997).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT VAL-35.
RX PubMed=15014171; DOI=10.1093/molbev/msh100;
RA Kitano T., Liu Y.-H., Ueda S., Saitou N.;
RT "Human-specific amino acid changes found in 103 protein-coding genes.";
RL Mol. Biol. Evol. 21:936-944(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Zhang Y., Zhang B., Zhou Y., Peng X., Yuan J., Qiang B.;
RL Submitted (AUG-2001) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT VAL-35.
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 [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT VAL-35.
RC TISSUE=Eye;
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 [12]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 178-219.
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 [13]
RP IDENTIFICATION OF NTRK1 AS THE HIGH AFFINITY NGF RECEPTOR.
RX PubMed=1849459; DOI=10.1016/0092-8674(91)90419-y;
RA Klein R., Jing S., Nanduri V., O'Rourke E., Barbacid M.;
RT "The trk proto-oncogene encodes a receptor for nerve growth factor.";
RL Cell 65:189-197(1991).
RN [14]
RP FUNCTION, AND INTERACTION WITH ADAM10.
RX PubMed=20164177; DOI=10.1074/jbc.m110.100479;
RA Wijeyewickrema L.C., Gardiner E.E., Gladigau E.L., Berndt M.C.,
RA Andrews R.K.;
RT "Nerve growth factor inhibits metalloproteinase-disintegrins and blocks
RT ectodomain shedding of platelet glycoprotein VI.";
RL J. Biol. Chem. 285:11793-11799(2010).
RN [15] {ECO:0007744|PDB:1WWW}
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 122-241 IN COMPLEX WITH NTRK1,
RP FUNCTION, SUBUNIT, AND DISULFIDE BONDS.
RX PubMed=10490030; DOI=10.1038/43705;
RA Wiesmann C., Ultsch M.H., Bass S.H., de Vos A.M.;
RT "Crystal structure of nerve growth factor in complex with the ligand-
RT binding domain of the TrkA receptor.";
RL Nature 401:184-188(1999).
RN [16] {ECO:0007744|PDB:1SG1}
RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 122-241 IN COMPLEX WITH NGFR,
RP FUNCTION, SUBUNIT, AND DISULFIDE BONDS.
RX PubMed=15131306; DOI=10.1126/science.1095190;
RA He X.L., Garcia K.C.;
RT "Structure of nerve growth factor complexed with the shared neurotrophin
RT receptor p75.";
RL Science 304:870-875(2004).
RN [17] {ECO:0007744|PDB:2IFG}
RP X-RAY CRYSTALLOGRAPHY (3.40 ANGSTROMS) OF 122-241 IN COMPLEX WITH NTRK1,
RP SUBUNIT, AND DISULFIDE BONDS.
RX PubMed=17196528; DOI=10.1016/j.neuron.2006.09.034;
RA Wehrman T., He X., Raab B., Dukipatti A., Blau H., Garcia K.C.;
RT "Structural and mechanistic insights into nerve growth factor interactions
RT with the TrkA and p75 receptors.";
RL Neuron 53:25-38(2007).
RN [18]
RP VARIANT VAL-35.
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 [19]
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 [20]
RP VARIANT HSAN5 TRP-221, AND FUNCTION.
RX PubMed=14976160; DOI=10.1093/hmg/ddh096;
RA Einarsdottir E., Carlsson A., Minde J., Toolanen G., Svensson O.,
RA Solders G., Holmgren G., Holmberg D., Holmberg M.;
RT "A mutation in the nerve growth factor beta gene (NGFB) causes loss of pain
RT perception.";
RL Hum. Mol. Genet. 13:799-805(2004).
RN [21]
RP CHARACTERIZATION OF VARIANT HSAN5 TRP-221, FUNCTION, AND SUBCELLULAR
RP LOCATION.
RX PubMed=20978020; DOI=10.1136/jmg.2010.081455;
RA Carvalho O.P., Thornton G.K., Hertecant J., Houlden H., Nicholas A.K.,
RA Cox J.J., Rielly M., Al-Gazali L., Woods C.G.;
RT "A novel NGF mutation clarifies the molecular mechanism and extends the
RT phenotypic spectrum of the HSAN5 neuropathy.";
RL J. Med. Genet. 48:131-135(2011).
RN [22]
RP VARIANT HSAN5 GLY-GLU-162 INS, AND VARIANT ASN-187.
RX PubMed=22302274; DOI=10.1007/s00415-011-6397-y;
RA Davidson G.L., Murphy S.M., Polke J.M., Laura M., Salih M.A., Muntoni F.,
RA Blake J., Brandner S., Davies N., Horvath R., Price S., Donaghy M.,
RA Roberts M., Foulds N., Ramdharry G., Soler D., Lunn M.P., Manji H.,
RA Davis M.B., Houlden H., Reilly M.M.;
RT "Frequency of mutations in the genes associated with hereditary sensory and
RT autonomic neuropathy in a UK cohort.";
RL J. Neurol. 259:1673-1685(2012).
CC -!- FUNCTION: Nerve growth factor is important for the development and
CC maintenance of the sympathetic and sensory nervous systems
CC (PubMed:14976160, PubMed:20978020). Extracellular ligand for the NTRK1
CC and NGFR receptors, activates cellular signaling cascades to regulate
CC neuronal proliferation, differentiation and survival (PubMed:20978020)
CC (Probable). The immature NGF precursor (proNGF) functions as ligand for
CC the heterodimeric receptor formed by SORCS2 and NGFR, and activates
CC cellular signaling cascades that lead to inactivation of RAC1 and/or
CC RAC2, reorganization of the actin cytoskeleton and neuronal growth cone
CC collapse. In contrast to mature NGF, the precursor form (proNGF)
CC promotes neuronal apoptosis (in vitro) (By similarity). Inhibits
CC metalloproteinase-dependent proteolysis of platelet glycoprotein VI
CC (PubMed:20164177). Binds lysophosphatidylinositol and
CC lysophosphatidylserine between the two chains of the homodimer. The
CC lipid-bound form promotes histamine relase from mast cells, contrary to
CC the lipid-free form (By similarity). {ECO:0000250|UniProtKB:P01139,
CC ECO:0000269|PubMed:14976160, ECO:0000269|PubMed:20164177,
CC ECO:0000269|PubMed:20978020, ECO:0000305|PubMed:10490030,
CC ECO:0000305|PubMed:15131306}.
CC -!- SUBUNIT: Homodimer (PubMed:10490030, PubMed:15131306, PubMed:17196528).
CC The homodimer interacts with a single NTRK1 chain (PubMed:10490030,
CC PubMed:17196528). The homodimer interacts with a single NGFR chain
CC (PubMed:15131306). The NGF dimer interacts with a single SORCS2 chain
CC (via extracellular domain) (By similarity). The NGF precursor (proNGF)
CC binds to a receptor complex formed by SORT1 and NGFR, which leads to
CC NGF endocytosis. Both mature NGF and the immature NGF precursor
CC (proNGF) interact with SORCS2 and with the heterodimer formed by SORCS2
CC and NGFR (via extracellular domains) (By similarity). The NGF precursor
CC (proNGF) has much higher affinity for SORCS2 than mature NGF. The NGF
CC precursor (proNGF) has much higher affinity for SORT1 than mature NGF
CC (By similarity). Interacts with ADAM10 in a divalent cation-dependent
CC manner (PubMed:20164177). {ECO:0000250|UniProtKB:P01139,
CC ECO:0000269|PubMed:10490030, ECO:0000269|PubMed:15131306,
CC ECO:0000269|PubMed:17196528, ECO:0000269|PubMed:20164177}.
CC -!- INTERACTION:
CC P01138; P05067: APP; NbExp=9; IntAct=EBI-1028250, EBI-77613;
CC P01138; P20042: EIF2S2; NbExp=3; IntAct=EBI-1028250, EBI-711977;
CC P01138; P08138: NGFR; NbExp=2; IntAct=EBI-1028250, EBI-1387782;
CC P01138; P04629: NTRK1; NbExp=3; IntAct=EBI-1028250, EBI-1028226;
CC P01138; Q99523: SORT1; NbExp=5; IntAct=EBI-1028250, EBI-1057058;
CC P01138; P07174: Ngfr; Xeno; NbExp=3; IntAct=EBI-1028250, EBI-1038810;
CC PRO_0000019599; Q99523: SORT1; NbExp=2; IntAct=EBI-9345310, EBI-1057058;
CC PRO_0000019600; P08138: NGFR; NbExp=2; IntAct=EBI-9249861, EBI-1387782;
CC PRO_0000019600; P04629: NTRK1; NbExp=2; IntAct=EBI-9249861, EBI-1028226;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:20978020}. Endosome
CC lumen {ECO:0000250|UniProtKB:P01139}. Note=ProNGF is endocytosed after
CC binding to the cell surface receptor formed by SORT1 and NGFR.
CC {ECO:0000250|UniProtKB:P01139}.
CC -!- DISEASE: Neuropathy, hereditary sensory and autonomic, 5 (HSAN5)
CC [MIM:608654]: A form of hereditary sensory and autonomic neuropathy, a
CC genetically and clinically heterogeneous group of disorders
CC characterized by degeneration of dorsal root and autonomic ganglion
CC cells, and by sensory and/or autonomic abnormalities. HSAN5 patients
CC manifest loss of pain perception and impaired temperature sensitivity,
CC ulcers, and in some cases self-mutilation. The autonomic involvement is
CC variable. {ECO:0000269|PubMed:14976160, ECO:0000269|PubMed:20978020,
CC ECO:0000269|PubMed:22302274}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the NGF-beta family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH32517.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Nerve growth factor entry;
CC URL="https://en.wikipedia.org/wiki/Nerve_growth_factor";
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DR EMBL; V01511; CAA24755.1; -; Genomic_DNA.
DR EMBL; M21062; AAA59931.1; -; Genomic_DNA.
DR EMBL; AF150960; AAD55975.1; -; Genomic_DNA.
DR EMBL; AB037517; BAA90437.1; -; Genomic_DNA.
DR EMBL; AF411526; AAL05874.1; -; mRNA.
DR EMBL; CR541855; CAG46653.1; -; mRNA.
DR EMBL; BT019733; AAV38538.1; -; mRNA.
DR EMBL; AL049825; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471122; EAW56629.1; -; Genomic_DNA.
DR EMBL; BC032517; AAH32517.2; ALT_INIT; mRNA.
DR EMBL; BC126148; AAI26149.1; -; mRNA.
DR EMBL; BC126150; AAI26151.1; -; mRNA.
DR EMBL; X52599; CAA36832.1; -; mRNA.
DR CCDS; CCDS882.1; -.
DR PIR; A01399; NGHUBM.
DR RefSeq; NP_002497.2; NM_002506.2.
DR RefSeq; XP_006710726.1; XM_006710663.3.
DR PDB; 1SG1; X-ray; 2.40 A; A/B=122-241.
DR PDB; 1WWW; X-ray; 2.20 A; V/W=122-241.
DR PDB; 2IFG; X-ray; 3.40 A; E/F=122-241.
DR PDB; 4EDW; X-ray; 2.48 A; V=122-241.
DR PDB; 4EDX; X-ray; 2.50 A; V/W=122-241.
DR PDB; 4ZBN; X-ray; 2.45 A; A/B=122-241.
DR PDB; 5JZ7; X-ray; 3.40 A; A/B/E/F=128-237.
DR PDB; 6YW8; NMR; -; A/B=122-239.
DR PDBsum; 1SG1; -.
DR PDBsum; 1WWW; -.
DR PDBsum; 2IFG; -.
DR PDBsum; 4EDW; -.
DR PDBsum; 4EDX; -.
DR PDBsum; 4ZBN; -.
DR PDBsum; 5JZ7; -.
DR PDBsum; 6YW8; -.
DR AlphaFoldDB; P01138; -.
DR SASBDB; P01138; -.
DR SMR; P01138; -.
DR BioGRID; 110869; 10.
DR CORUM; P01138; -.
DR DIP; DIP-5712N; -.
DR IntAct; P01138; 7.
DR MINT; P01138; -.
DR STRING; 9606.ENSP00000358525; -.
DR BindingDB; P01138; -.
DR ChEMBL; CHEMBL1649058; -.
DR DrugBank; DB01407; Clenbuterol.
DR DrugBank; DB12157; Fasinumab.
DR DrugBank; DB09221; Polaprezinc.
DR DrugBank; DB05892; RI 624.
DR GlyGen; P01138; 2 sites.
DR iPTMnet; P01138; -.
DR PhosphoSitePlus; P01138; -.
DR BioMuta; NGF; -.
DR PaxDb; P01138; -.
DR PeptideAtlas; P01138; -.
DR PRIDE; P01138; -.
DR ProteomicsDB; 51338; -.
DR ABCD; P01138; 72 sequenced antibodies.
DR Antibodypedia; 20173; 1041 antibodies from 44 providers.
DR DNASU; 4803; -.
DR Ensembl; ENST00000369512.3; ENSP00000358525.2; ENSG00000134259.6.
DR Ensembl; ENST00000675637.2; ENSP00000502831.1; ENSG00000134259.6.
DR Ensembl; ENST00000676038.2; ENSP00000502380.1; ENSG00000134259.6.
DR Ensembl; ENST00000679806.1; ENSP00000506492.1; ENSG00000134259.6.
DR Ensembl; ENST00000680116.1; ENSP00000505694.1; ENSG00000134259.6.
DR Ensembl; ENST00000680540.1; ENSP00000506569.1; ENSG00000134259.6.
DR Ensembl; ENST00000680752.1; ENSP00000505558.1; ENSG00000134259.6.
DR GeneID; 4803; -.
DR KEGG; hsa:4803; -.
DR MANE-Select; ENST00000369512.3; ENSP00000358525.2; NM_002506.3; NP_002497.2.
DR UCSC; uc001efu.2; human.
DR CTD; 4803; -.
DR DisGeNET; 4803; -.
DR GeneCards; NGF; -.
DR GeneReviews; NGF; -.
DR HGNC; HGNC:7808; NGF.
DR HPA; ENSG00000134259; Tissue enhanced (heart muscle, ovary).
DR MalaCards; NGF; -.
DR MIM; 162030; gene.
DR MIM; 608654; phenotype.
DR neXtProt; NX_P01138; -.
DR OpenTargets; ENSG00000134259; -.
DR Orphanet; 64752; Hereditary sensory and autonomic neuropathy type 5.
DR PharmGKB; PA162397475; -.
DR VEuPathDB; HostDB:ENSG00000134259; -.
DR eggNOG; ENOG502RYPU; Eukaryota.
DR GeneTree; ENSGT00390000007725; -.
DR HOGENOM; CLU_059942_1_1_1; -.
DR InParanoid; P01138; -.
DR OMA; PLNRTHR; -.
DR OrthoDB; 1156054at2759; -.
DR PhylomeDB; P01138; -.
DR TreeFam; TF106463; -.
DR PathwayCommons; P01138; -.
DR Reactome; R-HSA-167021; PLC-gamma1 signalling.
DR Reactome; R-HSA-167044; Signalling to RAS.
DR Reactome; R-HSA-167060; NGF processing.
DR Reactome; R-HSA-170968; Frs2-mediated activation.
DR Reactome; R-HSA-170984; ARMS-mediated activation.
DR Reactome; R-HSA-177504; Retrograde neurotrophin signalling.
DR Reactome; R-HSA-187042; TRKA activation by NGF.
DR Reactome; R-HSA-187706; Signalling to p38 via RIT and RIN.
DR Reactome; R-HSA-193648; NRAGE signals death through JNK.
DR Reactome; R-HSA-193670; p75NTR negatively regulates cell cycle via SC1.
DR Reactome; R-HSA-193681; Ceramide signalling.
DR Reactome; R-HSA-198203; PI3K/AKT activation.
DR Reactome; R-HSA-198745; Signalling to STAT3.
DR Reactome; R-HSA-205017; NFG and proNGF binds to p75NTR.
DR Reactome; R-HSA-205025; NADE modulates death signalling.
DR Reactome; R-HSA-205043; NRIF signals cell death from the nucleus.
DR Reactome; R-HSA-209543; p75NTR recruits signalling complexes.
DR Reactome; R-HSA-209560; NF-kB is activated and signals survival.
DR Reactome; R-HSA-209563; Axonal growth stimulation.
DR SignaLink; P01138; -.
DR SIGNOR; P01138; -.
DR BioGRID-ORCS; 4803; 13 hits in 1070 CRISPR screens.
DR ChiTaRS; NGF; human.
DR EvolutionaryTrace; P01138; -.
DR GeneWiki; Nerve_growth_factor; -.
DR GenomeRNAi; 4803; -.
DR Pharos; P01138; Tchem.
DR PRO; PR:P01138; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P01138; protein.
DR Bgee; ENSG00000134259; Expressed in cartilage tissue and 107 other tissues.
DR Genevisible; P01138; HS.
DR GO; GO:0030424; C:axon; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0030425; C:dendrite; IBA:GO_Central.
DR GO; GO:0031904; C:endosome lumen; IEA:UniProtKB-SubCell.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0005796; C:Golgi lumen; TAS:Reactome.
DR GO; GO:0008021; C:synaptic vesicle; IBA:GO_Central.
DR GO; GO:0008656; F:cysteine-type endopeptidase activator activity involved in apoptotic process; IGI:ARUK-UCL.
DR GO; GO:0038177; F:death receptor agonist activity; IGI:ARUK-UCL.
DR GO; GO:0008083; F:growth factor activity; IBA:GO_Central.
DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR GO; GO:0008191; F:metalloendopeptidase inhibitor activity; IDA:UniProtKB.
DR GO; GO:0005163; F:nerve growth factor receptor binding; IPI:BHF-UCL.
DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; IGI:ARUK-UCL.
DR GO; GO:0008625; P:extrinsic apoptotic signaling pathway via death domain receptors; 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:0008285; P:negative regulation of cell population proliferation; TAS:ARUK-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:0051402; P:neuron apoptotic process; IGI:ARUK-UCL.
DR GO; GO:0048812; P:neuron projection morphogenesis; IDA:MGI.
DR GO; GO:0007422; P:peripheral nervous system development; IBA:GO_Central.
DR GO; GO:0048672; P:positive regulation of collateral sprouting; IBA:GO_Central.
DR GO; GO:0043388; P:positive regulation of DNA binding; ISS:ARUK-UCL.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:UniProtKB.
DR GO; GO:0045666; P:positive regulation of neuron differentiation; TAS:ARUK-UCL.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IBA:GO_Central.
DR GO; GO:0046579; P:positive regulation of Ras protein signal transduction; ISS:ParkinsonsUK-UCL.
DR GO; GO:0045664; P:regulation of neuron differentiation; IBA:GO_Central.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
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; IPR020425; Nerve_growth_factor_bsu.
DR InterPro; IPR020437; Nerve_growth_factor_bsu_mml.
DR InterPro; IPR019846; Nerve_growth_factor_CS.
DR PANTHER; PTHR11589; PTHR11589; 1.
DR Pfam; PF00243; NGF; 1.
DR PIRSF; PIRSF001789; NGF; 1.
DR PRINTS; PR01925; MAMLNGFBETA.
DR PRINTS; PR00268; NGF.
DR PRINTS; PR01913; NGFBETA.
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; Cleavage on pair of basic residues; Disease variant;
KW Disulfide bond; Endosome; Glycoprotein; Growth factor; Lipid-binding;
KW Metalloenzyme inhibitor; Metalloprotease inhibitor; Neurodegeneration;
KW Neuropathy; Protease inhibitor; Reference proteome; Secreted; Signal.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT PROPEP 19..121
FT /id="PRO_0000019599"
FT CHAIN 122..241
FT /note="Beta-nerve growth factor"
FT /id="PRO_0000019600"
FT BINDING 173
FT /ligand="a 1-acyl-sn-glycero-3-phospho-(1D-myo-inositol)"
FT /ligand_id="ChEBI:CHEBI:64771"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:P01139"
FT BINDING 209
FT /ligand="a 1-acyl-sn-glycero-3-phospho-(1D-myo-inositol)"
FT /ligand_id="ChEBI:CHEBI:64771"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000250|UniProtKB:P01139"
FT BINDING 209
FT /ligand="a 1-acyl-sn-glycero-3-phospho-L-serine"
FT /ligand_id="ChEBI:CHEBI:64379"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000250|UniProtKB:P01139"
FT CARBOHYD 69
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 114
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 136..201
FT /evidence="ECO:0000269|PubMed:10490030,
FT ECO:0007744|PDB:1SG1, ECO:0007744|PDB:1WWW,
FT ECO:0007744|PDB:2IFG, ECO:0007744|PDB:4EDW,
FT ECO:0007744|PDB:4EDX, ECO:0007744|PDB:4ZBN,
FT ECO:0007744|PDB:5JZ7"
FT DISULFID 179..229
FT /evidence="ECO:0000269|PubMed:10490030,
FT ECO:0007744|PDB:1SG1, ECO:0007744|PDB:1WWW,
FT ECO:0007744|PDB:2IFG, ECO:0007744|PDB:4EDW,
FT ECO:0007744|PDB:4EDX, ECO:0007744|PDB:4ZBN,
FT ECO:0007744|PDB:5JZ7"
FT DISULFID 189..231
FT /evidence="ECO:0000269|PubMed:10490030,
FT ECO:0007744|PDB:1SG1, ECO:0007744|PDB:1WWW,
FT ECO:0007744|PDB:2IFG, ECO:0007744|PDB:4EDW,
FT ECO:0007744|PDB:4EDX, ECO:0007744|PDB:4ZBN,
FT ECO:0007744|PDB:5JZ7"
FT VARIANT 35
FT /note="A -> V (in dbSNP:rs6330)"
FT /evidence="ECO:0000269|PubMed:10391209,
FT ECO:0000269|PubMed:15014171, ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:2374737, ECO:0000269|PubMed:6327169,
FT ECO:0000269|PubMed:6688123, ECO:0000269|Ref.10"
FT /id="VAR_013783"
FT VARIANT 72
FT /note="V -> M (in dbSNP:rs11466110)"
FT /id="VAR_025553"
FT VARIANT 80
FT /note="R -> Q (in dbSNP:rs11466111)"
FT /id="VAR_025554"
FT VARIANT 162
FT /note="E -> EGE (in HSAN5; uncertain pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:22302274"
FT /id="VAR_068478"
FT VARIANT 187
FT /note="S -> N (found in a patient with congenital
FT insensitivity to pain; uncertain pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:22302274"
FT /id="VAR_068479"
FT VARIANT 221
FT /note="R -> W (in HSAN5; impaired processing of the
FT precursor to mature NGF; nearly abolishes secretion; loss
FT of function in stimulating cell differentiation; loss of
FT the ability to activate the NTRK1 receptor;
FT dbSNP:rs11466112)"
FT /evidence="ECO:0000269|PubMed:14976160,
FT ECO:0000269|PubMed:20978020"
FT /id="VAR_030659"
FT CONFLICT 164
FT /note="N -> S (in Ref. 6; AAL05874)"
FT /evidence="ECO:0000305"
FT CONFLICT 230
FT /note="V -> M (in Ref. 6; AAL05874)"
FT /evidence="ECO:0000305"
FT HELIX 127..130
FT /evidence="ECO:0007829|PDB:1WWW"
FT STRAND 133..136
FT /evidence="ECO:0007829|PDB:1WWW"
FT STRAND 138..143
FT /evidence="ECO:0007829|PDB:1WWW"
FT STRAND 148..151
FT /evidence="ECO:0007829|PDB:1WWW"
FT STRAND 156..159
FT /evidence="ECO:0007829|PDB:1WWW"
FT STRAND 161..171
FT /evidence="ECO:0007829|PDB:1WWW"
FT STRAND 174..179
FT /evidence="ECO:0007829|PDB:1WWW"
FT TURN 183..187
FT /evidence="ECO:0007829|PDB:6YW8"
FT STRAND 190..192
FT /evidence="ECO:0007829|PDB:1SG1"
FT TURN 194..196
FT /evidence="ECO:0007829|PDB:1WWW"
FT STRAND 197..213
FT /evidence="ECO:0007829|PDB:1WWW"
FT STRAND 215..235
FT /evidence="ECO:0007829|PDB:1WWW"
SQ SEQUENCE 241 AA; 26959 MW; 619DFC65EB3BD671 CRC64;
MSMLFYTLIT AFLIGIQAEP HSESNVPAGH TIPQAHWTKL QHSLDTALRR ARSAPAAAIA
ARVAGQTRNI TVDPRLFKKR RLRSPRVLFS TQPPREAADT QDLDFEVGGA APFNRTHRSK
RSSSHPIFHR GEFSVCDSVS VWVGDKTTAT DIKGKEVMVL GEVNINNSVF KQYFFETKCR
DPNPVDSGCR GIDSKHWNSY CTTTHTFVKA LTMDGKQAAW RFIRIDTACV CVLSRKAVRR
A
