NGF_RAT
ID NGF_RAT Reviewed; 241 AA.
AC P25427;
DT 01-MAY-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 2.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=Beta-nerve growth factor;
DE Short=Beta-NGF;
DE Flags: Precursor;
GN Name=Ngf; Synonyms=Ngfb;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND TISSUE SPECIFICITY.
RX PubMed=3184206; DOI=10.1002/jnr.490200402;
RA Whittemore S.R., Friedman P.L., Larhammar D.G., Persson H.,
RA Gonzalez-Carvajal M., Holets V.R.;
RT "Rat beta-nerve growth factor sequence and site of synthesis in the adult
RT hippocampus.";
RL J. Neurosci. Res. 20:403-410(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 178-219.
RC STRAIN=Sprague-Dawley; TISSUE=Liver;
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).
CC -!- FUNCTION: Nerve growth factor is important for the development and
CC maintenance of the sympathetic and sensory nervous systems.
CC Extracellular ligand for the NTRK1 and NGFR receptors, activates
CC cellular signaling cascades to regulate neuronal proliferation,
CC differentiation and survival (By similarity). The immature NGF
CC precursor (proNGF) functions as ligand for the heterodimeric receptor
CC formed by SORCS2 and NGFR, and activates cellular signaling cascades
CC that lead to inactivation of RAC1 and/or RAC2, reorganization of the
CC actin cytoskeleton and neuronal growth cone collapse. In contrast to
CC mature NGF, the precursor form (proNGF) promotes neuronal apoptosis (in
CC vitro) (By similarity). Inhibits metalloproteinase-dependent
CC proteolysis of platelet glycoprotein VI (By similarity). Binds
CC lysophosphatidylinositol and lysophosphatidylserine between the two
CC chains of the homodimer. The lipid-bound form promotes histamine relase
CC from mast cells, contrary to the lipid-free form (By similarity).
CC {ECO:0000250|UniProtKB:P01138, ECO:0000250|UniProtKB:P01139}.
CC -!- SUBUNIT: Homodimer. The homodimer interacts with a single NTRK1 chain.
CC The homodimer interacts with a single NGFR chain (By similarity). The
CC NGF dimer interacts with a single SORCS2 chain (via extracellular
CC domain). The NGF precursor (proNGF) binds to a receptor complex formed
CC by SORT1 and NGFR, which leads to NGF endocytosis. Both mature NGF and
CC the immature NGF precursor (proNGF) interact with SORCS2 and with the
CC heterodimer formed by SORCS2 and NGFR (via extracellular domains). The
CC NGF precursor (proNGF) has much higher affinity for SORCS2 than mature
CC NGF. The NGF precursor (proNGF) has much higher affinity for SORT1 than
CC mature NGF (By similarity). Interacts with ADAM10 in a divalent cation-
CC dependent manner (By similarity). {ECO:0000250|UniProtKB:P01138,
CC ECO:0000250|UniProtKB:P01139}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P01138}. 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 -!- TISSUE SPECIFICITY: Detected in the granule and pyramidal cell layer in
CC the hippocampus. {ECO:0000269|PubMed:3184206}.
CC -!- SIMILARITY: Belongs to the NGF-beta family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA41697.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; M36589; AAA41697.1; ALT_INIT; Genomic_DNA.
DR PIR; I56570; I56570.
DR RefSeq; NP_001263984.1; NM_001277055.1.
DR RefSeq; XP_006233114.1; XM_006233052.3.
DR RefSeq; XP_006233115.1; XM_006233053.2.
DR AlphaFoldDB; P25427; -.
DR SMR; P25427; -.
DR STRING; 10116.ENSRNOP00000022200; -.
DR BindingDB; P25427; -.
DR GlyGen; P25427; 3 sites.
DR PaxDb; P25427; -.
DR ABCD; P25427; 50 sequenced antibodies.
DR Ensembl; ENSRNOT00000022200; ENSRNOP00000022200; ENSRNOG00000016571.
DR Ensembl; ENSRNOT00000116899; ENSRNOP00000097792; ENSRNOG00000016571.
DR GeneID; 310738; -.
DR KEGG; rno:310738; -.
DR CTD; 4803; -.
DR RGD; 1598328; Ngf.
DR eggNOG; ENOG502RYPU; Eukaryota.
DR GeneTree; ENSGT00390000007725; -.
DR HOGENOM; CLU_059942_1_1_1; -.
DR InParanoid; P25427; -.
DR OrthoDB; 1156054at2759; -.
DR PhylomeDB; P25427; -.
DR Reactome; R-RNO-167060; NGF processing.
DR Reactome; R-RNO-170968; Frs2-mediated activation.
DR Reactome; R-RNO-170984; ARMS-mediated activation.
DR Reactome; R-RNO-177504; Retrograde neurotrophin signalling.
DR Reactome; R-RNO-187042; TRKA activation by NGF.
DR Reactome; R-RNO-198203; PI3K/AKT activation.
DR Reactome; R-RNO-205017; NFG and proNGF binds to p75NTR.
DR Reactome; R-RNO-205025; NADE modulates death signalling.
DR Reactome; R-RNO-205043; NRIF signals cell death from the nucleus.
DR Reactome; R-RNO-209543; p75NTR recruits signalling complexes.
DR Reactome; R-RNO-209560; NF-kB is activated and signals survival.
DR Reactome; R-RNO-209563; Axonal growth stimulation.
DR PRO; PR:P25427; -.
DR Proteomes; UP000002494; Chromosome 2.
DR Bgee; ENSRNOG00000016571; Expressed in heart and 16 other tissues.
DR ExpressionAtlas; P25427; baseline and differential.
DR Genevisible; P25427; RN.
DR GO; GO:0030424; C:axon; IBA:GO_Central.
DR GO; GO:0030425; C:dendrite; IBA:GO_Central.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
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; IDA:RGD.
DR GO; GO:0005796; C:Golgi lumen; TAS:Reactome.
DR GO; GO:0044306; C:neuron projection terminus; ISO:RGD.
DR GO; GO:0008021; C:synaptic vesicle; IBA:GO_Central.
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; ISS:UniProtKB.
DR GO; GO:0005163; F:nerve growth factor receptor binding; ISO:RGD.
DR GO; GO:0030297; F:transmembrane receptor protein tyrosine kinase activator activity; ISO:RGD.
DR GO; GO:0008344; P:adult locomotory behavior; IMP:RGD.
DR GO; GO:0007568; P:aging; IEP:RGD.
DR GO; GO:0007623; P:circadian rhythm; ISO:RGD.
DR GO; GO:0097192; P:extrinsic apoptotic signaling pathway in absence of ligand; ISO:RGD.
DR GO; GO:0008625; P:extrinsic apoptotic signaling pathway via death domain receptors; ISO:RGD.
DR GO; GO:0006954; P:inflammatory response; IEP:RGD.
DR GO; GO:0007613; P:memory; IMP:RGD.
DR GO; GO:0050804; P:modulation of chemical synaptic transmission; IBA:GO_Central.
DR GO; GO:1902236; P:negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway; NAS:ParkinsonsUK-UCL.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IMP:UniProtKB.
DR GO; GO:2000675; P:negative regulation of type B pancreatic cell apoptotic process; IMP:RGD.
DR GO; GO:0021675; P:nerve development; IBA:GO_Central.
DR GO; GO:0038180; P:nerve growth factor signaling pathway; ISO:RGD.
DR GO; GO:0051402; P:neuron apoptotic process; ISO:RGD.
DR GO; GO:0048666; P:neuron development; ISO:RGD.
DR GO; GO:0031175; P:neuron projection development; IDA:RGD.
DR GO; GO:0048812; P:neuron projection morphogenesis; ISO:RGD.
DR GO; GO:0007422; P:peripheral nervous system development; ISO:RGD.
DR GO; GO:0045773; P:positive regulation of axon extension; ISO:RGD.
DR GO; GO:0030307; P:positive regulation of cell growth; IDA:RGD.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:RGD.
DR GO; GO:0048672; P:positive regulation of collateral sprouting; ISO:RGD.
DR GO; GO:0043388; P:positive regulation of DNA binding; ISO:RGD.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; IDA:MGI.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IDA:RGD.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:RGD.
DR GO; GO:0045666; P:positive regulation of neuron differentiation; IDA:RGD.
DR GO; GO:0014042; P:positive regulation of neuron maturation; ISO:RGD.
DR GO; GO:0010976; P:positive regulation of neuron projection development; ISO:RGD.
DR GO; GO:0051388; P:positive regulation of neurotrophin TRK receptor signaling pathway; IDA:MGI.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IBA:GO_Central.
DR GO; GO:0031954; P:positive regulation of protein autophosphorylation; IDA:MGI.
DR GO; GO:0032092; P:positive regulation of protein binding; IMP:UniProtKB.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; ISO:RGD.
DR GO; GO:0046579; P:positive regulation of Ras protein signal transduction; ISO:RGD.
DR GO; GO:2000648; P:positive regulation of stem cell proliferation; IDA:RGD.
DR GO; GO:0045664; P:regulation of neuron differentiation; ISO:RGD.
DR GO; GO:0046928; P:regulation of neurotransmitter secretion; ISO:RGD.
DR GO; GO:0051279; P:regulation of release of sequestered calcium ion into cytosol; ISO:RGD.
DR GO; GO:0051602; P:response to electrical stimulus; IEP:RGD.
DR GO; GO:0051384; P:response to glucocorticoid; IEP:RGD.
DR GO; GO:0032496; P:response to lipopolysaccharide; IEP:RGD.
DR GO; GO:0009612; P:response to mechanical stimulus; IEP:RGD.
DR GO; GO:0035094; P:response to nicotine; IEP:RGD.
DR GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD.
DR GO; GO:0010033; P:response to organic substance; IEP:RGD.
DR GO; GO:0010193; P:response to ozone; IEP:RGD.
DR GO; GO:0043434; P:response to peptide hormone; IEP:RGD.
DR GO; GO:0009314; P:response to radiation; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0019233; P:sensory perception of pain; IMP:RGD.
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 2: Evidence at transcript level;
KW Cleavage on pair of basic residues; Disulfide bond; Endosome; Glycoprotein;
KW Growth factor; Lipid-binding; Metalloenzyme inhibitor;
KW Metalloprotease inhibitor; Protease inhibitor; Reference proteome;
KW Secreted; Signal.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT PROPEP 19..121
FT /evidence="ECO:0000255"
FT /id="PRO_0000019609"
FT CHAIN 122..241
FT /note="Beta-nerve growth factor"
FT /id="PRO_0000019610"
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 CARBOHYD 166
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 136..201
FT /evidence="ECO:0000250|UniProtKB:P01138"
FT DISULFID 179..229
FT /evidence="ECO:0000250|UniProtKB:P01138"
FT DISULFID 189..231
FT /evidence="ECO:0000250|UniProtKB:P01138"
SQ SEQUENCE 241 AA; 27010 MW; 665F42371563213D CRC64;
MSMLFYTLIT AFLIGVQAEP YTDSNVPEGD SVPEAHWTKL QHSLDTALRR ARSAPAEPIA
ARVTGQTRNI TVDPKLFKKR RLRSPRVLFS TQPPPTSSDT LDLDFQAHGT ISFNRTHRSK
RSSTHPVFHM GEFSVCDSVS VWVGDKTTAT DIKGKEVTVL GEVNINNSVF KQYFFETKCR
APNPVESGCR GIDSKHWNSY CTTTHTFVKA LTTDDKQAAW RFIRIDTACV CVLSRKAARR
G
