NGF_PANTR
ID NGF_PANTR Reviewed; 241 AA.
AC Q9N2F1; Q5IS63; Q8HZH3;
DT 21-NOV-2003, integrated into UniProtKB/Swiss-Prot.
DT 15-MAR-2005, sequence version 2.
DT 03-AUG-2022, entry version 123.
DE RecName: Full=Beta-nerve growth factor;
DE Short=Beta-NGF;
DE Flags: Precursor;
GN Name=NGF; Synonyms=NGFB;
OS Pan troglodytes (Chimpanzee).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pan.
OX NCBI_TaxID=9598;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=Isolate 220;
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 [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=15620360; DOI=10.1016/j.cell.2004.11.040;
RA Dorus S., Vallender E.J., Evans P.D., Anderson J.R., Gilbert S.L.,
RA Mahowald M., Wyckoff G.J., Malcom C.M., Lahn B.T.;
RT "Accelerated evolution of nervous system genes in the origin of Homo
RT sapiens.";
RL Cell 119:1027-1040(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 15-224.
RA O'Huigin C., Tichy H., Klein J.;
RT "Molecular evolution in higher primates; gene specific and organism
RT specific characteristics.";
RL Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases.
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 -!- SIMILARITY: Belongs to the NGF-beta family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AB037518; BAA90438.1; -; Genomic_DNA.
DR EMBL; AY665265; AAV74303.1; -; mRNA.
DR EMBL; AY091925; AAM76543.1; -; Genomic_DNA.
DR RefSeq; NP_001012439.1; NM_001012437.1.
DR AlphaFoldDB; Q9N2F1; -.
DR SMR; Q9N2F1; -.
DR STRING; 9598.ENSPTRP00000001964; -.
DR PaxDb; Q9N2F1; -.
DR GeneID; 469423; -.
DR KEGG; ptr:469423; -.
DR CTD; 4803; -.
DR eggNOG; ENOG502RYPU; Eukaryota.
DR HOGENOM; CLU_059942_1_1_1; -.
DR InParanoid; Q9N2F1; -.
DR TreeFam; TF106463; -.
DR Proteomes; UP000002277; Unplaced.
DR GO; GO:0030424; C:axon; IBA:GO_Central.
DR GO; GO:0030425; C:dendrite; IBA:GO_Central.
DR GO; GO:0031904; C:endosome lumen; IEA:UniProtKB-SubCell.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
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; IBA:GO_Central.
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:0021675; P:nerve development; IBA:GO_Central.
DR GO; GO:0038180; P:nerve growth factor signaling pathway; IBA:GO_Central.
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:0048672; P:positive regulation of collateral sprouting; IBA:GO_Central.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IBA:GO_Central.
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 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:0000250"
FT /id="PRO_0000019603"
FT CHAIN 122..241
FT /note="Beta-nerve growth factor"
FT /id="PRO_0000019604"
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; 26888 MW; 10B5838912DA2300 CRC64;
MSMLFYTLIT AFLIGTQAEP HSESNVPAGH TIPQAHWTKL QHSLDTALRR ARSAPAAAIA
ARVAGQTRNI TVDPRLFKKR RLRSPRVLFS TQPPPEAADT QDLDFEVGGA APFNRTHRSK
RSSSHPIFHR GEFSVCDSVS VWVGDKTTAT DIKGKEVMVL GEVNINNSVF KQYFFETKCR
DPNPVDSGCR GIDSKHWNSY CTTTHTFVKA LTMDGKQAAW RFIRIDTACV CVLSRKAVRR
A
