NEUM_RAT
ID NEUM_RAT Reviewed; 226 AA.
AC P07936; A0JPM4;
DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1988, sequence version 1.
DT 03-AUG-2022, entry version 169.
DE RecName: Full=Neuromodulin;
DE AltName: Full=Axonal membrane protein GAP-43;
DE AltName: Full=Growth-associated protein 43;
DE AltName: Full=Protein F1;
GN Name=Gap43;
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 [MRNA], AND PARTIAL PROTEIN SEQUENCE.
RX PubMed=2437653; DOI=10.1126/science.2437653;
RA Karns L.R., Ng S.-C., Freeman J.A., Fishman M.C.;
RT "Cloning of complementary DNA for GAP-43, a neuronal growth-related
RT protein.";
RL Science 236:597-600(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 8-25.
RX PubMed=3581170; DOI=10.1016/0092-8674(87)90616-7;
RA Basi G.S., Jacobson R.D., Virag I., Schilling J., Skene J.H.P.;
RT "Primary structure and transcriptional regulation of GAP-43, a protein
RT associated with nerve growth.";
RL Cell 49:785-791(1987).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE.
RX PubMed=3428269; DOI=10.1002/j.1460-2075.1987.tb02696.x;
RA Rosenthal A., Chan S.Y., Henzel W., Haskell C., Kuang W.J., Chen E.,
RA Wilcox J.N., Ullrich A., Goeddel D.V., Routtenberg A.;
RT "Primary structure and mRNA localization of protein F1, a growth-related
RT protein kinase C substrate associated with synaptic plasticity.";
RL EMBO J. 6:3641-3646(1987).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=12106089; DOI=10.1111/j.1460-9568.1990.tb00393.x;
RA Grabczyk E., Zuber M.X., Federoff H.J., Ng S.C., Pack A., Fishman M.C.;
RT "Cloning and characterization of the rat gene encoding GAP-43.";
RL Eur. J. Neurosci. 2:822-827(1990).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [6]
RP PROTEIN SEQUENCE OF 20-30; 38-43; 68-80 AND 158-180, AND IDENTIFICATION BY
RP MASS SPECTROMETRY.
RC STRAIN=Sprague-Dawley; TISSUE=Brain, and Hippocampus;
RA Lubec G., Chen W.-Q., Kang S.U., Lubec S.;
RL Submitted (SEP-2007) to UniProtKB.
RN [7]
RP PHOSPHORYLATION AT SER-41; SER-96 AND THR-172.
RX PubMed=1533624; DOI=10.1016/s0021-9258(19)50388-x;
RA Spencer S.A., Schuh S.M., Liu W.-S., Willard M.B.;
RT "GAP-43, a protein associated with axon growth, is phosphorylated at three
RT sites in cultured neurons and rat brain.";
RL J. Biol. Chem. 267:9059-9064(1992).
RN [8]
RP PHOSPHORYLATION AT SER-41 BY PHK.
RX PubMed=8454596; DOI=10.1016/s0021-9258(18)53240-3;
RA Paudel H.K., Zwiers H., Wang J.H.;
RT "Phosphorylase kinase phosphorylates the calmodulin-binding regulatory
RT regions of neuronal tissue-specific proteins B-50 (GAP-43) and
RT neurogranin.";
RL J. Biol. Chem. 268:6207-6213(1993).
RN [9]
RP SUBCELLULAR LOCATION.
RX PubMed=10982410; DOI=10.1091/mbc.11.9.3191;
RA Mobarak C.D., Anderson K.D., Morin M., Beckel-Mitchener A., Rogers S.L.,
RA Furneaux H., King P., Perrone-Bizzozero N.I.;
RT "The RNA-binding protein HuD is required for GAP-43 mRNA stability, GAP-43
RT gene expression, and PKC-dependent neurite outgrowth in PC12 cells.";
RL Mol. Biol. Cell 11:3191-3203(2000).
RN [10]
RP TISSUE SPECIFICITY.
RX PubMed=11948657; DOI=10.1002/jnr.10175;
RA Perrone-Bizzozero N., Bolognani F.;
RT "Role of HuD and other RNA-binding proteins in neural development and
RT plasticity.";
RL J. Neurosci. Res. 68:121-126(2002).
RN [11]
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INDUCTION BY AXOTOMY.
RX PubMed=12957493; DOI=10.1016/s0014-4886(03)00103-1;
RA Anderson K.D., Merhege M.A., Morin M., Bolognani F.,
RA Perrone-Bizzozero N.I.;
RT "Increased expression and localization of the RNA-binding protein HuD and
RT GAP-43 mRNA to cytoplasmic granules in DRG neurons during nerve
RT regeneration.";
RL Exp. Neurol. 183:100-108(2003).
RN [12]
RP TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND INDUCTION BY SEIZURE.
RX PubMed=17577668; DOI=10.1007/s11064-007-9388-8;
RA Bolognani F., Tanner D.C., Nixon S., Okano H.J., Okano H.,
RA Perrone-Bizzozero N.I.;
RT "Coordinated expression of HuD and GAP-43 in hippocampal dentate granule
RT cells during developmental and adult plasticity.";
RL Neurochem. Res. 32:2142-2151(2007).
RN [13]
RP PHOSPHORYLATION AT THR-172, AND IDENTIFICATION BY MASS SPECTROMETRY.
RA Lubec G., Chen W.-Q.;
RL Submitted (FEB-2007) to UniProtKB.
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-86; SER-96; THR-172; SER-191
RP AND SER-192, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: This protein is associated with nerve growth. It is a major
CC component of the motile 'growth cones' that form the tips of elongating
CC axons. Plays a role in axonal and dendritic filopodia induction (By
CC similarity). {ECO:0000250|UniProtKB:P17677}.
CC -!- SUBUNIT: Identified in a complex containing FGFR4, NCAM1, CDH2, PLCG1,
CC FRS2, SRC, SHC1, GAP43 and CTTN (By similarity). Interacts (via IQ
CC domain) with calmodulin (By similarity). Binds calmodulin with a
CC greater affinity in the absence of Ca(2+) than in its presence (By
CC similarity). {ECO:0000250|UniProtKB:P06836,
CC ECO:0000250|UniProtKB:P06837}.
CC -!- INTERACTION:
CC P07936; Q5XIE8: Itm2b; NbExp=3; IntAct=EBI-26438795, EBI-15348306;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P17677};
CC Peripheral membrane protein {ECO:0000250|UniProtKB:P17677}; Cytoplasmic
CC side {ECO:0000250|UniProtKB:P17677}. Cell projection, growth cone
CC {ECO:0000269|PubMed:10982410}. Cell projection, growth cone membrane
CC {ECO:0000250|UniProtKB:P17677}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:P17677}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:P17677}. Synapse {ECO:0000250|UniProtKB:P17677}.
CC Cell projection, filopodium membrane {ECO:0000250|UniProtKB:P17677};
CC Peripheral membrane protein {ECO:0000250|UniProtKB:P17677}. Perikaryon
CC {ECO:0000269|PubMed:10982410, ECO:0000269|PubMed:12957493}. Cell
CC projection, dendrite {ECO:0000269|PubMed:10982410}. Cell projection,
CC axon {ECO:0000269|PubMed:10982410}. Cytoplasm
CC {ECO:0000269|PubMed:10982410, ECO:0000269|PubMed:12957493}.
CC Note=Cytoplasmic surface of growth cone and synaptic plasma membranes.
CC {ECO:0000250|UniProtKB:P17677}.
CC -!- TISSUE SPECIFICITY: Expressed in hippocampal neurons, with highest
CC levels of expression in the CA4 and CA3 neurons and lower levels in CA1
CC neurons (PubMed:11948657, PubMed:17577668). Expressed in the dorsal
CC root ganglion (PubMed:12957493). {ECO:0000269|PubMed:11948657,
CC ECO:0000269|PubMed:12957493, ECO:0000269|PubMed:17577668}.
CC -!- DEVELOPMENTAL STAGE: Expression in dentate granule cells of the
CC hippocampus at postnatal day P5, with disappearing expression in
CC dentate granule cells as early as P14. {ECO:0000269|PubMed:17577668}.
CC -!- INDUCTION: Up-regulated by kainic acid-induced seizures
CC (PubMed:17577668). Up-regulated after axotomy (PubMed:12957493).
CC {ECO:0000269|PubMed:12957493, ECO:0000269|PubMed:17577668}.
CC -!- PTM: Phosphorylated (PubMed:1533624, PubMed:8454596, Ref.13).
CC Phosphorylation of this protein by a protein kinase C is specifically
CC correlated with certain forms of synaptic plasticity (PubMed:1533624,
CC PubMed:8454596, Ref.13). {ECO:0000269|PubMed:1533624,
CC ECO:0000269|PubMed:8454596, ECO:0000269|Ref.13}.
CC -!- PTM: Palmitoylated by ZDHHC3 (By similarity). Palmitoylation is
CC regulated by ARF6 and is essential for plasma membrane association and
CC axonal and dendritic filopodia induction. Deacylated by LYPLA2 (By
CC similarity). {ECO:0000250|UniProtKB:P06837,
CC ECO:0000250|UniProtKB:P17677}.
CC -!- SIMILARITY: Belongs to the neuromodulin family. {ECO:0000305}.
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DR EMBL; M16228; AAA41190.1; -; mRNA.
DR EMBL; M16736; AAA41192.1; -; mRNA.
DR EMBL; X06338; CAA29644.1; -; mRNA.
DR EMBL; L21192; AAA41189.1; -; Genomic_DNA.
DR EMBL; L21190; AAA41189.1; JOINED; Genomic_DNA.
DR EMBL; L21191; AAA41189.1; JOINED; Genomic_DNA.
DR EMBL; BC127502; AAI27503.1; -; mRNA.
DR PIR; A26964; A26964.
DR RefSeq; NP_058891.1; NM_017195.3.
DR AlphaFoldDB; P07936; -.
DR SMR; P07936; -.
DR BioGRID; 248071; 5.
DR IntAct; P07936; 1.
DR MINT; P07936; -.
DR STRING; 10116.ENSRNOP00000002091; -.
DR iPTMnet; P07936; -.
DR PhosphoSitePlus; P07936; -.
DR SwissPalm; P07936; -.
DR jPOST; P07936; -.
DR PaxDb; P07936; -.
DR PRIDE; P07936; -.
DR Ensembl; ENSRNOT00000002091; ENSRNOP00000002091; ENSRNOG00000001528.
DR GeneID; 29423; -.
DR KEGG; rno:29423; -.
DR UCSC; RGD:62071; rat.
DR CTD; 2596; -.
DR RGD; 62071; Gap43.
DR eggNOG; ENOG502RXWF; Eukaryota.
DR GeneTree; ENSGT00730000111265; -.
DR HOGENOM; CLU_102989_0_0_1; -.
DR InParanoid; P07936; -.
DR OMA; GTPNKPE; -.
DR OrthoDB; 1531103at2759; -.
DR PhylomeDB; P07936; -.
DR TreeFam; TF333213; -.
DR Reactome; R-RNO-373760; L1CAM interactions.
DR PRO; PR:P07936; -.
DR Proteomes; UP000002494; Chromosome 11.
DR Bgee; ENSRNOG00000001528; Expressed in frontal cortex and 16 other tissues.
DR Genevisible; P07936; RN.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0030424; C:axon; ISO:RGD.
DR GO; GO:0071944; C:cell periphery; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0030425; C:dendrite; IEA:UniProtKB-SubCell.
DR GO; GO:0031527; C:filopodium membrane; ISO:RGD.
DR GO; GO:0098982; C:GABA-ergic synapse; IDA:SynGO.
DR GO; GO:0030426; C:growth cone; TAS:RGD.
DR GO; GO:0032584; C:growth cone membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR GO; GO:0014069; C:postsynaptic density; ISO:RGD.
DR GO; GO:0005516; F:calmodulin binding; IBA:GO_Central.
DR GO; GO:0035727; F:lysophosphatidic acid binding; IDA:RGD.
DR GO; GO:1901981; F:phosphatidylinositol phosphate binding; IDA:RGD.
DR GO; GO:0001786; F:phosphatidylserine binding; IDA:RGD.
DR GO; GO:0048708; P:astrocyte differentiation; IEA:Ensembl.
DR GO; GO:0016198; P:axon choice point recognition; ISO:RGD.
DR GO; GO:0007411; P:axon guidance; ISO:RGD.
DR GO; GO:0031103; P:axon regeneration; IBA:GO_Central.
DR GO; GO:0045165; P:cell fate commitment; ISO:RGD.
DR GO; GO:0010001; P:glial cell differentiation; ISO:RGD.
DR GO; GO:0007399; P:nervous system development; IEP:RGD.
DR GO; GO:0060019; P:radial glial cell differentiation; IEA:Ensembl.
DR GO; GO:0051489; P:regulation of filopodium assembly; ISO:RGD.
DR GO; GO:0040008; P:regulation of growth; IEA:UniProtKB-KW.
DR GO; GO:0099150; P:regulation of postsynaptic specialization assembly; IDA:SynGO.
DR GO; GO:0042246; P:tissue regeneration; IEP:RGD.
DR InterPro; IPR000048; IQ_motif_EF-hand-BS.
DR InterPro; IPR001422; Neuromodulin.
DR InterPro; IPR017454; Neuromodulin_C.
DR InterPro; IPR018947; Neuromodulin_gap-junction_N.
DR InterPro; IPR033137; Neuromodulin_P_site.
DR InterPro; IPR018243; Neuromodulin_palmitoyl_site.
DR Pfam; PF00612; IQ; 1.
DR Pfam; PF06614; Neuromodulin; 1.
DR Pfam; PF10580; Neuromodulin_N; 1.
DR PRINTS; PR00215; NEUROMODULIN.
DR SMART; SM00015; IQ; 1.
DR PROSITE; PS50096; IQ; 1.
DR PROSITE; PS00412; NEUROMODULIN_1; 1.
DR PROSITE; PS00413; NEUROMODULIN_2; 1.
PE 1: Evidence at protein level;
KW Calmodulin-binding; Cell membrane; Cell projection; Cytoplasm;
KW Developmental protein; Differentiation; Direct protein sequencing;
KW Growth regulation; Lipoprotein; Membrane; Neurogenesis; Palmitate;
KW Phosphoprotein; Reference proteome; Synapse.
FT CHAIN 1..226
FT /note="Neuromodulin"
FT /id="PRO_0000159599"
FT DOMAIN 31..60
FT /note="IQ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00116"
FT REGION 1..226
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 8..36
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 46..86
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 104..125
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 132..146
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 191..226
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 41
FT /note="Phosphoserine; by PHK and PKC"
FT /evidence="ECO:0000269|PubMed:1533624,
FT ECO:0000269|PubMed:8454596"
FT MOD_RES 86
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 96
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:1533624,
FT ECO:0007744|PubMed:22673903"
FT MOD_RES 142
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P06837"
FT MOD_RES 144
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P06837"
FT MOD_RES 145
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P06837"
FT MOD_RES 172
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:1533624, ECO:0000269|Ref.13,
FT ECO:0007744|PubMed:22673903"
FT MOD_RES 191
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 192
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT LIPID 3
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:P06836"
FT LIPID 4
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:P06836"
SQ SEQUENCE 226 AA; 23603 MW; 1314B2CDC61DB746 CRC64;
MLCCMRRTKQ VEKNDEDQKI EQDGVKPEDK AHKAATKIQA SFRGHITRKK LKDEKKGDAP
AAEAEAKEKD DAPVADGVEK KEGDGSATTD AAPATSPKAE EPSKAGDAPS EEKKGEGDAA
PSEEKAGSAE TESAAKATTD NSPSSKAEDG PAKEEPKQAD VPAAVTDAAA TTPAAEDAAK
AAQPPTETAE SSQAEEEKEA VDEAKPKESA RQDEGKEDPE ADQEHA
