NEUM_MOUSE
ID NEUM_MOUSE Reviewed; 227 AA.
AC P06837;
DT 01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1988, sequence version 1.
DT 03-AUG-2022, entry version 187.
DE RecName: Full=Neuromodulin;
DE AltName: Full=Axonal membrane protein GAP-43;
DE AltName: Full=Calmodulin-binding protein P-57;
DE AltName: Full=Growth-associated protein 43;
GN Name=Gap43; Synonyms=Basp2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2442159; DOI=10.1016/s0021-9258(18)45330-6;
RA Cimler B.M., Giebelhaus D.H., Wakim B.T., Storm D.R., Moon R.T.;
RT "Characterization of murine cDNAs encoding P-57, a neural-specific
RT calmodulin-binding protein.";
RL J. Biol. Chem. 262:12158-12163(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Retina;
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 [3]
RP PROTEIN SEQUENCE OF 84-104, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=OF1; TISSUE=Hippocampus;
RA Lubec G., Sunyer B., Chen W.-Q.;
RL Submitted (JAN-2009) to UniProtKB.
RN [4]
RP IDENTIFICATION IN A COMPLEX WITH NCAM1; CDH2; PLCG1; FRS2; SRC; FGFR4 AND
RP CTTN.
RX PubMed=11433297; DOI=10.1038/35083041;
RA Cavallaro U., Niedermeyer J., Fuxa M., Christofori G.;
RT "N-CAM modulates tumour-cell adhesion to matrix by inducing FGF-receptor
RT signalling.";
RL Nat. Cell Biol. 3:650-657(2001).
RN [5]
RP TISSUE SPECIFICITY.
RX PubMed=11573004; DOI=10.1073/pnas.191388398;
RA Quattrone A., Pascale A., Nogues X., Zhao W., Gusev P., Pacini A.,
RA Alkon D.L.;
RT "Posttranscriptional regulation of gene expression in learning by the
RT neuronal ELAV-like mRNA-stabilizing proteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:11668-11673(2001).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic brain;
RX PubMed=15345747; DOI=10.1074/mcp.m400085-mcp200;
RA Ballif B.A., Villen J., Beausoleil S.A., Schwartz D., Gygi S.P.;
RT "Phosphoproteomic analysis of the developing mouse brain.";
RL Mol. Cell. Proteomics 3:1093-1101(2004).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=16452087; DOI=10.1074/mcp.t500041-mcp200;
RA Trinidad J.C., Specht C.G., Thalhammer A., Schoepfer R., Burlingame A.L.;
RT "Comprehensive identification of phosphorylation sites in postsynaptic
RT density preparations.";
RL Mol. Cell. Proteomics 5:914-922(2006).
RN [8]
RP INTERACTION WITH CALMODULIN, TISSUE SPECIFICITY, AND PHOSPHORYLATION.
RX PubMed=18493953; DOI=10.1002/hipo.20442;
RA Tanner D.C., Qiu S., Bolognani F., Partridge L.D., Weeber E.J.,
RA Perrone-Bizzozero N.I.;
RT "Alterations in mossy fiber physiology and GAP-43 expression and function
RT in transgenic mice overexpressing HuD.";
RL Hippocampus 18:814-823(2008).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-86; SER-96; THR-138; SER-142;
RP SER-144; SER-145 AND THR-172, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, and Lung;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [10]
RP PALMITOYLATION AT CYS-3 AND CYS-4, AND MUTAGENESIS OF CYS-3 AND CYS-4.
RX PubMed=27875292; DOI=10.1074/jbc.m116.732768;
RA Kilpatrick C.L., Murakami S., Feng M., Wu X., Lal R., Chen G., Du K.,
RA Luscher B.;
RT "Dissociation of Golgi-associated DHHC-type Zinc Finger Protein (GODZ)- and
RT Sertoli Cell Gene with a Zinc Finger Domain-beta (SERZ-beta)-mediated
RT Palmitoylation by Loss of Function Analyses in Knock-out Mice.";
RL J. Biol. Chem. 291:27371-27386(2016).
RN [11]
RP TISSUE SPECIFICITY, AND INDUCTION BY NERVE INJURY.
RX PubMed=28111162; DOI=10.1016/j.brainres.2017.01.019;
RA Sanna M.D., Ghelardini C., Galeotti N.;
RT "HuD-mediated distinct BDNF regulatory pathways promote regeneration after
RT nerve injury.";
RL Brain Res. 1659:55-63(2017).
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.
CC {ECO:0000250|UniProtKB:P17677}.
CC -!- SUBUNIT: Identified in a complex containing FGFR4, NCAM1, CDH2, PLCG1,
CC FRS2, SRC, SHC1, GAP43 and CTTN (PubMed:11433297). Interacts (via IQ
CC domain) with calmodulin (PubMed:18493953). 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:0000269|PubMed:11433297, ECO:0000269|PubMed:18493953}.
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 membrane {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:0000250|UniProtKB:P07936}. Cell projection, dendrite
CC {ECO:0000250|UniProtKB:P07936}. Cell projection, axon
CC {ECO:0000250|UniProtKB:P07936}. Cytoplasm
CC {ECO:0000250|UniProtKB:P07936}. Note=Cytoplasmic surface of growth cone
CC and synaptic plasma membranes. {ECO:0000250|UniProtKB:P17677}.
CC -!- TISSUE SPECIFICITY: Expressed in the hippocampus (at protein level)
CC (PubMed:18493953, PubMed:11573004). Expressed in the dorsal root
CC ganglion and the spinal cord (at protein level) (PubMed:28111162).
CC {ECO:0000269|PubMed:11573004, ECO:0000269|PubMed:18493953,
CC ECO:0000269|PubMed:28111162}.
CC -!- INDUCTION: Up-regulated after memory training in radial arm maze
CC experiments (PubMed:11573004). Up-regulated after sciatic nerve injury
CC (PubMed:28111162). {ECO:0000269|PubMed:11573004,
CC ECO:0000269|PubMed:28111162}.
CC -!- PTM: Phosphorylated (PubMed:18493953). Phosphorylation of this protein
CC by a protein kinase C is specifically correlated with certain forms of
CC synaptic plasticity (By similarity). {ECO:0000250|UniProtKB:P07936,
CC ECO:0000269|PubMed:18493953}.
CC -!- PTM: Palmitoylated by ZDHHC3 (PubMed:27875292). 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:P17677,
CC ECO:0000269|PubMed:27875292}.
CC -!- SIMILARITY: Belongs to the neuromodulin family. {ECO:0000305}.
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DR EMBL; J02809; AAA37377.1; -; mRNA.
DR EMBL; BC028288; AAH28288.1; -; mRNA.
DR EMBL; BC080758; AAH80758.1; -; mRNA.
DR CCDS; CCDS28177.1; -.
DR PIR; A29800; A29800.
DR RefSeq; NP_032109.1; NM_008083.2.
DR PDB; 4E53; X-ray; 2.69 A; A/B=34-57.
DR PDBsum; 4E53; -.
DR AlphaFoldDB; P06837; -.
DR SMR; P06837; -.
DR BioGRID; 199828; 7.
DR CORUM; P06837; -.
DR IntAct; P06837; 3.
DR MINT; P06837; -.
DR STRING; 10090.ENSMUSP00000099881; -.
DR iPTMnet; P06837; -.
DR PhosphoSitePlus; P06837; -.
DR SwissPalm; P06837; -.
DR MaxQB; P06837; -.
DR PaxDb; P06837; -.
DR PeptideAtlas; P06837; -.
DR PRIDE; P06837; -.
DR ProteomicsDB; 252953; -.
DR Antibodypedia; 2805; 873 antibodies from 43 providers.
DR DNASU; 14432; -.
DR Ensembl; ENSMUST00000102817; ENSMUSP00000099881; ENSMUSG00000047261.
DR GeneID; 14432; -.
DR KEGG; mmu:14432; -.
DR UCSC; uc007zfv.1; mouse.
DR CTD; 2596; -.
DR MGI; MGI:95639; Gap43.
DR VEuPathDB; HostDB:ENSMUSG00000047261; -.
DR eggNOG; ENOG502RXWF; Eukaryota.
DR GeneTree; ENSGT00730000111265; -.
DR HOGENOM; CLU_102989_0_0_1; -.
DR InParanoid; P06837; -.
DR OMA; GTPNKPE; -.
DR OrthoDB; 1531103at2759; -.
DR PhylomeDB; P06837; -.
DR TreeFam; TF333213; -.
DR Reactome; R-MMU-373760; L1CAM interactions.
DR BioGRID-ORCS; 14432; 1 hit in 74 CRISPR screens.
DR ChiTaRS; Gap43; mouse.
DR PRO; PR:P06837; -.
DR Proteomes; UP000000589; Chromosome 16.
DR RNAct; P06837; protein.
DR Bgee; ENSMUSG00000047261; Expressed in embryonic brain and 227 other tissues.
DR Genevisible; P06837; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0030424; C:axon; IDA:MGI.
DR GO; GO:0071944; C:cell periphery; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0030425; C:dendrite; IEA:UniProtKB-SubCell.
DR GO; GO:0031527; C:filopodium membrane; ISO:MGI.
DR GO; GO:0098982; C:GABA-ergic synapse; ISO:MGI.
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; IDA:MGI.
DR GO; GO:0014069; C:postsynaptic density; IDA:MGI.
DR GO; GO:0005516; F:calmodulin binding; IBA:GO_Central.
DR GO; GO:0035727; F:lysophosphatidic acid binding; ISO:MGI.
DR GO; GO:1901981; F:phosphatidylinositol phosphate binding; ISO:MGI.
DR GO; GO:0001786; F:phosphatidylserine binding; ISO:MGI.
DR GO; GO:0048708; P:astrocyte differentiation; IMP:MGI.
DR GO; GO:0016198; P:axon choice point recognition; IMP:MGI.
DR GO; GO:0007411; P:axon guidance; IMP:MGI.
DR GO; GO:0031103; P:axon regeneration; IBA:GO_Central.
DR GO; GO:0045165; P:cell fate commitment; IMP:MGI.
DR GO; GO:0060019; P:radial glial cell differentiation; IMP:MGI.
DR GO; GO:0051489; P:regulation of filopodium assembly; ISO:MGI.
DR GO; GO:0040008; P:regulation of growth; IEA:UniProtKB-KW.
DR GO; GO:0099150; P:regulation of postsynaptic specialization assembly; ISO:MGI.
DR GO; GO:0042246; P:tissue regeneration; IBA:GO_Central.
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 3D-structure; Calmodulin-binding; Cell membrane; Cell projection;
KW Cytoplasm; Developmental protein; Differentiation;
KW Direct protein sequencing; Growth regulation; Lipoprotein; Membrane;
KW Neurogenesis; Palmitate; Phosphoprotein; Reference proteome; Synapse.
FT CHAIN 1..227
FT /note="Neuromodulin"
FT /id="PRO_0000159597"
FT DOMAIN 31..60
FT /note="IQ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00116"
FT REGION 1..227
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 51..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 192..227
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 41
FT /note="Phosphoserine; by PHK"
FT /evidence="ECO:0000250|UniProtKB:P06836, ECO:0000305"
FT MOD_RES 86
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 96
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 138
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 142
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 144
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 145
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 172
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 192
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000250|UniProtKB:P06836"
FT MOD_RES 193
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000250|UniProtKB:P06836"
FT LIPID 3
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000305|PubMed:27875292"
FT LIPID 4
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000305|PubMed:27875292"
FT MUTAGEN 3
FT /note="C->S: Loss of palmitoylation; when associated with
FT S-4."
FT /evidence="ECO:0000269|PubMed:27875292"
FT MUTAGEN 4
FT /note="C->S: Loss of palmitoylation; when associated with
FT S-3."
FT /evidence="ECO:0000269|PubMed:27875292"
FT HELIX 35..51
FT /evidence="ECO:0007829|PDB:4E53"
SQ SEQUENCE 227 AA; 23632 MW; 14803B2F8F0649F7 CRC64;
MLCCMRRTKQ VEKNDEDQKI EQDGVKPEDK AHKAATKIQA SFRGHITRKK LKGEKKGDAP
AAEAEAKEKD DAPVADGVEK KEGDGSATTD AAPATSPKAE EPSKAGDAPS EEKKGEGDAA
PSEEKAGSAE TESAAKATTD NSPSSKAEDG PAKEEPKQAD VPAAVTDAAA TTPAAEDAAT
KAAQPPTETA ESSQAEEEKD AVDEAKPKES ARQDEGKEDP EADQEHA
