NEUM_BOVIN
ID NEUM_BOVIN Reviewed; 242 AA.
AC P06836; Q17QB5; Q6XZP9;
DT 01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2007, sequence version 3.
DT 03-AUG-2022, entry version 154.
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;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP PROTEIN SEQUENCE.
RX PubMed=2962637; DOI=10.1021/bi00397a040;
RA Wakim B.T., Alexander K.A., Masure H.R., Cimler B.M., Storm D.R.,
RA Walsh K.A.;
RT "Amino acid sequence of P-57, a neurospecific calmodulin-binding protein.";
RL Biochemistry 26:7466-7470(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Haegeman A.;
RT "Bovine GAP43 cDNA.";
RL Submitted (DEC-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Fetal cerebellum;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (JUN-2006) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP PHOSPHORYLATION AT SER-41 BY PKC.
RX PubMed=2140056; DOI=10.1021/bi00461a017;
RA Apel E.D., Byford M.F., Au D., Walsh K.A., Storm D.R.;
RT "Identification of the protein kinase C phosphorylation site in
RT neuromodulin.";
RL Biochemistry 29:2330-2335(1990).
RN [5]
RP PHOSPHORYLATION AT SER-206 AND SER-207 BY CKII.
RX PubMed=1828073; DOI=10.1016/s0021-9258(18)99258-6;
RA Apel E.D., Litchfield D.W., Cllark R.H., Krebs E.G., Storm D.R.;
RT "Phosphorylation of neuromodulin (GAP-43) by casein kinase II.
RT Identification of phosphorylation sites and regulation by calmodulin.";
RL J. Biol. Chem. 266:10544-10551(1991).
RN [6]
RP INTERACTION WITH CALMODULIN.
RX PubMed=1824693; DOI=10.1016/s0021-9258(18)52422-4;
RA Chapman E.R., Au D., Alexander K.A., Nicolson T.A., Storm D.R.;
RT "Characterization of the calmodulin binding domain of neuromodulin.
RT Functional significance of serine 41 and phenylalanine 42.";
RL J. Biol. Chem. 266:207-213(1991).
RN [7]
RP PALMITOYLATION AT CYS-3 AND CYS-4, AND MUTAGENESIS OF CYS-3 AND CYS-4.
RX PubMed=8399217; DOI=10.1021/bi00091a023;
RA Liu Y., Fisher D.A., Storm D.R.;
RT "Analysis of the palmitoylation and membrane targeting domain of
RT neuromodulin (GAP-43) by site-specific mutagenesis.";
RL Biochemistry 32:10714-10719(1993).
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).
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 (PubMed:1824693). Binds calmodulin with a
CC greater affinity in the absence of Ca(2+) than in its presence
CC (PubMed:1824693). {ECO:0000250|UniProtKB:P06837,
CC ECO:0000269|PubMed:1824693}.
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 -!- PTM: Phosphorylated (PubMed:2140056, PubMed:1828073, PubMed:8454596).
CC Phosphorylation of this protein by a protein kinase C is specifically
CC correlated with certain forms of synaptic plasticity (PubMed:2140056).
CC {ECO:0000269|PubMed:1828073, ECO:0000269|PubMed:2140056,
CC ECO:0000269|PubMed:8454596}.
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; AY195838; AAO60065.1; -; mRNA.
DR EMBL; BC118452; AAI18453.1; -; mRNA.
DR PIR; A27225; A27225.
DR RefSeq; NP_976234.2; NM_203358.2.
DR AlphaFoldDB; P06836; -.
DR SMR; P06836; -.
DR STRING; 9913.ENSBTAP00000008460; -.
DR iPTMnet; P06836; -.
DR PaxDb; P06836; -.
DR PeptideAtlas; P06836; -.
DR PRIDE; P06836; -.
DR Ensembl; ENSBTAT00000077074; ENSBTAP00000062170; ENSBTAG00000006451.
DR GeneID; 281777; -.
DR KEGG; bta:281777; -.
DR CTD; 2596; -.
DR VEuPathDB; HostDB:ENSBTAG00000006451; -.
DR VGNC; VGNC:29247; GAP43.
DR eggNOG; ENOG502RXWF; Eukaryota.
DR GeneTree; ENSGT00730000111265; -.
DR HOGENOM; CLU_102989_0_0_1; -.
DR InParanoid; P06836; -.
DR OrthoDB; 1531103at2759; -.
DR TreeFam; TF333213; -.
DR Proteomes; UP000009136; Chromosome 1.
DR Bgee; ENSBTAG00000006451; Expressed in floor plate of diencephalon and 54 other tissues.
DR ExpressionAtlas; P06836; baseline and differential.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0030425; C:dendrite; IEA:UniProtKB-SubCell.
DR GO; GO:0031527; C:filopodium membrane; IEA:UniProtKB-SubCell.
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; IBA:GO_Central.
DR GO; GO:0014069; C:postsynaptic density; IBA:GO_Central.
DR GO; GO:0005516; F:calmodulin binding; IBA:GO_Central.
DR GO; GO:0035727; F:lysophosphatidic acid binding; IBA:GO_Central.
DR GO; GO:1901981; F:phosphatidylinositol phosphate binding; IBA:GO_Central.
DR GO; GO:0001786; F:phosphatidylserine binding; IBA:GO_Central.
DR GO; GO:0016198; P:axon choice point recognition; IBA:GO_Central.
DR GO; GO:0031103; P:axon regeneration; IBA:GO_Central.
DR GO; GO:0040008; P:regulation of growth; IEA:UniProtKB-KW.
DR GO; GO:0042246; P:tissue regeneration; IBA:GO_Central.
DR DisProt; DP00955; -.
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..242
FT /note="Neuromodulin"
FT /id="PRO_0000159595"
FT DOMAIN 31..60
FT /note="IQ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00116"
FT REGION 1..242
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 101..120
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 144..159
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 207..242
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:2140056,
FT ECO:0000269|PubMed:8454596"
FT MOD_RES 86
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P06837"
FT MOD_RES 155
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P06837"
FT MOD_RES 157
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P06837"
FT MOD_RES 158
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P06837"
FT MOD_RES 206
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000269|PubMed:1828073"
FT MOD_RES 207
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000269|PubMed:1828073"
FT LIPID 3
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:8399217"
FT LIPID 4
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:8399217"
FT MUTAGEN 3
FT /note="C->G: Lack of palmitoylation; when associated with
FT G-4."
FT /evidence="ECO:0000269|PubMed:8399217"
FT MUTAGEN 3
FT /note="C->L: Decreased palmitoylation level."
FT /evidence="ECO:0000269|PubMed:8399217"
FT MUTAGEN 4
FT /note="C->G: Lack of palmitoylation; when associated with
FT G-3."
FT /evidence="ECO:0000269|PubMed:8399217"
FT MUTAGEN 4
FT /note="C->L: Decreased palmitoylation level."
FT /evidence="ECO:0000269|PubMed:8399217"
FT CONFLICT 22
FT /note="Q -> R (in Ref. 3; AAI18453)"
FT /evidence="ECO:0000305"
FT CONFLICT 111..113
FT /note="Missing (in Ref. 1; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 134
FT /note="P -> L (in Ref. 2; AAO60065)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 242 AA; 25066 MW; FD1F9A014FA91796 CRC64;
MLCCMRRTKQ VEKNDEDQKI EQDGIKPEDK AHKAATKIQA SFRGHITRKK LKGEKKGDAP
AAEAEANEKD EAAVAEGTEK KEGEGSTPAE AAPGAGPKPE EKTGKAGETP SEEKKGEGAP
DAATEQAAPQ APAPSEEKAG SAETESATKA STDNSPSSKA EDAPAKEEPK QADVPAAVTA
AAATAPAAED AAAMATAQPP TETAESSQAE EKIEAVDETK PKDSARQDEG KGEEREADQE
HA
