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Protein

Neuromodulin

Gene

GAP43

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

This protein is associated with nerve growth. It is a major component of the motile "growth cones" that form the tips of elongating axons. Plays a role in axonal and dendritic filopodia induction.2 Publications

GO - Molecular functioni

GO - Biological processi

  • axon choice point recognition Source: Ensembl
  • axon development Source: GO_Central
  • cell fate commitment Source: Ensembl
  • glial cell differentiation Source: Ensembl
  • protein kinase C-activating G-protein coupled receptor signaling pathway Source: ProtInc
  • regulation of filopodium assembly Source: UniProtKB
  • regulation of growth Source: UniProtKB-KW
  • response to wounding Source: ProtInc
  • tissue regeneration Source: Ensembl

Keywordsi

Molecular functionCalmodulin-binding, Developmental protein
Biological processDifferentiation, Growth regulation, Neurogenesis

Enzyme and pathway databases

ReactomeiR-HSA-373760 L1CAM interactions
SignaLinkiP17677
SIGNORiP17677

Protein family/group databases

TCDBi1.A.71.2.1 the brain acid-soluble protein channel (basp1 channel) family

Names & Taxonomyi

Protein namesi
Recommended name:
Neuromodulin
Alternative name(s):
Axonal membrane protein GAP-43
Growth-associated protein 43
Neural phosphoprotein B-50
pp46
Gene namesi
Name:GAP43
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

EuPathDBiHostDB:ENSG00000172020.12
HGNCiHGNC:4140 GAP43
MIMi162060 gene
neXtProtiNX_P17677

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell junction, Cell membrane, Cell projection, Membrane, Synapse

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi3 – 4CC → SS: Inhibits axonal and dendritic filopodia formation and reduces dendritic and axonal branching. 1 Publication2

Organism-specific databases

DisGeNETi2596
OpenTargetsiENSG00000172020
PharmGKBiPA28553

Polymorphism and mutation databases

BioMutaiGAP43

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001595961 – 238NeuromodulinAdd BLAST238

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi3S-palmitoyl cysteineBy similarity1
Lipidationi4S-palmitoyl cysteineBy similarity1
Modified residuei41Phosphoserine; by PHK and PKCBy similarity1
Modified residuei151PhosphoserineBy similarity1
Modified residuei153PhosphoserineBy similarity1
Modified residuei154PhosphoserineBy similarity1
Modified residuei181PhosphothreonineBy similarity1
Modified residuei202Phosphoserine; by CK2By similarity1
Modified residuei203Phosphoserine; by CK2By similarity1

Post-translational modificationi

Phosphorylated at Ser-41 by PHK. Phosphorylation of this protein by a protein kinase C is specifically correlated with certain forms of synaptic plasticity.
Palmitoylation by ARF6 is essential for plasma membrane association and axonal and dendritic filopodia induction. Deacylated by LYPLA2.

Keywords - PTMi

Lipoprotein, Palmitate, Phosphoprotein

Proteomic databases

EPDiP17677
PaxDbiP17677
PeptideAtlasiP17677
PRIDEiP17677
ProteomicsDBi53504
53505 [P17677-2]

PTM databases

iPTMnetiP17677
PhosphoSitePlusiP17677
SwissPalmiP17677

Expressioni

Gene expression databases

BgeeiENSG00000172020
CleanExiHS_GAP43
ExpressionAtlasiP17677 baseline and differential
GenevisibleiP17677 HS

Organism-specific databases

HPAiCAB004417
HPA013392
HPA015600

Interactioni

Subunit structurei

Identified in a complex containing FGFR4, NCAM1, CDH2, PLCG1, FRS2, SRC, SHC1, GAP43 and CTTN. Binds calmodulin with a greater affinity in the absence of Ca2+ than in its presence.By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
PRKCDQ056554EBI-1267511,EBI-704279

GO - Molecular functioni

Protein-protein interaction databases

BioGridi108867, 27 interactors
DIPiDIP-452N
IntActiP17677, 1 interactor
STRINGi9606.ENSP00000377372

Structurei

3D structure databases

DisProtiDP00951
ProteinModelPortaliP17677
SMRiP17677
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini31 – 60IQPROSITE-ProRule annotationAdd BLAST30

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 4Important for membrane binding4

Sequence similaritiesi

Belongs to the neuromodulin family.Curated

Phylogenomic databases

eggNOGiENOG410IVZP Eukaryota
ENOG411256P LUCA
GeneTreeiENSGT00730000111265
HOGENOMiHOG000013014
HOVERGENiHBG006468
InParanoidiP17677
KOiK20041
OMAiCCMRRTK
OrthoDBiEOG091G0Z3Z
PhylomeDBiP17677
TreeFamiTF333213

Family and domain databases

InterProiView protein in InterPro
IPR000048 IQ_motif_EF-hand-BS
IPR001422 Neuromodulin
IPR017454 Neuromodulin_C
IPR018947 Neuromodulin_gap-junction_N
IPR033137 Neuromodulin_P_site
IPR018243 Neuromodulin_palmitoyl_site
PfamiView protein in Pfam
PF00612 IQ, 1 hit
PF06614 Neuromodulin, 1 hit
PF10580 Neuromodulin_N, 1 hit
PRINTSiPR00215 NEUROMODULIN
SMARTiView protein in SMART
SM00015 IQ, 1 hit
PROSITEiView protein in PROSITE
PS50096 IQ, 1 hit
PS00412 NEUROMODULIN_1, 1 hit
PS00413 NEUROMODULIN_2, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P17677-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MLCCMRRTKQ VEKNDDDQKI EQDGIKPEDK AHKAATKIQA SFRGHITRKK
60 70 80 90 100
LKGEKKDDVQ AAEAEANKKD EAPVADGVEK KGEGTTTAEA APATGSKPDE
110 120 130 140 150
PGKAGETPSE EKKGEGDAAT EQAAPQAPAS SEEKAGSAET ESATKASTDN
160 170 180 190 200
SPSSKAEDAP AKEEPKQADV PAAVTAAAAT TPAAEDAAAK ATAQPPTETG
210 220 230
ESSQAEENIE AVDETKPKES ARQDEGKEEE PEADQEHA
Length:238
Mass (Da):24,803
Last modified:August 1, 1990 - v1
Checksum:iB3536D012A127CC8
GO
Isoform 2 (identifier: P17677-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-10: MLCCMRRTKQ → MTKSCSELCHPALHFLPCLGGLRKNLQRAVRPSPYSLGFLTFWISR

Note: No experimental confirmation available.
Show »
Length:274
Mass (Da):28,766
Checksum:i5FC56C8954970362
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01417259V → I1 PublicationCorresponds to variant dbSNP:rs6291Ensembl.1
Natural variantiVAR_050271162K → E. Corresponds to variant dbSNP:rs11557762Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0427831 – 10MLCCMRRTKQ → MTKSCSELCHPALHFLPCLG GLRKNLQRAVRPSPYSLGFL TFWISR in isoform 2. 1 Publication10

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M25667 mRNA Translation: AAA52516.1
S66541, S66533, S66534 Genomic DNA Translation: AAB28649.1
AY842481 Genomic DNA Translation: AAV88094.1
AK289699 mRNA Translation: BAF82388.1
AK290100 mRNA Translation: BAF82789.1
AC012598 Genomic DNA No translation available.
AC092468 Genomic DNA No translation available.
AC119795 Genomic DNA No translation available.
BC007936 mRNA Translation: AAH07936.1
CCDSiCCDS33830.1 [P17677-1]
CCDS46890.1 [P17677-2]
PIRiI52638
RefSeqiNP_001123536.1, NM_001130064.1 [P17677-2]
NP_002036.1, NM_002045.3 [P17677-1]
XP_016861617.1, XM_017006128.1 [P17677-2]
UniGeneiHs.134974

Genome annotation databases

EnsembliENST00000305124; ENSP00000305010; ENSG00000172020 [P17677-1]
ENST00000393780; ENSP00000377372; ENSG00000172020 [P17677-2]
GeneIDi2596
KEGGihsa:2596
UCSCiuc003ebr.3 human [P17677-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiNEUM_HUMAN
AccessioniPrimary (citable) accession number: P17677
Secondary accession number(s): A8K0Y4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: August 1, 1990
Last modified: June 20, 2018
This is version 183 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

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