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Protein

Neuromodulin

Gene

GAP43

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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
  • axon guidance Source: Reactome
  • 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

HGNCiHGNC:4140. GAP43.

Subcellular locationi

GO - Cellular componenti

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.

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

Protein-protein interaction databases

BioGridi108867. 18 interactors.
DIPiDIP-452N.
IntActiP17677. 1 interactor.
MINTiMINT-4725081.
STRINGi9606.ENSP00000377372.

Structurei

3D structure databases

DisProtiDP00951.
ProteinModelPortaliP17677.
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.
OMAiPEADQEH.
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.
PANTHERiPTHR10699:SF23. PTHR10699:SF23. 1 hit.
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

Cross-referencesi

Web resourcesi

NIEHS-SNPs
Wikipedia

Gap-43 entry

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.

3D structure databases

DisProtiDP00951.
ProteinModelPortaliP17677.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108867. 18 interactors.
DIPiDIP-452N.
IntActiP17677. 1 interactor.
MINTiMINT-4725081.
STRINGi9606.ENSP00000377372.

Protein family/group databases

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

PTM databases

iPTMnetiP17677.
PhosphoSitePlusiP17677.
SwissPalmiP17677.

Polymorphism and mutation databases

BioMutaiGAP43.

Proteomic databases

EPDiP17677.
PaxDbiP17677.
PeptideAtlasiP17677.
PRIDEiP17677.

Protocols and materials databases

DNASUi2596.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi2596.
DisGeNETi2596.
GeneCardsiGAP43.
HGNCiHGNC:4140. GAP43.
HPAiCAB004417.
HPA013392.
HPA015600.
MIMi162060. gene.
neXtProtiNX_P17677.
OpenTargetsiENSG00000172020.
PharmGKBiPA28553.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

ReactomeiR-HSA-373760. L1CAM interactions.
SignaLinkiP17677.
SIGNORiP17677.

Miscellaneous databases

ChiTaRSiGAP43. human.
GeneWikiiGap-43_protein.
GenomeRNAii2596.
PROiP17677.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000172020.
CleanExiHS_GAP43.
ExpressionAtlasiP17677. baseline and differential.
GenevisibleiP17677. HS.

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.
PANTHERiPTHR10699:SF23. PTHR10699:SF23. 1 hit.
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.
ProtoNetiSearch...

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: March 15, 2017
This is version 174 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.