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P17677 (NEUM_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 152. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Neuromodulin
Alternative name(s):
Axonal membrane protein GAP-43
Growth-associated protein 43
Neural phosphoprotein B-50
pp46
Gene names
Name:GAP43
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length238 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.8 Ref.9

Subunit structure

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

Subcellular location

Cell membrane; Peripheral membrane protein; Cytoplasmic side. Cell projectiongrowth cone membrane; Peripheral membrane protein; Cytoplasmic side. Cell junctionsynapse. Cell projectionfilopodium membrane; Peripheral membrane protein. Note: Cytoplasmic surface of growth cone and synaptic plasma membranes. Ref.8

Post-translational modification

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.

Sequence similarities

Belongs to the neuromodulin family.

Contains 1 IQ domain.

Ontologies

Keywords
   Biological processDifferentiation
Growth regulation
Neurogenesis
   Cellular componentCell junction
Cell membrane
Cell projection
Membrane
Synapse
   Coding sequence diversityAlternative splicing
Polymorphism
   LigandCalmodulin-binding
   Molecular functionDevelopmental protein
   PTMLipoprotein
Palmitate
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processaxon choice point recognition

Inferred from electronic annotation. Source: Ensembl

cell fate commitment

Inferred from electronic annotation. Source: Ensembl

glial cell differentiation

Inferred from electronic annotation. Source: Ensembl

protein kinase C-activating G-protein coupled receptor signaling pathway

Traceable author statement Ref.1. Source: ProtInc

regulation of filopodium assembly

Inferred from direct assay Ref.8. Source: UniProtKB

regulation of growth

Inferred from electronic annotation. Source: UniProtKB-KW

response to wounding

Traceable author statement Ref.1. Source: ProtInc

tissue regeneration

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentaxon

Inferred from electronic annotation. Source: Ensembl

cell junction

Inferred from electronic annotation. Source: UniProtKB-KW

cytoplasm

Inferred from electronic annotation. Source: Ensembl

filopodium membrane

Inferred from direct assay Ref.8. Source: UniProtKB

growth cone membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

plasma membrane

Inferred from direct assay. Source: LIFEdb

synapse

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionprotein binding

Inferred from physical interaction PubMed 9139733. Source: IntAct

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

PRKCDQ056554EBI-1267511,EBI-704279

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P17677-1)

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.
Isoform 2 (identifier: P17677-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-10: MLCCMRRTKQ → MTKSCSELCHPALHFLPCLGGLRKNLQRAVRPSPYSLGFLTFWISR
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 238238Neuromodulin
PRO_0000159596

Regions

Domain31 – 6030IQ
Region1 – 44Important for membrane binding

Amino acid modifications

Modified residue411Phosphoserine; by PHK and PKC By similarity
Modified residue1811Phosphothreonine By similarity
Modified residue2021Phosphoserine; by CK2 By similarity
Modified residue2031Phosphoserine; by CK2 By similarity
Lipidation31S-palmitoyl cysteine By similarity
Lipidation41S-palmitoyl cysteine By similarity

Natural variations

Alternative sequence1 – 1010MLCCMRRTKQ → MTKSCSELCHPALHFLPCLG GLRKNLQRAVRPSPYSLGFL TFWISR in isoform 2.
VSP_042783
Natural variant591V → I. Ref.11
Corresponds to variant rs6291 [ dbSNP | Ensembl ].
VAR_014172
Natural variant1621K → E.
Corresponds to variant rs11557762 [ dbSNP | Ensembl ].
VAR_050271

Experimental info

Mutagenesis3 – 42CC → SS: Inhibits axonal and dendritic filopodia formation and reduces dendritic and axonal branching. Ref.8

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified August 1, 1990. Version 1.
Checksum: B3536D012A127CC8

FASTA23824,803
        10         20         30         40         50         60 
MLCCMRRTKQ VEKNDDDQKI EQDGIKPEDK AHKAATKIQA SFRGHITRKK LKGEKKDDVQ 

        70         80         90        100        110        120 
AAEAEANKKD EAPVADGVEK KGEGTTTAEA APATGSKPDE PGKAGETPSE EKKGEGDAAT 

       130        140        150        160        170        180 
EQAAPQAPAS SEEKAGSAET ESATKASTDN SPSSKAEDAP AKEEPKQADV PAAVTAAAAT 

       190        200        210        220        230 
TPAAEDAAAK ATAQPPTETG ESSQAEENIE AVDETKPKES ARQDEGKEEE PEADQEHA 

« Hide

Isoform 2 [UniParc].

Checksum: 5FC56C8954970362
Show »

FASTA27428,766

References

« Hide 'large scale' references
[1]"Human GAP-43: its deduced amino acid sequence and chromosomal localization in mouse and human."
Kosik K.S., Orecchio L.D., Bruns G.A.P., Benowitz L.I., McDonald G.P., Cox D.R., Neve R.
Neuron 1:127-132(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"Cloning of human GAP-43: growth association and ischemic resurgence."
Ng S.-C., de la Monte S.M., Conboy G.L., Karns L.R., Fishman M.C.
Neuron 1:133-139(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]"Structure of the human gene for the neural phosphoprotein B-50 (GAP-43)."
Nielander H.B., de Groen P.C., Eggen B.J., Schrama L.H., Gispen W.H., Schotman P.
Brain Res. Mol. Brain Res. 19:293-302(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]NIEHS SNPs program
Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Brain cortex and Subthalamic nucleus.
[6]"The DNA sequence, annotation and analysis of human chromosome 3."
Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. expand/collapse author list , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.
Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Brain.
[8]"Regulation of dendritic branching and filopodia formation in hippocampal neurons by specific acylated protein motifs."
Gauthier-Campbell C., Bredt D.S., Murphy T.H., El-Husseini A.
Mol. Biol. Cell 15:2205-2217(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF 3-CYS-CYS-4.
[9]"Acyl-protein thioesterase 2 catalyzes the deacylation of peripheral membrane-associated GAP-43."
Tomatis V.M., Trenchi A., Gomez G.A., Daniotti J.L.
PLoS ONE 5:E15045-E15045(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DEACYLATION BY LYPLA2.
[10]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]"Characterization of single-nucleotide polymorphisms in coding regions of human genes."
Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., Lander E.S.
Nat. Genet. 22:231-238(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ILE-59.
[12]Erratum
Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., Lander E.S.
Nat. Genet. 23:373-373(1999)
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS33830.1. [P17677-1]
CCDS46890.1. [P17677-2]
PIRI52638.
RefSeqNP_001123536.1. NM_001130064.1. [P17677-2]
NP_002036.1. NM_002045.3. [P17677-1]
UniGeneHs.134974.

3D structure databases

ProteinModelPortalP17677.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108867. 4 interactions.
DIPDIP-452N.
IntActP17677. 1 interaction.
MINTMINT-4725081.
STRING9606.ENSP00000377372.

Protein family/group databases

TCDB1.A.71.2.1. the brain acid-soluble protein channel (basp1 channel) family.

PTM databases

PhosphoSiteP17677.

Proteomic databases

MaxQBP17677.
PaxDbP17677.
PRIDEP17677.

Protocols and materials databases

DNASU2596.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000305124; ENSP00000305010; ENSG00000172020. [P17677-1]
ENST00000393780; ENSP00000377372; ENSG00000172020. [P17677-2]
GeneID2596.
KEGGhsa:2596.
UCSCuc003ebq.2. human. [P17677-1]
uc003ebr.2. human. [P17677-2]

Organism-specific databases

CTD2596.
GeneCardsGC03P115342.
HGNCHGNC:4140. GAP43.
HPACAB004417.
HPA013392.
HPA015600.
MIM162060. gene.
neXtProtNX_P17677.
PharmGKBPA28553.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG120480.
HOGENOMHOG000013014.
HOVERGENHBG006468.
OMAVEKKGEG.
OrthoDBEOG744TBB.
PhylomeDBP17677.
TreeFamTF333213.

Enzyme and pathway databases

SignaLinkP17677.

Gene expression databases

ArrayExpressP17677.
BgeeP17677.
CleanExHS_GAP43.
GenevestigatorP17677.

Family and domain databases

InterProIPR000048. IQ_motif_EF-hand-BS.
IPR001422. Neuromodulin.
IPR017454. Neuromodulin_C.
IPR018947. Neuromodulin_gap-junction_N.
IPR018243. Neuromodulin_palmitoyl/P_site.
[Graphical view]
PfamPF00612. IQ. 1 hit.
PF06614. Neuromodulin. 1 hit.
PF10580. Neuromodulin_N. 1 hit.
[Graphical view]
PRINTSPR00215. NEUROMODULIN.
SMARTSM00015. IQ. 1 hit.
[Graphical view]
PROSITEPS50096. IQ. 1 hit.
PS00412. NEUROMODULIN_1. 1 hit.
PS00413. NEUROMODULIN_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSGAP43. human.
GeneWikiGap-43_protein.
GenomeRNAi2596.
NextBio10267.
PROP17677.
SOURCESearch...

Entry information

Entry nameNEUM_HUMAN
AccessionPrimary (citable) accession number: P17677
Secondary accession number(s): A8K0Y4
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: August 1, 1990
Last modified: July 9, 2014
This is version 152 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 3

Human chromosome 3: entries, gene names and cross-references to MIM