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P17677

- NEUM_HUMAN

UniProt

P17677 - NEUM_HUMAN

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Protein
Neuromodulin
Gene
GAP43
Organism
Homo sapiens (Human)
Status
Reviewed - 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

  1. protein binding Source: IntAct
Complete GO annotation...

GO - Biological processi

  1. axon choice point recognition Source: Ensembl
  2. cell fate commitment Source: Ensembl
  3. glial cell differentiation Source: Ensembl
  4. protein kinase C-activating G-protein coupled receptor signaling pathway Source: ProtInc
  5. regulation of filopodium assembly Source: UniProtKB
  6. regulation of growth Source: UniProtKB-KW
  7. response to wounding Source: ProtInc
  8. tissue regeneration Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein

Keywords - Biological processi

Differentiation, Growth regulation, Neurogenesis

Keywords - Ligandi

Calmodulin-binding

Enzyme and pathway databases

SignaLinkiP17677.

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
ProteomesiUP000005640: Chromosome 3

Organism-specific databases

HGNCiHGNC:4140. GAP43.

Subcellular locationi

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.1 Publication

GO - Cellular componenti

  1. axon Source: Ensembl
  2. cell junction Source: UniProtKB-KW
  3. cytoplasm Source: Ensembl
  4. filopodium membrane Source: UniProtKB
  5. growth cone membrane Source: UniProtKB-SubCell
  6. plasma membrane Source: LIFEdb
  7. synapse Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

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

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi3 – 42CC → SS: Inhibits axonal and dendritic filopodia formation and reduces dendritic and axonal branching. 1 Publication

Organism-specific databases

PharmGKBiPA28553.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 238238Neuromodulin
PRO_0000159596Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Lipidationi3 – 31S-palmitoyl cysteine By similarity
Lipidationi4 – 41S-palmitoyl cysteine By similarity
Modified residuei41 – 411Phosphoserine; by PHK and PKC By similarity
Modified residuei181 – 1811Phosphothreonine By similarity
Modified residuei202 – 2021Phosphoserine; by CK2 By similarity
Modified residuei203 – 2031Phosphoserine; by CK2 By similarity

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

MaxQBiP17677.
PaxDbiP17677.
PRIDEiP17677.

PTM databases

PhosphoSiteiP17677.

Expressioni

Gene expression databases

ArrayExpressiP17677.
BgeeiP17677.
CleanExiHS_GAP43.
GenevestigatoriP17677.

Organism-specific databases

HPAiCAB004417.
HPA013392.
HPA015600.

Interactioni

Subunit structurei

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.

Binary interactionsi

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

Protein-protein interaction databases

BioGridi108867. 4 interactions.
DIPiDIP-452N.
IntActiP17677. 1 interaction.
MINTiMINT-4725081.
STRINGi9606.ENSP00000377372.

Structurei

3D structure databases

ProteinModelPortaliP17677.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini31 – 6030IQ
Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 44Important for membrane binding

Sequence similaritiesi

Belongs to the neuromodulin family.
Contains 1 IQ domain.

Phylogenomic databases

eggNOGiNOG120480.
HOGENOMiHOG000013014.
HOVERGENiHBG006468.
OMAiVEKKGEG.
OrthoDBiEOG744TBB.
PhylomeDBiP17677.
TreeFamiTF333213.

Family and domain databases

InterProiIPR000048. IQ_motif_EF-hand-BS.
IPR001422. Neuromodulin.
IPR017454. Neuromodulin_C.
IPR018947. Neuromodulin_gap-junction_N.
IPR018243. Neuromodulin_palmitoyl/P_site.
[Graphical view]
PfamiPF00612. IQ. 1 hit.
PF06614. Neuromodulin. 1 hit.
PF10580. Neuromodulin_N. 1 hit.
[Graphical view]
PRINTSiPR00215. NEUROMODULIN.
SMARTiSM00015. IQ. 1 hit.
[Graphical view]
PROSITEiPS50096. IQ. 1 hit.
PS00412. NEUROMODULIN_1. 1 hit.
PS00413. NEUROMODULIN_2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. Align

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

MLCCMRRTKQ VEKNDDDQKI EQDGIKPEDK AHKAATKIQA SFRGHITRKK    50
LKGEKKDDVQ AAEAEANKKD EAPVADGVEK KGEGTTTAEA APATGSKPDE 100
PGKAGETPSE EKKGEGDAAT EQAAPQAPAS SEEKAGSAET ESATKASTDN 150
SPSSKAEDAP AKEEPKQADV PAAVTAAAAT TPAAEDAAAK ATAQPPTETG 200
ESSQAEENIE AVDETKPKES ARQDEGKEEE PEADQEHA 238
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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti59 – 591V → I.1 Publication
Corresponds to variant rs6291 [ dbSNP | Ensembl ].
VAR_014172
Natural varianti162 – 1621K → E.
Corresponds to variant rs11557762 [ dbSNP | Ensembl ].
VAR_050271

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 1010MLCCMRRTKQ → MTKSCSELCHPALHFLPCLG GLRKNLQRAVRPSPYSLGFL TFWISR in isoform 2.
VSP_042783

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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]
UniGeneiHs.134974.

Genome annotation databases

EnsembliENST00000305124; ENSP00000305010; ENSG00000172020. [P17677-1]
ENST00000393780; ENSP00000377372; ENSG00000172020. [P17677-2]
GeneIDi2596.
KEGGihsa:2596.
UCSCiuc003ebq.2. human. [P17677-1]
uc003ebr.2. human. [P17677-2]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

NIEHS-SNPs
Wikipedia

Gap-43 entry

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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 .
CCDSi CCDS33830.1. [P17677-1 ]
CCDS46890.1. [P17677-2 ]
PIRi I52638.
RefSeqi NP_001123536.1. NM_001130064.1. [P17677-2 ]
NP_002036.1. NM_002045.3. [P17677-1 ]
UniGenei Hs.134974.

3D structure databases

ProteinModelPortali P17677.
ModBasei Search...

Protein-protein interaction databases

BioGridi 108867. 4 interactions.
DIPi DIP-452N.
IntActi P17677. 1 interaction.
MINTi MINT-4725081.
STRINGi 9606.ENSP00000377372.

Protein family/group databases

TCDBi 1.A.71.2.1. the brain acid-soluble protein channel (basp1 channel) family.

PTM databases

PhosphoSitei P17677.

Proteomic databases

MaxQBi P17677.
PaxDbi P17677.
PRIDEi P17677.

Protocols and materials databases

DNASUi 2596.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000305124 ; ENSP00000305010 ; ENSG00000172020 . [P17677-1 ]
ENST00000393780 ; ENSP00000377372 ; ENSG00000172020 . [P17677-2 ]
GeneIDi 2596.
KEGGi hsa:2596.
UCSCi uc003ebq.2. human. [P17677-1 ]
uc003ebr.2. human. [P17677-2 ]

Organism-specific databases

CTDi 2596.
GeneCardsi GC03P115342.
HGNCi HGNC:4140. GAP43.
HPAi CAB004417.
HPA013392.
HPA015600.
MIMi 162060. gene.
neXtProti NX_P17677.
PharmGKBi PA28553.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG120480.
HOGENOMi HOG000013014.
HOVERGENi HBG006468.
OMAi VEKKGEG.
OrthoDBi EOG744TBB.
PhylomeDBi P17677.
TreeFami TF333213.

Enzyme and pathway databases

SignaLinki P17677.

Miscellaneous databases

ChiTaRSi GAP43. human.
GeneWikii Gap-43_protein.
GenomeRNAii 2596.
NextBioi 10267.
PROi P17677.
SOURCEi Search...

Gene expression databases

ArrayExpressi P17677.
Bgeei P17677.
CleanExi HS_GAP43.
Genevestigatori P17677.

Family and domain databases

InterProi IPR000048. IQ_motif_EF-hand-BS.
IPR001422. Neuromodulin.
IPR017454. Neuromodulin_C.
IPR018947. Neuromodulin_gap-junction_N.
IPR018243. Neuromodulin_palmitoyl/P_site.
[Graphical view ]
Pfami PF00612. IQ. 1 hit.
PF06614. Neuromodulin. 1 hit.
PF10580. Neuromodulin_N. 1 hit.
[Graphical view ]
PRINTSi PR00215. NEUROMODULIN.
SMARTi SM00015. IQ. 1 hit.
[Graphical view ]
PROSITEi PS50096. IQ. 1 hit.
PS00412. NEUROMODULIN_1. 1 hit.
PS00413. NEUROMODULIN_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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.
    , 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. Cited for: VARIANT ILE-59.

Entry informationi

Entry nameiNEUM_HUMAN
AccessioniPrimary (citable) accession number: P17677
Secondary accession number(s): A8K0Y4
Entry historyi
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 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

External Data

Dasty 3

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