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P17677

- NEUM_HUMAN

UniProt

P17677 - NEUM_HUMAN

Protein

Neuromodulin

Gene

GAP43

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 153 (01 Oct 2014)
      Sequence version 1 (01 Aug 1990)
      Previous versions | rss
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    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

    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

    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 1 Publication; Peripheral membrane protein 1 Publication; Cytoplasmic side 1 Publication. Cell projectiongrowth cone membrane 1 Publication; Peripheral membrane protein 1 Publication; Cytoplasmic side 1 Publication. Cell junctionsynapse 1 Publication. Cell projectionfilopodium membrane 1 Publication; Peripheral membrane protein 1 Publication
    Note: Cytoplasmic surface of growth cone and synaptic plasma membranes.

    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

    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 – 238238NeuromodulinPRO_0000159596Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Lipidationi3 – 31S-palmitoyl cysteineBy similarity
    Lipidationi4 – 41S-palmitoyl cysteineBy similarity
    Modified residuei41 – 411Phosphoserine; by PHK and PKCBy similarity
    Modified residuei181 – 1811PhosphothreonineBy similarity
    Modified residuei202 – 2021Phosphoserine; by CK2By similarity
    Modified residuei203 – 2031Phosphoserine; by CK2By 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. 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.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini31 – 6030IQPROSITE-ProRule annotationAdd
    BLAST

    Region

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

    Sequence similaritiesi

    Belongs to the neuromodulin family.Curated
    Contains 1 IQ domain.PROSITE-ProRule annotation

    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. 1 PublicationVSP_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...
    MobiDBi 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

    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: October 1, 2014
    This is version 153 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