Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Basket 0
(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

P62166

- NCS1_HUMAN

UniProt

P62166 - NCS1_HUMAN

Protein

Neuronal calcium sensor 1

Gene

NCS1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
    • BLAST
    • Align
    • Format
    • Add to basket
    • History
      Entry version 116 (01 Oct 2014)
      Sequence version 2 (23 Jan 2007)
      Previous versions | rss
    • Help video
    • Feedback
    • Comment

    Functioni

    Neuronal calcium sensor, regulator of G protein-coupled receptor phosphorylation in a calcium dependent manner. Directly regulates GRK1 (RHOK), but not GRK2 to GRK5. Can substitute for calmodulin By similarity. Stimulates PI4KB kinase activity By similarity. Involved in long-term synaptic plasticity through its interaction with PICK1 By similarity. May also play a role in neuron differentiation through inhibition of the activity of N-type voltage-gated calcium channel By similarity.By similarity

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Calcium bindingi73 – 84121Add
    BLAST
    Calcium bindingi109 – 120122Add
    BLAST
    Calcium bindingi157 – 168123Add
    BLAST

    GO - Molecular functioni

    1. calcium ion binding Source: UniProtKB
    2. magnesium ion binding Source: Ensembl
    3. protein binding Source: UniProtKB
    4. voltage-gated calcium channel activity Source: UniProtKB

    GO - Biological processi

    1. calcium ion transmembrane transport Source: GOC
    2. phosphatidylinositol-mediated signaling Source: Ensembl
    3. positive regulation of exocytosis Source: Ensembl
    4. regulation of neuron projection development Source: UniProtKB

    Keywords - Ligandi

    Calcium, Metal-binding

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Neuronal calcium sensor 1
    Short name:
    NCS-1
    Alternative name(s):
    Frequenin homolog
    Frequenin-like protein
    Frequenin-like ubiquitous protein
    Gene namesi
    Name:NCS1
    Synonyms:FLUP, FREQ
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 9

    Organism-specific databases

    HGNCiHGNC:3953. NCS1.

    Subcellular locationi

    Golgi apparatusGolgi stack membrane; Peripheral membrane protein. Cell junctionsynapsepostsynaptic cell membranepostsynaptic density By similarity. Cytoplasmperinuclear region. Cell membrane; Peripheral membrane protein
    Note: Associated with Golgi stacks. Post-synaptic densities of dendrites, and in the pre-synaptic nerve terminal at neuromuscular junctions.

    GO - Cellular componenti

    1. axon Source: Ensembl
    2. cell junction Source: UniProtKB-KW
    3. cytoplasm Source: UniProtKB
    4. cytoplasmic vesicle Source: Ensembl
    5. cytosol Source: Ensembl
    6. dendrite Source: Ensembl
    7. extracellular vesicular exosome Source: UniProt
    8. Golgi cisterna membrane Source: UniProtKB-SubCell
    9. intracellular membrane-bounded organelle Source: HPA
    10. perinuclear region of cytoplasm Source: UniProtKB-SubCell
    11. plasma membrane Source: UniProtKB
    12. postsynaptic density Source: UniProtKB-SubCell
    13. postsynaptic membrane Source: UniProtKB-KW

    Keywords - Cellular componenti

    Cell junction, Cell membrane, Cytoplasm, Golgi apparatus, Membrane, Postsynaptic cell membrane, Synapse

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi81 – 811E → T: Reduces calcium binding; when associated with A-117 or A-165. Abolishes calcium binding; when associated with A-117 and A-165. 1 Publication
    Mutagenesisi117 – 1171T → A: Reduces calcium binding; when associated with T-81. Abolishes calcium binding; when associated with T-81 and A-165. 1 Publication
    Mutagenesisi165 – 1651T → A: Reduces calcium binding; when associated with A-117. Abolishes calcium binding; when associated with T-81 and A-117. 1 Publication

    Organism-specific databases

    PharmGKBiPA28371.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11RemovedBy similarity
    Chaini2 – 190189Neuronal calcium sensor 1PRO_0000073788Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Lipidationi2 – 21N-myristoyl glycineBy similarity

    Keywords - PTMi

    Lipoprotein, Myristate

    Proteomic databases

    MaxQBiP62166.
    PaxDbiP62166.
    PRIDEiP62166.

    PTM databases

    PhosphoSiteiP62166.

    Expressioni

    Gene expression databases

    BgeeiP62166.
    CleanExiHS_FREQ.
    GenevestigatoriP62166.

    Organism-specific databases

    HPAiCAB018587.
    HPA019713.

    Interactioni

    Subunit structurei

    Interacts with KCND2. Interacts in a calcium-independent manner with PI4KB. This binding competes with CALN2/CABP7 binding to PI4KB By similarity. Interacts with ARF1, ARF3, ARF5 and ARF6. Interacts in a calcium-dependent manner with PICK1 (via AH domain) By similarity. Interacts with IL1RAPL1.By similarity3 Publications

    Protein-protein interaction databases

    BioGridi116985. 13 interactions.
    IntActiP62166. 1 interaction.
    MINTiMINT-1436213.
    STRINGi9606.ENSP00000361475.

    Structurei

    Secondary structure

    1
    190
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi3 – 53
    Helixi10 – 189
    Beta strandi20 – 223
    Helixi24 – 3714
    Beta strandi41 – 433
    Helixi45 – 5511
    Helixi62 – 7211
    Beta strandi77 – 815
    Helixi82 – 9413
    Helixi97 – 10812
    Beta strandi109 – 1113
    Beta strandi113 – 1175
    Helixi118 – 13215
    Beta strandi142 – 1443
    Helixi145 – 15612
    Helixi157 – 1593
    Beta strandi161 – 1644
    Helixi166 – 17510
    Helixi177 – 1837

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1G8IX-ray1.90A/B1-190[»]
    2LCPNMR-A1-190[»]
    4GUKX-ray1.75A/B/C/D6-188[»]
    ProteinModelPortaliP62166.
    SMRiP62166. Positions 3-188.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP62166.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini24 – 5936EF-hand 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini60 – 9536EF-hand 2PROSITE-ProRule annotationAdd
    BLAST
    Domaini96 – 13136EF-hand 3PROSITE-ProRule annotationAdd
    BLAST
    Domaini144 – 17936EF-hand 4PROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni174 – 19017Interaction with IL1RAPL1Add
    BLAST

    Sequence similaritiesi

    Belongs to the recoverin family.Curated
    Contains 4 EF-hand domains.PROSITE-ProRule annotation

    Keywords - Domaini

    Repeat

    Phylogenomic databases

    eggNOGiCOG5126.
    HOGENOMiHOG000233019.
    HOVERGENiHBG108179.
    InParanoidiP62166.
    OMAiASFVFKV.
    OrthoDBiEOG7GJ6F3.
    PhylomeDBiP62166.
    TreeFamiTF300009.

    Family and domain databases

    Gene3Di1.10.238.10. 3 hits.
    InterProiIPR011992. EF-hand-dom_pair.
    IPR018247. EF_Hand_1_Ca_BS.
    IPR002048. EF_hand_dom.
    IPR028846. Recoverin.
    [Graphical view]
    PANTHERiPTHR23055. PTHR23055. 1 hit.
    PfamiPF00036. EF-hand_1. 3 hits.
    [Graphical view]
    SMARTiSM00054. EFh. 3 hits.
    [Graphical view]
    PROSITEiPS00018. EF_HAND_1. 3 hits.
    PS50222. EF_HAND_2. 3 hits.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: P62166-1) [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

    MGKSNSKLKP EVVEELTRKT YFTEKEVQQW YKGFIKDCPS GQLDAAGFQK    50
    IYKQFFPFGD PTKFATFVFN VFDENKDGRI EFSEFIQALS VTSRGTLDEK 100
    LRWAFKLYDL DNDGYITRNE MLDIVDAIYQ MVGNTVELPE EENTPEKRVD 150
    RIFAMMDKNA DGKLTLQEFQ EGSKADPSIV QALSLYDGLV 190
    Length:190
    Mass (Da):21,879
    Last modified:January 23, 2007 - v2
    Checksum:i9AF8E26A23F80D4F
    GO
    Isoform 2 (identifier: P62166-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         2-22: GKSNSKLKPEVVEELTRKTYF → MATI

    Note: No experimental confirmation available.

    Show »
    Length:173
    Mass (Da):19,859
    Checksum:i81222A8D4235A698
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti90 – 901S → P in AAF01804. 1 PublicationCurated
    Sequence conflicti178 – 1781S → P in AAF01804. 1 PublicationCurated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei2 – 2221GKSNS…RKTYF → MATI in isoform 2. 1 PublicationVSP_046312Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X84048 mRNA. Translation: CAA58867.1.
    AF134479 mRNA. Translation: AAP97256.1.
    AF186409 mRNA. Translation: AAF01804.1.
    AL360004 Genomic DNA. Translation: CAI16951.1.
    BC004856 mRNA. Translation: AAH04856.1.
    BQ880305 mRNA. No translation available.
    CCDSiCCDS6932.1. [P62166-1]
    RefSeqiNP_001122298.1. NM_001128826.1.
    NP_055101.2. NM_014286.3. [P62166-1]
    UniGeneiHs.642946.
    Hs.714951.

    Genome annotation databases

    EnsembliENST00000372398; ENSP00000361475; ENSG00000107130. [P62166-1]
    GeneIDi23413.
    KEGGihsa:23413.
    UCSCiuc004bzi.2. human. [P62166-1]

    Polymorphism databases

    DMDMi49065666.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X84048 mRNA. Translation: CAA58867.1 .
    AF134479 mRNA. Translation: AAP97256.1 .
    AF186409 mRNA. Translation: AAF01804.1 .
    AL360004 Genomic DNA. Translation: CAI16951.1 .
    BC004856 mRNA. Translation: AAH04856.1 .
    BQ880305 mRNA. No translation available.
    CCDSi CCDS6932.1. [P62166-1 ]
    RefSeqi NP_001122298.1. NM_001128826.1.
    NP_055101.2. NM_014286.3. [P62166-1 ]
    UniGenei Hs.642946.
    Hs.714951.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1G8I X-ray 1.90 A/B 1-190 [» ]
    2LCP NMR - A 1-190 [» ]
    4GUK X-ray 1.75 A/B/C/D 6-188 [» ]
    ProteinModelPortali P62166.
    SMRi P62166. Positions 3-188.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 116985. 13 interactions.
    IntActi P62166. 1 interaction.
    MINTi MINT-1436213.
    STRINGi 9606.ENSP00000361475.

    PTM databases

    PhosphoSitei P62166.

    Polymorphism databases

    DMDMi 49065666.

    Proteomic databases

    MaxQBi P62166.
    PaxDbi P62166.
    PRIDEi P62166.

    Protocols and materials databases

    DNASUi 23413.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000372398 ; ENSP00000361475 ; ENSG00000107130 . [P62166-1 ]
    GeneIDi 23413.
    KEGGi hsa:23413.
    UCSCi uc004bzi.2. human. [P62166-1 ]

    Organism-specific databases

    CTDi 23413.
    GeneCardsi GC09P132934.
    HGNCi HGNC:3953. NCS1.
    HPAi CAB018587.
    HPA019713.
    MIMi 603315. gene.
    neXtProti NX_P62166.
    PharmGKBi PA28371.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG5126.
    HOGENOMi HOG000233019.
    HOVERGENi HBG108179.
    InParanoidi P62166.
    OMAi ASFVFKV.
    OrthoDBi EOG7GJ6F3.
    PhylomeDBi P62166.
    TreeFami TF300009.

    Miscellaneous databases

    EvolutionaryTracei P62166.
    GeneWikii Neuronal_calcium_sensor-1.
    GenomeRNAii 23413.
    NextBioi 45611.
    PROi P62166.
    SOURCEi Search...

    Gene expression databases

    Bgeei P62166.
    CleanExi HS_FREQ.
    Genevestigatori P62166.

    Family and domain databases

    Gene3Di 1.10.238.10. 3 hits.
    InterProi IPR011992. EF-hand-dom_pair.
    IPR018247. EF_Hand_1_Ca_BS.
    IPR002048. EF_hand_dom.
    IPR028846. Recoverin.
    [Graphical view ]
    PANTHERi PTHR23055. PTHR23055. 1 hit.
    Pfami PF00036. EF-hand_1. 3 hits.
    [Graphical view ]
    SMARTi SM00054. EFh. 3 hits.
    [Graphical view ]
    PROSITEi PS00018. EF_HAND_1. 3 hits.
    PS50222. EF_HAND_2. 3 hits.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Frequenin-like Ca2+-binding protein (flup) modulates fast inactivation of mammalian presynaptic A-type K-channel."
      Lindemeier J.R., Hauenschild A., Pongs O.
      Submitted (JAN-1995) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    2. "Cloning of a new human cDNA homologous to Rattus norvegicus neuronal calcium sensor (NCS-1)."
      Bao X.G., Yu L., Zhao S.Y.
      Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    3. Nef S.
      Submitted (JUN-1999) to UniProtKB
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    4. "Sequence of human frequenin."
      Pongs O., Hauenschild A., Dannenberg J.
      Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    5. "DNA sequence and analysis of human chromosome 9."
      Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L.
      , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I.
      Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    6. "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] (ISOFORMS 1 AND 2).
      Tissue: Ovary and Spinal ganglion.
    7. "A role for frequenin, a Ca2+-binding protein, as a regulator of Kv4 K+-currents."
      Nakamura T.Y., Pountney D.J., Ozaita A., Nandi S., Ueda S., Rudy B., Coetzee W.A.
      Proc. Natl. Acad. Sci. U.S.A. 98:12808-12813(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH KCND2.
    8. "IL1 receptor accessory protein like, a protein involved in X-linked mental retardation, interacts with Neuronal Calcium Sensor-1 and regulates exocytosis."
      Bahi N., Friocourt G., Carrie A., Graham M.E., Weiss J.L., Chafey P., Fauchereau F., Burgoyne R.D., Chelly J.
      Hum. Mol. Genet. 12:1415-1425(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH IL1RAPL1.
    9. "Specificity, promiscuity and localization of ARF protein interactions with NCS-1 and phosphatidylinositol-4 kinase-III beta."
      Haynes L.P., Sherwood M.W., Dolman N.J., Burgoyne R.D.
      Traffic 8:1080-1092(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH ARF1; ARF3; ARF5 AND ARF6, SUBCELLULAR LOCATION.
    10. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    11. "Immunocytochemical localization and crystal structure of human frequenin (neuronal calcium sensor 1)."
      Bourne Y., Dannenberg J., Pollmann V., Marchot P., Pongs O.
      J. Biol. Chem. 276:11949-11955(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS), MUTAGENESIS OF GLU-81; THR-117 AND THR-165, CALCIUM-BINDING, SUBCELLULAR LOCATION.

    Entry informationi

    Entry nameiNCS1_HUMAN
    AccessioniPrimary (citable) accession number: P62166
    Secondary accession number(s): E9PAY3, P36610, Q9UK26
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: June 21, 2004
    Last sequence update: January 23, 2007
    Last modified: October 1, 2014
    This is version 116 of the entry and version 2 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

    Miscellaneous

    Binds 3 calcium ions via the second, third and fourth EF-hand.

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 9
      Human chromosome 9: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    4. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3