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P62166

- NCS1_HUMAN

UniProt

P62166 - NCS1_HUMAN

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Protein

Neuronal calcium sensor 1

Gene
NCS1, FLUP, FREQ
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

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.

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Calcium bindingi73 – 841211 PublicationAdd
BLAST
Calcium bindingi109 – 1201221 PublicationAdd
BLAST
Calcium bindingi157 – 1681231 PublicationAdd
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
Complete GO annotation...

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.2 Publications

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
Complete GO annotation...

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 – 11Removed By similarity
Chaini2 – 190189Neuronal calcium sensor 1PRO_0000073788Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Lipidationi2 – 21N-myristoyl glycine By 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 IL1RAPL1.3 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.

Miscellaneous databases

EvolutionaryTraceiP62166.

Family & Domainsi

Domains and Repeats

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

Region

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

Sequence similaritiesi

Belongs to the recoverin family.
Contains 4 EF-hand domains.

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

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei2 – 2221GKSNS…RKTYF → MATI in isoform 2. VSP_046312Add
BLAST

Sequence conflict

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

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]
ENST00000458469; ENSP00000404103; ENSG00000107130. [P62166-2]
ENST00000599518; ENSP00000472360; ENSG00000268733. [P62166-2]
ENST00000601889; ENSP00000470938; ENSG00000268733. [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 ]
ENST00000458469 ; ENSP00000404103 ; ENSG00000107130 . [P62166-2 ]
ENST00000599518 ; ENSP00000472360 ; ENSG00000268733 . [P62166-2 ]
ENST00000601889 ; ENSP00000470938 ; ENSG00000268733 . [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

« Hide 'large scale' publications
  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: September 3, 2014
This is version 115 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

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