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P62166 (NCS1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 114. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Neuronal calcium sensor 1

Short name=NCS-1
Alternative name(s):
Frequenin homolog
Frequenin-like protein
Frequenin-like ubiquitous protein
Gene names
Name:NCS1
Synonyms:FLUP, FREQ
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length190 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Subunit structure

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. Ref.7 Ref.8 Ref.9

Subcellular location

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. Ref.9 Ref.11

Miscellaneous

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

Sequence similarities

Belongs to the recoverin family.

Contains 4 EF-hand domains.

Ontologies

Keywords
   Cellular componentCell junction
Cell membrane
Cytoplasm
Golgi apparatus
Membrane
Postsynaptic cell membrane
Synapse
   Coding sequence diversityAlternative splicing
   DomainRepeat
   LigandCalcium
Metal-binding
   PTMLipoprotein
Myristate
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcalcium ion transmembrane transport

Inferred from sequence or structural similarity. Source: GOC

phosphatidylinositol-mediated signaling

Inferred from electronic annotation. Source: Ensembl

positive regulation of exocytosis

Inferred from electronic annotation. Source: Ensembl

regulation of neuron projection development

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentGolgi cisterna membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

axon

Inferred from electronic annotation. Source: Ensembl

cell junction

Inferred from electronic annotation. Source: UniProtKB-KW

cytoplasm

Inferred from direct assay Ref.8. Source: UniProtKB

cytoplasmic vesicle

Inferred from electronic annotation. Source: Ensembl

cytosol

Inferred from electronic annotation. Source: Ensembl

dendrite

Inferred from electronic annotation. Source: Ensembl

intracellular membrane-bounded organelle

Inferred from direct assay. Source: HPA

perinuclear region of cytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

plasma membrane

Inferred from direct assay Ref.8. Source: UniProtKB

postsynaptic density

Inferred from electronic annotation. Source: UniProtKB-SubCell

postsynaptic membrane

Inferred from electronic annotation. Source: UniProtKB-KW

   Molecular_functioncalcium ion binding

Traceable author statement Ref.11. Source: UniProtKB

magnesium ion binding

Inferred from electronic annotation. Source: Ensembl

protein binding

Inferred from physical interaction Ref.8. Source: UniProtKB

voltage-gated calcium channel activity

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P62166-1)

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: P62166-2)

The sequence of this isoform differs from the canonical sequence as follows:
     2-22: GKSNSKLKPEVVEELTRKTYF → MATI
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 190189Neuronal calcium sensor 1
PRO_0000073788

Regions

Domain24 – 5936EF-hand 1
Domain60 – 9536EF-hand 2
Domain96 – 13136EF-hand 3
Domain144 – 17936EF-hand 4
Calcium binding73 – 84121 Ref.11
Calcium binding109 – 120122 Ref.11
Calcium binding157 – 168123 Ref.11
Region174 – 19017Interaction with IL1RAPL1

Amino acid modifications

Lipidation21N-myristoyl glycine By similarity

Natural variations

Alternative sequence2 – 2221GKSNS…RKTYF → MATI in isoform 2.
VSP_046312

Experimental info

Mutagenesis811E → T: Reduces calcium binding; when associated with A-117 or A-165. Abolishes calcium binding; when associated with A-117 and A-165. Ref.11
Mutagenesis1171T → A: Reduces calcium binding; when associated with T-81. Abolishes calcium binding; when associated with T-81 and A-165. Ref.11
Mutagenesis1651T → A: Reduces calcium binding; when associated with A-117. Abolishes calcium binding; when associated with T-81 and A-117. Ref.11
Sequence conflict901S → P in AAF01804. Ref.4
Sequence conflict1781S → P in AAF01804. Ref.4

Secondary structure

.................................. 190
Helix Strand Turn

Details...

Sequences

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

Last modified January 23, 2007. Version 2.
Checksum: 9AF8E26A23F80D4F

FASTA19021,879
        10         20         30         40         50         60 
MGKSNSKLKP EVVEELTRKT YFTEKEVQQW YKGFIKDCPS GQLDAAGFQK IYKQFFPFGD 

        70         80         90        100        110        120 
PTKFATFVFN VFDENKDGRI EFSEFIQALS VTSRGTLDEK LRWAFKLYDL DNDGYITRNE 

       130        140        150        160        170        180 
MLDIVDAIYQ MVGNTVELPE EENTPEKRVD RIFAMMDKNA DGKLTLQEFQ EGSKADPSIV 

       190 
QALSLYDGLV 

« Hide

Isoform 2 [UniParc].

Checksum: 81222A8D4235A698
Show »

FASTA17319,859

References

« Hide 'large scale' references
[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. expand/collapse author list , 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]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS48043.1. [P62166-2]
CCDS6932.1. [P62166-1]
RefSeqNP_001122298.1. NM_001128826.1.
NP_055101.2. NM_014286.3. [P62166-1]
UniGeneHs.642946.
Hs.714951.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1G8IX-ray1.90A/B1-190[»]
2LCPNMR-A1-190[»]
4GUKX-ray1.75A/B/C/D6-188[»]
ProteinModelPortalP62166.
SMRP62166. Positions 3-188.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid116985. 13 interactions.
IntActP62166. 1 interaction.
MINTMINT-1436213.
STRING9606.ENSP00000361475.

PTM databases

PhosphoSiteP62166.

Polymorphism databases

DMDM49065666.

Proteomic databases

MaxQBP62166.
PaxDbP62166.
PRIDEP62166.

Protocols and materials databases

DNASU23413.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000372398; ENSP00000361475; ENSG00000107130. [P62166-1]
ENST00000458469; ENSP00000404103; ENSG00000107130. [P62166-2]
ENST00000599518; ENSP00000472360; ENSG00000268733. [P62166-2]
ENST00000601889; ENSP00000470938; ENSG00000268733. [P62166-1]
GeneID23413.
KEGGhsa:23413.
UCSCuc004bzi.2. human. [P62166-1]

Organism-specific databases

CTD23413.
GeneCardsGC09P132934.
HGNCHGNC:3953. NCS1.
HPACAB018587.
HPA019713.
MIM603315. gene.
neXtProtNX_P62166.
PharmGKBPA28371.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5126.
HOGENOMHOG000233019.
HOVERGENHBG108179.
InParanoidP62166.
OMAASFVFKV.
OrthoDBEOG7GJ6F3.
PhylomeDBP62166.
TreeFamTF300009.

Gene expression databases

BgeeP62166.
CleanExHS_FREQ.
GenevestigatorP62166.

Family and domain databases

Gene3D1.10.238.10. 3 hits.
InterProIPR011992. EF-hand-dom_pair.
IPR018247. EF_Hand_1_Ca_BS.
IPR002048. EF_hand_dom.
IPR028846. Recoverin.
[Graphical view]
PANTHERPTHR23055. PTHR23055. 1 hit.
PfamPF00036. EF-hand_1. 3 hits.
[Graphical view]
SMARTSM00054. EFh. 3 hits.
[Graphical view]
PROSITEPS00018. EF_HAND_1. 3 hits.
PS50222. EF_HAND_2. 3 hits.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP62166.
GeneWikiNeuronal_calcium_sensor-1.
GenomeRNAi23413.
NextBio45611.
PROP62166.
SOURCESearch...

Entry information

Entry nameNCS1_HUMAN
AccessionPrimary (citable) accession number: P62166
Secondary accession number(s): E9PAY3, P36610, Q9UK26
Entry history
Integrated into UniProtKB/Swiss-Prot: June 21, 2004
Last sequence update: January 23, 2007
Last modified: July 9, 2014
This is version 114 of the entry and version 2 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

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

Human chromosome 9

Human chromosome 9: entries, gene names and cross-references to MIM