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Protein

Neuronal calcium sensor 1

Gene

NCS1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: 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).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. voltage-gated calcium channel activity Source: UniProtKB

GO - Biological processi

  1. phosphatidylinositol-mediated signaling Source: Ensembl
  2. positive regulation of exocytosis Source: Ensembl
  3. 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 Componenti: Chromosome 9

Organism-specific databases

HGNCiHGNC:3953. NCS1.

Subcellular locationi

  1. Golgi apparatusGolgi stack membrane; Peripheral membrane protein
  2. Cell junctionsynapsepostsynaptic cell membranepostsynaptic density By similarity
  3. Cytoplasmperinuclear region
  4. Cell membrane; Peripheral membrane protein

  5. 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. cytosol Source: Ensembl
  5. dendrite Source: Ensembl
  6. dense core granule Source: Ensembl
  7. extracellular vesicular exosome Source: UniProtKB
  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.

Polymorphism and mutation databases

BioMutaiNCS1.
DMDMi49065666.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11Removed
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.
ExpressionAtlasiP62166. baseline and differential.
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

Binary interactionsi

WithEntry#Exp.IntActNotes
DTX2Q4ZH495EBI-746987,EBI-10192429
DTX2Q86UW95EBI-746987,EBI-740376
NBL1P412713EBI-746987,EBI-10208650

Protein-protein interaction databases

BioGridi116985. 22 interactions.
IntActiP62166. 3 interactions.
MINTiMINT-1436213.
STRINGi9606.ENSP00000361475.

Structurei

Secondary structure

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

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
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.
GeneTreeiENSGT00760000118820.
HOGENOMiHOG000233019.
HOVERGENiHBG108179.
InParanoidiP62166.
OMAiFITYAEM.
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. AlignAdd to basket

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

        10         20         30         40         50
MGKSNSKLKP EVVEELTRKT YFTEKEVQQW YKGFIKDCPS GQLDAAGFQK
60 70 80 90 100
IYKQFFPFGD PTKFATFVFN VFDENKDGRI EFSEFIQALS VTSRGTLDEK
110 120 130 140 150
LRWAFKLYDL DNDGYITRNE MLDIVDAIYQ MVGNTVELPE EENTPEKRVD
160 170 180 190
RIFAMMDKNA DGKLTLQEFQ EGSKADPSIV QALSLYDGLV
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:
     1-22: MGKSNSKLKPEVVEELTRKTYF → MATI

Note: No experimental confirmation available.

Show »
Length:172
Mass (Da):19,728
Checksum:i8A8063D0D705465C
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti90 – 901S → P in AAF01804 (Ref. 4) Curated
Sequence conflicti178 – 1781S → P in AAF01804 (Ref. 4) Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 2222MGKSN…RKTYF → MATI in isoform 2. 1 PublicationVSP_046312Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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. [P62166-2]
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 and mutation databases

BioMutaiNCS1.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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. [P62166-2]
NP_055101.2. NM_014286.3. [P62166-1]
UniGeneiHs.642946.
Hs.714951.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
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...

Protein-protein interaction databases

BioGridi116985. 22 interactions.
IntActiP62166. 3 interactions.
MINTiMINT-1436213.
STRINGi9606.ENSP00000361475.

PTM databases

PhosphoSiteiP62166.

Polymorphism and mutation databases

BioMutaiNCS1.
DMDMi49065666.

Proteomic databases

MaxQBiP62166.
PaxDbiP62166.
PRIDEiP62166.

Protocols and materials databases

DNASUi23413.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi23413.
GeneCardsiGC09P132934.
HGNCiHGNC:3953. NCS1.
HPAiCAB018587.
HPA019713.
MIMi603315. gene.
neXtProtiNX_P62166.
PharmGKBiPA28371.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG5126.
GeneTreeiENSGT00760000118820.
HOGENOMiHOG000233019.
HOVERGENiHBG108179.
InParanoidiP62166.
OMAiFITYAEM.
OrthoDBiEOG7GJ6F3.
PhylomeDBiP62166.
TreeFamiTF300009.

Miscellaneous databases

ChiTaRSiNCS1. human.
EvolutionaryTraceiP62166.
GeneWikiiNeuronal_calcium_sensor-1.
GenomeRNAii23413.
NextBioi45611.
PROiP62166.
SOURCEiSearch...

Gene expression databases

BgeeiP62166.
CleanExiHS_FREQ.
ExpressionAtlasiP62166. baseline and differential.
GenevestigatoriP62166.

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]
ProtoNetiSearch...

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: April 29, 2015
This is version 122 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.