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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

Miscellaneous

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

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Calcium bindingi73 – 8411 PublicationAdd BLAST12
Calcium bindingi109 – 12021 PublicationAdd BLAST12
Calcium bindingi157 – 16831 PublicationAdd BLAST12

GO - Molecular functioni

GO - Biological processi

Keywordsi

LigandCalcium, 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
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

EuPathDBiHostDB:ENSG00000107130.9.
HGNCiHGNC:3953. NCS1.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

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

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi81E → T: Reduces calcium binding; when associated with A-117 or A-165. Abolishes calcium binding; when associated with A-117 and A-165. 1 Publication1
Mutagenesisi117T → A: Reduces calcium binding; when associated with T-81. Abolishes calcium binding; when associated with T-81 and A-165. 1 Publication1
Mutagenesisi165T → A: Reduces calcium binding; when associated with A-117. Abolishes calcium binding; when associated with T-81 and A-117. 1 Publication1

Organism-specific databases

DisGeNETi23413.
OpenTargetsiENSG00000107130.
PharmGKBiPA28371.

Polymorphism and mutation databases

BioMutaiNCS1.
DMDMi49065666.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved1 Publication
ChainiPRO_00000737882 – 190Neuronal calcium sensor 1Add BLAST189

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi2N-myristoyl glycine1 Publication1

Keywords - PTMi

Lipoprotein, Myristate

Proteomic databases

EPDiP62166.
MaxQBiP62166.
PaxDbiP62166.
PeptideAtlasiP62166.
PRIDEiP62166.
TopDownProteomicsiP62166-1. [P62166-1]

PTM databases

iPTMnetiP62166.
PhosphoSitePlusiP62166.

Expressioni

Gene expression databases

BgeeiENSG00000107130.
CleanExiHS_FREQ.
ExpressionAtlasiP62166. baseline and differential.
GenevisibleiP62166. HS.

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

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi116985. 32 interactors.
IntActiP62166. 13 interactors.
MINTiMINT-1436213.
STRINGi9606.ENSP00000361475.

Structurei

Secondary structure

1190
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi3 – 5Combined sources3
Helixi10 – 18Combined sources9
Beta strandi20 – 22Combined sources3
Helixi24 – 37Combined sources14
Beta strandi41 – 43Combined sources3
Helixi45 – 55Combined sources11
Helixi62 – 72Combined sources11
Beta strandi77 – 81Combined sources5
Helixi82 – 94Combined sources13
Helixi97 – 108Combined sources12
Beta strandi109 – 111Combined sources3
Beta strandi113 – 117Combined sources5
Helixi118 – 132Combined sources15
Beta strandi134 – 136Combined sources3
Beta strandi142 – 144Combined sources3
Helixi145 – 156Combined sources12
Helixi157 – 159Combined sources3
Beta strandi161 – 164Combined sources4
Helixi166 – 175Combined sources10
Helixi177 – 183Combined sources7

3D structure databases

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

Miscellaneous databases

EvolutionaryTraceiP62166.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini24 – 59EF-hand 1Add BLAST36
Domaini60 – 95EF-hand 2Add BLAST36
Domaini96 – 131EF-hand 3Add BLAST36
Domaini144 – 179EF-hand 4Add BLAST36

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni174 – 190Interaction with IL1RAPL11 PublicationAdd BLAST17

Sequence similaritiesi

Belongs to the recoverin family.Curated

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG0044. Eukaryota.
COG5126. LUCA.
GeneTreeiENSGT00760000118820.
HOGENOMiHOG000233019.
HOVERGENiHBG108179.
InParanoidiP62166.
KOiK19932.
OMAiKRELQQW.
OrthoDBiEOG091G11T4.
PhylomeDBiP62166.
TreeFamiTF300009.

Family and domain databases

CDDicd00051. EFh. 2 hits.
InterProiView protein in InterPro
IPR011992. EF-hand-dom_pair.
IPR018247. EF_Hand_1_Ca_BS.
IPR002048. EF_hand_dom.
PfamiView protein in Pfam
PF00036. EF-hand_1. 1 hit.
PF13499. EF-hand_7. 1 hit.
SMARTiView protein in SMART
SM00054. EFh. 3 hits.
SUPFAMiSSF47473. SSF47473. 1 hit.
PROSITEiView protein in PROSITE
PS00018. EF_HAND_1. 3 hits.
PS50222. EF_HAND_2. 3 hits.

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)DescriptionActionsGraphical viewLength
Sequence conflicti90S → P in AAF01804 (Ref. 4) Curated1
Sequence conflicti178S → P in AAF01804 (Ref. 4) Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0463121 – 22MGKSN…RKTYF → MATI in isoform 2. 1 PublicationAdd BLAST22

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. No translation available.
BC004856 mRNA. Translation: AAH04856.1.
BQ880305 mRNA. No translation available.
CCDSiCCDS6932.1. [P62166-1]
CCDS78448.1. [P62166-2]
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]
ENST00000630865; ENSP00000486695; ENSG00000107130. [P62166-2]
GeneIDi23413.
KEGGihsa:23413.
UCSCiuc004bzi.2. human. [P62166-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiNCS1_HUMAN
AccessioniPrimary (citable) accession number: P62166
Secondary accession number(s): E9PAY3, P36610, Q9UK26
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 21, 2004
Last sequence update: January 23, 2007
Last modified: October 25, 2017
This is version 148 of the entry and version 2 of the sequence. See 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

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