P62166 (NCS1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	190 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 apparatus › Golgi stack membrane; Peripheral membrane protein. Cell junction › synapse › postsynaptic cell membrane › postsynaptic density By similarity. Cytoplasm › perinuclear 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 component	Cell junction Cell membrane Cytoplasm Golgi apparatus Membrane Postsynaptic cell membrane Synapse
Coding sequence diversity	Alternative splicing
Domain	Repeat
Ligand	Calcium Metal-binding
PTM	Lipoprotein Myristate
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	phosphatidylinositol-mediated signaling Inferred from electronic annotation. Source: Compara positive regulation of exocytosis Inferred from electronic annotation. Source: Compara regulation of neuron projection development Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	Golgi cisterna membrane Inferred from electronic annotation. Source: UniProtKB-SubCell axon Inferred from electronic annotation. Source: Compara 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: Compara cytosol Inferred from electronic annotation. Source: Compara 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_function	calcium ion binding Traceable author statement Ref.11. 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:
     1-22: MGKSNSKLKPEVVEELTRKTYF → MATI

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed By similarity

Chain

2 – 190

189

Neuronal calcium sensor 1

PRO_0000073788

Regions

Domain

24 – 59

36

EF-hand 1

Domain

60 – 95

36

EF-hand 2

Domain

96 – 131

36

EF-hand 3

Domain

144 – 179

36

EF-hand 4

Calcium binding

73 – 84

12

1 Ref.11

Calcium binding

109 – 120

12

2 Ref.11

Calcium binding

157 – 168

12

3 Ref.11

Region

174 – 190

17

Interaction with IL1RAPL1

Amino acid modifications

Lipidation

2

1

N-myristoyl glycine By similarity

Natural variations

Alternative sequence

1 – 22

22

MGKSN…RKTYF → MATI in isoform 2.

VSP_046312

Experimental info

Mutagenesis

81

1

E → 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

Mutagenesis

117

1

T → A: Reduces calcium binding; when associated with T-81. Abolishes calcium binding; when associated with T-81 and A-165. Ref.11

Mutagenesis

165

1

T → A: Reduces calcium binding; when associated with A-117. Abolishes calcium binding; when associated with T-81 and A-117. Ref.11

Sequence conflict

90

1

S → P in AAF01804. Ref.4

Sequence conflict

178

1

S → P in AAF01804. Ref.4

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

190

Helix Strand Turn

Details...

Helix

3 – 5

3

Helix

10 – 18

9

Beta strand

20 – 22

3

Helix

24 – 37

14

Beta strand

41 – 44

4

Helix

45 – 55

11

Helix

62 – 72

11

Beta strand

77 – 81

5

Helix

82 – 94

13

Helix

97 – 108

12

Beta strand

109 – 111

3

Beta strand

113 – 117

5

Helix

118 – 131

14

Helix

140 – 142

3

Helix

145 – 156

12

Helix

157 – 159

3

Beta strand

161 – 165

5

Helix

166 – 175

10

Helix

177 – 183

7

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 23, 2007. Version 2. Checksum: 9AF8E26A23F80D4F	FASTA	190	21,879
	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
	Isoform 2 [UniParc]. Checksum: 8A8063D0D705465C	FASTA	172	19,728
	10 20 30 40 50 60 MATITEKEVQ QWYKGFIKDC PSGQLDAAGF QKIYKQFFPF GDPTKFATFV FNVFDENKDG 70 80 90 100 110 120 RIEFSEFIQA LSVTSRGTLD EKLRWAFKLY DLDNDGYITR NEMLDIVDAI YQMVGNTVEL 130 140 150 160 170 PEEENTPEKR VDRIFAMMDK NADGKLTLQE FQEGSKADPS IVQALSLYDG LV

References

	« Hide 'large scale' referencesShow '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. , 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.

IPI

IPI00219110.
IPI00900321.

RefSeq

NP_001122298.1. NM_001128826.1.
NP_055101.2. NM_014286.3.

UniGene

Hs.642946.
Hs.714951.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1G8I	X-ray	1.90	A/B	1-190	[»]
2LCP	NMR	-	A	1-190	[»]

ProteinModelPortal

P62166.

ModBase

Search...

Protein-protein interaction databases

IntAct

P62166. 1 interaction.

MINT

MINT-1436213.

STRING

9606.ENSP00000361475.

PTM databases

PhosphoSite

P62166.

Polymorphism databases

DMDM

49065666.

Proteomic databases

PaxDb

P62166.

PRIDE

P62166.

Protocols and materials databases

DNASU

23413.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000372398; ENSP00000361475; ENSG00000107130.
ENST00000458469; ENSP00000404103; ENSG00000107130.
ENST00000599518; ENSP00000472360; ENSG00000268733.
ENST00000601889; ENSP00000470938; ENSG00000268733.

GeneID

23413.

KEGG

hsa:23413.

UCSC

uc004bzi.2. human.

Organism-specific databases

CTD

23413.

GeneCards

GC09P132934.

HGNC

HGNC:3953. NCS1.

HPA

CAB018587.
HPA019713.

MIM

603315. gene.

neXtProt

NX_P62166.

PharmGKB

PA28371.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5126.

HOGENOM

HOG000233019.

HOVERGEN

HBG108179.

InParanoid

P62166.

OMA

FADYVFN.

OrthoDB

EOG4MGS8D.

PhylomeDB

P62166.

Gene expression databases

ArrayExpress

P62166.

Bgee

P62166.

CleanEx

HS_FREQ.

Genevestigator

P62166.

GermOnline

ENSG00000107130. Homo sapiens.

Family and domain databases

Gene3D

1.10.238.10. 3 hits.

InterPro

IPR011992. EF-hand-like_dom.
IPR018247. EF_Hand_1_Ca_BS.
IPR002048. EF_hand_dom.
IPR001125. Recoverin.
[Graphical view]

Pfam

PF13499. EF_hand_5. 1 hit.
PF00036. efhand. 3 hits.
[Graphical view]

PRINTS

PR00450. RECOVERIN.

SMART

SM00054. EFh. 3 hits.
[Graphical view]

PROSITE

PS00018. EF_HAND_1. 3 hits.
PS50222. EF_HAND_2. 3 hits.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P62166.

GenomeRNAi

23413.

NextBio

45611.

SOURCE

Search...

Entry information

Entry name

NCS1_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 101 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.