Full text data of NCS1
NCS1
(FLUP, FREQ)
[Confidence: low (only semi-automatic identification from reviews)]
Neuronal calcium sensor 1; NCS-1 (Frequenin homolog; Frequenin-like protein; Frequenin-like ubiquitous protein)
Neuronal calcium sensor 1; NCS-1 (Frequenin homolog; Frequenin-like protein; Frequenin-like ubiquitous protein)
UniProt
P62166
ID NCS1_HUMAN Reviewed; 190 AA.
AC P62166; E9PAY3; P36610; Q9UK26;
DT 21-JUN-2004, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 2.
DT 22-JAN-2014, entry version 108.
DE RecName: Full=Neuronal calcium sensor 1;
DE Short=NCS-1;
DE AltName: Full=Frequenin homolog;
DE AltName: Full=Frequenin-like protein;
DE AltName: Full=Frequenin-like ubiquitous protein;
GN Name=NCS1; Synonyms=FLUP, FREQ;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Lindemeier J.R., Hauenschild A., Pongs O.;
RT "Frequenin-like Ca2+-binding protein (flup) modulates fast
RT inactivation of mammalian presynaptic A-type K-channel.";
RL Submitted (JAN-1995) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Bao X.G., Yu L., Zhao S.Y.;
RT "Cloning of a new human cDNA homologous to Rattus norvegicus neuronal
RT calcium sensor (NCS-1).";
RL Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Nef S.;
RL Submitted (JUN-1999) to UniProtKB.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Pongs O., Hauenschild A., Dannenberg J.;
RT "Sequence of human frequenin.";
RL Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E.,
RA Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S.,
RA Babbage A.K., Babbage S., Bagguley C.L., Bailey J., Banerjee R.,
RA Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W.,
RA Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G.,
RA Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M.,
RA Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W.,
RA Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A.,
RA Frankland J.A., French L., Fricker D.G., Garner P., Garnett J.,
RA Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M.,
RA Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S.,
RA McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J.,
RA Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R.,
RA Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M.,
RA Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M.,
RA Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A.,
RA Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W.,
RA Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S.,
RA Rogers J., Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Ovary, and Spinal ganglion;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP INTERACTION WITH KCND2.
RX PubMed=11606724; DOI=10.1073/pnas.221168498;
RA Nakamura T.Y., Pountney D.J., Ozaita A., Nandi S., Ueda S., Rudy B.,
RA Coetzee W.A.;
RT "A role for frequenin, a Ca2+-binding protein, as a regulator of Kv4
RT K+-currents.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:12808-12813(2001).
RN [8]
RP INTERACTION WITH IL1RAPL1.
RX PubMed=12783849; DOI=10.1093/hmg/ddg147;
RA Bahi N., Friocourt G., Carrie A., Graham M.E., Weiss J.L., Chafey P.,
RA Fauchereau F., Burgoyne R.D., Chelly J.;
RT "IL1 receptor accessory protein like, a protein involved in X-linked
RT mental retardation, interacts with Neuronal Calcium Sensor-1 and
RT regulates exocytosis.";
RL Hum. Mol. Genet. 12:1415-1425(2003).
RN [9]
RP INTERACTION WITH ARF1; ARF3; ARF5 AND ARF6, AND SUBCELLULAR LOCATION.
RX PubMed=17555535; DOI=10.1111/j.1600-0854.2007.00594.x;
RA Haynes L.P., Sherwood M.W., Dolman N.J., Burgoyne R.D.;
RT "Specificity, promiscuity and localization of ARF protein interactions
RT with NCS-1 and phosphatidylinositol-4 kinase-III beta.";
RL Traffic 8:1080-1092(2007).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS), MUTAGENESIS OF GLU-81; THR-117
RP AND THR-165, CALCIUM-BINDING, AND SUBCELLULAR LOCATION.
RX PubMed=11092894; DOI=10.1074/jbc.M009373200;
RA Bourne Y., Dannenberg J., Pollmann V., Marchot P., Pongs O.;
RT "Immunocytochemical localization and crystal structure of human
RT frequenin (neuronal calcium sensor 1).";
RL J. Biol. Chem. 276:11949-11955(2001).
CC -!- FUNCTION: Neuronal calcium sensor, regulator of G protein-coupled
CC receptor phosphorylation in a calcium dependent manner. Directly
CC regulates GRK1 (RHOK), but not GRK2 to GRK5. Can substitute for
CC calmodulin (By similarity). Stimulates PI4KB kinase activity (By
CC similarity). Involved in long-term synaptic plasticity through its
CC interaction with PICK1 (By similarity). May also play a role in
CC neuron differentiation through inhibition of the activity of N-
CC type voltage-gated calcium channel (By similarity).
CC -!- SUBUNIT: Interacts with KCND2. Interacts in a calcium-independent
CC manner with PI4KB. This binding competes with CALN2/CABP7 binding
CC to PI4KB (By similarity). Interacts with ARF1, ARF3, ARF5 and
CC ARF6. Interacts in a calcium-dependent manner with PICK1 (via AH
CC domain) (By similarity). Interacts with IL1RAPL1.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus, Golgi stack membrane;
CC Peripheral membrane protein. Cell junction, synapse, postsynaptic
CC cell membrane, postsynaptic density (By similarity). Cytoplasm,
CC perinuclear region. Cell membrane; Peripheral membrane protein.
CC Note=Associated with Golgi stacks. Post-synaptic densities of
CC dendrites, and in the pre-synaptic nerve terminal at neuromuscular
CC junctions.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P62166-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P62166-2; Sequence=VSP_046312;
CC Note=No experimental confirmation available;
CC -!- MISCELLANEOUS: Binds 3 calcium ions via the second, third and
CC fourth EF-hand.
CC -!- SIMILARITY: Belongs to the recoverin family.
CC -!- SIMILARITY: Contains 4 EF-hand domains.
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DR EMBL; X84048; CAA58867.1; -; mRNA.
DR EMBL; AF134479; AAP97256.1; -; mRNA.
DR EMBL; AF186409; AAF01804.1; -; mRNA.
DR EMBL; AL360004; CAI16951.1; -; Genomic_DNA.
DR EMBL; BC004856; AAH04856.1; -; mRNA.
DR EMBL; BQ880305; -; NOT_ANNOTATED_CDS; mRNA.
DR RefSeq; NP_001122298.1; NM_001128826.1.
DR RefSeq; NP_055101.2; NM_014286.3.
DR UniGene; Hs.642946; -.
DR UniGene; Hs.714951; -.
DR PDB; 1G8I; X-ray; 1.90 A; A/B=1-190.
DR PDB; 2LCP; NMR; -; A=1-190.
DR PDBsum; 1G8I; -.
DR PDBsum; 2LCP; -.
DR ProteinModelPortal; P62166; -.
DR SMR; P62166; 3-188.
DR IntAct; P62166; 1.
DR MINT; MINT-1436213; -.
DR STRING; 9606.ENSP00000361475; -.
DR PhosphoSite; P62166; -.
DR DMDM; 49065666; -.
DR PaxDb; P62166; -.
DR PRIDE; P62166; -.
DR DNASU; 23413; -.
DR Ensembl; ENST00000372398; ENSP00000361475; ENSG00000107130.
DR Ensembl; ENST00000458469; ENSP00000404103; ENSG00000107130.
DR Ensembl; ENST00000599518; ENSP00000472360; ENSG00000268733.
DR Ensembl; ENST00000601889; ENSP00000470938; ENSG00000268733.
DR GeneID; 23413; -.
DR KEGG; hsa:23413; -.
DR UCSC; uc010myz.1; human.
DR CTD; 23413; -.
DR GeneCards; GC09P132934; -.
DR HGNC; HGNC:3953; NCS1.
DR HPA; CAB018587; -.
DR HPA; HPA019713; -.
DR MIM; 603315; gene.
DR neXtProt; NX_P62166; -.
DR PharmGKB; PA28371; -.
DR eggNOG; COG5126; -.
DR HOGENOM; HOG000233019; -.
DR HOVERGEN; HBG108179; -.
DR InParanoid; P62166; -.
DR OMA; ASFVFKV; -.
DR OrthoDB; EOG7GJ6F3; -.
DR PhylomeDB; P62166; -.
DR EvolutionaryTrace; P62166; -.
DR GeneWiki; Neuronal_calcium_sensor-1; -.
DR GenomeRNAi; 23413; -.
DR NextBio; 45611; -.
DR PRO; PR:P62166; -.
DR Bgee; P62166; -.
DR CleanEx; HS_FREQ; -.
DR Genevestigator; P62166; -.
DR GO; GO:0030424; C:axon; IEA:Ensembl.
DR GO; GO:0030054; C:cell junction; IEA:UniProtKB-KW.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:Ensembl.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0030425; C:dendrite; IEA:Ensembl.
DR GO; GO:0032580; C:Golgi cisterna membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0014069; C:postsynaptic density; IEA:UniProtKB-SubCell.
DR GO; GO:0045211; C:postsynaptic membrane; IEA:UniProtKB-KW.
DR GO; GO:0005509; F:calcium ion binding; TAS:UniProtKB.
DR GO; GO:0005245; F:voltage-gated calcium channel activity; ISS:UniProtKB.
DR GO; GO:0048015; P:phosphatidylinositol-mediated signaling; IEA:Ensembl.
DR GO; GO:0045921; P:positive regulation of exocytosis; IEA:Ensembl.
DR GO; GO:0010975; P:regulation of neuron projection development; ISS:UniProtKB.
DR Gene3D; 1.10.238.10; -; 3.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR InterPro; IPR002048; EF_hand_dom.
DR InterPro; IPR001125; Recoverin_like.
DR Pfam; PF00036; EF-hand_1; 3.
DR PRINTS; PR00450; RECOVERIN.
DR SMART; SM00054; EFh; 3.
DR PROSITE; PS00018; EF_HAND_1; 3.
DR PROSITE; PS50222; EF_HAND_2; 3.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Calcium; Cell junction;
KW Cell membrane; Complete proteome; Cytoplasm; Golgi apparatus;
KW Lipoprotein; Membrane; Metal-binding; Myristate;
KW Postsynaptic cell membrane; Reference proteome; Repeat; Synapse.
FT INIT_MET 1 1 Removed (By similarity).
FT CHAIN 2 190 Neuronal calcium sensor 1.
FT /FTId=PRO_0000073788.
FT DOMAIN 24 59 EF-hand 1.
FT DOMAIN 60 95 EF-hand 2.
FT DOMAIN 96 131 EF-hand 3.
FT DOMAIN 144 179 EF-hand 4.
FT CA_BIND 73 84 1.
FT CA_BIND 109 120 2.
FT CA_BIND 157 168 3.
FT REGION 174 190 Interaction with IL1RAPL1.
FT LIPID 2 2 N-myristoyl glycine (By similarity).
FT VAR_SEQ 1 22 MGKSNSKLKPEVVEELTRKTYF -> MATI (in
FT isoform 2).
FT /FTId=VSP_046312.
FT MUTAGEN 81 81 E->T: Reduces calcium binding; when
FT associated with A-117 or A-165. Abolishes
FT calcium binding; when associated with A-
FT 117 and A-165.
FT MUTAGEN 117 117 T->A: Reduces calcium binding; when
FT associated with T-81. Abolishes calcium
FT binding; when associated with T-81 and A-
FT 165.
FT MUTAGEN 165 165 T->A: Reduces calcium binding; when
FT associated with A-117. Abolishes calcium
FT binding; when associated with T-81 and A-
FT 117.
FT CONFLICT 90 90 S -> P (in Ref. 4; AAF01804).
FT CONFLICT 178 178 S -> P (in Ref. 4; AAF01804).
FT HELIX 3 5
FT HELIX 10 18
FT STRAND 20 22
FT HELIX 24 37
FT STRAND 41 44
FT HELIX 45 55
FT HELIX 62 72
FT STRAND 77 81
FT HELIX 82 94
FT HELIX 97 108
FT STRAND 109 111
FT STRAND 113 117
FT HELIX 118 131
FT HELIX 140 142
FT HELIX 145 156
FT HELIX 157 159
FT STRAND 161 165
FT HELIX 166 175
FT HELIX 177 183
SQ SEQUENCE 190 AA; 21879 MW; 9AF8E26A23F80D4F CRC64;
MGKSNSKLKP EVVEELTRKT YFTEKEVQQW YKGFIKDCPS GQLDAAGFQK IYKQFFPFGD
PTKFATFVFN VFDENKDGRI EFSEFIQALS VTSRGTLDEK LRWAFKLYDL DNDGYITRNE
MLDIVDAIYQ MVGNTVELPE EENTPEKRVD RIFAMMDKNA DGKLTLQEFQ EGSKADPSIV
QALSLYDGLV
//
ID NCS1_HUMAN Reviewed; 190 AA.
AC P62166; E9PAY3; P36610; Q9UK26;
DT 21-JUN-2004, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 2.
DT 22-JAN-2014, entry version 108.
DE RecName: Full=Neuronal calcium sensor 1;
DE Short=NCS-1;
DE AltName: Full=Frequenin homolog;
DE AltName: Full=Frequenin-like protein;
DE AltName: Full=Frequenin-like ubiquitous protein;
GN Name=NCS1; Synonyms=FLUP, FREQ;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Lindemeier J.R., Hauenschild A., Pongs O.;
RT "Frequenin-like Ca2+-binding protein (flup) modulates fast
RT inactivation of mammalian presynaptic A-type K-channel.";
RL Submitted (JAN-1995) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Bao X.G., Yu L., Zhao S.Y.;
RT "Cloning of a new human cDNA homologous to Rattus norvegicus neuronal
RT calcium sensor (NCS-1).";
RL Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Nef S.;
RL Submitted (JUN-1999) to UniProtKB.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Pongs O., Hauenschild A., Dannenberg J.;
RT "Sequence of human frequenin.";
RL Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E.,
RA Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S.,
RA Babbage A.K., Babbage S., Bagguley C.L., Bailey J., Banerjee R.,
RA Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W.,
RA Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G.,
RA Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M.,
RA Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W.,
RA Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A.,
RA Frankland J.A., French L., Fricker D.G., Garner P., Garnett J.,
RA Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M.,
RA Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S.,
RA McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J.,
RA Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R.,
RA Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M.,
RA Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M.,
RA Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A.,
RA Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W.,
RA Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S.,
RA Rogers J., Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Ovary, and Spinal ganglion;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP INTERACTION WITH KCND2.
RX PubMed=11606724; DOI=10.1073/pnas.221168498;
RA Nakamura T.Y., Pountney D.J., Ozaita A., Nandi S., Ueda S., Rudy B.,
RA Coetzee W.A.;
RT "A role for frequenin, a Ca2+-binding protein, as a regulator of Kv4
RT K+-currents.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:12808-12813(2001).
RN [8]
RP INTERACTION WITH IL1RAPL1.
RX PubMed=12783849; DOI=10.1093/hmg/ddg147;
RA Bahi N., Friocourt G., Carrie A., Graham M.E., Weiss J.L., Chafey P.,
RA Fauchereau F., Burgoyne R.D., Chelly J.;
RT "IL1 receptor accessory protein like, a protein involved in X-linked
RT mental retardation, interacts with Neuronal Calcium Sensor-1 and
RT regulates exocytosis.";
RL Hum. Mol. Genet. 12:1415-1425(2003).
RN [9]
RP INTERACTION WITH ARF1; ARF3; ARF5 AND ARF6, AND SUBCELLULAR LOCATION.
RX PubMed=17555535; DOI=10.1111/j.1600-0854.2007.00594.x;
RA Haynes L.P., Sherwood M.W., Dolman N.J., Burgoyne R.D.;
RT "Specificity, promiscuity and localization of ARF protein interactions
RT with NCS-1 and phosphatidylinositol-4 kinase-III beta.";
RL Traffic 8:1080-1092(2007).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS), MUTAGENESIS OF GLU-81; THR-117
RP AND THR-165, CALCIUM-BINDING, AND SUBCELLULAR LOCATION.
RX PubMed=11092894; DOI=10.1074/jbc.M009373200;
RA Bourne Y., Dannenberg J., Pollmann V., Marchot P., Pongs O.;
RT "Immunocytochemical localization and crystal structure of human
RT frequenin (neuronal calcium sensor 1).";
RL J. Biol. Chem. 276:11949-11955(2001).
CC -!- FUNCTION: Neuronal calcium sensor, regulator of G protein-coupled
CC receptor phosphorylation in a calcium dependent manner. Directly
CC regulates GRK1 (RHOK), but not GRK2 to GRK5. Can substitute for
CC calmodulin (By similarity). Stimulates PI4KB kinase activity (By
CC similarity). Involved in long-term synaptic plasticity through its
CC interaction with PICK1 (By similarity). May also play a role in
CC neuron differentiation through inhibition of the activity of N-
CC type voltage-gated calcium channel (By similarity).
CC -!- SUBUNIT: Interacts with KCND2. Interacts in a calcium-independent
CC manner with PI4KB. This binding competes with CALN2/CABP7 binding
CC to PI4KB (By similarity). Interacts with ARF1, ARF3, ARF5 and
CC ARF6. Interacts in a calcium-dependent manner with PICK1 (via AH
CC domain) (By similarity). Interacts with IL1RAPL1.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus, Golgi stack membrane;
CC Peripheral membrane protein. Cell junction, synapse, postsynaptic
CC cell membrane, postsynaptic density (By similarity). Cytoplasm,
CC perinuclear region. Cell membrane; Peripheral membrane protein.
CC Note=Associated with Golgi stacks. Post-synaptic densities of
CC dendrites, and in the pre-synaptic nerve terminal at neuromuscular
CC junctions.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P62166-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P62166-2; Sequence=VSP_046312;
CC Note=No experimental confirmation available;
CC -!- MISCELLANEOUS: Binds 3 calcium ions via the second, third and
CC fourth EF-hand.
CC -!- SIMILARITY: Belongs to the recoverin family.
CC -!- SIMILARITY: Contains 4 EF-hand domains.
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DR EMBL; X84048; CAA58867.1; -; mRNA.
DR EMBL; AF134479; AAP97256.1; -; mRNA.
DR EMBL; AF186409; AAF01804.1; -; mRNA.
DR EMBL; AL360004; CAI16951.1; -; Genomic_DNA.
DR EMBL; BC004856; AAH04856.1; -; mRNA.
DR EMBL; BQ880305; -; NOT_ANNOTATED_CDS; mRNA.
DR RefSeq; NP_001122298.1; NM_001128826.1.
DR RefSeq; NP_055101.2; NM_014286.3.
DR UniGene; Hs.642946; -.
DR UniGene; Hs.714951; -.
DR PDB; 1G8I; X-ray; 1.90 A; A/B=1-190.
DR PDB; 2LCP; NMR; -; A=1-190.
DR PDBsum; 1G8I; -.
DR PDBsum; 2LCP; -.
DR ProteinModelPortal; P62166; -.
DR SMR; P62166; 3-188.
DR IntAct; P62166; 1.
DR MINT; MINT-1436213; -.
DR STRING; 9606.ENSP00000361475; -.
DR PhosphoSite; P62166; -.
DR DMDM; 49065666; -.
DR PaxDb; P62166; -.
DR PRIDE; P62166; -.
DR DNASU; 23413; -.
DR Ensembl; ENST00000372398; ENSP00000361475; ENSG00000107130.
DR Ensembl; ENST00000458469; ENSP00000404103; ENSG00000107130.
DR Ensembl; ENST00000599518; ENSP00000472360; ENSG00000268733.
DR Ensembl; ENST00000601889; ENSP00000470938; ENSG00000268733.
DR GeneID; 23413; -.
DR KEGG; hsa:23413; -.
DR UCSC; uc010myz.1; human.
DR CTD; 23413; -.
DR GeneCards; GC09P132934; -.
DR HGNC; HGNC:3953; NCS1.
DR HPA; CAB018587; -.
DR HPA; HPA019713; -.
DR MIM; 603315; gene.
DR neXtProt; NX_P62166; -.
DR PharmGKB; PA28371; -.
DR eggNOG; COG5126; -.
DR HOGENOM; HOG000233019; -.
DR HOVERGEN; HBG108179; -.
DR InParanoid; P62166; -.
DR OMA; ASFVFKV; -.
DR OrthoDB; EOG7GJ6F3; -.
DR PhylomeDB; P62166; -.
DR EvolutionaryTrace; P62166; -.
DR GeneWiki; Neuronal_calcium_sensor-1; -.
DR GenomeRNAi; 23413; -.
DR NextBio; 45611; -.
DR PRO; PR:P62166; -.
DR Bgee; P62166; -.
DR CleanEx; HS_FREQ; -.
DR Genevestigator; P62166; -.
DR GO; GO:0030424; C:axon; IEA:Ensembl.
DR GO; GO:0030054; C:cell junction; IEA:UniProtKB-KW.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:Ensembl.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0030425; C:dendrite; IEA:Ensembl.
DR GO; GO:0032580; C:Golgi cisterna membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0014069; C:postsynaptic density; IEA:UniProtKB-SubCell.
DR GO; GO:0045211; C:postsynaptic membrane; IEA:UniProtKB-KW.
DR GO; GO:0005509; F:calcium ion binding; TAS:UniProtKB.
DR GO; GO:0005245; F:voltage-gated calcium channel activity; ISS:UniProtKB.
DR GO; GO:0048015; P:phosphatidylinositol-mediated signaling; IEA:Ensembl.
DR GO; GO:0045921; P:positive regulation of exocytosis; IEA:Ensembl.
DR GO; GO:0010975; P:regulation of neuron projection development; ISS:UniProtKB.
DR Gene3D; 1.10.238.10; -; 3.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR InterPro; IPR002048; EF_hand_dom.
DR InterPro; IPR001125; Recoverin_like.
DR Pfam; PF00036; EF-hand_1; 3.
DR PRINTS; PR00450; RECOVERIN.
DR SMART; SM00054; EFh; 3.
DR PROSITE; PS00018; EF_HAND_1; 3.
DR PROSITE; PS50222; EF_HAND_2; 3.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Calcium; Cell junction;
KW Cell membrane; Complete proteome; Cytoplasm; Golgi apparatus;
KW Lipoprotein; Membrane; Metal-binding; Myristate;
KW Postsynaptic cell membrane; Reference proteome; Repeat; Synapse.
FT INIT_MET 1 1 Removed (By similarity).
FT CHAIN 2 190 Neuronal calcium sensor 1.
FT /FTId=PRO_0000073788.
FT DOMAIN 24 59 EF-hand 1.
FT DOMAIN 60 95 EF-hand 2.
FT DOMAIN 96 131 EF-hand 3.
FT DOMAIN 144 179 EF-hand 4.
FT CA_BIND 73 84 1.
FT CA_BIND 109 120 2.
FT CA_BIND 157 168 3.
FT REGION 174 190 Interaction with IL1RAPL1.
FT LIPID 2 2 N-myristoyl glycine (By similarity).
FT VAR_SEQ 1 22 MGKSNSKLKPEVVEELTRKTYF -> MATI (in
FT isoform 2).
FT /FTId=VSP_046312.
FT MUTAGEN 81 81 E->T: Reduces calcium binding; when
FT associated with A-117 or A-165. Abolishes
FT calcium binding; when associated with A-
FT 117 and A-165.
FT MUTAGEN 117 117 T->A: Reduces calcium binding; when
FT associated with T-81. Abolishes calcium
FT binding; when associated with T-81 and A-
FT 165.
FT MUTAGEN 165 165 T->A: Reduces calcium binding; when
FT associated with A-117. Abolishes calcium
FT binding; when associated with T-81 and A-
FT 117.
FT CONFLICT 90 90 S -> P (in Ref. 4; AAF01804).
FT CONFLICT 178 178 S -> P (in Ref. 4; AAF01804).
FT HELIX 3 5
FT HELIX 10 18
FT STRAND 20 22
FT HELIX 24 37
FT STRAND 41 44
FT HELIX 45 55
FT HELIX 62 72
FT STRAND 77 81
FT HELIX 82 94
FT HELIX 97 108
FT STRAND 109 111
FT STRAND 113 117
FT HELIX 118 131
FT HELIX 140 142
FT HELIX 145 156
FT HELIX 157 159
FT STRAND 161 165
FT HELIX 166 175
FT HELIX 177 183
SQ SEQUENCE 190 AA; 21879 MW; 9AF8E26A23F80D4F CRC64;
MGKSNSKLKP EVVEELTRKT YFTEKEVQQW YKGFIKDCPS GQLDAAGFQK IYKQFFPFGD
PTKFATFVFN VFDENKDGRI EFSEFIQALS VTSRGTLDEK LRWAFKLYDL DNDGYITRNE
MLDIVDAIYQ MVGNTVELPE EENTPEKRVD RIFAMMDKNA DGKLTLQEFQ EGSKADPSIV
QALSLYDGLV
//
MIM
603315
*RECORD*
*FIELD* NO
603315
*FIELD* TI
*603315 FREQUENIN, DROSOPHILA, HOMOLOG OF; FREQ
;;NEURONAL CALCIUM SENSOR 1; NCS1
*FIELD* TX
read more
DESCRIPTION
Frequenin, a member of a large family of myristoyl-switch
calcium-binding proteins, functions as a calcium-ion sensor to modulate
synaptic activity and secretion (Bourne et al., 2001).
CLONING
DeCastro et al. (1995) cloned the rat and C. elegans orthologs of NCS1.
Amino acid sequence analysis of rat NCS1 detected 3 potential EF-hand
calcium-binding domains.
Using information from previously cloned mammalian homologs of
Drosophila Frq, Bourne et al. (2001) cloned human FREQ from first-strand
cDNA. FREQ encodes a deduced 190-amino acid protein that shares 100%
amino acid identity with the mouse and rat homologs and over 99%
identity with the Xenopus homolog. FREQ and its yeast homolog are also
highly homologous, with 75% of amino acids either identical or
corresponding to conservative replacements. The human protein contains 4
EF-hand motifs that represent potential Ca(2+)-binding domains, and a
consensus sequence for myristoylation in the N terminus.
BIOCHEMICAL FEATURES
- Crystal Structure
Bourne et al. (2001) determined the crystal structure of
unmyristoylated, calcium-bound human frequenin to 1.9-angstrom
resolution. Its overall fold is similar to those of other family members
such as recoverin, with 2 pairs of calcium-binding hands and 3 bound
calcium ions. Frequenin does, however, have significant structural
differences, including a novel large conformation shift of the C
terminus that creates a wide hydrophobic crevice at the surface of the
protein.
GENE FUNCTION
DeCastro et al. (1995) showed that several calcium sensors, including
NCS1, recoverin (179618), VILIP (600817), and S-modulin, can inhibit
rhodopsin (180380) phosphorylation in a calcium-dependent manner.
McFerran et al. (1998) found that NCS1, the mammalian homolog of
Drosophila frequenin, is expressed not only in bovine neurons, but also
in neuroendocrine cells. Colocalization and fractionation assays showed
that NCS1 may be associated with secretory granules. McFerran et al.
(1998) concluded that NCS1 may be involved in the regulation of
neurosecretion.
Nakamura et al. (2001) provided direct evidence that frequenin strongly
and specifically modulates Kv4 channels (the molecular components of
subthreshold-activating A-type K+ currents). The effect was specific for
Kv4.2 currents (605410); frequenin had negligible effects on Kv4.1
current inactivation time course. Coimmunoprecipitation experiments
demonstrated that a physical interaction occurs between frequenin and
Kv4.2 protein in brain membranes.
Bourne et al. (2001) determined that frequenin colocalizes with ARF1
GTPase (103180) in COS-7 cells and occurs in similar cellular
compartments as the phosphatidylinositol-4-OH kinase PI4K-beta (602758),
the mammalian homolog of the yeast kinase PIK1.
In a Xenopus model of the neuromuscular junction, Wang et al. (2001)
demonstrated that frequenin acted downstream of glial-derived
neurotrophic factor (GDNF; 600837) to enhance presynaptic calcium efflux
via N-type calcium channels, resulting in increased synaptic
transmission. P/Q-type presynaptic calcium currents undergo
activity-dependent facilitation during repetitive activation at the
calyx of the Held synapse. Tsujimoto et al. (2002) demonstrated that
direct loading of NCS1 into the nerve terminal mimicked
activity-dependent P/Q-type presynaptic calcium current facilitation by
accelerating the activation time of the current in a calcium-dependent
manner. A presynaptically loaded carboxyl-terminal peptide of NCS1
abolished the presynaptic calcium current facilitation. Tsujimoto et al.
(2002) concluded that residual calcium activates endogenous NCS1,
thereby facilitating P/Q-type presynaptic calcium currents. Because both
the calcium channels and NCS1 are widely expressed in mammalian nerve
terminals, NCS1 may contribute to the activity-dependent synaptic
facilitation at many synapses.
In cultured rat hippocampal cells, Sippy et al. (2003) showed that
increases in NCS1 can switch paired-pulse depression to facilitation
without altering basal synaptic transmission or initial neurotransmitter
release probability. Facilitation persisted during high-frequency trains
of stimulation, indicating that NCS1 can recruit dormant vesicles. Sippy
et al. (2003) suggested that NCS1 acts as a calcium sensor for
short-term synaptic plasticity by facilitating neurotransmitter output.
By screening a human fetal brain library using a yeast 2-hybrid system
with the intracellular domain of IL1RAPL (300206) as bait, Bahi et al.
(2003) determined that IL1RAPL interacts with NCS1 through its specific
C-terminal domain. Transient transfection and immunostaining detected
both proteins in the cytosol and demonstrated significant overlap in the
staining at the periphery of the transfected cells, suggesting a
colocalization at the plasma membrane.
Gromada et al. (2005) found that Ncs1 increased exocytosis in rodent
pancreatic beta cells by promoting priming of secretory granules for
release and increasing the number of granules residing in the readily
releasable pool. The effect of Ncs1 on exocytosis was mediated through
increased Pi4k-beta activity and generation of phosphoinositides,
specifically phosphatidylinositol 4-phosphate (PtdIns(4)P) and
PtdIns(4,5)P2. In turn, PtdIns(4,5)P2 controlled exocytosis through
Ca(2+)-dependent activator protein for secretion (CADPS; 604667).
Gromada et al. (2005) concluded that NCS1 and its downstream target,
PI4K-beta, are critical for glucose-induced insulin secretion due to
their capacity to regulate the release competence of secretory granules.
MAPPING
By sequence analysis, Bourne et al. (2001) mapped the FREQ gene to
chromosome 9q34.
*FIELD* RF
1. Bahi, N.; Friocourt, G.; Carrie, A.; Graham, M. E.; Weiss, J. L.;
Chafey, P.; Fauchereau, F.; Burgoyne, R. D.; Chelly, J.: IL1 receptor
accessory protein like, a protein involved in X-linked mental retardation,
interacts with neuronal calcium sensor-1 and regulates exocytosis. Hum.
Molec. Genet. 12: 1415-1425, 2003.
2. Bourne, Y.; Dannenberg, J.; Pollmann, V.; Marchot, P.; Pongs, O.
: Immunocytochemical localization and crystal structure of human frequenin
(neuronal calcium sensor 1). J. Biol. Chem. 276: 11949-11955, 2001.
3. De Castro, E.; Nef, S.; Fiumelli, H.; Lenz, S. E.; Kawamura, S.;
Nef, P.: Regulation of rhodopsin phosphorylation by a family of neuronal
calcium sensors. Biochem. Biophys. Res. Commun. 216: 133-140, 1995.
4. Gromada, J.; Bark, C.; Smidt, K.; Efanov, A. M.; Janson, J.; Mandic,
S. A.; Webb, D.-L.; Zhang, W.; Meister, B.; Jeromin, A.; Berggren,
P.-O.: Neuronal calcium sensor-1 potentiates glucose-dependent exocytosis
in pancreatic beta cells through activation of phosphatidylinositol
4-kinase beta. Proc. Nat. Acad. Sci. 102: 10303-10308, 2005.
5. McFerran, B. W.; Graham, M. E.; Burgoyne, R. D.: Neuronal Ca(2+)
sensor 1, the mammalian homologue of frequenin, is expressed in chromaffin
and PC12 cells and regulates neurosecretion from dense-core granules. J.
Biol. Chem. 273: 22768-22772, 1998.
6. Nakamura, T. Y.; Pountney, D. J.; Ozaita, A.; Nandi, S.; Ueda,
S.; Rudy, B.; Coetzee, W. A.: A role for frequenin, a Ca(2+)-binding
protein, as a regulator of Kv4 K(+)-currents. Proc. Nat. Acad. Sci. 98:
12808-12813, 2001.
7. Sippy, T.; Cruz-Martin, A.; Jeromin, A.; Schweizer, F. E.: Acute
changes in short-term plasticity at synapses with elevated levels
of neuronal calcium sensor-1. Nature Neurosci. 6: 1031-1038, 2003.
8. Tsujimoto, T.; Jeromin, A.; Saitoh, N.; Roder, J. C.; Takahashi,
T.: Neuronal calcium sensor 1 and activity-dependent facilitation
of P/Q-type calcium currents at presynaptic nerve terminals. Science 295:
2276-2279, 2002.
9. Wang, C.-Y.; Yang, F.; He, X.; Chow, A.; Du, J.; Russell, J. T.;
Lu, B.: Ca(2+) binding protein frequenin mediates GDNF-induced potentiation
of Ca(2+) channels and transmitter release. Neuron 32: 99-112, 2001.
*FIELD* CN
Patricia A. Hartz - updated: 09/01/2006
Cassandra L. Kniffin - updated: 8/22/2005
George E. Tiller - updated: 3/21/2005
Cassandra L. Kniffin - updated: 9/4/2003
Ada Hamosh - updated: 3/26/2002
Carol A. Bocchini - updated: 2/25/2002
Victor A. McKusick - updated: 1/14/2002
*FIELD* CD
Jennifer P. Macke: 11/24/1998
*FIELD* ED
mgross: 09/01/2006
carol: 8/29/2005
ckniffin: 8/22/2005
alopez: 3/21/2005
alopez: 10/16/2003
tkritzer: 9/8/2003
ckniffin: 9/4/2003
alopez: 3/26/2002
terry: 3/26/2002
mgross: 2/25/2002
carol: 2/25/2002
carol: 1/20/2002
mcapotos: 1/14/2002
alopez: 11/24/1998
*RECORD*
*FIELD* NO
603315
*FIELD* TI
*603315 FREQUENIN, DROSOPHILA, HOMOLOG OF; FREQ
;;NEURONAL CALCIUM SENSOR 1; NCS1
*FIELD* TX
read more
DESCRIPTION
Frequenin, a member of a large family of myristoyl-switch
calcium-binding proteins, functions as a calcium-ion sensor to modulate
synaptic activity and secretion (Bourne et al., 2001).
CLONING
DeCastro et al. (1995) cloned the rat and C. elegans orthologs of NCS1.
Amino acid sequence analysis of rat NCS1 detected 3 potential EF-hand
calcium-binding domains.
Using information from previously cloned mammalian homologs of
Drosophila Frq, Bourne et al. (2001) cloned human FREQ from first-strand
cDNA. FREQ encodes a deduced 190-amino acid protein that shares 100%
amino acid identity with the mouse and rat homologs and over 99%
identity with the Xenopus homolog. FREQ and its yeast homolog are also
highly homologous, with 75% of amino acids either identical or
corresponding to conservative replacements. The human protein contains 4
EF-hand motifs that represent potential Ca(2+)-binding domains, and a
consensus sequence for myristoylation in the N terminus.
BIOCHEMICAL FEATURES
- Crystal Structure
Bourne et al. (2001) determined the crystal structure of
unmyristoylated, calcium-bound human frequenin to 1.9-angstrom
resolution. Its overall fold is similar to those of other family members
such as recoverin, with 2 pairs of calcium-binding hands and 3 bound
calcium ions. Frequenin does, however, have significant structural
differences, including a novel large conformation shift of the C
terminus that creates a wide hydrophobic crevice at the surface of the
protein.
GENE FUNCTION
DeCastro et al. (1995) showed that several calcium sensors, including
NCS1, recoverin (179618), VILIP (600817), and S-modulin, can inhibit
rhodopsin (180380) phosphorylation in a calcium-dependent manner.
McFerran et al. (1998) found that NCS1, the mammalian homolog of
Drosophila frequenin, is expressed not only in bovine neurons, but also
in neuroendocrine cells. Colocalization and fractionation assays showed
that NCS1 may be associated with secretory granules. McFerran et al.
(1998) concluded that NCS1 may be involved in the regulation of
neurosecretion.
Nakamura et al. (2001) provided direct evidence that frequenin strongly
and specifically modulates Kv4 channels (the molecular components of
subthreshold-activating A-type K+ currents). The effect was specific for
Kv4.2 currents (605410); frequenin had negligible effects on Kv4.1
current inactivation time course. Coimmunoprecipitation experiments
demonstrated that a physical interaction occurs between frequenin and
Kv4.2 protein in brain membranes.
Bourne et al. (2001) determined that frequenin colocalizes with ARF1
GTPase (103180) in COS-7 cells and occurs in similar cellular
compartments as the phosphatidylinositol-4-OH kinase PI4K-beta (602758),
the mammalian homolog of the yeast kinase PIK1.
In a Xenopus model of the neuromuscular junction, Wang et al. (2001)
demonstrated that frequenin acted downstream of glial-derived
neurotrophic factor (GDNF; 600837) to enhance presynaptic calcium efflux
via N-type calcium channels, resulting in increased synaptic
transmission. P/Q-type presynaptic calcium currents undergo
activity-dependent facilitation during repetitive activation at the
calyx of the Held synapse. Tsujimoto et al. (2002) demonstrated that
direct loading of NCS1 into the nerve terminal mimicked
activity-dependent P/Q-type presynaptic calcium current facilitation by
accelerating the activation time of the current in a calcium-dependent
manner. A presynaptically loaded carboxyl-terminal peptide of NCS1
abolished the presynaptic calcium current facilitation. Tsujimoto et al.
(2002) concluded that residual calcium activates endogenous NCS1,
thereby facilitating P/Q-type presynaptic calcium currents. Because both
the calcium channels and NCS1 are widely expressed in mammalian nerve
terminals, NCS1 may contribute to the activity-dependent synaptic
facilitation at many synapses.
In cultured rat hippocampal cells, Sippy et al. (2003) showed that
increases in NCS1 can switch paired-pulse depression to facilitation
without altering basal synaptic transmission or initial neurotransmitter
release probability. Facilitation persisted during high-frequency trains
of stimulation, indicating that NCS1 can recruit dormant vesicles. Sippy
et al. (2003) suggested that NCS1 acts as a calcium sensor for
short-term synaptic plasticity by facilitating neurotransmitter output.
By screening a human fetal brain library using a yeast 2-hybrid system
with the intracellular domain of IL1RAPL (300206) as bait, Bahi et al.
(2003) determined that IL1RAPL interacts with NCS1 through its specific
C-terminal domain. Transient transfection and immunostaining detected
both proteins in the cytosol and demonstrated significant overlap in the
staining at the periphery of the transfected cells, suggesting a
colocalization at the plasma membrane.
Gromada et al. (2005) found that Ncs1 increased exocytosis in rodent
pancreatic beta cells by promoting priming of secretory granules for
release and increasing the number of granules residing in the readily
releasable pool. The effect of Ncs1 on exocytosis was mediated through
increased Pi4k-beta activity and generation of phosphoinositides,
specifically phosphatidylinositol 4-phosphate (PtdIns(4)P) and
PtdIns(4,5)P2. In turn, PtdIns(4,5)P2 controlled exocytosis through
Ca(2+)-dependent activator protein for secretion (CADPS; 604667).
Gromada et al. (2005) concluded that NCS1 and its downstream target,
PI4K-beta, are critical for glucose-induced insulin secretion due to
their capacity to regulate the release competence of secretory granules.
MAPPING
By sequence analysis, Bourne et al. (2001) mapped the FREQ gene to
chromosome 9q34.
*FIELD* RF
1. Bahi, N.; Friocourt, G.; Carrie, A.; Graham, M. E.; Weiss, J. L.;
Chafey, P.; Fauchereau, F.; Burgoyne, R. D.; Chelly, J.: IL1 receptor
accessory protein like, a protein involved in X-linked mental retardation,
interacts with neuronal calcium sensor-1 and regulates exocytosis. Hum.
Molec. Genet. 12: 1415-1425, 2003.
2. Bourne, Y.; Dannenberg, J.; Pollmann, V.; Marchot, P.; Pongs, O.
: Immunocytochemical localization and crystal structure of human frequenin
(neuronal calcium sensor 1). J. Biol. Chem. 276: 11949-11955, 2001.
3. De Castro, E.; Nef, S.; Fiumelli, H.; Lenz, S. E.; Kawamura, S.;
Nef, P.: Regulation of rhodopsin phosphorylation by a family of neuronal
calcium sensors. Biochem. Biophys. Res. Commun. 216: 133-140, 1995.
4. Gromada, J.; Bark, C.; Smidt, K.; Efanov, A. M.; Janson, J.; Mandic,
S. A.; Webb, D.-L.; Zhang, W.; Meister, B.; Jeromin, A.; Berggren,
P.-O.: Neuronal calcium sensor-1 potentiates glucose-dependent exocytosis
in pancreatic beta cells through activation of phosphatidylinositol
4-kinase beta. Proc. Nat. Acad. Sci. 102: 10303-10308, 2005.
5. McFerran, B. W.; Graham, M. E.; Burgoyne, R. D.: Neuronal Ca(2+)
sensor 1, the mammalian homologue of frequenin, is expressed in chromaffin
and PC12 cells and regulates neurosecretion from dense-core granules. J.
Biol. Chem. 273: 22768-22772, 1998.
6. Nakamura, T. Y.; Pountney, D. J.; Ozaita, A.; Nandi, S.; Ueda,
S.; Rudy, B.; Coetzee, W. A.: A role for frequenin, a Ca(2+)-binding
protein, as a regulator of Kv4 K(+)-currents. Proc. Nat. Acad. Sci. 98:
12808-12813, 2001.
7. Sippy, T.; Cruz-Martin, A.; Jeromin, A.; Schweizer, F. E.: Acute
changes in short-term plasticity at synapses with elevated levels
of neuronal calcium sensor-1. Nature Neurosci. 6: 1031-1038, 2003.
8. Tsujimoto, T.; Jeromin, A.; Saitoh, N.; Roder, J. C.; Takahashi,
T.: Neuronal calcium sensor 1 and activity-dependent facilitation
of P/Q-type calcium currents at presynaptic nerve terminals. Science 295:
2276-2279, 2002.
9. Wang, C.-Y.; Yang, F.; He, X.; Chow, A.; Du, J.; Russell, J. T.;
Lu, B.: Ca(2+) binding protein frequenin mediates GDNF-induced potentiation
of Ca(2+) channels and transmitter release. Neuron 32: 99-112, 2001.
*FIELD* CN
Patricia A. Hartz - updated: 09/01/2006
Cassandra L. Kniffin - updated: 8/22/2005
George E. Tiller - updated: 3/21/2005
Cassandra L. Kniffin - updated: 9/4/2003
Ada Hamosh - updated: 3/26/2002
Carol A. Bocchini - updated: 2/25/2002
Victor A. McKusick - updated: 1/14/2002
*FIELD* CD
Jennifer P. Macke: 11/24/1998
*FIELD* ED
mgross: 09/01/2006
carol: 8/29/2005
ckniffin: 8/22/2005
alopez: 3/21/2005
alopez: 10/16/2003
tkritzer: 9/8/2003
ckniffin: 9/4/2003
alopez: 3/26/2002
terry: 3/26/2002
mgross: 2/25/2002
carol: 2/25/2002
carol: 1/20/2002
mcapotos: 1/14/2002
alopez: 11/24/1998