CPNE6_MOUSE
ID CPNE6_MOUSE Reviewed; 557 AA.
AC Q9Z140;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=Copine-6 {ECO:0000305};
DE AltName: Full=Copine VI {ECO:0000250|UniProtKB:Q99829, ECO:0000312|MGI:MGI:1334445};
DE AltName: Full=Neuronal-copine {ECO:0000303|PubMed:9645480};
DE Short=N-copine {ECO:0000303|PubMed:9645480};
GN Name=Cpne6 {ECO:0000312|MGI:MGI:1334445};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], INDUCTION, AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=9645480; DOI=10.1016/s0014-5793(98)00497-9;
RA Nakayama T., Yaoi T., Yasui M., Kuwajima G.;
RT "N-copine: a novel two C2-domain-containing protein with neuronal activity-
RT regulated expression.";
RL FEBS Lett. 428:80-84(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP INTERACTION WITH OS9.
RX PubMed=10403379; DOI=10.1016/s0014-5793(99)00700-0;
RA Nakayama T., Yaoi T., Kuwajima G., Yoshie O., Sakata T.;
RT "Ca2(+)-dependent interaction of N-copine, a member of the two C2 domain
RT protein family, with OS-9, the product of a gene frequently amplified in
RT osteosarcoma.";
RL FEBS Lett. 453:77-80(1999).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, DOMAIN, AND TISSUE SPECIFICITY.
RX PubMed=9886090; DOI=10.1046/j.1471-4159.1999.0720373.x;
RA Nakayama T., Yaoi T., Kuwajima G.;
RT "Localization and subcellular distribution of N-copine in mouse brain.";
RL J. Neurochem. 72:373-379(1999).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, and Liver;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP SUBCELLULAR LOCATION, AND DOMAIN.
RX PubMed=21087455; DOI=10.1111/j.1742-4658.2010.07935.x;
RA Perestenko P.V., Pooler A.M., Noorbakhshnia M., Gray A., Bauccio C.,
RA Jeffrey McIlhinney R.A.;
RT "Copines-1, -2, -3, -6 and -7 show different calcium-dependent
RT intracellular membrane translocation and targeting.";
RL FEBS J. 277:5174-5189(2010).
RN [7]
RP SUBCELLULAR LOCATION, DOMAIN, AND MUTAGENESIS OF ASP-33; ASP-35; ASP-93;
RP ASP-96; ASP-167; ASP-173; ASP-229; ASP-231; LYS-272; LYS-273; LYS-274;
RP VAL-282; VAL-283; LEU-284; GLN-286; CYS-287 AND THR-288.
RX PubMed=26175110; DOI=10.1111/febs.13370;
RA Perestenko P., Watanabe M., Beusnard-Bee T., Guna P., McIlhinney J.;
RT "The second C2-domain of copines -2, -6 and -7 is responsible for their
RT calcium-dependent membrane association.";
RL FEBS J. 282:3722-3736(2015).
CC -!- FUNCTION: Calcium-dependent phospholipid-binding protein that plays a
CC role in calcium-mediated intracellular processes. Binds phospholipid
CC membranes in a calcium-dependent manner (PubMed:9886090). Plays a role
CC in dendrite formation by melanocytes (By similarity).
CC {ECO:0000250|UniProtKB:O95741, ECO:0000269|PubMed:9886090}.
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00041};
CC -!- SUBUNIT: Interacts (via second C2 domain) with OS9 (via C-terminus);
CC this interaction occurs in a calcium-dependent manner in vitro
CC (PubMed:10403379). May interact with NECAB1 (By similarity).
CC {ECO:0000250|UniProtKB:O95741, ECO:0000269|PubMed:10403379}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:21087455,
CC ECO:0000269|PubMed:9886090}. Cell membrane
CC {ECO:0000269|PubMed:21087455, ECO:0000269|PubMed:26175110}. Endosome
CC {ECO:0000269|PubMed:21087455}. Cytoplasmic vesicle, clathrin-coated
CC vesicle {ECO:0000269|PubMed:21087455}. Perikaryon
CC {ECO:0000269|PubMed:9886090}. Cell projection, dendrite
CC {ECO:0000269|PubMed:9886090}. Note=Mainly cytoplasmic in absence of
CC calcium. Associated predominantly with membranes in presence of calcium
CC (PubMed:9886090). Translocates to the cell membrane in a calcium-
CC dependent manner (PubMed:21087455, PubMed:26175110). Colocalized with
CC transferrin in intracellular clathrin-coated membrane vesicles in a
CC calcium-dependent manner (PubMed:21087455).
CC {ECO:0000269|PubMed:21087455, ECO:0000269|PubMed:26175110,
CC ECO:0000269|PubMed:9886090}.
CC -!- TISSUE SPECIFICITY: Expressed in the brain (PubMed:9645480). Expressed
CC in pyramidal cells, granule cells, and neurons in the dentate gyrus of
CC the hippocampus and in granule cells of the olfactory bulb (at protein
CC level). Expressed in pyramidal cells of the CA1-CA3 regions, in granule
CC cells of the dentate gyrus, in granule cells of the olfactory bulbs, in
CC the mitral cell layer and in neurons of the cerebral cortex layer II,
CC brainstem and spinal cord (PubMed:9886090). Not detected in glial cells
CC (PubMed:9645480, PubMed:9886090). {ECO:0000269|PubMed:9645480,
CC ECO:0000269|PubMed:9886090}.
CC -!- INDUCTION: Up-regulated by long-term potentiation (PubMed:9645480). Up-
CC regulated by kainate in an NMDA-type glutamate receptor-dependent
CC manner (PubMed:9645480). {ECO:0000269|PubMed:9645480}.
CC -!- DOMAIN: The C2 domain 1 binds phospholipids in a calcium-independent
CC manner and is not necessary for calcium-mediated translocation and
CC association to the plasma membrane (PubMed:9886090, PubMed:26175110).
CC The C2 domain 2 binds phospholipids in a calcium-dependent manner and
CC is necessary for calcium-mediated translocation and association to the
CC plasma membrane (PubMed:9886090, PubMed:26175110). The linker region
CC contributes to the calcium-dependent translocation and association to
CC the plasma membrane (PubMed:21087455, PubMed:26175110). The VWFA domain
CC is necessary for association with intracellular clathrin-coated
CC vesicles in a calcium-dependent manner (PubMed:21087455).
CC {ECO:0000269|PubMed:21087455, ECO:0000269|PubMed:26175110,
CC ECO:0000269|PubMed:9886090}.
CC -!- SIMILARITY: Belongs to the copine family. {ECO:0000305}.
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DR EMBL; AB008893; BAA75898.1; -; mRNA.
DR EMBL; BC050766; AAH50766.1; -; mRNA.
DR CCDS; CCDS27112.1; -.
DR RefSeq; NP_001129529.1; NM_001136057.2.
DR RefSeq; NP_034077.1; NM_009947.3.
DR RefSeq; XP_006518569.1; XM_006518506.3.
DR AlphaFoldDB; Q9Z140; -.
DR SMR; Q9Z140; -.
DR BioGRID; 198861; 9.
DR IntAct; Q9Z140; 2.
DR MINT; Q9Z140; -.
DR STRING; 10090.ENSMUSP00000073847; -.
DR iPTMnet; Q9Z140; -.
DR PhosphoSitePlus; Q9Z140; -.
DR SwissPalm; Q9Z140; -.
DR jPOST; Q9Z140; -.
DR MaxQB; Q9Z140; -.
DR PaxDb; Q9Z140; -.
DR PeptideAtlas; Q9Z140; -.
DR PRIDE; Q9Z140; -.
DR ProteomicsDB; 283938; -.
DR Antibodypedia; 22599; 169 antibodies from 26 providers.
DR DNASU; 12891; -.
DR Ensembl; ENSMUST00000074225; ENSMUSP00000073847; ENSMUSG00000022212.
DR Ensembl; ENSMUST00000163767; ENSMUSP00000126493; ENSMUSG00000022212.
DR Ensembl; ENSMUST00000171643; ENSMUSP00000128555; ENSMUSG00000022212.
DR GeneID; 12891; -.
DR KEGG; mmu:12891; -.
DR UCSC; uc007tyr.2; mouse.
DR CTD; 9362; -.
DR MGI; MGI:1334445; Cpne6.
DR VEuPathDB; HostDB:ENSMUSG00000022212; -.
DR eggNOG; KOG1327; Eukaryota.
DR GeneTree; ENSGT00940000161567; -.
DR InParanoid; Q9Z140; -.
DR OMA; PLRCPQG; -.
DR OrthoDB; 1067545at2759; -.
DR PhylomeDB; Q9Z140; -.
DR TreeFam; TF316419; -.
DR Reactome; R-MMU-1483206; Glycerophospholipid biosynthesis.
DR BioGRID-ORCS; 12891; 1 hit in 74 CRISPR screens.
DR PRO; PR:Q9Z140; -.
DR Proteomes; UP000000589; Chromosome 14.
DR RNAct; Q9Z140; protein.
DR Bgee; ENSMUSG00000022212; Expressed in CA3 field of hippocampus and 115 other tissues.
DR ExpressionAtlas; Q9Z140; baseline and differential.
DR Genevisible; Q9Z140; MM.
DR GO; GO:0030424; C:axon; IDA:MGI.
DR GO; GO:0045334; C:clathrin-coated endocytic vesicle; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0030425; C:dendrite; IDA:MGI.
DR GO; GO:0005768; C:endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0005544; F:calcium-dependent phospholipid binding; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0001786; F:phosphatidylserine binding; IDA:MGI.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0071277; P:cellular response to calcium ion; IMP:UniProtKB.
DR GO; GO:1903861; P:positive regulation of dendrite extension; ISO:MGI.
DR CDD; cd04047; C2B_Copine; 1.
DR CDD; cd01459; vWA_copine_like; 1.
DR Gene3D; 2.60.40.150; -; 2.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR037768; C2B_Copine.
DR InterPro; IPR045052; Copine.
DR InterPro; IPR010734; Copine_C.
DR InterPro; IPR002035; VWF_A.
DR InterPro; IPR036465; vWFA_dom_sf.
DR PANTHER; PTHR10857; PTHR10857; 1.
DR Pfam; PF00168; C2; 2.
DR Pfam; PF07002; Copine; 1.
DR SMART; SM00239; C2; 2.
DR SMART; SM00327; VWA; 1.
DR SUPFAM; SSF49562; SSF49562; 2.
DR SUPFAM; SSF53300; SSF53300; 1.
DR PROSITE; PS50004; C2; 2.
DR PROSITE; PS50234; VWFA; 1.
PE 1: Evidence at protein level;
KW Calcium; Cell membrane; Cell projection; Cytoplasm; Cytoplasmic vesicle;
KW Differentiation; Endosome; Membrane; Metal-binding; Reference proteome;
KW Repeat.
FT CHAIN 1..557
FT /note="Copine-6"
FT /id="PRO_0000144846"
FT DOMAIN 1..127
FT /note="C2 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 134..263
FT /note="C2 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 306..526
FT /note="VWFA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00219"
FT REGION 244..303
FT /note="Linker region"
FT /evidence="ECO:0000269|PubMed:21087455,
FT ECO:0000269|PubMed:26175110"
FT BINDING 167
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 167
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 173
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 229
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 229
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 231
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 231
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 237
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT MUTAGEN 33
FT /note="D->N: Does not inhibit calcium-dependent
FT translocation to the cell membrane; when associated with N-
FT 35; N-93 and N-96."
FT /evidence="ECO:0000269|PubMed:26175110"
FT MUTAGEN 35
FT /note="D->N: Does not inhibit calcium-dependent
FT translocation to the cell membrane; when associated with N-
FT 33; N-93 and N-96."
FT /evidence="ECO:0000269|PubMed:26175110"
FT MUTAGEN 93
FT /note="D->N: Does not inhibit calcium-dependent
FT translocation to the cell membrane; when associated with N-
FT 33; N-35 and N-96."
FT /evidence="ECO:0000269|PubMed:26175110"
FT MUTAGEN 96
FT /note="D->N: Does not inhibit calcium-dependent
FT translocation to the cell membrane; when associated with N-
FT 33; N-35 and N-93."
FT /evidence="ECO:0000269|PubMed:26175110"
FT MUTAGEN 167
FT /note="D->N: Inhibits strongly calcium-dependent
FT translocation to the cell membrane. Inhibits strongly
FT calcium-dependent translocation to the cell membrane; when
FT associated with N-173. Leads to the constitutive (calcium-
FT independent) attachment to the cell membrane; when
FT associated with N-173; N-229 and N-231."
FT /evidence="ECO:0000269|PubMed:26175110"
FT MUTAGEN 173
FT /note="D->N: Inhibits strongly calcium-dependent
FT translocation to the cell membrane. Inhibits strongly
FT calcium-dependent translocation to the cell membrane; when
FT associated with N-167. Leads to the constitutive (calcium-
FT independent) attachment to the cell membrane; when
FT associated with N-167; N-229 and N-231."
FT /evidence="ECO:0000269|PubMed:26175110"
FT MUTAGEN 229
FT /note="D->N: Inhibits strongly calcium-dependent
FT translocation to the cell membrane; when associated with N-
FT 231. Leads to the constitutive (calcium-independent)
FT attachment to the cell membrane; when associated with N-
FT 167; N-173 and N-231."
FT /evidence="ECO:0000269|PubMed:26175110"
FT MUTAGEN 231
FT /note="D->N: Does not inhibit calcium-dependent
FT translocation to the cell membrane. Inhibits strongly
FT calcium-dependent translocation to the cell membrane; when
FT associated with N-229. Leads to the constitutive (calcium-
FT independent) attachment to the cell membrane; when
FT associated with N-167; N-173 and N-229."
FT /evidence="ECO:0000269|PubMed:26175110"
FT MUTAGEN 272
FT /note="K->A: Does not inhibit calcium-dependent
FT translocation to the cell membrane; when associated with A-
FT 273 and A-274."
FT /evidence="ECO:0000269|PubMed:26175110"
FT MUTAGEN 273
FT /note="K->A: Does not inhibit calcium-dependent
FT translocation to the cell membrane; when associated with A-
FT 272 and A-274."
FT /evidence="ECO:0000269|PubMed:26175110"
FT MUTAGEN 274
FT /note="K->A: Does not inhibit calcium-dependent
FT translocation to the cell membrane; when associated with A-
FT 272 and A-273."
FT /evidence="ECO:0000269|PubMed:26175110"
FT MUTAGEN 282
FT /note="V->G: Does not inhibit calcium-dependent
FT translocation to the cell membrane. Inhibits calcium-
FT dependent translocation to the cell membrane; when
FT associated with G-283 and G-284."
FT /evidence="ECO:0000269|PubMed:26175110"
FT MUTAGEN 282
FT /note="V->S: Inhibits calcium-dependent translocation to
FT the cell membrane; when associated with S-283 and S-284."
FT /evidence="ECO:0000269|PubMed:26175110"
FT MUTAGEN 283
FT /note="V->G: Does not inhibit calcium-dependent
FT translocation to the cell membrane. Inhibits calcium-
FT dependent translocation to the cell membrane; when
FT associated with G-282 and G-284."
FT /evidence="ECO:0000269|PubMed:26175110"
FT MUTAGEN 283
FT /note="V->S: Inhibits calcium-dependent translocation to
FT the cell membrane; when associated with S-282 and S-284."
FT /evidence="ECO:0000269|PubMed:26175110"
FT MUTAGEN 284
FT /note="L->G: Inhibits partially calcium-dependent
FT translocation to the cell membrane. Inhibits calcium-
FT dependent translocation to the cell membrane; when
FT associated with G-282 and G-283."
FT /evidence="ECO:0000269|PubMed:26175110"
FT MUTAGEN 284
FT /note="L->S: Inhibits calcium-dependent translocation to
FT the cell membrane; when associated with S-282 and S-283."
FT /evidence="ECO:0000269|PubMed:26175110"
FT MUTAGEN 286
FT /note="Q->A: Does not inhibit calcium-dependent
FT translocation to the cell membrane; when associated with G-
FT 287 and G-288."
FT /evidence="ECO:0000269|PubMed:26175110"
FT MUTAGEN 287
FT /note="C->A: Does not inhibit calcium-dependent
FT translocation to the cell membrane; when associated with G-
FT 286 and G-288."
FT /evidence="ECO:0000269|PubMed:26175110"
FT MUTAGEN 288
FT /note="T->A: Does not inhibit calcium-dependent
FT translocation to the cell membrane; when associated with G-
FT 286 and G-287."
FT /evidence="ECO:0000269|PubMed:26175110"
SQ SEQUENCE 557 AA; 61781 MW; 043D6C1487E2ECAC CRC64;
MSDPEMGWVP EPPAMTLGAS RVELRVSCHG LLDRDTLTKP HPCVLLKLYS DEQWVEVERT
EVLRSCSSPV FSRVLAIEYF FEEKQPLQFH VFDAEDGATS PSSDTFLGST ECTLGQIVSQ
TKVTKPLLLK NGKTAGKSTI TIVAEEVSGT NDYVQLTFRA HKLDNKDLFS KSDPFMEIYK
TNGDQSDQLV WRTEVVKNNL NPSWEPFRLS LHSLCSCDIH RPLKFLVYDY DSSGKHDFIG
EFTSTFQEMQ EGTANPGQEM QWDCINPKYR DKKKNYKSSG TVVLAQCTVE KVHTFLDYIM
GGCQISFTVA IDFTASNGDP RSSQSLHCLS PRQPNHYLQA LRTVGGICQD YDSDKRFPAF
GFGARIPPNF EVSHDFAINF DPENPECEEI SGVIASYRRC LPQIQLYGPT NVAPIINRVA
EPAQREQSTG QATKYSVLLV LTDGVVSDMA ETRTAIVRAS RLPMSIIIVG VGNADFSDMR
LLDGDDGPLR CPKGVPAARD IVQFVPFRDF KDAAPSALAK CVLAEVPRQV VEYYASQGIS
PGAPRPSTPA MTPSPSP
