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CPNE2_HUMAN
ID   CPNE2_HUMAN             Reviewed;         548 AA.
AC   Q96FN4; Q68D19; Q719H8; Q86XP9;
DT   28-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT   15-AUG-2003, sequence version 3.
DT   03-AUG-2022, entry version 159.
DE   RecName: Full=Copine-2 {ECO:0000305};
DE   AltName: Full=Copine II {ECO:0000250|UniProtKB:Q99829, ECO:0000312|HGNC:HGNC:2315};
GN   Name=CPNE2 {ECO:0000312|HGNC:HGNC:2315};
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC   TISSUE=Placenta;
RA   Ding P., Han W., Shi S., Rui M., Wang Y., Song Q., Ma D.;
RL   Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RA   Zhang D.L., Cai J.J., Ma D.L.;
RT   "Cloning and characterization of a novel human gene encoding a protein of
RT   446 amino acids.";
RL   Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15616553; DOI=10.1038/nature03187;
RA   Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA   Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA   Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA   Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA   Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA   Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA   Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA   Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA   Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA   Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA   Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA   Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA   Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA   Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA   Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA   Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA   Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA   Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA   Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA   DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA   Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA   Myers R.M., Rubin E.M., Pennacchio L.A.;
RT   "The sequence and analysis of duplication-rich human chromosome 16.";
RL   Nature 432:988-994(2004).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Pancreas;
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   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 20-548 (ISOFORM 1).
RC   TISSUE=Fetal brain;
RX   PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA   Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA   Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA   Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA   Wiemann S., Schupp I.;
RT   "The full-ORF clone resource of the German cDNA consortium.";
RL   BMC Genomics 8:399-399(2007).
RN   [6]
RP   TISSUE SPECIFICITY.
RX   PubMed=12949241; DOI=10.1189/jlb.0203083;
RA   Cowland J.B., Carter D., Bjerregaard M.D., Johnsen A.H., Borregaard N.,
RA   Lollike K.;
RT   "Tissue expression of copines and isolation of copines I and III from the
RT   cytosol of human neutrophils.";
RL   J. Leukoc. Biol. 74:379-388(2003).
RN   [7]
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., Buerckstuemmer T.,
RA   Bennett K.L., Superti-Furga G., Colinge J.;
RT   "Initial characterization of the human central proteome.";
RL   BMC Syst. Biol. 5:17-17(2011).
CC   -!- FUNCTION: Calcium-dependent phospholipid-binding protein that plays a
CC       role in calcium-mediated intracellular processes. Exhibits calcium-
CC       dependent cell membrane binding properties.
CC       {ECO:0000250|UniProtKB:P59108}.
CC   -!- COFACTOR:
CC       Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC         Evidence={ECO:0000255|PROSITE-ProRule:PRU00041};
CC       Note=Binds 3 Ca(2+) ions per C2 domain. {ECO:0000255|PROSITE-
CC       ProRule:PRU00041};
CC   -!- INTERACTION:
CC       Q96FN4; Q8WUE5: CT55; NbExp=5; IntAct=EBI-7097057, EBI-6873363;
CC       Q96FN4; Q5JST6: EFHC2; NbExp=3; IntAct=EBI-7097057, EBI-2349927;
CC       Q96FN4; Q8N8V2: GBP7; NbExp=3; IntAct=EBI-7097057, EBI-21835810;
CC       Q96FN4; Q9H079: KATNBL1; NbExp=5; IntAct=EBI-7097057, EBI-715394;
CC       Q96FN4; Q8TBB1: LNX1; NbExp=3; IntAct=EBI-7097057, EBI-739832;
CC       Q96FN4; A8MW99: MEI4; NbExp=3; IntAct=EBI-7097057, EBI-19944212;
CC       Q96FN4; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-7097057, EBI-16439278;
CC       Q96FN4; Q9NZQ3-3: NCKIPSD; NbExp=3; IntAct=EBI-7097057, EBI-10963850;
CC       Q96FN4; Q9NRD5: PICK1; NbExp=3; IntAct=EBI-7097057, EBI-79165;
CC       Q96FN4; Q04864: REL; NbExp=3; IntAct=EBI-7097057, EBI-307352;
CC       Q96FN4; Q04864-2: REL; NbExp=3; IntAct=EBI-7097057, EBI-10829018;
CC       Q96FN4; O60504: SORBS3; NbExp=6; IntAct=EBI-7097057, EBI-741237;
CC       Q96FN4; P15884-3: TCF4; NbExp=3; IntAct=EBI-7097057, EBI-13636688;
CC       Q96FN4; Q9NYB0: TERF2IP; NbExp=2; IntAct=EBI-7097057, EBI-750109;
CC       Q96FN4; Q8WY91: THAP4; NbExp=5; IntAct=EBI-7097057, EBI-726691;
CC       Q96FN4; P14373: TRIM27; NbExp=6; IntAct=EBI-7097057, EBI-719493;
CC       Q96FN4; Q8TBC4: UBA3; NbExp=6; IntAct=EBI-7097057, EBI-717567;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P59108}. Nucleus
CC       {ECO:0000250|UniProtKB:P59108}. Cell membrane
CC       {ECO:0000250|UniProtKB:P59108}. Note=Translocates to the cell membrane
CC       and the nucleus in a calcium-dependent manner. Colocalizes with CD2 at
CC       the cell membrane. {ECO:0000250|UniProtKB:P59108}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q96FN4-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q96FN4-2; Sequence=VSP_055536;
CC   -!- TISSUE SPECIFICITY: Expressed in the brain. Expressed in neutrophil
CC       precursors from the bone marrow and peripheral blood (PubMed:12949241).
CC   -!- DOMAIN: The C2 domain 2, but not the C2 domain 1, is necessary for
CC       calcium-mediated membrane association. The linker region is necessary
CC       for calcium-dependent cell membrane association.
CC       {ECO:0000250|UniProtKB:P59108}.
CC   -!- SIMILARITY: Belongs to the copine family. {ECO:0000305}.
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DR   EMBL; AF492484; AAO85483.1; -; mRNA.
DR   EMBL; AF542551; AAQ09534.1; -; mRNA.
DR   EMBL; AC009090; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC053658; AAH53658.1; -; mRNA.
DR   EMBL; CR749617; CAH18411.1; -; mRNA.
DR   CCDS; CCDS10774.1; -. [Q96FN4-1]
DR   RefSeq; NP_689940.3; NM_152727.5. [Q96FN4-1]
DR   AlphaFoldDB; Q96FN4; -.
DR   SMR; Q96FN4; -.
DR   BioGRID; 128695; 121.
DR   IntAct; Q96FN4; 59.
DR   MINT; Q96FN4; -.
DR   STRING; 9606.ENSP00000290776; -.
DR   iPTMnet; Q96FN4; -.
DR   PhosphoSitePlus; Q96FN4; -.
DR   BioMuta; CPNE2; -.
DR   DMDM; 33860150; -.
DR   EPD; Q96FN4; -.
DR   jPOST; Q96FN4; -.
DR   MassIVE; Q96FN4; -.
DR   MaxQB; Q96FN4; -.
DR   PaxDb; Q96FN4; -.
DR   PeptideAtlas; Q96FN4; -.
DR   PRIDE; Q96FN4; -.
DR   ProteomicsDB; 68592; -.
DR   ProteomicsDB; 76546; -. [Q96FN4-1]
DR   Antibodypedia; 63170; 62 antibodies from 18 providers.
DR   DNASU; 221184; -.
DR   Ensembl; ENST00000290776.13; ENSP00000290776.8; ENSG00000140848.17. [Q96FN4-1]
DR   Ensembl; ENST00000535318.6; ENSP00000439018.2; ENSG00000140848.17. [Q96FN4-1]
DR   Ensembl; ENST00000565874.5; ENSP00000456042.1; ENSG00000140848.17. [Q96FN4-1]
DR   GeneID; 221184; -.
DR   KEGG; hsa:221184; -.
DR   MANE-Select; ENST00000290776.13; ENSP00000290776.8; NM_152727.6; NP_689940.3.
DR   UCSC; uc002eks.3; human. [Q96FN4-1]
DR   CTD; 221184; -.
DR   GeneCards; CPNE2; -.
DR   HGNC; HGNC:2315; CPNE2.
DR   HPA; ENSG00000140848; Tissue enhanced (brain).
DR   MIM; 604206; gene.
DR   neXtProt; NX_Q96FN4; -.
DR   OpenTargets; ENSG00000140848; -.
DR   PharmGKB; PA26832; -.
DR   VEuPathDB; HostDB:ENSG00000140848; -.
DR   eggNOG; KOG1327; Eukaryota.
DR   GeneTree; ENSGT00940000157653; -.
DR   HOGENOM; CLU_020452_3_2_1; -.
DR   InParanoid; Q96FN4; -.
DR   OMA; APMKDAH; -.
DR   OrthoDB; 1067545at2759; -.
DR   PhylomeDB; Q96FN4; -.
DR   TreeFam; TF316419; -.
DR   PathwayCommons; Q96FN4; -.
DR   SignaLink; Q96FN4; -.
DR   BioGRID-ORCS; 221184; 20 hits in 1076 CRISPR screens.
DR   ChiTaRS; CPNE2; human.
DR   GenomeRNAi; 221184; -.
DR   Pharos; Q96FN4; Tdark.
DR   PRO; PR:Q96FN4; -.
DR   Proteomes; UP000005640; Chromosome 16.
DR   RNAct; Q96FN4; protein.
DR   Bgee; ENSG00000140848; Expressed in C1 segment of cervical spinal cord and 172 other tissues.
DR   ExpressionAtlas; Q96FN4; baseline and differential.
DR   Genevisible; Q96FN4; HS.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR   GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR   GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
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:0071277; P:cellular response to calcium ion; IBA:GO_Central.
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.
PE   1: Evidence at protein level;
KW   Alternative splicing; Calcium; Cell membrane; Cytoplasm; Membrane;
KW   Metal-binding; Nucleus; Reference proteome; Repeat.
FT   CHAIN           1..548
FT                   /note="Copine-2"
FT                   /id="PRO_0000144836"
FT   DOMAIN          5..131
FT                   /note="C2 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT   DOMAIN          138..263
FT                   /note="C2 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT   DOMAIN          305..507
FT                   /note="VWFA"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00219"
FT   REGION          247..304
FT                   /note="Linker region"
FT                   /evidence="ECO:0000250|UniProtKB:P59108"
FT   BINDING         39
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT   BINDING         39
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT   BINDING         45
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT   BINDING         97
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT   BINDING         97
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT   BINDING         99
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT   BINDING         99
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT   BINDING         99
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT   BINDING         102
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT   BINDING         109
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT   BINDING         109
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT   BINDING         170
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="4"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT   BINDING         170
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="5"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT   BINDING         176
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="4"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT   BINDING         232
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="4"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT   BINDING         232
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="5"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT   BINDING         234
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="4"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT   BINDING         234
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="5"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT   BINDING         240
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="5"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT   VAR_SEQ         1..102
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|Ref.2"
FT                   /id="VSP_055536"
FT   CONFLICT        100
FT                   /note="K -> E (in Ref. 5; CAH18411)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   548 AA;  61190 MW;  39B962C82C591DA0 CRC64;
     MAHIPSGGAP AAGAAPMGPQ YCVCKVELSV SGQNLLDRDV TSKSDPFCVL FTENNGRWIE
     YDRTETAINN LNPAFSKKFV LDYHFEEVQK LKFALFDQDK SSMRLDEHDF LGQFSCSLGT
     IVSSKKITRP LLLLNDKPAG KGLITIAAQE LSDNRVITLS LAGRRLDKKD LFGKSDPFLE
     FYKPGDDGKW MLVHRTEVIK YTLDPVWKPF TVPLVSLCDG DMEKPIQVMC YDYDNDGGHD
     FIGEFQTSVS QMCEARDSVP LEFECINPKK QRKKKNYKNS GIIILRSCKI NRDYSFLDYI
     LGGCQLMFTV GIDFTASNGN PLDPSSLHYI NPMGTNEYLS AIWAVGQIIQ DYDSDKMFPA
     LGFGAQLPPD WKVSHEFAIN FNPTNPFCSG VDGIAQAYSA CLPHIRFYGP TNFSPIVNHV
     ARFAAQATQQ RTATQYFILL IITDGVISDM EETRHAVVQA SKLPMSIIIV GVGNADFAAM
     EFLDGDSRML RSHTGEEAAR DIVQFVPFRE FRNAAKETLA KAVLAELPQQ VVQYFKHKNL
     PPTNSEPA
 
 
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