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 24-JAN-2024, entry version 167.
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; 129.
DR IntAct; Q96FN4; 59.
DR MINT; Q96FN4; -.
DR STRING; 9606.ENSP00000290776; -.
DR GlyGen; Q96FN4; 1 site, 1 O-linked glycan (1 site).
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; 9606-ENSP00000290776; -.
DR PeptideAtlas; Q96FN4; -.
DR ProteomicsDB; 68592; -.
DR ProteomicsDB; 76546; -. [Q96FN4-1]
DR Pumba; Q96FN4; -.
DR Antibodypedia; 63170; 73 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 AGR; HGNC:2315; -.
DR CTD; 221184; -.
DR GeneCards; CPNE2; -.
DR HGNC; HGNC:2315; CPNE2.
DR HPA; ENSG00000140848; Low tissue specificity.
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; AHDSHSK; -.
DR OrthoDB; 672483at2759; -.
DR PhylomeDB; Q96FN4; -.
DR TreeFam; TF316419; -.
DR PathwayCommons; Q96FN4; -.
DR SignaLink; Q96FN4; -.
DR BioGRID-ORCS; 221184; 20 hits in 1154 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 174 other cell types or 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; cd04048; C2A_Copine; 1.
DR CDD; cd04047; C2B_Copine; 1.
DR CDD; cd01459; vWA_copine_like; 1.
DR Gene3D; 2.60.40.150; C2 domain; 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; COPINE; 1.
DR PANTHER; PTHR10857:SF3; COPINE-2; 1.
DR Pfam; PF00168; C2; 2.
DR Pfam; PF07002; Copine; 1.
DR SMART; SM00239; C2; 2.
DR SMART; SM00327; VWA; 1.
DR SUPFAM; SSF49562; C2 domain (Calcium/lipid-binding domain, CaLB); 2.
DR SUPFAM; SSF53300; vWA-like; 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
//
