Entry euk:CPNE3_HUMAN

ID   CPNE3_HUMAN             Reviewed;         537 AA.
AC   O75131; A8KA47; Q8IYA1;
DT   01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1998, sequence version 1.
DT   12-APR-2017, entry version 149.
DE   RecName: Full=Copine-3 {ECO:0000305};
DE   AltName: Full=Copine III {ECO:0000303|PubMed:11041869, ECO:0000312|HGNC:HGNC:2316};
GN   Name=CPNE3 {ECO:0000312|HGNC:HGNC:2316};
GN   Synonyms=CPN3, KIAA0636 {ECO:0000303|PubMed:9734811};
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], PARTIAL PROTEIN SEQUENCE, TISSUE
RP   SPECIFICITY, AND PHOSPHORYLATION.
RX   PubMed=11041869; DOI=10.1021/bi001250v;
RA   Caudell E.G., Caudell J.J., Tang C.-H., Yu T.-K., Frederick M.J.,
RA   Grimm E.A.;
RT   "Characterization of human copine III as a phosphoprotein with
RT   associated kinase activity.";
RL   Biochemistry 39:13034-13043(2000).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain;
RX   PubMed=9734811; DOI=10.1093/dnares/5.3.169;
RA   Ishikawa K., Nagase T., Suyama M., Miyajima N., Tanaka A., Kotani H.,
RA   Nomura N., Ohara O.;
RT   "Prediction of the coding sequences of unidentified human genes. X.
RT   The complete sequences of 100 new cDNA clones from brain which can
RT   code for large proteins in vitro.";
RL   DNA Res. 5:169-176(1998).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT MET-412.
RC   TISSUE=Trachea;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA   Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA   Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA   Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA   Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA   Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA   Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA   Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA   Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA   Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA   Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA   Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA   Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA   Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA   Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA   Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA   Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA   Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA   Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA   Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain, and Skin;
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   [5]
RP   SUBUNIT, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND MASS
RP   SPECTROMETRY.
RX   PubMed=12949241; DOI=10.1189/jlb.0203083;
RA   Cowland J.B., Carter D., Bjerregaard M.D., Johnsen A.H.,
RA   Borregaard N., Lollike K.;
RT   "Tissue expression of copines and isolation of copines I and III from
RT   the cytosol of human neutrophils.";
RL   J. Leukoc. Biol. 74:379-388(2003).
RN   [6]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA   Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA   Elledge S.J., Gygi S.P.;
RT   "A quantitative atlas of mitotic phosphorylation.";
RL   Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN   [7]
RP   SUBCELLULAR LOCATION.
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   [8]
RP   FUNCTION, INTERACTION WITH ERBB2; RACK1 AND SHC1, SUBCELLULAR
RP   LOCATION, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX   PubMed=20010870; DOI=10.1038/onc.2009.456;
RA   Heinrich C., Keller C., Boulay A., Vecchi M., Bianchi M., Sack R.,
RA   Lienhard S., Duss S., Hofsteenge J., Hynes N.E.;
RT   "Copine-III interacts with ErbB2 and promotes tumor cell migration.";
RL   Oncogene 29:1598-1610(2010).
RN   [9]
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   [10]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-14 AND SER-243, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma, and Erythroleukemia;
RX   PubMed=23186163; DOI=10.1021/pr300630k;
RA   Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA   Mohammed S.;
RT   "Toward a comprehensive characterization of a human cancer cell
RT   phosphoproteome.";
RL   J. Proteome Res. 12:260-271(2013).
RN   [11]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-14 AND SER-197, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA   Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D.,
RA   Wang L., Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human
RT   liver phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
CC   -!- FUNCTION: Calcium-dependent phospholipid-binding protein that
CC       plays a role in ERBB2-mediated tumor cell migration in response to
CC       growth factor heregulin stimulation (PubMed:20010870).
CC       {ECO:0000269|PubMed:20010870}.
CC   -!- SUBUNIT: Monomer (PubMed:12949241). Interacts with ERBB2
CC       (preferentially with the tyrosine phosphorylated form); this
CC       interaction occurs at the cell membrane and is increased in a
CC       growth factor heregulin-dependent manner (PubMed:20010870).
CC       Interacts with SHC1; this interaction may mediate the binding of
CC       CPNE3 with ERBB2 (PubMed:20010870). Interacts with RACK1
CC       (PubMed:20010870). {ECO:0000269|PubMed:12949241,
CC       ECO:0000269|PubMed:20010870}.
CC   -!- INTERACTION:
CC       Q9BSI4:TINF2; NbExp=2; IntAct=EBI-718988, EBI-717399;
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:20010870,
CC       ECO:0000269|PubMed:21087455}. Cytoplasm
CC       {ECO:0000269|PubMed:12949241, ECO:0000269|PubMed:20010870,
CC       ECO:0000269|PubMed:21087455}. Cell membrane
CC       {ECO:0000269|PubMed:20010870, ECO:0000269|PubMed:21087455}. Cell
CC       junction {ECO:0000269|PubMed:20010870}. Cell junction, focal
CC       adhesion {ECO:0000269|PubMed:20010870}. Note=Associates to the
CC       membrane in a calcium-dependent manner (PubMed:20010870).
CC       Translocates to the cell membrane and the nucleus in a calcium- or
CC       growth factor heregulin-dependent manner (PubMed:21087455,
CC       PubMed:20010870). Colocalizes with the tyrosine phosphorylated
CC       ERBB2 form at cell membrane and focal adhesions in a calcium- or
CC       growth factor heregulin-dependent manner (PubMed:20010870).
CC       {ECO:0000269|PubMed:20010870, ECO:0000269|PubMed:21087455}.
CC   -!- TISSUE SPECIFICITY: Expressed in breast and weakly in prostate and
CC       ovarian tissues (PubMed:20010870). Expressed in neutrophils (at
CC       protein level) (PubMed:12949241). Widely expressed
CC       (PubMed:11041869). Expressed in the brain. Expressed in neutrophil
CC       precursors from the bone marrow and peripheral blood
CC       (PubMed:12949241). Expressed in primary breast tumors and ovarian
CC       endometrioid adenocarcinoma (PubMed:20010870).
CC       {ECO:0000269|PubMed:11041869, ECO:0000269|PubMed:12949241,
CC       ECO:0000269|PubMed:20010870}.
CC   -!- PTM: Phosphorylated on serine and threonine residues
CC       (PubMed:11041869). {ECO:0000269|PubMed:11041869}.
CC   -!- SIMILARITY: Belongs to the copine family. {ECO:0000305}.
CC   -!- CAUTION: Was reported to have a protein kinase activity.
CC       {ECO:0000305|PubMed:11041869}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=BAA31611.2; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR   EMBL; AF077226; AAD46074.2; -; mRNA.
DR   EMBL; AB014536; BAA31611.2; ALT_INIT; mRNA.
DR   EMBL; AK292912; BAF85601.1; -; mRNA.
DR   EMBL; BC036242; AAH36242.1; -; mRNA.
DR   EMBL; BC066597; AAH66597.1; -; mRNA.
DR   CCDS; CCDS6243.1; -.
DR   RefSeq; NP_003900.1; NM_003909.4.
DR   RefSeq; XP_005251150.1; XM_005251093.4.
DR   RefSeq; XP_016869434.1; XM_017013945.1.
DR   UniGene; Hs.191219; -.
DR   ProteinModelPortal; O75131; -.
DR   SMR; O75131; -.
DR   BioGrid; 114412; 22.
DR   IntAct; O75131; 9.
DR   MINT; MINT-4526920; -.
DR   STRING; 9606.ENSP00000198765; -.
DR   iPTMnet; O75131; -.
DR   PhosphoSitePlus; O75131; -.
DR   SwissPalm; O75131; -.
DR   BioMuta; CPNE3; -.
DR   EPD; O75131; -.
DR   MaxQB; O75131; -.
DR   PaxDb; O75131; -.
DR   PeptideAtlas; O75131; -.
DR   PRIDE; O75131; -.
DR   DNASU; 8895; -.
DR   Ensembl; ENST00000517490; ENSP00000477590; ENSG00000085719.
DR   GeneID; 8895; -.
DR   KEGG; hsa:8895; -.
DR   UCSC; uc033bsf.1; human.
DR   CTD; 8895; -.
DR   DisGeNET; 8895; -.
DR   GeneCards; CPNE3; -.
DR   HGNC; HGNC:2316; CPNE3.
DR   HPA; HPA029552; -.
DR   MIM; 604207; gene.
DR   neXtProt; NX_O75131; -.
DR   OpenTargets; ENSG00000085719; -.
DR   PharmGKB; PA26833; -.
DR   eggNOG; KOG1327; Eukaryota.
DR   eggNOG; ENOG410XPC8; LUCA.
DR   GeneTree; ENSGT00760000119085; -.
DR   HOGENOM; HOG000220898; -.
DR   HOVERGEN; HBG066841; -.
DR   InParanoid; O75131; -.
DR   OMA; IDYYFEL; -.
DR   OrthoDB; EOG091G05IT; -.
DR   PhylomeDB; O75131; -.
DR   TreeFam; TF316419; -.
DR   Reactome; R-HSA-1483206; Glycerophospholipid biosynthesis.
DR   Reactome; R-HSA-6798695; Neutrophil degranulation.
DR   ChiTaRS; CPNE3; human.
DR   GenomeRNAi; 8895; -.
DR   PRO; PR:O75131; -.
DR   Proteomes; UP000005640; Chromosome 8.
DR   Bgee; ENSG00000085719; -.
DR   CleanEx; HS_CPNE3; -.
DR   ExpressionAtlas; O75131; baseline and differential.
DR   Genevisible; O75131; HS.
DR   GO; GO:0035577; C:azurophil granule membrane; TAS:Reactome.
DR   GO; GO:0030054; C:cell junction; IDA:UniProtKB.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR   GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR   GO; GO:0070062; C:extracellular exosome; IDA:UniProtKB.
DR   GO; GO:0005925; C:focal adhesion; IDA:UniProtKB.
DR   GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR   GO; GO:0005730; C:nucleolus; IDA:HPA.
DR   GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR   GO; GO:0005544; F:calcium-dependent phospholipid binding; IDA:UniProtKB.
DR   GO; GO:0048306; F:calcium-dependent protein binding; IDA:UniProtKB.
DR   GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR   GO; GO:0030971; F:receptor tyrosine kinase binding; IPI:UniProtKB.
DR   GO; GO:0003723; F:RNA binding; IDA:UniProtKB.
DR   GO; GO:0005215; F:transporter activity; TAS:ProtInc.
DR   GO; GO:0071277; P:cellular response to calcium ion; IDA:UniProtKB.
DR   GO; GO:0071363; P:cellular response to growth factor stimulus; IDA:UniProtKB.
DR   GO; GO:0038128; P:ERBB2 signaling pathway; IDA:UniProtKB.
DR   GO; GO:0046474; P:glycerophospholipid biosynthetic process; TAS:Reactome.
DR   GO; GO:0006629; P:lipid metabolic process; TAS:ProtInc.
DR   GO; GO:0043312; P:neutrophil degranulation; TAS:Reactome.
DR   GO; GO:0030335; P:positive regulation of cell migration; IMP:UniProtKB.
DR   GO; GO:0016192; P:vesicle-mediated transport; TAS:ProtInc.
DR   CDD; cd01459; vWA_copine_like; 1.
DR   Gene3D; 2.60.40.150; -; 2.
DR   Gene3D; 3.40.50.410; -; 1.
DR   InterPro; IPR000008; C2_dom.
DR   InterPro; IPR010734; Copine.
DR   InterPro; IPR002035; VWF_A.
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   Cell junction; Cell membrane; Complete proteome; Cytoplasm;
KW   Direct protein sequencing; Membrane; Nucleus; Phosphoprotein;
KW   Polymorphism; Reference proteome; Repeat.
FT   CHAIN         1    537       Copine-3.
FT                                /FTId=PRO_0000144838.
FT   DOMAIN        2     99       C2 1. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00041}.
FT   DOMAIN      125    230       C2 2. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00041}.
FT   DOMAIN      291    513       VWFA. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00219}.
FT   MOD_RES      14     14       Phosphoserine.
FT                                {ECO:0000244|PubMed:23186163,
FT                                ECO:0000244|PubMed:24275569}.
FT   MOD_RES     197    197       Phosphoserine.
FT                                {ECO:0000244|PubMed:24275569}.
FT   MOD_RES     243    243       Phosphoserine.
FT                                {ECO:0000244|PubMed:23186163}.
FT   VARIANT     252    252       E -> D (in dbSNP:rs41333046).
FT                                /FTId=VAR_048848.
FT   VARIANT     412    412       T -> M (in dbSNP:rs2304789).
FT                                {ECO:0000269|PubMed:14702039}.
FT                                /FTId=VAR_024424.
FT   CONFLICT    394    394       P -> Q (in Ref. 4; AAH36242).
FT                                {ECO:0000305}.
FT   CONFLICT    419    419       Q -> R (in Ref. 4; AAH36242).
FT                                {ECO:0000305}.
FT   CONFLICT    475    475       R -> H (in Ref. 4; AAH36242).
FT                                {ECO:0000305}.
CC   --------------------------------------------------------------------------
CC   The following FT lines are automated annotations from the MyHits database.
CC   --------------------------------------------------------------------------
FT   MYHIT       139    245       ismart:C2 [T]
FT   MYHIT       138    230       iprf:C2 [T]
FT   MYHIT         1     99       iprf:C2 [T]
FT   MYHIT       310    524       ipfam:Copine [T]
FT   MYHIT        13    112       ipfam:C2 [T]
FT   MYHIT       289    491       ismart:VWA [T]
FT   MYHIT         7    114       ismart:C2 [T]
FT   MYHIT       145    239       ipfam:C2 [T]
SQ   SEQUENCE   537 AA;  60131 MW;  91F2C5EAD611B842 CRC64;
     MAAQCVTKVA LNVSCANLLD KDIGSKSDPL CVLFLNTSGQ QWYEVERTER IKNCLNPQFS
     KTFIIDYYFE VVQKLKFGVY DIDNKTIELS DDDFLGECEC TLGQIVSSKK LTRPLVMKTG
     RPAGKGSITI SAEEIKDNRV VLFEMEARKL DNKDLFGKSD PYLEFHKQTS DGNWLMVHRT
     EVVKNNLNPV WRPFKISLNS LCYGDMDKTI KVECYDYDND GSHDLIGTFQ TTMTKLKEAS
     RSSPVEFECI NEKKRQKKKS YKNSGVISVK QCEITVECTF LDYIMGGCQL NFTVGVDFTG
     SNGDPRSPDS LHYISPNGVN EYLTALWSVG LVIQDYDADK MFPAFGFGAQ IPPQWQVSHE
     FPMNFNPSNP YCNGIQGIVE AYRSCLPQIK LYGPTNFSPI INHVARFAAA ATQQQTASQY
     FVLLIITDGV ITDLDETRQA IVNASRLPMS IIIVGVGGAD FSAMEFLDGD GGSLRSPLGE
     VAIRDIVQFV PFRQFQNAPK EALAQCVLAE IPQQVVGYFN TYKLLPPKNP ATKQQKQ
//