CCNE2_HUMAN
ID CCNE2_HUMAN Reviewed; 404 AA.
AC O96020; O95439;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 193.
DE RecName: Full=G1/S-specific cyclin-E2;
GN Name=CCNE2;
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] (ISOFORMS LONG AND SHORT).
RC TISSUE=Fetal lung;
RX PubMed=9858585; DOI=10.1128/mcb.19.1.612;
RA Gudas J.M., Payton M., Thukral S., Chen E., Bass M., Robinson M.O.,
RA Coats S.;
RT "Cyclin E2, a novel G1 cyclin that binds Cdk2 and is aberrantly expressed
RT in human cancers.";
RL Mol. Cell. Biol. 19:612-622(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=B-cell;
RX PubMed=9840927; DOI=10.1038/sj.onc.1202477;
RA Lauper N., Beck A.R.P., Cariou S., Richman L., Hofmann K., Reith W.,
RA Slingerland J.M., Amati B.;
RT "Cyclin E2: a novel CDK2 partner in the late G1 and S phases of the
RT mammalian cell cycle.";
RL Oncogene 17:2637-2643(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP THR-392.
RC TISSUE=Keratinocyte;
RX PubMed=9840943; DOI=10.1038/sj.onc.1202505;
RA Zariwala M., Liu J., Xiong Y.;
RT "Cyclin E2, a novel human G1 cyclin and activating partner of CDK2 and
RT CDK3, is induced by viral oncoproteins.";
RL Oncogene 17:2787-2798(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT SER-387.
RG NIEHS SNPs program;
RL Submitted (DEC-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-383 AND THR-392, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-21, AND IDENTIFICATION BY
RP 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 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-21, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-21, AND IDENTIFICATION BY
RP 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).
CC -!- FUNCTION: Essential for the control of the cell cycle at the late G1
CC and early S phase.
CC -!- SUBUNIT: Interacts with the CDK2 (in vivo) and CDK3 (in vitro) protein
CC kinases to form a serine/threonine kinase holoenzyme complex. The
CC cyclin subunit imparts substrate specificity to the complex.
CC -!- INTERACTION:
CC O96020; P24941: CDK2; NbExp=11; IntAct=EBI-375033, EBI-375096;
CC O96020; P38936: CDKN1A; NbExp=6; IntAct=EBI-375033, EBI-375077;
CC O96020; P46527: CDKN1B; NbExp=3; IntAct=EBI-375033, EBI-519280;
CC O96020; P42858: HTT; NbExp=6; IntAct=EBI-375033, EBI-466029;
CC O96020; O76024: WFS1; NbExp=3; IntAct=EBI-375033, EBI-720609;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:9840943}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Long;
CC IsoId=O96020-1; Sequence=Displayed;
CC Name=Short; Synonyms=SV;
CC IsoId=O96020-2; Sequence=VSP_001256;
CC -!- TISSUE SPECIFICITY: According to PubMed:9858585, highest levels of
CC expression in adult testis, thymus and brain. Lower levels in placenta,
CC spleen and colon. Consistently elevated levels in tumor-derived cells
CC compared to non-transformed proliferating cells. According to
CC PubMed:9840927: low levels in thymus, prostate, brain, skeletal muscle,
CC and kidney. Elevated levels in lung. According to PubMed:9840943 highly
CC expressed in testis, placenta, thymus and brain. In a lesser extent in
CC small intestine and colon.
CC -!- INDUCTION: Activated by papilloma viral oncoproteins E6 and E7 which
CC bind to and inactivate p53 and Rb, respectively.
CC -!- PTM: Phosphorylation by CDK2 triggers its release from CDK2 and
CC degradation via the ubiquitin proteasome pathway. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the cyclin family. Cyclin E subfamily.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/ccne2/";
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DR EMBL; AF106690; AAD08816.1; -; mRNA.
DR EMBL; AF112857; AAD08819.1; -; mRNA.
DR EMBL; AF091433; AAC80528.1; -; mRNA.
DR EMBL; AF102778; AAC78145.1; -; mRNA.
DR EMBL; AY850195; AAV97813.1; -; Genomic_DNA.
DR CCDS; CCDS6264.1; -. [O96020-1]
DR RefSeq; NP_477097.1; NM_057749.2. [O96020-1]
DR RefSeq; XP_016869446.1; XM_017013957.1.
DR RefSeq; XP_016869447.1; XM_017013958.1. [O96020-1]
DR RefSeq; XP_016869448.1; XM_017013959.1. [O96020-1]
DR AlphaFoldDB; O96020; -.
DR SMR; O96020; -.
DR BioGRID; 114582; 23.
DR ComplexPortal; CPX-2016; Cyclin E2-CDK2 complex.
DR DIP; DIP-31733N; -.
DR IntAct; O96020; 19.
DR MINT; O96020; -.
DR STRING; 9606.ENSP00000429089; -.
DR BindingDB; O96020; -.
DR ChEMBL; CHEMBL2094126; -.
DR ChEMBL; CHEMBL4523633; -.
DR ChEMBL; CHEMBL4523635; -.
DR iPTMnet; O96020; -.
DR PhosphoSitePlus; O96020; -.
DR BioMuta; CCNE2; -.
DR EPD; O96020; -.
DR jPOST; O96020; -.
DR MassIVE; O96020; -.
DR MaxQB; O96020; -.
DR PaxDb; O96020; -.
DR PeptideAtlas; O96020; -.
DR PRIDE; O96020; -.
DR ProteomicsDB; 51213; -. [O96020-1]
DR ProteomicsDB; 51214; -. [O96020-2]
DR Antibodypedia; 3593; 372 antibodies from 38 providers.
DR DNASU; 9134; -.
DR Ensembl; ENST00000308108.9; ENSP00000309181.4; ENSG00000175305.18. [O96020-1]
DR Ensembl; ENST00000520509.5; ENSP00000429089.1; ENSG00000175305.18. [O96020-1]
DR GeneID; 9134; -.
DR KEGG; hsa:9134; -.
DR MANE-Select; ENST00000308108.9; ENSP00000309181.4; NM_057749.3; NP_477097.1.
DR UCSC; uc003yhc.4; human. [O96020-1]
DR CTD; 9134; -.
DR DisGeNET; 9134; -.
DR GeneCards; CCNE2; -.
DR HGNC; HGNC:1590; CCNE2.
DR HPA; ENSG00000175305; Tissue enhanced (bone).
DR MIM; 603775; gene.
DR neXtProt; NX_O96020; -.
DR OpenTargets; ENSG00000175305; -.
DR PharmGKB; PA26155; -.
DR VEuPathDB; HostDB:ENSG00000175305; -.
DR eggNOG; KOG0655; Eukaryota.
DR GeneTree; ENSGT00940000156934; -.
DR InParanoid; O96020; -.
DR OMA; KRHQYEI; -.
DR PhylomeDB; O96020; -.
DR TreeFam; TF101005; -.
DR PathwayCommons; O96020; -.
DR Reactome; R-HSA-1538133; G0 and Early G1.
DR Reactome; R-HSA-187577; SCF(Skp2)-mediated degradation of p27/p21.
DR Reactome; R-HSA-2559586; DNA Damage/Telomere Stress Induced Senescence.
DR Reactome; R-HSA-390471; Association of TriC/CCT with target proteins during biosynthesis.
DR Reactome; R-HSA-6804116; TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest.
DR Reactome; R-HSA-69017; CDK-mediated phosphorylation and removal of Cdc6.
DR Reactome; R-HSA-69200; Phosphorylation of proteins involved in G1/S transition by active Cyclin E:Cdk2 complexes.
DR Reactome; R-HSA-69202; Cyclin E associated events during G1/S transition.
DR Reactome; R-HSA-69231; Cyclin D associated events in G1.
DR Reactome; R-HSA-69563; p53-Dependent G1 DNA Damage Response.
DR Reactome; R-HSA-9661069; Defective binding of RB1 mutants to E2F1,(E2F2, E2F3).
DR SignaLink; O96020; -.
DR SIGNOR; O96020; -.
DR BioGRID-ORCS; 9134; 24 hits in 1085 CRISPR screens.
DR ChiTaRS; CCNE2; human.
DR GenomeRNAi; 9134; -.
DR Pharos; O96020; Tbio.
DR PRO; PR:O96020; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; O96020; protein.
DR Bgee; ENSG00000175305; Expressed in endometrium epithelium and 151 other tissues.
DR ExpressionAtlas; O96020; baseline and differential.
DR Genevisible; O96020; HS.
DR GO; GO:0005813; C:centrosome; IBA:GO_Central.
DR GO; GO:0097134; C:cyclin E1-CDK2 complex; IBA:GO_Central.
DR GO; GO:0097135; C:cyclin E2-CDK2 complex; IBA:GO_Central.
DR GO; GO:0000307; C:cyclin-dependent protein kinase holoenzyme complex; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0016538; F:cyclin-dependent protein serine/threonine kinase regulator activity; IBA:GO_Central.
DR GO; GO:0019901; F:protein kinase binding; IEA:Ensembl.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0006270; P:DNA replication initiation; IEA:Ensembl.
DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; IBA:GO_Central.
DR GO; GO:0007129; P:homologous chromosome pairing at meiosis; IEA:Ensembl.
DR GO; GO:0044772; P:mitotic cell cycle phase transition; IBA:GO_Central.
DR GO; GO:0000079; P:regulation of cyclin-dependent protein serine/threonine kinase activity; IBA:GO_Central.
DR GO; GO:0032880; P:regulation of protein localization; IEA:Ensembl.
DR GO; GO:0000723; P:telomere maintenance; IEA:Ensembl.
DR CDD; cd00043; CYCLIN; 1.
DR InterPro; IPR039361; Cyclin.
DR InterPro; IPR013763; Cyclin-like.
DR InterPro; IPR036915; Cyclin-like_sf.
DR InterPro; IPR004367; Cyclin_C-dom.
DR InterPro; IPR028858; Cyclin_E.
DR InterPro; IPR006671; Cyclin_N.
DR PANTHER; PTHR10177; PTHR10177; 1.
DR PANTHER; PTHR10177:SF70; PTHR10177:SF70; 1.
DR Pfam; PF02984; Cyclin_C; 1.
DR Pfam; PF00134; Cyclin_N; 1.
DR SMART; SM00385; CYCLIN; 1.
DR SMART; SM01332; Cyclin_C; 1.
DR SUPFAM; SSF47954; SSF47954; 2.
DR PROSITE; PS00292; CYCLINS; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell cycle; Cell division; Cyclin; Nucleus;
KW Phosphoprotein; Reference proteome.
FT CHAIN 1..404
FT /note="G1/S-specific cyclin-E2"
FT /id="PRO_0000080461"
FT REGION 1..44
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 6..30
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 21
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163"
FT MOD_RES 383
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976"
FT MOD_RES 392
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18691976"
FT VAR_SEQ 167..211
FT /note="Missing (in isoform Short)"
FT /evidence="ECO:0000303|PubMed:9858585"
FT /id="VSP_001256"
FT VARIANT 387
FT /note="N -> S (in dbSNP:rs28399585)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_021347"
FT MUTAGEN 392
FT /note="T->A: Increase of steady state level."
FT /evidence="ECO:0000269|PubMed:9840943"
SQ SEQUENCE 404 AA; 46757 MW; D7DC9BEEF3FD62EC CRC64;
MSRRSSRLQA KQQPQPSQTE SPQEAQIIQA KKRKTTQDVK KRREEVTKKH QYEIRNCWPP
VLSGGISPCI IIETPHKEIG TSDFSRFTNY RFKNLFINPS PLPDLSWGCS KEVWLNMLKK
ESRYVHDKHF EVLHSDLEPQ MRSILLDWLL EVCEVYTLHR ETFYLAQDFF DRFMLTQKDI
NKNMLQLIGI TSLFIASKLE EIYAPKLQEF AYVTDGACSE EDILRMELII LKALKWELCP
VTIISWLNLF LQVDALKDAP KVLLPQYSQE TFIQIAQLLD LCILAIDSLE FQYRILTAAA
LCHFTSIEVV KKASGLEWDS ISECVDWMVP FVNVVKSTSP VKLKTFKKIP MEDRHNIQTH
TNYLAMLEEV NYINTFRKGG QLSPVCNGGI MTPPKSTEKP PGKH
