Human Gene CCNE2 (ENST00000520509.5) Description and Page Index
  Description: Essential for the control of the cell cycle at the late G1 and early S phase. (from UniProt O96020)
RefSeq Summary (NM_057749): The protein encoded by this gene belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance through the cell cycle. Cyclins function as regulators of CDK kinases. Different cyclins exhibit distinct expression and degradation patterns which contribute to the temporal coordination of each mitotic event. This cyclin forms a complex with and functions as a regulatory subunit of CDK2. This cyclin has been shown to specifically interact with CIP/KIP family of CDK inhibitors, and plays a role in cell cycle G1/S transition. The expression of this gene peaks at the G1-S phase and exhibits a pattern of tissue specificity distinct from that of cyclin E1. A significantly increased expression level of this gene was observed in tumor-derived cells. [provided by RefSeq, Jul 2008]. Publication Note: This RefSeq record includes a subset of the publications that are available for this gene. Please see the Gene record to access additional publications. ##Evidence-Data-START## Transcript exon combination :: SRR1660805.199067.1, SRR1660807.186854.1 [ECO:0000332] RNAseq introns :: mixed/partial sample support SAMEA1965299, SAMEA1966682 [ECO:0000350] ##Evidence-Data-END## ##RefSeq-Attributes-START## RefSeq Select criteria :: based on conservation, expression, longest protein ##RefSeq-Attributes-END##
Gencode Transcript: ENST00000520509.5
Gencode Gene: ENSG00000175305.17
Transcript (Including UTRs)
   Position: hg38 chr8:94,879,770-94,896,678 Size: 16,909 Total Exon Count: 12 Strand: -
Coding Region
   Position: hg38 chr8:94,881,632-94,894,221 Size: 12,590 Coding Exon Count: 11 

Page IndexSequence and LinksUniProtKB CommentsCTDRNA-Seq ExpressionMicroarray Expression
RNA StructureProtein StructureOther SpeciesGO AnnotationsmRNA DescriptionsPathways
Other NamesMethods
Data last updated: 2019-09-04

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr8:94,879,770-94,896,678)mRNA (may differ from genome)Protein (404 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaBioGPS
CGAPEnsemblExonPrimerGeneCardsHGNCHPRD
LynxMGIneXtProtPubMedReactomeStanford SOURCE
UniProtKB

-  Comments and Description Text from UniProtKB
  ID: CCNE2_HUMAN
DESCRIPTION: RecName: Full=G1/S-specific cyclin-E2;
FUNCTION: Essential for the control of the cell cycle at the late G1 and early S phase.
SUBUNIT: Interacts with the CDK2 (in vivo) and CDK3 (in vitro) protein kinases to form a serine/threonine kinase holoenzyme complex. The cyclin subunit imparts substrate specificity to the complex.
INTERACTION: P24941:CDK2; NbExp=5; IntAct=EBI-375033, EBI-375096; P38936:CDKN1A; NbExp=2; IntAct=EBI-375033, EBI-375077; P46527:CDKN1B; NbExp=2; IntAct=EBI-375033, EBI-519280;
SUBCELLULAR LOCATION: Nucleus.
TISSUE SPECIFICITY: According to PubMed:9858585, highest levels of expression in adult testis, thymus and brain. Lower levels in placenta, spleen and colon. Consistently elevated levels in tumor- derived cells compared to non-transformed proliferating cells. According to PubMed:9840927: low levels in thymus, prostate, brain, skeletal muscle, and kidney. Elevated levels in lung. According to PubMed:9840943 highly expressed in testis, placenta, thymus and brain. In a lesser extent in small intestine and colon.
INDUCTION: Activated by papilloma viral oncoproteins E6 and E7 which bind to and inactivate p53 and Rb, respectively.
PTM: Phosphorylation by CDK2 triggers its release from CDK2 and degradation via the ubiquitin proteasome pathway (By similarity).
SIMILARITY: Belongs to the cyclin family. Cyclin E subfamily.
WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/ccne2/";

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene
  • D000082 Acetaminophen
  • D001564 Benzo(a)pyrene
  • D016572 Cyclosporine
  • D017239 Paclitaxel
  • D013749 Tetrachlorodibenzodioxin
  • C017947 sodium arsenite
  • C517041 (4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)
  • C028474 1,4-bis(2-(3,5-dichloropyridyloxy))benzene
  • C029497 2,3-bis(3'-hydroxybenzyl)butyrolactone
  • C532162 2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine
          more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 5.69 RPKM in Brain - Spinal cord (cervical c-1)
Total median expression: 40.96 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -95.60253-0.378 Picture PostScript Text
3' UTR -403.401862-0.217 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR013763 - Cyclin-like
IPR014400 - Cyclin_A/B/D/E
IPR004367 - Cyclin_C
IPR006671 - Cyclin_N

Pfam Domains:
PF02984 - Cyclin, C-terminal domain
PF00134 - Cyclin, N-terminal domain

ModBase Predicted Comparative 3D Structure on O96020
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-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGD    
Protein SequenceProtein Sequence    
AlignmentAlignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0004693 cyclin-dependent protein serine/threonine kinase activity
GO:0005515 protein binding
GO:0016538 cyclin-dependent protein serine/threonine kinase regulator activity
GO:0019901 protein kinase binding

Biological Process:
GO:0000079 regulation of cyclin-dependent protein serine/threonine kinase activity
GO:0000082 G1/S transition of mitotic cell cycle
GO:0000723 telomere maintenance
GO:0006270 DNA replication initiation
GO:0007049 cell cycle
GO:0007129 synapsis
GO:0051301 cell division
GO:0051726 regulation of cell cycle
GO:0070192 chromosome organization involved in meiotic cell cycle
GO:1903827 regulation of cellular protein localization

Cellular Component:
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005829 cytosol
GO:0097135 cyclin E2-CDK2 complex


-  Descriptions from all associated GenBank mRNAs
  LF206390 - JP 2014500723-A/13893: Polycomb-Associated Non-Coding RNAs.
MA441967 - JP 2018138019-A/13893: Polycomb-Associated Non-Coding RNAs.
AF091433 - Homo sapiens cyclin E2 mRNA, complete cds.
JD548838 - Sequence 529862 from Patent EP1572962.
JD037922 - Sequence 18946 from Patent EP1572962.
JD284783 - Sequence 265807 from Patent EP1572962.
JD214052 - Sequence 195076 from Patent EP1572962.
JD282350 - Sequence 263374 from Patent EP1572962.
BC007015 - Homo sapiens cyclin E2, mRNA (cDNA clone MGC:12348 IMAGE:3997513), complete cds.
JD557843 - Sequence 538867 from Patent EP1572962.
JD206549 - Sequence 187573 from Patent EP1572962.
JD181700 - Sequence 162724 from Patent EP1572962.
CU675495 - Synthetic construct Homo sapiens gateway clone IMAGE:100022225 5' read CCNE2 mRNA.
AF102778 - Homo sapiens cyclin E2 mRNA, complete cds.
AF106690 - Homo sapiens cyclin E2 mRNA, complete cds.
AF112857 - Homo sapiens cyclin E2 splice variant 1 mRNA, complete cds.
KJ901946 - Synthetic construct Homo sapiens clone ccsbBroadEn_11340 CCNE2 gene, encodes complete protein.
AB590470 - Synthetic construct DNA, clone: pFN21AE1879, Homo sapiens CCNE2 gene for cyclin E2, without stop codon, in Flexi system.
BC020729 - Homo sapiens cyclin E2, mRNA (cDNA clone MGC:22538 IMAGE:4774554), complete cds.
DQ893494 - Synthetic construct clone IMAGE:100006124; FLH193678.01X; RZPDo839A1179D cyclin E2 (CCNE2) gene, encodes complete protein.
DQ896366 - Synthetic construct Homo sapiens clone IMAGE:100010826; FLH193674.01L; RZPDo839A1169D cyclin E2 (CCNE2) gene, encodes complete protein.
KJ901947 - Synthetic construct Homo sapiens clone ccsbBroadEn_11341 CCNE2 gene, encodes complete protein.
CU676668 - Synthetic construct Homo sapiens gateway clone IMAGE:100022270 5' read CCNE2 mRNA.
LF353855 - JP 2014500723-A/161358: Polycomb-Associated Non-Coding RNAs.
MA589432 - JP 2018138019-A/161358: Polycomb-Associated Non-Coding RNAs.
LF353854 - JP 2014500723-A/161357: Polycomb-Associated Non-Coding RNAs.
MA589431 - JP 2018138019-A/161357: Polycomb-Associated Non-Coding RNAs.
LF353853 - JP 2014500723-A/161356: Polycomb-Associated Non-Coding RNAs.
MA589430 - JP 2018138019-A/161356: Polycomb-Associated Non-Coding RNAs.
JD344924 - Sequence 325948 from Patent EP1572962.
JD477961 - Sequence 458985 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04110 - Cell cycle
hsa04114 - Oocyte meiosis
hsa04115 - p53 signaling pathway
hsa05200 - Pathways in cancer
hsa05215 - Prostate cancer
hsa05222 - Small cell lung cancer

Reactome (by CSHL, EBI, and GO)

Protein O96020 (Reactome details) participates in the following event(s):

R-HSA-69191 Formation of Cyclin E:Cdk2 complexes
R-HSA-69199 Dephosphorylation of Cyclin E:Cdk2 complexes by Cdc25A
R-HSA-69195 Phosphorylation of Cyclin E:Cdk2 complexes by Wee-1
R-HSA-188386 Association of Rb with Cyclin E:Cdk2 complexes
R-HSA-188350 CAK-mediated phosphorylation of Cyclin E:Cdk2
R-HSA-69562 Inactivation of Cyclin E:Cdk2 complexes by p27/p21
R-HSA-157906 Translocation of Cyclin E:Cdk2 complex to the nucleus
R-HSA-390470 Association of CCT/TriC with other substrates during biosynthesis (unknown chaperone)
R-HSA-188390 Cyclin E:Cdk2-mediated phosphorylation of Rb
R-HSA-1363303 p130 (RBL2) in complex with E2F4/5:DP1/2 binds to cyclin E/A:CDK2
R-HSA-1363306 p130 (RBL2) binds Cyclin E/A:CDK2
R-HSA-1363311 p107 (RBL1) in complex with E2F4:DP1/2 binds to cyclin E/A:CDK2
R-HSA-1363314 p107 (RBL1) binds CyclinE/A:CDK2
R-HSA-187520 Cyclin E/A:Cdk2-mediated phosphorylation of p27/p21
R-HSA-187552 Binding of phospho-p27/p21:Cdk2:Cyclin E/A to the SCF(Skp2):Cks1 complex
R-HSA-69005 Cdc6 protein is phosphorylated by CDK
R-HSA-187575 Ubiquitination of phospho-p27/p21
R-HSA-69202 Cyclin E associated events during G1/S transition
R-HSA-69563 p53-Dependent G1 DNA Damage Response
R-HSA-2559586 DNA Damage/Telomere Stress Induced Senescence
R-HSA-6804116 TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest
R-HSA-69206 G1/S Transition
R-HSA-390471 Association of TriC/CCT with target proteins during biosynthesis
R-HSA-69200 Phosphorylation of proteins involved in G1/S transition by active Cyclin E:Cdk2 complexes
R-HSA-187577 SCF(Skp2)-mediated degradation of p27/p21
R-HSA-69580 p53-Dependent G1/S DNA damage checkpoint
R-HSA-2559583 Cellular Senescence
R-HSA-6791312 TP53 Regulates Transcription of Cell Cycle Genes
R-HSA-1538133 G0 and Early G1
R-HSA-453279 Mitotic G1-G1/S phases
R-HSA-390466 Chaperonin-mediated protein folding
R-HSA-69656 Cyclin A:Cdk2-associated events at S phase entry
R-HSA-69017 CDK-mediated phosphorylation and removal of Cdc6
R-HSA-69615 G1/S DNA Damage Checkpoints
R-HSA-2262752 Cellular responses to stress
R-HSA-3700989 Transcriptional Regulation by TP53
R-HSA-69278 Cell Cycle (Mitotic)
R-HSA-391251 Protein folding
R-HSA-69242 S Phase
R-HSA-69052 Switching of origins to a post-replicative state
R-HSA-69620 Cell Cycle Checkpoints
R-HSA-8953897 Cellular responses to external stimuli
R-HSA-212436 Generic Transcription Pathway
R-HSA-1640170 Cell Cycle
R-HSA-392499 Metabolism of proteins
R-HSA-69239 Synthesis of DNA
R-HSA-73857 RNA Polymerase II Transcription
R-HSA-69306 DNA Replication
R-HSA-74160 Gene expression (Transcription)

-  Other Names for This Gene
  Alternate Gene Symbols: AF091433, CCNE2_HUMAN, O95439, O96020, uc064osf.1
UCSC ID: uc064osf.1
RefSeq Accession: NM_057749
Protein: O96020 (aka CCNE2_HUMAN)
CCDS: CCDS6264.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.