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Protein

G1/S-specific cyclin-E2

Gene

CCNE2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Essential for the control of the cell cycle at the late G1 and early S phase.

GO - Molecular functioni

  1. cyclin-dependent protein serine/threonine kinase regulator activity Source: Ensembl

GO - Biological processi

  1. cell cycle checkpoint Source: ProtInc
  2. cell division Source: UniProtKB-KW
  3. DNA replication initiation Source: Ensembl
  4. G1/S transition of mitotic cell cycle Source: Reactome
  5. mitotic cell cycle Source: Reactome
  6. regulation of cyclin-dependent protein serine/threonine kinase activity Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

Cyclin

Keywords - Biological processi

Cell cycle, Cell division

Enzyme and pathway databases

ReactomeiREACT_111214. G0 and Early G1.
REACT_1574. Cyclin E associated events during G1/S transition.
REACT_1625. p53-Dependent G1 DNA Damage Response.
REACT_169185. DNA Damage/Telomere Stress Induced Senescence.
REACT_308. Phosphorylation of proteins involved in G1/S transition by active Cyclin E:Cdk2 complexes.
REACT_9003. SCF(Skp2)-mediated degradation of p27/p21.
SignaLinkiO96020.

Names & Taxonomyi

Protein namesi
Recommended name:
G1/S-specific cyclin-E2
Gene namesi
Name:CCNE2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 8

Organism-specific databases

HGNCiHGNC:1590. CCNE2.

Subcellular locationi

Nucleus 1 Publication

GO - Cellular componenti

  1. cytosol Source: Reactome
  2. nucleoplasm Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi392 – 3921T → A: Increase of steady state level. 1 Publication

Organism-specific databases

PharmGKBiPA26155.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 404404G1/S-specific cyclin-E2PRO_0000080461Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei21 – 211Phosphoserine2 Publications
Modified residuei383 – 3831Phosphoserine1 Publication
Modified residuei392 – 3921Phosphothreonine1 Publication

Post-translational modificationi

Phosphorylation by CDK2 triggers its release from CDK2 and degradation via the ubiquitin proteasome pathway.By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiO96020.
PaxDbiO96020.
PRIDEiO96020.

PTM databases

PhosphoSiteiO96020.

Expressioni

Tissue specificityi

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.

Inductioni

Activated by papilloma viral oncoproteins E6 and E7 which bind to and inactivate p53 and Rb, respectively.

Gene expression databases

BgeeiO96020.
CleanExiHS_CCNE2.
ExpressionAtlasiO96020. baseline and differential.
GenevestigatoriO96020.

Organism-specific databases

HPAiCAB007825.
CAB019374.

Interactioni

Subunit structurei

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.

Binary interactionsi

WithEntry#Exp.IntActNotes
CDK2P249417EBI-375033,EBI-375096
CDKN1AP389362EBI-375033,EBI-375077
CDKN1BP465272EBI-375033,EBI-519280

Protein-protein interaction databases

BioGridi114582. 16 interactions.
DIPiDIP-31733N.
IntActiO96020. 8 interactions.
MINTiMINT-1353336.
STRINGi9606.ENSP00000309181.

Structurei

3D structure databases

ProteinModelPortaliO96020.
SMRiO96020. Positions 100-369.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the cyclin family. Cyclin E subfamily.Curated

Phylogenomic databases

eggNOGiCOG5024.
GeneTreeiENSGT00760000118939.
HOGENOMiHOG000231743.
HOVERGENiHBG050834.
InParanoidiO96020.
KOiK06626.
OMAiYSQEKFI.
OrthoDBiEOG7HB595.
PhylomeDBiO96020.
TreeFamiTF101005.

Family and domain databases

Gene3Di1.10.472.10. 2 hits.
InterProiIPR013763. Cyclin-like.
IPR004367. Cyclin_C-dom.
IPR028858. Cyclin_E.
IPR006671. Cyclin_N.
[Graphical view]
PANTHERiPTHR10177:SF70. PTHR10177:SF70. 1 hit.
PfamiPF02984. Cyclin_C. 1 hit.
PF00134. Cyclin_N. 1 hit.
[Graphical view]
SMARTiSM00385. CYCLIN. 1 hit.
[Graphical view]
SUPFAMiSSF47954. SSF47954. 2 hits.
PROSITEiPS00292. CYCLINS. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform Long (identifier: O96020-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSRRSSRLQA KQQPQPSQTE SPQEAQIIQA KKRKTTQDVK KRREEVTKKH
60 70 80 90 100
QYEIRNCWPP VLSGGISPCI IIETPHKEIG TSDFSRFTNY RFKNLFINPS
110 120 130 140 150
PLPDLSWGCS KEVWLNMLKK ESRYVHDKHF EVLHSDLEPQ MRSILLDWLL
160 170 180 190 200
EVCEVYTLHR ETFYLAQDFF DRFMLTQKDI NKNMLQLIGI TSLFIASKLE
210 220 230 240 250
EIYAPKLQEF AYVTDGACSE EDILRMELII LKALKWELCP VTIISWLNLF
260 270 280 290 300
LQVDALKDAP KVLLPQYSQE TFIQIAQLLD LCILAIDSLE FQYRILTAAA
310 320 330 340 350
LCHFTSIEVV KKASGLEWDS ISECVDWMVP FVNVVKSTSP VKLKTFKKIP
360 370 380 390 400
MEDRHNIQTH TNYLAMLEEV NYINTFRKGG QLSPVCNGGI MTPPKSTEKP

PGKH
Length:404
Mass (Da):46,757
Last modified:April 30, 1999 - v1
Checksum:iD7DC9BEEF3FD62EC
GO
Isoform Short (identifier: O96020-2) [UniParc]FASTAAdd to basket

Also known as: SV

The sequence of this isoform differs from the canonical sequence as follows:
     167-211: Missing.

Show »
Length:359
Mass (Da):41,465
Checksum:i2A774B409828EC47
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti387 – 3871N → S.1 Publication
Corresponds to variant rs28399585 [ dbSNP | Ensembl ].
VAR_021347

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei167 – 21145Missing in isoform Short. 1 PublicationVSP_001256Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF106690 mRNA. Translation: AAD08816.1.
AF112857 mRNA. Translation: AAD08819.1.
AF091433 mRNA. Translation: AAC80528.1.
AF102778 mRNA. Translation: AAC78145.1.
AY850195 Genomic DNA. Translation: AAV97813.1.
CCDSiCCDS6264.1. [O96020-1]
RefSeqiNP_477097.1. NM_057749.2. [O96020-1]
UniGeneiHs.521693.

Genome annotation databases

EnsembliENST00000308108; ENSP00000309181; ENSG00000175305. [O96020-1]
ENST00000520509; ENSP00000429089; ENSG00000175305. [O96020-1]
GeneIDi9134.
KEGGihsa:9134.
UCSCiuc003yhc.3. human. [O96020-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF106690 mRNA. Translation: AAD08816.1.
AF112857 mRNA. Translation: AAD08819.1.
AF091433 mRNA. Translation: AAC80528.1.
AF102778 mRNA. Translation: AAC78145.1.
AY850195 Genomic DNA. Translation: AAV97813.1.
CCDSiCCDS6264.1. [O96020-1]
RefSeqiNP_477097.1. NM_057749.2. [O96020-1]
UniGeneiHs.521693.

3D structure databases

ProteinModelPortaliO96020.
SMRiO96020. Positions 100-369.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114582. 16 interactions.
DIPiDIP-31733N.
IntActiO96020. 8 interactions.
MINTiMINT-1353336.
STRINGi9606.ENSP00000309181.

Chemistry

BindingDBiO96020.
ChEMBLiCHEMBL2094126.

PTM databases

PhosphoSiteiO96020.

Proteomic databases

MaxQBiO96020.
PaxDbiO96020.
PRIDEiO96020.

Protocols and materials databases

DNASUi9134.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000308108; ENSP00000309181; ENSG00000175305. [O96020-1]
ENST00000520509; ENSP00000429089; ENSG00000175305. [O96020-1]
GeneIDi9134.
KEGGihsa:9134.
UCSCiuc003yhc.3. human. [O96020-1]

Organism-specific databases

CTDi9134.
GeneCardsiGC08M095892.
HGNCiHGNC:1590. CCNE2.
HPAiCAB007825.
CAB019374.
MIMi603775. gene.
neXtProtiNX_O96020.
PharmGKBiPA26155.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG5024.
GeneTreeiENSGT00760000118939.
HOGENOMiHOG000231743.
HOVERGENiHBG050834.
InParanoidiO96020.
KOiK06626.
OMAiYSQEKFI.
OrthoDBiEOG7HB595.
PhylomeDBiO96020.
TreeFamiTF101005.

Enzyme and pathway databases

ReactomeiREACT_111214. G0 and Early G1.
REACT_1574. Cyclin E associated events during G1/S transition.
REACT_1625. p53-Dependent G1 DNA Damage Response.
REACT_169185. DNA Damage/Telomere Stress Induced Senescence.
REACT_308. Phosphorylation of proteins involved in G1/S transition by active Cyclin E:Cdk2 complexes.
REACT_9003. SCF(Skp2)-mediated degradation of p27/p21.
SignaLinkiO96020.

Miscellaneous databases

ChiTaRSiCCNE2. human.
GenomeRNAii9134.
NextBioi34249.
PROiO96020.
SOURCEiSearch...

Gene expression databases

BgeeiO96020.
CleanExiHS_CCNE2.
ExpressionAtlasiO96020. baseline and differential.
GenevestigatoriO96020.

Family and domain databases

Gene3Di1.10.472.10. 2 hits.
InterProiIPR013763. Cyclin-like.
IPR004367. Cyclin_C-dom.
IPR028858. Cyclin_E.
IPR006671. Cyclin_N.
[Graphical view]
PANTHERiPTHR10177:SF70. PTHR10177:SF70. 1 hit.
PfamiPF02984. Cyclin_C. 1 hit.
PF00134. Cyclin_N. 1 hit.
[Graphical view]
SMARTiSM00385. CYCLIN. 1 hit.
[Graphical view]
SUPFAMiSSF47954. SSF47954. 2 hits.
PROSITEiPS00292. CYCLINS. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Cyclin E2, a novel G1 cyclin that binds Cdk2 and is aberrantly expressed in human cancers."
    Gudas J.M., Payton M., Thukral S., Chen E., Bass M., Robinson M.O., Coats S.
    Mol. Cell. Biol. 19:612-622(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS LONG AND SHORT).
    Tissue: Fetal lung.
  2. "Cyclin E2: a novel CDK2 partner in the late G1 and S phases of the mammalian cell cycle."
    Lauper N., Beck A.R.P., Cariou S., Richman L., Hofmann K., Reith W., Slingerland J.M., Amati B.
    Oncogene 17:2637-2643(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: B-cell.
  3. "Cyclin E2, a novel human G1 cyclin and activating partner of CDK2 and CDK3, is induced by viral oncoproteins."
    Zariwala M., Liu J., Xiong Y.
    Oncogene 17:2787-2798(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, MUTAGENESIS OF THR-392.
    Tissue: Keratinocyte.
  4. NIEHS SNPs program
    Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT SER-387.
  5. "Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
    Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
    Mol. Cell 31:438-448(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-383 AND THR-392, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  6. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-21, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  7. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  8. "Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
    Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
    Sci. Signal. 2:RA46-RA46(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-21, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Leukemic T-cell.

Entry informationi

Entry nameiCCNE2_HUMAN
AccessioniPrimary (citable) accession number: O96020
Secondary accession number(s): O95439
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 14, 1999
Last sequence update: April 30, 1999
Last modified: March 31, 2015
This is version 138 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.