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P24864 (CCNE1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 153. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
G1/S-specific cyclin-E1
Gene names
Name:CCNE1
Synonyms:CCNE
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length410 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Essential for the control of the cell cycle at the G1/S (start) transition. Ref.3

Subunit structure

Interacts with a member of the CDK2/CDK protein kinases to form a serine/threonine kinase holoenzyme complex. The cyclin subunit imparts substrate specificity to the complex. Found in a complex with CDK2, CABLES1 and CCNA1 By similarity. Part of a complex consisting of UHRF2, CDK2 and CCNE1. Interacts directly with UHRF2; the interaction ubiquitinates CCNE1 and appears to occur independently of CCNE1 phosphorylation. Ref.13 Ref.17

Subcellular location

Nucleus Ref.3.

Tissue specificity

Highly expressed in testis and placenta. Low levels in bronchial epithelial cells. Ref.11

Post-translational modification

Phosphorylation of both Thr-395 by GSK3 and Ser-399 by CDK2 creates a high affinity degron recognized by FBXW7, and accelerates degradation via the ubiquitin proteasome pathway. Phosphorylation at Thr-77 creates a low affinity degron also recognized by FBXW7.

Ubiquitinated by UHRF2; appears to occur independently of phosphorylation. Ref.17

Sequence similarities

Belongs to the cyclin family. Cyclin E subfamily.

Ontologies

Keywords
   Biological processCell cycle
Cell division
   Cellular componentNucleus
   Coding sequence diversityAlternative splicing
   Molecular functionCyclin
   PTMPhosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processDNA replication initiation

Inferred from electronic annotation. Source: Ensembl

G1/S transition of mitotic cell cycle

Non-traceable author statement Ref.9. Source: UniProtKB

Wnt signaling pathway

Inferred from electronic annotation. Source: Ensembl

androgen receptor signaling pathway

Non-traceable author statement PubMed 15572661. Source: UniProtKB

cell division

Inferred from electronic annotation. Source: UniProtKB-KW

mitotic cell cycle

Traceable author statement. Source: Reactome

positive regulation of transcription, DNA-templated

Non-traceable author statement PubMed 15572661. Source: UniProtKB

protein phosphorylation

Inferred from mutant phenotype PubMed 10500095. Source: MGI

regulation of cyclin-dependent protein serine/threonine kinase activity

Inferred from electronic annotation. Source: InterPro

regulation of transcription involved in G1/S transition of mitotic cell cycle

Traceable author statement. Source: Reactome

   Cellular_componentcyclin-dependent protein kinase holoenzyme complex

Inferred from electronic annotation. Source: Ensembl

cytosol

Traceable author statement. Source: Reactome

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay. Source: HPA

   Molecular_functionandrogen receptor binding

Non-traceable author statement PubMed 15572661. Source: UniProtKB

cyclin-dependent protein serine/threonine kinase regulator activity

Inferred from electronic annotation. Source: Ensembl

kinase activity

Inferred from electronic annotation. Source: Ensembl

transcription coactivator activity

Non-traceable author statement PubMed 15572661. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform E1L (identifier: P24864-1)

Also known as: E-L;

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.
Isoform E1S (identifier: P24864-2)

The sequence of this isoform differs from the canonical sequence as follows:
     154-196: Missing.
Note: Lacks 49 residues within the cyclin box and cannot complex with CDK2.
Isoform 3 (identifier: P24864-3)

Also known as: E-S;

The sequence of this isoform differs from the canonical sequence as follows:
     1-15: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 410410G1/S-specific cyclin-E1
PRO_0000080449

Amino acid modifications

Modified residue771Phosphothreonine Ref.12 Ref.19
Modified residue1031Phosphoserine Ref.14 Ref.16
Modified residue3871Phosphoserine Ref.12 Ref.14 Ref.16
Modified residue3951Phosphothreonine; by GSK3 Ref.10 Ref.12 Ref.14 Ref.19
Modified residue3991Phosphoserine; by CDK2 Ref.12 Ref.19

Natural variations

Alternative sequence1 – 1515Missing in isoform 3.
VSP_037381
Alternative sequence154 – 19643Missing in isoform E1S.
VSP_001253

Experimental info

Sequence conflict91D → K no nucleotide entry Ref.3

Secondary structure

....................................... 410
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform E1L (E-L) [UniParc].

Last modified July 15, 1998. Version 2.
Checksum: 424DF0B253B7047E

FASTA41047,077
        10         20         30         40         50         60 
MPRERRERDA KERDTMKEDG GAEFSARSRK RKANVTVFLQ DPDEEMAKID RTARDQCGSQ 

        70         80         90        100        110        120 
PWDNNAVCAD PCSLIPTPDK EDDDRVYPNS TCKPRIIAPS RGSPLPVLSW ANREEVWKIM 

       130        140        150        160        170        180 
LNKEKTYLRD QHFLEQHPLL QPKMRAILLD WLMEVCEVYK LHRETFYLAQ DFFDRYMATQ 

       190        200        210        220        230        240 
ENVVKTLLQL IGISSLFIAA KLEEIYPPKL HQFAYVTDGA CSGDEILTME LMIMKALKWR 

       250        260        270        280        290        300 
LSPLTIVSWL NVYMQVAYLN DLHEVLLPQY PQQIFIQIAE LLDLCVLDVD CLEFPYGILA 

       310        320        330        340        350        360 
ASALYHFSSS ELMQKVSGYQ WCDIENCVKW MVPFAMVIRE TGSSKLKHFR GVADEDAHNI 

       370        380        390        400        410 
QTHRDSLDLL DKARAKKAML SEQNRASPLP SGLLTPPQSG KKQSSGPEMA 

« Hide

Isoform E1S [UniParc].

Checksum: 526E59736D99D3C6
Show »

FASTA36741,982
Isoform 3 (E-S) [UniParc].

Checksum: 4E55D1F80BCFB3EB
Show »

FASTA39545,150

References

« Hide 'large scale' references
[1]"Isolation of three novel human cyclins by rescue of G1 cyclin (Cln) function in yeast."
Lew D.J., Dulic V., Reed S.I.
Cell 66:1197-1206(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
[2]"Human cyclin E, a new cyclin that interacts with two members of the CDC2 gene family."
Koff A., Cross F., Fisher A., Schumacher J., le Guellec K., Philippe M., Roberts J.M.
Cell 66:1217-1228(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
[3]"Human cyclin E, a nuclear protein essential for the G1-to-S phase transition."
Ohtsubo M., Theodoras A.M., Schumacher J., Roberts J.M., Pagano M.
Mol. Cell. Biol. 15:2612-2624(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS E1L AND 3), FUNCTION, SUBCELLULAR LOCATION, ALTERNATIVE SPLICING.
[4]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM E1L).
Tissue: Placenta.
[5]NIEHS SNPs program
Submitted (JUN-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM E1L).
Tissue: Placenta.
[7]"Regulation of cyclin E transcription by E2Fs and retinoblastoma protein."
Geng Y., Eaton E.N., Picon M., Roberts J.M., Lundberg A.S., Gifford A., Sardet C., Weinberg R.A.
Oncogene 12:1173-1180(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-42.
[8]"Molecular cloning and chromosomal localization of the human cyclin C (CCNC) and cyclin E (CCNE) genes: deletion of the CCNC gene in human tumors."
Li H., Lahti J.M., Valentine M., Saito M., Reed S.I., Look A.T., Kidd V.J.
Genomics 32:253-259(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 281-370.
[9]"Alternative splicing of human cyclin E."
Sewing A., Roenicke V., Buerger C., Funk M., Mueller R.
J. Cell Sci. 107:581-588(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: ALTERNATIVE SPLICING.
[10]"Activation of cyclin E/CDK2 is coupled to site-specific autophosphorylation and ubiquitin-dependent degradation of cyclin E."
Won K.A., Reed S.I.
EMBO J. 15:4182-4193(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT THR-395.
[11]"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(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[12]"Multisite phosphorylation by Cdk2 and GSK3 controls cyclin E degradation."
Welcker M., Singer J., Loeb K.R., Grim J., Bloecher A., Gurien-West M., Clurman B.E., Roberts J.M.
Mol. Cell 12:381-392(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT THR-77; SER-387; THR-395 AND SER-399.
[13]"NIRF induces G1 arrest and associates with Cdk2."
Li Y., Mori T., Hata H., Homma Y., Kochi H.
Biochem. Biophys. Res. Commun. 319:464-468(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN A COMPLEX WITH UHRF2 AND CDK2.
[14]"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(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-103; SER-387 AND THR-395, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[15]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[16]"Large-scale proteomics analysis of the human kinome."
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H.
Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-103 AND SER-387, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[17]"NIRF constitutes a nodal point in the cell cycle network and is a candidate tumor suppressor."
Mori T., Ikeda D.D., Fukushima T., Takenoshita S., Kochi H.
Cell Cycle 10:3284-3299(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION, INTERACTION WITH UHRF2.
[18]"The structure of cyclin E1/CDK2: implications for CDK2 activation and CDK2-independent roles."
Honda R., Lowe E.D., Dubinina E., Skamnaki V., Cook A., Brown N.R., Johnson L.N.
EMBO J. 24:452-463(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) OF 96-378 IN COMPLEX WITH CDK2.
[19]"Structure of a Fbw7-Skp1-cyclin E complex: multisite-phosphorylated substrate recognition by SCF ubiquitin ligases."
Hao B., Oehlmann S., Sowa M.E., Harper J.W., Pavletich N.P.
Mol. Cell 26:131-143(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 73-80 IN COMPLEX WITH SKP1 AND FBXW7, PHOSPHORYLATION AT THR-77; THR-395 AND SER-399.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M74093 mRNA. No translation available.
M73812 mRNA. No translation available.
AK291549 mRNA. Translation: BAF84238.1.
AF518727 Genomic DNA. Translation: AAM54043.1.
BC035498 mRNA. Translation: AAH35498.1.
X95406 Genomic DNA. Translation: CAA64687.1.
X95406 Genomic DNA. Translation: CAA64688.1.
AH003247 Genomic DNA. Translation: AAA83269.1.
PIRA40270.
RefSeqNP_001229.1. NM_001238.2.
UniGeneHs.244723.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1W98X-ray2.15B96-378[»]
ProteinModelPortalP24864.
SMRP24864. Positions 103-372.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107338. 73 interactions.
DIPDIP-149N.
IntActP24864. 13 interactions.
MINTMINT-1514839.
STRING9606.ENSP00000262643.

Chemistry

BindingDBP24864.
ChEMBLCHEMBL1907605.

PTM databases

PhosphoSiteP24864.

Polymorphism databases

DMDM3041657.

Proteomic databases

PaxDbP24864.
PRIDEP24864.

Protocols and materials databases

DNASU898.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000262643; ENSP00000262643; ENSG00000105173. [P24864-1]
ENST00000444983; ENSP00000410179; ENSG00000105173. [P24864-3]
GeneID898.
KEGGhsa:898.
UCSCuc002nsn.3. human. [P24864-1]

Organism-specific databases

CTD898.
GeneCardsGC19P030302.
HGNCHGNC:1589. CCNE1.
HPACAB000308.
CAB016682.
HPA018169.
MIM123837. gene.
neXtProtNX_P24864.
PharmGKBPA96.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5024.
HOGENOMHOG000231743.
HOVERGENHBG050834.
InParanoidP24864.
KOK06626.
OMAPLLQPKM.
OrthoDBEOG7HB595.
PhylomeDBP24864.
TreeFamTF101005.

Enzyme and pathway databases

ReactomeREACT_115566. Cell Cycle.
REACT_120956. Cellular responses to stress.
SignaLinkP24864.

Gene expression databases

ArrayExpressP24864.
BgeeP24864.
CleanExHS_CCNE1.
GenevestigatorP24864.

Family and domain databases

Gene3D1.10.472.10. 2 hits.
InterProIPR013763. Cyclin-like.
IPR014400. Cyclin_A/B/D/E.
IPR004367. Cyclin_C-dom.
IPR028858. Cyclin_E.
IPR006671. Cyclin_N.
[Graphical view]
PANTHERPTHR10177:SF71. PTHR10177:SF71. 1 hit.
PfamPF02984. Cyclin_C. 1 hit.
PF00134. Cyclin_N. 1 hit.
[Graphical view]
PIRSFPIRSF001771. Cyclin_A_B_D_E. 1 hit.
SMARTSM00385. CYCLIN. 1 hit.
[Graphical view]
SUPFAMSSF47954. SSF47954. 2 hits.
PROSITEPS00292. CYCLINS. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP24864.
GeneWikiCyclin_E1.
GenomeRNAi898.
NextBio3708.
PMAP-CutDBP24864.
PROP24864.
SOURCESearch...

Entry information

Entry nameCCNE1_HUMAN
AccessionPrimary (citable) accession number: P24864
Secondary accession number(s): A8K684 expand/collapse secondary AC list , Q14091, Q8NFG1, Q92501, Q9UD21
Entry history
Integrated into UniProtKB/Swiss-Prot: March 1, 1992
Last sequence update: July 15, 1998
Last modified: April 16, 2014
This is version 153 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM