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UniProtKB - P24864 (CCNE1_HUMAN)

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Protein

G1/S-specific cyclin-E1

Gene

CCNE1

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 G1/S (start) transition.1 Publication

GO - Molecular functioni

  • androgen receptor binding Source: UniProtKB
  • cyclin-dependent protein serine/threonine kinase regulator activity Source: Ensembl
  • kinase activity Source: Ensembl
  • protein kinase binding Source: Ensembl
  • transcription coactivator activity Source: UniProtKB
Complete GO annotation...

GO - Biological processi

Complete GO annotation...

Keywordsi

Molecular functionCyclin
Biological processCell cycle, Cell division

Enzyme and pathway databases

ReactomeiR-HSA-1538133. G0 and Early G1.
R-HSA-187577. SCF(Skp2)-mediated degradation of p27/p21.
R-HSA-2559586. DNA Damage/Telomere Stress Induced Senescence.
R-HSA-390471. Association of TriC/CCT with target proteins during biosynthesis.
R-HSA-539107. Activation of E2F1 target genes at G1/S.
R-HSA-6804116. TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest.
R-HSA-69200. Phosphorylation of proteins involved in G1/S transition by active Cyclin E:Cdk2 complexes.
R-HSA-69202. Cyclin E associated events during G1/S transition.
R-HSA-69563. p53-Dependent G1 DNA Damage Response.
R-HSA-8849470. PTK6 Regulates Cell Cycle.
SignaLinkiP24864.
SIGNORiP24864.

Names & Taxonomyi

Protein namesi
Recommended name:
G1/S-specific cyclin-E1
Gene namesi
Name:CCNE1
Synonyms:CCNE
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:1589. CCNE1.

Subcellular locationi

GO - Cellular componenti

  • cyclin E1-CDK2 complex Source: Ensembl
  • cytosol Source: Reactome
  • nucleoplasm Source: HPA
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi898.
OpenTargetsiENSG00000105173.
PharmGKBiPA96.

Chemistry databases

ChEMBLiCHEMBL3617.

Polymorphism and mutation databases

BioMutaiCCNE1.
DMDMi3041657.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000804491 – 410G1/S-specific cyclin-E1Add BLAST410

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei77Phosphothreonine2 Publications1
Modified residuei103PhosphoserineCombined sources1
Modified residuei387PhosphoserineCombined sources1 Publication1
Modified residuei395Phosphothreonine; by GSK3Combined sources3 Publications1
Modified residuei399Phosphoserine; by CDK22 Publications1

Post-translational modificationi

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 FBXW7.4 Publications
Ubiquitinated by UHRF2; appears to occur independently of phosphorylation.1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP24864.
MaxQBiP24864.
PaxDbiP24864.
PeptideAtlasiP24864.
PRIDEiP24864.

PTM databases

iPTMnetiP24864.
PhosphoSitePlusiP24864.

Miscellaneous databases

PMAP-CutDBiP24864.

Expressioni

Tissue specificityi

Highly expressed in testis and placenta. Low levels in bronchial epithelial cells.1 Publication

Gene expression databases

BgeeiENSG00000105173.
CleanExiHS_CCNE1.
ExpressionAtlasiP24864. baseline and differential.
GenevisibleiP24864. HS.

Organism-specific databases

HPAiCAB000308.
CAB016682.
HPA018169.

Interactioni

Subunit structurei

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.By similarity4 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • androgen receptor binding Source: UniProtKB
  • protein kinase binding Source: Ensembl
Complete GO annotation...

Protein-protein interaction databases

BioGridi107338. 74 interactors.
DIPiDIP-149N.
IntActiP24864. 19 interactors.
MINTiMINT-1514839.
STRINGi9606.ENSP00000262643.

Chemistry databases

BindingDBiP24864.

Structurei

Secondary structure

1410
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi109 – 111Combined sources3
Helixi113 – 123Combined sources11
Turni124 – 126Combined sources3
Helixi133 – 136Combined sources4
Helixi142 – 158Combined sources17
Helixi163 – 179Combined sources17
Helixi185 – 187Combined sources3
Helixi188 – 203Combined sources16
Helixi210 – 215Combined sources6
Turni216 – 219Combined sources4
Helixi223 – 236Combined sources14
Turni237 – 239Combined sources3
Helixi246 – 257Combined sources12
Beta strandi265 – 267Combined sources3
Helixi272 – 287Combined sources16
Helixi289 – 293Combined sources5
Helixi296 – 306Combined sources11
Helixi310 – 316Combined sources7
Helixi321 – 341Combined sources21
Helixi354 – 359Combined sources6
Helixi366 – 370Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1W98X-ray2.15B96-378[»]
5L2WX-ray2.80B96-378[»]
ProteinModelPortaliP24864.
SMRiP24864.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP24864.

Family & Domainsi

Sequence similaritiesi

Belongs to the cyclin family. Cyclin E subfamily.Curated

Phylogenomic databases

eggNOGiKOG0655. Eukaryota.
ENOG410XS2J. LUCA.
GeneTreeiENSGT00760000118939.
HOGENOMiHOG000231743.
HOVERGENiHBG050834.
InParanoidiP24864.
KOiK06626.
OMAiPKLHQFA.
OrthoDBiEOG091G0DAW.
PhylomeDBiP24864.
TreeFamiTF101005.

Family and domain databases

Gene3Di1.10.472.10. 2 hits.
InterProiView protein in InterPro
IPR013763. Cyclin-like.
IPR004367. Cyclin_C-dom.
IPR028858. Cyclin_E.
IPR006671. Cyclin_N.
PANTHERiPTHR10177:SF288. PTHR10177:SF288. 1 hit.
PfamiView protein in Pfam
PF02984. Cyclin_C. 1 hit.
PF00134. Cyclin_N. 1 hit.
SMARTiView protein in SMART
SM00385. CYCLIN. 1 hit.
SM01332. Cyclin_C. 1 hit.
SUPFAMiSSF47954. SSF47954. 2 hits.
PROSITEiView protein in PROSITE
PS00292. CYCLINS. 1 hit.

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform E1L (identifier: P24864-1) [UniParc]FASTAAdd to basket
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.

« Hide

        10         20         30         40         50
MPRERRERDA KERDTMKEDG GAEFSARSRK RKANVTVFLQ DPDEEMAKID 
        60         70         80         90        100
RTARDQCGSQ PWDNNAVCAD PCSLIPTPDK EDDDRVYPNS TCKPRIIAPS 
       110        120        130        140        150
RGSPLPVLSW ANREEVWKIM LNKEKTYLRD QHFLEQHPLL QPKMRAILLD 
       160        170        180        190        200
WLMEVCEVYK LHRETFYLAQ DFFDRYMATQ ENVVKTLLQL IGISSLFIAA 
       210        220        230        240        250
KLEEIYPPKL HQFAYVTDGA CSGDEILTME LMIMKALKWR LSPLTIVSWL 
       260        270        280        290        300
NVYMQVAYLN DLHEVLLPQY PQQIFIQIAE LLDLCVLDVD CLEFPYGILA 
       310        320        330        340        350
ASALYHFSSS ELMQKVSGYQ WCDIENCVKW MVPFAMVIRE TGSSKLKHFR 
       360        370        380        390        400
GVADEDAHNI QTHRDSLDLL DKARAKKAML SEQNRASPLP SGLLTPPQSG 
       410
KKQSSGPEMA
Length:410
Mass (Da):47,077
Last modified:July 15, 1998 - v2
Checksum:i424DF0B253B7047E
GO
Isoform E1S (identifier: P24864-2) [UniParc]FASTAAdd to basket

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.
Show »
Length:367
Mass (Da):41,982
Checksum:i526E59736D99D3C6
GO
Isoform 3 (identifier: P24864-3) [UniParc]FASTAAdd to basket
Also known as: E-S

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

Show »
Length:395
Mass (Da):45,150
Checksum:i4E55D1F80BCFB3EB
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti9D → K no nucleotide entry (PubMed:7739542).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0373811 – 15Missing in isoform 3. 3 PublicationsAdd BLAST15
Alternative sequenceiVSP_001253154 – 196Missing in isoform E1S. CuratedAdd BLAST43

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS12419.1. [P24864-1]
PIRiA40270.
RefSeqiNP_001229.1. NM_001238.3. [P24864-1]
NP_001309191.1. NM_001322262.1. [P24864-3]
UniGeneiHs.244723.

Genome annotation databases

EnsembliENST00000262643; ENSP00000262643; ENSG00000105173. [P24864-1]
ENST00000444983; ENSP00000410179; ENSG00000105173. [P24864-3]
GeneIDi898.
KEGGihsa:898.
UCSCiuc002nsn.4. human. [P24864-1]

Keywords - Coding sequence diversityi

Alternative splicing

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 one 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.

Entry informationi

Entry nameiCCNE1_HUMAN
AccessioniPrimary (citable) accession number: P24864
Secondary accession number(s): A8K684
, Q14091, Q8NFG1, Q92501, Q9UD21
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 1, 1992
Last sequence update: July 15, 1998
Last modified: July 5, 2017
This is version 186 of the entry and version 2 of the sequence. See 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families