O96020 (CCNE2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
G1/S-specific cyclin-E2

Gene names

Name:

CCNE2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	404 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Essential for the control of the cell cycle at the late G1 and early S phase.
Subunit structure	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.
Subcellular location	Nucleus Ref.3.
Tissue specificity	According to Ref.1, 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 Ref.2: low levels in thymus, prostate, brain, skeletal muscle, and kidney. Elevated levels in lung. According to Ref.3 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.
Post-translational modification	Phosphorylation by CDK2 triggers its release from CDK2 and degradation via the ubiquitin proteasome pathway By similarity.
Sequence similarities	Belongs to the cyclin family. Cyclin E subfamily.

Ontologies

Keywords
Biological process	Cell cycle Cell division
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Molecular function	Cyclin
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	DNA replication initiation Inferred from electronic annotation. Source: Compara G1/S transition of mitotic cell cycle Traceable author statement. Source: Reactome cell cycle checkpoint Traceable author statement Ref.1. Source: ProtInc cell division Inferred from electronic annotation. Source: UniProtKB-KW regulation of cyclin-dependent protein serine/threonine kinase activity Traceable author statement Ref.3. Source: ProtInc
Cellular_component	cytosol Traceable author statement. Source: Reactome nucleoplasm Traceable author statement. Source: Reactome
Molecular_function	cyclin-dependent protein serine/threonine kinase regulator activity Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CDK2	P24941	6	EBI-375033,EBI-375096
CDKN1A	P38936	2	EBI-375033,EBI-375077
CDKN1B	P46527	2	EBI-375033,EBI-519280

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform Long (identifier: O96020-1)

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 Short (identifier: O96020-2)

Also known as: SV;

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

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 404	404	G1/S-specific cyclin-E2		PRO_0000080461
Amino acid modifications
	Modified residue	21	1	Phosphoserine Ref.6 Ref.8
	Modified residue	383	1	Phosphoserine Ref.5
	Modified residue	392	1	Phosphothreonine Ref.5
Natural variations
	Alternative sequence	167 – 211	45	Missing in isoform Short.		VSP_001256
	Natural variant	387	1	N → S. Ref.4 Corresponds to variant rs28399585 [ dbSNP | Ensembl ].		VAR_021347
Experimental info
	Mutagenesis	392	1	T → A: Increase of steady state level. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform Long [UniParc]. Last modified May 1, 1999. Version 1. Checksum: D7DC9BEEF3FD62EC	FASTA	404	46,757
	10 20 30 40 50 60 MSRRSSRLQA KQQPQPSQTE SPQEAQIIQA KKRKTTQDVK KRREEVTKKH QYEIRNCWPP 70 80 90 100 110 120 VLSGGISPCI IIETPHKEIG TSDFSRFTNY RFKNLFINPS PLPDLSWGCS KEVWLNMLKK 130 140 150 160 170 180 ESRYVHDKHF EVLHSDLEPQ MRSILLDWLL EVCEVYTLHR ETFYLAQDFF DRFMLTQKDI 190 200 210 220 230 240 NKNMLQLIGI TSLFIASKLE EIYAPKLQEF AYVTDGACSE EDILRMELII LKALKWELCP 250 260 270 280 290 300 VTIISWLNLF LQVDALKDAP KVLLPQYSQE TFIQIAQLLD LCILAIDSLE FQYRILTAAA 310 320 330 340 350 360 LCHFTSIEVV KKASGLEWDS ISECVDWMVP FVNVVKSTSP VKLKTFKKIP MEDRHNIQTH 370 380 390 400 TNYLAMLEEV NYINTFRKGG QLSPVCNGGI MTPPKSTEKP PGKH
	Isoform Short (SV) [UniParc]. Checksum: 2A774B409828EC47	FASTA	359	41,465
	10 20 30 40 50 60 MSRRSSRLQA KQQPQPSQTE SPQEAQIIQA KKRKTTQDVK KRREEVTKKH QYEIRNCWPP 70 80 90 100 110 120 VLSGGISPCI IIETPHKEIG TSDFSRFTNY RFKNLFINPS PLPDLSWGCS KEVWLNMLKK 130 140 150 160 170 180 ESRYVHDKHF EVLHSDLEPQ MRSILLDWLL EVCEVYTLHR ETFYLAYVTD GACSEEDILR 190 200 210 220 230 240 MELIILKALK WELCPVTIIS WLNLFLQVDA LKDAPKVLLP QYSQETFIQI AQLLDLCILA 250 260 270 280 290 300 IDSLEFQYRI LTAAALCHFT SIEVVKKASG LEWDSISECV DWMVPFVNVV KSTSPVKLKT 310 320 330 340 350 FKKIPMEDRH NIQTHTNYLA MLEEVNYINT FRKGGQLSPV CNGGIMTPPK STEKPPGKH

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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(1999) [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(1998) [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(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, MUTAGENESIS OF THR-392. Tissue: Keratinocyte.
[4]	NIEHS SNPs program Submitted (DEC-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(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-383 AND THR-392, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[6]	"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: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-21, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[7]	"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: 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(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-21, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases
EMBL GenBank DDBJ	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.
IPI	IPI00014085. IPI00219502.
RefSeq	NP_477097.1. NM_057749.2.
UniGene	Hs.521693.
3D structure databases
ProteinModelPortal	O96020.
ModBase	Search...
Protein-protein interaction databases
IntAct	O96020. 7 interactions.
MINT	MINT-1353336.
STRING	9606.ENSP00000309181.
PTM databases
PhosphoSite	O96020.
Proteomic databases
PaxDb	O96020.
PRIDE	O96020.
Protocols and materials databases
DNASU	9134.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000308108; ENSP00000309181; ENSG00000175305. ENST00000520509; ENSP00000429089; ENSG00000175305.
GeneID	9134.
KEGG	hsa:9134.
UCSC	uc003yhc.3. human.
Organism-specific databases
CTD	9134.
GeneCards	GC08M095892.
HGNC	HGNC:1590. CCNE2.
HPA	CAB007825. CAB019374.
MIM	603775. gene.
neXtProt	NX_O96020.
PharmGKB	PA26155.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG5024.
HOGENOM	HOG000231743.
HOVERGEN	HBG050834.
InParanoid	O96020.
KO	K06626.
OMA	FIQIAQL.
OrthoDB	EOG4Z36F4.
PhylomeDB	O96020.
Enzyme and pathway databases
Reactome	REACT_115566. Cell Cycle.
Gene expression databases
ArrayExpress	O96020.
Bgee	O96020.
CleanEx	HS_CCNE2.
Genevestigator	O96020.
GermOnline	ENSG00000175305. Homo sapiens.
Family and domain databases
Gene3D	1.10.472.10. 2 hits.
InterPro	IPR013763. Cyclin-like. IPR014400. Cyclin_A/B/D/E. IPR004367. Cyclin_C-dom. IPR006671. Cyclin_N. [Graphical view]
Pfam	PF02984. Cyclin_C. 1 hit. PF00134. Cyclin_N. 1 hit. [Graphical view]
PIRSF	PIRSF001771. Cyclin_A_B_D_E. 1 hit.
SMART	SM00385. CYCLIN. 1 hit. [Graphical view]
SUPFAM	SSF47954. Cyclin_like. 1 hit.
PROSITE	PS00292. CYCLINS. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	O96020.
ChEMBL	CHEMBL2884.
ChiTaRS	CCNE2. human.
GenomeRNAi	9134.
NextBio	34249.
SOURCE	Search...

Entry information

Entry name

CCNE2_HUMAN

Accession

Primary (citable) accession number: O96020
Secondary accession number(s): O95439

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	May 1, 1999
Last modified:	May 1, 2013
This is version 118 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.