P24864 (CCNE1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
G1/S-specific cyclin-E1

Gene names

Name:	CCNE1
Synonyms:	CCNE

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	410 AA.
Sequence status	Complete.
Protein existence	Evidence 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 Thr-395 by GSK3 and of Ser-399 by CDK2 accelerates degradation via the ubiquitin proteasome pathway. Ubiquitinated by UHRF2; appears to occur independently of phosphorylation. Ref.17
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
Molecular function	Cyclin
PTM	Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	DNA replication initiation Inferred from electronic annotation. Source: Compara Wnt receptor signaling pathway Inferred from electronic annotation. Source: Compara androgen receptor signaling pathway Non-traceable author statement PubMed 15572661. Source: UniProtKB cell division Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of transcription, DNA-dependent 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 phase of mitotic cell cycle Traceable author statement. Source: Reactome
Cellular_component	cyclin-dependent protein kinase holoenzyme complex Inferred from electronic annotation. Source: Compara cytosol Traceable author statement. Source: Reactome nucleoplasm Traceable author statement. Source: Reactome
Molecular_function	androgen receptor binding Non-traceable author statement PubMed 15572661. Source: UniProtKB cyclin-dependent protein serine/threonine kinase regulator activity Inferred from electronic annotation. Source: Compara kinase activity Inferred from electronic annotation. Source: Compara transcription coactivator activity Non-traceable author statement PubMed 15572661. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
BRCA1	P38398	2	EBI-519526,EBI-349905
CDK2	P24941	10	EBI-519526,EBI-375096
CDKN1A	P38936	7	EBI-519526,EBI-375077
CDKN1B	P46527	6	EBI-519526,EBI-519280
UHRF2	Q96PU4	4	EBI-519526,EBI-625304

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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 410

410

G1/S-specific cyclin-E1

PRO_0000080449

Amino acid modifications

Modified residue

77

1

Phosphothreonine Ref.12

Modified residue

103

1

Phosphoserine Ref.14 Ref.16

Modified residue

387

1

Phosphoserine Ref.12 Ref.14 Ref.16

Modified residue

395

1

Phosphothreonine; by GSK3 Ref.10 Ref.12 Ref.14

Modified residue

399

1

Phosphoserine; by CDK2 Ref.12

Natural variations

Alternative sequence

1 – 15

15

Missing in isoform 3.

VSP_037381

Alternative sequence

154 – 196

43

Missing in isoform E1S.

VSP_001253

Experimental info

Sequence conflict

9

1

D → K no nucleotide entry Ref.3

Secondary structure

1

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410

Helix Strand Turn

Details...

Beta strand

109 – 111

3

Helix

113 – 123

11

Turn

124 – 126

3

Helix

133 – 136

4

Helix

142 – 158

17

Helix

163 – 179

17

Helix

185 – 187

3

Helix

188 – 203

16

Helix

210 – 215

6

Turn

216 – 219

4

Helix

223 – 236

14

Turn

237 – 239

3

Helix

246 – 257

12

Beta strand

265 – 267

3

Helix

272 – 287

16

Helix

289 – 293

5

Helix

296 – 306

11

Helix

310 – 316

7

Helix

321 – 341

21

Helix

354 – 359

6

Helix

366 – 370

5

Sequences

	Sequence		Length	Mass (Da)
	Isoform E1L (E-L) [UniParc]. Last modified July 15, 1998. Version 2. Checksum: 424DF0B253B7047E	FASTA	410	47,077
	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
	Isoform E1S [UniParc]. Checksum: 526E59736D99D3C6	FASTA	367	41,982
	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 WLMFIAAKLE EIYPPKLHQF AYVTDGACSG 190 200 210 220 230 240 DEILTMELMI MKALKWRLSP LTIVSWLNVY MQVAYLNDLH EVLLPQYPQQ IFIQIAELLD 250 260 270 280 290 300 LCVLDVDCLE FPYGILAASA LYHFSSSELM QKVSGYQWCD IENCVKWMVP FAMVIRETGS 310 320 330 340 350 360 SKLKHFRGVA DEDAHNIQTH RDSLDLLDKA RAKKAMLSEQ NRASPLPSGL LTPPQSGKKQ SSGPEMA
	Isoform 3 (E-S) [UniParc]. Checksum: 4E55D1F80BCFB3EB	FASTA	395	45,150
	10 20 30 40 50 60 MKEDGGAEFS ARSRKRKANV TVFLQDPDEE MAKIDRTARD QCGSQPWDNN AVCADPCSLI 70 80 90 100 110 120 PTPDKEDDDR VYPNSTCKPR IIAPSRGSPL PVLSWANREE VWKIMLNKEK TYLRDQHFLE 130 140 150 160 170 180 QHPLLQPKMR AILLDWLMEV CEVYKLHRET FYLAQDFFDR YMATQENVVK TLLQLIGISS 190 200 210 220 230 240 LFIAAKLEEI YPPKLHQFAY VTDGACSGDE ILTMELMIMK ALKWRLSPLT IVSWLNVYMQ 250 260 270 280 290 300 VAYLNDLHEV LLPQYPQQIF IQIAELLDLC VLDVDCLEFP YGILAASALY HFSSSELMQK 310 320 330 340 350 360 VSGYQWCDIE NCVKWMVPFA MVIRETGSSK LKHFRGVADE DAHNIQTHRD SLDLLDKARA 370 380 390 KKAMLSEQNR ASPLPSGLLT PPQSGKKQSS GPEMA

References

	« Hide 'large scale' referencesShow '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. , 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, MASS SPECTROMETRY. 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, MASS SPECTROMETRY.
[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.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

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.

IPI

IPI00031077.
IPI00376965.
IPI01012689.

PIR

A40270.

RefSeq

NP_001229.1. NM_001238.2.

UniGene

Hs.244723.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1W98	X-ray	2.15	B	96-378	[»]

ProteinModelPortal

P24864.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-149N.

IntAct

P24864. 12 interactions.

MINT

MINT-1514839.

STRING

9606.ENSP00000262643.

PTM databases

PhosphoSite

P24864.

Polymorphism databases

DMDM

3041657.

Proteomic databases

PaxDb

P24864.

PRIDE

P24864.

Protocols and materials databases

DNASU

898.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000262643; ENSP00000262643; ENSG00000105173.
ENST00000444983; ENSP00000410179; ENSG00000105173.

GeneID

898.

KEGG

hsa:898.

UCSC

uc002nsn.3. human.

Organism-specific databases

CTD

898.

GeneCards

GC19P030302.

HGNC

HGNC:1589. CCNE1.

HPA

CAB000308.
CAB016682.
HPA018169.

MIM

123837. gene.

neXtProt

NX_P24864.

PharmGKB

PA96.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5024.

HOGENOM

HOG000231743.

HOVERGEN

HBG050834.

InParanoid

P24864.

KO

K06626.

OMA

PLLQPKM.

PhylomeDB

P24864.

Enzyme and pathway databases

Pathway_Interaction_DB

bard1pathway. BARD1 signaling events.
foxm1pathway. FOXM1 transcription factor network.
prlsignalingeventspathway. Signaling events mediated by PRL.

Reactome

REACT_115566. Cell Cycle.

Gene expression databases

ArrayExpress

P24864.

Bgee

P24864.

CleanEx

HS_CCNE1.

Genevestigator

P24864.

GermOnline

ENSG00000105173. 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

P24864.

ChEMBL

CHEMBL3617.

EvolutionaryTrace

P24864.

GenomeRNAi

898.

NextBio

3708.

PMAP-CutDB

P24864.

SOURCE

Search...

Entry information

Entry name

CCNE1_HUMAN

Accession

Primary (citable) accession number: P24864
Secondary accession number(s): A8K684 , Q14091, Q8NFG1, Q92501, Q9UD21

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 1, 1992
Last sequence update:	July 15, 1998
Last modified:	May 1, 2013
This is version 142 of the entry and version 2 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.