Histopathology image classification: Highlighting the gap between manual analysis and AI automation

CCNE1
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	1W98
Identifiers
Aliases	CCNE1, CCNE, pcyclin E1
External IDs	OMIM: 123837; MGI: 88316; HomoloGene: 14452; GeneCards: CCNE1; OMA:CCNE1 - orthologs
Gene location (Human)
Chr.	Chromosome 19 (human)
End	29,824,312 bp
Gene location (Mouse)
Chr.	Chromosome 7 (mouse)
End	37,806,959 bp
RNA expression pattern
	Top expressed in
	Top expressed in
	More reference expression data
	More reference expression data
Gene ontology
Molecular function
Cellular component
Biological process
	Sources:Amigo / QuickGO
Orthologs
	898
	12447
	ENSG00000105173
	ENSMUSG00000002068
	P24864
	Q61457
	NM_001238; NM_057182; NM_001322259; NM_001322261; NM_001322262
	NM_007633
NP_001229; NP_001309188; NP_001309190; NP_001309191; NP_001309188.1;
	NP_001309190.1
	NP_031659
	Wikidata
View/Edit Human	View/Edit Mouse

G1/S-specific cyclin-E1 is a protein that in humans is encoded by the CCNE1 gene.^[5]

Function

The protein encoded by this gene belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance through the cell cycle. Cyclins function as regulators of CDK. Different cyclins exhibit distinct expression and degradation patterns which contribute to the temporal coordination of each mitotic event. This cyclin forms a complex with and functions as a regulatory subunit of CDK2, whose activity is required for cell cycle G1/S transition. This protein accumulates at the G1-S phase boundary and is degraded as cells progress through S phase. Overexpression of this gene has been observed in many tumors, which results in chromosome instability, and thus may contribute to tumorigenesis. This protein was found to associate with, and be involved in, the phosphorylation of NPAT protein (nuclear protein mapped to the ATM locus), which participates in cell-cycle regulated histone gene expression and plays a critical role in promoting cell-cycle progression in the absence of pRB. Two alternatively spliced transcript variants of this gene, which encode distinct isoforms, have been described. Two additional splice variants were reported but detailed nucleotide sequence information is not yet available.^[6]

Interactions

Cyclin E1 has been shown to interact with:

CDC25A,^[7]^[8]
CDKN1B,^[7]^[9]
CUL3^[10]
Cdk1,^[7]^[11]
Cyclin-dependent kinase 2,^[7]^[9]^[11]^[12]^[13]^[14]
HERC5,^[15]
P21,^[12]
Retinoblastoma-like protein 2,^[7]^[16] and
SMARCA4.^[7]^[17]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000105173 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000002068 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Lew DJ, Dulić V, Reed SI (October 1991). "Isolation of three novel human cyclins by rescue of G1 cyclin (Cln) function in yeast". Cell. 66 (6): 1197–206. doi:10.1016/0092-8674(91)90042-W. PMID 1833066. S2CID 12166415.
^ "Entrez Gene: CCNE1 cyclin E1".
^ ^a ^b ^c ^d ^e ^f Shanahan F, Seghezzi W, Parry D, Mahony D, Lees E (February 1999). "Cyclin E associates with BAF155 and BRG1, components of the mammalian SWI-SNF complex, and alters the ability of BRG1 to induce growth arrest". Mol. Cell. Biol. 19 (2): 1460–9. doi:10.1128/mcb.19.2.1460. PMC 116074. PMID 9891079.
^ Xu X, Burke SP (March 1996). "Roles of active site residues and the NH2-terminal domain in the catalysis and substrate binding of human Cdc25". J. Biol. Chem. 271 (9): 5118–24. doi:10.1074/jbc.271.9.5118. PMID 8617791.
^ ^a ^b Connor MK, Kotchetkov R, Cariou S, Resch A, Lupetti R, Beniston RG, Melchior F, Hengst L, Slingerland JM (January 2003). "CRM1/Ran-mediated nuclear export of p27(Kip1) involves a nuclear export signal and links p27 export and proteolysis". Mol. Biol. Cell. 14 (1): 201–13. doi:10.1091/mbc.E02-06-0319. PMC 140238. PMID 12529437.
^ Singer JD, Gurian-West M, Clurman B, Roberts JM (September 1999). "Cullin-3 targets cyclin E for ubiquitination and controls S phase in mammalian cells". Genes Dev. 13 (18): 2375–87. doi:10.1101/gad.13.18.2375. PMC 317026. PMID 10500095.
^ ^a ^b Koff A, Giordano A, Desai D, Yamashita K, Harper JW, Elledge S, Nishimoto T, Morgan DO, Franza BR, Roberts JM (September 1992). "Formation and activation of a cyclin E-cdk2 complex during the G1 phase of the human cell cycle". Science. 257 (5077): 1689–94. Bibcode:1992Sci...257.1689K. doi:10.1126/science.1388288. PMID 1388288.
^ ^a ^b McKenzie PP, Danks MK, Kriwacki RW, Harris LC (July 2003). "P21Waf1/Cip1 dysfunction in neuroblastoma: a novel mechanism of attenuating G0-G1 cell cycle arrest". Cancer Res. 63 (13): 3840–4. PMID 12839982.
^ Mayer C, Zhao J, Yuan X, Grummt I (February 2004). "mTOR-dependent activation of the transcription factor TIF-IA links rRNA synthesis to nutrient availability". Genes Dev. 18 (4): 423–34. doi:10.1101/gad.285504. PMC 359396. PMID 15004009.
^ Boudrez A, Beullens M, Groenen P, Van Eynde A, Vulsteke V, Jagiello I, Murray M, Krainer AR, Stalmans W, Bollen M (August 2000). "NIPP1-mediated interaction of protein phosphatase-1 with CDC5L, a regulator of pre-mRNA splicing and mitotic entry". J. Biol. Chem. 275 (33): 25411–7. doi:10.1074/jbc.M001676200. PMID 10827081.
^ Mitsui K, Nakanishi M, Ohtsuka S, Norwood TH, Okabayashi K, Miyamoto C, Tanaka K, Yoshimura A, Ohtsubo M (December 1999). "A novel human gene encoding HECT domain and RCC1-like repeats interacts with cyclins and is potentially regulated by the tumor suppressor proteins". Biochem. Biophys. Res. Commun. 266 (1): 115–22. doi:10.1006/bbrc.1999.1777. PMID 10581175.
^ Li Y, Graham C, Lacy S, Duncan AM, Whyte P (December 1993). "The adenovirus E1A-associated 130-kD protein is encoded by a member of the retinoblastoma gene family and physically interacts with cyclins A and E". Genes Dev. 7 (12A): 2366–77. doi:10.1101/gad.7.12a.2366. PMID 8253383.
^ Wong AK, Shanahan F, Chen Y, Lian L, Ha P, Hendricks K, Ghaffari S, Iliev D, Penn B, Woodland AM, Smith R, Salada G, Carillo A, Laity K, Gupte J, Swedlund B, Tavtigian SV, Teng DH, Lees E (November 2000). "BRG1, a component of the SWI-SNF complex, is mutated in multiple human tumor cell lines". Cancer Res. 60 (21): 6171–7. PMID 11085541.

Akita H (2003). "[Prognostic importance of altered expression of cell cycle regulators in lung cancer]". Nippon Rinsho. 60. Suppl 5: 267–71. PMID 12101670.
Mazumder S, DuPree EL, Almasan A (2004). "A dual role of cyclin E in cell proliferation and apoptosis may provide a target for cancer therapy". Current Cancer Drug Targets. 4 (1): 65–75. doi:10.2174/1568009043481669. PMC 1307511. PMID 14965268.
Hinds PW, Mittnacht S, Dulic V, Arnold A, Reed SI, Weinberg RA (1992). "Regulation of retinoblastoma protein functions by ectopic expression of human cyclins". Cell. 70 (6): 993–1006. doi:10.1016/0092-8674(92)90249-C. PMID 1388095. S2CID 30799229.
Koff A, Giordano A, Desai D, Yamashita K, Harper JW, Elledge S, Nishimoto T, Morgan DO, Franza BR, Roberts JM (1992). "Formation and activation of a cyclin E-cdk2 complex during the G1 phase of the human cell cycle". Science. 257 (5077): 1689–94. Bibcode:1992Sci...257.1689K. doi:10.1126/science.1388288. PMID 1388288.
Koff A, Cross F, Fisher A, Schumacher J, Leguellec K, Philippe M, Roberts JM (1991). "Human cyclin E, a new cyclin that interacts with two members of the CDC2 gene family". Cell. 66 (6): 1217–28. doi:10.1016/0092-8674(91)90044-Y. PMID 1833068. S2CID 38910227.
Demetrick DJ, Matsumoto S, Hannon GJ, Okamoto K, Xiong Y, Zhang H, Beach DH (1995). "Chromosomal mapping of the genes for the human cell cycle proteins cyclin C (CCNC), cyclin E (CCNE), p21 (CDKN1) and KAP (CDKN3)". Cytogenet. Cell Genet. 69 (3–4): 190–2. doi:10.1159/000133960. PMID 7698009.
Ohtsubo M, Theodoras AM, Schumacher J, Roberts JM, Pagano M (1995). "Human cyclin E, a nuclear protein essential for the G1-to-S phase transition". Mol. Cell. Biol. 15 (5): 2612–24. doi:10.1128/mcb.15.5.2612. PMC 230491. PMID 7739542.
Sewing A, Rönicke V, Bürger C, Funk M, Müller R (1994). "Alternative splicing of human cyclin E.". J. Cell Sci. 107. ( Pt 2) (2): 581–8. doi:10.1242/jcs.107.2.581. PMID 8207080.
Dyson N, Dembski M, Fattaey A, Ngwu C, Ewen M, Helin K (1993). "Analysis of p107-associated proteins: p107 associates with a form of E2F that differs from pRB-associated E2F-1". J. Virol. 67 (12): 7641–7. doi:10.1128/JVI.67.12.7641-7647.1993. PMC 238233. PMID 8230483.
Li Y, Graham C, Lacy S, Duncan AM, Whyte P (1994). "The adenovirus E1A-associated 130-kD protein is encoded by a member of the retinoblastoma gene family and physically interacts with cyclins A and E." Genes Dev. 7 (12A): 2366–77. doi:10.1101/gad.7.12a.2366. PMID 8253383.
Xu X, Burke SP (1996). "Roles of active site residues and the NH2-terminal domain in the catalysis and substrate binding of human Cdc25". J. Biol. Chem. 271 (9): 5118–24. doi:10.1074/jbc.271.9.5118. PMID 8617791.
Ohtani K, DeGregori J, Nevins JR (1996). "Regulation of the cyclin E gene by transcription factor E2F1". Proc. Natl. Acad. Sci. U.S.A. 92 (26): 12146–50. doi:10.1073/pnas.92.26.12146. PMC 40313. PMID 8618861.
Geng Y, Eaton EN, Picón M, Roberts JM, Lundberg AS, Gifford A, Sardet C, Weinberg RA (1996). "Regulation of cyclin E transcription by E2Fs and retinoblastoma protein". Oncogene. 12 (6): 1173–80. PMID 8649818.
Poon RY, Jiang W, Toyoshima H, Hunter T (1996). "Cyclin-dependent kinases are inactivated by a combination of p21 and Thr-14/Tyr-15 phosphorylation after UV-induced DNA damage". J. Biol. Chem. 271 (22): 13283–91. doi:10.1074/jbc.271.22.13283. PMID 8662825.
Chen J, Saha P, Kornbluth S, Dynlacht BD, Dutta A (1996). "Cyclin-binding motifs are essential for the function of p21CIP1". Mol. Cell. Biol. 16 (9): 4673–82. doi:10.1128/MCB.16.9.4673. PMC 231467. PMID 8756624.
Li H, Lahti JM, Valentine M, Saito M, Reed SI, Look AT, Kidd VJ (1997). "Molecular cloning and chromosomal localization of the human cyclin C (CCNC) and cyclin E (CCNE) genes: deletion of the CCNC gene in human tumors". Genomics. 32 (2): 253–9. doi:10.1006/geno.1996.0112. PMID 8833152.
Won KA, Reed SI (1996). "Activation of cyclin E/CDK2 is coupled to site-specific autophosphorylation and ubiquitin-dependent degradation of cyclin E." EMBO J. 15 (16): 4182–93. doi:10.1002/j.1460-2075.1996.tb00793.x. PMC 452142. PMID 8861947.
Sala A, Kundu M, Casella I, Engelhard A, Calabretta B, Grasso L, Paggi MG, Giordano A, Watson RJ, Khalili K, Peschle C (1997). "Activation of human B-MYB by cyclins". Proc. Natl. Acad. Sci. U.S.A. 94 (2): 532–6. Bibcode:1997PNAS...94..532S. doi:10.1073/pnas.94.2.532. PMC 19547. PMID 9012818.
Mumberg D, Wick M, Bürger C, Haas K, Funk M, Müller R (1997). "Cyclin ET, a new splice variant of human cyclin E with a unique expression pattern during cell cycle progression and differentiation". Nucleic Acids Res. 25 (11): 2098–105. doi:10.1093/nar/25.11.2098. PMC 146711. PMID 9153308.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000105173 – Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000002068 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid1833066-5] Lew DJ, Dulić V, Reed SI (October 1991). "Isolation of three novel human cyclins by rescue of G1 cyclin (Cln) function in yeast". Cell. 66 (6): 1197–206. doi:10.1016/0092-8674(91)90042-W. PMID 1833066. S2CID 12166415.

[entrez-6] "Entrez Gene: CCNE1 cyclin E1".

[pmid9891079-7] ^ ^a ^b ^c ^d ^e ^f Shanahan F, Seghezzi W, Parry D, Mahony D, Lees E (February 1999). "Cyclin E associates with BAF155 and BRG1, components of the mammalian SWI-SNF complex, and alters the ability of BRG1 to induce growth arrest". Mol. Cell. Biol. 19 (2): 1460–9. doi:10.1128/mcb.19.2.1460. PMC 116074. PMID 9891079.

[pmid8617791-8] Xu X, Burke SP (March 1996). "Roles of active site residues and the NH2-terminal domain in the catalysis and substrate binding of human Cdc25". J. Biol. Chem. 271 (9): 5118–24. doi:10.1074/jbc.271.9.5118. PMID 8617791.

[pmid12529437-9] Connor MK, Kotchetkov R, Cariou S, Resch A, Lupetti R, Beniston RG, Melchior F, Hengst L, Slingerland JM (January 2003). "CRM1/Ran-mediated nuclear export of p27(Kip1) involves a nuclear export signal and links p27 export and proteolysis". Mol. Biol. Cell. 14 (1): 201–13. doi:10.1091/mbc.E02-06-0319. PMC 140238. PMID 12529437.

[pmid10500095-10] Singer JD, Gurian-West M, Clurman B, Roberts JM (September 1999). "Cullin-3 targets cyclin E for ubiquitination and controls S phase in mammalian cells". Genes Dev. 13 (18): 2375–87. doi:10.1101/gad.13.18.2375. PMC 317026. PMID 10500095.

[pmid1388288-11] Koff A, Giordano A, Desai D, Yamashita K, Harper JW, Elledge S, Nishimoto T, Morgan DO, Franza BR, Roberts JM (September 1992). "Formation and activation of a cyclin E-cdk2 complex during the G1 phase of the human cell cycle". Science. 257 (5077): 1689–94. Bibcode:1992Sci...257.1689K. doi:10.1126/science.1388288. PMID 1388288.

[pmid12839982-12] McKenzie PP, Danks MK, Kriwacki RW, Harris LC (July 2003). "P21Waf1/Cip1 dysfunction in neuroblastoma: a novel mechanism of attenuating G0-G1 cell cycle arrest". Cancer Res. 63 (13): 3840–4. PMID 12839982.

[pmid15004009-13] Mayer C, Zhao J, Yuan X, Grummt I (February 2004). "mTOR-dependent activation of the transcription factor TIF-IA links rRNA synthesis to nutrient availability". Genes Dev. 18 (4): 423–34. doi:10.1101/gad.285504. PMC 359396. PMID 15004009.

[pmid10827081-14] Boudrez A, Beullens M, Groenen P, Van Eynde A, Vulsteke V, Jagiello I, Murray M, Krainer AR, Stalmans W, Bollen M (August 2000). "NIPP1-mediated interaction of protein phosphatase-1 with CDC5L, a regulator of pre-mRNA splicing and mitotic entry". J. Biol. Chem. 275 (33): 25411–7. doi:10.1074/jbc.M001676200. PMID 10827081.

[pmid10581175-15] Mitsui K, Nakanishi M, Ohtsuka S, Norwood TH, Okabayashi K, Miyamoto C, Tanaka K, Yoshimura A, Ohtsubo M (December 1999). "A novel human gene encoding HECT domain and RCC1-like repeats interacts with cyclins and is potentially regulated by the tumor suppressor proteins". Biochem. Biophys. Res. Commun. 266 (1): 115–22. doi:10.1006/bbrc.1999.1777. PMID 10581175.

[pmid8253383-16] Li Y, Graham C, Lacy S, Duncan AM, Whyte P (December 1993). "The adenovirus E1A-associated 130-kD protein is encoded by a member of the retinoblastoma gene family and physically interacts with cyclins A and E". Genes Dev. 7 (12A): 2366–77. doi:10.1101/gad.7.12a.2366. PMID 8253383.

[pmid11085541-17] Wong AK, Shanahan F, Chen Y, Lian L, Ha P, Hendricks K, Ghaffari S, Iliev D, Penn B, Woodland AM, Smith R, Salada G, Carillo A, Laity K, Gupte J, Swedlund B, Tavtigian SV, Teng DH, Lees E (November 2000). "BRG1, a component of the SWI-SNF complex, is mutated in multiple human tumor cell lines". Cancer Res. 60 (21): 6171–7. PMID 11085541.

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Histopathology image classification: Highlighting the gap between manual analysis and AI automation

Function

Interactions

See also

References

Further reading