Full text data of CCNA2
CCNA2
(CCN1, CCNA)
[Confidence: low (only semi-automatic identification from reviews)]
Cyclin-A2; Cyclin-A
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Cyclin-A2; Cyclin-A
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P20248
ID CCNA2_HUMAN Reviewed; 432 AA.
AC P20248; A8K7B6; Q2M3U6; Q4W5P4; Q6LER8;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
read moreDT 02-NOV-2010, sequence version 2.
DT 22-JAN-2014, entry version 146.
DE RecName: Full=Cyclin-A2;
DE Short=Cyclin-A;
GN Name=CCNA2; Synonyms=CCN1, CCNA;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT VAL-163.
RX PubMed=1967822; DOI=10.1038/343555a0;
RA Wang J., Chenivesse X., Henglein B., Brechot C.;
RT "Hepatitis B virus integration in a cyclin A gene in a hepatocellular
RT carcinoma.";
RL Nature 343:555-557(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT VAL-163.
RX PubMed=8202514; DOI=10.1073/pnas.91.12.5490;
RA Henglein B., Chenivesse X., Wang D., Eick D., Brechot C.;
RT "Structure and cell cycle-regulated transcription of the human cyclin
RT A gene.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:5490-5494(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT VAL-163.
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT VAL-163.
RG NIEHS SNPs program;
RL Submitted (JUN-2002) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT VAL-163.
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H.,
RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
RA Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N.,
RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
RA McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D.,
RA Waterston R.H., Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2
RT and 4.";
RL Nature 434:724-731(2005).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT VAL-163.
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT VAL-163.
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP INTERACTION WITH SCAPER, AND SUBCELLULAR LOCATION.
RX PubMed=17698606; DOI=10.1083/jcb.200701166;
RA Tsang W.Y., Wang L., Chen Z., Sanchez I., Dynlacht B.D.;
RT "SCAPER, a novel cyclin A-interacting protein that regulates cell
RT cycle progression.";
RL J. Cell Biol. 178:621-633(2007).
RN [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, PHOSPHORYLATION [LARGE
RP SCALE ANALYSIS] AT SER-5 AND SER-55, AND MASS SPECTROMETRY.
RX PubMed=19369195; DOI=10.1074/mcp.M800588-MCP200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [12]
RP UBIQUITINATION, AND DEUBIQUITINATION BY USP37.
RX PubMed=21596315; DOI=10.1016/j.molcel.2011.03.027;
RA Huang X., Summers M.K., Pham V., Lill J.R., Liu J., Lee G.,
RA Kirkpatrick D.S., Jackson P.K., Fang G., Dixit V.M.;
RT "Deubiquitinase USP37 is activated by CDK2 to antagonize APC(CDH1) and
RT promote S phase entry.";
RL Mol. Cell 42:511-523(2011).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 173-432 COMPLEXED WITH CDK2.
RX PubMed=7630397; DOI=10.1038/376313a0;
RA Jeffrey P.D., Russo A.A., Polyak K., Gibbs E., Hurwitz J.,
RA Massague J., Pavletich N.P.;
RT "Mechanism of CDK activation revealed by the structure of a cyclinA-
RT CDK2 complex.";
RL Nature 376:313-320(1995).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 173-432 IN CDK2/KIP1 COMPLEX.
RX PubMed=8684460; DOI=10.1038/382325a0;
RA Russo A.A., Jeffrey P.D., Patten A.K., Massague J., Pavletich N.P.;
RT "Crystal structure of the p27Kip1 cyclin-dependent-kinase inhibitor
RT bound to the cyclin A-Cdk2 complex.";
RL Nature 382:325-331(1996).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 173-432 COMPLEXED WITH CDK2.
RX PubMed=8756328; DOI=10.1038/nsb0896-696;
RA Russo A.A., Jeffrey P.D., Pavletich N.P.;
RT "Structural basis of cyclin-dependent kinase activation by
RT phosphorylation.";
RL Nat. Struct. Biol. 3:696-700(1996).
RN [17]
RP VARIANT [LARGE SCALE ANALYSIS] VAL-163, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
CC -!- FUNCTION: Essential for the control of the cell cycle at the G1/S
CC (start) and the G2/M (mitosis) transitions.
CC -!- SUBUNIT: Interacts with the CDK1 and CDK2 protein kinases to form
CC a serine/threonine kinase holoenzyme complex. The cyclin subunit
CC imparts substrate specificity to the complex. When associated with
CC CDK2 (but not with CDK1), interacts with SCAPER.
CC -!- INTERACTION:
CC P03070:- (xeno); NbExp=2; IntAct=EBI-457097, EBI-617698;
CC P24941:CDK2; NbExp=19; IntAct=EBI-457097, EBI-375096;
CC P38936:CDKN1A; NbExp=2; IntAct=EBI-457097, EBI-375077;
CC P46527:CDKN1B; NbExp=13; IntAct=EBI-457097, EBI-519280;
CC Q96PU4:UHRF2; NbExp=2; IntAct=EBI-457097, EBI-625304;
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=Cytoplasmic when
CC associated with SCAPER.
CC -!- DEVELOPMENTAL STAGE: Accumulates steadily during G2 and is
CC abruptly destroyed at mitosis.
CC -!- PTM: Polyubiquitinated via 'Lys-11'-linked ubiquitin by the
CC anaphase-promoting complex (APC/C), leading to its degradation by
CC the proteasome. Deubiquitinated and stabilized by USP37 enables
CC entry into S phase (By similarity).
CC -!- SIMILARITY: Belongs to the cyclin family. Cyclin AB subfamily.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/ccna2/";
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DR EMBL; X51688; CAA35986.1; -; mRNA.
DR EMBL; X68303; CAA48375.1; -; Genomic_DNA.
DR EMBL; CR407692; CAG28620.1; -; mRNA.
DR EMBL; AF518006; AAM54042.1; -; Genomic_DNA.
DR EMBL; AK291931; BAF84620.1; -; mRNA.
DR EMBL; AC079341; AAY40969.1; -; Genomic_DNA.
DR EMBL; CH471056; EAX05246.1; -; Genomic_DNA.
DR EMBL; BC104783; AAI04784.1; -; mRNA.
DR EMBL; BC104787; AAI04788.1; -; mRNA.
DR PIR; S08277; S08277.
DR RefSeq; NP_001228.1; NM_001237.3.
DR UniGene; Hs.58974; -.
DR PDB; 1E9H; X-ray; 2.50 A; B/D=175-432.
DR PDB; 1FIN; X-ray; 2.30 A; B/D=173-432.
DR PDB; 1FVV; X-ray; 2.80 A; B/D=173-432.
DR PDB; 1GY3; X-ray; 2.70 A; B/D=175-432.
DR PDB; 1H1P; X-ray; 2.10 A; B/D=175-432.
DR PDB; 1H1Q; X-ray; 2.50 A; B/D=175-432.
DR PDB; 1H1R; X-ray; 2.00 A; B/D=175-432.
DR PDB; 1H1S; X-ray; 2.00 A; B/D=175-432.
DR PDB; 1H24; X-ray; 2.50 A; B/D=175-432.
DR PDB; 1H25; X-ray; 2.50 A; B/D=175-432.
DR PDB; 1H26; X-ray; 2.24 A; B/D=175-432.
DR PDB; 1H27; X-ray; 2.20 A; B/D=175-432.
DR PDB; 1H28; X-ray; 2.80 A; B/D=175-432.
DR PDB; 1JST; X-ray; 2.60 A; B/D=175-432.
DR PDB; 1JSU; X-ray; 2.30 A; B=173-432.
DR PDB; 1OGU; X-ray; 2.60 A; B/D=174-432.
DR PDB; 1OI9; X-ray; 2.10 A; B/D=174-432.
DR PDB; 1OIU; X-ray; 2.00 A; B/D=174-432.
DR PDB; 1OIY; X-ray; 2.40 A; B/D=174-432.
DR PDB; 1OKV; X-ray; 2.40 A; B/D=173-432.
DR PDB; 1OKW; X-ray; 2.50 A; B/D=173-432.
DR PDB; 1OL1; X-ray; 2.90 A; B/D=173-432.
DR PDB; 1OL2; X-ray; 2.60 A; B/D=173-432.
DR PDB; 1P5E; X-ray; 2.22 A; B/D=175-432.
DR PDB; 1PKD; X-ray; 2.30 A; B/D=175-432.
DR PDB; 1QMZ; X-ray; 2.20 A; B/D=174-432.
DR PDB; 1URC; X-ray; 2.60 A; B/D=173-432.
DR PDB; 1VYW; X-ray; 2.30 A; B/D=174-432.
DR PDB; 2BKZ; X-ray; 2.60 A; B/D=173-432.
DR PDB; 2BPM; X-ray; 2.40 A; B/D=174-432.
DR PDB; 2C4G; X-ray; 2.70 A; B/D=173-432.
DR PDB; 2C5N; X-ray; 2.10 A; B/D=174-432.
DR PDB; 2C5O; X-ray; 2.10 A; B/D=173-432.
DR PDB; 2C5V; X-ray; 2.90 A; B/D=174-432.
DR PDB; 2C5X; X-ray; 2.90 A; B/D=174-432.
DR PDB; 2C6T; X-ray; 2.61 A; B/D=175-432.
DR PDB; 2CCH; X-ray; 1.70 A; B/D=173-432.
DR PDB; 2CCI; X-ray; 2.70 A; B/D=175-432.
DR PDB; 2CJM; X-ray; 2.30 A; B/D=175-432.
DR PDB; 2I40; X-ray; 2.80 A; B/D=173-432.
DR PDB; 2IW6; X-ray; 2.30 A; B/D=174-432.
DR PDB; 2IW8; X-ray; 2.30 A; B/D=174-432.
DR PDB; 2IW9; X-ray; 2.00 A; B/D=174-432.
DR PDB; 2UUE; X-ray; 2.06 A; B/D=174-432.
DR PDB; 2UZB; X-ray; 2.70 A; B/D=175-432.
DR PDB; 2UZD; X-ray; 2.72 A; B/D=175-432.
DR PDB; 2UZE; X-ray; 2.40 A; B/D=175-432.
DR PDB; 2UZL; X-ray; 2.40 A; B/D=175-432.
DR PDB; 2V22; X-ray; 2.60 A; B/D=174-432.
DR PDB; 2WEV; X-ray; 2.30 A; B/D=173-432.
DR PDB; 2WFY; X-ray; 2.53 A; B/D=173-432.
DR PDB; 2WHB; X-ray; 2.90 A; B/D=173-432.
DR PDB; 2WIH; X-ray; 2.50 A; B/D=173-432.
DR PDB; 2WIP; X-ray; 2.80 A; B/D=173-432.
DR PDB; 2WMA; X-ray; 2.80 A; B/D=174-432.
DR PDB; 2WMB; X-ray; 2.60 A; B/D=174-432.
DR PDB; 2WPA; X-ray; 2.51 A; B/D=173-432.
DR PDB; 2WXV; X-ray; 2.60 A; B/D=173-432.
DR PDB; 2X1N; X-ray; 2.75 A; B/D=172-432.
DR PDB; 3EID; X-ray; 3.15 A; B/D=173-432.
DR PDB; 3EJ1; X-ray; 3.22 A; B/D=173-432.
DR PDB; 3EOC; X-ray; 3.20 A; B/D=173-432.
DR PDB; 3F5X; X-ray; 2.40 A; B/D=177-432.
DR PDB; 4BCK; X-ray; 2.05 A; B/D=171-432.
DR PDB; 4BCM; X-ray; 2.45 A; B/D=171-432.
DR PDB; 4BCN; X-ray; 2.10 A; B=171-432, D=171-431.
DR PDB; 4BCP; X-ray; 2.26 A; B/D=171-432.
DR PDB; 4EOI; X-ray; 2.00 A; B/D=175-432.
DR PDB; 4EOJ; X-ray; 1.65 A; B/D=175-432.
DR PDB; 4EOK; X-ray; 2.57 A; B/D=175-432.
DR PDB; 4EOL; X-ray; 2.40 A; B/D=175-432.
DR PDB; 4EOM; X-ray; 2.10 A; B/D=175-432.
DR PDB; 4EON; X-ray; 2.40 A; B/D=175-432.
DR PDB; 4EOO; X-ray; 2.10 A; B/D=175-432.
DR PDB; 4EOP; X-ray; 1.99 A; B/D=175-432.
DR PDB; 4EOQ; X-ray; 2.15 A; B/D=175-432.
DR PDB; 4EOR; X-ray; 2.20 A; B/D=175-432.
DR PDB; 4EOS; X-ray; 2.57 A; B/D=175-432.
DR PDB; 4FX3; X-ray; 2.75 A; B/D=175-432.
DR PDBsum; 1E9H; -.
DR PDBsum; 1FIN; -.
DR PDBsum; 1FVV; -.
DR PDBsum; 1GY3; -.
DR PDBsum; 1H1P; -.
DR PDBsum; 1H1Q; -.
DR PDBsum; 1H1R; -.
DR PDBsum; 1H1S; -.
DR PDBsum; 1H24; -.
DR PDBsum; 1H25; -.
DR PDBsum; 1H26; -.
DR PDBsum; 1H27; -.
DR PDBsum; 1H28; -.
DR PDBsum; 1JST; -.
DR PDBsum; 1JSU; -.
DR PDBsum; 1OGU; -.
DR PDBsum; 1OI9; -.
DR PDBsum; 1OIU; -.
DR PDBsum; 1OIY; -.
DR PDBsum; 1OKV; -.
DR PDBsum; 1OKW; -.
DR PDBsum; 1OL1; -.
DR PDBsum; 1OL2; -.
DR PDBsum; 1P5E; -.
DR PDBsum; 1PKD; -.
DR PDBsum; 1QMZ; -.
DR PDBsum; 1URC; -.
DR PDBsum; 1VYW; -.
DR PDBsum; 2BKZ; -.
DR PDBsum; 2BPM; -.
DR PDBsum; 2C4G; -.
DR PDBsum; 2C5N; -.
DR PDBsum; 2C5O; -.
DR PDBsum; 2C5V; -.
DR PDBsum; 2C5X; -.
DR PDBsum; 2C6T; -.
DR PDBsum; 2CCH; -.
DR PDBsum; 2CCI; -.
DR PDBsum; 2CJM; -.
DR PDBsum; 2I40; -.
DR PDBsum; 2IW6; -.
DR PDBsum; 2IW8; -.
DR PDBsum; 2IW9; -.
DR PDBsum; 2UUE; -.
DR PDBsum; 2UZB; -.
DR PDBsum; 2UZD; -.
DR PDBsum; 2UZE; -.
DR PDBsum; 2UZL; -.
DR PDBsum; 2V22; -.
DR PDBsum; 2WEV; -.
DR PDBsum; 2WFY; -.
DR PDBsum; 2WHB; -.
DR PDBsum; 2WIH; -.
DR PDBsum; 2WIP; -.
DR PDBsum; 2WMA; -.
DR PDBsum; 2WMB; -.
DR PDBsum; 2WPA; -.
DR PDBsum; 2WXV; -.
DR PDBsum; 2X1N; -.
DR PDBsum; 3EID; -.
DR PDBsum; 3EJ1; -.
DR PDBsum; 3EOC; -.
DR PDBsum; 3F5X; -.
DR PDBsum; 4BCK; -.
DR PDBsum; 4BCM; -.
DR PDBsum; 4BCN; -.
DR PDBsum; 4BCP; -.
DR PDBsum; 4EOI; -.
DR PDBsum; 4EOJ; -.
DR PDBsum; 4EOK; -.
DR PDBsum; 4EOL; -.
DR PDBsum; 4EOM; -.
DR PDBsum; 4EON; -.
DR PDBsum; 4EOO; -.
DR PDBsum; 4EOP; -.
DR PDBsum; 4EOQ; -.
DR PDBsum; 4EOR; -.
DR PDBsum; 4EOS; -.
DR PDBsum; 4FX3; -.
DR ProteinModelPortal; P20248; -.
DR SMR; P20248; 176-432.
DR DIP; DIP-638N; -.
DR IntAct; P20248; 27.
DR MINT; MINT-141826; -.
DR STRING; 9606.ENSP00000274026; -.
DR BindingDB; P20248; -.
DR ChEMBL; CHEMBL2582; -.
DR PhosphoSite; P20248; -.
DR DMDM; 311033358; -.
DR PaxDb; P20248; -.
DR PRIDE; P20248; -.
DR Ensembl; ENST00000274026; ENSP00000274026; ENSG00000145386.
DR GeneID; 890; -.
DR KEGG; hsa:890; -.
DR UCSC; uc003iec.4; human.
DR CTD; 890; -.
DR GeneCards; GC04M122737; -.
DR HGNC; HGNC:1578; CCNA2.
DR HPA; CAB000114; -.
DR HPA; HPA020626; -.
DR MIM; 123835; gene.
DR neXtProt; NX_P20248; -.
DR PharmGKB; PA94; -.
DR eggNOG; COG5024; -.
DR HOGENOM; HOG000167672; -.
DR HOVERGEN; HBG106244; -.
DR InParanoid; P20248; -.
DR KO; K06627; -.
DR OMA; NPEKAAP; -.
DR OrthoDB; EOG7G7KQ0; -.
DR PhylomeDB; P20248; -.
DR Reactome; REACT_115566; Cell Cycle.
DR Reactome; REACT_120956; Cellular responses to stress.
DR Reactome; REACT_383; DNA Replication.
DR Reactome; REACT_6850; Cdc20:Phospho-APC/C mediated degradation of Cyclin A.
DR SignaLink; P20248; -.
DR EvolutionaryTrace; P20248; -.
DR GeneWiki; Cyclin_A2; -.
DR GenomeRNAi; 890; -.
DR NextBio; 3682; -.
DR PMAP-CutDB; P20248; -.
DR PRO; PR:P20248; -.
DR Bgee; P20248; -.
DR CleanEx; HS_CCNA2; -.
DR Genevestigator; P20248; -.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0001939; C:female pronucleus; IEA:Ensembl.
DR GO; GO:0001940; C:male pronucleus; IEA:Ensembl.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0000086; P:G2/M transition of mitotic cell cycle; TAS:Reactome.
DR GO; GO:0007067; P:mitosis; IEA:UniProtKB-KW.
DR GO; GO:0007095; P:mitotic G2 DNA damage checkpoint; TAS:ProtInc.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-dependent; IEA:Ensembl.
DR GO; GO:0007265; P:Ras protein signal transduction; IEP:BHF-UCL.
DR GO; GO:0000079; P:regulation of cyclin-dependent protein serine/threonine kinase activity; IEA:InterPro.
DR Gene3D; 1.10.472.10; -; 2.
DR InterPro; IPR013763; Cyclin-like.
DR InterPro; IPR014400; Cyclin_A/B/D/E.
DR InterPro; IPR004367; Cyclin_C-dom.
DR InterPro; IPR006671; Cyclin_N.
DR Pfam; PF02984; Cyclin_C; 1.
DR Pfam; PF00134; Cyclin_N; 1.
DR PIRSF; PIRSF001771; Cyclin_A_B_D_E; 1.
DR SMART; SM00385; CYCLIN; 2.
DR SUPFAM; SSF47954; SSF47954; 2.
DR PROSITE; PS00292; CYCLINS; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Cell cycle; Cell division;
KW Complete proteome; Cyclin; Cytoplasm; Mitosis; Nucleus;
KW Phosphoprotein; Polymorphism; Reference proteome; Ubl conjugation.
FT CHAIN 1 432 Cyclin-A2.
FT /FTId=PRO_0000080338.
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 5 5 Phosphoserine.
FT MOD_RES 55 55 Phosphoserine.
FT VARIANT 163 163 I -> V (in dbSNP:rs769242).
FT /FTId=VAR_018819.
FT CONFLICT 156 156 H -> R (in Ref. 3; CAG28620).
FT HELIX 176 178
FT HELIX 179 192
FT HELIX 199 202
FT HELIX 208 224
FT HELIX 229 243
FT HELIX 250 252
FT HELIX 253 268
FT STRAND 269 271
FT HELIX 275 281
FT TURN 282 284
FT HELIX 288 301
FT TURN 302 304
FT HELIX 311 319
FT STRAND 322 324
FT HELIX 327 342
FT HELIX 344 347
FT HELIX 352 368
FT HELIX 374 380
FT HELIX 384 400
FT HELIX 401 403
FT HELIX 408 412
FT STRAND 413 415
FT HELIX 416 418
FT HELIX 421 423
SQ SEQUENCE 432 AA; 48551 MW; 97763A2897DD35F4 CRC64;
MLGNSAPGPA TREAGSALLA LQQTALQEDQ ENINPEKAAP VQQPRTRAAL AVLKSGNPRG
LAQQQRPKTR RVAPLKDLPV NDEHVTVPPW KANSKQPAFT IHVDEAEKEA QKKPAESQKI
EREDALAFNS AISLPGPRKP LVPLDYPMDG SFESPHTMDM SIILEDEKPV SVNEVPDYHE
DIHTYLREME VKCKPKVGYM KKQPDITNSM RAILVDWLVE VGEEYKLQNE TLHLAVNYID
RFLSSMSVLR GKLQLVGTAA MLLASKFEEI YPPEVAEFVY ITDDTYTKKQ VLRMEHLVLK
VLTFDLAAPT VNQFLTQYFL HQQPANCKVE SLAMFLGELS LIDADPYLKY LPSVIAGAAF
HLALYTVTGQ SWPESLIRKT GYTLESLKPC LMDLHQTYLK APQHAQQSIR EKYKNSKYHG
VSLLNPPETL NL
//
ID CCNA2_HUMAN Reviewed; 432 AA.
AC P20248; A8K7B6; Q2M3U6; Q4W5P4; Q6LER8;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
read moreDT 02-NOV-2010, sequence version 2.
DT 22-JAN-2014, entry version 146.
DE RecName: Full=Cyclin-A2;
DE Short=Cyclin-A;
GN Name=CCNA2; Synonyms=CCN1, CCNA;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT VAL-163.
RX PubMed=1967822; DOI=10.1038/343555a0;
RA Wang J., Chenivesse X., Henglein B., Brechot C.;
RT "Hepatitis B virus integration in a cyclin A gene in a hepatocellular
RT carcinoma.";
RL Nature 343:555-557(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT VAL-163.
RX PubMed=8202514; DOI=10.1073/pnas.91.12.5490;
RA Henglein B., Chenivesse X., Wang D., Eick D., Brechot C.;
RT "Structure and cell cycle-regulated transcription of the human cyclin
RT A gene.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:5490-5494(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT VAL-163.
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT VAL-163.
RG NIEHS SNPs program;
RL Submitted (JUN-2002) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT VAL-163.
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H.,
RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
RA Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N.,
RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
RA McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D.,
RA Waterston R.H., Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2
RT and 4.";
RL Nature 434:724-731(2005).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT VAL-163.
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT VAL-163.
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP INTERACTION WITH SCAPER, AND SUBCELLULAR LOCATION.
RX PubMed=17698606; DOI=10.1083/jcb.200701166;
RA Tsang W.Y., Wang L., Chen Z., Sanchez I., Dynlacht B.D.;
RT "SCAPER, a novel cyclin A-interacting protein that regulates cell
RT cycle progression.";
RL J. Cell Biol. 178:621-633(2007).
RN [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, PHOSPHORYLATION [LARGE
RP SCALE ANALYSIS] AT SER-5 AND SER-55, AND MASS SPECTROMETRY.
RX PubMed=19369195; DOI=10.1074/mcp.M800588-MCP200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [12]
RP UBIQUITINATION, AND DEUBIQUITINATION BY USP37.
RX PubMed=21596315; DOI=10.1016/j.molcel.2011.03.027;
RA Huang X., Summers M.K., Pham V., Lill J.R., Liu J., Lee G.,
RA Kirkpatrick D.S., Jackson P.K., Fang G., Dixit V.M.;
RT "Deubiquitinase USP37 is activated by CDK2 to antagonize APC(CDH1) and
RT promote S phase entry.";
RL Mol. Cell 42:511-523(2011).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 173-432 COMPLEXED WITH CDK2.
RX PubMed=7630397; DOI=10.1038/376313a0;
RA Jeffrey P.D., Russo A.A., Polyak K., Gibbs E., Hurwitz J.,
RA Massague J., Pavletich N.P.;
RT "Mechanism of CDK activation revealed by the structure of a cyclinA-
RT CDK2 complex.";
RL Nature 376:313-320(1995).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 173-432 IN CDK2/KIP1 COMPLEX.
RX PubMed=8684460; DOI=10.1038/382325a0;
RA Russo A.A., Jeffrey P.D., Patten A.K., Massague J., Pavletich N.P.;
RT "Crystal structure of the p27Kip1 cyclin-dependent-kinase inhibitor
RT bound to the cyclin A-Cdk2 complex.";
RL Nature 382:325-331(1996).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 173-432 COMPLEXED WITH CDK2.
RX PubMed=8756328; DOI=10.1038/nsb0896-696;
RA Russo A.A., Jeffrey P.D., Pavletich N.P.;
RT "Structural basis of cyclin-dependent kinase activation by
RT phosphorylation.";
RL Nat. Struct. Biol. 3:696-700(1996).
RN [17]
RP VARIANT [LARGE SCALE ANALYSIS] VAL-163, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
CC -!- FUNCTION: Essential for the control of the cell cycle at the G1/S
CC (start) and the G2/M (mitosis) transitions.
CC -!- SUBUNIT: Interacts with the CDK1 and CDK2 protein kinases to form
CC a serine/threonine kinase holoenzyme complex. The cyclin subunit
CC imparts substrate specificity to the complex. When associated with
CC CDK2 (but not with CDK1), interacts with SCAPER.
CC -!- INTERACTION:
CC P03070:- (xeno); NbExp=2; IntAct=EBI-457097, EBI-617698;
CC P24941:CDK2; NbExp=19; IntAct=EBI-457097, EBI-375096;
CC P38936:CDKN1A; NbExp=2; IntAct=EBI-457097, EBI-375077;
CC P46527:CDKN1B; NbExp=13; IntAct=EBI-457097, EBI-519280;
CC Q96PU4:UHRF2; NbExp=2; IntAct=EBI-457097, EBI-625304;
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=Cytoplasmic when
CC associated with SCAPER.
CC -!- DEVELOPMENTAL STAGE: Accumulates steadily during G2 and is
CC abruptly destroyed at mitosis.
CC -!- PTM: Polyubiquitinated via 'Lys-11'-linked ubiquitin by the
CC anaphase-promoting complex (APC/C), leading to its degradation by
CC the proteasome. Deubiquitinated and stabilized by USP37 enables
CC entry into S phase (By similarity).
CC -!- SIMILARITY: Belongs to the cyclin family. Cyclin AB subfamily.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/ccna2/";
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DR EMBL; X51688; CAA35986.1; -; mRNA.
DR EMBL; X68303; CAA48375.1; -; Genomic_DNA.
DR EMBL; CR407692; CAG28620.1; -; mRNA.
DR EMBL; AF518006; AAM54042.1; -; Genomic_DNA.
DR EMBL; AK291931; BAF84620.1; -; mRNA.
DR EMBL; AC079341; AAY40969.1; -; Genomic_DNA.
DR EMBL; CH471056; EAX05246.1; -; Genomic_DNA.
DR EMBL; BC104783; AAI04784.1; -; mRNA.
DR EMBL; BC104787; AAI04788.1; -; mRNA.
DR PIR; S08277; S08277.
DR RefSeq; NP_001228.1; NM_001237.3.
DR UniGene; Hs.58974; -.
DR PDB; 1E9H; X-ray; 2.50 A; B/D=175-432.
DR PDB; 1FIN; X-ray; 2.30 A; B/D=173-432.
DR PDB; 1FVV; X-ray; 2.80 A; B/D=173-432.
DR PDB; 1GY3; X-ray; 2.70 A; B/D=175-432.
DR PDB; 1H1P; X-ray; 2.10 A; B/D=175-432.
DR PDB; 1H1Q; X-ray; 2.50 A; B/D=175-432.
DR PDB; 1H1R; X-ray; 2.00 A; B/D=175-432.
DR PDB; 1H1S; X-ray; 2.00 A; B/D=175-432.
DR PDB; 1H24; X-ray; 2.50 A; B/D=175-432.
DR PDB; 1H25; X-ray; 2.50 A; B/D=175-432.
DR PDB; 1H26; X-ray; 2.24 A; B/D=175-432.
DR PDB; 1H27; X-ray; 2.20 A; B/D=175-432.
DR PDB; 1H28; X-ray; 2.80 A; B/D=175-432.
DR PDB; 1JST; X-ray; 2.60 A; B/D=175-432.
DR PDB; 1JSU; X-ray; 2.30 A; B=173-432.
DR PDB; 1OGU; X-ray; 2.60 A; B/D=174-432.
DR PDB; 1OI9; X-ray; 2.10 A; B/D=174-432.
DR PDB; 1OIU; X-ray; 2.00 A; B/D=174-432.
DR PDB; 1OIY; X-ray; 2.40 A; B/D=174-432.
DR PDB; 1OKV; X-ray; 2.40 A; B/D=173-432.
DR PDB; 1OKW; X-ray; 2.50 A; B/D=173-432.
DR PDB; 1OL1; X-ray; 2.90 A; B/D=173-432.
DR PDB; 1OL2; X-ray; 2.60 A; B/D=173-432.
DR PDB; 1P5E; X-ray; 2.22 A; B/D=175-432.
DR PDB; 1PKD; X-ray; 2.30 A; B/D=175-432.
DR PDB; 1QMZ; X-ray; 2.20 A; B/D=174-432.
DR PDB; 1URC; X-ray; 2.60 A; B/D=173-432.
DR PDB; 1VYW; X-ray; 2.30 A; B/D=174-432.
DR PDB; 2BKZ; X-ray; 2.60 A; B/D=173-432.
DR PDB; 2BPM; X-ray; 2.40 A; B/D=174-432.
DR PDB; 2C4G; X-ray; 2.70 A; B/D=173-432.
DR PDB; 2C5N; X-ray; 2.10 A; B/D=174-432.
DR PDB; 2C5O; X-ray; 2.10 A; B/D=173-432.
DR PDB; 2C5V; X-ray; 2.90 A; B/D=174-432.
DR PDB; 2C5X; X-ray; 2.90 A; B/D=174-432.
DR PDB; 2C6T; X-ray; 2.61 A; B/D=175-432.
DR PDB; 2CCH; X-ray; 1.70 A; B/D=173-432.
DR PDB; 2CCI; X-ray; 2.70 A; B/D=175-432.
DR PDB; 2CJM; X-ray; 2.30 A; B/D=175-432.
DR PDB; 2I40; X-ray; 2.80 A; B/D=173-432.
DR PDB; 2IW6; X-ray; 2.30 A; B/D=174-432.
DR PDB; 2IW8; X-ray; 2.30 A; B/D=174-432.
DR PDB; 2IW9; X-ray; 2.00 A; B/D=174-432.
DR PDB; 2UUE; X-ray; 2.06 A; B/D=174-432.
DR PDB; 2UZB; X-ray; 2.70 A; B/D=175-432.
DR PDB; 2UZD; X-ray; 2.72 A; B/D=175-432.
DR PDB; 2UZE; X-ray; 2.40 A; B/D=175-432.
DR PDB; 2UZL; X-ray; 2.40 A; B/D=175-432.
DR PDB; 2V22; X-ray; 2.60 A; B/D=174-432.
DR PDB; 2WEV; X-ray; 2.30 A; B/D=173-432.
DR PDB; 2WFY; X-ray; 2.53 A; B/D=173-432.
DR PDB; 2WHB; X-ray; 2.90 A; B/D=173-432.
DR PDB; 2WIH; X-ray; 2.50 A; B/D=173-432.
DR PDB; 2WIP; X-ray; 2.80 A; B/D=173-432.
DR PDB; 2WMA; X-ray; 2.80 A; B/D=174-432.
DR PDB; 2WMB; X-ray; 2.60 A; B/D=174-432.
DR PDB; 2WPA; X-ray; 2.51 A; B/D=173-432.
DR PDB; 2WXV; X-ray; 2.60 A; B/D=173-432.
DR PDB; 2X1N; X-ray; 2.75 A; B/D=172-432.
DR PDB; 3EID; X-ray; 3.15 A; B/D=173-432.
DR PDB; 3EJ1; X-ray; 3.22 A; B/D=173-432.
DR PDB; 3EOC; X-ray; 3.20 A; B/D=173-432.
DR PDB; 3F5X; X-ray; 2.40 A; B/D=177-432.
DR PDB; 4BCK; X-ray; 2.05 A; B/D=171-432.
DR PDB; 4BCM; X-ray; 2.45 A; B/D=171-432.
DR PDB; 4BCN; X-ray; 2.10 A; B=171-432, D=171-431.
DR PDB; 4BCP; X-ray; 2.26 A; B/D=171-432.
DR PDB; 4EOI; X-ray; 2.00 A; B/D=175-432.
DR PDB; 4EOJ; X-ray; 1.65 A; B/D=175-432.
DR PDB; 4EOK; X-ray; 2.57 A; B/D=175-432.
DR PDB; 4EOL; X-ray; 2.40 A; B/D=175-432.
DR PDB; 4EOM; X-ray; 2.10 A; B/D=175-432.
DR PDB; 4EON; X-ray; 2.40 A; B/D=175-432.
DR PDB; 4EOO; X-ray; 2.10 A; B/D=175-432.
DR PDB; 4EOP; X-ray; 1.99 A; B/D=175-432.
DR PDB; 4EOQ; X-ray; 2.15 A; B/D=175-432.
DR PDB; 4EOR; X-ray; 2.20 A; B/D=175-432.
DR PDB; 4EOS; X-ray; 2.57 A; B/D=175-432.
DR PDB; 4FX3; X-ray; 2.75 A; B/D=175-432.
DR PDBsum; 1E9H; -.
DR PDBsum; 1FIN; -.
DR PDBsum; 1FVV; -.
DR PDBsum; 1GY3; -.
DR PDBsum; 1H1P; -.
DR PDBsum; 1H1Q; -.
DR PDBsum; 1H1R; -.
DR PDBsum; 1H1S; -.
DR PDBsum; 1H24; -.
DR PDBsum; 1H25; -.
DR PDBsum; 1H26; -.
DR PDBsum; 1H27; -.
DR PDBsum; 1H28; -.
DR PDBsum; 1JST; -.
DR PDBsum; 1JSU; -.
DR PDBsum; 1OGU; -.
DR PDBsum; 1OI9; -.
DR PDBsum; 1OIU; -.
DR PDBsum; 1OIY; -.
DR PDBsum; 1OKV; -.
DR PDBsum; 1OKW; -.
DR PDBsum; 1OL1; -.
DR PDBsum; 1OL2; -.
DR PDBsum; 1P5E; -.
DR PDBsum; 1PKD; -.
DR PDBsum; 1QMZ; -.
DR PDBsum; 1URC; -.
DR PDBsum; 1VYW; -.
DR PDBsum; 2BKZ; -.
DR PDBsum; 2BPM; -.
DR PDBsum; 2C4G; -.
DR PDBsum; 2C5N; -.
DR PDBsum; 2C5O; -.
DR PDBsum; 2C5V; -.
DR PDBsum; 2C5X; -.
DR PDBsum; 2C6T; -.
DR PDBsum; 2CCH; -.
DR PDBsum; 2CCI; -.
DR PDBsum; 2CJM; -.
DR PDBsum; 2I40; -.
DR PDBsum; 2IW6; -.
DR PDBsum; 2IW8; -.
DR PDBsum; 2IW9; -.
DR PDBsum; 2UUE; -.
DR PDBsum; 2UZB; -.
DR PDBsum; 2UZD; -.
DR PDBsum; 2UZE; -.
DR PDBsum; 2UZL; -.
DR PDBsum; 2V22; -.
DR PDBsum; 2WEV; -.
DR PDBsum; 2WFY; -.
DR PDBsum; 2WHB; -.
DR PDBsum; 2WIH; -.
DR PDBsum; 2WIP; -.
DR PDBsum; 2WMA; -.
DR PDBsum; 2WMB; -.
DR PDBsum; 2WPA; -.
DR PDBsum; 2WXV; -.
DR PDBsum; 2X1N; -.
DR PDBsum; 3EID; -.
DR PDBsum; 3EJ1; -.
DR PDBsum; 3EOC; -.
DR PDBsum; 3F5X; -.
DR PDBsum; 4BCK; -.
DR PDBsum; 4BCM; -.
DR PDBsum; 4BCN; -.
DR PDBsum; 4BCP; -.
DR PDBsum; 4EOI; -.
DR PDBsum; 4EOJ; -.
DR PDBsum; 4EOK; -.
DR PDBsum; 4EOL; -.
DR PDBsum; 4EOM; -.
DR PDBsum; 4EON; -.
DR PDBsum; 4EOO; -.
DR PDBsum; 4EOP; -.
DR PDBsum; 4EOQ; -.
DR PDBsum; 4EOR; -.
DR PDBsum; 4EOS; -.
DR PDBsum; 4FX3; -.
DR ProteinModelPortal; P20248; -.
DR SMR; P20248; 176-432.
DR DIP; DIP-638N; -.
DR IntAct; P20248; 27.
DR MINT; MINT-141826; -.
DR STRING; 9606.ENSP00000274026; -.
DR BindingDB; P20248; -.
DR ChEMBL; CHEMBL2582; -.
DR PhosphoSite; P20248; -.
DR DMDM; 311033358; -.
DR PaxDb; P20248; -.
DR PRIDE; P20248; -.
DR Ensembl; ENST00000274026; ENSP00000274026; ENSG00000145386.
DR GeneID; 890; -.
DR KEGG; hsa:890; -.
DR UCSC; uc003iec.4; human.
DR CTD; 890; -.
DR GeneCards; GC04M122737; -.
DR HGNC; HGNC:1578; CCNA2.
DR HPA; CAB000114; -.
DR HPA; HPA020626; -.
DR MIM; 123835; gene.
DR neXtProt; NX_P20248; -.
DR PharmGKB; PA94; -.
DR eggNOG; COG5024; -.
DR HOGENOM; HOG000167672; -.
DR HOVERGEN; HBG106244; -.
DR InParanoid; P20248; -.
DR KO; K06627; -.
DR OMA; NPEKAAP; -.
DR OrthoDB; EOG7G7KQ0; -.
DR PhylomeDB; P20248; -.
DR Reactome; REACT_115566; Cell Cycle.
DR Reactome; REACT_120956; Cellular responses to stress.
DR Reactome; REACT_383; DNA Replication.
DR Reactome; REACT_6850; Cdc20:Phospho-APC/C mediated degradation of Cyclin A.
DR SignaLink; P20248; -.
DR EvolutionaryTrace; P20248; -.
DR GeneWiki; Cyclin_A2; -.
DR GenomeRNAi; 890; -.
DR NextBio; 3682; -.
DR PMAP-CutDB; P20248; -.
DR PRO; PR:P20248; -.
DR Bgee; P20248; -.
DR CleanEx; HS_CCNA2; -.
DR Genevestigator; P20248; -.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0001939; C:female pronucleus; IEA:Ensembl.
DR GO; GO:0001940; C:male pronucleus; IEA:Ensembl.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0000086; P:G2/M transition of mitotic cell cycle; TAS:Reactome.
DR GO; GO:0007067; P:mitosis; IEA:UniProtKB-KW.
DR GO; GO:0007095; P:mitotic G2 DNA damage checkpoint; TAS:ProtInc.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-dependent; IEA:Ensembl.
DR GO; GO:0007265; P:Ras protein signal transduction; IEP:BHF-UCL.
DR GO; GO:0000079; P:regulation of cyclin-dependent protein serine/threonine kinase activity; IEA:InterPro.
DR Gene3D; 1.10.472.10; -; 2.
DR InterPro; IPR013763; Cyclin-like.
DR InterPro; IPR014400; Cyclin_A/B/D/E.
DR InterPro; IPR004367; Cyclin_C-dom.
DR InterPro; IPR006671; Cyclin_N.
DR Pfam; PF02984; Cyclin_C; 1.
DR Pfam; PF00134; Cyclin_N; 1.
DR PIRSF; PIRSF001771; Cyclin_A_B_D_E; 1.
DR SMART; SM00385; CYCLIN; 2.
DR SUPFAM; SSF47954; SSF47954; 2.
DR PROSITE; PS00292; CYCLINS; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Cell cycle; Cell division;
KW Complete proteome; Cyclin; Cytoplasm; Mitosis; Nucleus;
KW Phosphoprotein; Polymorphism; Reference proteome; Ubl conjugation.
FT CHAIN 1 432 Cyclin-A2.
FT /FTId=PRO_0000080338.
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 5 5 Phosphoserine.
FT MOD_RES 55 55 Phosphoserine.
FT VARIANT 163 163 I -> V (in dbSNP:rs769242).
FT /FTId=VAR_018819.
FT CONFLICT 156 156 H -> R (in Ref. 3; CAG28620).
FT HELIX 176 178
FT HELIX 179 192
FT HELIX 199 202
FT HELIX 208 224
FT HELIX 229 243
FT HELIX 250 252
FT HELIX 253 268
FT STRAND 269 271
FT HELIX 275 281
FT TURN 282 284
FT HELIX 288 301
FT TURN 302 304
FT HELIX 311 319
FT STRAND 322 324
FT HELIX 327 342
FT HELIX 344 347
FT HELIX 352 368
FT HELIX 374 380
FT HELIX 384 400
FT HELIX 401 403
FT HELIX 408 412
FT STRAND 413 415
FT HELIX 416 418
FT HELIX 421 423
SQ SEQUENCE 432 AA; 48551 MW; 97763A2897DD35F4 CRC64;
MLGNSAPGPA TREAGSALLA LQQTALQEDQ ENINPEKAAP VQQPRTRAAL AVLKSGNPRG
LAQQQRPKTR RVAPLKDLPV NDEHVTVPPW KANSKQPAFT IHVDEAEKEA QKKPAESQKI
EREDALAFNS AISLPGPRKP LVPLDYPMDG SFESPHTMDM SIILEDEKPV SVNEVPDYHE
DIHTYLREME VKCKPKVGYM KKQPDITNSM RAILVDWLVE VGEEYKLQNE TLHLAVNYID
RFLSSMSVLR GKLQLVGTAA MLLASKFEEI YPPEVAEFVY ITDDTYTKKQ VLRMEHLVLK
VLTFDLAAPT VNQFLTQYFL HQQPANCKVE SLAMFLGELS LIDADPYLKY LPSVIAGAAF
HLALYTVTGQ SWPESLIRKT GYTLESLKPC LMDLHQTYLK APQHAQQSIR EKYKNSKYHG
VSLLNPPETL NL
//
MIM
123835
*RECORD*
*FIELD* NO
123835
*FIELD* TI
*123835 CYCLIN A2; CCNA2
;;CYCLIN A; CCNA
*FIELD* TX
DESCRIPTION
Cyclin A2 is an essential component of all embryonic and somatic cell
read morecycles in mammals (Murphy et al., 1997).
CLONING
Wang et al. (1990) cloned a single hepatitis B virus integration site in
a human hepatocellular carcinoma at an early stage of development, and
also cloned its germline counterpart. The normal locus was found to be
transcribed into 2 polyadenylated mRNA species of 1.8 and 2.7 kb. Wang
et al. (1990) isolated a cDNA clone from a normal adult human liver that
had an open reading frame with a coding capacity for a protein of 432
amino acids and relative molecular mass of 48,536. Strong homologies in
amino acid sequence identified the protein as a human cyclin A. The HBV
integration was found to have occurred within an intron.
GENE FUNCTION
Wang et al. (1990) suggested that disruption of the cyclin A gene by
viral insertion was responsible for tumorigenesis. Cyclins are highly
conserved proteins associated with proliferating cells. They show a
steady accumulation throughout interphase until the G2/M transition,
followed by rapid disappearance at the onset of anaphase. They are
highly conserved in evolution, having been identified in yeast, clam,
starfish, sea urchin, and Drosophila. Two groups of cyclins, A and B,
are distinguished on the basis of their sequence and pattern of
accumulation during the cell cycle. Both cyclins will complex with and
activate the serine-threonine kinase p34(cdc2) during the G2/M phase
transition; see 116940. Cyclins are also referred to as proliferating
cell nuclear antigens (176740). Nonrandom integration of HBV in
hepatocellular carcinoma has been related to chromosome 11 (114550) and
to chromosome 4 (123835). Furthermore, interruption of the coding region
of the gene for retinoic acid receptor beta (RARB; 180220) by viral DNA
has been reported (summary by Wang et al., 1990).
Girard et al. (1991) showed that cyclin A protein is synthesized and
localized into the nucleus at the onset of S phase in nontransformed
mammalian fibroblasts. Inhibition of cyclin A synthesis or activity
through microinjection of plasmids encoding antisense cyclin A cDNA or
affinity-purified anti-cyclin A antibodies during G1 phase abolished the
nuclear staining for cyclin A and inhibited DNA synthesis. No similar
effect was observed with injection of other antisense vectors, including
antisense cyclin B. Girard et al. (1991) suggested that cyclin A plays a
major role in the control of DNA replication. Henglein et al. (1994)
cloned and sequenced the human CCNA gene and cDNAs representing its
mRNAs and characterized its promoter. Using synchronized cultures of NIH
3T3 cells stably transfected with cyclin A promoter/luciferase
constructs, they showed that the promoter is repressed during the G1
phase of the cell cycle and is activated at S-phase entry. Cell cycle
regulation of the CCNA promoter is mediated by sequences extending from
-79 to +100 relative to the predominant transcription start site. The
presence of a functional retinoblastoma protein is not required.
Hunter and Pines (1991) gave a review of the role of cyclins in cancer.
Kabeche and Compton (2013) found that kinetochore-microtubule (k-MT)
attachments in prometaphase cells are considerably less stable than in
metaphase cells, and that the switch to more stable k-MT attachments in
metaphase requires the proteasome-dependent destruction of cyclin A in
prometaphase. Persistent cyclin A expression prevents k-MT stabilization
even in cells with aligned chromosomes. By contrast, k-MTs are
prematurely stabilized in cyclin A-deficient cells. Consequently, cells
lacking cyclin A display higher rates of chromosome missegregation.
Thus, the stability of k-MT attachments increases decisively in a
coordinated fashion among all chromosomes as cells transit from
prometaphase to metaphase. Cyclin A creates a cellular environment that
promotes microtubule detachment from kinetochores in prometaphase to
ensure efficient error correction and faithful chromosome segregation.
MAPPING
By in situ hybridization, Blanquet et al. (1990) mapped the CCNA gene to
4q26-q27. They pointed to the interest of this finding in connection
with the demonstrated loss of heterozygosity for markers on 4q in tumor
tissue of patients with liver cancer (Buetow et al., 1989). By genetic
mapping using a cyclin A probe, Lock et al. (1992) demonstrated a single
Cyca gene on mouse chromosome 3.
ANIMAL MODEL
The mammalian A-type cyclin family consists of 2 members, cyclin A1
(CCNA1; 604036) and cyclin A2 (CCNA2). Cyclin A2 promotes both G1/S and
G2/M transitions (Pagano et al., 1992). Murphy et al. (1997)
demonstrated that a targeted deletion of the murine Ccna2 gene is
embryonically lethal, although homozygous null mutant embryos developed
normally until postimplantation, approximately day 5.5 postcoitum. The
authors suggested that the embryos survived either because a maternal
pool of cyclin A2 protein persists until at least the blastocyst stage,
or because cyclin A1 plays an unexpected role during early embryo
development. In an erratum, the authors stated that maternal cyclin A2
cannot be considered to persist to the blastocyst stage during early
mouse development. Cyclin A1 is expressed in mice exclusively in the
germline lineage (Sweeney et al., 1996) and is expressed in humans at
highest levels in the testis and certain myeloid leukemia cells (Yang et
al., 1997).
*FIELD* RF
1. Blanquet, V.; Wang, J.; Chenivesse, X.; Henglein, B.; Garreau,
F.; Brechot, C.; Turleau, C.: Assignment of a human cyclin A gene
to 4q26-q27. Genomics 8: 595-597, 1990.
2. Buetow, K. H.; Murray, J. E.; Israel, J. L.; London, W. T.; Smith,
M.; Kew, M.; Blanquet, V.; Brechot, C.; Redeker, A.; Govindarajah,
S.: Loss of heterozygosity suggests tumor suppressor gene responsible
for primary hepatocellular carcinoma. Proc. Nat. Acad. Sci. 86:
8852-8856, 1989.
3. Girard, F.; Strausfeld, U.; Fernandez, A.; Lamb, N. J. C.: Cyclin
A is required for the onset of DNA replication in mammalian fibroblasts. Cell 67:
1169-1179, 1991.
4. Henglein, B.; Chenivesse, X.; Wang, J.; Eick, D.; Brechot, C.:
Structure and cell cycle-regulated transcription of the human cyclin
A gene. Proc. Nat. Acad. Sci. 91: 5490-5494, 1994.
5. Hunter, T.; Pines, J.: Cyclins and cancer. Cell 66: 1071-1074,
1991.
6. Kabeche, L.; Compton, D. A.: Cyclin A regulates kinetochore microtubules
to promote faithful chromosome segregation. Nature 502: 110-113,
2013.
7. Lock, L. F.; Pines, J.; Hunter, T.; Gilbert, D. J.; Gopalan, G.;
Jenkins, N. A.; Copeland, N. G.; Donovan, P. J.: A single cyclin
A gene and multiple cyclin B1-related sequences are dispersed in the
mouse genome. Genomics 13: 415-424, 1992.
8. Murphy, M.; Stinnakre, M. G.; Senamaud-Beaufort, C.; Winston, N.
J.; Sweeney, C.; Kubelka, M.; Carrington, M.; Brechot, C.; Sobczak-Thepot,
J.: Delayed early embryonic lethality following disruption of the
murine cyclin A2 gene. Nature Genet. 15: 83-86, 1997. Note: Erratum:
Nature Genet. 23: 481 only, 1999.
9. Pagano, M.; Pepperkok, R.; Verde, F.; Ansorge, W.; Draetta, G.
: Cyclin A is required at two points in the human cell cycle. EMBO
J. 11: 961-971, 1992.
10. Sweeney, C.; Murphy, M.; Kubelka, M.; Ravnik. S. E.; Hawkins,
C. F.; Wolgenmuth, D. J.; Carrington, M.: A distinct cyclin A is
expressed in germ cells in the mouse. Development 122: 53-64, 1996.
11. Wang, J.; Chenivesse, X.; Henglein, B.; Brechot, C.: Hepatitis
B virus integration in a cyclin A gene in a hepatocellular carcinoma. Nature 343:
555-557, 1990.
12. Yang, R.; Morosetti, R.; Koeffler, H. P.: Characterization of
a second human cyclin A that is highly expressed in testis and in
several leukemic cell lines. Cancer Res. 57: 913-920, 1997.
*FIELD* CN
Ada Hamosh - updated: 12/05/2013
Rebekah S. Rasooly - updated: 7/21/1999
Victor A. McKusick - updated: 11/30/1998
*FIELD* CD
Victor A. McKusick: 2/27/1990
*FIELD* ED
alopez: 12/05/2013
carol: 12/17/2012
alopez: 2/23/2011
terry: 5/20/2010
terry: 1/22/2001
mgross: 7/21/1999
dkim: 12/2/1998
alopez: 12/1/1998
terry: 11/30/1998
carol: 6/28/1994
jason: 6/22/1994
carol: 3/9/1993
carol: 6/24/1992
supermim: 3/16/1992
carol: 2/17/1992
*RECORD*
*FIELD* NO
123835
*FIELD* TI
*123835 CYCLIN A2; CCNA2
;;CYCLIN A; CCNA
*FIELD* TX
DESCRIPTION
Cyclin A2 is an essential component of all embryonic and somatic cell
read morecycles in mammals (Murphy et al., 1997).
CLONING
Wang et al. (1990) cloned a single hepatitis B virus integration site in
a human hepatocellular carcinoma at an early stage of development, and
also cloned its germline counterpart. The normal locus was found to be
transcribed into 2 polyadenylated mRNA species of 1.8 and 2.7 kb. Wang
et al. (1990) isolated a cDNA clone from a normal adult human liver that
had an open reading frame with a coding capacity for a protein of 432
amino acids and relative molecular mass of 48,536. Strong homologies in
amino acid sequence identified the protein as a human cyclin A. The HBV
integration was found to have occurred within an intron.
GENE FUNCTION
Wang et al. (1990) suggested that disruption of the cyclin A gene by
viral insertion was responsible for tumorigenesis. Cyclins are highly
conserved proteins associated with proliferating cells. They show a
steady accumulation throughout interphase until the G2/M transition,
followed by rapid disappearance at the onset of anaphase. They are
highly conserved in evolution, having been identified in yeast, clam,
starfish, sea urchin, and Drosophila. Two groups of cyclins, A and B,
are distinguished on the basis of their sequence and pattern of
accumulation during the cell cycle. Both cyclins will complex with and
activate the serine-threonine kinase p34(cdc2) during the G2/M phase
transition; see 116940. Cyclins are also referred to as proliferating
cell nuclear antigens (176740). Nonrandom integration of HBV in
hepatocellular carcinoma has been related to chromosome 11 (114550) and
to chromosome 4 (123835). Furthermore, interruption of the coding region
of the gene for retinoic acid receptor beta (RARB; 180220) by viral DNA
has been reported (summary by Wang et al., 1990).
Girard et al. (1991) showed that cyclin A protein is synthesized and
localized into the nucleus at the onset of S phase in nontransformed
mammalian fibroblasts. Inhibition of cyclin A synthesis or activity
through microinjection of plasmids encoding antisense cyclin A cDNA or
affinity-purified anti-cyclin A antibodies during G1 phase abolished the
nuclear staining for cyclin A and inhibited DNA synthesis. No similar
effect was observed with injection of other antisense vectors, including
antisense cyclin B. Girard et al. (1991) suggested that cyclin A plays a
major role in the control of DNA replication. Henglein et al. (1994)
cloned and sequenced the human CCNA gene and cDNAs representing its
mRNAs and characterized its promoter. Using synchronized cultures of NIH
3T3 cells stably transfected with cyclin A promoter/luciferase
constructs, they showed that the promoter is repressed during the G1
phase of the cell cycle and is activated at S-phase entry. Cell cycle
regulation of the CCNA promoter is mediated by sequences extending from
-79 to +100 relative to the predominant transcription start site. The
presence of a functional retinoblastoma protein is not required.
Hunter and Pines (1991) gave a review of the role of cyclins in cancer.
Kabeche and Compton (2013) found that kinetochore-microtubule (k-MT)
attachments in prometaphase cells are considerably less stable than in
metaphase cells, and that the switch to more stable k-MT attachments in
metaphase requires the proteasome-dependent destruction of cyclin A in
prometaphase. Persistent cyclin A expression prevents k-MT stabilization
even in cells with aligned chromosomes. By contrast, k-MTs are
prematurely stabilized in cyclin A-deficient cells. Consequently, cells
lacking cyclin A display higher rates of chromosome missegregation.
Thus, the stability of k-MT attachments increases decisively in a
coordinated fashion among all chromosomes as cells transit from
prometaphase to metaphase. Cyclin A creates a cellular environment that
promotes microtubule detachment from kinetochores in prometaphase to
ensure efficient error correction and faithful chromosome segregation.
MAPPING
By in situ hybridization, Blanquet et al. (1990) mapped the CCNA gene to
4q26-q27. They pointed to the interest of this finding in connection
with the demonstrated loss of heterozygosity for markers on 4q in tumor
tissue of patients with liver cancer (Buetow et al., 1989). By genetic
mapping using a cyclin A probe, Lock et al. (1992) demonstrated a single
Cyca gene on mouse chromosome 3.
ANIMAL MODEL
The mammalian A-type cyclin family consists of 2 members, cyclin A1
(CCNA1; 604036) and cyclin A2 (CCNA2). Cyclin A2 promotes both G1/S and
G2/M transitions (Pagano et al., 1992). Murphy et al. (1997)
demonstrated that a targeted deletion of the murine Ccna2 gene is
embryonically lethal, although homozygous null mutant embryos developed
normally until postimplantation, approximately day 5.5 postcoitum. The
authors suggested that the embryos survived either because a maternal
pool of cyclin A2 protein persists until at least the blastocyst stage,
or because cyclin A1 plays an unexpected role during early embryo
development. In an erratum, the authors stated that maternal cyclin A2
cannot be considered to persist to the blastocyst stage during early
mouse development. Cyclin A1 is expressed in mice exclusively in the
germline lineage (Sweeney et al., 1996) and is expressed in humans at
highest levels in the testis and certain myeloid leukemia cells (Yang et
al., 1997).
*FIELD* RF
1. Blanquet, V.; Wang, J.; Chenivesse, X.; Henglein, B.; Garreau,
F.; Brechot, C.; Turleau, C.: Assignment of a human cyclin A gene
to 4q26-q27. Genomics 8: 595-597, 1990.
2. Buetow, K. H.; Murray, J. E.; Israel, J. L.; London, W. T.; Smith,
M.; Kew, M.; Blanquet, V.; Brechot, C.; Redeker, A.; Govindarajah,
S.: Loss of heterozygosity suggests tumor suppressor gene responsible
for primary hepatocellular carcinoma. Proc. Nat. Acad. Sci. 86:
8852-8856, 1989.
3. Girard, F.; Strausfeld, U.; Fernandez, A.; Lamb, N. J. C.: Cyclin
A is required for the onset of DNA replication in mammalian fibroblasts. Cell 67:
1169-1179, 1991.
4. Henglein, B.; Chenivesse, X.; Wang, J.; Eick, D.; Brechot, C.:
Structure and cell cycle-regulated transcription of the human cyclin
A gene. Proc. Nat. Acad. Sci. 91: 5490-5494, 1994.
5. Hunter, T.; Pines, J.: Cyclins and cancer. Cell 66: 1071-1074,
1991.
6. Kabeche, L.; Compton, D. A.: Cyclin A regulates kinetochore microtubules
to promote faithful chromosome segregation. Nature 502: 110-113,
2013.
7. Lock, L. F.; Pines, J.; Hunter, T.; Gilbert, D. J.; Gopalan, G.;
Jenkins, N. A.; Copeland, N. G.; Donovan, P. J.: A single cyclin
A gene and multiple cyclin B1-related sequences are dispersed in the
mouse genome. Genomics 13: 415-424, 1992.
8. Murphy, M.; Stinnakre, M. G.; Senamaud-Beaufort, C.; Winston, N.
J.; Sweeney, C.; Kubelka, M.; Carrington, M.; Brechot, C.; Sobczak-Thepot,
J.: Delayed early embryonic lethality following disruption of the
murine cyclin A2 gene. Nature Genet. 15: 83-86, 1997. Note: Erratum:
Nature Genet. 23: 481 only, 1999.
9. Pagano, M.; Pepperkok, R.; Verde, F.; Ansorge, W.; Draetta, G.
: Cyclin A is required at two points in the human cell cycle. EMBO
J. 11: 961-971, 1992.
10. Sweeney, C.; Murphy, M.; Kubelka, M.; Ravnik. S. E.; Hawkins,
C. F.; Wolgenmuth, D. J.; Carrington, M.: A distinct cyclin A is
expressed in germ cells in the mouse. Development 122: 53-64, 1996.
11. Wang, J.; Chenivesse, X.; Henglein, B.; Brechot, C.: Hepatitis
B virus integration in a cyclin A gene in a hepatocellular carcinoma. Nature 343:
555-557, 1990.
12. Yang, R.; Morosetti, R.; Koeffler, H. P.: Characterization of
a second human cyclin A that is highly expressed in testis and in
several leukemic cell lines. Cancer Res. 57: 913-920, 1997.
*FIELD* CN
Ada Hamosh - updated: 12/05/2013
Rebekah S. Rasooly - updated: 7/21/1999
Victor A. McKusick - updated: 11/30/1998
*FIELD* CD
Victor A. McKusick: 2/27/1990
*FIELD* ED
alopez: 12/05/2013
carol: 12/17/2012
alopez: 2/23/2011
terry: 5/20/2010
terry: 1/22/2001
mgross: 7/21/1999
dkim: 12/2/1998
alopez: 12/1/1998
terry: 11/30/1998
carol: 6/28/1994
jason: 6/22/1994
carol: 3/9/1993
carol: 6/24/1992
supermim: 3/16/1992
carol: 2/17/1992