ID CCNA2_MOUSE Reviewed; 422 AA. AC P51943; Q61459; Q8BRG1; DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot. DT 27-JUL-2011, sequence version 2. DT 24-JAN-2024, entry version 178. DE RecName: Full=Cyclin-A2 {ECO:0000303|PubMed:8575639}; DE Short=Cyclin-A {ECO:0000303|PubMed:8565853}; GN Name=Ccna2 {ECO:0000312|MGI:MGI:108069}; GN Synonyms=Ccna, Cyca, Cyca2 {ECO:0000303|PubMed:8575639}; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE. RX PubMed=8575639; DOI=10.1006/dbio.1996.0007; RA Ravnik S.E., Wolgemuth D.J.; RT "The developmentally restricted pattern of expression in the male germ line RT of a murine cyclin A, cyclin A2, suggests roles in both mitotic and meiotic RT cell cycles."; RL Dev. Biol. 173:69-78(1996). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE. RC TISSUE=Thymus; RX PubMed=8565853; DOI=10.1242/dev.122.1.53; RA Sweeney C., Murphy M., Kubelka M., Ravnik S.E., Hawkins C.F., RA Wolgemuth D.J., Carrington M.; RT "A distinct cyclin A is expressed in germ cells in the mouse."; RL Development 122:53-64(1996). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=C57BL/6J; TISSUE=Embryo; RX PubMed=16141072; DOI=10.1126/science.1112014; RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J., RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. 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 project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP INTERACTION WITH CDK2, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND RP DEVELOPMENTAL STAGE. RC STRAIN=Swiss Webster; RX PubMed=10068472; DOI=10.1006/dbio.1998.9156; RA Ravnik S.E., Wolgemuth D.J.; RT "Regulation of meiosis during mammalian spermatogenesis: the A-type cyclins RT and their associated cyclin-dependent kinases are differentially expressed RT in the germ-cell lineage."; RL Dev. Biol. 207:408-418(1999). RN [7] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Spleen; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). RN [8] RP SUBCELLULAR LOCATION, AND INTERACTION WITH MOUSE CYTOMEGALOVIRUS KINASE M97 RP (MICROBIAL INFECTION). RX PubMed=32973148; DOI=10.1038/s41467-020-18542-1; RA Bogdanow B., Schmidt M., Weisbach H., Gruska I., Vetter B., Imami K., RA Ostermann E., Brune W., Selbach M., Hagemeier C., Wiebusch L.; RT "Cross-regulation of viral kinases with cyclin A secures shutoff of host RT DNA synthesis."; RL Nat. Commun. 11:4845-4845(2020). CC -!- FUNCTION: Cyclin which controls both the G1/S and the G2/M transition CC phases of the cell cycle. Functions through the formation of specific CC serine/threonine kinase holoenzyme complexes with the cyclin-dependent CC protein kinases CDK1 and CDK2. The cyclin subunit confers the substrate CC specificity of these complexes and differentially interacts with and CC activates CDK1 and CDK2 throughout the cell cycle. CC {ECO:0000250|UniProtKB:P20248}. CC -!- SUBUNIT: Interacts with the CDK1 and CDK2 protein kinases to form CC serine/threonine kinase holoenzyme complexes (PubMed:10068472). CC Interacts with CDK1 (hyperphosphorylated form in G1 and CC underphosphorylated forms in S and G2). Interacts with CDK2; the CC interaction increases from G1 to G2. Interacts (associated with CDK2 CC but not with CDK1) with SCAPER; regulates the activity of CCNA2/CDK2 by CC transiently maintaining CCNA2 in the cytoplasm. Forms a ternary complex CC with CDK2 and CDKN1B; CDKN1B inhibits the kinase activity of CDK2 CC through conformational rearrangements (By similarity). Interacts with CC INCA1 (By similarity). {ECO:0000250|UniProtKB:P20248, CC ECO:0000269|PubMed:10068472}. CC -!- SUBUNIT: (Microbial infection) Interacts with mouse CC cytomegalovirus/MCMV kinase M97; this interaction sequesters CCNA2 to CC the cytoplasm. {ECO:0000269|PubMed:32973148}. CC -!- INTERACTION: CC P51943; P11440: Cdk1; NbExp=2; IntAct=EBI-846980, EBI-846949; CC P51943; P97377: Cdk2; NbExp=3; IntAct=EBI-846980, EBI-847048; CC P51943; P24941: CDK2; Xeno; NbExp=2; IntAct=EBI-846980, EBI-375096; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:32973148}. Cytoplasm CC {ECO:0000269|PubMed:32973148}. Note=Exclusively nuclear during CC interphase. Detected in the nucleus and the cytoplasm at prophase. CC Cytoplasmic when associated with SCAPER. CC {ECO:0000250|UniProtKB:P20248}. CC -!- TISSUE SPECIFICITY: Ubiquitous (PubMed:8565853). In the testis, CC expressed in germ cells and in the ovary, in both germline and somatic CC cells (PubMed:8575639, PubMed:10068472). {ECO:0000269|PubMed:10068472, CC ECO:0000269|PubMed:8565853, ECO:0000269|PubMed:8575639}. CC -!- DEVELOPMENTAL STAGE: Accumulates steadily during G2 and is abruptly CC destroyed at mitosis. Expressed in spermatogonia and is most abundant CC in preleptotene spermatocytes, cells which will enter the meiotic CC pathway. {ECO:0000269|PubMed:10068472, ECO:0000269|PubMed:8565853, CC ECO:0000269|PubMed:8575639}. CC -!- PTM: Polyubiquitinated via 'Lys-11'-linked ubiquitin by the anaphase- CC promoting complex (APC/C), leading to its degradation by the CC proteasome. Deubiquitinated and stabilized by USP37 enables entry into CC S phase. {ECO:0000250|UniProtKB:P20248}. CC -!- SIMILARITY: Belongs to the cyclin family. Cyclin AB subfamily. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; Z26580; CAA81331.1; -; mRNA. DR EMBL; X75483; CAA53212.1; -; mRNA. DR EMBL; AK044924; BAC32144.1; -; mRNA. DR EMBL; CH466530; EDL35081.1; -; Genomic_DNA. DR EMBL; BC052730; AAH52730.1; -; mRNA. DR CCDS; CCDS17313.1; -. DR PIR; S37280; S37280. DR PIR; S38501; S38501. DR RefSeq; NP_033958.2; NM_009828.2. DR RefSeq; XP_017174933.1; XM_017319444.1. DR PDB; 3QHR; X-ray; 2.17 A; B/D=163-422. DR PDB; 3QHW; X-ray; 1.91 A; B/D=163-422. DR PDB; 4I3Z; X-ray; 2.05 A; B/D=165-421. DR PDB; 4II5; X-ray; 2.15 A; B/D=165-422. DR PDBsum; 3QHR; -. DR PDBsum; 3QHW; -. DR PDBsum; 4I3Z; -. DR PDBsum; 4II5; -. DR AlphaFoldDB; P51943; -. DR SMR; P51943; -. DR BioGRID; 198545; 12. DR ComplexPortal; CPX-2062; Cyclin A2-CDK1 complex. DR ComplexPortal; CPX-2066; Cyclin A2-CDK2 complex. DR CORUM; P51943; -. DR DIP; DIP-45864N; -. DR IntAct; P51943; 4. DR STRING; 10090.ENSMUSP00000029270; -. DR iPTMnet; P51943; -. DR PhosphoSitePlus; P51943; -. DR EPD; P51943; -. DR MaxQB; P51943; -. DR PaxDb; 10090-ENSMUSP00000029270; -. DR PeptideAtlas; P51943; -. DR ProteomicsDB; 280010; -. DR Pumba; P51943; -. DR Antibodypedia; 3665; 863 antibodies from 44 providers. DR DNASU; 12428; -. DR Ensembl; ENSMUST00000029270.10; ENSMUSP00000029270.4; ENSMUSG00000027715.10. DR GeneID; 12428; -. DR KEGG; mmu:12428; -. DR UCSC; uc012cov.1; mouse. DR AGR; MGI:108069; -. DR CTD; 890; -. DR MGI; MGI:108069; Ccna2. DR VEuPathDB; HostDB:ENSMUSG00000027715; -. DR eggNOG; KOG0654; Eukaryota. DR GeneTree; ENSGT00940000155372; -. DR HOGENOM; CLU_020695_3_2_1; -. DR InParanoid; P51943; -. DR OMA; HQPFSIH; -. DR OrthoDB; 5474295at2759; -. DR PhylomeDB; P51943; -. DR TreeFam; TF101002; -. DR Reactome; R-MMU-1538133; G0 and Early G1. DR Reactome; R-MMU-171319; Telomere Extension By Telomerase. DR Reactome; R-MMU-174184; Cdc20:Phospho-APC/C mediated degradation of Cyclin A. DR Reactome; R-MMU-176408; Regulation of APC/C activators between G1/S and early anaphase. DR Reactome; R-MMU-187577; SCF(Skp2)-mediated degradation of p27/p21. DR Reactome; R-MMU-2559582; Senescence-Associated Secretory Phenotype (SASP). DR Reactome; R-MMU-2559586; DNA Damage/Telomere Stress Induced Senescence. DR Reactome; R-MMU-5689880; Ub-specific processing proteases. DR Reactome; R-MMU-5693607; Processing of DNA double-strand break ends. DR Reactome; R-MMU-6804116; TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest. DR Reactome; R-MMU-6804756; Regulation of TP53 Activity through Phosphorylation. DR Reactome; R-MMU-6804757; Regulation of TP53 Degradation. DR Reactome; R-MMU-68911; G2 Phase. DR Reactome; R-MMU-68949; Orc1 removal from chromatin. DR Reactome; R-MMU-69017; CDK-mediated phosphorylation and removal of Cdc6. DR Reactome; R-MMU-69273; Cyclin A/B1/B2 associated events during G2/M transition. DR Reactome; R-MMU-69563; p53-Dependent G1 DNA Damage Response. DR Reactome; R-MMU-69656; Cyclin A:Cdk2-associated events at S phase entry. DR BioGRID-ORCS; 12428; 25 hits in 79 CRISPR screens. DR ChiTaRS; Ccna2; mouse. DR PRO; PR:P51943; -. DR Proteomes; UP000000589; Chromosome 3. DR RNAct; P51943; Protein. DR Bgee; ENSMUSG00000027715; Expressed in fetal liver hematopoietic progenitor cell and 221 other cell types or tissues. DR ExpressionAtlas; P51943; baseline and differential. DR GO; GO:0097122; C:cyclin A2-CDK1 complex; IPI:ComplexPortal. DR GO; GO:0097124; C:cyclin A2-CDK2 complex; IDA:MGI. DR GO; GO:0000307; C:cyclin-dependent protein kinase holoenzyme complex; ISO:MGI. DR GO; GO:0005737; C:cytoplasm; IDA:MGI. DR GO; GO:0005829; C:cytosol; ISO:MGI. DR GO; GO:0001939; C:female pronucleus; IDA:MGI. DR GO; GO:0001940; C:male pronucleus; IDA:MGI. DR GO; GO:0005654; C:nucleoplasm; ISO:MGI. DR GO; GO:0005634; C:nucleus; IDA:MGI. DR GO; GO:0016538; F:cyclin-dependent protein serine/threonine kinase regulator activity; ISS:UniProtKB. DR GO; GO:0019904; F:protein domain specific binding; ISO:MGI. DR GO; GO:0019901; F:protein kinase binding; IPI:MGI. DR GO; GO:0031100; P:animal organ regeneration; IEA:Ensembl. DR GO; GO:0044843; P:cell cycle G1/S phase transition; ISS:UniProtKB. DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW. DR GO; GO:0071314; P:cellular response to cocaine; IEA:Ensembl. DR GO; GO:0071392; P:cellular response to estradiol stimulus; IEA:Ensembl. DR GO; GO:0071456; P:cellular response to hypoxia; IEA:Ensembl. DR GO; GO:1990314; P:cellular response to insulin-like growth factor stimulus; IEA:Ensembl. DR GO; GO:0044320; P:cellular response to leptin stimulus; IEA:Ensembl. DR GO; GO:0071373; P:cellular response to luteinizing hormone stimulus; IEA:Ensembl. DR GO; GO:0071732; P:cellular response to nitric oxide; IEA:Ensembl. DR GO; GO:0036120; P:cellular response to platelet-derived growth factor stimulus; IEA:Ensembl. DR GO; GO:0090102; P:cochlea development; IEA:Ensembl. DR GO; GO:0006351; P:DNA-templated transcription; IMP:MGI. DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; NAS:ComplexPortal. DR GO; GO:0000086; P:G2/M transition of mitotic cell cycle; ISS:UniProtKB. DR GO; GO:0044772; P:mitotic cell cycle phase transition; IBA:GO_Central. DR GO; GO:2000573; P:positive regulation of DNA biosynthetic process; ISO:MGI. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IMP:MGI. DR GO; GO:0048146; P:positive regulation of fibroblast proliferation; ISO:MGI. DR GO; GO:0043687; P:post-translational protein modification; ISO:MGI. DR GO; GO:0007265; P:Ras protein signal transduction; IEA:Ensembl. DR GO; GO:0006275; P:regulation of DNA replication; ISS:UniProtKB. DR GO; GO:0033762; P:response to glucagon; IEA:Ensembl. DR CDD; cd20561; CYCLIN_CCNA2_rpt1; 1. DR CDD; cd20564; CYCLIN_CCNA2_rpt2; 1. DR Gene3D; 1.10.472.10; Cyclin-like; 2. DR IDEAL; IID50253; -. DR InterPro; IPR039361; Cyclin. DR InterPro; IPR032447; Cyclin-A_N. DR InterPro; IPR013763; Cyclin-like_dom. DR InterPro; IPR036915; Cyclin-like_sf. DR InterPro; IPR046965; Cyclin_A/B-like. DR InterPro; IPR004367; Cyclin_C-dom. DR InterPro; IPR006671; Cyclin_N. DR InterPro; IPR048258; Cyclins_cyclin-box. DR PANTHER; PTHR10177:SF444; CYCLIN-A2; 1. DR PANTHER; PTHR10177; CYCLINS; 1. DR Pfam; PF02984; Cyclin_C; 1. DR Pfam; PF00134; Cyclin_N; 1. DR Pfam; PF16500; Cyclin_N2; 1. DR PIRSF; PIRSF001771; Cyclin_A_B_D_E; 1. DR SMART; SM00385; CYCLIN; 2. DR SMART; SM01332; Cyclin_C; 1. DR SUPFAM; SSF47954; Cyclin-like; 2. DR PROSITE; PS00292; CYCLINS; 1. DR Genevisible; P51943; MM. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Cell cycle; Cell division; Cyclin; Cytoplasm; KW Mitosis; Nucleus; Phosphoprotein; Reference proteome; Ubl conjugation. FT CHAIN 1..422 FT /note="Cyclin-A2" FT /id="PRO_0000080340" FT REGION 1..62 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 1 FT /note="N-acetylmethionine" FT /evidence="ECO:0000250|UniProtKB:P20248" FT MOD_RES 5 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P20248" FT CONFLICT 127 FT /note="G -> A (in Ref. 1; CAA81331 and 2; CAA53212)" FT /evidence="ECO:0000305" FT CONFLICT 391 FT /note="A -> P (in Ref. 2; CAA53212)" FT /evidence="ECO:0000305" FT HELIX 166..182 FT /evidence="ECO:0007829|PDB:3QHW" FT HELIX 189..192 FT /evidence="ECO:0007829|PDB:3QHW" FT HELIX 198..214 FT /evidence="ECO:0007829|PDB:3QHW" FT HELIX 219..235 FT /evidence="ECO:0007829|PDB:3QHW" FT HELIX 240..242 FT /evidence="ECO:0007829|PDB:3QHW" FT HELIX 243..258 FT /evidence="ECO:0007829|PDB:3QHW" FT HELIX 265..271 FT /evidence="ECO:0007829|PDB:3QHW" FT STRAND 274..276 FT /evidence="ECO:0007829|PDB:3QHW" FT HELIX 278..291 FT /evidence="ECO:0007829|PDB:3QHW" FT TURN 292..294 FT /evidence="ECO:0007829|PDB:3QHW" FT HELIX 301..308 FT /evidence="ECO:0007829|PDB:3QHW" FT HELIX 309..311 FT /evidence="ECO:0007829|PDB:3QHW" FT STRAND 312..314 FT /evidence="ECO:0007829|PDB:3QHW" FT HELIX 317..332 FT /evidence="ECO:0007829|PDB:3QHW" FT HELIX 334..337 FT /evidence="ECO:0007829|PDB:3QHW" FT HELIX 342..358 FT /evidence="ECO:0007829|PDB:3QHW" FT HELIX 364..370 FT /evidence="ECO:0007829|PDB:3QHW" FT HELIX 374..390 FT /evidence="ECO:0007829|PDB:3QHW" FT HELIX 391..393 FT /evidence="ECO:0007829|PDB:3QHW" FT HELIX 398..402 FT /evidence="ECO:0007829|PDB:3QHW" FT HELIX 406..408 FT /evidence="ECO:0007829|PDB:3QHW" FT HELIX 411..413 FT /evidence="ECO:0007829|PDB:3QHW" SQ SEQUENCE 422 AA; 47269 MW; 1818B92552E4D0D1 CRC64; MPGTSRHSGR DAGSALLSLH QEDQENVNPE KLAPAQQPRA QAVLKAGNVR GPAPQQKLKT RRVAPLKDLP INDEHVTAGP SWKAVSKQPA FTIHVDEAEE TQKRPAELKE TECEDALAFN AAVSLPGARK PLTPLDYPMD GSFESPHAMD MSIVLEDKPV NVNEVPDYQE DIHTYLREME VKCKPKVGYM KRQPDITNSM RAILVDWLVE VGEEYKLQNE TLHLAVNYID RFLSSMSVLR GKLQLVGTAA MLLASKFEEI YPPEVAEFVY ITDDTYSKKQ VLRMEHLVLK VLAFDLAAPT VNQFLTQYFL HLQPANCKVE SLAMFLGELS LIDADPYLKY LPSLIAGAAF HLALYTVTGQ SWPESLAQQT GYTLESLKPC LVDLHQTYLK APQHAQQSIR EKYKHSKYHS VSLLNPPETL SV //