CCNA2_MOUSE
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 03-AUG-2022, entry version 170.
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}.
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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; 11.
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; P51943; -.
DR PeptideAtlas; P51943; -.
DR PRIDE; P51943; -.
DR ProteomicsDB; 280010; -.
DR Antibodypedia; 3665; 787 antibodies from 44 providers.
DR DNASU; 12428; -.
DR Ensembl; ENSMUST00000029270; ENSMUSP00000029270; ENSMUSG00000027715.
DR GeneID; 12428; -.
DR KEGG; mmu:12428; -.
DR UCSC; uc012cov.1; mouse.
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; QDLHQTY; -.
DR OrthoDB; 993640at2759; -.
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 74 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 218 other tissues.
DR ExpressionAtlas; P51943; baseline and differential.
DR Genevisible; P51943; MM.
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:0000086; P:G2/M transition of mitotic cell cycle; ISS:UniProtKB.
DR GO; GO:0016572; P:histone phosphorylation; ISO:MGI.
DR GO; GO:0044772; P:mitotic cell cycle phase transition; IBA:GO_Central.
DR GO; GO:0048146; P:positive regulation of fibroblast proliferation; ISO:MGI.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IMP:MGI.
DR GO; GO:0007265; P:Ras protein signal transduction; IEA:Ensembl.
DR GO; GO:0000079; P:regulation of cyclin-dependent protein serine/threonine kinase activity; IBA:GO_Central.
DR GO; GO:0006275; P:regulation of DNA replication; ISS:UniProtKB.
DR GO; GO:0033762; P:response to glucagon; IEA:Ensembl.
DR GO; GO:0006351; P:transcription, DNA-templated; IMP:MGI.
DR CDD; cd00043; CYCLIN; 2.
DR IDEAL; IID50253; -.
DR InterPro; IPR039361; Cyclin.
DR InterPro; IPR032447; Cyclin-A_N.
DR InterPro; IPR013763; Cyclin-like.
DR InterPro; IPR036915; Cyclin-like_sf.
DR InterPro; IPR004367; Cyclin_C-dom.
DR InterPro; IPR006671; Cyclin_N.
DR PANTHER; PTHR10177; PTHR10177; 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; SSF47954; 2.
DR PROSITE; PS00292; CYCLINS; 1.
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
