CCNT2_MOUSE
ID CCNT2_MOUSE Reviewed; 723 AA.
AC Q7TQK0; K4N0L9; K4N2S3;
DT 13-APR-2016, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2003, sequence version 1.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=Cyclin-T2 {ECO:0000303|PubMed:23060074};
DE Short=CycT2 {ECO:0000303|PubMed:23060074};
GN Name=Ccnt2 {ECO:0000312|MGI:MGI:1920199};
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, SUBCELLULAR LOCATION, AND
RP FUNCTION (ISOFORMS 1 AND 2).
RC TISSUE=Skeletal muscle;
RX PubMed=23060074; DOI=10.1002/jcb.24414;
RA Marchesi I., Nieddu V., Caracciolo V., Maioli M., Gaspa L., Giordano A.,
RA Bagella L.;
RT "Activation and function of murine Cyclin T2A and Cyclin T2B during
RT skeletal muscle differentiation.";
RL J. Cell. Biochem. 114:728-734(2013).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Limb;
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 [5]
RP INTERACTION WITH MYOD1 AND CDK9, AND FUNCTION.
RX PubMed=12037670; DOI=10.1038/sj.onc.1205493;
RA Simone C., Stiegler P., Bagella L., Pucci B., Bellan C., De Falco G.,
RA De Luca A., Guanti G., Puri P.L., Giordano A.;
RT "Activation of MyoD-dependent transcription by cdk9/cyclin T2.";
RL Oncogene 21:4137-4148(2002).
RN [6]
RP FUNCTION.
RX PubMed=16245309; DOI=10.1002/jcp.20523;
RA Giacinti C., Bagella L., Puri P.L., Giordano A., Simone C.;
RT "MyoD recruits the cdk9/cyclin T2 complex on myogenic-genes regulatory
RT regions.";
RL J. Cell. Physiol. 206:807-813(2006).
RN [7]
RP DISRUPTION PHENOTYPE, DEVELOPMENTAL STAGE, TISSUE SPECIFICITY, AND
RP FUNCTION.
RX PubMed=19364821; DOI=10.1128/mcb.00172-09;
RA Kohoutek J., Li Q., Blazek D., Luo Z., Jiang H., Peterlin B.M.;
RT "Cyclin T2 is essential for mouse embryogenesis.";
RL Mol. Cell. Biol. 29:3280-3285(2009).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-477 AND SER-596, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Kidney, Liver, Lung, Pancreas, Spleen, and Testis;
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).
CC -!- FUNCTION: Regulatory subunit of the cyclin-dependent kinase pair
CC (CDK9/cyclin T) complex, also called positive transcription elongation
CC factor B (P-TEFB), which is proposed to facilitate the transition from
CC abortive to production elongation by phosphorylating the CTD (carboxy-
CC terminal domain) of the large subunit of RNA polymerase II (RNAP II).
CC The activity of this complex is regulated by binding with 7SK snRNA (By
CC similarity). Plays a role during muscle differentiation; P-TEFB complex
CC interacts with MYOD1; this tripartite complex promotes the
CC transcriptional activity of MYOD1 through its CDK9-mediated
CC phosphorylation and binds the chromatin of promoters and enhancers of
CC muscle-specific genes; this event correlates with hyperphosphorylation
CC of the CTD domain of RNA pol II (PubMed:16245309, PubMed:23060074,
CC PubMed:12037670). In addition, enhances MYOD1-dependent transcription
CC through interaction with PKN1 (By similarity). Involved in early embryo
CC development (PubMed:19364821). {ECO:0000250|UniProtKB:O60583,
CC ECO:0000269|PubMed:12037670, ECO:0000269|PubMed:16245309,
CC ECO:0000269|PubMed:19364821, ECO:0000269|PubMed:23060074}.
CC -!- SUBUNIT: Interacts with CDK9 to form P-TEFb. Interacts with POLR2A (via
CC the C-terminal domain (CTD)); mediates transcriptional activity.
CC Interacts with HEXIM1; mediates formation of a tripartite complex with
CC KPNA2. Interacts with HEXIM2. Interacts with PKN1; enhances MYOD1-
CC dependent transcription. P-TEFB complex interacts with RB1; promotes
CC phosphorylation of RB1 (By similarity). P-TEFB complex interacts with
CC MYOD1; promotes the transcriptional activity of MYOD1 through its CDK9-
CC mediated phosphorylation (PubMed:12037670). Interacts with MDFI and
CC MDFIC (By similarity). {ECO:0000250|UniProtKB:O60583,
CC ECO:0000269|PubMed:12037670}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, perinuclear region
CC {ECO:0000269|PubMed:23060074}. Nucleus {ECO:0000269|PubMed:23060074}.
CC Note=Nucleus in differentiating cells. {ECO:0000269|PubMed:23060074}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=cyclin T2A {ECO:0000303|PubMed:23060074}, CycT2a
CC {ECO:0000303|PubMed:23060074};
CC IsoId=Q7TQK0-1; Sequence=Displayed;
CC Name=2; Synonyms=cyclin T2B {ECO:0000303|PubMed:23060074}, CycT2b
CC {ECO:0000303|PubMed:23060074};
CC IsoId=Q7TQK0-2; Sequence=VSP_058225, VSP_058226;
CC -!- TISSUE SPECIFICITY: [Isoform 2]: Highly expressed in all phases of
CC skeletal muscle differentiation, particularly in later stages
CC (PubMed:23060074). Highly expressed in skeletal muscle. Significantly
CC expressed in heart, brain, kidney, liver, testis, and pancreas
CC (PubMed:19364821). {ECO:0000269|PubMed:19364821,
CC ECO:0000269|PubMed:23060074}.
CC -!- DEVELOPMENTAL STAGE: Expressed in all forming organs and supporting
CC tissues in 10.5 to 14.5 dpc. Expressed in embryonic ectoderm and the
CC forming brain and neural tube in 7.5 and 8.5/9.5 dpc embryos,
CC respectively. {ECO:0000269|PubMed:19364821}.
CC -!- DISRUPTION PHENOTYPE: The homozygous knockout of Ccnt2 is embryonic
CC lethal. {ECO:0000269|PubMed:19364821}.
CC -!- SIMILARITY: Belongs to the cyclin family. Cyclin C subfamily.
CC {ECO:0000305}.
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DR EMBL; JX965957; AFV36779.1; -; mRNA.
DR EMBL; JX965958; AFV36780.1; -; mRNA.
DR EMBL; AK154439; BAE32588.1; -; mRNA.
DR EMBL; AC121883; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC054122; AAH54122.1; -; mRNA.
DR CCDS; CCDS15248.1; -. [Q7TQK0-1]
DR RefSeq; NP_082675.1; NM_028399.1. [Q7TQK0-1]
DR AlphaFoldDB; Q7TQK0; -.
DR SMR; Q7TQK0; -.
DR ComplexPortal; CPX-323; Positive transcription elongation factor B, CDK9-cyclinT2a complex. [Q7TQK0-2]
DR ComplexPortal; CPX-324; Positive transcription elongation factor B, CDK9-cyclinT2b complex. [Q7TQK0-1]
DR IntAct; Q7TQK0; 1.
DR STRING; 10090.ENSMUSP00000027587; -.
DR iPTMnet; Q7TQK0; -.
DR PhosphoSitePlus; Q7TQK0; -.
DR EPD; Q7TQK0; -.
DR jPOST; Q7TQK0; -.
DR MaxQB; Q7TQK0; -.
DR PaxDb; Q7TQK0; -.
DR PRIDE; Q7TQK0; -.
DR ProteomicsDB; 281343; -. [Q7TQK0-1]
DR ProteomicsDB; 281344; -. [Q7TQK0-2]
DR Antibodypedia; 1420; 111 antibodies from 27 providers.
DR DNASU; 72949; -.
DR Ensembl; ENSMUST00000027587; ENSMUSP00000027587; ENSMUSG00000026349. [Q7TQK0-1]
DR Ensembl; ENSMUST00000112570; ENSMUSP00000108189; ENSMUSG00000026349. [Q7TQK0-2]
DR GeneID; 72949; -.
DR KEGG; mmu:72949; -.
DR UCSC; uc007ckz.1; mouse. [Q7TQK0-1]
DR CTD; 905; -.
DR MGI; MGI:1920199; Ccnt2.
DR VEuPathDB; HostDB:ENSMUSG00000026349; -.
DR eggNOG; KOG0834; Eukaryota.
DR GeneTree; ENSGT00940000155759; -.
DR HOGENOM; CLU_012994_1_1_1; -.
DR InParanoid; Q7TQK0; -.
DR OMA; DGNHEYS; -.
DR OrthoDB; 1437076at2759; -.
DR PhylomeDB; Q7TQK0; -.
DR TreeFam; TF101014; -.
DR Reactome; R-MMU-112382; Formation of RNA Pol II elongation complex.
DR Reactome; R-MMU-2173796; SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription.
DR Reactome; R-MMU-674695; RNA Polymerase II Pre-transcription Events.
DR Reactome; R-MMU-6796648; TP53 Regulates Transcription of DNA Repair Genes.
DR Reactome; R-MMU-6807505; RNA polymerase II transcribes snRNA genes.
DR Reactome; R-MMU-75955; RNA Polymerase II Transcription Elongation.
DR BioGRID-ORCS; 72949; 0 hits in 76 CRISPR screens.
DR ChiTaRS; Ccnt2; mouse.
DR PRO; PR:Q7TQK0; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q7TQK0; protein.
DR Bgee; ENSMUSG00000026349; Expressed in metanephric cortical collecting duct and 252 other tissues.
DR GO; GO:0008024; C:cyclin/CDK positive transcription elongation factor complex; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0097322; F:7SK snRNA binding; ISS:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; IDA:UniProtKB.
DR GO; GO:0061575; F:cyclin-dependent protein serine/threonine kinase activator activity; IBA:GO_Central.
DR GO; GO:0016538; F:cyclin-dependent protein serine/threonine kinase regulator activity; IBA:GO_Central.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR GO; GO:0070063; F:RNA polymerase binding; ISO:MGI.
DR GO; GO:0001223; F:transcription coactivator binding; ISO:MGI.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0019085; P:early viral transcription; ISO:MGI.
DR GO; GO:0019086; P:late viral transcription; ISO:MGI.
DR GO; GO:1903655; P:phosphorylation of RNA polymerase II C-terminal domain serine 2 residues involved in positive regulation of transcription elongation from RNA polymerase II promoter; IC:ComplexPortal.
DR GO; GO:1903654; P:phosphorylation of RNA polymerase II C-terminal domain serine 5 residues involved in positive regulation of transcription elongation from RNA polymerase II promoter; IC:ComplexPortal.
DR GO; GO:0032786; P:positive regulation of DNA-templated transcription, elongation; IBA:GO_Central.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:0032968; P:positive regulation of transcription elongation from RNA polymerase II promoter; ISO:MGI.
DR GO; GO:0006468; P:protein phosphorylation; ISO:MGI.
DR GO; GO:0051147; P:regulation of muscle cell differentiation; ISS:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0007519; P:skeletal muscle tissue development; IDA:UniProtKB.
DR GO; GO:0006351; P:transcription, DNA-templated; IEA:InterPro.
DR CDD; cd00043; CYCLIN; 1.
DR InterPro; IPR028862; CCNT2.
DR InterPro; IPR013763; Cyclin-like.
DR InterPro; IPR036915; Cyclin-like_sf.
DR InterPro; IPR043198; Cyclin/Ssn8.
DR InterPro; IPR006671; Cyclin_N.
DR PANTHER; PTHR10026; PTHR10026; 1.
DR PANTHER; PTHR10026:SF43; PTHR10026:SF43; 1.
DR Pfam; PF00134; Cyclin_N; 1.
DR SMART; SM00385; CYCLIN; 2.
DR SUPFAM; SSF47954; SSF47954; 2.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell cycle; Cell division; Cyclin; Cytoplasm;
KW Host-virus interaction; Isopeptide bond; Nucleus; Phosphoprotein;
KW Reference proteome; Transcription; Transcription regulation;
KW Ubl conjugation.
FT CHAIN 1..723
FT /note="Cyclin-T2"
FT /id="PRO_0000436037"
FT DOMAIN 12..147
FT /note="Cyclin N-terminal"
FT /evidence="ECO:0000255"
FT REGION 1..298
FT /note="Interaction with MDFIC and MDFI"
FT /evidence="ECO:0000250|UniProtKB:O60583"
FT REGION 250..298
FT /note="Interaction with POLR2A"
FT /evidence="ECO:0000250|UniProtKB:O60583"
FT REGION 297..325
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 340..364
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 385..428
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 458..645
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 389..413
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 466..483
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 486..505
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 515..560
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 561..579
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 630..645
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 477
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 596
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT CROSSLNK 404
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:O60583"
FT VAR_SEQ 637..657
FT /note="SSSSSSSVKQYLSSHSSVFNH -> GLRTSQHPRETGQETSGAPRS (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:23060074"
FT /id="VSP_058225"
FT VAR_SEQ 658..723
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:23060074"
FT /id="VSP_058226"
FT CONFLICT 470
FT /note="V -> A (in Ref. 1; AFV36780/AFV36779)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 723 AA; 80252 MW; 68DEBB95F66A2FB4 CRC64;
MASGRGASSR WFFTREQLEN TPSRRCGVEA DEELSHRQQA ANLIQDMGQR LNVSQLTINT
AIVYMHRFYM HHSFTKFNRN IISPTALFLA AKVEEQARKL EHVIKVAHAC LHPLEPLLDT
KCDAYLQQTQ ELVLLETIML QTLGFEITIE HPHTDVVKCT QLVRASKDLA QTSYFMATNS
LHLTTFCLQY KPTVIACVCI HLACKWSNWE IPVSTDGKHW WEYVDPTVTL ELLDELTHEF
LQILEKTPSR LKRIRNWRAM AKKPKVDGQV SETPLLGSSL VQNSILVDSV TGVPANPSFQ
KPSTSTFPAP IPLNSGSTSV QDSRASDNLS VLAAGMPSTS YSLSSHQEWP QHPDSARTDP
VYTQKQEATL SGSQYISFQQ GPSMALHSGL HHRPDKVADH SSAKQEYTHK AGSSKHHGPI
PATPGMLPQK MSLDKYREKR KLETLDVDTR DHYLAAHAEQ QHKHGPAQAV TGTSVTSPIK
MKLPLTNSDR PEKHVAEKKE RSGSLKLRIP IPPPDKGPSK EELKMKIKVA SSERHSSSDE
GSGKSKHSSP HISRDHKEKH KEHPANRHHS SHKYLHMHSG GSKHTADGMP PTVLRSPVGL
GPEGVSSASS ARKKLHSSEA SHNHHSKMSK SSKSAGSSSS SSSVKQYLSS HSSVFNHPLP
PPPPVTYQVG YGHLSTLVKL DKKPVEPHGP EANHEYSTSS QHMDYKDTFD MLDSLLSAQG
MNM
