CDKA1_ARATH
ID CDKA1_ARATH Reviewed; 294 AA.
AC P24100; Q29Q50; Q8RX68; Q9M307;
DT 01-MAR-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-1992, sequence version 1.
DT 03-AUG-2022, entry version 184.
DE RecName: Full=Cyclin-dependent kinase A-1 {ECO:0000305|PubMed:11971144};
DE Short=CDKA;1 {ECO:0000303|PubMed:11971144};
DE EC=2.7.11.22 {ECO:0000269|PubMed:15863515, ECO:0000269|PubMed:16856985};
DE EC=2.7.11.23 {ECO:0000269|PubMed:15863515, ECO:0000269|PubMed:16856985};
DE AltName: Full=Cell division control protein 2 homolog A {ECO:0000303|PubMed:1618302, ECO:0000303|PubMed:1937013};
DE Short=CDC2aAt {ECO:0000303|PubMed:8893539};
GN Name=CDKA-1 {ECO:0000303|PubMed:11971144};
GN Synonyms=CDC2 {ECO:0000303|PubMed:1634002, ECO:0000303|PubMed:1840925},
GN CDC2A {ECO:0000303|PubMed:1618302, ECO:0000303|PubMed:1937013};
GN OrderedLocusNames=At3g48750 {ECO:0000312|Araport:AT3G48750};
GN ORFNames=T21J18.20 {ECO:0000312|EMBL:CAB87903.1};
OS Arabidopsis thaliana (Mouse-ear cress).
OC Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae;
OC rosids; malvids; Brassicales; Brassicaceae; Camelineae; Arabidopsis.
OX NCBI_TaxID=3702;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=cv. Columbia;
RX PubMed=1937013; DOI=10.1016/0378-1119(91)90146-3;
RA Hirayama T., Imajuku Y., Anai T., Matsui M., Oka A.;
RT "Identification of two cell-cycle-controlling cdc2 gene homologs in
RT Arabidopsis thaliana.";
RL Gene 105:159-165(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=cv. Columbia;
RX PubMed=1840925; DOI=10.2307/3869358;
RA Ferreira P.C.G., Hemerly A.S., Villarroel R., van Montagu M., Inze D.;
RT "The Arabidopsis functional homolog of the p34cdc2 protein kinase.";
RL Plant Cell 3:531-540(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=cv. Columbia;
RX PubMed=1634002; DOI=10.1042/bst0200080;
RA Inze D., Ferreira P.C.G., Hemerly A.S., van Montagu M.;
RT "Control of cell division in plants.";
RL Biochem. Soc. Trans. 20:80-84(1992).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=cv. Columbia;
RX PubMed=1618302; DOI=10.1016/0014-5793(92)80592-5;
RA Imajuku Y., Hirayama T., Endoh H., Oka A.;
RT "Exon-intron organization of the Arabidopsis thaliana protein kinase genes
RT CDC2a and CDC2b.";
RL FEBS Lett. 304:73-77(1992).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=cv. Columbia;
RX PubMed=11130713; DOI=10.1038/35048706;
RA Salanoubat M., Lemcke K., Rieger M., Ansorge W., Unseld M., Fartmann B.,
RA Valle G., Bloecker H., Perez-Alonso M., Obermaier B., Delseny M.,
RA Boutry M., Grivell L.A., Mache R., Puigdomenech P., De Simone V.,
RA Choisne N., Artiguenave F., Robert C., Brottier P., Wincker P.,
RA Cattolico L., Weissenbach J., Saurin W., Quetier F., Schaefer M.,
RA Mueller-Auer S., Gabel C., Fuchs M., Benes V., Wurmbach E., Drzonek H.,
RA Erfle H., Jordan N., Bangert S., Wiedelmann R., Kranz H., Voss H.,
RA Holland R., Brandt P., Nyakatura G., Vezzi A., D'Angelo M., Pallavicini A.,
RA Toppo S., Simionati B., Conrad A., Hornischer K., Kauer G., Loehnert T.-H.,
RA Nordsiek G., Reichelt J., Scharfe M., Schoen O., Bargues M., Terol J.,
RA Climent J., Navarro P., Collado C., Perez-Perez A., Ottenwaelder B.,
RA Duchemin D., Cooke R., Laudie M., Berger-Llauro C., Purnelle B., Masuy D.,
RA de Haan M., Maarse A.C., Alcaraz J.-P., Cottet A., Casacuberta E.,
RA Monfort A., Argiriou A., Flores M., Liguori R., Vitale D., Mannhaupt G.,
RA Haase D., Schoof H., Rudd S., Zaccaria P., Mewes H.-W., Mayer K.F.X.,
RA Kaul S., Town C.D., Koo H.L., Tallon L.J., Jenkins J., Rooney T., Rizzo M.,
RA Walts A., Utterback T., Fujii C.Y., Shea T.P., Creasy T.H., Haas B.,
RA Maiti R., Wu D., Peterson J., Van Aken S., Pai G., Militscher J.,
RA Sellers P., Gill J.E., Feldblyum T.V., Preuss D., Lin X., Nierman W.C.,
RA Salzberg S.L., White O., Venter J.C., Fraser C.M., Kaneko T., Nakamura Y.,
RA Sato S., Kato T., Asamizu E., Sasamoto S., Kimura T., Idesawa K.,
RA Kawashima K., Kishida Y., Kiyokawa C., Kohara M., Matsumoto M., Matsuno A.,
RA Muraki A., Nakayama S., Nakazaki N., Shinpo S., Takeuchi C., Wada T.,
RA Watanabe A., Yamada M., Yasuda M., Tabata S.;
RT "Sequence and analysis of chromosome 3 of the plant Arabidopsis thaliana.";
RL Nature 408:820-822(2000).
RN [6]
RP GENOME REANNOTATION.
RC STRAIN=cv. Columbia;
RX PubMed=27862469; DOI=10.1111/tpj.13415;
RA Cheng C.Y., Krishnakumar V., Chan A.P., Thibaud-Nissen F., Schobel S.,
RA Town C.D.;
RT "Araport11: a complete reannotation of the Arabidopsis thaliana reference
RT genome.";
RL Plant J. 89:789-804(2017).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=cv. Columbia;
RX PubMed=14593172; DOI=10.1126/science.1088305;
RA Yamada K., Lim J., Dale J.M., Chen H., Shinn P., Palm C.J., Southwick A.M.,
RA Wu H.C., Kim C.J., Nguyen M., Pham P.K., Cheuk R.F., Karlin-Newmann G.,
RA Liu S.X., Lam B., Sakano H., Wu T., Yu G., Miranda M., Quach H.L.,
RA Tripp M., Chang C.H., Lee J.M., Toriumi M.J., Chan M.M., Tang C.C.,
RA Onodera C.S., Deng J.M., Akiyama K., Ansari Y., Arakawa T., Banh J.,
RA Banno F., Bowser L., Brooks S.Y., Carninci P., Chao Q., Choy N., Enju A.,
RA Goldsmith A.D., Gurjal M., Hansen N.F., Hayashizaki Y., Johnson-Hopson C.,
RA Hsuan V.W., Iida K., Karnes M., Khan S., Koesema E., Ishida J., Jiang P.X.,
RA Jones T., Kawai J., Kamiya A., Meyers C., Nakajima M., Narusaka M.,
RA Seki M., Sakurai T., Satou M., Tamse R., Vaysberg M., Wallender E.K.,
RA Wong C., Yamamura Y., Yuan S., Shinozaki K., Davis R.W., Theologis A.,
RA Ecker J.R.;
RT "Empirical analysis of transcriptional activity in the Arabidopsis
RT genome.";
RL Science 302:842-846(2003).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=cv. Columbia;
RA Shinn P., Chen H., Kim C.J., Ecker J.R.;
RT "Arabidopsis ORF clones.";
RL Submitted (MAR-2006) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=cv. Columbia;
RA Totoki Y., Seki M., Ishida J., Nakajima M., Enju A., Kamiya A.,
RA Narusaka M., Shin-i T., Nakagawa M., Sakamoto N., Oishi K., Kohara Y.,
RA Kobayashi M., Toyoda A., Sakaki Y., Sakurai T., Iida K., Akiyama K.,
RA Satou M., Toyoda T., Konagaya A., Carninci P., Kawai J., Hayashizaki Y.,
RA Shinozaki K.;
RT "Large-scale analysis of RIKEN Arabidopsis full-length (RAFL) cDNAs.";
RL Submitted (JUL-2006) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Brover V.V., Troukhan M.E., Alexandrov N.A., Lu Y.-P., Flavell R.B.,
RA Feldmann K.A.;
RT "Full-length cDNA from Arabidopsis thaliana.";
RL Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=8893539; DOI=10.1046/j.1365-313x.1996.10040601.x;
RA Segers G., Gadisseur I., Bergounioux C., de Almeida Engler J., Jacqmard A.,
RA van Montagu M., Inze D.;
RT "The Arabidopsis cyclin-dependent kinase gene cdc2bAt is preferentially
RT expressed during S and G2 phases of the cell cycle.";
RL Plant J. 10:601-612(1996).
RN [12]
RP INDUCTION.
RX PubMed=9011085; DOI=10.1046/j.1365-313x.1996.10061037.x;
RA Niebel A., de Almeida Engler J., Hemerly A.S., Ferreira P.C.G., Inze D.,
RA van Montagu M., Gheysen G.;
RT "Induction of cdc2a and cyc1At expression in Arabidopsis thaliana during
RT early phases of nematode-induced feeding cell formation.";
RL Plant J. 10:1037-1043(1996).
RN [13]
RP INTERACTION WITH CKS1.
RX PubMed=9276444; DOI=10.1016/s0014-5793(97)00822-3;
RA de Veylder L., Segers G., Glab N., Casteels P., van Montagu M., Inze D.;
RT "The Arabidopsis Cks1At protein binds the cyclin-dependent kinases Cdc2aAt
RT and Cdc2bAt.";
RL FEBS Lett. 412:446-452(1997).
RN [14]
RP INTERACTION WITH KRP1/ICK1.
RX PubMed=9087400; DOI=10.1038/386451a0;
RA Wang H., Fowke L.C., Crosby W.L.;
RT "A plant cyclin-dependent kinase inhibitor gene.";
RL Nature 386:451-452(1997).
RN [15]
RP INTERACTION WITH KRP1/ICK1 AND CYCD3-1.
RX PubMed=9753775; DOI=10.1046/j.1365-313x.1998.00231.x;
RA Wang H., Qi Q., Schorr P., Cutler A.J., Crosby W.L., Fowke L.C.;
RT "ICK1, a cyclin-dependent protein kinase inhibitor from Arabidopsis
RT thaliana interacts with both Cdc2a and CycD3, and its expression is induced
RT by abscisic acid.";
RL Plant J. 15:501-510(1998).
RN [16]
RP INTERACTION WITH CKS1 AND CYCD1-1, AND MUTAGENESIS OF THR-14; TYR-15;
RP ASP-146; PRO-156; THR-166 AND 234-LEU--ASP-236.
RX PubMed=10100639; DOI=10.1016/s0014-5793(99)00211-2;
RA Porceddu A., de Veylder L., Hayles J., van Montagu M., Inze D., Mironov V.;
RT "Mutational analysis of two Arabidopsis thaliana cyclin-dependent kinases
RT in fission yeast.";
RL FEBS Lett. 446:182-188(1999).
RN [17]
RP INTERACTION WITH CYCD4-1.
RX PubMed=10420643; DOI=10.1007/s004250050582;
RA de Veylder L., de Almeida Engler J., Burssens S., Manevski A., Lescure B.,
RA van Montagu M., Engler G., Inze D.;
RT "A new D-type cyclin of Arabidopsis thaliana expressed during lateral root
RT primordia formation.";
RL Planta 208:453-462(1999).
RN [18]
RP DEVELOPMENTAL STAGE.
RX PubMed=10521519; DOI=10.2307/3871084;
RA Yoshizumi T., Nagata N., Shimada H., Matsui M.;
RT "An Arabidopsis cell cycle-dependent kinase-related gene, CDC2b, plays a
RT role in regulating seedling growth in darkness.";
RL Plant Cell 11:1883-1896(1999).
RN [19]
RP INDUCTION.
RX PubMed=11089675; DOI=10.1007/s004250000334;
RA Burssens S., Himanen K., van de Cotte B., Beeckman T., van Montagu M.,
RA Inze D., Verbruggen N.;
RT "Expression of cell cycle regulatory genes and morphological alterations in
RT response to salt stress in Arabidopsis thaliana.";
RL Planta 211:632-640(2000).
RN [20]
RP INTERACTION WITH KRP2/ICK2.
RX PubMed=10758489; DOI=10.1046/j.1365-313x.2000.00688.x;
RA Lui H., Wang H., Delong C., Fowke L.C., Crosby W.L., Fobert P.R.;
RT "The Arabidopsis Cdc2a-interacting protein ICK2 is structurally related to
RT ICK1 and is a potent inhibitor of cyclin-dependent kinase activity in
RT vitro.";
RL Plant J. 21:379-385(2000).
RN [21]
RP FUNCTION, AND MUTAGENESIS OF ASP-146.
RX PubMed=10929107; DOI=10.1046/j.1365-313x.2000.00800.x;
RA Hemerly A.S., Ferreira P.C.G., van Montagu M., Engler G., Inze D.;
RT "Cell division events are essential for embryo patterning and
RT morphogenesis: studies on dominant-negative cdc2aAt mutants of
RT Arabidopsis.";
RL Plant J. 23:123-130(2000).
RN [22]
RP INTERACTION WITH CYCD2-1 AND CYCD3-1.
RX PubMed=11096103; DOI=10.1074/jbc.m009074200;
RA Healy J.M.S., Menges M., Doonan J.H., Murray J.A.H.;
RT "The Arabidopsis D-type cyclins CycD2 and CycD3 both interact in vivo with
RT the PSTAIRE cyclin-dependent kinase Cdc2a but are differentially
RT controlled.";
RL J. Biol. Chem. 276:7041-7047(2001).
RN [23]
RP INTERACTION WITH KRP1/ICK1; KRP2/ICK2; KRP3/ICK6; KRP4/ICK7; KRP6/ICK4 AND
RP KRP7/ICK5.
RX PubMed=11449057; DOI=10.2307/3871392;
RA de Veylder L., Beeckman T., Beemster G.T.S., Krols L., Terras F.,
RA Landrieu I., van der Schueren E., Maes S., Naudts M., Inze D.;
RT "Functional analysis of cyclin-dependent kinase inhibitors of
RT Arabidopsis.";
RL Plant Cell 13:1653-1667(2001).
RN [24]
RP INTERACTION WITH CKS1.
RX PubMed=11319029; DOI=10.1046/j.1365-313x.2001.00996.x;
RA de Veylder L., Beemster G.T.S., Beeckman T., Inze D.;
RT "CKS1At overexpression in Arabidopsis thaliana inhibits growth by reducing
RT meristem size and inhibiting cell-cycle progression.";
RL Plant J. 25:617-626(2001).
RN [25]
RP INTERACTION WITH CYCD2-1.
RX PubMed=11722776; DOI=10.1046/j.1365-313x.2001.01160.x;
RA Boniotti M.B., Gutierrez C.;
RT "A cell-cycle-regulated kinase activity phosphorylates plant retinoblastoma
RT protein and contains, in Arabidopsis, a CDKA/cyclin D complex.";
RL Plant J. 28:341-350(2001).
RN [26]
RP GENE FAMILY, AND NOMENCLATURE.
RX PubMed=11971144; DOI=10.1105/tpc.010445;
RA Vandepoele K., Raes J., de Veylder L., Rouze P., Rombauts S., Inze D.;
RT "Genome-wide analysis of core cell cycle genes in Arabidopsis.";
RL Plant Cell 14:903-916(2002).
RN [27]
RP INTERACTION WITH KRP1/ICK1.
RX PubMed=12566574; DOI=10.1105/tpc.008342;
RA Schnittger A., Weinl C., Bouyer D., Schoebinger U., Huelskamp M.;
RT "Misexpression of the cyclin-dependent kinase inhibitor ICK1/KRP1 in
RT single-celled Arabidopsis trichomes reduces endoreduplication and cell size
RT and induces cell death.";
RL Plant Cell 15:303-315(2003).
RN [28]
RP INTERACTION WITH CYCD4-1.
RX PubMed=12857813; DOI=10.1104/pp.103.020644;
RA Kono A., Umeda-Hara C., Lee J., Ito M., Uchimiya H., Umeda M.;
RT "Arabidopsis D-type cyclin CYCD4;1 is a novel cyclin partner of B2-type
RT cyclin-dependent kinase.";
RL Plant Physiol. 132:1315-1321(2003).
RN [29]
RP INTERACTION WITH TIF4A-1/EIF4A-1.
RX PubMed=14706832; DOI=10.1016/s0014-5793(03)01382-6;
RA Hutchins A.P., Roberts G.R., Lloyd C.W., Doonan J.H.;
RT "In vivo interaction between CDKA and eIF4A: a possible mechanism linking
RT translation and cell proliferation.";
RL FEBS Lett. 556:91-94(2004).
RN [30]
RP INTERACTION WITH CYCU1-1; CYCU2-1; CYCU2-2; CYCU3-1; CYCU4-1; CYCU4-2 AND
RP CYCU4-3.
RX PubMed=15197472; DOI=10.1007/s00018-004-4057-4;
RA Torres Acosta J.A., de Almeida Engler J., Raes J., Magyar Z., de Groodt R.,
RA Inze D., de Veylder L.;
RT "Molecular characterization of Arabidopsis PHO80-like proteins, a novel
RT class of CDKA;1-interacting cyclins.";
RL Cell. Mol. Life Sci. 61:1485-1497(2004).
RN [31]
RP INTERACTION WITH CDT1A.
RC STRAIN=cv. Columbia;
RX PubMed=15316110; DOI=10.1105/tpc.104.022400;
RA del Mar Castellano M., Boniotti M.B., Caro E., Schnittger A., Gutierrez C.;
RT "DNA replication licensing affects cell proliferation or endoreplication in
RT a cell type-specific manner.";
RL Plant Cell 16:2380-2393(2004).
RN [32]
RP INTERACTION WITH CYCH1-1.
RX PubMed=15486101; DOI=10.1105/tpc.104.025601;
RA Shimotohno A., Umeda-Hara C., Bisova K., Uchimiya H., Umeda M.;
RT "The plant-specific kinase CDKF;1 is involved in activating phosphorylation
RT of cyclin-dependent kinase-activating kinases in Arabidopsis.";
RL Plant Cell 16:2954-2966(2004).
RN [33]
RP ACTIVITY REGULATION, INTERACTION WITH KRP2/ICK2, AND CATALYTIC ACTIVITY.
RX PubMed=15863515; DOI=10.1105/tpc.105.032383;
RA Verkest A., de Oliveira Manes C.L., Vercruysse S., Maes S.,
RA van der Schueren E., Beeckman T., Genschik P., Kuiper M., Inze D.,
RA de Veylder L.;
RT "The cyclin-dependent kinase inhibitor KRP2 controls the onset of the
RT endoreduplication cycle during Arabidopsis leaf development through
RT inhibition of mitotic CDKA;1 kinase complexes.";
RL Plant Cell 17:1723-1736(2005).
RN [34]
RP REVIEW.
RX PubMed=17094738; DOI=10.1146/annurev.genet.40.110405.090431;
RA Inze D., de Veylder L.;
RT "Cell cycle regulation in plant development.";
RL Annu. Rev. Genet. 40:77-105(2006).
RN [35]
RP ACTIVITY REGULATION.
RX PubMed=16376885; DOI=10.1016/j.febslet.2005.12.018;
RA Nakai T., Kato K., Shinmyo A., Sekine M.;
RT "Arabidopsis KRPs have distinct inhibitory activity toward cyclin D2-
RT associated kinases, including plant-specific B-type cyclin-dependent
RT kinase.";
RL FEBS Lett. 580:336-340(2006).
RN [36]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH CYCA2-3.
RX PubMed=16415207; DOI=10.1105/tpc.105.037309;
RA Imai K.K., Ohashi Y., Tsuge T., Yoshizumi T., Matsui M., Oka A., Aoyama T.;
RT "The A-type cyclin CYCA2;3 is a key regulator of ploidy levels in
RT Arabidopsis endoreduplication.";
RL Plant Cell 18:382-396(2006).
RN [37]
RP INTERACTION WITH CYCD3-1.
RX PubMed=16517759; DOI=10.1105/tpc.105.039636;
RA Menges M., Samland A.K., Planchais S., Murray J.A.H.;
RT "The D-type cyclin CYCD3;1 is limiting for the G1-to-S-phase transition in
RT Arabidopsis.";
RL Plant Cell 18:893-906(2006).
RN [38]
RP INTERACTION WITH PAS2.
RX PubMed=16698944; DOI=10.1105/tpc.105.040485;
RA Da Costa M., Bach L., Landrieu I., Bellec Y., Catrice O., Brown S.,
RA De Veylder L., Lippens G., Inze D., Faure J.-D.;
RT "Arabidopsis PASTICCINO2 is an antiphosphatase involved in regulation of
RT cyclin-dependent kinase A.";
RL Plant Cell 18:1426-1437(2006).
RN [39]
RP INTERACTION WITH CYCD4-2.
RX PubMed=16408177; DOI=10.1007/s00299-005-0075-4;
RA Kono A., Ohno R., Umeda-Hara C., Uchimiya H., Umeda M.;
RT "A distinct type of cyclin D, CYCD4;2, involved in the activation of cell
RT division in Arabidopsis.";
RL Plant Cell Rep. 25:540-545(2006).
RN [40]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=16460514; DOI=10.1111/j.1365-313x.2005.02643.x;
RA Iwakawa H., Shinmyo A., Sekine M.;
RT "Arabidopsis CDKA;1, a cdc2 homologue, controls proliferation of generative
RT cells in male gametogenesis.";
RL Plant J. 45:819-831(2006).
RN [41]
RP ACTIVITY REGULATION, PHOSPHORYLATION AT TYR-15, INTERACTION WITH CYCH1-1,
RP MUTAGENESIS OF TYR-15, AND CATALYTIC ACTIVITY.
RX PubMed=16856985; DOI=10.1111/j.1365-313x.2006.02820.x;
RA Shimotohno A., Ohno R., Bisova K., Sakaguchi N., Huang J., Koncz C.,
RA Uchimiya H., Umeda M.;
RT "Diverse phosphoregulatory mechanisms controlling cyclin-dependent kinase-
RT activating kinases in Arabidopsis.";
RL Plant J. 47:701-710(2006).
RN [42]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH KRP1/ICK1.
RX PubMed=16845478; DOI=10.1007/s11103-006-9019-9;
RA Zhou Y., Niu H., Brandizzi F., Fowke L.C., Wang H.;
RT "Molecular control of nuclear and subnuclear targeting of the plant CDK
RT inhibitor ICK1 and ICK1-mediated nuclear transport of CDKA.";
RL Plant Mol. Biol. 62:261-278(2006).
RN [43]
RP INDUCTION, PHOSPHORYLATION, AND INTERACTION WITH WEE1.
RX PubMed=17209125; DOI=10.1105/tpc.106.045047;
RA de Schutter K., Joubes J., Cools T., Verkest A., Corellou F., Babiychuk E.,
RA van der Schueren E., Beeckman T., Kushnir S., Inze D., de Veylder L.;
RT "Arabidopsis WEE1 kinase controls cell cycle arrest in response to
RT activation of the DNA integrity checkpoint.";
RL Plant Cell 19:211-225(2007).
RN [44]
RP FUNCTION, PHOSPHORYLATION AT THR-161, AND MUTAGENESIS OF THR-161.
RX PubMed=17369369; DOI=10.1105/tpc.107.050401;
RA Dissmeyer N., Nowack M.K., Pusch S., Stals H., Inze D., Grini P.E.,
RA Schnittger A.;
RT "T-loop phosphorylation of Arabidopsis CDKA;1 is required for its function
RT and can be partially substituted by an aspartate residue.";
RL Plant Cell 19:972-985(2007).
RN [45]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-161, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Root;
RX PubMed=18433157; DOI=10.1021/pr8000173;
RA de la Fuente van Bentem S., Anrather D., Dohnal I., Roitinger E.,
RA Csaszar E., Joore J., Buijnink J., Carreri A., Forzani C., Lorkovic Z.J.,
RA Barta A., Lecourieux D., Verhounig A., Jonak C., Hirt H.;
RT "Site-specific phosphorylation profiling of Arabidopsis proteins by mass
RT spectrometry and peptide chip analysis.";
RL J. Proteome Res. 7:2458-2470(2008).
RN [46]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=cv. Columbia;
RX PubMed=19245862; DOI=10.1016/j.jprot.2009.02.004;
RA Jones A.M.E., MacLean D., Studholme D.J., Serna-Sanz A., Andreasson E.,
RA Rathjen J.P., Peck S.C.;
RT "Phosphoproteomic analysis of nuclei-enriched fractions from Arabidopsis
RT thaliana.";
RL J. Proteomics 72:439-451(2009).
RN [47]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19376835; DOI=10.1104/pp.109.138677;
RA Reiland S., Messerli G., Baerenfaller K., Gerrits B., Endler A.,
RA Grossmann J., Gruissem W., Baginsky S.;
RT "Large-scale Arabidopsis phosphoproteome profiling reveals novel
RT chloroplast kinase substrates and phosphorylation networks.";
RL Plant Physiol. 150:889-903(2009).
RN [48]
RP INTERACTION WITH SMR3; SMR4; SMR5; SMR6; SMR8 AND AT4G14310.
RX PubMed=20706207; DOI=10.1038/msb.2010.53;
RA Van Leene J., Hollunder J., Eeckhout D., Persiau G., Van De Slijke E.,
RA Stals H., Van Isterdael G., Verkest A., Neirynck S., Buffel Y., De Bodt S.,
RA Maere S., Laukens K., Pharazyn A., Ferreira P.C.G., Eloy N., Renne C.,
RA Meyer C., Faure J.-D., Steinbrenner J., Beynon J., Larkin J.C.,
RA Van de Peer Y., Hilson P., Kuiper M., De Veylder L., Van Onckelen H.,
RA Inze D., Witters E., De Jaeger G.;
RT "Targeted interactomics reveals a complex core cell cycle machinery in
RT Arabidopsis thaliana.";
RL Mol. Syst. Biol. 6:397-397(2010).
RN [49]
RP FUNCTION, DISRUPTION PHENOTYPE, AND INTERACTION WITH CYCD3-2.
RC STRAIN=cv. Columbia;
RX PubMed=24687979; DOI=10.1093/jxb/eru139;
RA Yang K., Wang H., Xue S., Qu X., Zou J., Le J.;
RT "Requirement for A-type cyclin-dependent kinase and cyclins for the
RT terminal division in the stomatal lineage of Arabidopsis.";
RL J. Exp. Bot. 65:2449-2461(2014).
RN [50]
RP INTERACTION WITH MYB3R3 AND MYB3R4.
RC STRAIN=cv. Columbia;
RX PubMed=26069325; DOI=10.15252/embj.201490899;
RA Kobayashi K., Suzuki T., Iwata E., Nakamichi N., Suzuki T., Chen P.,
RA Ohtani M., Ishida T., Hosoya H., Mueller S., Leviczky T.,
RA Pettko-Szandtner A., Darula Z., Iwamoto A., Nomoto M., Tada Y.,
RA Higashiyama T., Demura T., Doonan J.H., Hauser M.T., Sugimoto K., Umeda M.,
RA Magyar Z., Boegre L., Ito M.;
RT "Transcriptional repression by MYB3R proteins regulates plant organ
RT growth.";
RL EMBO J. 34:1992-2007(2015).
RN [51]
RP FUNCTION, DISRUPTION PHENOTYPE, MUTAGENESIS OF ASP-146, AND INTERACTION
RP WITH SPCH.
RC STRAIN=cv. Columbia;
RX PubMed=25680231; DOI=10.1016/j.molp.2014.12.014;
RA Yang K.-Z., Jiang M., Wang M., Xue S., Zhu L.-L., Wang H.-Z., Zou J.-J.,
RA Lee E.-K., Sack F., Le J.;
RT "Phosphorylation of serine 186 of bHLH transcription factor SPEECHLESS
RT promotes stomatal development in Arabidopsis.";
RL Mol. Plant 8:783-795(2015).
CC -!- FUNCTION: Involved in the control of the cell cycle. Essential for both
CC G1/S and G2/M (mitosis) phase transitions. Functions in cell
CC morphogenesis as well as cell proliferation. Required for cell division
CC (entry into mitosis) of the generative cell in male gametogenesis.
CC Required to trigger guard mother cells (GMC) symmetric divisions at the
CC late stage of stomatal development, probably via the regulation of G1
CC to S transition in the cell cycle. Required for the function of SPCH in
CC entering the stomatal lineage (PubMed:25680231). Promotes divisions in
CC the guard cells (GCs) after the guard mother cells (GMC) symmetric
CC division when in the presence of CYCD3-2 via the phosphorylation of
CC SPCH (PubMed:24687979, PubMed:25680231). {ECO:0000269|PubMed:10929107,
CC ECO:0000269|PubMed:16460514, ECO:0000269|PubMed:17369369,
CC ECO:0000269|PubMed:24687979, ECO:0000269|PubMed:25680231}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.22;
CC Evidence={ECO:0000269|PubMed:15863515, ECO:0000269|PubMed:16856985};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.22; Evidence={ECO:0000269|PubMed:15863515,
CC ECO:0000269|PubMed:16856985};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[DNA-directed RNA polymerase] + ATP = ADP + H(+) + phospho-
CC [DNA-directed RNA polymerase]; Xref=Rhea:RHEA:10216, Rhea:RHEA-
CC COMP:11321, Rhea:RHEA-COMP:11322, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43176, ChEBI:CHEBI:68546,
CC ChEBI:CHEBI:456216; EC=2.7.11.23;
CC Evidence={ECO:0000269|PubMed:15863515, ECO:0000269|PubMed:16856985};
CC -!- ACTIVITY REGULATION: CDK kinase activated by CDKF-1. CDK kinase
CC activity inhibited by KRP1/ICK1, KRP2/ICK2, KRP3/ICK6, KRP4/ICK7,
CC KRP5/ICK3, KRP6/ICK4 and KRP7/ICK5. Down-regulated by phosphorylation
CC by WEE1. {ECO:0000269|PubMed:15863515, ECO:0000269|PubMed:16376885,
CC ECO:0000269|PubMed:16856985}.
CC -!- SUBUNIT: Interacts with CDT1A, CYCA2-3, CYCD2-1, CYCD3-1, CYCD4-1,
CC CYCD4-2, CYCH1-1, CYCU1-1, CYCU2-1, CYCU2-2, CYCU3-1, CYCU4-1, CYCU4-2,
CC CYCU4-3, CKS1, KRP2/ICK2, KRP3/ICK6, KRP4/ICK7, KRP6/ICK4, KRP7/ICK5,
CC and C-terminal domain of KRP1/ICK1. Interacts with WEE1 and TIF4A-
CC 1/EIF4A-1. Interacts with PAS2; when phosphorylated at Tyr-15.
CC Interacts with SMR3, SMR4, SMR5, SMR6, SMR8 and At4g14310. Binds to
CC CYCD3-2 (PubMed:24687979). Component of a DREAM-like complex which
CC modulates a variety of developmentally regulated genes and of the
CC mitotic genes in proliferating and differentiated cells. Interacts with
CC MYB3R3 at later and with MYB3R4 at earlier stages of leaf development
CC (PubMed:26069325). May interact with SPCH (PubMed:25680231).
CC {ECO:0000269|PubMed:10100639, ECO:0000269|PubMed:10420643,
CC ECO:0000269|PubMed:10758489, ECO:0000269|PubMed:11096103,
CC ECO:0000269|PubMed:11319029, ECO:0000269|PubMed:11449057,
CC ECO:0000269|PubMed:11722776, ECO:0000269|PubMed:12566574,
CC ECO:0000269|PubMed:12857813, ECO:0000269|PubMed:14706832,
CC ECO:0000269|PubMed:15197472, ECO:0000269|PubMed:15316110,
CC ECO:0000269|PubMed:15486101, ECO:0000269|PubMed:15863515,
CC ECO:0000269|PubMed:16408177, ECO:0000269|PubMed:16415207,
CC ECO:0000269|PubMed:16517759, ECO:0000269|PubMed:16698944,
CC ECO:0000269|PubMed:16845478, ECO:0000269|PubMed:16856985,
CC ECO:0000269|PubMed:17209125, ECO:0000269|PubMed:20706207,
CC ECO:0000269|PubMed:24687979, ECO:0000269|PubMed:25680231,
CC ECO:0000269|PubMed:26069325, ECO:0000269|PubMed:9087400,
CC ECO:0000269|PubMed:9276444, ECO:0000269|PubMed:9753775}.
CC -!- INTERACTION:
CC P24100; O23249: CKS1; NbExp=9; IntAct=EBI-371713, EBI-1253127;
CC P24100; P42752: CYCD2-1; NbExp=4; IntAct=EBI-371713, EBI-1253160;
CC P24100; P42753: CYCD3-1; NbExp=5; IntAct=EBI-371713, EBI-1253610;
CC P24100; Q8LGA1: CYCD4-1; NbExp=4; IntAct=EBI-371713, EBI-1253202;
CC P24100; Q9LJ45: CYCU1-1; NbExp=2; IntAct=EBI-371713, EBI-1773749;
CC P24100; O80513: CYCU4-1; NbExp=2; IntAct=EBI-371713, EBI-1773819;
CC P24100; Q9FKF6: CYCU4-3; NbExp=2; IntAct=EBI-371713, EBI-1773829;
CC P24100; P41376: EIF4A1; NbExp=2; IntAct=EBI-371713, EBI-371706;
CC P24100; Q67Y93: KRP1; NbExp=10; IntAct=EBI-371713, EBI-1636730;
CC P24100; Q9SCR2: KRP2; NbExp=6; IntAct=EBI-371713, EBI-1636748;
CC P24100; Q9FKB5: KRP3; NbExp=4; IntAct=EBI-371713, EBI-1773302;
CC P24100; Q8GYJ3: KRP4; NbExp=4; IntAct=EBI-371713, EBI-1253225;
CC P24100; Q9LRY0: KRP5; NbExp=3; IntAct=EBI-371713, EBI-1636764;
CC P24100; Q0WNX9: KRP6; NbExp=3; IntAct=EBI-371713, EBI-1253171;
CC P24100; Q94CL9: KRP7; NbExp=3; IntAct=EBI-371713, EBI-1773344;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Mainly cytoplasmic.
CC Nuclear distribution increases after binding to ICK1/KRP1.
CC -!- TISSUE SPECIFICITY: Expressed in roots, stems, flowers and siliques.
CC {ECO:0000269|PubMed:8893539}.
CC -!- DEVELOPMENTAL STAGE: Expressed throughout the cell cycle. Expressed in
CC actively dividing cells: root and shoot apical meristems, leaf
CC primordia and emerging lateral root meristem. Expressed in light-grown
CC seedlings from 1 up to 7 days after germination with a peak at 2 and 3
CC days. {ECO:0000269|PubMed:10521519, ECO:0000269|PubMed:8893539}.
CC -!- INDUCTION: By nematode infection in roots. Down-regulated by salt
CC stress in root meristem and replication blocking agents (hydroxyurea
CC and aphidicolin). {ECO:0000269|PubMed:11089675,
CC ECO:0000269|PubMed:17209125, ECO:0000269|PubMed:9011085}.
CC -!- PTM: Phosphorylated at Tyr-15 by WEE1. Phosphorylation at Thr-161 is
CC important for the kinase activity and substrate binding. Binding to the
CC anti-phosphatase PAS2 prevents dephosphorylation.
CC {ECO:0000269|PubMed:16856985, ECO:0000269|PubMed:17209125,
CC ECO:0000269|PubMed:17369369}.
CC -!- DISRUPTION PHENOTYPE: Plants display lethal male gametophyte
CC (PubMed:16460514, PubMed:25680231). Impaired stomata formation with
CC arrested guard mother cells (GMC) divisions (PubMed:25680231). Impaired
CC last mitotic division in the male gametophyte, leading to 50 percent of
CC pollen with two gametes (PubMed:25680231). The double mutant flp-1
CC myb88 displays an enhanced stomatal phenotype with more and larger
CC stomatal clusters. Triple mutants cdka;1 flp-1 myb88 don't have guard
CC cells stacks but accumulates sGCs (PubMed:24687979).
CC {ECO:0000269|PubMed:16460514, ECO:0000269|PubMed:24687979,
CC ECO:0000269|PubMed:25680231}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr
CC protein kinase family. CDC2/CDKX subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAL91258.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=CAB87903.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; M59198; AAA32831.1; -; mRNA.
DR EMBL; S45387; AAB23643.1; -; mRNA.
DR EMBL; X57839; CAA40971.1; -; mRNA.
DR EMBL; D10850; BAA01623.1; -; Genomic_DNA.
DR EMBL; AL132963; CAB87903.1; ALT_SEQ; Genomic_DNA.
DR EMBL; CP002686; AEE78452.1; -; Genomic_DNA.
DR EMBL; AY090353; AAL91258.1; ALT_FRAME; mRNA.
DR EMBL; BT024706; ABD59044.1; -; mRNA.
DR EMBL; AK226373; BAE98520.1; -; mRNA.
DR EMBL; AY085153; AAM61706.1; -; mRNA.
DR PIR; S23095; S23095.
DR PIR; T49271; T49271.
DR RefSeq; NP_566911.1; NM_114734.4.
DR AlphaFoldDB; P24100; -.
DR SMR; P24100; -.
DR BioGRID; 9354; 107.
DR IntAct; P24100; 74.
DR STRING; 3702.AT3G48750.1; -.
DR iPTMnet; P24100; -.
DR PaxDb; P24100; -.
DR PRIDE; P24100; -.
DR ProteomicsDB; 220603; -.
DR EnsemblPlants; AT3G48750.1; AT3G48750.1; AT3G48750.
DR GeneID; 824036; -.
DR Gramene; AT3G48750.1; AT3G48750.1; AT3G48750.
DR KEGG; ath:AT3G48750; -.
DR Araport; AT3G48750; -.
DR TAIR; locus:2099478; AT3G48750.
DR eggNOG; KOG0594; Eukaryota.
DR HOGENOM; CLU_000288_181_1_1; -.
DR InParanoid; P24100; -.
DR OMA; NNDVWPE; -.
DR OrthoDB; 1010560at2759; -.
DR PhylomeDB; P24100; -.
DR BRENDA; 2.7.11.22; 399.
DR PRO; PR:P24100; -.
DR Proteomes; UP000006548; Chromosome 3.
DR ExpressionAtlas; P24100; baseline and differential.
DR Genevisible; P24100; AT.
DR GO; GO:0010005; C:cortical microtubule, transverse to long axis; IDA:TAIR.
DR GO; GO:0000307; C:cyclin-dependent protein kinase holoenzyme complex; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; IDA:TAIR.
DR GO; GO:0005634; C:nucleus; IDA:TAIR.
DR GO; GO:0009574; C:preprophase band; TAS:TAIR.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0030332; F:cyclin binding; IBA:GO_Central.
DR GO; GO:0004693; F:cyclin-dependent protein serine/threonine kinase activity; ISS:TAIR.
DR GO; GO:0016301; F:kinase activity; IMP:TAIR.
DR GO; GO:0004672; F:protein kinase activity; IDA:TAIR.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0008353; F:RNA polymerase II CTD heptapeptide repeat kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0008356; P:asymmetric cell division; IGI:TAIR.
DR GO; GO:0000911; P:cytokinesis by cell plate formation; IMP:TAIR.
DR GO; GO:0042023; P:DNA endoreduplication; IMP:TAIR.
DR GO; GO:0009793; P:embryo development ending in seed dormancy; IMP:TAIR.
DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; IBA:GO_Central.
DR GO; GO:0048229; P:gametophyte development; IMP:TAIR.
DR GO; GO:0010235; P:guard mother cell cytokinesis; IMP:UniProtKB.
DR GO; GO:0010444; P:guard mother cell differentiation; IMP:UniProtKB.
DR GO; GO:0033206; P:meiotic cytokinesis; IMP:TAIR.
DR GO; GO:0009555; P:pollen development; IMP:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:TAIR.
DR GO; GO:0006468; P:protein phosphorylation; IBA:GO_Central.
DR GO; GO:1902806; P:regulation of cell cycle G1/S phase transition; IMP:UniProtKB.
DR GO; GO:0010389; P:regulation of G2/M transition of mitotic cell cycle; IBA:GO_Central.
DR GO; GO:0010468; P:regulation of gene expression; IBA:GO_Central.
DR GO; GO:0051445; P:regulation of meiotic cell cycle; IBA:GO_Central.
DR GO; GO:0040020; P:regulation of meiotic nuclear division; IMP:TAIR.
DR GO; GO:0009409; P:response to cold; IEP:TAIR.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR GO; GO:0098725; P:symmetric cell division; IMP:UniProtKB.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cell cycle; Cell division; Cytoplasm; Kinase; Mitosis;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..294
FT /note="Cyclin-dependent kinase A-1"
FT /id="PRO_0000085749"
FT DOMAIN 4..287
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT ACT_SITE 127
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 10..18
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 33
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 15
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:16856985"
FT MOD_RES 161
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:17369369,
FT ECO:0007744|PubMed:18433157"
FT MUTAGEN 14
FT /note="T->A: Increased kinase activity; when associated
FT with F-15."
FT /evidence="ECO:0000269|PubMed:10100639"
FT MUTAGEN 15
FT /note="Y->F: Abolishes phosphorylation by WEE1. Increased
FT kinase activity; when associated with A-14."
FT /evidence="ECO:0000269|PubMed:10100639,
FT ECO:0000269|PubMed:16856985"
FT MUTAGEN 146
FT /note="D->N: Decreased kinase activity and disturbed cell
FT cycle. Reduced frequency of cell division during embryo
FT development. Altered stomatal production. Interacts with
FT SPCH."
FT /evidence="ECO:0000269|PubMed:10100639,
FT ECO:0000269|PubMed:10929107, ECO:0000269|PubMed:25680231"
FT MUTAGEN 156
FT /note="P->L: Decreased kinase activity and disturbed cell
FT cycle."
FT /evidence="ECO:0000269|PubMed:10100639"
FT MUTAGEN 161
FT /note="T->D: Strong reduction in kinase activity and
FT ability to bind substrate. Strong reduction in plant
FT growth. Sterile plants."
FT /evidence="ECO:0000269|PubMed:17369369"
FT MUTAGEN 161
FT /note="T->V: Strong reduction in kinase activity and
FT ability to bind substrate."
FT /evidence="ECO:0000269|PubMed:17369369"
FT MUTAGEN 166
FT /note="T->I: Decreased kinase activity and disturbed cell
FT cycle."
FT /evidence="ECO:0000269|PubMed:10100639"
FT MUTAGEN 234..236
FT /note="Missing: No change in kinase activity, but disturbed
FT cell cycle. Loss of interaction with CKS1."
FT /evidence="ECO:0000269|PubMed:10100639"
SQ SEQUENCE 294 AA; 34030 MW; B5FAE55FA9EC366E CRC64;
MDQYEKVEKI GEGTYGVVYK ARDKVTNETI ALKKIRLEQE DEGVPSTAIR EISLLKEMQH
SNIVKLQDVV HSEKRLYLVF EYLDLDLKKH MDSTPDFSKD LHMIKTYLYQ ILRGIAYCHS
HRVLHRDLKP QNLLIDRRTN SLKLADFGLA RAFGIPVRTF THEVVTLWYR APEILLGSHH
YSTPVDIWSV GCIFAEMISQ KPLFPGDSEI DQLFKIFRIM GTPYEDTWRG VTSLPDYKSA
FPKWKPTDLE TFVPNLDPDG VDLLSKMLLM DPTKRINARA ALEHEYFKDL GGMP
