ID CDK12_HUMAN Reviewed; 1490 AA. AC Q9NYV4; A7E2B2; B4DYX4; B9EIQ6; O94978; DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot. DT 05-OCT-2010, sequence version 2. DT 18-APR-2012, entry version 109. DE RecName: Full=Cyclin-dependent kinase 12; DE EC=2.7.11.22; DE EC=2.7.11.23; DE AltName: Full=Cdc2-related kinase, arginine/serine-rich; DE Short=CrkRS; DE AltName: Full=Cell division cycle 2-related protein kinase 7; DE Short=CDC2-related protein kinase 7; DE AltName: Full=Cell division protein kinase 12; DE Short=hCDK12; GN Name=CDK12; Synonyms=CRK7, CRKRS, KIAA0904; 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] (ISOFORM 1), TISSUE SPECIFICITY, RP SUBCELLULAR LOCATION, AND FUNCTION. RX MEDLINE=21539573; PubMed=11683387; RA Ko T.K., Kelly E., Pines J.; RT "CrkRS: a novel conserved Cdc2-related protein kinase that colocalises RT with SC35 speckles."; RL J. Cell Sci. 114:2591-2603(2001). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Brain; RX MEDLINE=99156230; PubMed=10048485; DOI=10.1093/dnares/5.6.355; RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., RA Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. XII. RT The complete sequences of 100 new cDNA clones from brain which code RT for large proteins in vitro."; RL DNA Res. 5:355-364(1998). RN [3] RP SEQUENCE REVISION. RX MEDLINE=22158633; PubMed=12168954; DOI=10.1093/dnares/9.3.99; RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.; RT "Construction of expression-ready cDNA clones for KIAA genes: manual RT curation of 330 KIAA cDNA clones."; RL DNA Res. 9:99-106(2002). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RC TISSUE=Testis; 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16625196; DOI=10.1038/nature04689; RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., RA Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., RA Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., RA Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., RA Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., RA Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., RA Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., RA Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.; RT "DNA sequence of human chromosome 17 and analysis of rearrangement in RT the human lineage."; RL Nature 440:1045-1049(2006). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). 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 [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-215; SER-249; SER-265; RP SER-293; SER-303; SER-423; THR-692 AND SER-1083, AND MASS RP SPECTROMETRY. RC TISSUE=Cervix carcinoma; RX PubMed=15302935; DOI=10.1073/pnas.0404720101; RA Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., RA Li J., Cohn M.A., Cantley L.C., Gygi S.P.; RT "Large-scale characterization of HeLa cell nuclear phosphoproteins."; RL Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-77; SER-78; SER-80; RP SER-84; SER-274; SER-276; SER-423; SER-681 AND SER-685, AND MASS RP SPECTROMETRY. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., RA Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in RT signaling networks."; RL Cell 127:635-648(2006). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-423 AND THR-692, AND RP MASS SPECTROMETRY. RC TISSUE=Cervix carcinoma; RX PubMed=16964243; DOI=10.1038/nbt1240; RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.; RT "A probability-based approach for high-throughput protein RT phosphorylation analysis and site localization."; RL Nat. Biotechnol. 24:1285-1292(2006). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-274; SER-276; SER-383; RP SER-385; SER-423; SER-681; SER-685 AND THR-893, AND MASS SPECTROMETRY. RC TISSUE=Leukemic T-cell; RX PubMed=17192257; DOI=10.1074/mcp.T600062-MCP200; RA Wissing J., Jaensch L., Nimtz M., Dieterich G., Hornberger R., RA Keri G., Wehland J., Daub H.; RT "Proteomics analysis of protein kinases by target class-selective RT prefractionation and tandem mass spectrometry."; RL Mol. Cell. Proteomics 6:537-547(2007). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1083, AND MASS RP SPECTROMETRY. RC TISSUE=Cervix carcinoma; RX PubMed=19007248; DOI=10.1021/ac801708p; RA Wang B., Malik R., Nigg E.A., Korner R.; RT "Evaluation of the low-specificity protease elastase for large-scale RT phosphoproteome analysis."; RL Anal. Chem. 80:9526-9533(2008). RN [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-24; SER-25; SER-32; RP THR-57; TYR-73; SER-77; SER-78; SER-80; SER-84; SER-236; SER-238; RP SER-249; SER-274; SER-276; SER-291; SER-293; SER-301; SER-303; RP SER-341; SER-343; SER-383; SER-385; SER-400; SER-423; THR-514; RP SER-681; SER-685; THR-692; THR-893; SER-1083 AND THR-1244, AND MASS RP 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). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-249; SER-301; SER-303; RP SER-318; SER-320; SER-323; SER-325; SER-332; SER-333; SER-334; RP SER-343; SER-345; SER-382; SER-383; SER-385; SER-400; SER-423; RP SER-681; SER-685 AND THR-692, AND MASS SPECTROMETRY. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-681; SER-685; THR-692; RP THR-1076; SER-1082 AND SER-1083, AND MASS SPECTROMETRY. RC TISSUE=Embryonic kidney; RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., RA Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in RT a refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [16] RP FUNCTION. RX PubMed=19651820; DOI=10.1093/carcin/bgp187; RA Iorns E., Martens-de Kemp S.R., Lord C.J., Ashworth A.; RT "CRK7 modifies the MAPK pathway and influences the response to RT endocrine therapy."; RL Carcinogenesis 30:1696-1701(2009). RN [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-14; SER-24; SER-29; RP THR-57; SER-62; THR-82; SER-84; SER-228; SER-236; SER-249; SER-274; RP SER-276; SER-291; SER-293; SER-301; SER-303; SER-323; SER-325; RP SER-332; SER-333; SER-334; SER-382; SER-383; SER-385; SER-393; RP SER-420; SER-423; SER-434; THR-514; SER-681; SER-685; THR-692; RP TYR-892; THR-893; SER-1053; THR-1070; THR-1074; THR-1076; SER-1082; RP SER-1083 AND THR-1244, 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 [18] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-236; SER-383; SER-385; RP SER-681; SER-685 AND THR-1244, AND MASS SPECTROMETRY. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [19] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-504, AND MASS SPECTROMETRY. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [20] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=20952539; DOI=10.1101/gad.1968210; RA Bartkowiak B., Liu P., Phatnani H.P., Fuda N.J., Cooper J.J., RA Price D.H., Adelman K., Lis J.T., Greenleaf A.L.; RT "CDK12 is a transcription elongation-associated CTD kinase, the RT metazoan ortholog of yeast Ctk1."; RL Genes Dev. 24:2303-2316(2010). RN [21] RP CHROMOSOMAL REARRANGEMENT WITH ERBB2, AND POSSIBLE INVOLVEMENT IN RP GASTRIC CANCER. RX PubMed=21097718; DOI=10.1158/0008-5472.CAN-10-1749; RA Zang Z.J., Ong C.K., Cutcutache I., Yu W., Zhang S.L., Huang D., RA Ler L.D., Dykema K., Gan A., Tao J., Lim S., Liu Y., Futreal P.A., RA Grabsch H., Furge K.A., Goh L.K., Rozen S., Teh B.T., Tan P.; RT "Genetic and structural variation in the gastric cancer kinome RT revealed through targeted deep sequencing."; RL Cancer Res. 71:29-39(2011). RN [22] 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 [23] RP VARIANTS [LARGE SCALE ANALYSIS] ALA-530; HIS-912; GLN-1189 AND RP LEU-1275. RX PubMed=17344846; DOI=10.1038/nature05610; RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., RA Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., RA O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., RA Bhamra G., Buck G., Choudhury B., Clements J., Cole J., Dicks E., RA Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., RA Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., RA Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., RA West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., RA Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., RA DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., RA Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., RA Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.; RT "Patterns of somatic mutation in human cancer genomes."; RL Nature 446:153-158(2007). CC -!- FUNCTION: Cyclin-dependent kinase which displays CTD kinase CC activity and is required for RNA splicing. Has CTD kinase activity CC by hyperphosphorylating the C-terminal heptapeptide repeat domain CC (CTD) of the largest RNA polymerase II subunit RPB1, thereby CC acting as a key regulator of transcription elongation. Required CC for RNA splicing, possibly by phosphorylating SRSF1/SF2. Involved CC in regulation of MAP kinase activity, possibly leading to affect CC the response to estrogn inhibitors. CC -!- CATALYTIC ACTIVITY: ATP + [DNA-directed RNA polymerase] = ADP + CC [DNA-directed RNA polymerase] phosphate. CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. CC -!- SUBUNIT: Interacts with CCNL1 and CCNL2 (By similarity). CC -!- SUBCELLULAR LOCATION: Nucleus. Nucleus speckle. Note=Colocalized CC with nuclear speckles throughout interphase. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q9NYV4-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9NYV4-2; Sequence=VSP_030284; CC Name=3; CC IsoId=Q9NYV4-3; Sequence=VSP_040908, VSP_040909, VSP_040910; CC Note=No experimental confirmation available; CC -!- TISSUE SPECIFICITY: Ubiquitously expressed. CC -!- DISEASE: Note=Chromosomal aberrations involving CDK12 may be a CC cause gastric cancer. Deletions within 17q12 region producing CC fusion transcripts with ERBB2, leading to CDK12-ERBB2 fusion CC leading to trunctated CDK12 protein not in-frame with ERBB2. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC CC Ser/Thr protein kinase family. CDC2/CDKX subfamily. CC -!- SIMILARITY: Contains 1 protein kinase domain. CC -!- SEQUENCE CAUTION: CC Sequence=BAA74927.2; Type=Erroneous initiation; Note=Translation N-terminally shortened; 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; AF227198; AAF36401.1; -; mRNA. DR EMBL; AB020711; BAA74927.2; ALT_INIT; mRNA. DR EMBL; AK302645; BAG63886.1; -; mRNA. DR EMBL; AC009283; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471152; EAW60577.1; -; Genomic_DNA. DR EMBL; BC140854; AAI40855.1; -; mRNA. DR EMBL; BC150265; AAI50266.1; -; mRNA. DR IPI; IPI00021175; -. DR IPI; IPI00868781; -. DR IPI; IPI00910891; -. DR RefSeq; NP_055898.1; NM_015083.1. DR RefSeq; NP_057591.2; NM_016507.2. DR UniGene; Hs.416108; -. DR ProteinModelPortal; Q9NYV4; -. DR SMR; Q9NYV4; 723-1023. DR IntAct; Q9NYV4; 2. DR MINT; MINT-1191969; -. DR STRING; Q9NYV4; -. DR PhosphoSite; Q9NYV4; -. DR DMDM; 308153421; -. DR PRIDE; Q9NYV4; -. DR DNASU; 51755; -. DR Ensembl; ENST00000300647; ENSP00000300647; ENSG00000167258. DR Ensembl; ENST00000430627; ENSP00000407720; ENSG00000167258. DR Ensembl; ENST00000447079; ENSP00000398880; ENSG00000167258. DR GeneID; 51755; -. DR KEGG; hsa:51755; -. DR UCSC; uc002hrw.4; human. DR UCSC; uc010cvv.3; human. DR CTD; 51755; -. DR GeneCards; GC17P037618; -. DR H-InvDB; HIX0013777; -. DR HGNC; HGNC:24224; CDK12. DR HPA; HPA008038; -. DR neXtProt; NX_Q9NYV4; -. DR PharmGKB; PA142672078; -. DR PharmGKB; PA165431656; -. DR eggNOG; COG0515; -. DR GeneTree; ENSGT00620000087895; -. DR HOGENOM; HBG282140; -. DR HOVERGEN; HBG050852; -. DR InParanoid; Q9NYV4; -. DR KO; K08819; -. DR OMA; DSYKKSP; -. DR OrthoDB; EOG498V0D; -. DR PhylomeDB; Q9NYV4; -. DR BRENDA; 2.7.11.22; 2681. DR NextBio; 55858; -. DR ArrayExpress; Q9NYV4; -. DR Bgee; Q9NYV4; -. DR CleanEx; HS_CRKRS; -. DR Genevestigator; Q9NYV4; -. DR GO; GO:0019908; C:nuclear cyclin-dependent protein kinase holoenzyme complex; ISS:UniProtKB. DR GO; GO:0016607; C:nuclear speck; IDA:UniProtKB. DR GO; GO:0005730; C:nucleolus; IDA:HPA. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0004693; F:cyclin-dependent protein kinase activity; IEA:EC. DR GO; GO:0008353; F:RNA polymerase II carboxy-terminal domain kinase activity; IMP:UniProtKB. DR GO; GO:0006397; P:mRNA processing; IEA:UniProtKB-KW. DR GO; GO:0070816; P:phosphorylation of RNA polymerase II C-terminal domain; IMP:UniProtKB. DR GO; GO:0046777; P:protein autophosphorylation; IDA:HGNC. DR GO; GO:0043405; P:regulation of MAP kinase activity; IMP:UniProtKB. DR GO; GO:0008380; P:RNA splicing; ISS:UniProtKB. DR InterPro; IPR011009; Kinase-like_dom. DR InterPro; IPR000719; Prot_kinase_cat_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR InterPro; IPR002290; Ser/Thr_dual-sp_kinase_dom. DR InterPro; IPR008271; Ser/Thr_kinase_AS. DR Pfam; PF00069; Pkinase; 1. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF56112; Kinase_like; 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 Acetylation; Alternative splicing; ATP-binding; KW Chromosomal rearrangement; Complete proteome; Kinase; mRNA processing; KW mRNA splicing; Nucleotide-binding; Nucleus; Phosphoprotein; KW Polymorphism; Reference proteome; Serine/threonine-protein kinase; KW Transferase. FT CHAIN 1 1490 Cyclin-dependent kinase 12. FT /FTId=PRO_0000085715. FT DOMAIN 727 1020 Protein kinase. FT NP_BIND 733 741 ATP (By similarity). FT COMPBIAS 407 413 Poly-Ala. FT COMPBIAS 535 540 Poly-Pro. FT COMPBIAS 1266 1280 Poly-Pro. FT ACT_SITE 859 859 Proton acceptor (By similarity). FT BINDING 756 756 ATP (By similarity). FT MOD_RES 14 14 Phosphoserine. FT MOD_RES 24 24 Phosphoserine. FT MOD_RES 25 25 Phosphoserine. FT MOD_RES 29 29 Phosphoserine. FT MOD_RES 32 32 Phosphoserine. FT MOD_RES 57 57 Phosphothreonine. FT MOD_RES 62 62 Phosphoserine. FT MOD_RES 73 73 Phosphotyrosine. FT MOD_RES 77 77 Phosphoserine. FT MOD_RES 78 78 Phosphoserine. FT MOD_RES 80 80 Phosphoserine. FT MOD_RES 82 82 Phosphothreonine. FT MOD_RES 84 84 Phosphoserine. FT MOD_RES 215 215 Phosphoserine. FT MOD_RES 228 228 Phosphoserine. FT MOD_RES 236 236 Phosphoserine. FT MOD_RES 238 238 Phosphoserine. FT MOD_RES 249 249 Phosphoserine. FT MOD_RES 265 265 Phosphoserine. FT MOD_RES 274 274 Phosphoserine. FT MOD_RES 276 276 Phosphoserine. FT MOD_RES 279 279 Phosphotyrosine (By similarity). FT MOD_RES 291 291 Phosphoserine. FT MOD_RES 293 293 Phosphoserine. FT MOD_RES 301 301 Phosphoserine. FT MOD_RES 303 303 Phosphoserine. FT MOD_RES 318 318 Phosphoserine. FT MOD_RES 319 319 Phosphotyrosine (By similarity). FT MOD_RES 320 320 Phosphoserine. FT MOD_RES 323 323 Phosphoserine. FT MOD_RES 325 325 Phosphoserine. FT MOD_RES 332 332 Phosphoserine. FT MOD_RES 333 333 Phosphoserine. FT MOD_RES 334 334 Phosphoserine. FT MOD_RES 341 341 Phosphoserine. FT MOD_RES 343 343 Phosphoserine. FT MOD_RES 345 345 Phosphoserine. FT MOD_RES 382 382 Phosphoserine. FT MOD_RES 383 383 Phosphoserine. FT MOD_RES 385 385 Phosphoserine. FT MOD_RES 393 393 Phosphoserine. FT MOD_RES 400 400 Phosphoserine. FT MOD_RES 420 420 Phosphoserine. FT MOD_RES 423 423 Phosphoserine. FT MOD_RES 434 434 Phosphoserine. FT MOD_RES 504 504 N6-acetyllysine. FT MOD_RES 514 514 Phosphothreonine. FT MOD_RES 681 681 Phosphoserine. FT MOD_RES 685 685 Phosphoserine. FT MOD_RES 692 692 Phosphothreonine. FT MOD_RES 892 892 Phosphotyrosine. FT MOD_RES 893 893 Phosphothreonine. FT MOD_RES 1053 1053 Phosphoserine. FT MOD_RES 1070 1070 Phosphothreonine. FT MOD_RES 1074 1074 Phosphothreonine. FT MOD_RES 1076 1076 Phosphothreonine. FT MOD_RES 1082 1082 Phosphoserine. FT MOD_RES 1083 1083 Phosphoserine. FT MOD_RES 1244 1244 Phosphothreonine. FT VAR_SEQ 349 349 Missing (in isoform 3). FT /FTId=VSP_040908. FT VAR_SEQ 1205 1274 DMQNILAVLLSQLMKTQEPAGSLEENNSDKNSGPQGPRRTP FT TMPQEEAAACPPHILPPEKRPPEPPGPPP -> ILWYMQRP FT NCKTMGSWGQEPLGPAAQEQAFTGGAQLSLLLMENSIGGLQ FT ESHQEGEEGEEFLTNPETSVS (in isoform 3). FT /FTId=VSP_040909. FT VAR_SEQ 1254 1262 Missing (in isoform 2). FT /FTId=VSP_030284. FT VAR_SEQ 1275 1490 Missing (in isoform 3). FT /FTId=VSP_040910. FT VARIANT 530 530 P -> A (in dbSNP:rs56121596). FT /FTId=VAR_041968. FT VARIANT 912 912 R -> H (in a colorectal adenocarcinoma FT sample; somatic mutation). FT /FTId=VAR_041969. FT VARIANT 1189 1189 L -> Q (in dbSNP:rs56362165). FT /FTId=VAR_041970. FT VARIANT 1275 1275 P -> L (in dbSNP:rs34070318). FT /FTId=VAR_041971. FT CONFLICT 133 133 S -> G (in Ref. 4; BAG63886). FT CONFLICT 268 268 S -> G (in Ref. 4; BAG63886). FT CONFLICT 639 639 D -> G (in Ref. 1; AAF36401). FT CONFLICT 737 737 T -> I (in Ref. 4; BAG63886). FT CONFLICT 745 745 K -> R (in Ref. 1; AAF36401). FT CONFLICT 822 822 G -> V (in Ref. 4; BAG63886). FT CONFLICT 1195 1195 T -> M (in Ref. 1; AAF36401, 2; BAA74927 FT and 6; AAI50266). SQ SEQUENCE 1490 AA; 164155 MW; D6B04B998ECDE58E CRC64; MPNSERHGGK KDGSGGASGT LQPSSGGGSS NSRERHRLVS KHKRHKSKHS KDMGLVTPEA ASLGTVIKPL VEYDDISSDS DTFSDDMAFK LDRRENDERR GSDRSDRLHK HRHHQHRRSR DLLKAKQTEK EKSQEVSSKS GSMKDRISGS SKRSNEETDD YGKAQVAKSS SKESRSSKLH KEKTRKEREL KSGHKDRSKS HRKRETPKSY KTVDSPKRRS RSPHRKWSDS SKQDDSPSGA SYGQDYDLSP SRSHTSSNYD SYKKSPGSTS RRQSVSPPYK EPSAYQSSTR SPSPYSRRQR SVSPYSRRRS SSYERSGSYS GRSPSPYGRR RSSSPFLSKR SLSRSPLPSR KSMKSRSRSP AYSRHSSSHS KKKRSSSRSR HSSISPVRLP LNSSLGAELS RKKKERAAAA AAAKMDGKES KGSPVFLPRK ENSSVEAKDS GLESKKLPRS VKLEKSAPDT ELVNVTHLNT EVKNSSDTGK VKLDENSEKH LVKDLKAQGT RDSKPIALKE EIVTPKETET SEKETPPPLP TIASPPPPLP TTTPPPQTPP LPPLPPIPAL PQQPPLPPSQ PAFSQVPASS TSTLPPSTHS KTSAVSSQAN SQPPVQVSVK TQVSVTAAIP HLKTSTLPPL PLPPLLPGDD DMDSPKETLP SKPVKKEKEQ RTRHLLTDLP LPPELPGGDL SPPDSPEPKA ITPPQQPYKK RPKICCPRYG ERRQTESDWG KRCVDKFDII GIIGEGTYGQ VYKAKDKDTG ELVALKKVRL DNEKEGFPIT AIREIKILRQ LIHRSVVNMK EIVTDKQDAL DFKKDKGAFY LVFEYMDHDL MGLLESGLVH FSEDHIKSFM KQLMEGLEYC HKKNFLHRDI KCSNILLNNS GQIKLADFGL ARLYNSEESR PYTNKVITLW YRPPELLLGE ERYTPAIDVW SCGCILGELF TKKPIFQANL ELAQLELISR LCGSPCPAVW PDVIKLPYFN TMKPKKQYRR RLREEFSFIP SAALDLLDHM LTLDPSKRCT AEQTLQSDFL KDVELSKMAP PDLPHWQDCH ELWSKKRRRQ RQSGVVVEEP PPSKTSRKET TSGTSTEPVK NSSPAPPQPA PGKVESGAGD AIGLADITQQ LNQSELAVLL NLLQSQTDLS IPQMAQLLNI HSNPEMQQQL EALNQSISAL TEATSQQQDS ETMAPEESLK EAPSAPVILP SAEQTTLEAS STPADMQNIL AVLLSQLMKT QEPAGSLEEN NSDKNSGPQG PRRTPTMPQE EAAACPPHIL PPEKRPPEPP GPPPPPPPPP LVEGDLSSAP QELNPAVTAA LLQLLSQPEA EPPGHLPHEH QALRPMEYST RPRPNRTYGN TDGPETGFSA IDTDERNSGP ALTESLVQTL VKNRTFSGSL SHLGESSSYQ GTGSVQFPGD QDLRFARVPL ALHPVVGQPF LKAEGSSNSV VHAETKLQNY GELGPGTTGA SSSGAGLHWG GPTQSSAYGK LYRGPTRVPP RGGRGRGVPY //