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 27-MAR-2024, entry version 207. DE RecName: Full=Cyclin-dependent kinase 12; DE EC=2.7.11.22; DE EC=2.7.11.23 {ECO:0000305|PubMed:20952539}; 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; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, SUBCELLULAR RP LOCATION, AND FUNCTION. RX PubMed=11683387; DOI=10.1242/jcs.114.14.2591; RA Ko T.K., Kelly E., Pines J.; RT "CrkRS: a novel conserved Cdc2-related protein kinase that colocalises with RT SC35 speckles."; RL J. Cell Sci. 114:2591-2603(2001). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Brain; RX PubMed=10048485; DOI=10.1093/dnares/5.6.355; RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N., RA Tanaka A., Kotani H., Nomura N., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. XII. The RT complete sequences of 100 new cDNA clones from brain which code for large RT proteins in vitro."; RL DNA Res. 5:355-364(1998). RN [3] RP SEQUENCE REVISION. RX 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., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., 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., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA 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., Gnerre S., RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., RA Schwartz D.C., 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 the RT 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., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., 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 project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-681 AND SER-685, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. 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., Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling RT networks."; RL Cell 127:635-648(2006). RN [9] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. 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 phosphorylation RT analysis and site localization."; RL Nat. Biotechnol. 24:1285-1292(2006). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-57; TYR-73; SER-400; SER-423; RP THR-514; SER-681; SER-685 AND THR-692, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. 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 the RT kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-249; SER-301; SER-303; RP SER-318; SER-323; SER-325; SER-332; SER-333; SER-334; SER-345; SER-383; RP SER-385; SER-400; SER-681; SER-685 AND THR-692, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. 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 [12] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [13] 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 endocrine RT therapy."; RL Carcinogenesis 30:1696-1701(2009). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-420; SER-423; SER-681; RP SER-685; THR-692 AND SER-1053, AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. 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 [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-236; SER-383; SER-385; RP SER-681; SER-685 AND THR-1244, AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. 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 [16] 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., Price D.H., RA Adelman K., Lis J.T., Greenleaf A.L.; RT "CDK12 is a transcription elongation-associated CTD kinase, the metazoan RT ortholog of yeast Ctk1."; RL Genes Dev. 24:2303-2316(2010). RN [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-236; SER-249; SER-385; RP SER-400; SER-423; SER-681; SER-685; THR-893 AND SER-1083, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [18] 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., Buerckstuemmer T., RA 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 [19] RP CHROMOSOMAL REARRANGEMENT WITH ERBB2, AND POSSIBLE INVOLVEMENT IN GASTRIC RP 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., Ler L.D., RA Dykema K., Gan A., Tao J., Lim S., Liu Y., Futreal P.A., Grabsch H., RA Furge K.A., Goh L.K., Rozen S., Teh B.T., Tan P.; RT "Genetic and structural variation in the gastric cancer kinome revealed RT through targeted deep sequencing."; RL Cancer Res. 71:29-39(2011). RN [20] RP FUNCTION, SUBUNIT, AND SUBCELLULAR LOCATION. RX PubMed=22012619; DOI=10.1101/gad.16962311; RA Blazek D., Kohoutek J., Bartholomeeusen K., Johansen E., Hulinkova P., RA Luo Z., Cimermancic P., Ule J., Peterlin B.M.; RT "The Cyclin K/Cdk12 complex maintains genomic stability via regulation of RT expression of DNA damage response genes."; RL Genes Dev. 25:2158-2172(2011). RN [21] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-236; SER-249; SER-274; RP SER-276; SER-301; SER-303; SER-310; SER-312; SER-332; SER-333; SER-334; RP SER-338; SER-423; SER-681; SER-685; THR-893 AND SER-1083, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [22] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-236; SER-249; SER-265; RP SER-274; SER-276; SER-318; SER-323; SER-325; SER-332; SER-333; SER-334; RP SER-341; SER-343; SER-345; SER-423; THR-514; SER-614; SER-681; THR-692; RP SER-889; THR-893; SER-1053 AND SER-1083, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [23] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-423; SER-681 AND SER-685, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [24] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-263; LYS-509 AND LYS-655, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=28112733; DOI=10.1038/nsmb.3366; RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C., RA Nielsen M.L.; RT "Site-specific mapping of the human SUMO proteome reveals co-modification RT with phosphorylation."; RL Nat. Struct. Mol. Biol. 24:325-336(2017). RN [25] RP INTERACTION WITH HHV-1 TRANSCRIPTIONAL REGULATOR ICP22 (MICROBIAL RP INFECTION). RX PubMed=34696162; DOI=10.3390/vaccines9101054; RA Isa N.F., Bensaude O., Aziz N.C., Murphy S.; RT "HSV-1 ICP22 Is a Selective Viral Repressor of Cellular RNA Polymerase II- RT Mediated Transcription Elongation."; RL Vaccines (Basel) 9:0-0(2021). RN [26] RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 714-1063 IN COMPLEX WITH THE ATP RP ANALOG ADP; TRANSITION STATE ANALOG AND CCNK, FUNCTION, CATALYTIC ACTIVITY, RP SUBUNIT, INTERACTION WITH CCNK, PHOSPHORYLATION AT THR-893, IDENTIFICATION RP BY MASS SPECTROMETRY, MUTAGENESIS OF ASP-877, AND ACTIVITY REGULATION. RX PubMed=24662513; DOI=10.1038/ncomms4505; RA Boesken C.A., Farnung L., Hintermair C., Merzel Schachter M., RA Vogel-Bachmayr K., Blazek D., Anand K., Fisher R.P., Eick D., Geyer M.; RT "The structure and substrate specificity of human Cdk12/Cyclin K."; RL Nat. Commun. 5:3505-3505(2014). RN [27] RP VARIANTS [LARGE SCALE ANALYSIS] ALA-530; HIS-912; GLN-1189 AND LEU-1275. RX PubMed=17344846; DOI=10.1038/nature05610; RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G., RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., RA 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 that phosphorylates the C-terminal CC domain (CTD) of the large subunit of RNA polymerase II (POLR2A), CC thereby acting as a key regulator of transcription elongation. CC Regulates the expression of genes involved in DNA repair and is CC required for the maintenance of genomic stability. Preferentially CC phosphorylates 'Ser-5' in CTD repeats that are already phosphorylated CC at 'Ser-7', but can also phosphorylate 'Ser-2'. Required for RNA CC splicing, possibly by phosphorylating SRSF1/SF2. Involved in regulation CC of MAP kinase activity, possibly leading to affect the response to CC estrogen inhibitors. {ECO:0000269|PubMed:11683387, CC ECO:0000269|PubMed:19651820, ECO:0000269|PubMed:20952539, CC ECO:0000269|PubMed:22012619, ECO:0000269|PubMed:24662513}. 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:0000305|PubMed:20952539}; 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 -!- 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; CC -!- ACTIVITY REGULATION: Inhibited by the ATP analog flavopiridol, CC purvalanol A, purvalanol B, staurosporine and CR8. CC {ECO:0000269|PubMed:24662513}. CC -!- SUBUNIT: Interacts with CCNL1 and CCNL2 (By similarity). Interacts with CC CCNK. {ECO:0000250, ECO:0000269|PubMed:22012619, CC ECO:0000269|PubMed:24662513}. CC -!- SUBUNIT: (Microbial infection) Interacts with human herpes virus 1 CC (HHV-1) transcriptional regulator ICP22. {ECO:0000269|PubMed:34696162}. CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11683387}. Nucleus CC speckle {ECO:0000269|PubMed:11683387}. Note=Colocalized with nuclear CC speckles throughout interphase. {ECO:0000269|PubMed:11683387}. 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 -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:11683387}. CC -!- PTM: Phosphorylation at Thr-893 increases kinase activity. CC {ECO:0000269|PubMed:24662513}. CC -!- DISEASE: Note=Chromosomal aberrations involving CDK12 may be a cause CC gastric cancer. Deletions within 17q12 region producing fusion CC transcripts with ERBB2, leading to CDK12-ERBB2 fusion leading to CC trunctated CDK12 protein not in-frame with ERBB2. 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=BAA74927.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; 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 CCDS; CCDS11337.1; -. [Q9NYV4-1] DR CCDS; CCDS45666.1; -. [Q9NYV4-2] DR RefSeq; NP_055898.1; NM_015083.2. [Q9NYV4-2] DR RefSeq; NP_057591.2; NM_016507.3. [Q9NYV4-1] DR PDB; 4CXA; X-ray; 3.15 A; A/C=715-1052. DR PDB; 4NST; X-ray; 2.20 A; A/C=714-1063. DR PDB; 4UN0; X-ray; 3.15 A; C/D=715-1038. DR PDB; 5ACB; X-ray; 2.70 A; C/D=715-1052. DR PDB; 6B3E; X-ray; 3.06 A; A/C=717-1036. DR PDB; 6CKX; X-ray; 2.80 A; A/C=714-1063. DR PDB; 6TD3; X-ray; 3.46 A; B/E/H=712-1051. DR PDB; 7NXK; X-ray; 3.00 A; A/C=714-1063. DR PDB; 8BU1; X-ray; 2.98 A; B/E/H=712-1051. DR PDB; 8BU2; X-ray; 3.13 A; B/E/H=712-1051. DR PDB; 8BU3; X-ray; 3.42 A; B/E/H=712-1051. DR PDB; 8BU4; X-ray; 3.09 A; B/E/H=712-1051. DR PDB; 8BU5; X-ray; 3.13 A; B/E/H=712-1051. DR PDB; 8BU6; X-ray; 3.45 A; B/E/H=712-1051. DR PDB; 8BU7; X-ray; 3.25 A; B/E/H=712-1051. DR PDB; 8BU9; X-ray; 3.51 A; B/E/H=712-1051. DR PDB; 8BUA; X-ray; 3.19 A; B/E/H=712-1051. DR PDB; 8BUB; X-ray; 3.42 A; B/E/H=712-1051. DR PDB; 8BUC; X-ray; 3.85 A; B/E/H=712-1051. DR PDB; 8BUD; X-ray; 3.20 A; B/E/H=712-1051. DR PDB; 8BUE; X-ray; 3.25 A; B/E/H=712-1051. DR PDB; 8BUF; X-ray; 3.30 A; B/E/H=712-1051. DR PDB; 8BUG; X-ray; 3.53 A; B/E/H=712-1051. DR PDB; 8BUH; X-ray; 3.79 A; B/E/H=712-1051. DR PDB; 8BUI; X-ray; 3.50 A; B/E/H=712-1051. DR PDB; 8BUJ; X-ray; 3.62 A; B/E/H=712-1051. DR PDB; 8BUK; X-ray; 3.41 A; B/E/H=712-1051. DR PDB; 8BUL; X-ray; 3.40 A; B/E/H=712-1052. DR PDB; 8BUM; X-ray; 3.36 A; B/E/H=712-1051. DR PDB; 8BUN; X-ray; 3.08 A; B/E/H=712-1051. DR PDB; 8BUO; X-ray; 3.58 A; B/E/H=712-1051. DR PDB; 8BUP; X-ray; 3.41 A; B/E/H=712-1051. DR PDB; 8BUQ; X-ray; 3.20 A; B/E/H=712-1051. DR PDB; 8BUR; X-ray; 3.64 A; B/E/H=712-1051. DR PDB; 8BUS; X-ray; 3.26 A; B/E/H=712-1051. DR PDB; 8BUT; X-ray; 3.25 A; B/E/H=712-1051. DR PDB; 8P81; X-ray; 2.68 A; A=714-1063. DR PDBsum; 4CXA; -. DR PDBsum; 4NST; -. DR PDBsum; 4UN0; -. DR PDBsum; 5ACB; -. DR PDBsum; 6B3E; -. DR PDBsum; 6CKX; -. DR PDBsum; 6TD3; -. DR PDBsum; 7NXK; -. DR PDBsum; 8BU1; -. DR PDBsum; 8BU2; -. DR PDBsum; 8BU3; -. DR PDBsum; 8BU4; -. DR PDBsum; 8BU5; -. DR PDBsum; 8BU6; -. DR PDBsum; 8BU7; -. DR PDBsum; 8BU9; -. DR PDBsum; 8BUA; -. DR PDBsum; 8BUB; -. DR PDBsum; 8BUC; -. DR PDBsum; 8BUD; -. DR PDBsum; 8BUE; -. DR PDBsum; 8BUF; -. DR PDBsum; 8BUG; -. DR PDBsum; 8BUH; -. DR PDBsum; 8BUI; -. DR PDBsum; 8BUJ; -. DR PDBsum; 8BUK; -. DR PDBsum; 8BUL; -. DR PDBsum; 8BUM; -. DR PDBsum; 8BUN; -. DR PDBsum; 8BUO; -. DR PDBsum; 8BUP; -. DR PDBsum; 8BUQ; -. DR PDBsum; 8BUR; -. DR PDBsum; 8BUS; -. DR PDBsum; 8BUT; -. DR PDBsum; 8P81; -. DR AlphaFoldDB; Q9NYV4; -. DR SMR; Q9NYV4; -. DR BioGRID; 119715; 263. DR ComplexPortal; CPX-241; Cyclin K-CDK12 complex. DR CORUM; Q9NYV4; -. DR DIP; DIP-39768N; -. DR IntAct; Q9NYV4; 31. DR MINT; Q9NYV4; -. DR STRING; 9606.ENSP00000398880; -. DR BindingDB; Q9NYV4; -. DR ChEMBL; CHEMBL3559692; -. DR GuidetoPHARMACOLOGY; 1965; -. DR CarbonylDB; Q9NYV4; -. DR GlyConnect; 2877; 1 O-GlcNAc glycan (2 sites). DR GlyCosmos; Q9NYV4; 6 sites, 1 glycan. DR GlyGen; Q9NYV4; 15 sites, 1 O-linked glycan (15 sites). DR iPTMnet; Q9NYV4; -. DR PhosphoSitePlus; Q9NYV4; -. DR SwissPalm; Q9NYV4; -. DR BioMuta; CDK12; -. DR DMDM; 308153421; -. DR CPTAC; non-CPTAC-2958; -. DR CPTAC; non-CPTAC-2959; -. DR EPD; Q9NYV4; -. DR jPOST; Q9NYV4; -. DR MassIVE; Q9NYV4; -. DR MaxQB; Q9NYV4; -. DR PaxDb; 9606-ENSP00000398880; -. DR PeptideAtlas; Q9NYV4; -. DR ProteomicsDB; 83279; -. [Q9NYV4-1] DR ProteomicsDB; 83280; -. [Q9NYV4-2] DR ProteomicsDB; 83281; -. [Q9NYV4-3] DR Pumba; Q9NYV4; -. DR Antibodypedia; 2096; 258 antibodies from 32 providers. DR CPTC; Q9NYV4; 2 antibodies. DR DNASU; 51755; -. DR Ensembl; ENST00000430627.6; ENSP00000407720.2; ENSG00000167258.16. [Q9NYV4-2] DR Ensembl; ENST00000447079.6; ENSP00000398880.4; ENSG00000167258.16. [Q9NYV4-1] DR GeneID; 51755; -. DR KEGG; hsa:51755; -. DR MANE-Select; ENST00000447079.6; ENSP00000398880.4; NM_016507.4; NP_057591.2. DR UCSC; uc002hrw.6; human. [Q9NYV4-1] DR AGR; HGNC:24224; -. DR CTD; 51755; -. DR DisGeNET; 51755; -. DR GeneCards; CDK12; -. DR HGNC; HGNC:24224; CDK12. DR HPA; ENSG00000167258; Low tissue specificity. DR MIM; 615514; gene. DR neXtProt; NX_Q9NYV4; -. DR OpenTargets; ENSG00000167258; -. DR PharmGKB; PA165431656; -. DR VEuPathDB; HostDB:ENSG00000167258; -. DR eggNOG; KOG0600; Eukaryota. DR GeneTree; ENSGT00940000157595; -. DR InParanoid; Q9NYV4; -. DR OMA; HWGAPAQ; -. DR OrthoDB; 5402490at2759; -. DR PhylomeDB; Q9NYV4; -. DR TreeFam; TF101060; -. DR BRENDA; 2.7.11.22; 2681. DR BRENDA; 2.7.11.23; 2681. DR PathwayCommons; Q9NYV4; -. DR Reactome; R-HSA-6796648; TP53 Regulates Transcription of DNA Repair Genes. DR SignaLink; Q9NYV4; -. DR SIGNOR; Q9NYV4; -. DR BioGRID-ORCS; 51755; 350 hits in 1217 CRISPR screens. DR ChiTaRS; CDK12; human. DR GeneWiki; CRKRS; -. DR GenomeRNAi; 51755; -. DR Pharos; Q9NYV4; Tchem. DR PRO; PR:Q9NYV4; -. DR Proteomes; UP000005640; Chromosome 17. DR RNAct; Q9NYV4; Protein. DR Bgee; ENSG00000167258; Expressed in buccal mucosa cell and 175 other cell types or tissues. DR ExpressionAtlas; Q9NYV4; baseline and differential. DR GO; GO:0002944; C:cyclin K-CDK12 complex; IPI:MGI. DR GO; GO:0008024; C:cyclin/CDK positive transcription elongation factor complex; IBA:GO_Central. DR GO; GO:0019908; C:nuclear cyclin-dependent protein kinase holoenzyme complex; ISS:UniProtKB. DR GO; GO:0016607; C:nuclear speck; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IBA:GO_Central. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0030332; F:cyclin binding; IPI:MGI. DR GO; GO:0004693; F:cyclin-dependent protein serine/threonine kinase activity; IEA:UniProtKB-EC. DR GO; GO:0004672; F:protein kinase activity; IDA:HGNC-UCL. DR GO; GO:0019901; F:protein kinase binding; IEA:Ensembl. DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA. DR GO; GO:0008353; F:RNA polymerase II CTD heptapeptide repeat kinase activity; IDA:GO_Central. DR GO; GO:0006397; P:mRNA processing; IEA:UniProtKB-KW. DR GO; GO:2000737; P:negative regulation of stem cell differentiation; IEA:Ensembl. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:UniProtKB. DR GO; GO:0032968; P:positive regulation of transcription elongation by RNA polymerase II; IDA:ComplexPortal. DR GO; GO:0046777; P:protein autophosphorylation; IDA:HGNC-UCL. DR GO; GO:0043405; P:regulation of MAP kinase activity; IMP:UniProtKB. DR GO; GO:0008380; P:RNA splicing; ISS:UniProtKB. DR GO; GO:0006366; P:transcription by RNA polymerase II; IDA:GO_Central. DR CDD; cd07864; STKc_CDK12; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. 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 PANTHER; PTHR24056; CELL DIVISION PROTEIN KINASE; 1. DR PANTHER; PTHR24056:SF126; CYCLIN-DEPENDENT KINASE 12; 1. DR Pfam; PF12330; Haspin_kinase; 1. DR Pfam; PF00069; Pkinase; 1. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. DR Genevisible; Q9NYV4; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; ATP-binding; Chromosomal rearrangement; KW Host-virus interaction; Isopeptide bond; Kinase; mRNA processing; KW mRNA splicing; Nucleotide-binding; Nucleus; Phosphoprotein; KW Reference proteome; Serine/threonine-protein kinase; Transferase; KW Ubl conjugation. FT CHAIN 1..1490 FT /note="Cyclin-dependent kinase 12" FT /id="PRO_0000085715" FT DOMAIN 727..1020 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT REGION 1..703 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1047..1098 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1161..1189 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1220..1348 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1441..1460 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1466..1490 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 17..33 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 36..50 FT /note="Basic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 85..105 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 106..121 FT /note="Basic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 122..139 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 149..163 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 173..194 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 233..364 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 365..379 FT /note="Basic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 398..412 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 432..456 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 462..476 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 477..523 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 528..572 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 573..621 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 640..665 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 675..695 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1066..1081 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1220..1243 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1259..1284 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1333..1348 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 859 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10027" FT BINDING 733..741 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT BINDING 756 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT BINDING 814..819 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT BINDING 1040 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT MOD_RES 57 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:18691976" FT MOD_RES 73 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:18691976" FT MOD_RES 236 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163" FT MOD_RES 249 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163" FT MOD_RES 265 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 274 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163" FT MOD_RES 276 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163" FT MOD_RES 301 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:21406692" FT MOD_RES 303 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:21406692" FT MOD_RES 310 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692" FT MOD_RES 312 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692" FT MOD_RES 318 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MOD_RES 323 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MOD_RES 325 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MOD_RES 332 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163" FT MOD_RES 333 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163" FT MOD_RES 334 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163" FT MOD_RES 338 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692" FT MOD_RES 341 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 343 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 345 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MOD_RES 383 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332" FT MOD_RES 385 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231" FT MOD_RES 400 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:20068231" FT MOD_RES 420 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19369195" FT MOD_RES 423 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18691976, FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163, FT ECO:0007744|PubMed:24275569" FT MOD_RES 514 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:18691976, FT ECO:0007744|PubMed:23186163" FT MOD_RES 614 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 644 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q3MJK5" FT MOD_RES 681 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:18691976, FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569" FT MOD_RES 685 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:18691976, FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:24275569" FT MOD_RES 692 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:19369195, FT ECO:0007744|PubMed:23186163" FT MOD_RES 889 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 893 FT /note="Phosphothreonine" FT /evidence="ECO:0000269|PubMed:24662513, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163" FT MOD_RES 1053 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19369195, FT ECO:0007744|PubMed:23186163" FT MOD_RES 1083 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163" FT MOD_RES 1244 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:19690332" FT MOD_RES 1246 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q14AX6" FT CROSSLNK 263 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 509 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 655 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT VAR_SEQ 349 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_040908" FT VAR_SEQ 1205..1274 FT /note="DMQNILAVLLSQLMKTQEPAGSLEENNSDKNSGPQGPRRTPTMPQEEAAACP FT PHILPPEKRPPEPPGPPP -> ILWYMQRPNCKTMGSWGQEPLGPAAQEQAFTGGAQLS FT LLLMENSIGGLQESHQEGEEGEEFLTNPETSVS (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_040909" FT VAR_SEQ 1254..1262 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:10048485, FT ECO:0000303|PubMed:15489334" FT /id="VSP_030284" FT VAR_SEQ 1275..1490 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_040910" FT VARIANT 530 FT /note="P -> A (in dbSNP:rs56121596)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041968" FT VARIANT 912 FT /note="R -> H (in a colorectal adenocarcinoma sample; FT somatic mutation)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041969" FT VARIANT 1189 FT /note="L -> Q (in dbSNP:rs56362165)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041970" FT VARIANT 1275 FT /note="P -> L (in dbSNP:rs34070318)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041971" FT MUTAGEN 877 FT /note="D->N: Abolishes kinase activity." FT /evidence="ECO:0000269|PubMed:24662513" FT CONFLICT 133 FT /note="S -> G (in Ref. 4; BAG63886)" FT /evidence="ECO:0000305" FT CONFLICT 268 FT /note="S -> G (in Ref. 4; BAG63886)" FT /evidence="ECO:0000305" FT CONFLICT 639 FT /note="D -> G (in Ref. 1; AAF36401)" FT /evidence="ECO:0000305" FT CONFLICT 737 FT /note="T -> I (in Ref. 4; BAG63886)" FT /evidence="ECO:0000305" FT CONFLICT 745 FT /note="K -> R (in Ref. 1; AAF36401)" FT /evidence="ECO:0000305" FT CONFLICT 822 FT /note="G -> V (in Ref. 4; BAG63886)" FT /evidence="ECO:0000305" FT CONFLICT 1195 FT /note="T -> M (in Ref. 1; AAF36401, 2; BAA74927 and 6; FT AAI50266)" FT /evidence="ECO:0000305" FT HELIX 724..726 FT /evidence="ECO:0007829|PDB:4NST" FT STRAND 727..735 FT /evidence="ECO:0007829|PDB:4NST" FT STRAND 737..746 FT /evidence="ECO:0007829|PDB:4NST" FT TURN 747..749 FT /evidence="ECO:0007829|PDB:4NST" FT STRAND 752..758 FT /evidence="ECO:0007829|PDB:4NST" FT STRAND 761..763 FT /evidence="ECO:0007829|PDB:5ACB" FT STRAND 764..767 FT /evidence="ECO:0007829|PDB:6CKX" FT HELIX 769..778 FT /evidence="ECO:0007829|PDB:4NST" FT STRAND 789..794 FT /evidence="ECO:0007829|PDB:4NST" FT TURN 802..804 FT /evidence="ECO:0007829|PDB:5ACB" FT STRAND 809..814 FT /evidence="ECO:0007829|PDB:4NST" FT STRAND 817..819 FT /evidence="ECO:0007829|PDB:4NST" FT HELIX 820..826 FT /evidence="ECO:0007829|PDB:4NST" FT HELIX 833..852 FT /evidence="ECO:0007829|PDB:4NST" FT HELIX 862..864 FT /evidence="ECO:0007829|PDB:4NST" FT STRAND 865..867 FT /evidence="ECO:0007829|PDB:4NST" FT STRAND 873..875 FT /evidence="ECO:0007829|PDB:4NST" FT HELIX 878..880 FT /evidence="ECO:0007829|PDB:6TD3" FT STRAND 886..888 FT /evidence="ECO:0007829|PDB:4NST" FT HELIX 899..901 FT /evidence="ECO:0007829|PDB:4NST" FT HELIX 904..907 FT /evidence="ECO:0007829|PDB:4NST" FT HELIX 916..931 FT /evidence="ECO:0007829|PDB:4NST" FT HELIX 941..952 FT /evidence="ECO:0007829|PDB:4NST" FT TURN 957..959 FT /evidence="ECO:0007829|PDB:4NST" FT HELIX 961..965 FT /evidence="ECO:0007829|PDB:4NST" FT TURN 967..971 FT /evidence="ECO:0007829|PDB:4NST" FT HELIX 982..985 FT /evidence="ECO:0007829|PDB:4NST" FT TURN 986..988 FT /evidence="ECO:0007829|PDB:4NST" FT HELIX 991..1000 FT /evidence="ECO:0007829|PDB:4NST" FT TURN 1005..1007 FT /evidence="ECO:0007829|PDB:4NST" FT HELIX 1011..1014 FT /evidence="ECO:0007829|PDB:4NST" FT HELIX 1018..1021 FT /evidence="ECO:0007829|PDB:4NST" FT HELIX 1025..1027 FT /evidence="ECO:0007829|PDB:4NST" FT STRAND 1035..1037 FT /evidence="ECO:0007829|PDB:4NST" FT HELIX 1041..1045 FT /evidence="ECO:0007829|PDB:4NST" 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 //