ID CDK12_AILME Reviewed; 1491 AA. AC D2H526; DT 05-APR-2011, integrated into UniProtKB/Swiss-Prot. DT 09-FEB-2010, sequence version 1. DT 24-JAN-2024, entry version 84. DE RecName: Full=Cyclin-dependent kinase 12; DE EC=2.7.11.22; DE EC=2.7.11.23; DE AltName: Full=Cell division protein kinase 12; GN Name=CDK12; ORFNames=PANDA_004952; OS Ailuropoda melanoleuca (Giant panda). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Ursidae; Ailuropoda. OX NCBI_TaxID=9646; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=20010809; DOI=10.1038/nature08696; RA Li R., Fan W., Tian G., Zhu H., He L., Cai J., Huang Q., Cai Q., Li B., RA Bai Y., Zhang Z., Zhang Y., Wang W., Li J., Wei F., Li H., Jian M., Li J., RA Zhang Z., Nielsen R., Li D., Gu W., Yang Z., Xuan Z., Ryder O.A., RA Leung F.C., Zhou Y., Cao J., Sun X., Fu Y., Fang X., Guo X., Wang B., RA Hou R., Shen F., Mu B., Ni P., Lin R., Qian W., Wang G., Yu C., Nie W., RA Wang J., Wu Z., Liang H., Min J., Wu Q., Cheng S., Ruan J., Wang M., RA Shi Z., Wen M., Liu B., Ren X., Zheng H., Dong D., Cook K., Shan G., RA Zhang H., Kosiol C., Xie X., Lu Z., Zheng H., Li Y., Steiner C.C., RA Lam T.T., Lin S., Zhang Q., Li G., Tian J., Gong T., Liu H., Zhang D., RA Fang L., Ye C., Zhang J., Hu W., Xu A., Ren Y., Zhang G., Bruford M.W., RA Li Q., Ma L., Guo Y., An N., Hu Y., Zheng Y., Shi Y., Li Z., Liu Q., RA Chen Y., Zhao J., Qu N., Zhao S., Tian F., Wang X., Wang H., Xu L., Liu X., RA Vinar T., Wang Y., Lam T.W., Yiu S.M., Liu S., Zhang H., Li D., Huang Y., RA Wang X., Yang G., Jiang Z., Wang J., Qin N., Li L., Li J., Bolund L., RA Kristiansen K., Wong G.K., Olson M., Zhang X., Li S., Yang H., Wang J., RA Wang J.; RT "The sequence and de novo assembly of the giant panda genome."; RL Nature 463:311-317(2010). 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 (By similarity). {ECO:0000250}. 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 -!- 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 -!- SUBUNIT: Interacts with CCNL1 and CCNL2. {ECO:0000250}. CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}. Nucleus speckle CC {ECO:0000250}. Note=Colocalized with nuclear speckles throughout CC interphase. {ECO:0000250}. CC -!- PTM: Phosphorylation at Thr-894 increases kinase activity. CC {ECO:0000250}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr CC protein kinase family. CDC2/CDKX subfamily. {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; GL192497; EFB19924.1; -; Genomic_DNA. DR RefSeq; XP_002916839.1; XM_002916793.3. DR AlphaFoldDB; D2H526; -. DR SMR; D2H526; -. DR STRING; 9646.ENSAMEP00000004181; -. DR Ensembl; ENSAMET00000004348.2; ENSAMEP00000004181.1; ENSAMEG00000003944.2. DR GeneID; 100467815; -. DR KEGG; aml:100467815; -. DR CTD; 51755; -. DR eggNOG; KOG0600; Eukaryota. DR GeneTree; ENSGT00940000157595; -. DR HOGENOM; CLU_004166_2_1_1; -. DR InParanoid; D2H526; -. DR OMA; HWGAPAQ; -. DR OrthoDB; 5402490at2759; -. DR TreeFam; TF101060; -. DR Proteomes; UP000008912; Unassembled WGS sequence. DR GO; GO:0002944; C:cyclin K-CDK12 complex; IEA:Ensembl. DR GO; GO:0019908; C:nuclear cyclin-dependent protein kinase holoenzyme complex; ISS:UniProtKB. DR GO; GO:0016607; C:nuclear speck; ISS:UniProtKB. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0030332; F:cyclin binding; IEA:Ensembl. DR GO; GO:0004693; F:cyclin-dependent protein serine/threonine kinase activity; IEA:UniProtKB-EC. 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; ISS:UniProtKB. 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:0016310; P:phosphorylation; IEA:UniProtKB-KW. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB. DR GO; GO:0032968; P:positive regulation of transcription elongation by RNA polymerase II; IEA:Ensembl. DR GO; GO:0043405; P:regulation of MAP kinase activity; ISS:UniProtKB. DR GO; GO:0008380; P:RNA splicing; ISS:UniProtKB. DR GO; GO:0006366; P:transcription by RNA polymerase II; IEA:Ensembl. 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. PE 3: Inferred from homology; KW ATP-binding; Isopeptide bond; Kinase; mRNA processing; mRNA splicing; KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; KW Serine/threonine-protein kinase; Transferase; Ubl conjugation. FT CHAIN 1..1491 FT /note="Cyclin-dependent kinase 12" FT /id="PRO_0000406957" FT DOMAIN 728..1021 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT REGION 1..704 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1051..1105 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1162..1204 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1221..1371 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1469..1491 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 174..195 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 234..365 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 366..380 FT /note="Basic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 399..413 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 433..457 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 478..524 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 529..573 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 575..622 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 641..666 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 674..696 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1067..1082 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1190..1204 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1221..1244 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1260..1285 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1334..1371 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 860 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10027" FT BINDING 734..742 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 757 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 815..820 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 1041 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT MOD_RES 57 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q9NYV4" FT MOD_RES 73 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:Q9NYV4" FT MOD_RES 237 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9NYV4" FT MOD_RES 250 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9NYV4" FT MOD_RES 266 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9NYV4" FT MOD_RES 275 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9NYV4" FT MOD_RES 277 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9NYV4" FT MOD_RES 302 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9NYV4" FT MOD_RES 304 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9NYV4" FT MOD_RES 311 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9NYV4" FT MOD_RES 313 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9NYV4" FT MOD_RES 319 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9NYV4" FT MOD_RES 324 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9NYV4" FT MOD_RES 326 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9NYV4" FT MOD_RES 333 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9NYV4" FT MOD_RES 334 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9NYV4" FT MOD_RES 335 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9NYV4" FT MOD_RES 339 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9NYV4" FT MOD_RES 342 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9NYV4" FT MOD_RES 344 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9NYV4" FT MOD_RES 346 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9NYV4" FT MOD_RES 384 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9NYV4" FT MOD_RES 386 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9NYV4" FT MOD_RES 401 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9NYV4" FT MOD_RES 421 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9NYV4" FT MOD_RES 424 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9NYV4" FT MOD_RES 515 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q9NYV4" FT MOD_RES 615 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9NYV4" FT MOD_RES 645 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q3MJK5" FT MOD_RES 682 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9NYV4" FT MOD_RES 686 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9NYV4" FT MOD_RES 693 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q9NYV4" FT MOD_RES 890 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9NYV4" FT MOD_RES 894 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q9NYV4" FT MOD_RES 1054 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9NYV4" FT MOD_RES 1084 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9NYV4" FT MOD_RES 1245 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q9NYV4" FT MOD_RES 1247 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q14AX6" FT CROSSLNK 264 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000250|UniProtKB:Q9NYV4" FT CROSSLNK 510 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000250|UniProtKB:Q9NYV4" FT CROSSLNK 656 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000250|UniProtKB:Q9NYV4" SQ SEQUENCE 1491 AA; 164479 MW; BA53304B554D1195 CRC64; MPNPERHGGK KDGSGGASGT LQPSSGGGSS NSRERHRLVS KHKRHKSKHS KDMGLVTPEA APLGTIIKPL VEYDDISSDS DTFSDDMAFK LDRRENDERR GTDRSDRLHK HRHHQHRRSR DLLKTKQTEK EKNQEVSSKS GSMKDRISGS SKRSNEENED YGKAQISKSS SNKESRSSKL HKEKTRKERE LKSGHKDRSK SHRKRETPKS YKTVDSPKRR SRSPHRKWSD SPKQDDSPSG ASYGQDYDLS PPRSHTSSNY DSYKKSPGST SRRQSISPPY KEPSAYQSST RSPSPYSRRQ RSVSPYSRRR SSSYERSGSY SGRSPSPYGR RRSSSPFMSK RSLSRSPLPS RKSMKSRSRS PAYSRHSSSH SKKKRSGSRS RHSSISPVRL PLNSSLGAEL SRKKKERAAA AAAAKMDGKE SKGSPIFLPR KENSLVEAKD SGLESKKLTR GVKLEKSAPD TELVNIPHLN TEVKNSLDTG KVKLDENSEK HPIKDLKAQG SRDSKPIALK EEIVTPKETE TSEKETPPPV PAVTSPPPPL PTTSPPPQTP PLPPLPPLPA IPQQPPLPPP QPAFSHVLAS STSTLPPSTH PRTSTLSSQA NSQPLAQVSV KTQVSVTAAI PHLKTSTLPP LPLPPLLPGD DDMDSPKETP PSKPVKKEKE QRPRHLLTDL PLPPELPGGD PSPPDSPEPK AVTPPQQPYK KRPKICCPRY GERRQTESDW GKRCVDKFDI IGIIGEGTYG QVYKAKDKDT GELVALKKVR LDNEKEGFPI TAIREIKILR QLIHRSVVNM KEIVTDKQDA LDFKKDKGAF YLVFEYMDHD LMGLLESGLV HFSEDHIKSF MKQLMEGLDY CHKKNFLHRD IKCSNILLNN SGQIKLADFG LARLYNSEES RPYTNKVITL WYRPPELLLG EERYTPAIDV WSCGCILGEL FTKKPIFQAN LELAQLELIS RLCGSPCPAV WPDVIKLPYF NTMKPKKQYR RRLREEFSFI PSAALDLLDH MLTLDPSKRC TAEQTLQSDF LKDVELSKMD PPDLPHWQDC HELWSKKRRR QRQSGVVIEE PPPSKASRKE TTSGTSAEPV KNSSPAPPQP ASGKVEPGTG DAIGLGDITQ QLNQSELAVL LNLLQSQTDL SIPQMAQLLN IHSNPEMQQQ LEALNQSISA LTEATSQQQD SEHMAPEESL KEAPPALVVQ PSAEQTTSEA SSTPADMQNM LAVLLSQLMK TQEPAGSLEE NNSDKNSGPQ GPRRTPTMPQ EEAAACPPHI LPPEKRPPEP PGPPPPPPPP PLIEGDLSSA PQELNPAVTA ALLQLLSQPE AEPPGHLPHE HQALRPMEYS TRPHPNRTYG NTDGPETGFS ATDTDERNSG PALTESLTQT LVKNRTFSGS VSHLGESSSY QGTGSVQFPG DQDLRFARVP LPLHSVVGQP FLKAEGSSNS VVHAETKLQN YGELGPGTTG ASSSGAGLNW GGSAQSSAYG KLYRGPTRVP PRGGRGRGVP Y //