CDK12_AILME
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 03-AUG-2022, entry version 78.
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}.
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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 PRIDE; D2H526; -.
DR Ensembl; ENSAMET00000004348; ENSAMEP00000004181; ENSAMEG00000003944.
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; STKHNRE; -.
DR OrthoDB; 925637at2759; -.
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:0070816; P:phosphorylation of RNA polymerase II C-terminal domain; ISS:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; IEA:Ensembl.
DR GO; GO:0043405; P:regulation of MAP kinase activity; ISS:UniProtKB.
DR GO; GO:0008380; P:RNA splicing; ISS: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 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
