CDK12_BOVIN
ID CDK12_BOVIN Reviewed; 1264 AA.
AC E1BB50;
DT 05-APR-2011, integrated into UniProtKB/Swiss-Prot.
DT 02-NOV-2010, sequence version 1.
DT 03-AUG-2022, entry version 56.
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;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=19390049; DOI=10.1126/science.1169588;
RG The bovine genome sequencing and analysis consortium;
RT "The genome sequence of taurine cattle: a window to ruminant biology and
RT evolution.";
RL Science 324:522-528(2009).
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-893 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; AAFC03033685; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAFC03036812; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAFC03053477; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAFC03053478; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR AlphaFoldDB; E1BB50; -.
DR SMR; E1BB50; -.
DR STRING; 9913.ENSBTAP00000002005; -.
DR PaxDb; E1BB50; -.
DR PRIDE; E1BB50; -.
DR eggNOG; KOG0600; Eukaryota.
DR InParanoid; E1BB50; -.
DR OrthoDB; 925637at2759; -.
DR Proteomes; UP000009136; Unplaced.
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:0004693; F:cyclin-dependent protein serine/threonine kinase activity; IEA:UniProtKB-EC.
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:0070816; P:phosphorylation of RNA polymerase II C-terminal domain; ISS:UniProtKB.
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..1264
FT /note="Cyclin-dependent kinase 12"
FT /id="PRO_0000406958"
FT DOMAIN 727..1022
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..455
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 471..611
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 623..703
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1052..1103
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1163..1264
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..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..455
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 477..524
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 530..572
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 573..611
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 673..695
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1191..1245
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 /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 756
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 814..819
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 1042
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 236
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NYV4"
FT MOD_RES 249
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NYV4"
FT MOD_RES 265
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NYV4"
FT MOD_RES 274
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NYV4"
FT MOD_RES 276
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NYV4"
FT MOD_RES 301
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NYV4"
FT MOD_RES 303
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NYV4"
FT MOD_RES 310
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NYV4"
FT MOD_RES 312
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NYV4"
FT MOD_RES 318
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NYV4"
FT MOD_RES 323
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NYV4"
FT MOD_RES 325
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NYV4"
FT MOD_RES 332
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 338
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NYV4"
FT MOD_RES 341
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NYV4"
FT MOD_RES 343
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NYV4"
FT MOD_RES 345
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NYV4"
FT MOD_RES 383
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NYV4"
FT MOD_RES 385
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NYV4"
FT MOD_RES 400
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NYV4"
FT MOD_RES 420
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NYV4"
FT MOD_RES 423
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 614
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NYV4"
FT MOD_RES 644
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q3MJK5"
FT MOD_RES 681
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NYV4"
FT MOD_RES 685
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NYV4"
FT MOD_RES 692
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9NYV4"
FT MOD_RES 889
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NYV4"
FT MOD_RES 893
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9NYV4"
FT MOD_RES 1055
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NYV4"
FT MOD_RES 1085
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NYV4"
FT MOD_RES 1246
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9NYV4"
FT MOD_RES 1248
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: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 655
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q9NYV4"
SQ SEQUENCE 1264 AA; 140642 MW; A074D89C354DBAC7 CRC64;
MPNPERHGGK KDGSGGASGT LQPSSGGGSS NSRERHRLGS KHKRHKSKHS KDMGLVTPEA
APLGTVIKPL VEYDDISSDS DTFSDDLAFK VDRRENDERR GTDRSDRLHK HRHHQHRRTR
DLLKTKQTEK EKNLEASSKS GSTKDRISGS SKRSNEENDD HGKAQISKSS NKESRSSKLH
KEKTRKEREL KSGHKDRSKS HRKRETPKSY KTVDSPKRRS RSPHRKWSDS PKQDDSPSGA
SYGQDYDLSP PRSHTSSNYD SYKKSPGSTS RRQSISPPYK EPSAYQSSTR SPSPYSRRQR
SVSPYSRRRS SSYERSGSYS GRSPSPYGRR RSSSPFLSKR SLSRSPLPSR KSMKSRSRSP
AYSRHSSSHS KKKRSGSRSR HSSISPVRLP LNSSLGAELS RKKKERAAAA AAAKMDGKES
KGSPIFLPKK ENSSVEAKDS GLEPKKLPRG VKLEKSAPDT ELVNVTHLNT EVKNSLDTGK
VKLDENSEKH PVLKDTKVQG TKDSKPVALK EEIVTPKETE TSEKETLPPL PTVTSPPPLP
TTTPPPQTPP LPPLPPLPAI PQQPPLPPPQ PTFSQVLSSS TSTLPPSVHP RTSTLSSQAN
SQPSVQVSVK TQVSVTAAIP HLKTSTLPPL PLPPLLLGDD DMDSPKETLP SKPVKKEKEQ
RPRHLLTDLP LPPELPGGDP SPPDSPEPKA ITPPQQPYKK RPKICCPRYG ERRQTESDWG
KRCVDKFDII GIIGEGTYGQ VYKAKDKDTG ELVALKKVRL DNEKEGFPIT AIREIKILRQ
LIHRSVVNMK EIVTDKQDAL DFKKDKGAFY LVFEYMDHDL MGLLESGLVH FSEDHIKSFM
KQLMEGLDYC HKKNFLHRDI KCSNILLNNS GQIKLADFGL ARLYNSEESR PYTNKVITLW
YRPPELLLGE ERYTPAIDVW SCGCILGELF TKKPIFQANL ELAQLELISR LCGSPCPAVW
PDVIKLPYFN TMKPKKQYRR RLREEFSFFF LPWGALDLLD HMLTLDPSKR CTAEQTLQSD
FLKDVELSKM DPPDLPHWQD CHELWSKKRR RQRQSGVLVE EPPPPKASRK ETISGTSAEP
VKNSSPAPPQ PAPGKVEPGA GDAIGLGDIT QQLNQSELAV LLNLLQSQTD LSIPQMAQLL
NIHSNPEMQQ QLEALNQSIS ALTAATSQQQ DSEPTAPEES LKEIAPAPAV QPSAEQTTPE
ASSTPADMQN MLAVLLSQLM KTQEPAGNLE ENNSDKNSGP QGPRRTPTMP QEEAAGKQTG
HESH
