CDK12_XENTR
ID CDK12_XENTR Reviewed; 1239 AA.
AC B5DE93;
DT 05-APR-2011, integrated into UniProtKB/Swiss-Prot.
DT 14-OCT-2008, sequence version 1.
DT 03-AUG-2022, entry version 67.
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 Xenopus tropicalis (Western clawed frog) (Silurana tropicalis).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Silurana.
OX NCBI_TaxID=8364;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (AUG-2008) to the EMBL/GenBank/DDBJ databases.
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 (By similarity).
CC {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 -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}. Nucleus speckle
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; BC168577; AAI68577.1; -; mRNA.
DR RefSeq; NP_001128283.1; NM_001134811.1.
DR AlphaFoldDB; B5DE93; -.
DR SMR; B5DE93; -.
DR PaxDb; B5DE93; -.
DR PRIDE; B5DE93; -.
DR GeneID; 100038049; -.
DR KEGG; xtr:100038049; -.
DR CTD; 51755; -.
DR Xenbase; XB-GENE-493308; cdk12.
DR eggNOG; KOG0600; Eukaryota.
DR InParanoid; B5DE93; -.
DR OrthoDB; 925637at2759; -.
DR Reactome; R-XTR-6796648; TP53 Regulates Transcription of DNA Repair Genes.
DR Proteomes; UP000008143; Chromosome 10.
DR Proteomes; UP000790000; Unplaced.
DR GO; GO:0000307; C:cyclin-dependent protein kinase holoenzyme complex; IBA:GO_Central.
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; ISS:UniProtKB.
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; IBA:GO_Central.
DR GO; GO:0004693; F:cyclin-dependent protein serine/threonine kinase activity; IBA:GO_Central.
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:0032968; P:positive regulation of transcription elongation from RNA polymerase II promoter; IBA:GO_Central.
DR GO; GO:0006468; P:protein phosphorylation; IBA:GO_Central.
DR GO; GO:0043405; P:regulation of MAP kinase activity; ISS:UniProtKB.
DR GO; GO:0008380; P:RNA splicing; ISS:UniProtKB.
DR GO; GO:0006368; P:transcription elongation from RNA polymerase II promoter; IBA:GO_Central.
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 2: Evidence at transcript level;
KW ATP-binding; Kinase; mRNA processing; mRNA splicing; Nucleotide-binding;
KW Nucleus; Reference proteome; Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..1239
FT /note="Cyclin-dependent kinase 12"
FT /id="PRO_0000406959"
FT DOMAIN 710..1003
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..421
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 437..557
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 570..687
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1037..1074
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1146..1168
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1191..1239
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 12..31
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 51..66
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 78..97
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 98..114
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 115..132
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 147..189
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 222..237
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 246..261
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 268..337
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 456..504
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 508..556
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 570..587
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 622..650
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 656..684
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1196..1210
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1221..1239
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 842
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 716..724
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 739
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 797..802
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 1023
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
SQ SEQUENCE 1239 AA; 138328 MW; 8ADF1CECFCE9CB12 CRC64;
MPNPVRHGNK KDSGGSASTM PESSGSVNNK DRQRISSKHK RHKSKHLRES SVPEPQTLST
LKLVEYDDIS SDSDTFSDVP AKQERRENDE RRPSEKSDKM HKSRHRHQHK RLKEATRTKQ
VEKERKPEKT QEVMVNKVPS SKDKIISSAK RTADEQEEHG RTSKSSSKDS RSKMHKDKSR
REREMKSGHK ERSKSHRKRD SSKRYKTSDS PKRKGRSPRR KYGGSPKQDD SHSEGSCGQD
YDDSPSRVHA SGNFNETYRK NMDSPSYKEP AAYQSSARSP SPYSRKQRSV SPYRRRSSSY
ERGSGSYSGR SPSPYVRRRS SSPFVSRRSL SRSPAPRKSA KSRSRSPLYP RKSSSSSRSK
KQKSQSRSRH SSISPARLPL NSSLGAELSR KKKEIAAAAA AAGRESKGSP LILKKESGDS
RVASALDLKK ATKVLKLEKP VSEPEMVTAT SSETKTISAK KEESEKKPQV QAKDPKISGL
KDCKPAAIKE EVLTPKEGVT DRDKDVPPLP PILSPPPPLP TSPPSNIPPL PPLPPSPAVL
QQPPPPLPPP PTLTFLPLPT TVAASLTSSH YVRQSSLSTQ ANSQLPVPSP AKPQPPLIHM
VPHMKTSTLP PLPLPPLLLG EDDIESPKEI PPPKSVKKEK DKDRPRHLLT DLPLPPELPG
GDPSPPDSPE RKVVAPPQPP LKKRPKICCP RYGERKQTET DWGKRCVDKF DIIGIIGEGT
YGQVYKAKDK DTGELVALKK VRLDNEKEGF PITAIREIKI LRQLIHKSVV NMKEIVTDKQ
DALDFKKDKG AFYLVFEYMD HDLMGLLESG LVQFSEDHIK SFMKQLMEGL EYCHKKNFLH
RDIKCSNILL NNSGQIKLAD FGLARLYSSE ESRPYTNKVI TLWYRPPELL LGEERYTPAI
DVWSCGCILG ELFTKKPIFQ ANQELAQLEL ISRLCGSPCP AVWPDVIKLP YFNTMKPKKQ
YRRRLREEFS FVPTPALDLL DHMLTLDPSK RCTAEQTLQS DFLKDVDVCK MATPDLPHWQ
DCHELWSKKR RRQRQSGIVL EEPPAIKAPR KESVSVPGGD AMKNSSPAPT QPVKTESSVS
DLAVLGDITQ QLNQSELAVL LNLLQSQTDL SVSQISQLLN VQANPDMQLQ LEALNQSITA
LTGAAVPPQE VEPPKETPTL DQVDPLGAGT QGEVQNVLAV LLSQLLKPQE VVDAPGESNG
EQSGSNPTAH ITLEEEEEPD KHHEQNEEEE EDAGNYWSP
