CDK12_CAEEL
ID CDK12_CAEEL Reviewed; 730 AA.
AC P46551; C8JQQ9; C8JQR0; P46552;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 06-DEC-2002, sequence version 4.
DT 03-AUG-2022, entry version 166.
DE RecName: Full=Cyclin-dependent kinase 12;
DE EC=2.7.11.22 {ECO:0000269|PubMed:23903194};
DE EC=2.7.11.23 {ECO:0000269|PubMed:23903194};
DE AltName: Full=Cell division cycle 2-related protein kinase 7;
DE AltName: Full=Cell division protein kinase 12;
GN Name=cdk-12 {ECO:0000312|WormBase:B0285.1a};
GN Synonyms=cdtl-7 {ECO:0000312|WormBase:B0285.1a};
GN ORFNames=B0285.1 {ECO:0000312|WormBase:B0285.1a};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, AND DISRUPTION PHENOTYPE.
RX PubMed=23903194; DOI=10.1242/dev.095778;
RA Bowman E.A., Bowman C.R., Ahn J.H., Kelly W.G.;
RT "Phosphorylation of RNA polymerase II is independent of P-TEFb in the C.
RT elegans germline.";
RL Development 140:3703-3713(2013).
CC -!- FUNCTION: Cyclin-dependent kinase which displays CTD kinase activity:
CC hyperphosphorylates 'Ser-2' in the C-terminal heptapeptide repeat
CC domain (CTD) of the largest RNA polymerase II subunit, thereby acting
CC as a key regulator of transcription elongation. Required for normal
CC reproduction. {ECO:0000269|PubMed:23903194}.
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:0000269|PubMed:23903194};
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 Evidence={ECO:0000269|PubMed:23903194};
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; Evidence={ECO:0000269|PubMed:23903194};
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q9NYV4}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=a;
CC IsoId=P46551-1; Sequence=Displayed;
CC Name=c;
CC IsoId=P46551-2; Sequence=VSP_056772;
CC Name=b;
CC IsoId=P46551-3; Sequence=VSP_056771;
CC -!- DISRUPTION PHENOTYPE: Phosphorylation of 'Ser-2' of the RNA polymerase
CC II C-terminal domain is undetectable in primordial germ cells and
CC reduced by 60% in embryonic somatic nuclei. RNAi treatment causes
CC sterility. {ECO:0000269|PubMed:23903194}.
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; BX284603; CAA84302.3; -; Genomic_DNA.
DR EMBL; BX284603; CBB15978.1; -; Genomic_DNA.
DR EMBL; BX284603; CBB15981.1; -; Genomic_DNA.
DR PIR; T18689; T18689.
DR PIR; T18697; T18697.
DR RefSeq; NP_001254914.1; NM_001267985.1.
DR RefSeq; NP_001254915.1; NM_001267986.1.
DR RefSeq; NP_001254916.1; NM_001267987.1. [P46551-1]
DR AlphaFoldDB; P46551; -.
DR SMR; P46551; -.
DR BioGRID; 40795; 11.
DR STRING; 6239.B0285.1b; -.
DR iPTMnet; P46551; -.
DR EPD; P46551; -.
DR PaxDb; P46551; -.
DR PeptideAtlas; P46551; -.
DR EnsemblMetazoa; B0285.1a.1; B0285.1a.1; WBGene00007135. [P46551-1]
DR EnsemblMetazoa; B0285.1a.2; B0285.1a.2; WBGene00007135. [P46551-1]
DR EnsemblMetazoa; B0285.1b.1; B0285.1b.1; WBGene00007135. [P46551-3]
DR EnsemblMetazoa; B0285.1b.2; B0285.1b.2; WBGene00007135. [P46551-3]
DR EnsemblMetazoa; B0285.1c.1; B0285.1c.1; WBGene00007135. [P46551-2]
DR EnsemblMetazoa; B0285.1c.2; B0285.1c.2; WBGene00007135. [P46551-2]
DR GeneID; 175559; -.
DR CTD; 175559; -.
DR WormBase; B0285.1a; CE31401; WBGene00007135; cdk-12. [P46551-1]
DR WormBase; B0285.1b; CE44061; WBGene00007135; cdk-12. [P46551-3]
DR WormBase; B0285.1c; CE44020; WBGene00007135; cdk-12. [P46551-2]
DR eggNOG; KOG0600; Eukaryota.
DR GeneTree; ENSGT00940000176088; -.
DR HOGENOM; CLU_021707_0_0_1; -.
DR InParanoid; P46551; -.
DR OMA; FEHIMPR; -.
DR OrthoDB; 925637at2759; -.
DR PhylomeDB; P46551; -.
DR Reactome; R-CEL-6796648; TP53 Regulates Transcription of DNA Repair Genes.
DR Reactome; R-CEL-6798695; Neutrophil degranulation.
DR PRO; PR:P46551; -.
DR Proteomes; UP000001940; Chromosome III.
DR Bgee; WBGene00007135; Expressed in germ line (C elegans) and 4 other tissues.
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:0000791; C:euchromatin; IDA:WormBase.
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; IBA:GO_Central.
DR GO; GO:0002119; P:nematode larval development; IMP:UniProtKB.
DR GO; GO:0070816; P:phosphorylation of RNA polymerase II C-terminal domain; IMP: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:2001253; P:regulation of histone H3-K36 trimethylation; IMP: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 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Kinase; Nucleotide-binding; Nucleus;
KW Reference proteome; Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..730
FT /note="Cyclin-dependent kinase 12"
FT /id="PRO_0000085716"
FT DOMAIN 313..605
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..230
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 246..283
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 623..730
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..59
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 75..90
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 91..118
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 119..135
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 136..151
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 166..190
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 191..230
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 623..638
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 639..673
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 674..688
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 694..708
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 709..730
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 444
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q9NYV4,
FT ECO:0000255|PROSITE-ProRule:PRU00159, ECO:0000255|PROSITE-
FT ProRule:PRU10027"
FT BINDING 317..325
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9NYV4,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 340
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9NYV4,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 398..403
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9NYV4"
FT BINDING 625
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9NYV4"
FT VAR_SEQ 659
FT /note="R -> RVFEA (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_056771"
FT VAR_SEQ 660
FT /note="A -> AA (in isoform c)"
FT /evidence="ECO:0000305"
FT /id="VSP_056772"
SQ SEQUENCE 730 AA; 82429 MW; E347661352F39A0B CRC64;
MEISPGSSTH ERDRKGSYGH RERTRSHSGS PSRFYSKDKR GSSRQGVRPR DRDSKDSISP
QYKQRNWSRG GGGGGRDRGR NDFSYRKKGK DYNKRRDKRS RSRSRHRSPK RSGSSKKSKR
RNSSGSSSSD LMDTSLMSEL KKHGDYGSSS KSKKKSRKRR KHSSSSSSSS GEAMDLPVSS
NGMNVTAIPP PPSFNINPFQ PMFSQPPPPP LPPNSQFMTP PPRPPPAPFS IPPPSVDIHF
AATASFSLSS IPPPPPQTDG GASSSKRQDP LPMPPDSKRI ATRPVITTRR GHATNRPSDS
DSWYKTNLTH YTMLDQIGEG TYGQVYKAVN NLTGEQVALK RVRLENEKEG FPITAIREIK
ILRQLHHKNI VRLMDIVIDD ISMDELKRTR ANFYLVFEYV DHDLIGLLES KELVDFNKDQ
ICSLFKQLLE GLAYIHNTGF LHRDIKCSNI LVNNKGELKI ADLGLARLWE KESRLYTNRV
ITLWYRPPEL LLGDERYGPA IDVWSTGCML GELFTRKPLF NGNNEFGQLE LISKVCGSPN
VDNWPELTEL VGWNTFRMKR TYQRRIREEF EHIMPREAVD LLDKMLTLNP EKRISAKEAL
NHPWIRSLEH TTVQPLKLPQ HQDCHEMWSK KQKKSARLGR QAEGSSGSGH SIRATSHPRA
PTQPSTTTTK SNGSSNHHHH HHHSHHHASS LPPSGGHAPP PPPPPTQASS TSHNNHQPVP
QSQYQSVFFK
