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   27-MAR-2024, entry version 174.
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; 12.
DR   STRING; 6239.B0285.1b.1; -.
DR   iPTMnet; P46551; -.
DR   EPD; P46551; -.
DR   PaxDb; 6239-B0285-1b; -.
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   AGR; WB:WBGene00007135; -.
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; MVNARYC; -.
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 cell types or tissues.
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; 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; IBA:GO_Central.
DR   GO; GO:0002119; P:nematode larval development; IMP:UniProtKB.
DR   GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR   GO; GO:0032968; P:positive regulation of transcription elongation by RNA polymerase II; IBA:GO_Central.
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:SF573; 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   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
//