{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"P21127","secondaryAccessions":["B7ZVY7","J3KTL7","J3QR29","J3QR44","O95265","Q12817","Q12818","Q12819","Q12820","Q12822","Q8N530","Q9NZS5","Q9UBJ0","Q9UBQ1","Q9UBR0","Q9UNY2","Q9UP57","Q9UP58","Q9UP59"],"uniProtkbId":"CD11B_HUMAN","entryAudit":{"firstPublicDate":"1991-02-01","lastAnnotationUpdateDate":"2026-06-10","lastSequenceUpdateDate":"2018-03-28","entryVersion":246,"sequenceVersion":4},"annotationScore":5.0,"organism":{"scientificName":"Homo sapiens","commonName":"Human","taxonId":9606,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Primates","Haplorrhini","Catarrhini","Hominidae","Homo"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"value":"Cyclin-dependent kinase 11B"},"ecNumbers":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12501247"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"36104565"}],"value":"2.7.11.22"},{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"32367068"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"36104565"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"38019613"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"40858114"}],"value":"2.7.11.23"}]},"alternativeNames":[{"fullName":{"value":"Cell division cycle 2-like protein kinase 1"},"shortNames":[{"value":"CLK-1"}]},{"fullName":{"value":"Cell division protein kinase 11B"}},{"fullName":{"value":"Galactosyltransferase-associated protein kinase p58/GTA"}},{"fullName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"9750192"}],"value":"PITSLRE serine/threonine-protein kinase CDC2L1"}},{"fullName":{"value":"p58 CLK-1"}}]},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"40858114"},{"evidenceCode":"ECO:0000312","source":"HGNC","id":"HGNC:1729"}],"value":"CDK11B"},"synonyms":[{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"9750192"}],"value":"CDC2L1"},{"value":"CDK11"},{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"8195233"}],"value":"PITSLREA"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12501247"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18216018"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"32367068"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"36104565"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"38059508"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"40858114"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"41100585"}],"value":"Cyclin-dependent protein kinase that acts as a regulator of transcription and pre-mRNA splicing (PubMed:12501247, PubMed:18216018, PubMed:32367068, PubMed:36104565). Acts as a key regulator of pre-mRNA splicing by mediating phosphorylation of SF3B1, enabling the association between SF3B1 and U5 and U6 snRNAs in the activated spliceosome, thereby promoting spliceosome assembly (PubMed:36104565, PubMed:38059508). Also acts as a regulator of transcription by phosphorylating 'Ser-2' of the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAP II) POLR2A (PubMed:32367068, PubMed:40858114). Involved in replication-dependent transcription of histone genes: binds to histone genes and phosphorylates POLR2A at 'Ser-2' of the CTD to specifically control transcriptional elongation of histones and recruitment of 3'-end processing factors (PubMed:32367068). Part of a transcription checkpoint upstream of CDK9, which regulates promoter-proximal pausing by RNA polymerase II, a transcription halt following transcription initiation, but prior to elongation (PubMed:40858114). Probably regulates promoter-proximal pausing by mediating phosphorylation of POLR2A at 'Ser-2' of the CTD (PubMed:40858114). Activated by the CDK-activating kinase (CAK) complex consisting of CDK7, cyclin-H/CCNH and MAT1, which is a master regulator of CDK activity (PubMed:41100585)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12624090"}],"value":"Isoform expressed in a non-cell cycle-dependent manner"}],"commentType":"FUNCTION","molecule":"Isoform SV9"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12082095"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"2217177"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24436071"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"38019613"}],"value":"Isoform specifically expressed during the G2-M phases of the cell cycle (PubMed:12082095, PubMed:2217177). Phosphorylates 'Ser-2' of the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAP II) POLR2A (PubMed:38019613). Promotes centromeric transcription to maintain centromeric cohesion during mitosis (PubMed:24436071, PubMed:38019613)"}],"commentType":"FUNCTION","molecule":"Isoform 7"},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:17989"},{"database":"Rhea","id":"RHEA-COMP:9863"},{"database":"Rhea","id":"RHEA-COMP:11604"},{"database":"ChEBI","id":"CHEBI:15378"},{"database":"ChEBI","id":"CHEBI:29999"},{"database":"ChEBI","id":"CHEBI:30616"},{"database":"ChEBI","id":"CHEBI:83421"},{"database":"ChEBI","id":"CHEBI:456216"}],"ecNumber":"2.7.11.22","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12501247"}]},"physiologicalReactions":[{"directionType":"left-to-right","reactionCrossReference":{"database":"Rhea","id":"RHEA:17990"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12501247"}]}]},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:46608"},{"database":"Rhea","id":"RHEA-COMP:11060"},{"database":"Rhea","id":"RHEA-COMP:11605"},{"database":"ChEBI","id":"CHEBI:15378"},{"database":"ChEBI","id":"CHEBI:30013"},{"database":"ChEBI","id":"CHEBI:30616"},{"database":"ChEBI","id":"CHEBI:61977"},{"database":"ChEBI","id":"CHEBI:456216"}],"ecNumber":"2.7.11.22","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12501247"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"36104565"}]},"physiologicalReactions":[{"directionType":"left-to-right","reactionCrossReference":{"database":"Rhea","id":"RHEA:46609"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12501247"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"36104565"}]}]},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"[DNA-directed RNA polymerase] + ATP = phospho-[DNA-directed RNA polymerase] + ADP + H(+)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:10216"},{"database":"Rhea","id":"RHEA-COMP:11321"},{"database":"Rhea","id":"RHEA-COMP:11322"},{"database":"ChEBI","id":"CHEBI:15378"},{"database":"ChEBI","id":"CHEBI:30616"},{"database":"ChEBI","id":"CHEBI:43176"},{"database":"ChEBI","id":"CHEBI:68546"},{"database":"ChEBI","id":"CHEBI:456216"}],"ecNumber":"2.7.11.23","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"32367068"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"36104565"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"38019613"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"40858114"}]},"physiologicalReactions":[{"directionType":"left-to-right","reactionCrossReference":{"database":"Rhea","id":"RHEA:10217"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"32367068"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"36104565"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"38019613"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"40858114"}]}]},{"commentType":"COFACTOR","cofactors":[{"name":"Mg(2+)","evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"12501247"}],"cofactorCrossReference":{"database":"ChEBI","id":"CHEBI:18420"}}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P06493"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31511426"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"36104565"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"36327972"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"41100585"}],"value":"Inactivated by phosphorylation at Thr-448 or Tyr-449 (PubMed:41100585). Activated by phosphorylation at Thr-595 (PubMed:41100585). Phosphorylated and activated by CDK7 in the CDK-activating kinase (CAK) complex, and reciprocally phosphorylating its activating kinase CDK7 (PubMed:41100585). CDK11 (CDK11A and/or CDK11B) is specifically inhibited by the anticancer agent OTS964 (PubMed:31511426, PubMed:36104565, PubMed:36327972)"}],"commentType":"ACTIVITY REGULATION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11980906"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12501247"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"32367068"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"38059508"}],"value":"Associates with cyclin-L1 (CCNL1) or cyclin-L2 (CCNL2) to form an active cyclin-L-CDK11 cyclin-dependent protein kinase complex (PubMed:11980906, PubMed:12501247, PubMed:38059508). Interacts with SAP30BP; promoting assembly of the cyclin-L-CDK11 cyclin-dependent protein kinase complex (PubMed:38059508). Interacts with CASP8AP2/FLASH; promoting 3' end cleavage of histone pre-mRNAs (PubMed:32367068)"}],"commentType":"SUBUNIT"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11980906"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12501247"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12624090"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14511641"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25965346"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"38059508"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9580558"}],"value":"Associates with cyclin-L1 (CCNL1) or cyclin-L2 (CCNL2) to form an active cyclin-L-CDK11 cyclin-dependent protein kinase complex (PubMed:11980906, PubMed:12501247, PubMed:38059508). Interacts with SFRS7 (PubMed:12501247). Forms complexes with pre-mRNA-splicing factors, including at least SRSF1, SRSF2 and SRSF7/SLU7. Interacts with isoform 5 of MYO18A (PubMed:25965346). The cleaved p110 isoform, p110C, binds to the serine/threonine kinase PAK1 and RANBP9 (PubMed:12624090, PubMed:14511641). p110C interacts with RNPS1 (PubMed:9580558)"}],"commentType":"SUBUNIT","molecule":"Isoform SV9"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16710414"}],"value":"Associates with cyclin-D3 (CCND3) to form an active cyclin-dependent protein kinase complex"}],"commentType":"SUBUNIT","molecule":"Isoform 7"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34696162"}],"value":"(Microbial infection) Interacts with human herpes virus 1 (HHV-1) transcriptional regulator ICP22"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"P21127","intActId":"EBI-1298"},"interactantTwo":{"uniProtKBAccession":"O00303","geneName":"EIF3F","intActId":"EBI-711990"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P21127","intActId":"EBI-1298"},"interactantTwo":{"uniProtKBAccession":"Q13153","geneName":"PAK1","intActId":"EBI-1307"},"numberOfExperiments":4,"organismDiffer":false}]},{"commentType":"SUBCELLULAR LOCATION","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"32367068"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"40858114"}],"value":"Localizes to transcription start site (TSS) proximal regions"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8195233"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9580558"}],"value":"Nucleus","id":"SL-0191"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"40858114"}],"value":"Chromosome","id":"SL-0468"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8195233"}],"value":"Cytoplasm","id":"SL-0086"}}]},{"commentType":"SUBCELLULAR LOCATION","molecule":"Isoform SV9","subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12501247"}],"value":"Nucleus","id":"SL-0191"}}]},{"commentType":"SUBCELLULAR LOCATION","molecule":"Isoform 7","subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16710414"}],"value":"Nucleus","id":"SL-0191"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24436071"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"38019613"}],"value":"Chromosome, centromere","id":"SL-0047"}}]},{"commentType":"ALTERNATIVE PRODUCTS","events":["Alternative splicing","Alternative initiation"],"isoforms":[{"name":{"value":"SV9"},"synonyms":[{"value":"CDK11-p110"}],"isoformIds":["P21127-1"],"isoformSequenceStatus":"Displayed"},{"name":{"value":"SV1"},"synonyms":[{"value":"Alpha 2-1"}],"isoformIds":["P21127-2"],"sequenceIds":["VSP_008280"],"isoformSequenceStatus":"Described"},{"name":{"value":"2"},"synonyms":[{"value":"Alpha 2-2"}],"isoformIds":["P21127-3"],"sequenceIds":["VSP_008278","VSP_008279","VSP_008280"],"isoformSequenceStatus":"Described"},{"name":{"value":"3"},"synonyms":[{"value":"Alpha 1"}],"isoformIds":["P21127-4"],"sequenceIds":["VSP_008276"],"isoformSequenceStatus":"Described"},{"name":{"value":"SV4"},"isoformIds":["P21127-5"],"sequenceIds":["VSP_008275"],"isoformSequenceStatus":"Described"},{"name":{"value":"SV5"},"isoformIds":["P21127-6"],"sequenceIds":["VSP_008273","VSP_008277","VSP_008278","VSP_008280"],"isoformSequenceStatus":"Described"},{"name":{"value":"8"},"synonyms":[{"value":"Alpha 2-3"}],"isoformIds":["P21127-8"],"sequenceIds":["VSP_008278","VSP_008280"],"isoformSequenceStatus":"Described"},{"name":{"value":"SV10"},"isoformIds":["P21127-9"],"sequenceIds":["VSP_008273","VSP_008277","VSP_008280"],"isoformSequenceStatus":"Described"},{"name":{"value":"SV11"},"synonyms":[{"value":"Alpha 2-4"}],"isoformIds":["P21127-10"],"sequenceIds":["VSP_008274","VSP_008280"],"isoformSequenceStatus":"Described"},{"name":{"value":"7"},"synonyms":[{"value":"CDK11-p58"}],"isoformIds":["P21127-12"],"sequenceIds":["VSP_018834"],"isoformSequenceStatus":"Described"}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8195233"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9750192"}],"value":"Expressed ubiquitously. Some evidence of isoform-specific tissue distribution"}],"commentType":"TISSUE SPECIFICITY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10882096"}],"value":"Induced in G2/M phase of the cell cycle"}],"commentType":"INDUCTION","molecule":"Isoform 7"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12624090"}],"value":"During FAS- or TNF-induced apoptosis, isoform SV9 is cleaved by caspases to produce p110C, a fragment that contains the C-terminal kinase domain"}],"commentType":"PTM","molecule":"Isoform SV9"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15883043"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16327805"}],"value":"Phosphorylation at Ser-115 creates a binding site for 14-3-3 proteins. p110C can be autophosphorylated"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9750192"}],"value":"Duplicated gene. CDK11A and CDK11B encode almost identical protein kinases of 110 kDa that contain at their C-termini the open reading frame of a smaller 58 kDa isoform which is expressed following IRES-mediated alternative initiation of translation (PubMed:9750192). Many references talk about 'p110 isoforms' but it is not yet known if this refers to CDK11A and/or CDK11B or one/some of the isoforms of each (PubMed:9750192)"}],"commentType":"MISCELLANEOUS"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10882096"}],"value":"Produced by alternative initiation at Met-357 of isoform SV9 via an internal ribosomal entry site (IRES)"}],"commentType":"MISCELLANEOUS","molecule":"Isoform 7"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily"}],"commentType":"SIMILARITY"},{"commentType":"SEQUENCE CAUTION","sequenceCautionType":"Erroneous gene model prediction","sequence":"AAB59449.1","evidences":[{"evidenceCode":"ECO:0000305"}]},{"commentType":"SEQUENCE CAUTION","sequenceCautionType":"Erroneous gene model prediction","sequence":"AAC83664.1","evidences":[{"evidenceCode":"ECO:0000305"}]},{"commentType":"SEQUENCE CAUTION","sequenceCautionType":"Erroneous initiation","sequence":"AAF36538.1","note":"Extended N-terminus.","evidences":[{"evidenceCode":"ECO:0000305"}]}],"features":[{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":795,"modifier":"EXACT"}},"description":"Cyclin-dependent kinase 11B","featureId":"PRO_0000024311"},{"type":"Domain","location":{"start":{"value":438,"modifier":"EXACT"},"end":{"value":723,"modifier":"EXACT"}},"description":"Protein 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