cyclin-dependent kinase 11B; cell division cycle 2-like protein kinase 1; CLK-1; cell division protein kinase 11B; galactosyltransferase-associated protein kinase p58/GTA; PITSLRE serine/threonine-protein kinase CDC2L1; p58 CLK-1 (CDK11B, CDC2L1, CDK11, PITSLREA, PK58)

Function: - appears to play multiple roles in cell cycle progression, cytokinesis & apoptosis - the p110 isoforms have been suggested to be involved in pre-mRNA splicing, potentially by phosphorylating the splicing protein SFRS7 - the p58 isoform may act as a negative regulator of normal cell cycle progression - the cleaved p110 isoform, p110C, binds to the serine/threonine kinase PAK1 & RANBP9 - the cleaved p110 isoform interacts with RNPS1 - the p58 isoform but not the p110 isoforms or p110C interacts with CCND3 - the p110 isoforms are found in high molecular weight complexes containing CCNL1 & SFRS7 - phosphorylation at Thr-448 or Tyr-449 inactivates CDC2L1 - phosphorylation at Thr-595 activates CDC2L1 (putative) - during apoptosis, induced by Fas or tumor necrosis factor, - specific PITSLRE p110 isoforms are cleaved by caspases to produce a protein (p110C) that contains the C-terminal kinase domain of the PITSLRE proteins - P110C can be autophosphorylated Cofactor: Mg⁺² Structure: - belongs to the protein kinase superfamily, CMGC Ser/Thr protein kinase family, CDC2/CDKX subfamily - contains 1 protein kinase domain Compartment: cytoplasm. nucleus Alternative splicing: named isoforms=10 Alternative initiation: yes Expression: - expressed ubiquitously - some evidence of isoform-specific tissue distribution - p58 isoform is specifically induced in G2/M phase of the cell cycle Genetics: - duplicated gene - CDC2L1 & CDC2L2 encode almost identical protein kinases of 110 kD that contain at their C termini the open reading frame of a smaller 58 kD isoform which is expressed following IRES-mediated alternative initiation of translation Note: - also see CDK11A - many references talk about 'p110 isoforms' but it is not yet known if this refers to CDC2L1 &/or CDC2L2 or one/some of the isoforms of each

Properties

SIZE: entity length = 780 aa MW = 91 kD COMPARTMENT: cytoplasm cell nucleus STATE: active state MOTIF: glutamate-rich region {15-378} MOTIF: glutamate residue (SEVERAL) Ser phosphorylation site {S47} Ser phosphorylation site {S222} Ser phosphorylation site {S271} kinase domain SITE: 424-644 MOTIF: ATP-binding site NAME: ATP-binding site SITE: 429-437 Thr phosphorylation site {T433} Tyr phosphorylation site {Y434} ATP-binding site NAME: ATP-binding site SITE: 452-452 aspartate residue {D547} Tyr phosphorylation site {Y572} Ser phosphorylation site {S574} Thr phosphorylation site {T580} Thr phosphorylation site {T736} Ser phosphorylation site {S737} Thr phosphorylation site {T758}

Database Correlations

OMIM 176873 UniProt P21127 Pfam PF00069 Entrez Gene 984 Kegg hsa:984 ENZYME 2.7.11.22

References

UniProt :accession P21127