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cyclin-dependent kinase-12 (CDK12); Cdc2-related kinase, arginine/serine-rich; CrkRS; cell division cycle 2-related protein kinase 7; CDC2-related protein kinase 7; cell division protein kinase 12; hCDK12 (CRK7, CRKRS, KIAA0904)

Function: - cyclin-dependent kinase - displays CTD kinase activity by hyperphosphorylating the C-terminal heptapeptide repeat domain (CTD) of the largest RNA polymerase II subunit RPB1, thus acting as a regulator of transcription elongation. - required for RNA splicing, possibly by phosphorylating SRSF1/SF2 - role in regulation of MAP kinase activity, possibly leading to affect the response to estrogen inhibitors - interacts with CCNL1 & CCNL2 (putative) Structure: - belongs to the protein kinase superfamily, CMGC Ser/Thr protein kinase family, CDC2/CDKX subfamily - contains 1 protein kinase domain Compartment: - nucleus. nuclear speckle - colocalized with nuclear speckles throughout interphase Alternative splicing: named isoforms=3 Expression: ubiquitously expressed Pathology: - chromosomal deletion within 17q12 region involving CDK12 producing fusion transcripts with ERBB2 may be a cause of gastric cancer - deletion leads to CDK12-ERBB2 fusion with truncated CDK12 protein not in-frame with ERBB2

General

cyclin-dependent kinase (CDK) nuclear protein

Properties

SIZE: entity length = 1490 aa MW = 164 kD COMPARTMENT: cell nucleus MOTIF: Ser phosphorylation site {S14} Ser phosphorylation site {S24} Ser phosphorylation site {S25} Ser phosphorylation site {S29} Ser phosphorylation site {S32} Thr phosphorylation site {T57} Ser phosphorylation site {S62} Tyr phosphorylation site {Y73} Ser phosphorylation site {S77} Ser phosphorylation site {S78} Ser phosphorylation site {S80} Thr phosphorylation site {T82} Ser phosphorylation site {S84} Ser phosphorylation site {S215} Ser phosphorylation site {S228} Ser phosphorylation site {S236} Ser phosphorylation site {S238} Ser phosphorylation site {S249} Ser phosphorylation site {S265} Ser phosphorylation site {S274} Ser phosphorylation site {S276} Tyr phosphorylation site {Y279} Ser phosphorylation site {S291} Ser phosphorylation site {S293} Ser phosphorylation site {S301} Ser phosphorylation site {S303} Ser phosphorylation site {S318} Tyr phosphorylation site {Y319} Ser phosphorylation site {S320} Ser phosphorylation site {S323} Ser phosphorylation site {S325} Ser phosphorylation site {S332} Ser phosphorylation site {S333} Ser phosphorylation site {S334} Ser phosphorylation site {S341} Ser phosphorylation site {S343} Ser phosphorylation site {S345} Ser phosphorylation site {S382} Ser phosphorylation site {S383} Ser phosphorylation site {S385} Ser phosphorylation site {S393} Ser phosphorylation site {S400} alanine-rich region {407-413} MOTIF: alanine residue (SEVERAL) Ser phosphorylation site {S420} Ser phosphorylation site {S423} Ser phosphorylation site {S434} Thr phosphorylation site {T514} proline-rich region SITE: 535-540 MOTIF: proline residue (SEVERAL) Ser phosphorylation site {S681} Ser phosphorylation site {S685} Thr phosphorylation site {T692} kinase domain SITE: 727-1020 MOTIF: ATP-binding site NAME: ATP-binding site SITE: 733-741 ATP-binding site NAME: ATP-binding site SITE: 756-756 aspartate residue {D859} Tyr phosphorylation site {Y892} Thr phosphorylation site {T893} Ser phosphorylation site {S1053} Thr phosphorylation site {T1070} Thr phosphorylation site {T1074} Thr phosphorylation site {T1076} Ser phosphorylation site {S1082} Ser phosphorylation site {S1083} Thr phosphorylation site {T1244} proline-rich region SITE: 1266-1280 MOTIF: proline residue (SEVERAL) STATE: active state

Database Correlations

UniProt Q9NYV4 Pfam PF00069 Entrez Gene 51755 Kegg hsa:51755 ENZYME correlations

References

UniProt :accession Q9NYV4