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casein kinase 2

Function: - CK2 is not responsive to known 2nd messengers - phosphorylation of many substrates by CK2 is stimulated 2-3 fold by polyamines - CK2 can use either ATP or GTP - CK2 recognizes the sequence [ST]XX[EDS*T*], where the [ST] represents the Ser/Thr phosphorylation site, X is any non basic residue & [EDS*T*] is a negatively charged site representing an acidic residue or phosphorylated Ser/Thr - this specificity lends CK2 to participate in hierarchal phosphorylation of proteins with the motif [ST]XX[ST] - it may be of significance that several nuclear proteins (including SV40 large T antigen) contain nuclear localization signals proximal to CK2 consensus phosphorylation sites [4]. - participates in Wnt signaling - phosphorylates Ser-392 of p53/TP53 following UV irradiation Structure: - heterotetramer of a2b2 or aa'b2, i.e. (CSNK2A1)2(CSNK2B)2 or CSNK2A1 CSNK2A2 (CSNK2B)2

Interactions

molecular events

General

casein kinase multisubunit protein

Properties

SIZE: MW = 130 kD COMPARTMENT: cell nucleus cytoplasm STATE: active state MOTIF: S/T phosphorylation site kinase domain MOTIF: ATP-binding site NAME: ATP-binding site SUBUNITS: casein kinase 2-alpha chain MOTIF: kinase domain SITE: N-TERMINAL MOTIF: ATP-binding site NAME: ATP-binding site MOTIF: tyrosine residue {X} serine residue {X+1} nuclear translocation signal {K73} MOTIF-SEQUENCE: KKKK Thr phosphorylation site {T128} MOTIF-SEQUENCE: TLTD specific amino acid-enriched region {H148-H166} MOTIF: histidine residue (4) Thr phosphorylation site {T344} FOR-PHOSPHORYLATION-BY: cyclin-dependent kinase-1 Thr phosphorylation site {T360} FOR-PHOSPHORYLATION-BY: cyclin-dependent kinase-1 Ser phosphorylation site {S362} FOR-PHOSPHORYLATION-BY: cyclin-dependent kinase-1 Ser phosphorylation site {S370} FOR-PHOSPHORYLATION-BY: cyclin-dependent kinase-1 STATE: active state casein kinase 2-alpha' chain MOTIF: kinase domain SITE: 40-325 MOTIF: ATP-binding site NAME: ATP-binding site SITE: 46-54 ATP-binding site NAME: ATP-binding site SITE: 69-69 aspartate residue {D157} STATE: active state casein kinase 2-beta chain (2) MOTIF: Ser phosphorylation site {S2} FOR-PHOSPHORYLATION-BY: casein kinase 2-alpha chain Ser phosphorylation site {S3} FOR-PHOSPHORYLATION-BY: casein kinase 2-alpha chain ubiquitination site (destruction box, D-box) SITE: R47-S55 FOR-BINDING-OF: ubiquitin MOTIF-SEQUENCE: RAALAVLKS Zinc finger NAME: Zinc finger SITE: C109-C140 EFFECTOR-BOUND: Zn+2 binding site SITE: H171 FOR-BINDING-OF: casein kinase 2-alpha chain Ser phosphorylation site {S209} FOR-PHOSPHORYLATION-BY: cyclin-dependent kinase-1 MISC-INFO: RECOGNITION-MOTIF :SEQUENCE [ST]XX[EDS*T*] Kd [ATP] 10 UM Kd [GTP] 20 UM Ki [heparin] 1.4 PM LIGAND = 2_3_DIPHOSPHOGLYCERATE LIGAND = QUERCETIN

References

  1. Luscher B, Christenson E, Litchfield DW, Krebs EG, Eisenman RN. Myb DNA binding inhibited by phosphorylation at a site deleted during oncogenic activation. Nature. 1990 Apr 5;344(6266):517-22. PMID: 2157164
  2. Kemp BE, Pearson RB. Protein kinase recognition sequence motifs. Trends Biochem Sci. 1990 Sep;15(9):342-6. Review. PMID: 2238044 (recognition sequence)
  3. Davletov B, Sontag JM, Hata Y, Petrenko AG, Fykse EM, Jahn R, Sudhof TC. Phosphorylation of synaptotagmin I by casein kinase II. J Biol Chem. 1993 Mar 25;268(9):6816-22. PMID: 8454654
  4. Allende JE, Allende CC. Protein kinases. 4. Protein kinase CK2: an enzyme with multiple substrates and a puzzling regulation. FASEB J. 1995 Mar;9(5):313-23. Review. PMID: 7896000

Components

casein kinase 2-alpha chain (CSNK2A1) casein kinase 2-alpha' chain (CSNK2A2) casein kinase 2-beta chain (phosvitin, CSNK2B ,CK2N, G5A)