Cyclin-dependent kinase

From Proteopedia

(Difference between revisions)

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 •	'''CDK1''' binds cyclin and forms a complex which phosphorylates a variety of substrates which are involved in cell cycle progression. <br />
 •	'''CDK2''' is involved in the control of the cell cycle.  It interacts with the regulatory protein cyclin A2.  Phosphorylation at Thr14 or Tyr15 inactivates it; phosphorylation at Thr160 (T160P) – activates it.    See also [[Intrinsically Disordered Protein]].<br />
-•	'''CDK3''' binds cyclin C and functions during the G1 phase. <br />
+•'''CDK3''' binds cyclin C and functions during the G1 phase. <br />
-•	For details on '''CDK4''' see [[Cyclin Dependent Kinase-4]]. <br />
+•For details on '''CDK4''' see [[Cyclin Dependent Kinase-4]]. <br />
-*      '''CDK5''' binds p53 and functions during transcription. <br />
+*'''CDK5''' binds p53 and functions during transcription. <br />
-•      '''CDK6''' binds cyclin D and functions during the G1 phase. <br />
+•'''CDK6''' binds cyclin D and functions during the G1 phase. <br />
-•	'''CDK7''' may serve as a direct link between transcription regulation and the cell cycle.<br />
+*'''CDK7''' may serve as a direct link between transcription regulation and the cell cycle.<br />
-•      '''CDK8''' binds cyclin C and functions during transcription.<br />
+•'''CDK8''' binds cyclin C and functions during transcription.<br />
-•	'''CDK12''' phosphorylates the C-terminal domain of the large subunit of RNA polymerase II.  Acts as a regulator of transcription elongation.<br />
+•'''CDK12''' phosphorylates the C-terminal domain of the large subunit of RNA polymerase II.  Acts as a regulator of transcription elongation.<br />
-•	'''CDK16''' plays a role in vesicle-mediated transport processes and exocytosis.
+•'''CDK13''' is required for RNA splicing. <br />
+•'''CDK16''' plays a role in vesicle-mediated transport processes and exocytosis.
 See also [[Proteins involved in cancer]].
@@ Line 41: / Line 42: @@
 *CDK2
-**[[1pw2]], [[1hck]], [[1hcl]], [[1b38]], [[4ek3]] – hCDK2 – human<br />
+**[[1pw2]], [[1hck]], [[1hcl]], [[1b38]], [[4ek3]], [[5ano]] – hCDK2 – human<br />
 **[[1b39]] - hCDK2 T160P<br />
-**[[3ns9]], [[3le6]], [[2xmy]], [[2xnb]], [[3lfn]], [[3lfq]], [[3lfs]], [[3ig7]], [[3igg]], [[3fz1]], [[3ezr]], [[3ezv]], [[2w1h]], [[2w17]], [[2w05]], [[2w06]], [[2r64]], [[2vta]], [[2vth]], [[2vti]], [[2vtj]], [[2vtl]], [[2vtm]], [[2vtn]], [[2vto]], [[2vtp]], [[2vtq]], [[2vtr]], [[2vts]], [[2vtt]], [[2vu3]], [[2vv9]], [[2r3f]], [[2r3g]], [[2r3h]], [[2r3i]], [[2r3j]], [[2r3k]], [[2r3l]], [[2r3m]], [[2r3n]], [[2r3o]], [[2r3p]], [[2r3q]], [[2r3r]], [[2j9m]], [[2v0d]], [[2duv]], [[2clx]], [[2fvd]], [[2a4l]], [[1w8c]], [[2a0c]], [[2exm]], [[2bpm]], [[2c68]], [[2c69]], [[2c6i]], [[2c6k]], [[2c6l]], [[2c6m]], [[2c6o]], [[2c6t]], [[2btr]], [[2bts]], [[2b52]], [[2b53]], [[2b54]], [[2b55]], [[2bhe]], [[2bhh]], [[1y8y]], [[1y91]], [[1wcc]], [[1w0x]], [[1pye]], [[1vyz]], [[1vyw]], [[1v1k]], [[1urw]], [[1pxm]], [[1pxn]], [[1pxo]], [[1pxp]], [[1r78]], [[1pf8]], [[1pxi]], [[1pxj]], [[1pxk]], [[1pxl]], [[1oiq]], [[1oir]], [[1oit]], [[1p2a]], [[1h00]], [[1h01]], [[1h07]], [[1h08]], [[1h0v]], [[1h0w]], [[1gz8]], [[1ke5]], [[1ke6]], [[1ke7]], [[1ke8]], [[1ke9]], [[1gih]], [[1gii]], [[1gij]], [[1jvp]], [[1g5s]], [[1jsv]], [[1e1v]], [[1e1x]], [[1fvt]], [[1fvv]], [[1di8]], [[1dm2]], [[1ckp]], [[1aq1]], [[3pxf]], [[3pxq]], [[3pxr]], [[3pxy]], [[3pxz]], [[3py0]], [[3py1]], [[3pj8]], [[3s2p]],[[3ql8]], [[3qqf]], [[3qqg]], [[3qqh]], [[3qqj]], [[3qqk]], [[3qql]], [[3qrt]], [[3qru]], [[3qtq]], [[3qtr]], [[3qts]], [[3qtu]], [[3qtw]], [[3qtx]], [[3qtz]], [[3qu0]], [[3qwj]], [[3qwk]], [[3qx2]], [[3qx4]], [[3qxo]], [[3qxp]], [[3qzf]], [[3qzg]], [[3qzh]], [[3qzi]], [[3r1q]], [[3r1s]], [[3r1y]], [[3r28]], [[3r6x]], [[3r71]], [[3r73]], [[3r7e]], [[3r7i]], [[3r7u]], [[3r7v]], [[3r7y]], [[3r83]], [[3r8l]], [[3r8m]], [[3r8p]], [[3r8u]], [[3r8v]], [[3r8z]], [[3r9d]], [[3r9h]], [[3r9n]], [[3r9o]], [[3rah]], [[3rai]], [[3rak]], [[3ral]], [[3rjc]], [[3rk5]], [[3rk7]], [[3rk9]], [[3rkb]], [[3rm6]], [[3rm7]], [[3rmf]], [[3rni]], [[3roy]], [[3rpo]], [[3rpr]], [[3rpv]], [[3rpy]], [[3rzb]], [[3s00]], [[3s0o]], [[3s1h]], [[3sqq]], [[3sw4]], [[3sw7]], [[3ti1]], [[3tiy]], [[3tiz]], [[3uli]], [[3unj]], [[3unk]], [[3wbl]], [[4acm]], [[4bgh]], [[4ek4]], [[4ek5]], [[4ek6]], [[4ek8]], [[4ez3]], [[4ez7]], [[4fkg]], [[4fki]], [[4fkj]], [[4fkl]], [[4fko]], [[4fkp]], [[4fkq]], [[4fkr]], [[4fks]], [[4fkt]], [[4fku]], [[4fkv]], [[4fkw]], [[4gcj]], [[4kd1]], [[4lyn]], [[4nj3]], [[4bzd]], [[4rj3]] – hCDK2 + inhibitor<br />
+**[[3ns9]], [[3le6]], [[2xmy]], [[2xnb]], [[3lfn]], [[3lfq]], [[3lfs]], [[3ig7]], [[3igg]], [[3fz1]], [[3ezr]], [[3ezv]], [[2w1h]], [[2w17]], [[2w05]], [[2w06]], [[2r64]], [[2vta]], [[2vth]], [[2vti]], [[2vtj]], [[2vtl]], [[2vtm]], [[2vtn]], [[2vto]], [[2vtp]], [[2vtq]], [[2vtr]], [[2vts]], [[2vtt]], [[2vu3]], [[2vv9]], [[2r3f]], [[2r3g]], [[2r3h]], [[2r3i]], [[2r3j]], [[2r3k]], [[2r3l]], [[2r3m]], [[2r3n]], [[2r3o]], [[2r3p]], [[2r3q]], [[2r3r]], [[2j9m]], [[2v0d]], [[2duv]], [[2clx]], [[2fvd]], [[2a4l]], [[1w8c]], [[2a0c]], [[2exm]], [[2bpm]], [[2c68]], [[2c69]], [[2c6i]], [[2c6k]], [[2c6l]], [[2c6m]], [[2c6o]], [[2c6t]], [[2btr]], [[2bts]], [[2b52]], [[2b53]], [[2b54]], [[2b55]], [[2bhe]], [[2bhh]], [[1y8y]], [[1y91]], [[1wcc]], [[1w0x]], [[1pye]], [[1vyz]], [[1vyw]], [[1v1k]], [[1urw]], [[1pxm]], [[1pxn]], [[1pxo]], [[1pxp]], [[1r78]], [[1pf8]], [[1pxi]], [[1pxj]], [[1pxk]], [[1pxl]], [[1oiq]], [[1oir]], [[1oit]], [[1p2a]], [[1h00]], [[1h01]], [[1h07]], [[1h08]], [[1h0v]], [[1h0w]], [[1gz8]], [[1ke5]], [[1ke6]], [[1ke7]], [[1ke8]], [[1ke9]], [[1gih]], [[1gii]], [[1gij]], [[1jvp]], [[1g5s]], [[1jsv]], [[1e1v]], [[1e1x]], [[1fvt]], [[1fvv]], [[1di8]], [[1dm2]], [[1ckp]], [[1aq1]], [[3pxf]], [[3pxq]], [[3pxr]], [[3pxy]], [[3pxz]], [[3py0]], [[3py1]], [[3pj8]], [[3s2p]], [[3ql8]], [[3qqf]], [[3qqg]], [[3qqh]], [[3qqj]], [[3qqk]], [[3qql]], [[3qrt]], [[3qru]], [[3qtq]], [[3qtr]], [[3qts]], [[3qtu]], [[3qtw]], [[3qtx]], [[3qtz]], [[3qu0]], [[3qwj]], [[3qwk]], [[3qx2]], [[3qx4]], [[3qxo]], [[3qxp]], [[3qzf]], [[3qzg]], [[3qzh]], [[3qzi]], [[3r1q]], [[3r1s]], [[3r1y]], [[3r28]], [[3r6x]], [[3r71]], [[3r73]], [[3r7e]], [[3r7i]], [[3r7u]], [[3r7v]], [[3r7y]], [[3r83]], [[3r8l]], [[3r8m]], [[3r8p]], [[3r8u]], [[3r8v]], [[3r8z]], [[3r9d]], [[3r9h]], [[3r9n]], [[3r9o]], [[3rah]], [[3rai]], [[3rak]], [[3ral]], [[3rjc]], [[3rk5]], [[3rk7]], [[3rk9]], [[3rkb]], [[3rm6]], [[3rm7]], [[3rmf]], [[3rni]], [[3roy]], [[3rpo]], [[3rpr]], [[3rpv]], [[3rpy]], [[3rzb]], [[3s00]], [[3s0o]], [[3s1h]], [[3sqq]], [[3sw4]], [[3sw7]], [[3ti1]], [[3tiy]], [[3tiz]], [[3uli]], [[3unj]], [[3unk]], [[3wbl]], [[4acm]], [[4bgh]], [[4ek4]], [[4ek5]], [[4ek6]], [[4ek8]], [[4ez3]], [[4ez7]], [[4fkg]], [[4fki]], [[4fkj]], [[4fkl]], [[4fko]], [[4fkp]], [[4fkq]], [[4fkr]], [[4fks]], [[4fkt]], [[4fku]], [[4fkv]], [[4fkw]], [[4gcj]], [[4kd1]], [[4lyn]], [[4nj3]], [[4bzd]], [[4rj3]], [[5osj]], [[5oo0]], [[5mhq]], [[5k4j]], [[5jq8]], [[5jq5]], [[5iey]], [[5iex]], [[5fp6]], [[5fp5]], [[5d1j]], [[5ank]], [[5anj]], [[5ani]], [[5ang]], [[5ane]], [[5and]], [[5a14]], [[4d1z]], [[4d1x]] – hCDK2 + inhibitor<br />
-**[[2ds1]] – hCDK2 (mutant) + inhibitor<br />
+**[[2ds1]], [[5osm]] – hCDK2 (mutant) + inhibitor<br />
-**[[1fq1]] - hCDK2 +cyclin-dependent kinase inhibitor 3<br />
+**[[5iev]] – hCDK2 + drug<br />
-**[[1buh]] – hCDK2+ protein CKSHS1<br />
+**[[1fq1]] - hCDK2 + cyclin-dependent kinase inhibitor 3<br />
+**[[5uq3]] - hCDK2 + speedy protein A + cyclin-dependent kinase inhibitor 3<br />
+**[[5uq2]], [[5uq1]] - hCDK2 + speedy protein A <br />
+**[[1buh]] – hCDK2 + protein CKSHS1<br />
 **[[4erw]] – hCDK2 + staurosporine<br />
 *CDK2+cyclin
+**[[5if1]] – hCDK2 + cyclin A2 <br />
 **[[2jgz]] - hCDK2 T160P + cyclin B1<br />
-**[[1w98]] - hCDK2 + cyclin E1<br />
+**[[1w98]], [[5t2w]] - hCDK2 + cyclin E1<br />
 **[[2wma]], [[2wmb]], [[2x1n]], [[2wev]], [[2wfy]], [[2whb]], [[2v22]], [[2cch]], [[1okv]], [[1okw]], [[1ol1]], [[1ol2]], [[1urc]], [[1h24]], [[1h25]], [[1h26]], [[1h27]], [[1h28]], [[1gy3]], [[3qhr]], [[3qhw]] - hCDK2 + cyclin A2+peptide ligand<br />
 **[[2wpa]], [[2wxv]], [[2wih]], [[2wip]], [[3f5x]], [[3eoc]], [[3eid]], [[3ej1]], [[2uzb]], [[2uzd]], [[2uze]], [[2uzl]], [[2uzn]], [[2uzo]], [[2uue]], [[2i40]], [[2bkz]], [[2c5n]], [[2c5o]], [[2c5v]], [[2c5x]], [[2c5y]], [[1ykr]], [[2c4g]], [[1p5e]], [[1pkd]], [[1fin]], [[4bcm]], [[4bcn]], [[4bco]], [[4bcp]], [[4bcq]], [[4cfm]], [[4cfn]], [[4cfu]], [[4cfv]], [[4cfw]], [[4cfx]], [[4fx3]] – hCDK2 + cyclin A2 + inhibitor<br />
-**[[3ddp]], [[3dog]], [[3ddq]], [[3bht]], [[3bhu]], [[3bhv]], [[2iw6]], [[2iw8]], [[2iw9]], [[2g9x]], [[2cjm]], [[1oi9]], [[1oiu]], [[1oiy]], [[1ogu]], [[1h1p]], [[1h1q]], [[1h1r]], [[1h1s]], [[1jst]], [[3tnw]], [[4bck]], [[4eoi]], [[4eoj]], [[4eok]], [[4eol]], [[4eom]], [[4eon]], [[4eoo]], [[4eop]], [[4eoq]], [[4eor]], [[4eos]] - hCDK2 T160P+ cyclin A2 + inhibitor<br />
+**[[3ddp]], [[3dog]], [[3ddq]], [[3bht]], [[3bhu]], [[3bhv]], [[2iw6]], [[2iw8]], [[2iw9]], [[2g9x]], [[2cjm]], [[1oi9]], [[1oiu]], [[1oiy]], [[1ogu]], [[1h1p]], [[1h1q]], [[1h1r]], [[1h1s]], [[1jst]], [[3tnw]], [[4bck]], [[4eoi]], [[4eoj]], [[4eok]], [[4eol]], [[4eom]], [[4eon]], [[4eoo]], [[4eop]], [[4eoq]], [[4eor]], [[4eos]], [[5cyi]], [[5nev]], [[5lmk]] - hCDK2 T160P + cyclin A2 + inhibitor<br />
-**[[2cci]], [[1qmz]] - hCDK2 T160P + cyclin A2+peptide ligand<br />
+**[[2cci]], [[1qmz]] - hCDK2 T160P + cyclin A2 + peptide ligand<br />
 **[[1e9h]] - hCDK2 T160P + cyclin A3 + inhibitor<br />
 **[[1jsu]] - hCDK2 T160P + cyclin A2+ protein P27<br />
@@ Line 68: / Line 73: @@
 **[[2w96]], [[2w99]], [[2w9f]], [[2w9z]] – hCDK4 kinase domain + cyclin D1<br />
-**[[3g33]] - hCDK4 + cyclin D3
+**[[3g33]] - hCDK4 + cyclin D3<br />
+**[[5fwp]], [[5fwm]], [[5fwl]], [[5fwl]] - hCDK4-P + HSP 90 + CDC37 – cryo-EM<br />
 *CDK5
@@ Line 84: / Line 90: @@
 **[[1jow]] – hCDK6 + V-cyclin<br />
 **[[3nup]], [[3nux]], [[4aua]], [[4ez5]] – hCDK6 + inhibitor<br />
+**[[5l2t]], [[5l2s]], [[5l2i]] – hCDK6 + drug<br />
 **[[1xo2]], [[2f2c]], [[2euf]], [[4tth]] – hCDK6 + V-cyclin + inhibitor<br />
@@ Line 93: / Line 100: @@
 **[[4g6l]], [[4cri]] – hCDK8 + cyclin C <br />
-**[[3rgf]], [[4f6s]], [[4f6u]], [[4f6w]], [[4f70]], [[4f7j]], [[4f7l]], [[4f7n]], [[4c4l]], [[5bnj]], [[5cei]], [[5fgk]], [[5hbe]], [[5hbh]], [[5hbj]], [[5hnb]], [[5hvy]], [[5i5z]], [[5icp]], [[5idn]], [[5idp]] – hCDK8 + cyclin C + inhibitor<br />
+**[[3rgf]], [[4f6s]], [[4f6u]], [[4f6w]], [[4f70]], [[4f7j]], [[4f7l]], [[4f7n]], [[4c4l]], [[5bnj]], [[5cei]], [[5fgk]], [[5hbe]], [[5hbh]], [[5hbj]], [[5hnb]], [[5hvy]], [[5i5z]], [[5icp]], [[5idn]], [[5idp]], [[5xs2]], [[5xqx]], [[4f7s]] – hCDK8 + cyclin C + inhibitor<br />
-**[[4f7s]] – hCDK8 + cyclin C + phenylethyl-quinazolin-amine<br />
 *CDK9
@@ Line 103: / Line 109: @@
 **[[3blr]] – hCDK9-P + cyclin T1 + flavopiridol<br />
 **[[3mi9]], [[3mia]] – hCDK9-P + cyclin T1 + HIV-1 TAT<br />
+**[[5l1z]] – hCDK9-P + cyclin T1 + HIV-1 TAT + AF4/FMR2 + RNA<br />
 **[[4or5]], [[4ogr]] – hCDK9-P + cyclin T1 + HIV-1 TAT + major CDK9 elongation factor-associated protein<br />
 **[[4imy]] – hCDK9-P + cyclin T1 + CDK9 elongation factor-associated protein<br />
-*CDK12
+*CDK12 kinase domain
 **[[4un0]] – hCDK12-P + cyclin K<br />
 **[[4nst]] – hCDK12-P + cyclin K + AlF3<br />
 **[[4cxa]] – hCDK12-P + cyclin K + AMPPNP<br />
+**[[6b3e]], [[5acb]] – hCDK12-P + cyclin K + inhibitor<br />
+*CDK13
+**[[5efq]] – hCDK13-P residues 694-1039 + cyclin K + ADP<br />
 *CDK16

Revision as of 09:43, 16 April 2018

spinqualitylabelsall models

CDK2 (cyan) complex with cyclin A2 (green), ATP analog roscovitine and monothioglycerol (PDB code 3ddq)

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1 Function
2 Relevance
3 Structural highlights

Function

Cyclin-dependent kinase (CDK) or Cell division protein kinase are serine/threonine kinases which are important to the regulation of the cell cycle. CDKs are small proteins which contain just a kinase domain. In order to function, CDK binds the regulatory protein cyclin. CDKs phosphorylate their substrates at a consensus tetrapeptide. The CDK classes differ by the binding cyclin and their function in human.^[1]

• CDK1 binds cyclin and forms a complex which phosphorylates a variety of substrates which are involved in cell cycle progression.

• CDK2 is involved in the control of the cell cycle. It interacts with the regulatory protein cyclin A2. Phosphorylation at Thr14 or Tyr15 inactivates it; phosphorylation at Thr160 (T160P) – activates it. See also Intrinsically Disordered Protein.
•CDK3 binds cyclin C and functions during the G1 phase.
•For details on CDK4 see Cyclin Dependent Kinase-4.

CDK5 binds p53 and functions during transcription.

•CDK6 binds cyclin D and functions during the G1 phase.

CDK7 may serve as a direct link between transcription regulation and the cell cycle.

•CDK8 binds cyclin C and functions during transcription.
•CDK12 phosphorylates the C-terminal domain of the large subunit of RNA polymerase II. Acts as a regulator of transcription elongation.
•CDK13 is required for RNA splicing.
•CDK16 plays a role in vesicle-mediated transport processes and exocytosis.

Relevance

CDK is a potential target for anti-cancer therapy.

Structural highlights

The kinase is located in a . near the binding site is required for kinase activity.^[2]

3D structures of cyclin-dependent kinase

Updated on 16-April-2018

References

↑ Larsen NA, Turner JM, Stevens J, Rosser SJ, Basran A, Lerner RA, Bruce NC, Wilson IA. Crystal structure of a bacterial cocaine esterase. Nat Struct Biol. 2002 Jan;9(1):17-21. PMID:11742345 doi:10.1038/nsb742
↑ Bettayeb K, Oumata N, Echalier A, Ferandin Y, Endicott JA, Galons H, Meijer L. CR8, a potent and selective, roscovitine-derived inhibitor of cyclin-dependent kinases. Oncogene. 2008 Oct 2;27(44):5797-807. Epub 2008 Jun 23. PMID:18574471 doi:10.1038/onc.2008.191