| UniProt ID | CDK6_HUMAN | |
|---|---|---|
| UniProt AC | Q00534 | |
| Protein Name | Cyclin-dependent kinase 6 | |
| Gene Name | CDK6 | |
| Organism | Homo sapiens (Human). | |
| Sequence Length | 326 | |
| Subcellular Localization | Cytoplasm. Nucleus. Cell projection, ruffle. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome . Localized to the ruffling edge of spreading fibroblasts. Kinase activity only in nucleus. Localized to the cytosol of neurons and showed | |
| Protein Description | Serine/threonine-protein kinase involved in the control of the cell cycle and differentiation; promotes G1/S transition. Phosphorylates pRB/RB1 and NPM1. Interacts with D-type G1 cyclins during interphase at G1 to form a pRB/RB1 kinase and controls the entrance into the cell cycle. Involved in initiation and maintenance of cell cycle exit during cell differentiation; prevents cell proliferation and regulates negatively cell differentiation, but is required for the proliferation of specific cell types (e.g. erythroid and hematopoietic cells). Essential for cell proliferation within the dentate gyrus of the hippocampus and the subventricular zone of the lateral ventricles. Required during thymocyte development. Promotes the production of newborn neurons, probably by modulating G1 length. Promotes, at least in astrocytes, changes in patterns of gene expression, changes in the actin cytoskeleton including loss of stress fibers, and enhanced motility during cell differentiation. Prevents myeloid differentiation by interfering with RUNX1 and reducing its transcription transactivation activity, but promotes proliferation of normal myeloid progenitors. Delays senescence. Promotes the proliferation of beta-cells in pancreatic islets of Langerhans. May play a role in the centrosome organization during the cell cycle phases. [PubMed: 23918663] | |
| Protein Sequence | MEKDGLCRADQQYECVAEIGEGAYGKVFKARDLKNGGRFVALKRVRVQTGEEGMPLSTIREVAVLRHLETFEHPNVVRLFDVCTVSRTDRETKLTLVFEHVDQDLTTYLDKVPEPGVPTETIKDMMFQLLRGLDFLHSHRVVHRDLKPQNILVTSSGQIKLADFGLARIYSFQMALTSVVVTLWYRAPEVLLQSSYATPVDLWSVGCIFAEMFRRKPLFRGSSDVDQLGKILDVIGLPGEEDWPRDVALPRQAFHSKSAQPIEKFVTDIDELGKDLLLKCLTFNPAKRISAYSALSHPYFQDLERCKENLDSHLPPSQNTSELNTA | |
| Overview of Protein Modification Sites with Functional and Structural Information | ||
|
|
||
* ASA = Accessible Surface Area
| Locations | Modification | Substrate Peptides & Secondary Structure |
ASA (%) | Reference | Orthologous Protein Cluster |
|---|---|---|---|---|---|
| 1 | Acetylation | -------MEKDGLCR -------CCCCCCCC | 15.12 | 22814378 | |
| 3 | Ubiquitination | -----MEKDGLCRAD -----CCCCCCCCHH | 56.66 | 23000965 | |
| 3 | Ubiquitination | -----MEKDGLCRAD -----CCCCCCCCHH | 56.66 | - | |
| 3 | Acetylation | -----MEKDGLCRAD -----CCCCCCCCHH | 56.66 | 25953088 | |
| 3 | Methylation | -----MEKDGLCRAD -----CCCCCCCCHH | 56.66 | - | |
| 13 | Phosphorylation | LCRADQQYECVAEIG CCCHHHHEEEEEEEC | 12.98 | 19605366 | |
| 24 | Phosphorylation | AEIGEGAYGKVFKAR EEECCCCCCEEEEEE | 28.47 | 22322096 | |
| 26 | Acetylation | IGEGAYGKVFKARDL ECCCCCCEEEEEEEC | 31.64 | 23749302 | |
| 26 | Ubiquitination | IGEGAYGKVFKARDL ECCCCCCEEEEEEEC | 31.64 | 21906983 | |
| 29 | Ubiquitination | GAYGKVFKARDLKNG CCCCEEEEEEECCCC | 45.56 | 22817900 | |
| 34 | Ubiquitination | VFKARDLKNGGRFVA EEEEEECCCCCEEEE | 58.81 | 29967540 | |
| 43 | Acetylation | GGRFVALKRVRVQTG CCEEEEEEEEEEECC | 38.83 | 19608861 | |
| 43 | Ubiquitination | GGRFVALKRVRVQTG CCEEEEEEEEEEECC | 38.83 | 19608861 | |
| 49 | Phosphorylation | LKRVRVQTGEEGMPL EEEEEEECCCCCCCH | 43.64 | 26462736 | |
| 54 | Sulfoxidation | VQTGEEGMPLSTIRE EECCCCCCCHHHHHH | 3.23 | 21406390 | |
| 57 | Phosphorylation | GEEGMPLSTIREVAV CCCCCCHHHHHHHHH | 18.87 | 26074081 | |
| 70 | Phosphorylation | AVLRHLETFEHPNVV HHHHHHHHCCCCCEE | 40.46 | 22817900 | |
| 84 | Phosphorylation | VRLFDVCTVSRTDRE EEEEEEEEEECCCCC | 22.74 | 30001349 | |
| 86 | Phosphorylation | LFDVCTVSRTDRETK EEEEEEEECCCCCCE | 16.00 | 30576142 | |
| 93 | Ubiquitination | SRTDRETKLTLVFEH ECCCCCCEEEEEEEE | 34.42 | 29967540 | |
| 111 | Ubiquitination | DLTTYLDKVPEPGVP CHHHHHHCCCCCCCC | 58.03 | 29967540 | |
| 123 | Ubiquitination | GVPTETIKDMMFQLL CCCHHHHHHHHHHHH | 47.17 | 29967540 | |
| 138 | Phosphorylation | RGLDFLHSHRVVHRD HCHHHHHHCCEECCC | 18.35 | 26546556 | |
| 147 | Ubiquitination | RVVHRDLKPQNILVT CEECCCCCCCCEEEC | 49.17 | 21906983 | |
| 147 | Ubiquitination | RVVHRDLKPQNILVT CEECCCCCCCCEEEC | 49.17 | 21890473 | |
| 154 | Phosphorylation | KPQNILVTSSGQIKL CCCCEEECCCCCEEE | 17.46 | 19060867 | |
| 155 | Phosphorylation | PQNILVTSSGQIKLA CCCEEECCCCCEEEH | 25.62 | 22817900 | |
| 160 | Ubiquitination | VTSSGQIKLADFGLA ECCCCCEEEHHHCHH | 29.72 | 17623298 | |
| 170 | Phosphorylation | DFGLARIYSFQMALT HHCHHHHHHHHHHHH | 9.62 | 28857561 | |
| 171 | Phosphorylation | FGLARIYSFQMALTS HCHHHHHHHHHHHHH | 13.46 | 28857561 | |
| 177 | Phosphorylation | YSFQMALTSVVVTLW HHHHHHHHHHHHHHH | 15.22 | 28857561 | |
| 178 | Phosphorylation | SFQMALTSVVVTLWY HHHHHHHHHHHHHHH | 17.48 | 28857561 | |
| 222 | Phosphorylation | RKPLFRGSSDVDQLG CCCCCCCCCCHHHHH | 21.07 | 30576142 | |
| 223 | Phosphorylation | KPLFRGSSDVDQLGK CCCCCCCCCHHHHHH | 44.47 | 30576142 | |
| 230 | Ubiquitination | SDVDQLGKILDVIGL CCHHHHHHHHHHHCC | 49.00 | 21906983 | |
| 256 | Phosphorylation | LPRQAFHSKSAQPIE CCHHHHCCCCCCCHH | 23.11 | 24144214 | |
| 257 | Ubiquitination | PRQAFHSKSAQPIEK CHHHHCCCCCCCHHH | 41.04 | 21906983 | |
| 258 | Phosphorylation | RQAFHSKSAQPIEKF HHHHCCCCCCCHHHH | 34.84 | 24144214 | |
| 264 | Ubiquitination | KSAQPIEKFVTDIDE CCCCCHHHHCCCHHH | 45.94 | - | |
| 264 | Acetylation | KSAQPIEKFVTDIDE CCCCCHHHHCCCHHH | 45.94 | 19608861 | |
| 264 | Ubiquitination | KSAQPIEKFVTDIDE CCCCCHHHHCCCHHH | 45.94 | 23000965 | |
| 267 | Phosphorylation | QPIEKFVTDIDELGK CCHHHHCCCHHHHCH | 30.30 | - | |
| 274 | Ubiquitination | TDIDELGKDLLLKCL CCHHHHCHHHHHHHH | 58.80 | 22817900 | |
| 279 | Ubiquitination | LGKDLLLKCLTFNPA HCHHHHHHHHCCCHH | 27.45 | 22817900 | |
| 287 | Ubiquitination | CLTFNPAKRISAYSA HHCCCHHHHCHHHHH | 52.07 | 22505724 | |
| 287 | Acetylation | CLTFNPAKRISAYSA HHCCCHHHHCHHHHH | 52.07 | 25953088 | |
| 290 | Phosphorylation | FNPAKRISAYSALSH CCHHHHCHHHHHHCC | 25.78 | 28464451 | |
| 292 | Phosphorylation | PAKRISAYSALSHPY HHHHCHHHHHHCCHH | 6.41 | 25839225 | |
| 293 | Phosphorylation | AKRISAYSALSHPYF HHHCHHHHHHCCHHH | 23.58 | 28464451 | |
| 296 | Phosphorylation | ISAYSALSHPYFQDL CHHHHHHCCHHHHCH | 23.33 | 28464451 | |
| 299 | Phosphorylation | YSALSHPYFQDLERC HHHHCCHHHHCHHHH | 14.40 | - | |
| 307 | Ubiquitination | FQDLERCKENLDSHL HHCHHHHHHHHHHCC | 56.72 | 22505724 | |
| 317 | Phosphorylation | LDSHLPPSQNTSELN HHHCCCCCCCHHHCC | 33.84 | 30576142 | |
| 320 | Phosphorylation | HLPPSQNTSELNTA- CCCCCCCHHHCCCC- | 18.88 | 24850871 | |
| 321 | Phosphorylation | LPPSQNTSELNTA-- CCCCCCHHHCCCC-- | 47.86 | 24850871 | |
| 325 | Phosphorylation | QNTSELNTA------ CCHHHCCCC------ | 46.50 | 23918663 |
| Modified Location | Modified Residue | Modification | Type of Upstream Proteins | Gene Name of Upstream Proteins | UniProt AC of Upstream Proteins | Sources |
|---|---|---|---|---|---|---|
| 177 | T | Phosphorylation | Kinase | CDK7 | P50613 | PSP |
| Modified Location | Modified Residue | Modification | Function | Reference |
|---|---|---|---|---|
| 177 | T | Phosphorylation |
| 11828325 |
* Distance = the distance between SAP position and PTM sites.
| Modified Location | Modification | Variant Position (Distance <= 10) |
Residue Change | SAP | Related Disease | Reference |
|---|---|---|---|---|---|---|
Oops, there are no SNP-PTM records of CDK6_HUMAN !! | ||||||
| Kegg Disease | ||||||
|---|---|---|---|---|---|---|
| There are no disease associations of PTM sites. | ||||||
| OMIM Disease | ||||||
| 616080 | Microcephaly 12, primary, autosomal recessive (MCPH12) | |||||
| Kegg Drug | ||||||
| There are no disease associations of PTM sites. | ||||||
| DrugBank | ||||||
| There are no disease associations of PTM sites. | ||||||
loading...
| Acetylation | |
| Reference | PubMed |
| "Lysine acetylation targets protein complexes and co-regulates majorcellular functions."; Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.,Olsen J.V., Mann M.; Science 325:834-840(2009). Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-43 AND LYS-264, AND MASSSPECTROMETRY. | |
| Phosphorylation | |
| Reference | PubMed |
| "Large-scale proteomics analysis of the human kinome."; Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,Mann M., Daub H.; Mol. Cell. Proteomics 8:1751-1764(2009). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-24; THR-49; SER-57;THR-70; SER-86; THR-154; SER-155; SER-223; SER-290; SER-317 ANDTHR-325, AND MASS SPECTROMETRY. | |
| "Structural basis for CDK6 activation by a virus-encoded cyclin."; Schulze-Gahmen U., Kim S.-H.; Nat. Struct. Biol. 9:177-181(2002). Cited for: X-RAY CRYSTALLOGRAPHY (3.10 ANGSTROMS) OF 1-308 IN COMPLEX WITHHERPESVIRUS SAIMIRI VCYCLIN/ECLF2, AND PHOSPHORYLATION AT THR-177. | |
| "Immunoaffinity profiling of tyrosine phosphorylation in cancercells."; Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,Zha X.-M., Polakiewicz R.D., Comb M.J.; Nat. Biotechnol. 23:94-101(2005). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-13 AND TYR-24, AND MASSSPECTROMETRY. | |
