Cyclin-dependent kinase 1

Cyclin-dependent kinase 1

Plays a key role in the control of the eukaryotic cell cycle by modulating the centrosome cycle as well as mitotic onset; promotes G2-M transition via association with multiple interphase cyclins16407259,16933150,17459720,18356527,19509060,19917720,20171170,20935635,20937773,21063390,2188730,23355470,2344612,23601106,23602554,25556658,26829474,27814491,30139873,30704899,40440427. Phosphorylates PARVA/actopaxin, APC, AMPH, APC, ASB7, BARD1, Bcl-xL/BCL2L1, BRCA2, CALD1, CASP8, CDC7, CDC20, CDC25A, CDC25C, CC2D1A, CENPA, CSNK2 proteins/CKII, FZR1/CDH1, CDK7, CEBPB, CHAMP1, DMD/dystrophin, EEF1 proteins/EF-1, EZH2, KIF11/EG5, EGFR, FANCG, FOS, GFAP, GOLGA2/GM130, GRASP1, UBE2A/hHR6A, HIST1H1 proteins/histone H1, HMGA1, HIVEP3/KRC, UHRF1, KAT5, LMNA, LMNB, LBR, MKI67, LATS1, MAP1B, MAP4, MARCKS, MCM2, MCM4, MKLP1, MLST8, MYB, NEFH, NFIC, NPC/nuclear pore complex, PITPNM1/NIR2, NPM1, NCL, NUCKS1, NPM1/numatrin, ORC1, PRKAR2A, EEF1E1/p18, EIF3F/p47, p53/TP53, NONO/p54NRB, PAPOLA, PLEC/plectin, RB1, TPPP, UL40/R2, RAB4A, RAP1GAP, RBBP8/CtIP, RCC1, RPS6KB1/S6K1, KHDRBS1/SAM68, ESPL1, SKI, BIRC5/survivin, STIP1, TEX14, beta-tubulins, MAPT/TAU, NEDD1, VIM/vimentin, TK1, FOXO1, RUNX1/AML1, SAMHD1, SIRT2, CGAS, GLI2 and RUNX216407259,16933150,17459720,18356527,19202191,19509060,19917720,20171170,20935635,20937773,21063390,2188730,22411829,23355470,2344612,23601106,23602554,25012651,25556658,26829474,27814491,30704899,31279575,32351706,34741373,40440427. CDK1/CDC2-cyclin-B controls pronuclear union in interphase fertilized eggs18480403,20360007. Essential for early stages of embryonic development18480403,20360007. During G2 and early mitosis, CDC25A/B/C-mediated dephosphorylation activates CDK1/cyclin complexes which phosphorylate several substrates that trigger at least centrosome separation, Golgi dynamics, nuclear envelope breakdown and chromosome condensation18480403,20360007,2188730,2344612,30139873. Once chromosomes are condensed and aligned at the metaphase plate, CDK1 activity is switched off by WEE1- and PKMYT1-mediated phosphorylation to allow sister chromatid separation, chromosome decondensation, reformation of the nuclear envelope and cytokinesis18480403,20360007. Phosphorylates KRT5 during prometaphase and metaphase (By similarity). Activated by the CDK-activating kinase (CAK) complex consisting of CDK7, cyclin-H/CCNH and MAT1, which is a master regulator of CDK activity41100585. Inactivated by PKR/EIF2AK2- and WEE1-mediated phosphorylation upon DNA damage to stop cell cycle and genome replication at the G2 checkpoint thus facilitating DNA repair20360007. Reactivated after successful DNA repair through WIP1-dependent signaling leading to CDC25A/B/C-mediated dephosphorylation and restoring cell cycle progression20395957. Catalyzes lamin (LMNA, LMNB1 and LMNB2) phosphorylation at the onset of mitosis, promoting nuclear envelope breakdown2188730,2344612,37788673. In proliferating cells, CDK1-mediated FOXO1 phosphorylation at the G2-M phase represses FOXO1 interaction with 14-3-3 proteins and thereby promotes FOXO1 nuclear accumulation and transcription factor activity, leading to cell death of postmitotic neurons18356527. The phosphorylation of beta-tubulins regulates microtubule dynamics during mitosis16371510. NEDD1 phosphorylation promotes PLK1-mediated NEDD1 phosphorylation and subsequent targeting of the gamma-tubulin ring complex (gTuRC) to the centrosome, an important step for spindle formation19509060. In addition, CC2D1A phosphorylation regulates CC2D1A spindle pole localization and association with SCC1/RAD21 and centriole cohesion during mitosis20171170. The phosphorylation of Bcl-xL/BCL2L1 after prolongated G2 arrest upon DNA damage triggers apoptosis19917720. In contrast, CASP8 phosphorylation during mitosis prevents its activation by proteolysis and subsequent apoptosis20937773. This phosphorylation occurs in cancer cell lines, as well as in primary breast tissues and lymphocytes20937773. EZH2 phosphorylation promotes H3K27me3 maintenance and epigenetic gene silencing20935635. CALD1 phosphorylation promotes Schwann cell migration during peripheral nerve regeneration (By similarity). CDK1-cyclin-B complex phosphorylates NCKAP5L and mediates its dissociation from centrosomes during mitosis26549230. Regulates the amplitude of the cyclic expression of the core clock gene BMAL1 by phosphorylating its transcriptional repressor NR1D1, and this phosphorylation is necessary for SCF(FBXW7)-mediated ubiquitination and proteasomal degradation of NR1D127238018. Phosphorylates EML3 at 'Thr-881' which is essential for its interaction with HAUS augmin-like complex and TUBG130723163. Phosphorylates CGAS during mitosis, leading to its inhibition, thereby preventing CGAS activation by self DNA during mitosis32351706. Phosphorylates SKA3 on multiple sites during mitosis which promotes SKA3 binding to the NDC80 complex and anchoring of the SKA complex to kinetochores, to enable stable attachment of mitotic spindle microtubules to kinetochores28479321,31804178,32491969

(Microbial infection) Acts as a receptor for hepatitis C virus (HCV) in hepatocytes and facilitates its cell entry

Quoted from UniProt’s FUNCTION annotation for P06493 (reviewed). The superscript numbers are UniProt’s own PubMed citations, kept in the sentence and in order, each linking to the paper it names.

What it acts with

STRING’s highest-confidence human functional partners. The combined score mixes several kinds of evidence, so each channel is shown separately — a partner supported by experiment is a different claim from one supported only by text mining, and for a receptor this is where its coupling appears as evidence rather than as assertion.

Where it sits in the cell

• Nucleoplasm
• Cytosol
• Acrosomeadditional
• Perinuclear thecaadditional
• Connecting pieceadditional
• Flagellar centrioleadditional

Human Protein Atlas, by antibody immunofluorescence in cell lines — a different assay from the expression figures below, which are RNA.

UniProt, curated Nucleus · Cytoplasm · Mitochondrion · Cytoplasm, cytoskeleton, microtubule organizing center, centrosome · Cytoplasm, cytoskeleton, spindle

Expression by cell type

Single cell type RNA, the 12 highest of those the Human Protein Atlas reports for this gene. Transcript, not protein, and a cell type rather than a tissue.

• Late primary spermatocytes189.7 nCPM
• Extravillous trophoblasts161.3 nCPM
• Monocyte progenitors159 nCPM
• Gastric progenitor cells144.8 nCPM
• Migrating cytotrophoblasts143.4 nCPM
• Oocytes138.2 nCPM
• Erythrocyte progenitors125.8 nCPM
• Hofbauer cells97.9 nCPM
• Megakaryocyte progenitors97.8 nCPM
• Esophageal basal cells88.1 nCPM
• Cytotrophoblasts83.8 nCPM
• Enteric transient amplifying cells76.4 nCPM

Expression by tissue

The tissues this gene is enriched in, by consensus RNA. A tissue absent from this list is one the Atlas does not call specific for this gene, which is not the same as absent from it.

• lymphoid tissue68.9 nTPM
• bone marrow50.2 nTPM