UniProt Accession

 CDK1_HUMAN; P06493; A8K7C4; C9J497; O60764 

Genbank Protein ID

 X05360; Y00272; D88357; AK291939; BT007004; AF512554; AC022390; CH471083; BC014563 

Genbank Nucleotide ID

 CAA28963.1; CAA68376.1; BAA26001.1; BAF84628.1; AAP35650.1; AAM34793.1; EAW54204.1; AAH14563.1 

Protein Name

 Cyclin-dependent kinase 1 

Protein Synonyms/Alias

 CDK1; Cell division control protein 2 homolog; Cell division protein kinase 1; p34 protein kinase 

Gene Name

 CDK1 

Gene Synonyms/Alias

 CDC2; CDC28A; CDKN1; P34CDC2 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
6	**MEDYTKIEKIGEG	acetylation	[1]
6	**MEDYTKIEKIGEG	ubiquitination	[2, 3]
9	EDYTKIEKIGEGTYG	ubiquitination	[3, 4, 5, 6]
20	GTYGVVYKGRHKTTG	ubiquitination	[2, 3, 4, 5, 6, 7]
24	VVYKGRHKTTGQVVA	ubiquitination	[2, 3, 5]
33	TGQVVAMKKIRLESE	acetylation	[1]
33	TGQVVAMKKIRLESE	ubiquitination	[2, 3, 5, 7]
34	GQVVAMKKIRLESEE	ubiquitination	[3, 7]
56	IREISLLKELRHPNI	ubiquitination	[3, 4, 5, 6, 7]
130	RVLHRDLKPQNLLID	ubiquitination	[3, 4, 5, 7]
139	QNLLIDDKGTIKLAD	ubiquitination	[2, 3, 4, 5, 7, 8]
143	IDDKGTIKLADFGLA	ubiquitination	[2, 3, 4, 5, 6, 7]
201	FAELATKKPLFHGDS	ubiquitination	[2, 3, 4, 5, 6, 7, 9, 10, 11]
238	VESLQDYKNTFPKWK	ubiquitination	[2, 3, 4, 5, 7, 9, 11]
243	DYKNTFPKWKPGSLA	ubiquitination	[3, 9, 11]
245	KNTFPKWKPGSLASH	ubiquitination	[2, 3, 4, 5, 9, 11]
254	GSLASHVKNLDENGL	ubiquitination	[3, 4, 5, 6, 7, 9, 11]
266	NGLDLLSKMLIYDPA	ubiquitination	[2, 3, 4, 5, 6, 7, 9]
274	MLIYDPAKRISGKMA	ubiquitination	[2, 3, 5, 6, 7, 9, 11]
279	PAKRISGKMALNHPY	ubiquitination	[2, 3, 4, 5, 6, 7, 9, 11]
295	NDLDNQIKKM*****	ubiquitination	[2, 3, 4, 5, 7, 9, 11]
296	DLDNQIKKM******	ubiquitination	[3, 11]

Reference

 [1] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
 [2] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
 [3] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [4] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [5] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [6] Ubiquitin ligase substrate identification through quantitative proteomics at both the protein and peptide levels.
 Lee KA, Hammerle LP, Andrews PS, Stokes MP, Mustelin T, Silva JC, Black RA, Doedens JR.
 J Biol Chem. 2011 Dec 2;286(48):41530-8. [PMID: 21987572]
 [7] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [8] Mass spectrometric analysis of lysine ubiquitylation reveals promiscuity at site level.
 Danielsen JM, Sylvestersen KB, Bekker-Jensen S, Szklarczyk D, Poulsen JW, Horn H, Jensen LJ, Mailand N, Nielsen ML.
 Mol Cell Proteomics. 2011 Mar;10(3):M110.003590. [PMID: 21139048]
 [9] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
 [10] Proteome-wide identification of ubiquitylation sites by conjugation of engineered lysine-less ubiquitin.
 Oshikawa K, Matsumoto M, Oyamada K, Nakayama KI.
 J Proteome Res. 2012 Feb 3;11(2):796-807. [PMID: 22053931]
 [11] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302] 

Functional Description

 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, and regulates G1 progress and G1-S transition via association with multiple interphase cyclins. Required in higher cells for entry into S-phase and mitosis. Phosphorylates PARVA/actopaxin, APC, AMPH, APC, BARD1, Bcl- xL/BCL2L1, BRCA2, CALD1, CASP8, CDC7, CDC20, CDC25A, CDC25C, CC2D1A, 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, LMNA, LMNB, LMNC, LBR, LATS1, MAP1B, MAP4, MARCKS, MCM2, MCM4, MKLP1, 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, UL40/R2, RAB4A, RAP1GAP, RCC1, RPS6KB1/S6K1, KHDRBS1/SAM68, ESPL1, SKI, BIRC5/survivin, STIP1, TEX14, beta-tubulins, MAPT/TAU, NEDD1, VIM/vimentin, TK1, FOXO1, RUNX1/AML1 and RUNX2. CDK1/CDC2-cyclin-B controls pronuclear union in interphase fertilized eggs. Essential for early stages of embryonic development. 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 condensation. 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 cytokinesis. 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 repair. Reactivated after successful DNA repair through WIP1-dependent signaling leading to CDC25A/B/C- mediated dephosphorylation and restoring cell cycle progression. 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 neurons. The phosphorylation of beta-tubulins regulates microtubule dynamics during mitosis. 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 formation. In addition, CC2D1A phosphorylation regulates CC2D1A spindle pole localization and association with SCC1/RAD21 and centriole cohesion during mitosis. The phosphorylation of Bcl- xL/BCL2L1 after prolongated G2 arrest upon DNA damage triggers apoptosis. In contrast, CASP8 phosphorylation during mitosis prevents its activation by proteolysis and subsequent apoptosis. This phosphorylation occurs in cancer cell lines, as well as in primary breast tissues and lymphocytes. EZH2 phosphorylation promotes H3K27me3 maintenance and epigenetic gene silencing. CALD1 phosphorylation promotes Schwann cell migration during peripheral nerve regeneration. 

Sequence Annotation

 DOMAIN 4 287 Protein kinase.
 NP_BIND 10 18 ATP (By similarity).
 ACT_SITE 128 128 Proton acceptor (By similarity).
 BINDING 33 33 ATP (By similarity).
 MOD_RES 1 1 N-acetylmethionine.
 MOD_RES 4 4 Phosphotyrosine; by PKR.
 MOD_RES 6 6 N6-acetyllysine.
 MOD_RES 14 14 Phosphothreonine; by PKMYT1.
 MOD_RES 15 15 Phosphotyrosine; by PKMYT1, WEE1, WEE2
 MOD_RES 19 19 Phosphotyrosine.
 MOD_RES 39 39 Phosphoserine.
 MOD_RES 77 77 Phosphotyrosine.
 MOD_RES 161 161 Phosphothreonine; by CAK.
 MOD_RES 178 178 Phosphoserine.
 MOD_RES 222 222 Phosphothreonine.
 MOD_RES 248 248 Phosphoserine.
 CROSSLNK 89 89 Glycyl lysine isopeptide (Lys-Gly)  

Keyword

 3D-structure; Acetylation; Alternative splicing; Apoptosis; ATP-binding; Cell cycle; Cell division; Complete proteome; Cytoplasm; Cytoskeleton; Isopeptide bond; Kinase; Mitochondrion; Mitosis; Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; Serine/threonine-protein kinase; Transferase; Ubl conjugation. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 297 AA 

Protein Sequence

Gene Ontology

 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0005815; C:microtubule organizing center; IEA:UniProtKB-SubCell.
 GO:0030496; C:midbody; IDA:UniProtKB.
 GO:0005739; C:mitochondrion; TAS:UniProtKB.
 GO:0005654; C:nucleoplasm; TAS:Reactome.
 GO:0005876; C:spindle microtubule; IDA:UniProtKB.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0004693; F:cyclin-dependent protein serine/threonine kinase activity; IDA:UniProtKB.
 GO:0035173; F:histone kinase activity; IEA:Compara.
 GO:0008353; F:RNA polymerase II carboxy-terminal domain kinase activity; IDA:UniProtKB.
 GO:0000187; P:activation of MAPK activity; TAS:Reactome.
 GO:0000186; P:activation of MAPKK activity; TAS:Reactome.
 GO:0031145; P:anaphase-promoting complex-dependent proteasomal ubiquitin-dependent protein catabolic process; TAS:Reactome.
 GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
 GO:0007411; P:axon guidance; TAS:Reactome.
 GO:0007569; P:cell aging; IEA:Compara.
 GO:0051301; P:cell division; IEA:UniProtKB-KW.
 GO:0016477; P:cell migration; TAS:UniProtKB.
 GO:0070301; P:cellular response to hydrogen peroxide; IEA:Compara.
 GO:0007098; P:centrosome cycle; TAS:UniProtKB.
 GO:0030261; P:chromosome condensation; IEA:Compara.
 GO:0006281; P:DNA repair; TAS:UniProtKB.
 GO:0006260; P:DNA replication; TAS:UniProtKB.
 GO:0007173; P:epidermal growth factor receptor signaling pathway; TAS:Reactome.
 GO:0008543; P:fibroblast growth factor receptor signaling pathway; TAS:Reactome.
 GO:0000086; P:G2/M transition of mitotic cell cycle; TAS:Reactome.
 GO:0045087; P:innate immune response; TAS:Reactome.
 GO:0008286; P:insulin receptor signaling pathway; TAS:Reactome.
 GO:0007067; P:mitosis; IEA:UniProtKB-KW.
 GO:0007095; P:mitotic G2 DNA damage checkpoint; IEA:Compara.
 GO:0007077; P:mitotic nuclear envelope disassembly; TAS:Reactome.
 GO:0002755; P:MyD88-dependent toll-like receptor signaling pathway; TAS:Reactome.
 GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB.
 GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome.
 GO:0031100; P:organ regeneration; IEA:Compara.
 GO:0060045; P:positive regulation of cardiac muscle cell proliferation; IEA:Compara.
 GO:0045740; P:positive regulation of DNA replication; IEA:Compara.
 GO:0010628; P:positive regulation of gene expression; IEA:Compara.
 GO:0045931; P:positive regulation of mitotic cell cycle; IEA:Compara.
 GO:0033160; P:positive regulation of protein import into nucleus, translocation; IEA:Compara.
 GO:0051437; P:positive regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle; TAS:Reactome.
 GO:0007344; P:pronuclear fusion; TAS:UniProtKB.
 GO:0006461; P:protein complex assembly; IEA:Compara.
 GO:0034501; P:protein localization to kinetochore; IDA:BHF-UCL.
 GO:0007265; P:Ras protein signal transduction; TAS:Reactome.
 GO:0045995; P:regulation of embryonic development; TAS:UniProtKB.
 GO:0014038; P:regulation of Schwann cell differentiation; TAS:UniProtKB.
 GO:0000083; P:regulation of transcription involved in G1/S phase of mitotic cell cycle; TAS:Reactome.
 GO:0014823; P:response to activity; IEA:Compara.
 GO:0014075; P:response to amine stimulus; IEA:Compara.
 GO:0048678; P:response to axon injury; IEA:Compara.
 GO:0046686; P:response to cadmium ion; IEA:Compara.
 GO:0046688; P:response to copper ion; IEA:Compara.
 GO:0042493; P:response to drug; IEA:Compara.
 GO:0045471; P:response to ethanol; IEA:Compara.
 GO:0014070; P:response to organic cyclic compound; IEA:Compara.
 GO:0009636; P:response to toxic substance; IEA:Compara.
 GO:0051403; P:stress-activated MAPK cascade; TAS:Reactome.
 GO:0034166; P:toll-like receptor 10 signaling pathway; TAS:Reactome.
 GO:0034134; P:toll-like receptor 2 signaling pathway; TAS:Reactome.
 GO:0034138; P:toll-like receptor 3 signaling pathway; TAS:Reactome.
 GO:0034142; P:toll-like receptor 4 signaling pathway; TAS:Reactome.
 GO:0034146; P:toll-like receptor 5 signaling pathway; TAS:Reactome.
 GO:0034162; P:toll-like receptor 9 signaling pathway; TAS:Reactome.
 GO:0038123; P:toll-like receptor TLR1:TLR2 signaling pathway; TAS:Reactome.
 GO:0038124; P:toll-like receptor TLR6:TLR2 signaling pathway; TAS:Reactome.
 GO:0035666; P:TRIF-dependent toll-like receptor signaling pathway; TAS:Reactome.
 GO:0055015; P:ventricular cardiac muscle cell development; IEA:Compara. 

Interpro

 IPR011009; Kinase-like_dom.
 IPR000719; Prot_kinase_cat_dom.
 IPR017441; Protein_kinase_ATP_BS.
 IPR002290; Ser/Thr_dual-sp_kinase_dom.
 IPR008271; Ser/Thr_kinase_AS. 

Pfam

 PF00069; Pkinase 

SMART

 SM00220; S_TKc 

PROSITE

 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00108; PROTEIN_KINASE_ST 

PRINTS