Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Basket 0
(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

Q5RCH1

- CDK1_PONAB

UniProt

Q5RCH1 - CDK1_PONAB

Protein

Cyclin-dependent kinase 1

Gene

CDK1

Organism
Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
    • BLAST
    • Align
    • Format
    • Add to basket
    • History
      Entry version 76 (01 Oct 2014)
      Sequence version 1 (21 Dec 2004)
      Previous versions | rss
    • Help video
    • Feedback
    • Comment

    Functioni

    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, SIRT2 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 By similarity.By similarity

    Catalytic activityi

    ATP + a protein = ADP + a phosphoprotein.
    ATP + [DNA-directed RNA polymerase] = ADP + [DNA-directed RNA polymerase] phosphate.

    Enzyme regulationi

    Phosphorylation at Thr-14 or Tyr-15 inactivates the enzyme, while phosphorylation at Thr-161 activates it.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei33 – 331ATPPROSITE-ProRule annotation
    Active sitei128 – 1281Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi10 – 189ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. cyclin-dependent protein serine/threonine kinase activity Source: UniProtKB
    3. RNA polymerase II carboxy-terminal domain kinase activity Source: UniProtKB-EC

    GO - Biological processi

    1. apoptotic process Source: UniProtKB-KW
    2. mitotic nuclear division Source: UniProtKB-KW
    3. regulation of cell cycle Source: GOC

    Keywords - Molecular functioni

    Kinase, Serine/threonine-protein kinase, Transferase

    Keywords - Biological processi

    Apoptosis, Cell cycle, Cell division, Mitosis

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Cyclin-dependent kinase 1 (EC:2.7.11.22, EC:2.7.11.23)
    Short name:
    CDK1
    Alternative name(s):
    Cell division control protein 2 homolog
    Cell division protein kinase 1
    p34 protein kinase
    Gene namesi
    Name:CDK1
    Synonyms:CDC2, CDKN1
    OrganismiPongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii)
    Taxonomic identifieri9601 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaePongo
    ProteomesiUP000001595: Unplaced

    Subcellular locationi

    Nucleus By similarity. Cytoplasm By similarity. Mitochondrion By similarity. Cytoplasmcytoskeletonmicrotubule organizing centercentrosome By similarity. Cytoplasmcytoskeletonspindle By similarity
    Note: Cytoplasmic during the interphase. Reversibly translocated from cytoplasm to nucleus when phosphorylated before G2-M transition when associated with cyclin-B1. Accumulates in mitochondria in G2-arrested cells upon DNA-damage. Colocalizes with SIRT2 on centrosome during prophase and on splindle fibers during metaphase of the mitotic cell cycle By similarity.By similarity

    GO - Cellular componenti

    1. centrosome Source: UniProtKB
    2. mitochondrion Source: UniProtKB-SubCell
    3. mitotic spindle Source: UniProtKB
    4. nucleus Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cytoplasm, Cytoskeleton, Mitochondrion, Nucleus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 297297Cyclin-dependent kinase 1PRO_0000085726Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei1 – 11N-acetylmethionineBy similarity
    Modified residuei4 – 41Phosphotyrosine; by PKRBy similarity
    Modified residuei6 – 61N6-acetyllysineBy similarity
    Modified residuei9 – 91N6-acetyllysineBy similarity
    Modified residuei14 – 141Phosphothreonine; by PKMYT1By similarity
    Modified residuei15 – 151Phosphotyrosine; by PKMYT1, WEE1 and WEE2; alternateBy similarity
    Modified residuei15 – 151Phosphotyrosine; by WEE1 and WEE2; alternateBy similarity
    Modified residuei19 – 191PhosphotyrosineBy similarity
    Modified residuei39 – 391PhosphoserineBy similarity
    Modified residuei77 – 771PhosphotyrosineBy similarity
    Cross-linki89 – 89Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
    Modified residuei161 – 1611Phosphothreonine; by CAKBy similarity
    Modified residuei178 – 1781PhosphoserineBy similarity
    Modified residuei222 – 2221PhosphothreonineBy similarity
    Modified residuei245 – 2451N6-succinyllysineBy similarity
    Modified residuei248 – 2481PhosphoserineBy similarity

    Post-translational modificationi

    Phosphorylation at Thr-161 by CAK/CDK7 activates kinase activity. Phosphorylation at Thr-14 and Tyr-15 by PKMYT1 prevents nuclear translocation. Phosphorylation at Tyr-15 by WEE1 and WEE2 inhibits the protein kinase activity and acts as a negative regulator of entry into mitosis (G2 to M transition). Phosphorylation by PKMYT1 and WEE1 takes place during mitosis to keep CDK1-cyclin-B complexes inactive until the end of G2. By the end of G2, PKMYT1 and WEE1 are inactivated, but CDC25A and CDC25B are activated. Dephosphorylation by active CDC25A and CDC25B at Thr-14 and Tyr-15, leads to CDK1 activation at the G2-M transition. Phosphorylation at Tyr-15 by WEE2 during oogenesis is required to maintain meiotic arrest in oocytes during the germinal vesicle (GV) stage, a long period of quiescence at dictyate prophase I, leading to prevent meiotic reentry. Phosphorylation by WEE2 is also required for metaphase II exit during egg activation to ensure exit from meiosis in oocytes and promote pronuclear formation. Phosphorylated at Tyr-4 by PKR/EIF2AK2 upon genotoxic stress. This phosphorylation triggers CDK1 polyubiquitination and subsequent proteolysis, thus leading to G2 arrest By similarity.By similarity
    Polyubiquitinated upon genotoxic stress.By similarity

    Keywords - PTMi

    Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

    Proteomic databases

    PRIDEiQ5RCH1.

    Expressioni

    Inductioni

    Follow a cyclic expression; during interphase, accumulates gradually following G1, S to reach a critical threshold at the end of G2, which promotes self-activation and triggers onset of mitosis. Induced transiently by TGFB1 at an early phase of TGFB1-mediated apoptosis Probable.Curated

    Interactioni

    Subunit structurei

    Forms a stable but non-covalent complex with a regulatory subunit and with a cyclin. Interacts with cyclins-B (CCNB1, CCNB2 and CCNB3) to form a serine/threonine kinase holoenzyme complex also known as maturation promoting factor (MPF). The cyclin subunit imparts substrate specificity to the complex. Can also form CDK1-cylin-D and CDK1-cyclin-E complexes that phosphorylate RB1 in vitro. Binds to RB1 and other transcription factors such as FOXO1 and RUNX2. Promotes G2-M transition when in complex with a cyclin-B. Interacts with DLGAP5. Binds to the CDK inhibitors CDKN1A/p21 and CDKN1B/p27. Isoform 2 is unable to complex with cyclin-B1 and also fails to bind to CDKN1A/p21. Interacts with catalytically active CCNB1 and RALBP1 during mitosis to form an endocytotic complex during interphase. Associates with cyclins-A and B1 during S-phase in regenerating hepatocytes. Interacts with FANCC By similarity. Interacts with CEP63; this interaction recruits CDK1 to centrosomes By similarity.By similarity

    Structurei

    3D structure databases

    ProteinModelPortaliQ5RCH1.
    SMRiQ5RCH1. Positions 1-294.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini4 – 287284Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Contains 1 protein kinase domain.PROSITE-ProRule annotation

    Phylogenomic databases

    HOVERGENiHBG014652.
    InParanoidiQ5RCH1.
    KOiK02087.

    Family and domain databases

    InterProiIPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    IPR002290. Ser/Thr_dual-sp_kinase_dom.
    IPR008271. Ser/Thr_kinase_AS.
    [Graphical view]
    PfamiPF00069. Pkinase. 1 hit.
    [Graphical view]
    SMARTiSM00220. S_TKc. 1 hit.
    [Graphical view]
    SUPFAMiSSF56112. SSF56112. 1 hit.
    PROSITEiPS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q5RCH1-1 [UniParc]FASTAAdd to Basket

    « Hide

    MEDYTKIEKI GEGTYGVVYK GRHKTTGQVV TMKKIRLESE EEGVPSTAIR    50
    EISLLKELRH PNIVSLQDVL MQDSRLYLIF EFLSMDLKKY LDSIPPGQYM 100
    DSSLVKSYLY QILQGIVFCH SRRVLHRDLK PQNLLIDDKG TIKLADFGLA 150
    RAFGIPIRVY THEVVTLWYR SPEVLLGSAR YSTPVDIWSI GTIFAELATK 200
    KPLFHGDSEI DQLFRIFRAL GTPNNEVWPE VESLQDYKNT FPKWKPGSLA 250
    SHVKNLDENG LDLLSKMLIY DPAKRISGKM ALNHPYFNDL DNQIKKM 297
    Length:297
    Mass (Da):34,125
    Last modified:December 21, 2004 - v1
    Checksum:i612D7D14CBFE420A
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    CR858299 mRNA. Translation: CAH90536.1.
    RefSeqiNP_001125286.1. NM_001131814.1.
    UniGeneiPab.17445.

    Genome annotation databases

    GeneIDi100172184.
    KEGGipon:100172184.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    CR858299 mRNA. Translation: CAH90536.1 .
    RefSeqi NP_001125286.1. NM_001131814.1.
    UniGenei Pab.17445.

    3D structure databases

    ProteinModelPortali Q5RCH1.
    SMRi Q5RCH1. Positions 1-294.
    ModBasei Search...
    MobiDBi Search...

    Proteomic databases

    PRIDEi Q5RCH1.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 100172184.
    KEGGi pon:100172184.

    Organism-specific databases

    CTDi 983.

    Phylogenomic databases

    HOVERGENi HBG014652.
    InParanoidi Q5RCH1.
    KOi K02087.

    Family and domain databases

    InterProi IPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    IPR002290. Ser/Thr_dual-sp_kinase_dom.
    IPR008271. Ser/Thr_kinase_AS.
    [Graphical view ]
    Pfami PF00069. Pkinase. 1 hit.
    [Graphical view ]
    SMARTi SM00220. S_TKc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF56112. SSF56112. 1 hit.
    PROSITEi PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. The German cDNA consortium
      Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Heart.

    Entry informationi

    Entry nameiCDK1_PONAB
    AccessioniPrimary (citable) accession number: Q5RCH1
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 16, 2005
    Last sequence update: December 21, 2004
    Last modified: October 1, 2014
    This is version 76 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3