Protein name:
Cyclin-dependent kinase 4 ;
Alternative:
PSK-J3 ;Cell division protein kinase 4 ;
Organism:
Human (Homo sapiens).
General Annotation
Sub Unit:
Component of the D-CDK4 complex, composed of CDK4 and some D-type G1 cyclin (CCND1, CCND2 or CCND3). Interacts directly in the complex with CCND1, CCND2 or CCND3. Interacts with SEI1 and ZNF655. Forms a ternary complex, cyclin D-CDK4-CDKN1B, involved in modulating CDK4 enzymatic activity. Interacts directly with CDKN1B (phosphorylated on 'Tyr-88' and 'Tyr-89'); the interaction allows assembly of the cyclin D-CDK4 complex, Thr-172 phosphorylation, nuclear translocation and enhances the cyclin D-CDK4 complex activity. CDK4 activity is either inhibited or enhanced depending on stoichiometry of complex. The non-tyrosine-phosphorylated form of CDKN1B prevents T-loop phosphosphorylation of CDK4 producing inactive CDK4. Interacts (unphosphorylated form) with CDK2. Also forms ternary complexes with CDKN1A or CDKN2A. Interacts directly with CDKN1A (via its N-terminal); the interaction promotes the assembly of the cyclin D-CDK4 complex, its nuclear translocation and promotes the cyclin D-dependent enzyme activity of CDK4.
Function:
Ser/Thr-kinase component of cyclin D-CDK4 (DC) complexes that phosphorylate and inhibit members of the retinoblastoma (RB) protein family including RB1 and regulate the cell-cycle during G(1)/S transition. Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complexes and the subsequent transcription of E2F target genes which are responsible for the progression through the G(1) phase. Hypophosphorylates RB1 in early G(1) phase. Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals. Also phosphorylates SMAD3 in a cell-cycle-dependent manner and represses its transcriptional activity. Component of the ternary complex, cyclin D/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex.
Subcellular Location:
Cytoplasm
Nucleus
Membrane
Cytoplasmic when non-complexed. Forms a cyclin D-CDK4 complex in the cytoplasm as cells progress through G(1) phase. The complex accumulates on the nuclear membrane and enters the nucleus on transition from G(1) to S phase. Also present in nucleoli and heterochromatin lumps. Colocalizes with RB1 after release into the nucleus.
Protein Attributes:
50:
MATSRYEPVA | EIGVGAYGTV | YKARDPHSGH | FVALKSVRVP | NGGGGGGGLP |
100:
ISTVREVALL | RRLEAFEHPN | VVRLMDVCAT | SRTDREIKVT | LVFEHVDQDL |
150:
RTYLDKAPPP | GLPAETIKDL | MRQFLRGLDF | LHANCIVHRD | LKPENILVTS |
200:
GGTVKLADFG | LARIYSYQMA | LTPVVVTLWY | RAPEVLLQST | YATPVDMWSV |
250:
GCIFAEMFRR | KPLFCGNSEA | DQLGKIFDLI | GLPPEDDWPR | DVSLPRGAFP |
300:
PRGPRPVQSV | VPEMEESGAQ | LLLEMLTFNP | HKRISAFRAL | QHSYLHKDEG |
Vaild Sequence:
Related Databases
Uniprot:
ELISA Kit
CLIA Kit
Polyclonal Antibody
Monoclonal Antibody
Protein
FOR
Human
Bovine
Pig
Mouse
Rat
ELISA Kit for Human Cyclin-dependent kinase 4
ELISA Kit for Human Cyclin-dependent kinase 4
ELISA Kit for Human Cyclin-dependent kinase 4
ELISA Kit for Human Cyclin-dependent kinase 4
ELISA Kit for Human Cyclin-dependent kinase 4
CLIA Kit for Human Cyclin-dependent kinase 4
CLIA Kit for Human Cyclin-dependent kinase 4
CLIA Kit for Human Cyclin-dependent kinase 4
CLIA Kit for Human Cyclin-dependent kinase 4
CLIA Kit for Human Cyclin-dependent kinase 4
Polyclonal Antibody for Human Cyclin-dependent kinase 4
Polyclonal Antibody for Human Cyclin-dependent kinase 4
Polyclonal Antibody for Human Cyclin-dependent kinase 4
Polyclonal Antibody for Human Cyclin-dependent kinase 4
Polyclonal Antibody for Human Cyclin-dependent kinase 4
Monoclonal Antibody for Human Cyclin-dependent kinase 4
Monoclonal Antibody for Human Cyclin-dependent kinase 4
Monoclonal Antibody for Human Cyclin-dependent kinase 4
Monoclonal Antibody for Human Cyclin-dependent kinase 4
Monoclonal Antibody for Human Cyclin-dependent kinase 4
Protein for Human Cyclin-dependent kinase 4
Protein for Human Cyclin-dependent kinase 4
Protein for Human Cyclin-dependent kinase 4
Protein for Human Cyclin-dependent kinase 4
Protein for Human Cyclin-dependent kinase 4
R&D Technical Data
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Precision
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Recovery
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Linearity
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References
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Submitted (1987-02) to the EMBL/GenBank/DDBJ databases
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Cited for : NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)
2.
[15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s)
Cited for : NUCLEOTIDE SEQUENCE [GENOMIC DNA]
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[15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s)
Cited for : NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1);VARIANT CMM3 CYS-24;CHARACTERIZATION OF VARIANT CYS-24
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[15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s)
Cited for : NUCLEOTIDE SEQUENCE [GENOMIC DNA];VARIANT CMM3 CYS-24;CHARACTERIZATION OF VARIANT CYS-24
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[15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s)
Cited for : NUCLEOTIDE SEQUENCE [GENOMIC DNA];VARIANT GLN-82
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[
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[
Abstract ]
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Cited for : NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2)
tissue :
Embryo .
7.
[15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s)
Cited for : NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)
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Williamson A.L.
,
Wleczyk R.
,
Wooden H.S.
,
Wooden S.H.
,
Yen J.
,
Yoon L.
,
Yoon V.
,
Zorrilla S.E.
,
Nelson D.
,
Kucherlapati R.
,
Weinstock G.
,
Gibbs R.A.
more...
Nature440:346-351(2006)
[
PubMed ]
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Europe PMC ]
[
Abstract ]
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Cited for : NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]
9.
Mural R.J.
,
Istrail S.
,
Sutton G.G.
,
Florea L.
,
Halpern A.L.
,
Mobarry C.M.
,
Lippert R.
,
Walenz B.
,
Shatkay H.
,
Dew I.
,
Miller J.R.
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Flanigan M.J.
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Halldorsson B.V.
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Turner R.
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Yooseph S.
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Lu F.
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,
Shue B.C.
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Zheng X.H.
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Zhong F.
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Delcher A.L.
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Huson D.H.
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Kravitz S.A.
,
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,
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,
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,
Adams M.D.
,
Hunkapiller M.W.
,
Myers E.W.
,
Venter J.C.
more...
Submitted (2005-07) to the EMBL/GenBank/DDBJ databases
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Cited for : NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]
10.
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Cited for : NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)
tissue :
Muscle .
11.
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Cited for : NUCLEOTIDE SEQUENCE [MRNA] OF 88-188 (ISOFORM 1)
12.
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Cited for : NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 95-182
13.
"The consensus motif for phosphorylation by cyclin D1-Cdk4 is different from that for phosphorylation by cyclin A/E-Cdk2."
Kitagawa M.
,
Higashi H.
,
Jung H.K.
,
Suzuki-Takahashi I.
,
Ikeda M.
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Tamai K.
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Kato J.
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Segawa K.
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Yoshida E.
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Nishimura S.
,
Taya Y.
EMBO J.15:7060-7069(1996)
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PubMed ]
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Europe PMC ]
[
Abstract ]
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Cited for : FUNCTION
14.
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Cited for : INTERACTION WITH CDKN1A; CCND1 AND CCND3;SUBCELLULAR LOCATION;CATALYTIC ACTIVITY
15.
"Regulation of CDK4 activity by a novel CDK4-binding protein, p34(SEI-1)."
Sugimoto M.
,
Nakamura T.
,
Ohtani N.
,
Hampson L.
,
Hampson I.N.
,
Shimamoto A.
,
Furuichi Y.
,
Okumura K.
,
Niwa S.
,
Taya Y.
,
Hara E.
Genes Dev.13:3027-3033(1999)
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PubMed ]
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Europe PMC ]
[
Abstract ]
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Cited for : INTERACTION WITH SEI1
16.
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Cited for : FUNCTION
17.
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Cited for : INTERACTION WITH ZNF655
18.
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Cited for : PHOSPHORYLATION AT THR-172;INTERACTION WITH CCND1; CCND3; CDKN2A AND CDKN1B;MUTAGENESIS OF THR-172
19.
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Cited for : SUBCELLULAR LOCATION;FUNCTION;INTERACTION WITH CCND2
20.
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Cited for : ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2;IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS];CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS]
21.
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Cited for : INTERACTION WITH CCND1
22.
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Cited for : INTERACTION WITH CDKN1B;PHOSPHORYLATION;CATALYTIC ACTIVITY
23.
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Cited for : PHOSPHORYLATION AT THR-172;ENZYME REGULATION;MUTAGENESIS OF PRO-173
24.
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Cited for : PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-172;IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]
25.
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Cited for : IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]
26.
"Crystal structure of human CDK4 in complex with a D-type cyclin."
Day P.J.
,
Cleasby A.
,
Tickle I.J.
,
O'Reilly M.
,
Coyle J.E.
,
Holding F.P.
,
McMenamin R.L.
,
Yon J.
,
Chopra R.
,
Lengauer C.
,
Jhoti H.
Proc. Natl. Acad. Sci. U.S.A.106:4166-4170(2009)
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PubMed ]
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Europe PMC ]
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Cited for : X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF THR-172-PHOSPHORYLATED WILD TYPE AND MUTANTS ALA-172; PHE-172 AND ASP-172 IN COMPLEX WITH CCND1;IDENTIFICATION BY MASS SPECTROMETRY;PHOSPHORYLATION AT THR-172;CATALYTIC ACTIVITY
27.
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Cited for : X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF NONPHOSPHORYLATED FORM IN COMPLEX WITH CCND3;PHOSPHORYLATION AT THR-172;IDENTIFICATION BY MASS SPECTROMETRY
28.
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Cited for : VARIANT CMM3 SER-41
29.
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Cited for : VARIANT CMM3 HIS-24
30.
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Cited for : ERRATUM
31.
"Patterns of somatic mutation in human cancer genomes."
Greenman C.
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Stephens P.
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Smith R.
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Dalgliesh G.L.
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Hunter C.
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Bignell G.
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Davies H.
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Teague J.
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Butler A.
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Buck G.
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Choudhury B.
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Cole J.
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Gray K.
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Looijenga L.
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Weber B.L.
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Chiew Y.-E.
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Greaves M.F.
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Green A.R.
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Campbell P.
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Birney E.
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Easton D.F.
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Chenevix-Trench G.
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Tan M.-H.
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Khoo S.K.
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Teh B.T.
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Yuen S.T.
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Leung S.Y.
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Wooster R.
,
Futreal P.A.
,
Stratton M.R.
more...
Nature446:153-158(2007)
[
PubMed ]
[
Europe PMC ]
[
Abstract ]
[15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s)
Cited for : VARIANT [LARGE SCALE ANALYSIS] HIS-122