Target Interacting Protein Information

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Target General Information
Target Interacting Proteins
References
Target General Information  Top
Target ID T85799 Target Info
Target Name Cyclin-dependent kinase 4 (CDK4)
Synonyms PSK-J3; Cell division protein kinase 4
Target Type Successful Target
Gene Name CDK4
Biochemical Class Kinase
UniProt ID
CDK4_HUMAN 
Target Interacting Proteins  Top
Cell cycle related proteins [+] 7 Cell cycle related proteins +
Interacting Target Name G1/S-specific cyclin-D1 (CCND1) Clinical trial Target Interacting Protein Info
UniProt ID
CCND1_HUMAN 
Synonyms PRAD1 oncogene; PRAD1; Cyclin D1; BCL-1 oncogene; BCL-1; BCL1; B-cell lymphoma 1 protein
Evidence Score (E-score) 18 Experimental Evidences +
1 Affinity Capture-MS [1]
2 Affinity Capture-Western [2]
3 Affinity Capture-Western [3]
4 Affinity Capture-Western [4]
5 Affinity Capture-Western [5]
6 Affinity Capture-Western [6]
7 Affinity Capture-Western [7]
8 Affinity Capture-Western [8]
9 Affinity Capture-Western [9]
10 Affinity Capture-Western [10]
11 Affinity Capture-Western [11]
12 Affinity Capture-Western [12]
13 Co-fractionation [13]
14 Co-localization [14]
15 Reconstituted Complex [15]
16 Reconstituted Complex [16]
17 Yeast two hybrid [17]
18 Yeast two hybrid [18]
Interacting Target Name Multiple tumor suppressor 1 (CDKN2A) Literature-reported Target Interacting Protein Info
UniProt ID
CDN2A_HUMAN 
Synonyms Tumour suppressor gene p16; P16-INK4a; p16INK4A; P16-INK4; P16 gene; MTS-1; Cyclin-dependent kinase inhibitor 2A; Cyclin-dependent kinase 4 inhibitor A; CDK4I
Evidence Score (E-score) 15 Experimental Evidences +
1 Affinity Capture-MS [1]
2 Affinity Capture-MS [19]
3 Affinity Capture-MS [20]
4 Affinity Capture-MS [21]
5 Affinity Capture-MS [22]
6 Affinity Capture-MS [23]
7 Affinity Capture-Western [2]
8 Affinity Capture-Western [24]
9 Fluorescence Resonance Energy Transfer [25]
10 Protein-peptide [26]
11 Reconstituted Complex [2]
12 Reconstituted Complex [15]
13 Yeast two hybrid [2]
14 Yeast two hybrid [27]
15 Yeast two hybrid [28]
Interacting Protein Name Cyclin-dependent kinase 4 inhibitor B (CDKN2B) Interacting Protein Interacting Protein Info
UniProt ID
CDN2B_HUMAN 
Synonyms CDK4I; INK4B; MTS2; P15; TP15; p15INK4b
Evidence Score (E-score) 12 Experimental Evidences +
1 Affinity Capture-MS [1]
2 Affinity Capture-MS [19]
3 Affinity Capture-MS [21]
4 Affinity Capture-MS [22]
5 Affinity Capture-MS [23]
6 Affinity Capture-Western [22]
7 Fluorescence Resonance Energy Transfer [22]
8 Yeast two hybrid [29]
9 Yeast two hybrid [17]
10 Yeast two hybrid [30]
11 Yeast two hybrid [31]
12 Yeast two hybrid [32]
Interacting Target Name CDK inhibitor 4C p18-INK4c (CDKN2C) Literature-reported Target Interacting Protein Info
UniProt ID
CDN2C_HUMAN 
Synonyms P18-INK6; P18-INK4c; P18(INK4c) protein; P18(INK4c); P18 INK4c protein; Cyclin-dependent kinase 6 inhibitor; Cyclin-dependent kinase 4 inhibitor C
Evidence Score (E-score) 11 Experimental Evidences +
1 Affinity Capture-MS [19]
2 Affinity Capture-MS [20]
3 Affinity Capture-MS [22]
4 Affinity Capture-MS [23]
5 Affinity Capture-Western [33]
6 Fluorescence Resonance Energy Transfer [25]
7 Reconstituted Complex [33]
8 Yeast two hybrid [34]
9 Yeast two hybrid [17]
10 Yeast two hybrid [35]
11 Yeast two hybrid [27]
Interacting Target Name Cyclin D (CCND3) Literature-reported Target Interacting Protein Info
UniProt ID
CCND3_HUMAN 
Synonyms G1/S-specific cyclin-D3
Evidence Score (E-score) 9 Experimental Evidences +
1 Affinity Capture-MS [21]
2 Affinity Capture-Western [9]
3 Affinity Capture-Western [8]
4 Affinity Capture-Western [36]
5 Reconstituted Complex [37]
6 Yeast two hybrid [38]
7 Yeast two hybrid [17]
8 Yeast two hybrid [18]
9 Yeast two hybrid [39]
Interacting Protein Name Cyclin-dependent kinase 4 inhibitor D (CDKN2D) Interacting Protein Interacting Protein Info
UniProt ID
CDN2D_HUMAN 
Synonyms INK4D; p19; p19.INK4D
Evidence Score (E-score) 8 Experimental Evidences +
1 Affinity Capture-MS [1]
2 Affinity Capture-MS [19]
3 Affinity Capture-MS [22]
4 Affinity Capture-Western [40]
5 Yeast two hybrid [30]
6 Yeast two hybrid [34]
7 Yeast two hybrid [17]
8 Yeast two hybrid [18]
Interacting Protein Name G1/S-specific cyclin-D2 (CCND2) Interacting Protein Interacting Protein Info
UniProt ID
CCND2_HUMAN 
Synonyms KIAK0002; MPPH3
Evidence Score (E-score) 7 Experimental Evidences +
1 Affinity Capture-Western [9]
2 Affinity Capture-Western [41]
3 Affinity Capture-Western [42]
4 Fluorescence Resonance Energy Transfer [25]
5 Yeast two hybrid [17]
6 Yeast two hybrid [18]
7 Yeast two hybrid [39]
Cell division cycle proteins [+] 2 Cell division cycle proteins +
Interacting Protein Name Retinoblastoma-associated protein (RB1) Interacting Protein Interacting Protein Info
UniProt ID
RB_HUMAN 
Synonyms OSRC; PPP1R130; RB; p105.Rb; pRb; pp110
Evidence Score (E-score) 20 Experimental Evidences +
1 Affinity Capture-Western [43]
2 Affinity Capture-Western [44]
3 Biochemical Activity [45]
4 Biochemical Activity [46]
5 Biochemical Activity [47]
6 Biochemical Activity [48]
7 Biochemical Activity [49]
8 Biochemical Activity [13]
9 Biochemical Activity [50]
10 Biochemical Activity [51]
11 Biochemical Activity [52]
12 Biochemical Activity [5]
13 Biochemical Activity [53]
14 Biochemical Activity [54]
15 Biochemical Activity [55]
16 Biochemical Activity [56]
17 Biochemical Activity [57]
18 Biochemical Activity [58]
19 Biochemical Activity [59]
20 Biochemical Activity [60]
Interacting Target Name Hsp90 co-chaperone Cdc37 (CDC37) Literature-reported Target Interacting Protein Info
UniProt ID
CDC37_HUMAN 
Synonyms p50Cdc37; Hsp90 co-chaperone Cdc37, N-terminally processed; Hsp90 chaperone protein kinase-targeting subunit; CDC37A
Evidence Score (E-score) 7 Experimental Evidences +
1 Affinity Capture-MS [1]
2 Affinity Capture-MS [19]
3 Affinity Capture-MS [20]
4 Affinity Capture-Western [61]
5 Co-fractionation [62]
6 Co-fractionation [63]
7 Yeast two hybrid [64]
Heat shock proteins [+] 1 Heat shock proteins +
Interacting Target Name Heat shock protein 90 alpha (HSP90A) Successful Target Interacting Protein Info
UniProt ID
HS90A_HUMAN 
Synonyms Renal carcinoma antigen NY-REN-38; LPS-associated protein 2; Lipopolysaccharide-associated protein 2; LAP-2; HSPCA; HSPC1; HSP90A; HSP86; HSP 86; Heat shock protein HSP 90-alpha; Heat shock 86 kDa
Evidence Score (E-score) 6 Experimental Evidences +
1 Affinity Capture-Luminescence [65]
2 Affinity Capture-MS [1]
3 Affinity Capture-MS [19]
4 Affinity Capture-MS [23]
5 Affinity Capture-Western [66]
6 Co-fractionation [63]
Transcription regulators [+] 2 Transcription regulators +
Interacting Target Name Mothers against decapentaplegic homolog 3 (SMAD3) Successful Target Interacting Protein Info
UniProt ID
SMAD3_HUMAN 
Synonyms TGF-beta response effector Smad3; Smad3; SMAD family member 3; SMAD 3; Mothers against DPP homolog 3; MMad3; MADH3; Mad3; MAD homolog 3; JV15-2; HSMAD3; HMAD-3
Evidence Score (E-score) 2 Experimental Evidences +
1 Biochemical Activity [45]
2 Co-localization [14]
Interacting Target Name Proto-oncogene c-Myc (MYC) Literature-reported Target Interacting Protein Info
UniProt ID
MYC_HUMAN 
Synonyms Transcription factor p64; Proto-oncogene c-Myc; Myc proto-oncogene protein; C-myc oncogene; C-myc; Class E basic helix-loop-helix protein 39; bHLHe39
Evidence Score (E-score) 2 Experimental Evidences +
1 Biochemical Activity [67]
2 Yeast two hybrid [35]
Other proteins [+] 2 Other proteins +
Interacting Target Name CDK inhibitor 1B p27Kip1 (CDKN1B) Literature-reported Target Interacting Protein Info
UniProt ID
CDN1B_HUMAN 
Synonyms p27Kip1; KIP1; Cyclin-dependent kinase inhibitor p27; Cyclindependent kinase inhibitor p27; Cyclin-dependent kinase inhibitor 1B
Evidence Score (E-score) 16 Experimental Evidences +
1 Affinity Capture-MS [1]
2 Affinity Capture-MS [19]
3 Affinity Capture-MS [22]
4 Affinity Capture-Western [10]
5 Affinity Capture-Western [50]
6 Affinity Capture-Western [6]
7 Affinity Capture-Western [7]
8 Affinity Capture-Western [68]
9 Affinity Capture-Western [69]
10 Affinity Capture-Western [70]
11 Affinity Capture-Western [71]
12 Affinity Capture-Western [60]
13 Affinity Capture-Western [44]
14 Affinity Capture-Western [12]
15 Co-localization [14]
16 Reconstituted Complex [52]
Interacting Target Name Melanoma differentiation-associated protein 6 (CDKN1A) Literature-reported Target Interacting Protein Info
UniProt ID
CDN1A_HUMAN 
Synonyms WAF1; SDI1; PIC1; P21(WAF1); P21; Melanoma differentiation associated protein 6; MDA-6; MDA6; Cyclin-dependent kinase inhibitor 1; CIP1; CDK-interacting protein 1; CAP20
Evidence Score (E-score) 10 Experimental Evidences +
1 Affinity Capture-MS [1]
2 Affinity Capture-Western [72]
3 Affinity Capture-Western [73]
4 Affinity Capture-Western [50]
5 Affinity Capture-Western [68]
6 Affinity Capture-Western [70]
7 Affinity Capture-Western [71]
8 Affinity Capture-Western [60]
9 Reconstituted Complex [37]
10 Reconstituted Complex [47]
References  Top
REF 1 Architecture of the human interactome defines protein communities and disease networks. Nature. 2017 May 25;545(7655):505-509.
REF 2 A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4. Nature. 1993 Dec 16;366(6456):704-7.
REF 3 Akt-dependent phosphorylation of p21(Cip1) regulates PCNA binding and proliferation of endothelial cells. Mol Cell Biol. 2001 Aug;21(16):5644-57.
REF 4 BCR-ABL1-induced expression of HSPA8 promotes cell survival in chronic myeloid leukaemia. Br J Haematol. 2008 Aug;142(4):571-82.
REF 5 Inducible expression of cyclin D1 in T-47D human breast cancer cells is sufficient for Cdk2 activation and pRB hyperphosphorylation. J Cell Biochem. 1996 Mar 1;60(3):363-78.
REF 6 Cyclin D1 regulates p27(Kip1) stability in B cells. Cell Signal. 2011 Jan;23(1):171-9.
REF 7 RSK1 drives p27Kip1 phosphorylation at T198 to promote RhoA inhibition and increase cell motility. Proc Natl Acad Sci U S A. 2009 Jun 9;106(23):9268-73.
REF 8 Cyclin D3 is down-regulated by rapamycin in HER-2-overexpressing breast cancer cells. Mol Cancer Ther. 2006 Sep;5(9):2172-81.
REF 9 Cdk6-cyclin D3 complex evades inhibition by inhibitor proteins and uniquely controls cell's proliferation competence. Oncogene. 2001 Apr 12;20(16):2000-9.
REF 10 Down-regulation of p21WAF1/CIP1 or p27Kip1 abrogates antiestrogen-mediated cell cycle arrest in human breast cancer cells. Proc Natl Acad Sci U S A. 2000 Aug 1;97(16):9042-6.
REF 11 A dominant-negative cyclin D1 mutant prevents nuclear import of cyclin-dependent kinase 4 (CDK4) and its phosphorylation by CDK-activating kinase. Mol Cell Biol. 1997 Dec;17(12):7362-74.
REF 12 Fbxl12 triggers G1 arrest by mediating degradation of calmodulin kinase I. Cell Signal. 2013 Oct;25(10):2047-59.
REF 13 The cyclin D1-dependent kinase associates with the pre-replication complex and modulates RB.MCM7 binding. J Biol Chem. 2003 Mar 14;278(11):9754-60.
REF 14 Using an in situ proximity ligation assay to systematically profile endogenous protein-protein interactions in a pathway network. J Proteome Res. 2014 Dec 5;13(12):5339-46.
REF 15 Identification of CDK4 sequences involved in cyclin D1 and p16 binding. J Biol Chem. 1997 Jul 25;272(30):18869-74.
REF 16 Regulation of CDK4 activity by a novel CDK4-binding protein, p34(SEI-1). Genes Dev. 1999 Nov 15;13(22):3027-33.
REF 17 Widespread macromolecular interaction perturbations in human genetic disorders. Cell. 2015 Apr 23;161(3):647-660.
REF 18 Pooled-matrix protein interaction screens using Barcode Fusion Genetics. Mol Syst Biol. 2016 Apr 22;12(4):863.
REF 19 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell. 2015 Jul 16;162(2):425-440.
REF 20 Large-scale mapping of human protein-protein interactions by mass spectrometry. Mol Syst Biol. 2007;3:89.
REF 21 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell. 2015 Oct 22;163(3):712-23.
REF 22 The protein interaction landscape of the human CMGC kinase group. Cell Rep. 2013 Apr 25;3(4):1306-20.
REF 23 Interlaboratory reproducibility of large-scale human protein-complex analysis by standardized AP-MS. Nat Methods. 2013 Apr;10(4):307-14.
REF 24 A CDKN2A mutation in familial melanoma that abrogates binding of p16INK4a to CDK4 but not CDK6. Cancer Res. 2007 Oct 1;67(19):9134-41.
REF 25 OncoPPi-informed discovery of mitogen-activated protein kinase kinase 3 as a novel binding partner of c-Myc. Oncogene. 2017 Oct 19;36(42):5852-5860.
REF 26 Inhibition of pRb phosphorylation and cell-cycle progression by a 20-residue peptide derived from p16CDKN2/INK4A. Curr Biol. 1996 Jan 1;6(1):84-91.
REF 27 Novel insights into the INK4-CDK4/6-Rb pathway: counter action of gankyrin against INK4 proteins regulates the CDK4-mediated phosphorylation of Rb. Biochemistry. 2002 Mar 26;41(12):3977-83.
REF 28 Patients with both pancreatic adenocarcinoma and melanoma may harbor germline CDKN2A mutations. Genes Chromosomes Cancer. 2000 Apr;27(4):358-61.
REF 29 Shifted Transversal Design smart-pooling for high coverage interactome mapping. Genome Res. 2009 Jul;19(7):1262-9.
REF 30 Towards a proteome-scale map of the human protein-protein interaction network. Nature. 2005 Oct 20;437(7062):1173-8.
REF 31 A human protein-protein interaction network: a resource for annotating the proteome. Cell. 2005 Sep 23;122(6):957-68.
REF 32 A directed protein interaction network for investigating intracellular signal transduction. Sci Signal. 2011 Sep 6;4(189):rs8.
REF 33 Growth suppression by p18, a p16INK4/MTS1- and p14INK4B/MTS2-related CDK6 inhibitor, correlates with wild-type pRb function. Genes Dev. 1994 Dec 15;8(24):2939-52.
REF 34 A proteome-scale map of the human interactome network. Cell. 2014 Nov 20;159(5):1212-1226.
REF 35 Toward an understanding of the protein interaction network of the human liver. Mol Syst Biol. 2011 Oct 11;7:536.
REF 36 Developmentally regulated expression of cyclin D3 and its potential in vivo interacting proteins during murine gametogenesis. Endocrinology. 1999 Jun;140(6):2790-800.
REF 37 Self-assembling protein microarrays. Science. 2004 Jul 2;305(5680):86-90.
REF 38 Next-generation sequencing to generate interactome datasets. Nat Methods. 2011 Jun;8(6):478-80.
REF 39 rec-YnH enables simultaneous many-by-many detection of direct protein-protein and protein-RNA interactions. Nat Commun. 2018 Sep 14;9(1):3747.
REF 40 Identification of human protein interaction domains using an ORFeome-based yeast two-hybrid fragment library. J Proteome Res. 2013 Jul 5;12(7):3181-92.
REF 41 The role of cyclin D2 and p21/waf1 in human T-cell leukemia virus type 1 infected cells. Retrovirology. 2004 Apr 13;1:6.
REF 42 Human and mouse cyclin D2 splice variants: transforming activity and subcellular localization. Oncogene. 2008 Feb 21;27(9):1253-62.
REF 43 Shp-1 mediates the antiproliferative activity of tissue inhibitor of metalloproteinase-2 in human microvascular endothelial cells. J Biol Chem. 2006 Feb 10;281(6):3711-21.
REF 44 Interleukin-6 induces G1 arrest through induction of p27(Kip1), a cyclin-dependent kinase inhibitor, and neuron-like morphology in LNCaP prostate tumor cells. Biochem Biophys Res Commun. 1999 Apr 13;257(2):609-14.
REF 45 Cyclin-dependent kinases regulate the antiproliferative function of Smads. Nature. 2004 Jul 8;430(6996):226-31.
REF 46 The centrosomal protein Lats2 is a phosphorylation target of Aurora-A kinase. Genes Cells. 2004 May;9(5):383-97.
REF 47 Cyclin-binding motifs are essential for the function of p21CIP1. Mol Cell Biol. 1996 Sep;16(9):4673-82.
REF 48 Cyclin-dependent kinase-2 (Cdk2) forms an inactive complex with cyclin D1 since Cdk2 associated with cyclin D1 is not phosphorylated by Cdk7-cyclin-H. Eur J Biochem. 1996 Apr 15;237(2):460-7.
REF 49 Lysine 269 is essential for cyclin D1 ubiquitylation by the SCF(Fbx4/alphaB-crystallin) ligase and subsequent proteasome-dependent degradation. Oncogene. 2009 Dec 10;28(49):4317-25.
REF 50 Retinoic acid inhibits the proliferative response induced by CD40 activation and interleukin-4 in mantle cell lymphoma. Cancer Res. 2005 Jan 15;65(2):587-95.
REF 51 Regulated expression of cofilin and the consequent regulation of p27(kip1) are essential for G(1) phase progression. Cell Cycle. 2009 Aug;8(15):2365-74.
REF 52 C-terminal phosphorylation controls the stability and function of p27kip1. EMBO J. 2006 Nov 1;25(21):5159-70.
REF 53 Cyclin D1/Cdk4 regulates retinoblastoma protein-mediated cell cycle arrest by site-specific phosphorylation. Mol Biol Cell. 1997 Feb;8(2):287-301.
REF 54 The consensus motif for phosphorylation by cyclin D1-Cdk4 is different from that for phosphorylation by cyclin A/E-Cdk2. EMBO J. 1996 Dec 16;15(24):7060-9.
REF 55 Cyclin-dependent kinases phosphorylate p73 at threonine 86 in a cell cycle-dependent manner and negatively regulate p73. J Biol Chem. 2003 Jul 25;278(30):27421-31.
REF 56 Differential phosphorylation of the retinoblastoma protein by G1/S cyclin-dependent kinases. J Biol Chem. 1997 May 9;272(19):12738-46.
REF 57 Direct interaction of p21 cyclin-dependent kinase inhibitor with the retinoblastoma tumor suppressor protein. Biochem Biophys Res Commun. 1999 Sep 16;263(1):35-40.
REF 58 Discovery of aminothiazole inhibitors of cyclin-dependent kinase 2: synthesis, X-ray crystallographic analysis, and biological activities. J Med Chem. 2002 Aug 29;45(18):3905-27.
REF 59 Activated signal transducer and activator of transcription 3 (STAT3) supports the malignant phenotype of human pancreatic cancer. Gastroenterology. 2003 Sep;125(3):891-905.
REF 60 Interferon-induces expression of cyclin-dependent kinase-inhibitors p21WAF1 and p27Kip1 that prevent activation of cyclin-dependent kinase by CDK-activating kinase (CAK). Oncogene. 1998 Jan 15;16(2):217-25.
REF 61 Physical interaction of mammalian CDC37 with CDK4. J Biol Chem. 1996 Sep 6;271(36):22030-4.
REF 62 Mammalian p50Cdc37 is a protein kinase-targeting subunit of Hsp90 that binds and stabilizes Cdk4. Genes Dev. 1996 Jun 15;10(12):1491-502.
REF 63 C/EBPalpha triggers proteasome-dependent degradation of cdk4 during growth arrest. EMBO J. 2002 Mar 1;21(5):930-41.
REF 64 Interaction between Cdc37 and Cdk4 in human cells. Oncogene. 1997 Apr 24;14(16):1999-2004.
REF 65 Quantitative analysis of HSP90-client interactions reveals principles of substrate recognition. Cell. 2012 Aug 31;150(5):987-1001.
REF 66 Charged linker sequence modulates eukaryotic heat shock protein 90 (Hsp90) chaperone activity. Proc Natl Acad Sci U S A. 2012 Feb 21;109(8):2937-42.
REF 67 A systematic screen for CDK4/6 substrates links FOXM1 phosphorylation to senescence suppression in cancer cells. Cancer Cell. 2011 Nov 15;20(5):620-34.
REF 68 Cytoplasmic displacement of cyclin E-cdk2 inhibitors p21Cip1 and p27Kip1 in anchorage-independent cells. Oncogene. 1998 May;16(20):2575-83.
REF 69 S10 phosphorylation of p27 mediates atRA induced growth arrest in ovarian carcinoma cell lines. J Cell Physiol. 2008 Nov;217(2):558-68.
REF 70 Progesterone inhibits human endothelial cell proliferation through a p53-dependent pathway. Cell Mol Life Sci. 2008 Nov;65(23):3839-50.
REF 71 Progression of LNCaP prostate tumor cells during androgen deprivation: hormone-independent growth, repression of proliferation by androgen, and role for p27Kip1 in androgen-induced cell cycle arrest. Mol Endocrinol. 1998 Jul;12(7):941-53.
REF 72 Yin Yang-1 inhibits vascular smooth muscle cell growth and intimal thickening by repressing p21WAF1/Cip1 transcription and p21WAF1/Cip1-Cdk4-cyclin D1 assembly. Circ Res. 2007 Jul 20;101(2):146-55.
REF 73 Tyrosine phosphorylation of the p21 cyclin-dependent kinase inhibitor facilitates the development of proneural glioma. J Biol Chem. 2012 Nov 9;287(46):38523-30.

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