Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Cyclin-dependent kinase 4

Gene

CDK4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 G1/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 G1 phase. Hypophosphorylates RB1 in early G1 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.3 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.3 Publications

Enzyme regulationi

Both phosphorylation at Thr-172 and binding of a D-type cyclin are necessary for enzymatic activity. Full activation of the cyclin-D-CDK4 complex appears to require other factors such as recruitment of the substrate via a substrate recruitment motif, and/or formation of the CDKN1B ternary complex. Inhibited by INK4 family members. In resting cells, the non-tyrosine-phosphorylated form of CDKN1B prevents phosphorylation at Thr-172 and inactivation, while, in proliferating cells, tyrosine phosphorylation of CDKN1B allows phosphorylation of Thr-172 of CDK4 and subsequennt activation.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei35ATPPROSITE-ProRule annotation1
Active sitei140Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi12 – 20ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • cyclin binding Source: UniProtKB
  • cyclin-dependent protein serine/threonine kinase activity Source: BHF-UCL
  • cyclin-dependent protein serine/threonine kinase regulator activity Source: Reactome

GO - Biological processi

  • animal organ regeneration Source: Ensembl
  • cell division Source: UniProtKB-KW
  • circadian rhythm Source: Ensembl
  • G1/S transition of mitotic cell cycle Source: BHF-UCL
  • lens development in camera-type eye Source: Ensembl
  • negative regulation of cell cycle arrest Source: UniProtKB
  • positive regulation of apoptotic process Source: Ensembl
  • positive regulation of cell cycle Source: Reactome
  • positive regulation of cell proliferation Source: BHF-UCL
  • positive regulation of cell size Source: Ensembl
  • positive regulation of fibroblast proliferation Source: BHF-UCL
  • positive regulation of G2/M transition of mitotic cell cycle Source: UniProtKB
  • positive regulation of translation Source: Ensembl
  • protein phosphorylation Source: BHF-UCL
  • regulation of gene expression Source: BHF-UCL
  • response to drug Source: UniProtKB
  • response to hyperoxia Source: Ensembl
  • response to lead ion Source: Ensembl
  • response to testosterone Source: Ensembl
  • response to toxic substance Source: Ensembl
  • signal transduction Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Cell cycle, Cell division

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS06007-MONOMER.
BRENDAi2.7.11.22. 2681.
ReactomeiR-HSA-187577. SCF(Skp2)-mediated degradation of p27/p21.
R-HSA-2559580. Oxidative Stress Induced Senescence.
R-HSA-2559582. Senescence-Associated Secretory Phenotype (SASP).
R-HSA-2559585. Oncogene Induced Senescence.
R-HSA-3214858. RMTs methylate histone arginines.
R-HSA-381340. Transcriptional regulation of white adipocyte differentiation.
R-HSA-69229. Ubiquitin-dependent degradation of Cyclin D1.
R-HSA-69231. Cyclin D associated events in G1.
R-HSA-8849470. PTK6 Regulates Cell Cycle.
R-HSA-912446. Meiotic recombination.
SignaLinkiP11802.
SIGNORiP11802.

Names & Taxonomyi

Protein namesi
Recommended name:
Cyclin-dependent kinase 4 (EC:2.7.11.22)
Alternative name(s):
Cell division protein kinase 4
PSK-J3
Gene namesi
Name:CDK4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:1773. CDK4.

Subcellular locationi

  • Cytoplasm
  • Nucleus
  • Membrane

  • Note: Cytoplasmic when non-complexed. Forms a cyclin D-CDK4 complex in the cytoplasm as cells progress through G1 phase. The complex accumulates on the nuclear membrane and enters the nucleus on transition from G1 to S phase. Also present in nucleoli and heterochromatin lumps. Colocalizes with RB1 after release into the nucleus.

GO - Cellular componenti

  • bicellular tight junction Source: Ensembl
  • chromatin Source: UniProtKB
  • cyclin D2-CDK4 complex Source: Ensembl
  • cyclin-dependent protein kinase holoenzyme complex Source: UniProtKB
  • cytosol Source: UniProtKB
  • nuclear membrane Source: UniProtKB
  • nucleolus Source: UniProtKB
  • nucleoplasm Source: Reactome
  • nucleus Source: UniProtKB
  • perinuclear region of cytoplasm Source: Ensembl
  • transcription factor complex Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane, Nucleus

Pathology & Biotechi

Involvement in diseasei

Melanoma, cutaneous malignant 3 (CMM3)4 Publications
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA malignant neoplasm of melanocytes, arising de novo or from a pre-existing benign nevus, which occurs most often in the skin but also may involve other sites.
See also OMIM:609048
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00620024R → C in CMM3; somatic and familial; generates a dominant oncogene resistant to inhibition by p16(INK4a). 2 PublicationsCorresponds to variant rs11547328dbSNPEnsembl.1
Natural variantiVAR_00620124R → H in CMM3. 1 PublicationCorresponds to variant rs104894340dbSNPEnsembl.1
Natural variantiVAR_02115241N → S in CMM3; sporadic. 1 PublicationCorresponds to variant rs144890720dbSNPEnsembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi172T → A: Weak enzyme activity towards RB1, but no effect on binding of CCDN1 nor CCDN3. 1 Publication1
Mutagenesisi172T → E: Retains moderate enzyme activity. 1 Publication1
Mutagenesisi173P → S: No effect on in vitro phosphorylation by CDK7. Greatly reduced T-172 phosphorylation and enzyme activity. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi1019.
MalaCardsiCDK4.
MIMi609048. phenotype.
OpenTargetsiENSG00000135446.
Orphaneti99970. Dedifferentiated liposarcoma.
618. Familial melanoma.
99971. Well-differentiated liposarcoma.
PharmGKBiPA102.

Chemistry databases

ChEMBLiCHEMBL331.
DrugBankiDB09073. Palbociclib.
GuidetoPHARMACOLOGYi1976.

Polymorphism and mutation databases

BioMutaiCDK4.
DMDMi1168867.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00000857782 – 303Cyclin-dependent kinase 4Add BLAST302

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1
Modified residuei172PhosphothreonineCombined sources4 Publications1

Post-translational modificationi

Phosphorylation at Thr-172 is required for enzymatic activity. Phosphorylated, in vitro, at this site by CCNH-CDK7, but, in vivo, appears to be phosphorylated by a proline-directed kinase. In the cyclin D-CDK4-CDKN1B complex, this phosphorylation and consequent CDK4 enzyme activity, is dependent on the tyrosine phosphorylation state of CDKN1B. Thus, in proliferating cells, CDK4 within the complex is phosphorylated on Thr-172 in the T-loop. In resting cells, phosphorylation on Thr-172 is prevented by the non-tyrosine-phosphorylated form of CDKN1B.5 Publications

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP11802.
MaxQBiP11802.
PaxDbiP11802.
PeptideAtlasiP11802.
PRIDEiP11802.

PTM databases

iPTMnetiP11802.
PhosphoSitePlusiP11802.

Expressioni

Gene expression databases

BgeeiENSG00000135446.
CleanExiHS_CDK4.
ExpressionAtlasiP11802. baseline and differential.
GenevisibleiP11802. HS.

Interactioni

Subunit structurei

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 phosphorylation 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. Interacts with CCND1; the interaction is prevented with the binding of CCND1 to INSM1 during cell cycle progression. Interacts with CEBPA (when phosphorylated) (PubMed:15107404). Interacts with FNIP1 and FNIP2 (PubMed:27353360).By similarity11 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CCND1P2438522EBI-295644,EBI-375001
CCND2P302798EBI-295644,EBI-748789
CCND3P3028120EBI-295644,EBI-375013
CDC37Q165437EBI-295644,EBI-295634
CDKN1AP389365EBI-295644,EBI-375077
CDKN1BP465275EBI-295644,EBI-519280
CDKN2AP4277113EBI-295644,EBI-375053
CDKN2BP427729EBI-295644,EBI-711280
CDKN2CP427739EBI-295644,EBI-711290
CDKN2DP5527313EBI-295644,EBI-745859
HOOK1Q9UJC35EBI-295644,EBI-746704
HSP90AB1P082383EBI-295644,EBI-352572
MYCP011062EBI-295644,EBI-447544
RBL1P287492EBI-295644,EBI-971402
ZNF655Q8N7203EBI-295644,EBI-625509

GO - Molecular functioni

  • cyclin binding Source: UniProtKB

Protein-protein interaction databases

BioGridi107454. 147 interactors.
DIPiDIP-875N.
IntActiP11802. 89 interactors.
MINTiMINT-1201237.
STRINGi9606.ENSP00000257904.

Chemistry databases

BindingDBiP11802.

Structurei

Secondary structure

1303
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi7 – 13Combined sources7
Beta strandi15 – 17Combined sources3
Beta strandi20 – 24Combined sources5
Turni26 – 28Combined sources3
Beta strandi31 – 40Combined sources10
Helixi51 – 63Combined sources13
Helixi64 – 66Combined sources3
Beta strandi74 – 82Combined sources9
Beta strandi84 – 94Combined sources11
Beta strandi97 – 99Combined sources3
Helixi100 – 105Combined sources6
Turni109 – 111Combined sources3
Helixi114 – 133Combined sources20
Turni143 – 145Combined sources3
Beta strandi146 – 148Combined sources3
Turni150 – 152Combined sources3
Beta strandi154 – 156Combined sources3
Helixi162 – 169Combined sources8
Helixi172 – 175Combined sources4
Turni183 – 185Combined sources3
Beta strandi186 – 189Combined sources4
Helixi195 – 208Combined sources14
Beta strandi209 – 211Combined sources3
Helixi219 – 230Combined sources12
Turni235 – 237Combined sources3
Beta strandi242 – 244Combined sources3
Helixi246 – 248Combined sources3
Helixi257 – 260Combined sources4
Helixi266 – 275Combined sources10
Helixi280 – 282Combined sources3
Helixi286 – 290Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1LD2model-A1-303[»]
2W96X-ray2.30B1-303[»]
2W99X-ray2.80B1-303[»]
2W9FX-ray2.85B1-303[»]
2W9ZX-ray2.45B1-303[»]
3G33X-ray3.00A/C1-303[»]
5FWKelectron microscopy3.90K1-303[»]
5FWLelectron microscopy9.00K1-303[»]
5FWMelectron microscopy8.00K1-303[»]
ProteinModelPortaliP11802.
SMRiP11802.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP11802.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini6 – 295Protein kinasePROSITE-ProRule annotationAdd BLAST290

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni50 – 56Required for binding D-type cyclins7

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi42 – 48Poly-Gly7

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0594. Eukaryota.
ENOG410XPP3. LUCA.
GeneTreeiENSGT00830000128256.
HOGENOMiHOG000233024.
HOVERGENiHBG014652.
InParanoidiP11802.
KOiK02089.
OMAiKRPKDFC.
OrthoDBiEOG091G0I1Q.
PhylomeDBiP11802.
TreeFamiTF101022.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P11802-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MATSRYEPVA EIGVGAYGTV YKARDPHSGH FVALKSVRVP NGGGGGGGLP
60 70 80 90 100
ISTVREVALL RRLEAFEHPN VVRLMDVCAT SRTDREIKVT LVFEHVDQDL
110 120 130 140 150
RTYLDKAPPP GLPAETIKDL MRQFLRGLDF LHANCIVHRD LKPENILVTS
160 170 180 190 200
GGTVKLADFG LARIYSYQMA LTPVVVTLWY RAPEVLLQST YATPVDMWSV
210 220 230 240 250
GCIFAEMFRR KPLFCGNSEA DQLGKIFDLI GLPPEDDWPR DVSLPRGAFP
260 270 280 290 300
PRGPRPVQSV VPEMEESGAQ LLLEMLTFNP HKRISAFRAL QHSYLHKDEG

NPE
Length:303
Mass (Da):33,730
Last modified:November 1, 1995 - v2
Checksum:i0916A0C07403A33A
GO
Isoform 2 (identifier: P11802-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-120: Missing.

Note: No experimental confirmation available.
Show »
Length:183
Mass (Da):20,725
Checksum:i4CD51FFCEAD58E5B
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti117I → L in BAG36447 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00620024R → C in CMM3; somatic and familial; generates a dominant oncogene resistant to inhibition by p16(INK4a). 2 PublicationsCorresponds to variant rs11547328dbSNPEnsembl.1
Natural variantiVAR_00620124R → H in CMM3. 1 PublicationCorresponds to variant rs104894340dbSNPEnsembl.1
Natural variantiVAR_02115241N → S in CMM3; sporadic. 1 PublicationCorresponds to variant rs144890720dbSNPEnsembl.1
Natural variantiVAR_02915382R → Q.1 PublicationCorresponds to variant rs3211612dbSNPEnsembl.1
Natural variantiVAR_041976122R → H.1 PublicationCorresponds to variant rs34386532dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0564871 – 120Missing in isoform 2. 1 PublicationAdd BLAST120

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M14505 mRNA. Translation: AAA35673.1.
U81031 Genomic DNA. Translation: AAC39521.2.
Z48970 mRNA. Translation: CAA88834.1.
U37022 Genomic DNA. Translation: AAC50506.1.
AF507942 Genomic DNA. Translation: AAM23014.1.
AK297901 mRNA. Translation: BAG60221.1.
AK313701 mRNA. Translation: BAG36447.1.
CR407668 mRNA. Translation: CAG28596.1.
CR542247 mRNA. Translation: CAG47043.1.
AC025165 Genomic DNA. No translation available.
CH471054 Genomic DNA. Translation: EAW97058.1.
BC003644 mRNA. Translation: AAH03644.1.
BC005864 mRNA. Translation: AAH05864.1.
BC010153 mRNA. Translation: AAH10153.1.
S67448 Genomic DNA. Translation: AAD13991.1.
CCDSiCCDS8953.1. [P11802-1]
PIRiI52695.
S52841.
RefSeqiNP_000066.1. NM_000075.3. [P11802-1]
UniGeneiHs.95577.

Genome annotation databases

EnsembliENST00000257904; ENSP00000257904; ENSG00000135446. [P11802-1]
GeneIDi1019.
KEGGihsa:1019.
UCSCiuc001spv.4. human. [P11802-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology
NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M14505 mRNA. Translation: AAA35673.1.
U81031 Genomic DNA. Translation: AAC39521.2.
Z48970 mRNA. Translation: CAA88834.1.
U37022 Genomic DNA. Translation: AAC50506.1.
AF507942 Genomic DNA. Translation: AAM23014.1.
AK297901 mRNA. Translation: BAG60221.1.
AK313701 mRNA. Translation: BAG36447.1.
CR407668 mRNA. Translation: CAG28596.1.
CR542247 mRNA. Translation: CAG47043.1.
AC025165 Genomic DNA. No translation available.
CH471054 Genomic DNA. Translation: EAW97058.1.
BC003644 mRNA. Translation: AAH03644.1.
BC005864 mRNA. Translation: AAH05864.1.
BC010153 mRNA. Translation: AAH10153.1.
S67448 Genomic DNA. Translation: AAD13991.1.
CCDSiCCDS8953.1. [P11802-1]
PIRiI52695.
S52841.
RefSeqiNP_000066.1. NM_000075.3. [P11802-1]
UniGeneiHs.95577.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1LD2model-A1-303[»]
2W96X-ray2.30B1-303[»]
2W99X-ray2.80B1-303[»]
2W9FX-ray2.85B1-303[»]
2W9ZX-ray2.45B1-303[»]
3G33X-ray3.00A/C1-303[»]
5FWKelectron microscopy3.90K1-303[»]
5FWLelectron microscopy9.00K1-303[»]
5FWMelectron microscopy8.00K1-303[»]
ProteinModelPortaliP11802.
SMRiP11802.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107454. 147 interactors.
DIPiDIP-875N.
IntActiP11802. 89 interactors.
MINTiMINT-1201237.
STRINGi9606.ENSP00000257904.

Chemistry databases

BindingDBiP11802.
ChEMBLiCHEMBL331.
DrugBankiDB09073. Palbociclib.
GuidetoPHARMACOLOGYi1976.

PTM databases

iPTMnetiP11802.
PhosphoSitePlusiP11802.

Polymorphism and mutation databases

BioMutaiCDK4.
DMDMi1168867.

Proteomic databases

EPDiP11802.
MaxQBiP11802.
PaxDbiP11802.
PeptideAtlasiP11802.
PRIDEiP11802.

Protocols and materials databases

DNASUi1019.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000257904; ENSP00000257904; ENSG00000135446. [P11802-1]
GeneIDi1019.
KEGGihsa:1019.
UCSCiuc001spv.4. human. [P11802-1]

Organism-specific databases

CTDi1019.
DisGeNETi1019.
GeneCardsiCDK4.
HGNCiHGNC:1773. CDK4.
MalaCardsiCDK4.
MIMi123829. gene.
609048. phenotype.
neXtProtiNX_P11802.
OpenTargetsiENSG00000135446.
Orphaneti99970. Dedifferentiated liposarcoma.
618. Familial melanoma.
99971. Well-differentiated liposarcoma.
PharmGKBiPA102.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0594. Eukaryota.
ENOG410XPP3. LUCA.
GeneTreeiENSGT00830000128256.
HOGENOMiHOG000233024.
HOVERGENiHBG014652.
InParanoidiP11802.
KOiK02089.
OMAiKRPKDFC.
OrthoDBiEOG091G0I1Q.
PhylomeDBiP11802.
TreeFamiTF101022.

Enzyme and pathway databases

BioCyciZFISH:HS06007-MONOMER.
BRENDAi2.7.11.22. 2681.
ReactomeiR-HSA-187577. SCF(Skp2)-mediated degradation of p27/p21.
R-HSA-2559580. Oxidative Stress Induced Senescence.
R-HSA-2559582. Senescence-Associated Secretory Phenotype (SASP).
R-HSA-2559585. Oncogene Induced Senescence.
R-HSA-3214858. RMTs methylate histone arginines.
R-HSA-381340. Transcriptional regulation of white adipocyte differentiation.
R-HSA-69229. Ubiquitin-dependent degradation of Cyclin D1.
R-HSA-69231. Cyclin D associated events in G1.
R-HSA-8849470. PTK6 Regulates Cell Cycle.
R-HSA-912446. Meiotic recombination.
SignaLinkiP11802.
SIGNORiP11802.

Miscellaneous databases

ChiTaRSiCDK4. human.
EvolutionaryTraceiP11802.
GeneWikiiCyclin-dependent_kinase_4.
GenomeRNAii1019.
PROiP11802.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000135446.
CleanExiHS_CDK4.
ExpressionAtlasiP11802. baseline and differential.
GenevisibleiP11802. HS.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCDK4_HUMAN
AccessioniPrimary (citable) accession number: P11802
Secondary accession number(s): B2R9A0
, B4DNF9, O00576, Q6FG61
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1989
Last sequence update: November 1, 1995
Last modified: November 30, 2016
This is version 205 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.