CDK4

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

Activity 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 subsequent activation.1 Publication

Sites

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Binding siteⁱ	35	ATPPROSITE-ProRule annotation		1
Active siteⁱ	140	Proton acceptorPROSITE-ProRule annotation		1

Regions

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Nucleotide bindingⁱ	12 – 20	ATPPROSITE-ProRule annotation		9

GO - Molecular functionⁱ

ATP binding Source: UniProtKB-KW
cyclin binding
Source: UniProtKB
Inferred from physical interactionⁱ
- 19124461
cyclin-dependent protein serine/threonine kinase activity
Source: BHF-UCL
Inferred from direct assayⁱ
- 8114739
cyclin-dependent protein serine/threonine kinase regulator activity Source: Reactome
protein-containing complex binding Source: Ensembl

View the complete GO annotation on QuickGO ...

GO - Biological processⁱ

adipose tissue development Source: Ensembl
animal organ regeneration Source: Ensembl
cell division Source: UniProtKB-KW
cellular response to insulin stimulus Source: Ensembl
cellular response to interleukin-4 Source: Ensembl
cellular response to ionomycin Source: Ensembl
cellular response to lipopolysaccharide Source: Ensembl
cellular response to phorbol 13-acetate 12-myristate Source: Ensembl
circadian rhythm Source: Ensembl
G1/S transition of mitotic cell cycle
Source: BHF-UCL
Inferred from mutant phenotypeⁱ
- 7603984
lens development in camera-type eye Source: Ensembl
multicellular organism development Source: GO_Central
negative regulation of cell cycle arrest
Source: UniProtKB
Inferred from direct assayⁱ
- 19124461
negative regulation of cyclin-dependent protein serine/threonine kinase activity involved in G1/S transition of mitotic cell cycle Source: Reactome
positive regulation of apoptotic process Source: Ensembl
positive regulation of cell cycle Source: Reactome
positive regulation of cell proliferation
Source: BHF-UCL
Inferred from mutant phenotypeⁱ
- 7603984
positive regulation of cell size Source: Ensembl
positive regulation of fibroblast proliferation
Source: BHF-UCL
Inferred from mutant phenotypeⁱ
- 17420273
positive regulation of G2/M transition of mitotic cell cycle
Source: UniProtKB
Inferred from direct assayⁱ
- 19124461
positive regulation of translation Source: Ensembl
protein phosphorylation
Source: BHF-UCL
Inferred from direct assayⁱ
- 8114739
regulation of gene expression
Source: BHF-UCL
Inferred from mutant phenotypeⁱ
- 17420273
regulation of insulin receptor signaling pathway Source: Ensembl
regulation of lipid biosynthetic process Source: Ensembl
regulation of lipid catabolic process Source: Ensembl
regulation of multicellular organism growth Source: Ensembl
response to drug
Source: UniProtKB
Inferred from expression patternⁱ
- 18291362
response to hyperoxia Source: Ensembl
response to lead ion Source: Ensembl
response to organic substance Source: GO_Central
response to testosterone Source: Ensembl
response to toxic substance Source: Ensembl
signal transduction Source: GO_Central
transcription initiation from RNA polymerase II promoter Source: Reactome

View the complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	Kinase, Serine/threonine-protein kinase, Transferase
Biological process	Cell cycle, Cell division
Ligand	ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAⁱ	2.7.11.22 2681
Reactomeⁱ	R-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-8878166 Transcriptional regulation by RUNX2 R-HSA-912446 Meiotic recombination
SignaLinkⁱ	P11802
SIGNORⁱ	P11802

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
Organismⁱ	Homo sapiens (Human)
Taxonomic identifierⁱ	9606 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo
Proteomesⁱ	UP000005640 Componentⁱ: Chromosome 12

Organism-specific databases

EuPathDBⁱ	HostDB:ENSG00000135446.16
Human Gene Nomenclature Database More...HGNCⁱ	HGNC:1773 CDK4
MIMⁱ	123829 gene
neXtProtⁱ	NX_P11802

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.

Mutagenesis

Feature key	Position(s)	DescriptionActions	Length
Mutagenesisⁱ	172	T → A: Weak enzyme activity towards RB1, but no effect on binding of CCDN1 nor CCDN3. 1 Publication	1
Mutagenesisⁱ	172	T → E: Retains moderate enzyme activity. 1 Publication	1
Mutagenesisⁱ	173	P → S: No effect on in vitro phosphorylation by CDK7. Greatly reduced T-172 phosphorylation and enzyme activity. 1 Publication	1

Keywords - Diseaseⁱ

Disease mutation

Organism-specific databases

DisGeNET More...DisGeNETⁱ	1019
MalaCards human disease database More...MalaCardsⁱ	CDK4
MIMⁱ	609048 phenotype
Open Targets More...OpenTargetsⁱ	ENSG00000135446
Orphanetⁱ	99970 Dedifferentiated liposarcoma 618 Familial melanoma 99971 Well-differentiated liposarcoma
PharmGKBⁱ	PA102

Chemistry databases

ChEMBLⁱ	CHEMBL331
Drug and drug target database More...DrugBankⁱ	DB03496 Flavopiridol DB09073 Palbociclib DB02733 Purvalanol DB11730 Ribociclib
IUPHAR/BPS Guide to PHARMACOLOGY More...GuidetoPHARMACOLOGYⁱ	1976

Polymorphism and mutation databases

BioMutaⁱ	CDK4
DMDMⁱ	1168867

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Initiator methionineⁱ		RemovedCombined sources
ChainⁱPRO_0000085778	2 – 303	Cyclin-dependent kinase 4Add BLAST		302

Amino acid modifications

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Modified residueⁱ	2	N-acetylalanineCombined sources		1
Modified residueⁱ	172	PhosphothreonineCombined sources4 Publications		1

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

EPDⁱ	P11802
MaxQB - The MaxQuant DataBase More...MaxQBⁱ	P11802
PaxDbⁱ	P11802
PeptideAtlas More...PeptideAtlasⁱ	P11802
PRIDEⁱ	P11802
ProteomicsDBⁱ	52805

PTM databases

iPTMnetⁱ	P11802
PhosphoSitePlusⁱ	P11802

Expressionⁱ

Gene expression databases

Bgeeⁱ	ENSG00000135446 Expressed in 225 organ(s), highest expression level in right ovary
CleanExⁱ	HS_CDK4
ExpressionAtlasⁱ	P11802 baseline and differential
Genevisibleⁱ	P11802 HS

Organism-specific databases

Human Protein Atlas More...HPAⁱ	CAB013116 CAB069405 HPA006024

HPAⁱ

CAB013116
CAB069405
HPA006024

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. Probably forms a complex composed of chaperones HSP90 and HSP70, co-chaperones CDC37, PPP5C, TSC1 and client protein TSC2, CDK4, AKT, RAF1 and NR3C1; this complex does not contain co-chaperones STIP1/HOP and PTGES3/p23 (PubMed:29127155). Interacts with CEBPA (when phosphorylated) (PubMed:15107404). Interacts with FNIP1 and FNIP2 (PubMed:27353360).By similarity12 Publications

Binary interactionsⁱ

With	Entry	#Exp.	IntAct
CCND1	P24385	29	EBI-295644,EBI-375001
CCND2	P30279	12	EBI-295644,EBI-748789
CCND3	P30281	27	EBI-295644,EBI-375013
CDC37	Q16543	11	EBI-295644,EBI-295634
CDK7	P50613	2	EBI-295644,EBI-1245958
CDKN1A	P38936	5	EBI-295644,EBI-375077
CDKN1B	P46527	6	EBI-295644,EBI-519280
CDKN2A	P42771	13	EBI-295644,EBI-375053
CDKN2B	P42772	15	EBI-295644,EBI-711280
CDKN2C	P42773	17	EBI-295644,EBI-711290
CDKN2D	P55273	18	EBI-295644,EBI-745859
HOOK1	Q9UJC3	11	EBI-295644,EBI-746704
HSP90AB1	P08238	3	EBI-295644,EBI-352572
IKZF3	Q9UKT9	4	EBI-295644,EBI-747204
MYC	P01106	2	EBI-295644,EBI-447544
RBL1	P28749	2	EBI-295644,EBI-971402
ZNF655	Q8N720	5	EBI-295644,EBI-625509

GO - Molecular functionⁱ

cyclin binding
Source: UniProtKB
Inferred from physical interactionⁱ
- 19124461

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridⁱ	107454, 168 interactors
ComplexPortalⁱ	CPX-2010 Cyclin D1-CDK4 complex CPX-2011 Cyclin D2-CDK4 complex CPX-2012 Cyclin D3-CDK4 complex
CORUMⁱ	P11802
Database of interacting proteins More...DIPⁱ	DIP-875N
ELMⁱ	P11802
IntActⁱ	P11802, 98 interactors
Molecular INTeraction database More...MINTⁱ	P11802
STRINGⁱ	9606.ENSP00000257904

Chemistry databases

BindingDBⁱ

P11802

Structureⁱ

Secondary structure

Legend: HelixTurnBeta strandPDB Structure known for this area

Feature key	Position(s)	DescriptionActions	Length
Beta strandⁱ	7 – 13	Combined sources	7
Beta strandⁱ	15 – 17	Combined sources	3
Beta strandⁱ	20 – 24	Combined sources	5
Turnⁱ	26 – 28	Combined sources	3
Beta strandⁱ	31 – 40	Combined sources	10
Helixⁱ	51 – 63	Combined sources	13
Helixⁱ	64 – 66	Combined sources	3
Beta strandⁱ	74 – 82	Combined sources	9
Beta strandⁱ	84 – 94	Combined sources	11
Beta strandⁱ	97 – 99	Combined sources	3
Helixⁱ	100 – 105	Combined sources	6
Turnⁱ	109 – 111	Combined sources	3
Helixⁱ	114 – 133	Combined sources	20
Turnⁱ	143 – 145	Combined sources	3
Beta strandⁱ	146 – 148	Combined sources	3
Turnⁱ	150 – 152	Combined sources	3
Beta strandⁱ	154 – 156	Combined sources	3
Helixⁱ	162 – 169	Combined sources	8
Helixⁱ	172 – 175	Combined sources	4
Turnⁱ	183 – 185	Combined sources	3
Beta strandⁱ	186 – 189	Combined sources	4
Helixⁱ	195 – 208	Combined sources	14
Beta strandⁱ	209 – 211	Combined sources	3
Helixⁱ	219 – 230	Combined sources	12
Turnⁱ	235 – 237	Combined sources	3
Beta strandⁱ	242 – 244	Combined sources	3
Helixⁱ	246 – 248	Combined sources	3
Helixⁱ	257 – 260	Combined sources	4
Helixⁱ	266 – 275	Combined sources	10
Helixⁱ	280 – 282	Combined sources	3
Helixⁱ	286 – 290	Combined sources	5

Show more details

3D structure databases

ProteinModelPortalⁱ	P11802
SMRⁱ	P11802
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Miscellaneous databases

EvolutionaryTraceⁱ	P11802

EvolutionaryTraceⁱ

P11802

Family & Domainsⁱ

Domains and Repeats

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Domainⁱ	6 – 295	Protein kinasePROSITE-ProRule annotationAdd BLAST		290

Region

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Regionⁱ	50 – 56	Required for binding D-type cyclins		7

Compositional bias

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Compositional biasⁱ	42 – 48	Poly-Gly		7

Sequence similaritiesⁱ

Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily.Curated

Phylogenomic databases

eggNOGⁱ	KOG0594 Eukaryota ENOG410XPP3 LUCA
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00910000144030
HOGENOMⁱ	HOG000233024
HOVERGENⁱ	HBG014652
InParanoidⁱ	P11802
KEGG Orthology (KO) More...KOⁱ	K02089
OMAⁱ	ATPRYEP
Database of Orthologous Groups More...OrthoDBⁱ	EOG091G0I1Q
PhylomeDBⁱ	P11802
TreeFamⁱ	TF101022

Family and domain databases

InterProⁱ	View protein in InterPro IPR011009 Kinase-like_dom_sf IPR000719 Prot_kinase_dom IPR017441 Protein_kinase_ATP_BS IPR008271 Ser/Thr_kinase_AS
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF00069 Pkinase, 1 hit
SMARTⁱ	View protein in SMART SM00220 S_TKc, 1 hit
SUPFAMⁱ	SSF56112 SSF56112, 1 hit
PROSITEⁱ	View protein in PROSITE PS00107 PROTEIN_KINASE_ATP, 1 hit PS50011 PROTEIN_KINASE_DOM, 1 hit PS00108 PROTEIN_KINASE_ST, 1 hit

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. Align Add to basket

This entry has 2 described isoforms and 10 potential isoforms that are computationally mapped.Show all Align All

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

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

« Hide

        10         20         30         40         50
MRQFLRGLDF LHANCIVHRD LKPENILVTS GGTVKLADFG LARIYSYQMA 
        60         70         80         90        100
LTPVVVTLWY RAPEVLLQST YATPVDMWSV GCIFAEMFRR KPLFCGNSEA 
       110        120        130        140        150
DQLGKIFDLI GLPPEDDWPR DVSLPRGAFP PRGPRPVQSV VPEMEESGAQ 
       160        170        180 
LLLEMLTFNP HKRISAFRAL QHSYLHKDEG NPE

Note: No experimental confirmation available.

Show »

Length:183

Mass (Da):20,725

Checksum:ⁱ4CD51FFCEAD58E5B

GO

Computationally mapped potential isoform sequencesⁱ

There are 10 potential isoforms mapped to this entry.BLAST Align Show all Add to basket

Entry	Entry name	Protein names	Gene names	Length	Annotation

F8VTV8	F8VTV8_HUMAN	Cyclin-dependent kinase 4 Cyclin-dependent kinase 4	CDK4	201	Annotation score:
F8VWX7	F8VWX7_HUMAN	Cyclin-dependent kinase 4 Cyclin-dependent kinase 4	CDK4	203	Annotation score:
F8VYH9	F8VYH9_HUMAN	Cyclin-dependent kinase 4 Cyclin-dependent kinase 4	CDK4	170	Annotation score:
F8VZ51	F8VZ51_HUMAN	Cyclin-dependent kinase 4 Cyclin-dependent kinase 4	CDK4	208	Annotation score:
F8VZZ0	F8VZZ0_HUMAN	Cyclin-dependent kinase 4 Cyclin-dependent kinase 4	CDK4	186	Annotation score:
F8VXD2	F8VXD2_HUMAN	Cyclin-dependent kinase 4 Cyclin-dependent kinase 4	CDK4	132	Annotation score:
F8W1L8	F8W1L8_HUMAN	Cyclin-dependent kinase 4 Cyclin-dependent kinase 4	CDK4	115	Annotation score:
F8VYY1	F8VYY1_HUMAN	Cyclin-dependent kinase 4 Cyclin-dependent kinase 4	CDK4	74	Annotation score:
Q96BE9	Q96BE9_HUMAN	CDK4 protein CDK4 protein (Cyclin-dependent kinase 4) (Cyclin-dependent kinase 4, isoform CRA_c)	CDK4 hCG_40151	111	Annotation score:
F8VZ13	F8VZ13_HUMAN	Cyclin-dependent kinase 4 Cyclin-dependent kinase 4	CDK4	40	Annotation score:

Experimental Info

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Sequence conflictⁱ	117	I → L in BAG36447 (PubMed:14702039).Curated		1

Natural variant

Feature key	Position(s)	DescriptionActions	Length
Natural variantⁱVAR_006200	24	R → C in CMM3; somatic and familial; generates a dominant oncogene resistant to inhibition by p16(INK4a). 2 PublicationsCorresponds to variant dbSNP:rs11547328EnsemblClinVar.	1
Natural variantⁱVAR_006201	24	R → H in CMM3. 1 PublicationCorresponds to variant dbSNP:rs104894340EnsemblClinVar.	1
Natural variantⁱVAR_021152	41	N → S in CMM3; sporadic. 1 PublicationCorresponds to variant dbSNP:rs144890720EnsemblClinVar.	1
Natural variantⁱVAR_029153	82	R → Q1 PublicationCorresponds to variant dbSNP:rs3211612EnsemblClinVar.	1
Natural variantⁱVAR_041976	122	R → H1 PublicationCorresponds to variant dbSNP:rs34386532Ensembl.	1

Alternative sequence

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Alternative sequenceⁱVSP_056487	1 – 120	Missing in isoform 2. 1 PublicationAdd BLAST		120

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
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS8953.1 [P11802-1]
PIRⁱ	I52695 S52841
NCBI Reference Sequences More...RefSeqⁱ	NP_000066.1, NM_000075.3 [P11802-1]
UniGeneⁱ	Hs.95577

Genome annotation databases

Ensemblⁱ	ENST00000257904; ENSP00000257904; ENSG00000135446 [P11802-1]
GeneIDⁱ	1019
KEGGⁱ	hsa:1019
UCSC genome browser More...UCSCⁱ	uc001spv.4 human [P11802-1]

Keywords - Coding sequence diversityⁱ

Alternative splicing, Polymorphism

Similar proteinsⁱ

100% Identity
90% Identity
50% Identity

Protein	Similar proteins		Species	Score	Length	Source
P11802	Cyclin-dependent kinase 4, isoform CRA_a		HUMAN		303	UniRef100_P11802
CDK4 isoform 2		PANTR		303
Uncharacterized protein		PANPA		303
Cyclin dependent kinase 4		GORGO		303
Uncharacterized protein		MACMU		229
+12

Protein	Similar proteins		Species	Score	Length	Source
P11802	Cyclin-dependent kinase 4, isoform CRA_a		HUMAN		303	UniRef90_P11802
CDK4 isoform 2		PANTR		303
Uncharacterized protein		PANPA		303
Cyclin dependent kinase 4		GORGO		303
Uncharacterized protein		MACMU		229
+24

Protein	Similar proteins		Species	Score	Length	Source
P11802	Cyclin-dependent kinase 4, isoform CRA_a		HUMAN		303	UniRef50_P11802
CDK4 isoform 2		PANTR		303
Uncharacterized protein		PANPA		303
Cyclin dependent kinase 4		GORGO		303
Uncharacterized protein		MACMU		229
+72

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
CCDSⁱ	CCDS8953.1 [P11802-1]
PIRⁱ	I52695 S52841
RefSeqⁱ	NP_000066.1, NM_000075.3 [P11802-1]
UniGeneⁱ	Hs.95577

3D structure databases

Select the link destinations: Protein Data Bank Europe More...PDBeⁱ Protein Data Bank RCSB More...RCSB PDBⁱ Protein Data Bank Japan More...PDBjⁱ Links Updated	PDB entry	Method	Resolution (Å)	Chain	Positions	PDBsum
	1LD2	model	-	A	1-303	[»]
	2W96	X-ray	2.30	B	1-303	[»]
	2W99	X-ray	2.80	B	1-303	[»]
	2W9F	X-ray	2.85	B	1-303	[»]
	2W9Z	X-ray	2.45	B	1-303	[»]
	3G33	X-ray	3.00	A/C	1-303	[»]
	5FWK	electron microscopy	3.90	K	1-303	[»]
	5FWL	electron microscopy	9.00	K	1-303	[»]
	5FWM	electron microscopy	8.00	K	1-303	[»]
	5FWP	electron microscopy	7.20	K	1-303	[»]
ProteinModelPortalⁱ	P11802
SMRⁱ	P11802
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Protein-protein interaction databases

BioGridⁱ	107454, 168 interactors
ComplexPortalⁱ	CPX-2010 Cyclin D1-CDK4 complex CPX-2011 Cyclin D2-CDK4 complex CPX-2012 Cyclin D3-CDK4 complex
CORUMⁱ	P11802
DIPⁱ	DIP-875N
ELMⁱ	P11802
IntActⁱ	P11802, 98 interactors
MINTⁱ	P11802
STRINGⁱ	9606.ENSP00000257904

Chemistry databases

BindingDBⁱ	P11802
ChEMBLⁱ	CHEMBL331
DrugBankⁱ	DB03496 Flavopiridol DB09073 Palbociclib DB02733 Purvalanol DB11730 Ribociclib
GuidetoPHARMACOLOGYⁱ	1976

PTM databases

iPTMnetⁱ	P11802
PhosphoSitePlusⁱ	P11802

Polymorphism and mutation databases

BioMutaⁱ	CDK4
DMDMⁱ	1168867

Proteomic databases

EPDⁱ	P11802
MaxQBⁱ	P11802
PaxDbⁱ	P11802
PeptideAtlasⁱ	P11802
PRIDEⁱ	P11802
ProteomicsDBⁱ	52805

Protocols and materials databases

The DNASU plasmid repository More...DNASUⁱ	1019
Structural Biology Knowledgebase	Search...

Genome annotation databases

Ensemblⁱ	ENST00000257904; ENSP00000257904; ENSG00000135446 [P11802-1]
GeneIDⁱ	1019
KEGGⁱ	hsa:1019
UCSCⁱ	uc001spv.4 human [P11802-1]

Organism-specific databases

CTDⁱ	1019
DisGeNETⁱ	1019
EuPathDBⁱ	HostDB:ENSG00000135446.16
GeneCardsⁱ	CDK4
HGNCⁱ	HGNC:1773 CDK4
HPAⁱ	CAB013116 CAB069405 HPA006024
MalaCardsⁱ	CDK4
MIMⁱ	123829 gene 609048 phenotype
neXtProtⁱ	NX_P11802
OpenTargetsⁱ	ENSG00000135446
Orphanetⁱ	99970 Dedifferentiated liposarcoma 618 Familial melanoma 99971 Well-differentiated liposarcoma
PharmGKBⁱ	PA102
GenAtlas: human gene database More...GenAtlasⁱ	Search...

Phylogenomic databases

eggNOGⁱ	KOG0594 Eukaryota ENOG410XPP3 LUCA
GeneTreeⁱ	ENSGT00910000144030
HOGENOMⁱ	HOG000233024
HOVERGENⁱ	HBG014652
InParanoidⁱ	P11802
KOⁱ	K02089
OMAⁱ	ATPRYEP
OrthoDBⁱ	EOG091G0I1Q
PhylomeDBⁱ	P11802
TreeFamⁱ	TF101022

Enzyme and pathway databases

BRENDAⁱ	2.7.11.22 2681
Reactomeⁱ	R-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-8878166 Transcriptional regulation by RUNX2 R-HSA-912446 Meiotic recombination
SignaLinkⁱ	P11802
SIGNORⁱ	P11802

Miscellaneous databases

ChiTaRSⁱ	CDK4 human
EvolutionaryTraceⁱ	P11802
GeneWikiⁱ	Cyclin-dependent_kinase_4
GenomeRNAiⁱ	1019
Protein Ontology More...PROⁱ	PR:P11802
SOURCEⁱ	Search...

Gene expression databases

Bgeeⁱ	ENSG00000135446 Expressed in 225 organ(s), highest expression level in right ovary
CleanExⁱ	HS_CDK4
ExpressionAtlasⁱ	P11802 baseline and differential
Genevisibleⁱ	P11802 HS

Family and domain databases

InterProⁱ	View protein in InterPro IPR011009 Kinase-like_dom_sf IPR000719 Prot_kinase_dom IPR017441 Protein_kinase_ATP_BS IPR008271 Ser/Thr_kinase_AS
Pfamⁱ	View protein in Pfam PF00069 Pkinase, 1 hit
SMARTⁱ	View protein in SMART SM00220 S_TKc, 1 hit
SUPFAMⁱ	SSF56112 SSF56112, 1 hit
PROSITEⁱ	View protein in PROSITE PS00107 PROTEIN_KINASE_ATP, 1 hit PS50011 PROTEIN_KINASE_DOM, 1 hit PS00108 PROTEIN_KINASE_ST, 1 hit
ProtoNetⁱ	Search...

Entry informationⁱ

Entry nameⁱ	CDK4_HUMAN
Accessionⁱ	P11802Primary (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:	September 12, 2018
	This is version 223 of the entry and version 2 of the sequence. See complete history.
Entry statusⁱ	Reviewed (UniProtKB/Swiss-Prot)
Annotation program	Chordata Protein Annotation Program
Disclaimer	Any 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

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

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UniProtKB - P11802 (CDK4_HUMAN)

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Cyclin-dependent kinase 4

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Functionⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

Keywords - Cellular componentⁱ

Pathology & Biotechⁱ

Keywords - Diseaseⁱ

PTM / Processingⁱ

Keywords - PTMⁱ

Expressionⁱ

Interactionⁱ

GO - Molecular functionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Keywords - Coding sequence diversityⁱ

Cross-referencesⁱ

Web resourcesⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ