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Protein

Cyclin-dependent kinase 4

Gene

CDK4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the ‘protein existence’ evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>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

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi

<p>This subsection of the ‘Function’ section describes regulatory mechanisms for enzymes, transporters or microbial transcription factors, and reports the components which regulate (by activation or inhibition) the reaction.<p><a href='/help/activity_regulation' target='_top'>More...</a></p>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 keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Function’ section describes the interaction between a single amino acid and another chemical entity. Priority is given to the annotation of physiological ligands.<p><a href='/help/binding' target='_top'>More...</a></p>Binding sitei35ATPPROSITE-ProRule annotation1
<p>This subsection of the ‘Function’ section is used for enzymes and indicates the residues directly involved in catalysis.<p><a href='/help/act_site' target='_top'>More...</a></p>Active sitei140Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Function’ section describes a region in the protein which binds nucleotide phosphates. It always involves more than one amino acid and includes all residues involved in nucleotide-binding.<p><a href='/help/np_bind' target='_top'>More...</a></p>Nucleotide bindingi12 – 20ATPPROSITE-ProRule annotation9

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processCell cycle, Cell division
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDA Comprehensive Enzyme Information System

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BRENDAi
2.7.11.22 2681

Reactome - a knowledgebase of biological pathways and processes

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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

SignaLink: a signaling pathway resource with multi-layered regulatory networks

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SignaLinki
P11802

SIGNOR Signaling Network Open Resource

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SIGNORi
P11802

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Cyclin-dependent kinase 4 (EC:2.7.11.22)
Alternative name(s):
Cell division protein kinase 4
PSK-J3
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: ‘Name’, ‘Synonyms’, ‘Ordered locus names’ and ‘ORF names’.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:CDK4
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the ‘taxonomic identifier’ or ‘taxid’.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes_manual">proteome</a> can consist of several components. <br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 12

Organism-specific databases

Eukaryotic Pathogen Database Resources

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EuPathDBi
HostDB:ENSG00000135446.16

Human Gene Nomenclature Database

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HGNCi
HGNC:1773 CDK4

Online Mendelian Inheritance in Man (OMIM)

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MIMi
123829 gene

neXtProt; the human protein knowledge platform

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neXtProti
NX_P11802

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Membrane, Nucleus

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the ‘Pathology and Biotech’ section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>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
<p>This subsection of the ‘Sequence’ section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_00620024R → 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_00620124R → H in CMM3. 1 PublicationCorresponds to variant dbSNP:rs104894340EnsemblClinVar.1
Natural variantiVAR_02115241N → S in CMM3; sporadic. 1 PublicationCorresponds to variant dbSNP:rs144890720EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology_and_biotech_section">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>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

DisGeNET

More...
DisGeNETi
1019

MalaCards human disease database

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MalaCardsi
CDK4
MIMi609048 phenotype

Open Targets

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OpenTargetsi
ENSG00000135446

Orphanet; a database dedicated to information on rare diseases and orphan drugs

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Orphaneti
99970 Dedifferentiated liposarcoma
618 Familial melanoma
99971 Well-differentiated liposarcoma

The Pharmacogenetics and Pharmacogenomics Knowledge Base

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PharmGKBi
PA102

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

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ChEMBLi
CHEMBL331

Drug and drug target database

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DrugBanki
DB03496 Flavopiridol
DB09073 Palbociclib
DB02733 Purvalanol
DB11730 Ribociclib

IUPHAR/BPS Guide to PHARMACOLOGY

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GuidetoPHARMACOLOGYi
1976

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

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BioMutai
CDK4

Domain mapping of disease mutations (DMDM)

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DMDMi
1168867

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM / Processing</a> section indicates that the initiator methionine is cleaved from the mature protein.<p><a href='/help/init_met' target='_top'>More...</a></p>Initiator methionineiRemovedCombined sources
<p>This subsection of the ‘PTM / Processing’ section describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00000857782 – 303Cyclin-dependent kinase 4Add BLAST302

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei2N-acetylalanineCombined sources1
Modified residuei172PhosphothreonineCombined sources4 Publications1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>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

Encyclopedia of Proteome Dynamics

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EPDi
P11802

jPOST - Japan Proteome Standard Repository/Database

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jPOSTi
P11802

MaxQB - The MaxQuant DataBase

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MaxQBi
P11802

PaxDb, a database of protein abundance averages across all three domains of life

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PaxDbi
P11802

PeptideAtlas

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PeptideAtlasi
P11802

PRoteomics IDEntifications database

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PRIDEi
P11802

ProteomicsDB human proteome resource

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ProteomicsDBi
52805

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

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iPTMneti
P11802

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

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PhosphoSitePlusi
P11802

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

Bgee dataBase for Gene Expression Evolution

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Bgeei
ENSG00000135446 Expressed in 225 organ(s), highest expression level in right ovary

CleanEx database of gene expression profiles

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CleanExi
HS_CDK4

ExpressionAtlas, Differential and Baseline Expression

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ExpressionAtlasi
P11802 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

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Genevisiblei
P11802 HS

Organism-specific databases

Human Protein Atlas

More...
HPAi
CAB013116
CAB069405
HPA006024

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction_section">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>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

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction_section%27">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="http://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated on a monthly basis. Each binary interaction is displayed on a separate line.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

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BioGridi
107454, 206 interactors

ComplexPortal: manually curated resource of macromolecular complexes

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ComplexPortali
CPX-2010 Cyclin D1-CDK4 complex
CPX-2011 Cyclin D2-CDK4 complex
CPX-2012 Cyclin D3-CDK4 complex

CORUM comprehensive resource of mammalian protein complexes

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CORUMi
P11802

Database of interacting proteins

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DIPi
DIP-875N

The Eukaryotic Linear Motif resource for Functional Sites in Proteins

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ELMi
P11802

Protein interaction database and analysis system

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IntActi
P11802, 99 interactors

Molecular INTeraction database

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MINTi
P11802

STRING: functional protein association networks

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STRINGi
9606.ENSP00000257904

Chemistry databases

BindingDB database of measured binding affinities

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BindingDBi
P11802

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

1303
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

Select the link destinations:

Protein Data Bank Europe

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PDBei

Protein Data Bank RCSB

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RCSB PDBi

Protein Data Bank Japan

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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[»]
5FWPelectron microscopy7.20K1-303[»]

Protein Model Portal of the PSI-Nature Structural Biology Knowledgebase

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ProteinModelPortali
P11802

SWISS-MODEL Repository - a database of annotated 3D protein structure models

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SMRi
P11802

Database of comparative protein structure models

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ModBasei
Search...

MobiDB: a database of protein disorder and mobility annotations

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MobiDBi
Search...

Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence

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EvolutionaryTracei
P11802

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/family_and_domains_section">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini6 – 295Protein kinasePROSITE-ProRule annotationAdd BLAST290

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and Domains’ section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni50 – 56Required for binding D-type cyclins7

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and Domains’ section describes the position of regions of compositional bias within the protein and the particular amino acids that are over-represented within those regions.<p><a href='/help/compbias' target='_top'>More...</a></p>Compositional biasi42 – 48Poly-Gly7

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

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eggNOGi
KOG0594 Eukaryota
ENOG410XPP3 LUCA

Ensembl GeneTree

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GeneTreei
ENSGT00940000154770

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

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HOGENOMi
HOG000233024

The HOVERGEN Database of Homologous Vertebrate Genes

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HOVERGENi
HBG014652

InParanoid: Eukaryotic Ortholog Groups

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InParanoidi
P11802

KEGG Orthology (KO)

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KOi
K02089

Identification of Orthologs from Complete Genome Data

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OMAi
TFSPHKR

Database of Orthologous Groups

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OrthoDBi
988547at2759

Database for complete collections of gene phylogenies

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PhylomeDBi
P11802

TreeFam database of animal gene trees

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TreeFami
TF101022

Family and domain databases

Integrated resource of protein families, domains and functional sites

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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

Simple Modular Architecture Research Tool; a protein domain database

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SMARTi
View protein in SMART
SM00220 S_TKc, 1 hit

Superfamily database of structural and functional annotation

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SUPFAMi
SSF56112 SSF56112, 1 hit

PROSITE; a protein domain and family database

More...
PROSITEi
View protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>.<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (2+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 <p>This subsection of the ‘Sequence’ section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket

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

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
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> 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

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There are 10 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F8VTV8F8VTV8_HUMAN
Cyclin-dependent kinase 4
CDK4
201Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
F8VWX7F8VWX7_HUMAN
Cyclin-dependent kinase 4
CDK4
203Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
F8VYH9F8VYH9_HUMAN
Cyclin-dependent kinase 4
CDK4
170Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
F8VZ51F8VZ51_HUMAN
Cyclin-dependent kinase 4
CDK4
208Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
F8VZZ0F8VZZ0_HUMAN
Cyclin-dependent kinase 4
CDK4
186Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
F8VXD2F8VXD2_HUMAN
Cyclin-dependent kinase 4
CDK4
132Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
Q96BE9Q96BE9_HUMAN
CDK4 protein
CDK4 hCG_40151
111Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
F8W1L8F8W1L8_HUMAN
Cyclin-dependent kinase 4
CDK4
115Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
F8VYY1F8VYY1_HUMAN
Cyclin-dependent kinase 4
CDK4
74Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
F8VZ13F8VZ13_HUMAN
Cyclin-dependent kinase 4
CDK4
40Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>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 dbSNP:rs11547328EnsemblClinVar.1
Natural variantiVAR_00620124R → H in CMM3. 1 PublicationCorresponds to variant dbSNP:rs104894340EnsemblClinVar.1
Natural variantiVAR_02115241N → S in CMM3; sporadic. 1 PublicationCorresponds to variant dbSNP:rs144890720EnsemblClinVar.1
Natural variantiVAR_02915382R → Q1 PublicationCorresponds to variant dbSNP:rs3211612EnsemblClinVar.1
Natural variantiVAR_041976122R → H1 PublicationCorresponds to variant dbSNP:rs34386532Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting. The information stored in this subsection is used to automatically construct alternative protein sequence(s) for display.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_0564871 – 120Missing in isoform 2. 1 PublicationAdd BLAST120

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

More...
EMBLi

GenBank nucleotide sequence database

More...
GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...
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]

Protein sequence database of the Protein Information Resource

More...
PIRi
I52695
S52841

NCBI Reference Sequences

More...
RefSeqi
NP_000066.1, NM_000075.3 [P11802-1]

UniGene gene-oriented nucleotide sequence clusters

More...
UniGenei
Hs.95577

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...
Ensembli
ENST00000257904; ENSP00000257904; ENSG00000135446 [P11802-1]

Database of genes from NCBI RefSeq genomes

More...
GeneIDi
1019

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...
KEGGi
hsa:1019

UCSC genome browser

More...
UCSCi
uc001spv.4 human [P11802-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

<p>This subsection of the <a href="http://www.uniprot.org/manual/cross_references_section">Cross-references</a> section provides links to various web resources that are relevant for a specific protein.<p><a href='/help/web_resource' target='_top'>More...</a></p>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[»]
5FWPelectron microscopy7.20K1-303[»]
ProteinModelPortaliP11802
SMRiP11802
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107454, 206 interactors
ComplexPortaliCPX-2010 Cyclin D1-CDK4 complex
CPX-2011 Cyclin D2-CDK4 complex
CPX-2012 Cyclin D3-CDK4 complex
CORUMiP11802
DIPiDIP-875N
ELMiP11802
IntActiP11802, 99 interactors
MINTiP11802
STRINGi9606.ENSP00000257904

Chemistry databases

BindingDBiP11802
ChEMBLiCHEMBL331
DrugBankiDB03496 Flavopiridol
DB09073 Palbociclib
DB02733 Purvalanol
DB11730 Ribociclib
GuidetoPHARMACOLOGYi1976

PTM databases

iPTMnetiP11802
PhosphoSitePlusiP11802

Polymorphism and mutation databases

BioMutaiCDK4
DMDMi1168867

Proteomic databases

EPDiP11802
jPOSTiP11802
MaxQBiP11802
PaxDbiP11802
PeptideAtlasiP11802
PRIDEiP11802
ProteomicsDBi52805

Protocols and materials databases

The DNASU plasmid repository

More...
DNASUi
1019
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

Comparative Toxicogenomics Database

More...
CTDi
1019
DisGeNETi1019
EuPathDBiHostDB:ENSG00000135446.16

GeneCards: human genes, protein and diseases

More...
GeneCardsi
CDK4
HGNCiHGNC:1773 CDK4
HPAiCAB013116
CAB069405
HPA006024
MalaCardsiCDK4
MIMi123829 gene
609048 phenotype
neXtProtiNX_P11802
OpenTargetsiENSG00000135446
Orphaneti99970 Dedifferentiated liposarcoma
618 Familial melanoma
99971 Well-differentiated liposarcoma
PharmGKBiPA102

GenAtlas: human gene database

More...
GenAtlasi
Search...

Phylogenomic databases

eggNOGiKOG0594 Eukaryota
ENOG410XPP3 LUCA
GeneTreeiENSGT00940000154770
HOGENOMiHOG000233024
HOVERGENiHBG014652
InParanoidiP11802
KOiK02089
OMAiTFSPHKR
OrthoDBi988547at2759
PhylomeDBiP11802
TreeFamiTF101022

Enzyme and pathway databases

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-8878166 Transcriptional regulation by RUNX2
R-HSA-912446 Meiotic recombination
SignaLinkiP11802
SIGNORiP11802

Miscellaneous databases

ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

More...
ChiTaRSi
CDK4 human
EvolutionaryTraceiP11802

The Gene Wiki collection of pages on human genes and proteins

More...
GeneWikii
Cyclin-dependent_kinase_4

Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

More...
GenomeRNAii
1019

Protein Ontology

More...
PROi
PR:P11802

The Stanford Online Universal Resource for Clones and ESTs

More...
SOURCEi
Search...

Gene expression databases

BgeeiENSG00000135446 Expressed in 225 organ(s), highest expression level in right ovary
CleanExiHS_CDK4
ExpressionAtlasiP11802 baseline and differential
GenevisibleiP11802 HS

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit

ProtoNet; Automatic hierarchical classification of proteins

More...
ProtoNeti
Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the ‘Entry information’ section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiCDK4_HUMAN
<p>This subsection of the ‘Entry information’ section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called ‘Primary (citable) accession number’.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: P11802
Secondary accession number(s): B2R9A0
, B4DNF9, O00576, Q6FG61
<p>This subsection of the ‘Entry information’ section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification (‘Last modified’). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1989
Last sequence update: November 1, 1995
Last modified: January 16, 2019
This is version 226 of the entry and version 2 of the sequence. See complete history.
<p>This subsection of the ‘Entry information’ section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>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.

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

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