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P11802

- CDK4_HUMAN

UniProt

P11802 - CDK4_HUMAN

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Protein
Cyclin-dependent kinase 4
Gene
CDK4
Organism
Homo sapiens (Human)
Status
Reviewed - 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)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei35 – 351ATP By similarity
Active sitei140 – 1401Proton acceptor By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi12 – 209ATP By similarity

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. cyclin binding Source: UniProtKB
  3. cyclin-dependent protein serine/threonine kinase activity Source: BHF-UCL
  4. protein binding Source: UniProtKB
  5. protein serine/threonine kinase activity Source: InterPro

GO - Biological processi

  1. G1/S transition of mitotic cell cycle Source: BHF-UCL
  2. cell division Source: UniProtKB-KW
  3. circadian rhythm Source: Ensembl
  4. mitotic cell cycle Source: Reactome
  5. negative regulation of cell cycle arrest Source: UniProtKB
  6. organ regeneration Source: Ensembl
  7. positive regulation of G2/M transition of mitotic cell cycle Source: UniProtKB
  8. positive regulation of apoptotic process Source: Ensembl
  9. positive regulation of cell proliferation Source: BHF-UCL
  10. positive regulation of cell size Source: Ensembl
  11. positive regulation of fibroblast proliferation Source: BHF-UCL
  12. positive regulation of translation Source: Ensembl
  13. protein phosphorylation Source: BHF-UCL
  14. regulation of gene expression Source: BHF-UCL
  15. response to drug Source: UniProtKB
  16. response to hyperoxia Source: Ensembl
  17. response to lead ion Source: Ensembl
  18. response to testosterone Source: Ensembl
  19. response to toxic substance Source: Ensembl
  20. 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

BRENDAi2.7.11.22. 2681.
ReactomeiREACT_169168. Senescence-Associated Secretory Phenotype (SASP).
REACT_169325. Oncogene Induced Senescence.
REACT_169436. Oxidative Stress Induced Senescence.
REACT_27161. Transcriptional regulation of white adipocyte differentiation.
REACT_27271. Meiotic recombination.
REACT_4. Ubiquitin-dependent degradation of Cyclin D1.
REACT_821. Cyclin D associated events in G1.
SignaLinkiP11802.

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
ProteomesiUP000005640: 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.2 Publications

GO - Cellular componenti

  1. chromatin Source: UniProtKB
  2. cyclin-dependent protein kinase holoenzyme complex Source: UniProtKB
  3. cytosol Source: UniProtKB
  4. nuclear membrane Source: UniProtKB
  5. nucleolus Source: UniProtKB
  6. nucleoplasm Source: Reactome
  7. nucleus Source: UniProtKB
  8. perinuclear region of cytoplasm Source: Ensembl
  9. tight junction Source: Ensembl
  10. transcription factor complex Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane, Nucleus

Pathology & Biotechi

Involvement in diseasei

Melanoma, cutaneous malignant 3 (CMM3) [MIM:609048]: A 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.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry.4 Publications
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti24 – 241R → C in CMM3; somatic and familial; generates a dominant oncogene resistant to inhibition by p16(INK4a). 2 Publications
Corresponds to variant rs11547328 [ dbSNP | Ensembl ].
VAR_006200
Natural varianti24 – 241R → H in CMM3. 1 Publication
VAR_006201
Natural varianti41 – 411N → S in CMM3; sporadic. 1 Publication
VAR_021152

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi172 – 1721T → A: Weak enzyme activity towards RB1, but no effect on binding of CCDN1 nor CCDN3. 1 Publication
Mutagenesisi172 – 1721T → E: Retains moderate enzyme activity. 1 Publication
Mutagenesisi173 – 1731P → S: No effect on in vitro phosphorylation by CDK7. Greatly reduced T-172 phosphorylation and enzyme activity. 1 Publication

Keywords - Diseasei

Disease mutation

Organism-specific databases

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11Removed1 Publication
Chaini2 – 303302Cyclin-dependent kinase 4
PRO_0000085778Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanine1 Publication
Modified residuei172 – 1721Phosphothreonine5 Publications

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

MaxQBiP11802.
PaxDbiP11802.
PRIDEiP11802.

PTM databases

PhosphoSiteiP11802.

Expressioni

Gene expression databases

ArrayExpressiP11802.
BgeeiP11802.
CleanExiHS_CDK4.
GenevestigatoriP11802.

Organism-specific databases

HPAiCAB015153.

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.7 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CCND1P2438510EBI-295644,EBI-375001
CCND3P302818EBI-295644,EBI-375013
CDC37Q165436EBI-295644,EBI-295634
CDKN1AP389365EBI-295644,EBI-375077
CDKN1BP465274EBI-295644,EBI-519280
CDKN2AP427719EBI-295644,EBI-375053
CDKN2BP427728EBI-295644,EBI-711280
CDKN2CP427733EBI-295644,EBI-711290
HSP90AB1P082383EBI-295644,EBI-352572
MYCP011062EBI-295644,EBI-447544
RBL1P287492EBI-295644,EBI-971402
ZNF655Q8N7203EBI-295644,EBI-625509

Protein-protein interaction databases

BioGridi107454. 123 interactions.
DIPiDIP-24211N.
DIP-875N.
IntActiP11802. 72 interactions.
MINTiMINT-1201237.
STRINGi9606.ENSP00000257904.

Structurei

Secondary structure

Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi7 – 137
Beta strandi15 – 173
Beta strandi20 – 245
Turni26 – 283
Beta strandi31 – 4010
Helixi51 – 6313
Helixi64 – 663
Beta strandi74 – 829
Beta strandi84 – 9411
Beta strandi97 – 993
Helixi100 – 1056
Turni109 – 1113
Helixi114 – 13320
Turni143 – 1453
Beta strandi146 – 1483
Turni150 – 1523
Beta strandi154 – 1563
Helixi162 – 1698
Helixi172 – 1754
Turni183 – 1853
Beta strandi186 – 1894
Helixi195 – 20814
Beta strandi209 – 2113
Helixi219 – 23012
Turni235 – 2373
Beta strandi242 – 2443
Helixi246 – 2483
Helixi257 – 2604
Helixi266 – 27510
Helixi280 – 2823
Helixi286 – 2905

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
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[»]
ProteinModelPortaliP11802.
SMRiP11802. Positions 5-295.

Miscellaneous databases

EvolutionaryTraceiP11802.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini6 – 295290Protein kinase
Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni50 – 567Required for binding D-type cyclins

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi42 – 487Poly-Gly

Sequence similaritiesi

Phylogenomic databases

eggNOGiCOG0515.
HOGENOMiHOG000233024.
HOVERGENiHBG014652.
InParanoidiP11802.
KOiK02089.
OMAiIDQDLRT.
OrthoDBiEOG73JKVV.
PhylomeDBiP11802.
TreeFamiTF101022.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
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]

Sequencei

Sequence statusi: Complete.

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

P11802-1 [UniParc]FASTAAdd to Basket

« Hide

MATSRYEPVA EIGVGAYGTV YKARDPHSGH FVALKSVRVP NGGGGGGGLP    50
ISTVREVALL RRLEAFEHPN VVRLMDVCAT SRTDREIKVT LVFEHVDQDL 100
RTYLDKAPPP GLPAETIKDL MRQFLRGLDF LHANCIVHRD LKPENILVTS 150
GGTVKLADFG LARIYSYQMA LTPVVVTLWY RAPEVLLQST YATPVDMWSV 200
GCIFAEMFRR KPLFCGNSEA DQLGKIFDLI GLPPEDDWPR DVSLPRGAFP 250
PRGPRPVQSV VPEMEESGAQ LLLEMLTFNP HKRISAFRAL QHSYLHKDEG 300
NPE 303
Length:303
Mass (Da):33,730
Last modified:November 1, 1995 - v2
Checksum:i0916A0C07403A33A
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti24 – 241R → C in CMM3; somatic and familial; generates a dominant oncogene resistant to inhibition by p16(INK4a). 2 Publications
Corresponds to variant rs11547328 [ dbSNP | Ensembl ].
VAR_006200
Natural varianti24 – 241R → H in CMM3. 1 Publication
VAR_006201
Natural varianti41 – 411N → S in CMM3; sporadic. 1 Publication
VAR_021152
Natural varianti82 – 821R → Q.1 Publication
Corresponds to variant rs3211612 [ dbSNP | Ensembl ].
VAR_029153
Natural varianti122 – 1221R → H.1 Publication
Corresponds to variant rs34386532 [ dbSNP | Ensembl ].
VAR_041976

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti117 – 1171I → L in BAG36447. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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.
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.
PIRiI52695.
S52841.
RefSeqiNP_000066.1. NM_000075.3.
UniGeneiHs.95577.

Genome annotation databases

EnsembliENST00000257904; ENSP00000257904; ENSG00000135446.
GeneIDi1019.
KEGGihsa:1019.
UCSCiuc001spv.3. human.

Polymorphism databases

DMDMi1168867.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

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

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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 .
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.
PIRi I52695.
S52841.
RefSeqi NP_000066.1. NM_000075.3.
UniGenei Hs.95577.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
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 [» ]
ProteinModelPortali P11802.
SMRi P11802. Positions 5-295.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 107454. 123 interactions.
DIPi DIP-24211N.
DIP-875N.
IntActi P11802. 72 interactions.
MINTi MINT-1201237.
STRINGi 9606.ENSP00000257904.

Chemistry

BindingDBi P11802.
ChEMBLi CHEMBL3038472.
GuidetoPHARMACOLOGYi 1976.

PTM databases

PhosphoSitei P11802.

Polymorphism databases

DMDMi 1168867.

Proteomic databases

MaxQBi P11802.
PaxDbi P11802.
PRIDEi P11802.

Protocols and materials databases

DNASUi 1019.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000257904 ; ENSP00000257904 ; ENSG00000135446 .
GeneIDi 1019.
KEGGi hsa:1019.
UCSCi uc001spv.3. human.

Organism-specific databases

CTDi 1019.
GeneCardsi GC12M058142.
HGNCi HGNC:1773. CDK4.
HPAi CAB015153.
MIMi 123829. gene.
609048. phenotype.
neXtProti NX_P11802.
Orphaneti 99970. Dedifferentiated liposarcoma.
618. Familial melanoma.
99971. Well-differentiated liposarcoma.
PharmGKBi PA102.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG0515.
HOGENOMi HOG000233024.
HOVERGENi HBG014652.
InParanoidi P11802.
KOi K02089.
OMAi IDQDLRT.
OrthoDBi EOG73JKVV.
PhylomeDBi P11802.
TreeFami TF101022.

Enzyme and pathway databases

BRENDAi 2.7.11.22. 2681.
Reactomei REACT_169168. Senescence-Associated Secretory Phenotype (SASP).
REACT_169325. Oncogene Induced Senescence.
REACT_169436. Oxidative Stress Induced Senescence.
REACT_27161. Transcriptional regulation of white adipocyte differentiation.
REACT_27271. Meiotic recombination.
REACT_4. Ubiquitin-dependent degradation of Cyclin D1.
REACT_821. Cyclin D associated events in G1.
SignaLinki P11802.

Miscellaneous databases

ChiTaRSi Cdk4. human.
EvolutionaryTracei P11802.
GeneWikii Cyclin-dependent_kinase_4.
GenomeRNAii 1019.
NextBioi 35467861.
PROi P11802.
SOURCEi Search...

Gene expression databases

ArrayExpressi P11802.
Bgeei P11802.
CleanExi HS_CDK4.
Genevestigatori P11802.

Family and domain databases

InterProi IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view ]
Pfami PF00069. Pkinase. 1 hit.
[Graphical view ]
SMARTi SM00220. S_TKc. 1 hit.
[Graphical view ]
SUPFAMi SSF56112. SSF56112. 1 hit.
PROSITEi PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. Hanks S.K.
    Submitted (FEB-1987) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "Transcript mapping in a 46-kb sequenced region at the core of 12q13.3 amplification in human cancers."
    Elkahloun A.G., Krizman D.B., Wang Z., Hofmann T.A., Roe B.A., Meltzer P.S.
    Genomics 42:295-301(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  3. "A p16INK4a-insensitive CDK4 mutant targeted by cytolytic T lymphocytes in a human melanoma."
    Wolfel T., Hauer M., Schneider J., Serrano M., Wolfel C., Klehmann-Hieb E., De Plaen E., Hankeln T., Meyer Zum Bueschenfelde K.-H., Beach D.
    Science 269:1281-1284(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT CMM3 CYS-24, CHARACTERIZATION OF VARIANT CYS-24.
  4. "Germline mutations in the p16INK4a binding domain of CDK4 in familial melanoma."
    Zuo L., Weger J., Yang Q., Goldstein A.M., Tucker M.A., Walker G.J., Hayward N., Dracopoli N.C.
    Nat. Genet. 12:97-99(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT CMM3 CYS-24, CHARACTERIZATION OF VARIANT CYS-24.
  5. NIEHS SNPs program
    Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT GLN-82.
  6. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
  7. "Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
    Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
    Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
  8. "The finished DNA sequence of human chromosome 12."
    Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R.
    , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A.
    Nature 440:346-351(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  9. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  10. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Muscle.
  11. "Homology probing: identification of cDNA clones encoding members of the protein-serine kinase family."
    Hanks S.K.
    Proc. Natl. Acad. Sci. U.S.A. 84:388-392(1987) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 88-188.
  12. "Coamplification of the CDK4 gene with MDM2 and GLI in human sarcomas."
    Khatib Z.A., Matsushime H., Valentine M., Shapiro D.N., Sherr C.J., Look A.T.
    Cancer Res. 53:5535-5541(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 95-182.
  13. "The consensus motif for phosphorylation by cyclin D1-Cdk4 is different from that for phosphorylation by cyclin A/E-Cdk2."
    Kitagawa M., Higashi H., Jung H.K., Suzuki-Takahashi I., Ikeda M., Tamai K., Kato J., Segawa K., Yoshida E., Nishimura S., Taya Y.
    EMBO J. 15:7060-7069(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  14. Cited for: INTERACTION WITH CDKN1A; CCND1 AND CCND3, SUBCELLULAR LOCATION, CATALYTIC ACTIVITY.
  15. Cited for: INTERACTION WITH SEI1.
  16. "Cyclin-dependent kinases regulate the antiproliferative function of Smads."
    Matsuura I., Denissova N.G., Wang G., He D., Long J., Liu F.
    Nature 430:226-231(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  17. Cited for: INTERACTION WITH ZNF655.
  18. "Regulated activating Thr172 phosphorylation of cyclin-dependent kinase 4(CDK4): its relationship with cyclins and CDK 'inhibitors'."
    Bockstaele L., Kooken H., Libert F., Paternot S., Dumont J.E., de Launoit Y., Roger P.P., Coulonval K.
    Mol. Cell. Biol. 26:5070-5085(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT THR-172, INTERACTION WITH CCND1; CCND3; CDKN2A AND CDKN1B, MUTAGENESIS OF THR-172.
  19. "Migratory localization of cyclin D2-Cdk4 complex suggests a spatial regulation of the G1-S transition."
    Wang Z., Xie Y., Zhang L., Zhang H., An X., Wang T., Meng A.
    Cell Struct. Funct. 33:171-183(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, FUNCTION, INTERACTION WITH CCND2.
  20. "Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
    Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
    Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
  21. "Zinc finger transcription factor INSM1 interrupts cyclin D1 and CDK4 binding and induces cell cycle arrest."
    Zhang T., Liu W.D., Saunee N.A., Breslin M.B., Lan M.S.
    J. Biol. Chem. 284:5574-5581(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH CCND1.
  22. "p27Kip1 inhibits cyclin D-cyclin-dependent kinase 4 by two independent modes."
    Ray A., James M.K., Larochelle S., Fisher R.P., Blain S.W.
    Mol. Cell. Biol. 29:986-999(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH CDKN1B, PHOSPHORYLATION, CATALYTIC ACTIVITY.
  23. "Differential regulation of cyclin-dependent kinase 4 (CDK4) and CDK6, evidence that CDK4 might not be activated by CDK7, and design of a CDK6 activating mutation."
    Bockstaele L., Bisteau X., Paternot S., Roger P.P.
    Mol. Cell. Biol. 29:4188-4200(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT THR-172, ENZYME REGULATION, MUTAGENESIS OF PRO-173.
  24. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-172, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  25. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  26. Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF THR-172-PHOSPHORYLATED WILD TYPE AND MUTANTS ALA-172; PHE-172 AND ASP-172 IN COMPLEX WITH CCND1, IDENTIFICATION BY MASS SPECTROMETRY, PHOSPHORYLATION AT THR-172, CATALYTIC ACTIVITY.
  27. "The structure of CDK4/cyclin D3 has implications for models of CDK activation."
    Takaki T., Echalier A., Brown N.R., Hunt T., Endicott J.A., Noble M.E.
    Proc. Natl. Acad. Sci. U.S.A. 106:4171-4176(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF NONPHOSPHORYLATED FORM IN COMPLEX WITH CCND3, PHOSPHORYLATION AT THR-172, IDENTIFICATION BY MASS SPECTROMETRY.
  28. "Complete scanning of the CDK4 gene by denaturing gradient gel electrophoresis: a novel missense mutation but low overall frequency of mutations in sporadic metastatic malignant melanoma."
    Guldberg P., Kirkin A.F., Gronbaek K., thor Straten P., Ahrenkiel V., Zeuthen J.
    Int. J. Cancer 72:780-783(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT CMM3 SER-41.
  29. "Prevalence of p16 and CDK4 germline mutations in 48 melanoma-prone families in France."
    Soufir N., Avril M.-F., Chompret A., Demenais F., Bombled J., Spatz A., Stoppa-Lyonnet D., Benard J., Bressac-De Paillerets B.
    Hum. Mol. Genet. 7:209-216(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT CMM3 HIS-24.
  30. "Patterns of somatic mutation in human cancer genomes."
    Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.
    , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
    Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT [LARGE SCALE ANALYSIS] HIS-122.

Entry informationi

Entry nameiCDK4_HUMAN
AccessioniPrimary (citable) accession number: P11802
Secondary accession number(s): B2R9A0, O00576, Q6FG61
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1989
Last sequence update: November 1, 1995
Last modified: September 3, 2014
This is version 179 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

External Data

Dasty 3

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