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P11802 (CDK4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 175. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Cyclin-dependent kinase 4

EC=2.7.11.22
Alternative name(s):
Cell division protein kinase 4
PSK-J3
Gene names
Name:CDK4
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length303 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.12 Ref.15 Ref.18

Catalytic activity

ATP + a protein = ADP + a phosphoprotein. Ref.13 Ref.21 Ref.25

Enzyme regulation

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. Ref.22

Subunit structure

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. Ref.13 Ref.14 Ref.16 Ref.17 Ref.18 Ref.20 Ref.21

Subcellular location

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. Ref.13 Ref.18

Post-translational modification

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. Ref.17 Ref.21 Ref.22 Ref.25 Ref.26

Involvement in disease

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. Ref.3 Ref.4 Ref.27 Ref.28

Sequence similarities

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

Contains 1 protein kinase domain.

Ontologies

Keywords
   Biological processCell cycle
Cell division
   Cellular componentCytoplasm
Membrane
Nucleus
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMAcetylation
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processG1/S transition of mitotic cell cycle

Inferred from mutant phenotype PubMed 7603984. Source: BHF-UCL

cell division

Inferred from electronic annotation. Source: UniProtKB-KW

circadian rhythm

Inferred from electronic annotation. Source: Ensembl

mitotic cell cycle

Traceable author statement. Source: Reactome

negative regulation of cell cycle arrest

Inferred from direct assay Ref.20. Source: UniProtKB

organ regeneration

Inferred from electronic annotation. Source: Ensembl

positive regulation of G2/M transition of mitotic cell cycle

Inferred from direct assay Ref.20. Source: UniProtKB

positive regulation of apoptotic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell proliferation

Inferred from mutant phenotype PubMed 7603984. Source: BHF-UCL

positive regulation of cell size

Inferred from electronic annotation. Source: Ensembl

positive regulation of fibroblast proliferation

Inferred from mutant phenotype PubMed 17420273. Source: BHF-UCL

positive regulation of translation

Inferred from electronic annotation. Source: Ensembl

protein phosphorylation

Inferred from direct assay PubMed 8114739. Source: BHF-UCL

regulation of gene expression

Inferred from mutant phenotype PubMed 17420273. Source: BHF-UCL

response to drug

Inferred from genetic interaction PubMed 18291362. Source: UniProtKB

response to hyperoxia

Inferred from electronic annotation. Source: Ensembl

response to lead ion

Inferred from electronic annotation. Source: Ensembl

response to testosterone

Inferred from electronic annotation. Source: Ensembl

response to toxic substance

Inferred from electronic annotation. Source: Ensembl

signal transduction

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentchromatin

Inferred from direct assay Ref.18. Source: UniProtKB

cyclin-dependent protein kinase holoenzyme complex

Inferred from direct assay Ref.18. Source: UniProtKB

cytosol

Inferred from direct assay Ref.18. Source: UniProtKB

nuclear membrane

Inferred from direct assay Ref.18. Source: UniProtKB

nucleolus

Inferred from direct assay Ref.18. Source: UniProtKB

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay Ref.18. Source: UniProtKB

perinuclear region of cytoplasm

Inferred from electronic annotation. Source: Ensembl

tight junction

Inferred from electronic annotation. Source: Ensembl

transcription factor complex

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

cyclin binding

Inferred from physical interaction Ref.20. Source: UniProtKB

cyclin-dependent protein serine/threonine kinase activity

Inferred from direct assay PubMed 8114739. Source: BHF-UCL

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.19
Chain2 – 303302Cyclin-dependent kinase 4
PRO_0000085778

Regions

Domain6 – 295290Protein kinase
Nucleotide binding12 – 209ATP By similarity
Region50 – 567Required for binding D-type cyclins
Compositional bias42 – 487Poly-Gly

Sites

Active site1401Proton acceptor By similarity
Binding site351ATP By similarity

Amino acid modifications

Modified residue21N-acetylalanine Ref.19
Modified residue1721Phosphothreonine Ref.17 Ref.22 Ref.23 Ref.25 Ref.26

Natural variations

Natural variant241R → C in CMM3; somatic and familial; generates a dominant oncogene resistant to inhibition by p16(INK4a). Ref.3 Ref.4
Corresponds to variant rs11547328 [ dbSNP | Ensembl ].
VAR_006200
Natural variant241R → H in CMM3. Ref.28
VAR_006201
Natural variant411N → S in CMM3; sporadic. Ref.27
VAR_021152
Natural variant821R → Q. Ref.5
Corresponds to variant rs3211612 [ dbSNP | Ensembl ].
VAR_029153
Natural variant1221R → H. Ref.30
Corresponds to variant rs34386532 [ dbSNP | Ensembl ].
VAR_041976

Experimental info

Mutagenesis1721T → A: Weak enzyme activity towards RB1, but no effect on binding of CCDN1 nor CCDN3. Ref.17
Mutagenesis1721T → E: Retains moderate enzyme activity. Ref.17
Mutagenesis1731P → S: No effect on in vitro phosphorylation by CDK7. Greatly reduced T-172 phosphorylation and enzyme activity. Ref.22

Secondary structure

.......................................................... 303
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P11802 [UniParc].

Last modified November 1, 1995. Version 2.
Checksum: 0916A0C07403A33A

FASTA30333,730
        10         20         30         40         50         60 
MATSRYEPVA EIGVGAYGTV YKARDPHSGH FVALKSVRVP NGGGGGGGLP ISTVREVALL 

        70         80         90        100        110        120 
RRLEAFEHPN VVRLMDVCAT SRTDREIKVT LVFEHVDQDL RTYLDKAPPP GLPAETIKDL 

       130        140        150        160        170        180 
MRQFLRGLDF LHANCIVHRD LKPENILVTS GGTVKLADFG LARIYSYQMA LTPVVVTLWY 

       190        200        210        220        230        240 
RAPEVLLQST YATPVDMWSV GCIFAEMFRR KPLFCGNSEA DQLGKIFDLI GLPPEDDWPR 

       250        260        270        280        290        300 
DVSLPRGAFP PRGPRPVQSV VPEMEESGAQ LLLEMLTFNP HKRISAFRAL QHSYLHKDEG 


NPE 

« Hide

References

« Hide 'large scale' references
[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]"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].
[7]"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. expand/collapse author list , 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].
[8]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]"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.
[10]"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.
[11]"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.
[12]"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.
[13]"New functional activities for the p21 family of CDK inhibitors."
LaBaer J., Garrett M.D., Stevenson L.F., Slingerland J.M., Sandhu C., Chou H.S., Fattaey A., Harlow E.
Genes Dev. 11:847-862(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CDKN1A; CCND1 AND CCND3, SUBCELLULAR LOCATION, CATALYTIC ACTIVITY.
[14]"Regulation of CDK4 activity by a novel CDK4-binding protein, p34(SEI-1)."
Sugimoto M., Nakamura T., Ohtani N., Hampson L., Hampson I.N., Shimamoto A., Furuichi Y., Okumura K., Niwa S., Taya Y., Hara E.
Genes Dev. 13:3027-3033(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SEI1.
[15]"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.
[16]"Characterization of VIK-1: a new Vav-interacting Kruppel-like protein."
Houlard M., Romero-Portillo F., Germani A., Depaux A., Regnier-Ricard F., Gisselbrecht S., Varin-Blank N.
Oncogene 24:28-38(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ZNF655.
[17]"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.
[18]"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.
[19]"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].
[20]"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.
[21]"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.
[22]"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.
[23]"Large-scale proteomics analysis of the human kinome."
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H.
Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-172, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[24]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[25]"Crystal structure of human CDK4 in complex with a D-type cyclin."
Day P.J., Cleasby A., Tickle I.J., O'Reilly M., Coyle J.E., Holding F.P., McMenamin R.L., Yon J., Chopra R., Lengauer C., Jhoti H.
Proc. Natl. Acad. Sci. U.S.A. 106:4166-4170(2009) [PubMed] [Europe PMC] [Abstract]
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.
[26]"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.
[27]"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.
[28]"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.
[29]Erratum
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. 7:941-941(1998)
[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. expand/collapse author list , 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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
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.
PIRI52695.
S52841.
RefSeqNP_000066.1. NM_000075.3.
UniGeneHs.95577.

3D structure databases

PDBe
RCSB PDB
PDBj
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[»]
ProteinModelPortalP11802.
SMRP11802. Positions 5-295.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107454. 169 interactions.
DIPDIP-24211N.
DIP-875N.
IntActP11802. 72 interactions.
MINTMINT-1201237.
STRING9606.ENSP00000257904.

Chemistry

BindingDBP11802.
ChEMBLCHEMBL1907601.
GuidetoPHARMACOLOGY1976.

PTM databases

PhosphoSiteP11802.

Polymorphism databases

DMDM1168867.

Proteomic databases

PaxDbP11802.
PRIDEP11802.

Protocols and materials databases

DNASU1019.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000257904; ENSP00000257904; ENSG00000135446.
GeneID1019.
KEGGhsa:1019.
UCSCuc001spv.3. human.

Organism-specific databases

CTD1019.
GeneCardsGC12M058142.
HGNCHGNC:1773. CDK4.
HPACAB015153.
MIM123829. gene.
609048. phenotype.
neXtProtNX_P11802.
Orphanet99970. Dedifferentiated liposarcoma.
618. Familial melanoma.
99971. Well-differentiated liposarcoma.
PharmGKBPA102.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000233024.
HOVERGENHBG014652.
InParanoidP11802.
KOK02089.
OMAYLQKAEG.
OrthoDBEOG73JKVV.
PhylomeDBP11802.
TreeFamTF101022.

Enzyme and pathway databases

BRENDA2.7.11.22. 2681.
ReactomeREACT_111183. Meiosis.
REACT_115566. Cell Cycle.
REACT_120956. Cellular responses to stress.
SignaLinkP11802.

Gene expression databases

ArrayExpressP11802.
BgeeP11802.
CleanExHS_CDK4.
GenevestigatorP11802.

Family and domain databases

InterProIPR011009. 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]
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSCdk4. human.
EvolutionaryTraceP11802.
GeneWikiCyclin-dependent_kinase_4.
GenomeRNAi1019.
NextBio4283.
PROP11802.
SOURCESearch...

Entry information

Entry nameCDK4_HUMAN
AccessionPrimary (citable) accession number: P11802
Secondary accession number(s): O00576, Q6FG61
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1989
Last sequence update: November 1, 1995
Last modified: April 16, 2014
This is version 175 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

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

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM