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UniProtKB/Swiss-Prot entry P11802


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name CDK4_HUMAN
Primary accession number P11802
Secondary accession number O00576
Integrated into Swiss-Prot on October 1, 1989
Sequence was last modified on November 1, 1995 (Sequence version 2)
Annotations were last modified on    July 22, 2008 (Entry version 111)
Name and origin of the protein
Protein name Cell division protein kinase 4
Synonyms EC 2.7.11.22
Cyclin-dependent kinase 4
PSK-J3
Gene name
Name: CDK4
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [MRNA].
Hanks S.K.;
Submitted (FEB-1987) to the EMBL/GenBank/DDBJ databases.
[2]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
DOI=10.1006/geno.1997.4727; PubMed=9192850 [NCBI, ExPASy, EBI, Israel, Japan]
Elkahloun A.G., Krizman D.B., Wang Z., Hofmann T.A., Roe B.A., Meltzer P.S.;
"Transcript mapping in a 46-kb sequenced region at the core of 12q13.3 amplification in human cancers.";
Genomics 42:295-301(1997).
[3]
NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT CMM3 CYS-24.
PubMed=7652577 [NCBI, ExPASy, EBI, Israel, Japan]
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.;
"A p16INK4a-insensitive CDK4 mutant targeted by cytolytic T lymphocytes in a human melanoma.";
Science 269:1281-1284(1995).
[4]
NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT CMM3 CYS-24.
DOI=10.1038/ng0196-97; PubMed=8528263 [NCBI, ExPASy, EBI, Israel, Japan]
Zuo L., Weger J., Yang Q., Goldstein A.M., Tucker M.A., Walker G.J., Hayward N., Dracopoli N.C.;
"Germline mutations in the p16INK4a binding domain of CDK4 in familial melanoma.";
Nat. Genet. 12:97-99(1996).
[5]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Rieder M.J., Livingston R.J., Braun A.C., Montoya M.A., Chung M.-W., Miyamoto K.E., Nguyen C.P., Nguyen D.A., Poel C.L., Robertson P.D., Schackwitz W.S., Sherwood J.K., Witrak L.A., Nickerson D.A.;
"NIEHS-SNPs, environmental genome project, NIEHS ES15478, Department of Genome Sciences, Seattle, WA (URL: http://egp.gs.washington.edu).";
Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases.
[6]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Muscle;
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[7]
NUCLEOTIDE SEQUENCE [MRNA] OF 88-188.
PubMed=2948189 [NCBI, ExPASy, EBI, Israel, Japan]
Hanks S.K.;
"Homology probing: identification of cDNA clones encoding members of the protein-serine kinase family.";
Proc. Natl. Acad. Sci. U.S.A. 84:388-392(1987).
[8]
NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 95-182.
PubMed=8221695 [NCBI, ExPASy, EBI, Israel, Japan]
Khatib Z.A., Matsushime H., Valentine M., Shapiro D.N., Sherr C.J., Look A.T.;
"Coamplification of the CDK4 gene with MDM2 and GLI in human sarcomas.";
Cancer Res. 53:5535-5541(1993).
[9]
INTERACTION WITH SEI1.
DOI=10.1101/gad.13.22.3027; PubMed=10580009 [NCBI, ExPASy, EBI, Israel, Japan]
Sugimoto M., Nakamura T., Ohtani N., Hampson L., Hampson I.N., Shimamoto A., Furuichi Y., Okumura K., Niwa S., Taya Y., Hara E.;
"Regulation of CDK4 activity by a novel CDK4-binding protein, p34(SEI-1).";
Genes Dev. 13:3027-3033(1999).
[10]
INTERACTION WITH ZNF655/VIK.
DOI=10.1038/sj.onc.1208043; PubMed=15558030 [NCBI, ExPASy, EBI, Israel, Japan]
Houlard M., Romero-Portillo F., Germani A., Depaux A., Regnier-Ricard F., Gisselbrecht S., Varin-Blank N.;
"Characterization of VIK-1: a new Vav-interacting Kruppel-like protein.";
Oncogene 24:28-38(2005).
[11]
VARIANT CMM3 SER-41.
DOI=10.1002/(SICI)1097-0215(19970904)72:5<780::AID-IJC13>3.0.CO;2-D; PubMed=9311594 [NCBI, ExPASy, EBI, Israel, Japan]
Guldberg P., Kirkin A.F., Gronbaek K., thor Straten P., Ahrenkiel V., Zeuthen J.;
"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.";
Int. J. Cancer 72:780-783(1997).
[12]
VARIANT CMM3 HIS-24.
DOI=10.1093/hmg/7.2.209; PubMed=9425228 [NCBI, ExPASy, EBI, Israel, Japan]
Soufir N., Avril M.-F., Chompret A., Demenais F., Bombled J., Spatz A., Stoppa-Lyonnet D., Benard J., Bressac-De Paillerets B.;
"Prevalence of p16 and CDK4 germline mutations in 48 melanoma-prone families in France.";
Hum. Mol. Genet. 7:209-216(1998).
[13]
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).
[14]
VARIANT [LARGE SCALE ANALYSIS] HIS-122.
DOI=10.1038/nature05610; PubMed=17344846 [NCBI, ExPASy, EBI, Israel, Japan]
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.;
"Patterns of somatic mutation in human cancer genomes.";
Nature 446:153-158(2007).
Comments
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
M14505; AAA35673.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
U81031; AAC39521.2; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
Z48970; CAA88834.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
U37022; AAC50506.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF507942; AAM23014.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC003644; AAH03644.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC005864; AAH05864.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC010153; AAH10153.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
S67448; AAD13991.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
PIR I52695; I52695.
S52841; S52841.
RefSeq NP_000066.1; -.
UniGene Hs.95577
3D structure databases
PDB
1LD2; Model; -; A=1-303.[ExPASy / RCSB / EBI]
PDBsum 1LD2; -.
ModBase P11802.
Protein-protein interaction databases
DIP DIP:24211N; -.
DIP:875N; -.
IntAct P11802; -.
PTM databases
PhosphoSite P11802; -.
Enzyme and pathway databases
Reactome REACT_152; Cell Cycle, Mitotic.
Polymorphism databases
NIEHS-SNPs CDK4.
Organism-specific databases
H-InvDB HIX0010753; -.
HGNC HGNC:1773; CDK4.
GenAtlas CDK4.
HPA CAB015153; -.
MIM 123829; gene. [NCBI / EBI]
155600; phenotype. [NCBI / EBI]
609048; phenotype. [NCBI / EBI]
Orphanet 625; Atypical mole.
618; Melanoma, familial.
PharmGKB PA102; -.
GeneCards P11802.
Gene expression databases
ArrayExpress P11802; -.
CleanEx HS_CDK4; -.
GermOnline ENSG00000135446; Homo sapiens.
Ontologies
GO
GO:0000307; Cellular component: cyclin-dependent protein kinase holoenzyme complex (inferred from direct assay from UniProtKB).
GO:0005829; Cellular component: cytosol (inferred from experiment from Reactome).
GO:0005654; Cellular component: nucleoplasm (inferred from experiment from Reactome).
GO:0004693; Molecular function: cyclin-dependent protein kinase activity (inferred from direct assay from UniProtKB).
GO:0005515; Molecular function: protein binding (inferred from physical interaction from IntAct).
GO:0000082; Biological process: G1/S transition of mitotic cell cycle (inferred from mutant phenotype from UniProtKB).
GO:0048146; Biological process: positive regulation of fibroblast proliferation (inferred from mutant phenotype from UniProtKB).
GO:0006468; Biological process: protein amino acid phosphorylation (inferred from direct assay from UniProtKB).
GO:0010468; Biological process: regulation of gene expression (inferred from mutant phenotype from UniProtKB).
QuickGo view.
Family and domain databases
InterPro IPR000719; Prot_kinase_core.
IPR017441; Protein_kinase_ATP_bd_CS.
IPR017442; Se/Thr_pkinase-rel.
IPR008271; Ser_thr_pkin_AS.
IPR002290; Ser_thr_pkinase.
Graphical view of domain structure.
Pfam PF00069; Pkinase; 1.
Pfam graphical view of domain structure.
ProDom PD000001; Prot_kinase; 1.
[Domain structure / List of seq. sharing at least 1 domain]
SMART SM00220; S_TKc; 1.
SMART graphical view of domain structure.
PROSITE PS00107; PROTEIN_KINASE_ATP; 1.
PS50011; PROTEIN_KINASE_DOM; 1.
PS00108; PROTEIN_KINASE_ST; 1.
PROSITE graphical view of domain structure (profiles).
BLOCKS P11802.
Genome annotation databases
Ensembl ENSG00000135446; Homo sapiens. [Contig view]
GeneID 1019; -.
KEGG hsa:1019; -.
Phylogenomic databases
HOGENOM P11802; -.
HOVERGEN P11802; -.
Other
LinkHub P11802; -.
SOURCE CDK4; Homo sapiens.
ProtoNet P11802.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
3D-structure; ATP-binding; Cell cycle; Cell division; Disease mutation; Kinase; Nucleotide-binding; Phosphoprotein; Polymorphism; Proto-oncogene; Serine/threonine-protein kinase; Transferase.
Features
SEVIEWER logo Feature table viewer FT aligner logo Feature aligner
KeyFrom   To Length Description FTId
CHAIN   1   303  303     Cell division protein kinase 4. PRO_0000085778
DOMAIN   6   295  290     Protein kinase. 
NP_BIND   12    20  9     ATP (By similarity). 
COMPBIAS   42    48  7     Poly-Gly. 
ACT_SITE   140   140        Proton acceptor (By similarity). 
BINDING   35    35        ATP (By similarity). 
MOD_RES   172   172        Phosphothreonine; by CAK (By similarity). 
VARIANT   24    24  1     R -> C (in CMM3; somatic and familial; generates a dominant oncogene resistant to inhibition by p16(INK4a); dbSNP:rs11547328 [NCBI]). VAR_006200 
VARIANT   24    24  1     R -> H (in CMM3). VAR_006201 
VARIANT   41    41  1     N -> S (in CMM3; sporadic). VAR_021152 
VARIANT   82    82  1     R -> Q (in dbSNP:rs3211612 [NCBI]). VAR_029153 
VARIANT   122   122  1     R -> H. VAR_041976 
STRAND   7    15  9      
STRAND   18    25  8      
TURN   26    29  4      
STRAND   30    40  11      
TURN   46    48  3      
HELIX   51    66  16      
STRAND   74    81  8      
STRAND   83    94  12      
HELIX   100   104  5      
HELIX   114   133  20      
HELIX   143   145  3      
STRAND   146   148  3      
STRAND   154   156  3      
STRAND   164   166  3      
TURN   168   170  3      
STRAND   173   175  3      
HELIX   176   179  4      
HELIX   183   186  4      
HELIX   194   209  16      
HELIX   219   230  12      
HELIX   235   237  3      
HELIX   246   248  3      
HELIX   257   260  4      
HELIX   266   275  10      
TURN   280   282  3      
HELIX   286   291  6      
TURN   293   295  3      
Sequence information
Length: 303 AA [This is the length of the unprocessed precursor] Molecular weight: 33730 Da [This is the MW of the unprocessed precursor] CRC64: 0916A0C07403A33A [This is a checksum on the sequence]
        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 

P11802 in FASTA format

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