LOCUS       NM_000075               1865 bp    mRNA    linear   PRI 01-MAR-2025
DEFINITION  Homo sapiens cyclin dependent kinase 4 (CDK4), mRNA.
ACCESSION   NM_000075 NM_032913
VERSION     NM_000075.4
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (bases 1 to 1865)
  AUTHORS   Li,J., Zhao,L., Wu,Z., Huang,S., Wang,J., Chang,Y., Liu,L., Jin,H.,
            Lu,J., Huang,C., Xie,Q., Huang,H. and Su,Z.
  TITLE     SelK promotes glioblastoma cell proliferation by inhibiting
            beta-TrCP1 mediated ubiquitin-dependent degradation of CDK4
  JOURNAL   J Exp Clin Cancer Res 43 (1), 231 (2024)
   PUBMED   39155374
  REMARK    GeneRIF: SelK promotes glioblastoma cell proliferation by
            inhibiting beta-TrCP1 mediated ubiquitin-dependent degradation of
            CDK4.
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 1865)
  AUTHORS   Liu,X., Li,W., Yi,L., Wang,J., Liu,W., Cheng,H. and Ren,S.
  TITLE     CDK4/6 inhibitors dephosphorylate RNF26 to stabilize TSC1 and
            increase the sensitivity of ccRCC to mTOR inhibitors
  JOURNAL   Br J Cancer 131 (3), 444-456 (2024)
   PUBMED   38890443
REFERENCE   3  (bases 1 to 1865)
  AUTHORS   Shi,Y., Wang,Z., Shao,Y., Guang,Q., Zhang,J., Liu,B., Wu,C.,
            Wang,Y. and Sui,P.
  TITLE     Combined SET7/9 and CDK4 inhibition act synergistically against
            osteosarcoma
  JOURNAL   Biochem Biophys Res Commun 708, 149808 (2024)
   PUBMED   38520914
  REMARK    GeneRIF: Combined SET7/9 and CDK4 inhibition act synergistically
            against osteosarcoma.
REFERENCE   4  (bases 1 to 1865)
  AUTHORS   Magrath,J.W., Sampath,S.S., Flinchum,D.A., Hartono,A.B.,
            Goldberg,I.N., Boehling,J.R., Savkovic,S.D. and Lee,S.B.
  TITLE     Comprehensive Transcriptomic Analysis of EWSR1::WT1 Targets
            Identifies CDK4/6 Inhibitors as an Effective Therapy for
            Desmoplastic Small Round Cell Tumors
  JOURNAL   Cancer Res 84 (9), 1426-1442 (2024)
   PUBMED   38588409
  REMARK    GeneRIF: Comprehensive Transcriptomic Analysis of EWSR1::WT1
            Targets Identifies CDK4/6 Inhibitors as an Effective Therapy for
            Desmoplastic Small Round Cell Tumors.
REFERENCE   5  (bases 1 to 1865)
  AUTHORS   Feng,B., Wang,X., Qiu,D., Sun,H., Deng,J., Tan,Y., Ji,K., Xu,S.,
            Zhang,S. and Tang,C.
  TITLE     DDX18 Facilitates the Tumorigenesis of Lung Adenocarcinoma by
            Promoting Cell Cycle Progression through the Upregulation of CDK4
  JOURNAL   Int J Mol Sci 25 (9), 4953 (2024)
   PUBMED   38732173
  REMARK    GeneRIF: DDX18 Facilitates the Tumorigenesis of Lung Adenocarcinoma
            by Promoting Cell Cycle Progression through the Upregulation of
            CDK4.
            Publication Status: Online-Only
REFERENCE   6  (bases 1 to 1865)
  AUTHORS   Hall,M., Bates,S. and Peters,G.
  TITLE     Evidence for different modes of action of cyclin-dependent kinase
            inhibitors: p15 and p16 bind to kinases, p21 and p27 bind to
            cyclins
  JOURNAL   Oncogene 11 (8), 1581-1588 (1995)
   PUBMED   7478582
REFERENCE   7  (bases 1 to 1865)
  AUTHORS   Tassan,J.P., Jaquenoud,M., Leopold,P., Schultz,S.J. and Nigg,E.A.
  TITLE     Identification of human cyclin-dependent kinase 8, a putative
            protein kinase partner for cyclin C
  JOURNAL   Proc Natl Acad Sci U S A 92 (19), 8871-8875 (1995)
   PUBMED   7568034
REFERENCE   8  (bases 1 to 1865)
  AUTHORS   Medema,R.H., Herrera,R.E., Lam,F. and Weinberg,R.A.
  TITLE     Growth suppression by p16ink4 requires functional retinoblastoma
            protein
  JOURNAL   Proc Natl Acad Sci U S A 92 (14), 6289-6293 (1995)
   PUBMED   7603984
REFERENCE   9  (bases 1 to 1865)
  AUTHORS   Mitchell,E.L., White,G.R., Santibanez-Koref,M.F., Varley,J.M. and
            Heighway,J.
  TITLE     Mapping of gene loci in the Q13-Q15 region of chromosome 12
  JOURNAL   Chromosome Res 3 (4), 261-262 (1995)
   PUBMED   7606365
REFERENCE   10 (bases 1 to 1865)
  AUTHORS   Hanks,S.K.
  TITLE     Homology probing: identification of cDNA clones encoding members of
            the protein-serine kinase family
  JOURNAL   Proc Natl Acad Sci U S A 84 (2), 388-392 (1987)
   PUBMED   2948189
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from BI832658.1, BC003644.2,
            AC025165.27 and BQ773564.1.
            
            On Nov 22, 2018 this sequence version replaced NM_000075.3.
            
            Summary: The protein encoded by this gene is a member of the
            Ser/Thr protein kinase family. This protein is highly similar to
            the gene products of S. cerevisiae cdc28 and S. pombe cdc2. It is a
            catalytic subunit of the protein kinase complex that is important
            for cell cycle G1 phase progression. The activity of this kinase is
            restricted to the G1-S phase, which is controlled by the regulatory
            subunits D-type cyclins and CDK inhibitor p16(INK4a). This kinase
            was shown to be responsible for the phosphorylation of
            retinoblastoma gene product (Rb). Mutations in this gene as well as
            in its related proteins including D-type cyclins, p16(INK4a) and Rb
            were all found to be associated with tumorigenesis of a variety of
            cancers. Multiple polyadenylation sites of this gene have been
            reported. [provided by RefSeq, Jul 2008].
            
            Sequence Note: This RefSeq record was created from transcript and
            genomic sequence data to make the sequence consistent with the
            reference genome assembly. The genomic coordinates used for the
            transcript record were based on transcript alignments.
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: SRR1660805.53469.1,
                                           SRR1163658.534659.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1968189, SAMEA1968540
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000257904.11/ ENSP00000257904.5
            RefSeq Select criteria :: based on single protein-coding transcript
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-16                BI832658.1         138-153
            17-1372             BC003644.2         1-1356
            1373-1666           AC025165.27        141845-142138       c
            1667-1865           BQ773564.1         19-217              c
FEATURES             Location/Qualifiers
     source          1..1865
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="12"
                     /map="12q14.1"
     gene            1..1865
                     /gene="CDK4"
                     /gene_synonym="CMM3; PSK-J3"
                     /note="cyclin dependent kinase 4"
                     /db_xref="GeneID:1019"
                     /db_xref="HGNC:HGNC:1773"
                     /db_xref="MIM:123829"
     exon            1..136
                     /gene="CDK4"
                     /gene_synonym="CMM3; PSK-J3"
                     /inference="alignment:Splign:2.1.0"
     exon            137..373
                     /gene="CDK4"
                     /gene_synonym="CMM3; PSK-J3"
                     /inference="alignment:Splign:2.1.0"
     CDS             156..1067
                     /gene="CDK4"
                     /gene_synonym="CMM3; PSK-J3"
                     /EC_number="2.7.11.22"
                     /note="cell division protein kinase 4"
                     /codon_start=1
                     /product="cyclin-dependent kinase 4"
                     /protein_id="NP_000066.1"
                     /db_xref="CCDS:CCDS8953.1"
                     /db_xref="GeneID:1019"
                     /db_xref="HGNC:HGNC:1773"
                     /db_xref="MIM:123829"
                     /translation="MATSRYEPVAEIGVGAYGTVYKARDPHSGHFVALKSVRVPNGGG
                     GGGGLPISTVREVALLRRLEAFEHPNVVRLMDVCATSRTDREIKVTLVFEHVDQDLRT
                     YLDKAPPPGLPAETIKDLMRQFLRGLDFLHANCIVHRDLKPENILVTSGGTVKLADFG
                     LARIYSYQMALTPVVVTLWYRAPEVLLQSTYATPVDMWSVGCIFAEMFRRKPLFCGNS
                     EADQLGKIFDLIGLPPEDDWPRDVSLPRGAFPPRGPRPVQSVVPEMEESGAQLLLEML
                     TFNPHKRISAFRALQHSYLHKDEGNPE"
     exon            374..509
                     /gene="CDK4"
                     /gene_synonym="CMM3; PSK-J3"
                     /inference="alignment:Splign:2.1.0"
     exon            510..677
                     /gene="CDK4"
                     /gene_synonym="CMM3; PSK-J3"
                     /inference="alignment:Splign:2.1.0"
     exon            678..787
                     /gene="CDK4"
                     /gene_synonym="CMM3; PSK-J3"
                     /inference="alignment:Splign:2.1.0"
     exon            788..838
                     /gene="CDK4"
                     /gene_synonym="CMM3; PSK-J3"
                     /inference="alignment:Splign:2.1.0"
     exon            839..974
                     /gene="CDK4"
                     /gene_synonym="CMM3; PSK-J3"
                     /inference="alignment:Splign:2.1.0"
     exon            975..1865
                     /gene="CDK4"
                     /gene_synonym="CMM3; PSK-J3"
                     /inference="alignment:Splign:2.1.0"
     regulatory      1347..1352
                     /regulatory_class="polyA_signal_sequence"
                     /gene="CDK4"
                     /gene_synonym="CMM3; PSK-J3"
                     /note="hexamer: AATAAT"
     polyA_site      1348
                     /gene="CDK4"
                     /gene_synonym="CMM3; PSK-J3"
                     /note="major polyA site"
     polyA_site      1351
                     /gene="CDK4"
                     /gene_synonym="CMM3; PSK-J3"
     polyA_site      1447
                     /gene="CDK4"
                     /gene_synonym="CMM3; PSK-J3"
     regulatory      1846..1851
                     /regulatory_class="polyA_signal_sequence"
                     /gene="CDK4"
                     /gene_synonym="CMM3; PSK-J3"
                     /note="hexamer: AATATA"
     polyA_site      1861
                     /gene="CDK4"
                     /gene_synonym="CMM3; PSK-J3"
     polyA_site      1865
                     /gene="CDK4"
                     /gene_synonym="CMM3; PSK-J3"
ORIGIN      
        1 agcttgcggc ctgtgtctat ggtcgggccc tctgcgtcca gctgctccgg accgagctcg
       61 ggtgtatggg gccgtaggaa ccggctccgg ggccccgata acgggccgcc cccacagcac
      121 cccgggctgg cgtgagggtc tcccttgatc tgagaatggc tacctctcga tatgagccag
      181 tggctgaaat tggtgtcggt gcctatggga cagtgtacaa ggcccgtgat ccccacagtg
      241 gccactttgt ggccctcaag agtgtgagag tccccaatgg aggaggaggt ggaggaggcc
      301 ttcccatcag cacagttcgt gaggtggctt tactgaggcg actggaggct tttgagcatc
      361 ccaatgttgt ccggctgatg gacgtctgtg ccacatcccg aactgaccgg gagatcaagg
      421 taaccctggt gtttgagcat gtagaccagg acctaaggac atatctggac aaggcacccc
      481 caccaggctt gccagccgaa acgatcaagg atctgatgcg ccagtttcta agaggcctag
      541 atttccttca tgccaattgc atcgttcacc gagatctgaa gccagagaac attctggtga
      601 caagtggtgg aacagtcaag ctggctgact ttggcctggc cagaatctac agctaccaga
      661 tggcacttac acccgtggtt gttacactct ggtaccgagc tcccgaagtt cttctgcagt
      721 ccacatatgc aacacctgtg gacatgtgga gtgttggctg tatctttgca gagatgtttc
      781 gtcgaaagcc tctcttctgt ggaaactctg aagccgacca gttgggcaaa atctttgacc
      841 tgattgggct gcctccagag gatgactggc ctcgagatgt atccctgccc cgtggagcct
      901 ttccccccag agggccccgc ccagtgcagt cggtggtacc tgagatggag gagtcgggag
      961 cacagctgct gctggaaatg ctgactttta acccacacaa gcgaatctct gcctttcgag
     1021 ctctgcagca ctcttatcta cataaggatg aaggtaatcc ggagtgagca atggagtggc
     1081 tgccatggaa ggaagaaaag ctgccatttc ccttctggac actgagaggg caatctttgc
     1141 ctttatctct gaggctatgg agggtcctcc tccatctttc tacagagatt actttgctgc
     1201 cttaatgaca ttcccctccc acctctcctt ttgaggcttc tccttctcct tcccatttct
     1261 ctacactaag gggtatgttc cctcttgtcc ctttccctac ctttatattt ggggtccttt
     1321 tttatacagg aaaaacaaaa caaagaaata atggtctttt tttttttttt aatgtttctt
     1381 cctctgtttg gctttgccat tgtgcgattt ggaaaaacca cttggaagaa gggactttcc
     1441 tgcaaaacct taaagactgg ttaaattaca gggcctagga agtcagtgga gccccttgac
     1501 tgacaaagct tagaaaggaa ctgaaattgc ttctttgaat atggatttta ggcggggcgt
     1561 ggtggctcac gcctataatc ccagcacgtt gggaggccaa cgcgggtgga tcacctgagg
     1621 tcaggagttc gagaccagcc tgactaacat ggtgaaaccc tgtctctact aaaaatacaa
     1681 aattagtcag gcgtggtggt gcacacctgt aatcccagct acttgggaga ctgaggcagg
     1741 aggatcgctt gaacccggga ggcagaggtt gcggtgagcc gagatcatgc cattgcactc
     1801 cagcctgggc aacagagcaa gactctgtgt caaaaaaaaa aaaagaatat agatttttaa
     1861 atggc
//
