ID   CDK3_HUMAN              Reviewed;         305 AA.
AC   Q00526;
DT   01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT   01-APR-1993, sequence version 1.
DT   27-MAR-2024, entry version 218.
DE   RecName: Full=Cyclin-dependent kinase 3;
DE            EC=2.7.11.22;
DE   AltName: Full=Cell division protein kinase 3;
GN   Name=CDK3; Synonyms=CDKN3;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Fetal brain;
RX   PubMed=1639063; DOI=10.1002/j.1460-2075.1992.tb05360.x;
RA   Meyerson M., Enders G.H., Wu C.-L., Su L.-K., Gorka C., Nelson C.,
RA   Harlow E., Tsai L.-H.;
RT   "A family of human cdc2-related protein kinases.";
RL   EMBO J. 11:2909-2917(1992).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ILE-226 AND THR-264.
RG   NIEHS SNPs program;
RL   Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   FUNCTION IN G1-S TRANSITION.
RX   PubMed=8846921; DOI=10.1101/gad.10.7.851;
RA   Hofmann F., Livingston D.M.;
RT   "Differential effects of cdk2 and cdk3 on the control of pRb and E2F
RT   function during G1 exit.";
RL   Genes Dev. 10:851-861(1996).
RN   [4]
RP   FUNCTION AS RB1 KINASE, FUNCTION IN G0-G1 TRANSITION, AND INTERACTION WITH
RP   CCNC.
RX   PubMed=15084261; DOI=10.1016/s0092-8674(04)00300-9;
RA   Ren S., Rollins B.J.;
RT   "Cyclin C/cdk3 promotes Rb-dependent G0 exit.";
RL   Cell 117:239-251(2004).
RN   [5]
RP   FUNCTION AS ATF1 KINASE, TISSUE SPECIFICITY, AND INTERACTION WITH ATF1.
RX   PubMed=18794154; DOI=10.1158/0008-5472.can-08-1137;
RA   Zheng D., Cho Y.-Y., Lau A.T.Y., Zhang J., Ma W.-Y., Bode A.M., Dong Z.;
RT   "Cyclin-dependent kinase 3-mediated activating transcription factor 1
RT   phosphorylation enhances cell transformation.";
RL   Cancer Res. 68:7650-7660(2008).
RN   [6]
RP   VARIANTS [LARGE SCALE ANALYSIS] ASN-106; THR-124; HIS-214 AND THR-264.
RX   PubMed=17344846; DOI=10.1038/nature05610;
RA   Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA   Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA   Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA   Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA   Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA   Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA   Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA   Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA   Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA   Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA   Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA   Futreal P.A., Stratton M.R.;
RT   "Patterns of somatic mutation in human cancer genomes.";
RL   Nature 446:153-158(2007).
CC   -!- FUNCTION: Serine/threonine-protein kinase that plays a critical role in
CC       the control of the eukaryotic cell cycle; involved in G0-G1 and G1-S
CC       cell cycle transitions. Interacts with CCNC/cyclin-C during interphase.
CC       Phosphorylates histone H1, ATF1, RB1 and CABLES1. ATF1 phosphorylation
CC       triggers ATF1 transactivation and transcriptional activities, and
CC       promotes cell proliferation and transformation. CDK3/cyclin-C mediated
CC       RB1 phosphorylation is required for G0-G1 transition. Promotes G1-S
CC       transition probably by contributing to the activation of E2F1, E2F2 and
CC       E2F3 in a RB1-independent manner. {ECO:0000269|PubMed:15084261,
CC       ECO:0000269|PubMed:18794154, ECO:0000269|PubMed:8846921}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC         [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC         COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC         ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.22;
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC         threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC         Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC         ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC         EC=2.7.11.22;
CC   -!- SUBUNIT: Interacts with CABLES1 and CABLES2 (By similarity). Interacts
CC       with ATF1. Binding to CCNC/cyclin-C promotes RB1 phosphorylation.
CC       {ECO:0000250, ECO:0000269|PubMed:15084261,
CC       ECO:0000269|PubMed:18794154}.
CC   -!- INTERACTION:
CC       Q00526; P24863: CCNC; NbExp=7; IntAct=EBI-1245761, EBI-395261;
CC       Q00526; P30281: CCND3; NbExp=5; IntAct=EBI-1245761, EBI-375013;
CC       Q00526; P51946: CCNH; NbExp=3; IntAct=EBI-1245761, EBI-741406;
CC       Q00526; Q14094: CCNI; NbExp=3; IntAct=EBI-1245761, EBI-1104653;
CC       Q00526; P38936: CDKN1A; NbExp=6; IntAct=EBI-1245761, EBI-375077;
CC       Q00526; P61024: CKS1B; NbExp=5; IntAct=EBI-1245761, EBI-456371;
CC       Q00526; P33552: CKS2; NbExp=4; IntAct=EBI-1245761, EBI-711840;
CC       Q00526; O15409: FOXP2; NbExp=3; IntAct=EBI-1245761, EBI-983612;
CC       Q00526; P08238: HSP90AB1; NbExp=2; IntAct=EBI-1245761, EBI-352572;
CC       Q00526; Q9UBR4-2: LHX3; NbExp=3; IntAct=EBI-1245761, EBI-12039345;
CC       Q00526; Q969G2: LHX4; NbExp=3; IntAct=EBI-1245761, EBI-2865388;
CC       Q00526; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-1245761, EBI-16439278;
CC       Q00526; Q9H3P2: NELFA; NbExp=3; IntAct=EBI-1245761, EBI-5461341;
CC       Q00526; Q5TZ20: OR2G6; NbExp=3; IntAct=EBI-1245761, EBI-13334799;
CC       Q00526; P32243-2: OTX2; NbExp=3; IntAct=EBI-1245761, EBI-9087860;
CC       Q00526; Q02548: PAX5; NbExp=3; IntAct=EBI-1245761, EBI-296331;
CC       Q00526; P26367: PAX6; NbExp=3; IntAct=EBI-1245761, EBI-747278;
CC       Q00526; Q06710: PAX8; NbExp=3; IntAct=EBI-1245761, EBI-2683132;
CC       Q00526; Q9H0H5: RACGAP1; NbExp=3; IntAct=EBI-1245761, EBI-717233;
CC       Q00526; A6NLX3: SPDYE4; NbExp=3; IntAct=EBI-1245761, EBI-12047907;
CC       Q00526; P62258: YWHAE; NbExp=2; IntAct=EBI-1245761, EBI-356498;
CC       Q00526; A0A384NQ31; NbExp=3; IntAct=EBI-1245761, EBI-12903728;
CC   -!- TISSUE SPECIFICITY: Expressed in cancer cell lines and glioblastoma
CC       tissue. {ECO:0000269|PubMed:18794154}.
CC   -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr
CC       protein kinase family. CDC2/CDKX subfamily. {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC       URL="http://egp.gs.washington.edu/data/cdk3/";
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DR   EMBL; X66357; CAA47001.1; -; mRNA.
DR   EMBL; AY789470; AAV40830.1; -; Genomic_DNA.
DR   CCDS; CCDS11736.1; -.
DR   PIR; S23382; S23382.
DR   RefSeq; NP_001249.1; NM_001258.2.
DR   PDB; 7XQK; X-ray; 2.25 A; A=1-305.
DR   PDB; 8H4R; X-ray; 2.75 A; A=1-305.
DR   PDBsum; 7XQK; -.
DR   PDBsum; 8H4R; -.
DR   AlphaFoldDB; Q00526; -.
DR   SMR; Q00526; -.
DR   BioGRID; 107453; 160.
DR   ComplexPortal; CPX-330; Cyclin C-CDK3 complex.
DR   CORUM; Q00526; -.
DR   DIP; DIP-686N; -.
DR   ELM; Q00526; -.
DR   IntAct; Q00526; 62.
DR   MINT; Q00526; -.
DR   STRING; 9606.ENSP00000410561; -.
DR   BindingDB; Q00526; -.
DR   ChEMBL; CHEMBL4442; -.
DR   DrugCentral; Q00526; -.
DR   GuidetoPHARMACOLOGY; 1975; -.
DR   iPTMnet; Q00526; -.
DR   PhosphoSitePlus; Q00526; -.
DR   SwissPalm; Q00526; -.
DR   BioMuta; CDK3; -.
DR   DMDM; 231726; -.
DR   EPD; Q00526; -.
DR   jPOST; Q00526; -.
DR   MassIVE; Q00526; -.
DR   MaxQB; Q00526; -.
DR   PaxDb; 9606-ENSP00000400088; -.
DR   PeptideAtlas; Q00526; -.
DR   ProteomicsDB; 57848; -.
DR   Antibodypedia; 46111; 166 antibodies from 27 providers.
DR   DNASU; 1018; -.
DR   Ensembl; ENST00000425876.6; ENSP00000410561.1; ENSG00000250506.9.
DR   Ensembl; ENST00000448471.3; ENSP00000400088.1; ENSG00000250506.9.
DR   GeneID; 1018; -.
DR   KEGG; hsa:1018; -.
DR   MANE-Select; ENST00000448471.3; ENSP00000400088.1; NM_001258.4; NP_001249.1.
DR   UCSC; uc010dgt.3; human.
DR   AGR; HGNC:1772; -.
DR   CTD; 1018; -.
DR   DisGeNET; 1018; -.
DR   GeneCards; CDK3; -.
DR   HGNC; HGNC:1772; CDK3.
DR   HPA; ENSG00000250506; Low tissue specificity.
DR   MIM; 123828; gene.
DR   neXtProt; NX_Q00526; -.
DR   OpenTargets; ENSG00000250506; -.
DR   PharmGKB; PA26309; -.
DR   VEuPathDB; HostDB:ENSG00000250506; -.
DR   eggNOG; KOG0594; Eukaryota.
DR   GeneTree; ENSGT00940000153335; -.
DR   InParanoid; Q00526; -.
DR   OMA; PDETKWP; -.
DR   OrthoDB; 244018at2759; -.
DR   PhylomeDB; Q00526; -.
DR   TreeFam; TF101021; -.
DR   BRENDA; 2.7.11.22; 2681.
DR   PathwayCommons; Q00526; -.
DR   SignaLink; Q00526; -.
DR   SIGNOR; Q00526; -.
DR   BioGRID-ORCS; 1018; 18 hits in 1185 CRISPR screens.
DR   GeneWiki; Cyclin-dependent_kinase_3; -.
DR   GenomeRNAi; 1018; -.
DR   Pharos; Q00526; Tchem.
DR   PRO; PR:Q00526; -.
DR   Proteomes; UP000005640; Chromosome 17.
DR   RNAct; Q00526; Protein.
DR   Bgee; ENSG00000250506; Expressed in mucosa of transverse colon and 94 other cell types or tissues.
DR   ExpressionAtlas; Q00526; baseline and differential.
DR   GO; GO:0000307; C:cyclin-dependent protein kinase holoenzyme complex; IPI:ComplexPortal.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0030332; F:cyclin binding; IBA:GO_Central.
DR   GO; GO:0004693; F:cyclin-dependent protein serine/threonine kinase activity; IBA:GO_Central.
DR   GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR   GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR   GO; GO:0008283; P:cell population proliferation; TAS:UniProtKB.
DR   GO; GO:0006974; P:DNA damage response; IDA:MGI.
DR   GO; GO:0045023; P:G0 to G1 transition; IDA:ComplexPortal.
DR   GO; GO:0000082; P:G1/S transition of mitotic cell cycle; IBA:GO_Central.
DR   GO; GO:0045746; P:negative regulation of Notch signaling pathway; IDA:ComplexPortal.
DR   GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR   GO; GO:0010389; P:regulation of G2/M transition of mitotic cell cycle; IBA:GO_Central.
DR   GO; GO:0010468; P:regulation of gene expression; IBA:GO_Central.
DR   GO; GO:0010033; P:response to organic substance; IBA:GO_Central.
DR   GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR   CDD; cd07860; STKc_CDK2_3; 1.
DR   Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1.
DR   InterPro; IPR011009; Kinase-like_dom_sf.
DR   InterPro; IPR000719; Prot_kinase_dom.
DR   InterPro; IPR017441; Protein_kinase_ATP_BS.
DR   InterPro; IPR008271; Ser/Thr_kinase_AS.
DR   PANTHER; PTHR24056; CELL DIVISION PROTEIN KINASE; 1.
DR   PANTHER; PTHR24056:SF462; CYCLIN-DEPENDENT KINASE 3; 1.
DR   Pfam; PF00069; Pkinase; 1.
DR   SMART; SM00220; S_TKc; 1.
DR   SUPFAM; SSF56112; Protein kinase-like (PK-like); 1.
DR   PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR   PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR   PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
DR   Genevisible; Q00526; HS.
PE   1: Evidence at protein level;
KW   3D-structure; ATP-binding; Cell cycle; Cell division; Kinase; Mitosis;
KW   Nucleotide-binding; Reference proteome; Serine/threonine-protein kinase;
KW   Transferase.
FT   CHAIN           1..305
FT                   /note="Cyclin-dependent kinase 3"
FT                   /id="PRO_0000085776"
FT   DOMAIN          4..286
FT                   /note="Protein kinase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   ACT_SITE        127
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT                   ECO:0000255|PROSITE-ProRule:PRU10027"
FT   BINDING         10..18
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   BINDING         33
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   VARIANT         106
FT                   /note="S -> N (in a glioblastoma multiforme sample; somatic
FT                   mutation)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041973"
FT   VARIANT         124
FT                   /note="I -> T (in dbSNP:rs34918446)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041974"
FT   VARIANT         214
FT                   /note="R -> H (in dbSNP:rs34670267)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041975"
FT   VARIANT         226
FT                   /note="T -> I (in dbSNP:rs2069532)"
FT                   /evidence="ECO:0000269|Ref.2"
FT                   /id="VAR_021101"
FT   VARIANT         264
FT                   /note="M -> T (in dbSNP:rs17884251)"
FT                   /evidence="ECO:0000269|PubMed:17344846, ECO:0000269|Ref.2"
FT                   /id="VAR_021102"
SQ   SEQUENCE   305 AA;  35046 MW;  1128BE0096EA262A CRC64;
     MDMFQKVEKI GEGTYGVVYK AKNRETGQLV ALKKIRLDLE MEGVPSTAIR EISLLKELKH
     PNIVRLLDVV HNERKLYLVF EFLSQDLKKY MDSTPGSELP LHLIKSYLFQ LLQGVSFCHS
     HRVIHRDLKP QNLLINELGA IKLADFGLAR AFGVPLRTYT HEVVTLWYRA PEILLGSKFY
     TTAVDIWSIG CIFAEMVTRK ALFPGDSEID QLFRIFRMLG TPSEDTWPGV TQLPDYKGSF
     PKWTRKGLEE IVPNLEPEGR DLLMQLLQYD PSQRITAKTA LAHPYFSSPE PSPAARQYVL
     QRFRH
//