ID CDN1B_HUMAN Reviewed; 198 AA. AC P46527; Q16307; Q5U0H2; Q9BUS6; DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1995, sequence version 1. DT 24-NOV-2009, entry version 113. DE RecName: Full=Cyclin-dependent kinase inhibitor 1B; DE AltName: Full=Cyclin-dependent kinase inhibitor p27; DE AltName: Full=p27Kip1; GN Name=CDKN1B; Synonyms=KIP1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 28-79 AND 104-152. RC TISSUE=Kidney; RX MEDLINE=94306518; PubMed=8033212; DOI=10.1016/0092-8674(94)90572-X; RA Polyak K., Lee M.-H., Erdjument-Bromage H., Koff A., Roberts J.M., RA Tempst P., Massague J.; RT "Cloning of p27Kip1, a cyclin-dependent kinase inhibitor and a RT potential mediator of extracellular antimitogenic signals."; RL Cell 78:59-66(1994). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX MEDLINE=95188144; PubMed=7882309; RA Pietenpol J.A., Bohlander S.K., Sato Y., Papadopoulos N., Liu B., RA Friedman C., Trask B.J., Roberts J.M., Kinzler K.W., Rowley J.D.; RT "Assignment of the human p27Kip1 gene to 12p13 and its analysis in RT leukemias."; RL Cancer Res. 55:1206-1210(1995). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLY-109. RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor RT vector."; RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS TRP-15 AND GLY-109. RG NIEHS SNPs program; RL Submitted (FEB-2002) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLY-109. RC TISSUE=Cervix; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP UBIQUITINATION, AND PHOSPHORYLATION. RX PubMed=10323868; RA Montagnoli A., Fiore F., Eytan E., Carrano A.C., Draetta G.F., RA Hershko A., Pagano M.; RT "Ubiquitination of p27 is regulated by Cdk-dependent phosphorylation RT and trimeric complex formation."; RL Genes Dev. 13:1181-1189(1999). RN [7] RP PHOSPHORYLATION AT SER-10, AND FUNCTION. RX PubMed=10831586; DOI=10.1074/jbc.M001144200; RA Ishida N., Kitagawa M., Hatakeyama S., Nakayama K.; RT "Phosphorylation at serine 10, a major phosphorylation site of RT p27(Kip1), increases its protein stability."; RL J. Biol. Chem. 275:25146-25154(2000). RN [8] RP INTERACTION WITH UHMK1, PHOSPHORYLATION AT SER-10, SUBCELLULAR RP LOCATION, AND MUTAGENESIS OF SER-10 AND THR-187. RX PubMed=12093740; DOI=10.1093/emboj/cdf343; RA Boehm M., Yoshimoto T., Crook M.F., Nallamshetty S., True A., RA Nabel G.J., Nabel E.G.; RT "A growth factor-dependent nuclear kinase phosphorylates p27(Kip1) and RT regulates cell cycle progression."; RL EMBO J. 21:3390-3401(2002). RN [9] RP PHOSPHORYLATION AT SER-10; THR-187 AND THR-198, INTERACTION WITH AKT1 RP AND YWHAQ, SUBCELLULAR LOCATION, AND MUTAGENESIS OF SER-10; THR-157; RP THR-187 AND THR-198. RX PubMed=12042314; DOI=10.1074/jbc.M203668200; RA Fujita N., Sato S., Katayama K., Tsuruo T.; RT "Akt-dependent phosphorylation of p27Kip1 promotes binding to 14-3-3 RT and cytoplasmic localization."; RL J. Biol. Chem. 277:28706-28713(2002). RN [10] RP PHOSPHORYLATION AT THR-157, SUBCELLULAR LOCATION, ASSOCIATION WITH RP BREAST CANCER, AND MUTAGENESIS OF THR-157. RX PubMed=12244303; DOI=10.1038/nm762; RA Viglietto G., Motti M.L., Bruni P., Melillo R.M., D'Alessio A., RA Califano D., Vinci F., Chiappetta G., Tsichlis P., Bellacosa A., RA Fusco A., Santoro M.; RT "Cytoplasmic relocalization and inhibition of the cyclin-dependent RT kinase inhibitor p27(Kip1) by PKB/Akt-mediated phosphorylation in RT breast cancer."; RL Nat. Med. 8:1136-1144(2002). RN [11] RP PHOSPHORYLATION AT THR-157, INTERACTION WITH AKT1, SUBCELLULAR RP LOCATION, FUNCTION, AND MUTAGENESIS OF THR-157; SER-161 AND THR-162. RX PubMed=12244301; DOI=10.1038/nm759; RA Shin I., Yakes F.M., Rojo F., Shin N.-Y., Bakin A.V., Baselga J., RA Arteaga C.L.; RT "PKB/Akt mediates cell-cycle progression by phosphorylation of RT p27(Kip1) at threonine 157 and modulation of its cellular RT localization."; RL Nat. Med. 8:1145-1152(2002). RN [12] RP PHOSPHORYLATION AT SER-10 AND THR-198, INTERACTION WITH YWHAE; YWHAH; RP SFN; YWHAQ; RPS6KA4 AND RPS6KA5, SUBCELLULAR LOCATION, AND MUTAGENESIS RP OF THR-157 AND THR-198. RX PubMed=14504289; DOI=10.1074/jbc.M306614200; RA Fujita N., Sato S., Tsuruo T.; RT "Phosphorylation of p27Kip1 at threonine 198 by p90 ribosomal protein RT S6 kinases promotes its binding to 14-3-3 and cytoplasmic RT localization."; RL J. Biol. Chem. 278:49254-49260(2003). RN [13] RP INTERACTION WITH SPDYA. RX PubMed=12972555; DOI=10.1091/mbc.E02-12-0820; RA Porter L.A., Kong-Beltran M., Donoghue D.J.; RT "Spy1 interacts with p27Kip1 to allow G1/S progression."; RL Mol. Biol. Cell 14:3664-3674(2003). RN [14] RP PHOSPHORYLATION AT THR-198, SUBCELLULAR LOCATION, AND MUTAGENESIS OF RP SER-10; THR-157; THR-187 AND THR-198. RX PubMed=15280662; RA Motti M.L., De Marco C., Califano D., Fusco A., Viglietto G.; RT "Akt-dependent T198 phosphorylation of cyclin-dependent kinase RT inhibitor p27kip1 in breast cancer."; RL Cell Cycle 3:1074-1080(2004). RN [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-10, AND MASS RP SPECTROMETRY. RC TISSUE=Epithelium; RX PubMed=15302935; DOI=10.1073/pnas.0404720101; RA Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., RA Li J., Cohn M.A., Cantley L.C., Gygi S.P.; RT "Large-scale characterization of HeLa cell nuclear phosphoproteins."; RL Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004). RN [16] RP PHOSPHORYLATION AT TYR-88 AND TYR-89, DEPHOSPHORYLATION, INTERACTION RP WITH GRB2; CDK2 AND CDK4, SUBCELLULAR LOCATION, AND MUTAGENESIS OF RP TYR-74; TYR-88 AND TYR-89. RX PubMed=16195327; DOI=10.1182/blood-2005-05-1771; RA Kardinal C., Dangers M., Kardinal A., Koch A., Brandt D.T., Tamura T., RA Welte K.; RT "Tyrosine phosphorylation modulates binding preference to cyclin- RT dependent kinases and subcellular localization of p27Kip1 in the acute RT promyelocytic leukemia cell line NB4."; RL Blood 107:1133-1140(2006). RN [17] RP ASSOCIATION WITH MEN4. RX PubMed=17030811; DOI=10.1073/pnas.0603877103; RA Pellegata N.S., Quintanilla-Martinez L., Siggelkow H., Samson E., RA Bink K., Hoefler H., Fend F., Graw J., Atkinson M.J.; RT "Germ-line mutations in p27(Kip1) cause a multiple endocrine neoplasia RT syndrome in rats and humans."; RL Proc. Natl. Acad. Sci. U.S.A. 103:15558-15563(2006). RN [18] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-140, AND MASS RP SPECTROMETRY. RX PubMed=17525332; DOI=10.1126/science.1140321; RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, RA Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., RA Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.; RT "ATM and ATR substrate analysis reveals extensive protein networks RT responsive to DNA damage."; RL Science 316:1160-1166(2007). RN [19] RP INTERACTION WITH PIM1, AND PHOSPHORYLATION AT THR-157 AND THR-198. RX PubMed=18593906; DOI=10.1158/0008-5472.CAN-08-0634; RA Morishita D., Katayama R., Sekimizu K., Tsuruo T., Fujita N.; RT "Pim kinases promote cell cycle progression by phosphorylating and RT down-regulating p27Kip1 at the transcriptional and posttranscriptional RT levels."; RL Cancer Res. 68:5076-5085(2008). RN [20] RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 23-106 OF COMPLEX WITH CDK2 RP AND CG2A. RX MEDLINE=96300318; PubMed=8684460; DOI=10.1038/382325a0; RA Russo A.A., Jeffrey P.D., Patten A.K., Massague J., Pavletich N.P.; RT "Crystal structure of the p27Kip1 cyclin-dependent-kinase inhibitor RT bound to the cyclin A-Cdk2 complex."; RL Nature 382:325-331(1996). RN [21] RP STRUCTURE BY NMR OF 22-104, PHOSPHORYLATION AT TYR-88, FUNCTION, RP INDUCTION, INTERACTION WITH LYN, MASS SPECTROMETRY, AND MUTAGENESIS OF RP TYR-88 AND TYR-89. RX PubMed=17254966; DOI=10.1016/j.cell.2006.11.047; RA Grimmler M., Wang Y., Mund T., Cilensek Z., Keidel E.-M., RA Waddell M.B., Jaekel H., Kullmann M., Kriwacki R.W., Hengst L.; RT "Cdk-inhibitory activity and stability of p27Kip1 are directly RT regulated by oncogenic tyrosine kinases."; RL Cell 128:269-280(2007). CC -!- FUNCTION: Important regulator of cell cycle progression. Involved CC in G1 arrest. Potent inhibitor of cyclin E- and cyclin A-CDK2 CC complexes. Positive regulator of cyclin D-dependent kinases such CC as CDK4. Regulated by phosphorylation and degradation events. CC -!- SUBUNIT: Interacts with NUP50; the interaction leads to nuclear CC import and degradation of phosphorylated p27kip1. Interacts with CC COPS5, subunit of the COP9 signalosome complex; the interaction CC leads to p27KIP degradation. Interacts with SPDYA in the CC SPDYA/CDK2/p27kip1 complex. Interacts (Thr-198 phosphorylated- CC form) with 14-3-3 proteins, binds strongly YWHAQ, weakly YWHAE and CC YWHAH, but not YWHAB nor YWHAZ; the interaction with YWHAQ results CC in translocation to the cytoplasm. Interacts with AKT1, LYN and CC UHMK1; the interactions lead to cytoplasmic mislocation, CC phosphorylation of p27kip1 and inhibition of cell cycle arrest. CC Interacts (unphosphorylated form) with CDK2. Interacts CC (phosphorylated on Tyr-88 and Tyr-89) with CDK4; the interaction CC induces nuclear translocation. Interacts with GRB2. Interacts with CC PIM1. CC -!- INTERACTION: CC P00520:Abl1 (xeno); NbExp=1; IntAct=EBI-519280, EBI-914519; CC P20248:CCNA2; NbExp=4; IntAct=EBI-519280, EBI-457097; CC P14635:CCNB1; NbExp=1; IntAct=EBI-519280, EBI-495332; CC P24385:CCND1; NbExp=2; IntAct=EBI-519280, EBI-375001; CC P24864:CCNE1; NbExp=2; IntAct=EBI-519280, EBI-519526; CC O96020:CCNE2; NbExp=1; IntAct=EBI-519280, EBI-375033; CC P24941:CDK2; NbExp=6; IntAct=EBI-519280, EBI-375096; CC P11802:CDK4; NbExp=2; IntAct=EBI-519280, EBI-295644; CC Q00535:CDK5; NbExp=2; IntAct=EBI-519280, EBI-1041567; CC Q92905:COPS5; NbExp=1; IntAct=EBI-519280, EBI-594661; CC O00505:KPNA3; NbExp=1; IntAct=EBI-519280, EBI-358297; CC O15131:KPNA5; NbExp=3; IntAct=EBI-519280, EBI-540602; CC P07948:LYN; NbExp=2; IntAct=EBI-519280, EBI-79452; CC P12931:SRC; NbExp=1; IntAct=EBI-519280, EBI-621482; CC P16949:STMN1; NbExp=1; IntAct=EBI-519280, EBI-445909; CC P09936:UCHL1; NbExp=1; IntAct=EBI-519280, EBI-714860; CC P07947:YES1; NbExp=1; IntAct=EBI-519280, EBI-515331; CC P31946:YWHAB; NbExp=1; IntAct=EBI-519280, EBI-359815; CC P62258:YWHAE; NbExp=1; IntAct=EBI-519280, EBI-356498; CC P61981:YWHAG; NbExp=1; IntAct=EBI-519280, EBI-359832; CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=Nuclear and CC cytoplasmic in quiescent cells. AKT- or RSK-mediated CC phosphorylation on Thr-198, binds 14-3-3, translocates to the CC cytoplasm and promotes cell cycle progression. Mitogen-activated CC UHMK1 phosphorylation on Ser-10 also results in translocation to CC the cytoplasm and cell cycle progression. Phosphorylation on Ser- CC 10 facilitates nuclear export. Translocates to the nucleus on CC phosphorylation of Tyr-88 and Tyr-89. CC -!- TISSUE SPECIFICITY: Expressed in all tissues tested. Highest CC levels in skeletal muscle, lowest in liver and kidney. CC -!- INDUCTION: Maximal levels in quiescence cells and early G(1). CC Levels decrease after mitogen stimulation as cells progress toward CC S-phase. CC -!- DOMAIN: A peptide sequence containing only AA 28-79 retains CC substantial Kip1 cyclin A/CDK2 inhibitory activity. CC -!- PTM: Phosphorylated; phosphorylation occurs on serine, threonine CC and tyrosine residues. Phosphorylation on Ser-10 is the major site CC of phosphorylation in resting cells, takes place at the G(0)-G(1) CC phase and leads to protein stability. Phosphorylation on other CC sites is greatly enhanced by mitogens, growth factors, cMYC and in CC certain cancer cell lines. The phosphorylated form found in the CC cytoplasm is inactivate. Phosphorylation on Thr-198 is required CC for interaction with 14-3-3 proteins. Phosphorylation on Thr-187, CC by CDK2 leads to protein ubiquitination and proteasomal CC degradation. Tyrosine phosphorylation promotes this process. CC Phosphorylation by PKB/AKT1 can be suppressed by LY294002, an CC inhibitor of the catalytic subunit of PI3K. Phosphorylation on CC Tyr-88 and Tyr-89 has no effect on binding CDK2, but is required CC for binding CDK4. Dephosphorylated on tyrosine residues by G-CSF. CC -!- PTM: Ubiquitinated; in the cytoplasm by the KPC1/KPC2 complex and, CC in the nucleus, by SCF/SKP2. The latter requires prior CC phosphorylation on Thr-187. CC -!- DISEASE: Defects in CDKN1B are the cause of multiple endocrine CC neoplasia type 4 (MEN4) [MIM:610755]. Multiple endocrine neoplasia CC (MEN) syndromes are inherited cancer syndromes of the thyroid. CC MEN4 is a MEN-like syndrome with a phenotypic overlap of both MEN1 CC and MEN2. CC -!- MISCELLANEOUS: Decreased levels of p27Kip1, mainly due to CC proteosomal degradation, are found in various epithelial tumors CC originating from lung, breast, colon, ovary, esophagus, thyroid CC and prostate. CC -!- SIMILARITY: Belongs to the CDI family. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology CC and Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/CDKN1BID116.html"; CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/cdkn1b/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U10906; AAA20240.1; -; mRNA. DR EMBL; S76988; AAD14244.1; -; Genomic_DNA. DR EMBL; S76986; AAD14244.1; JOINED; Genomic_DNA. DR EMBL; BT019553; AAV38360.1; -; mRNA. DR EMBL; BT019554; AAV38361.1; -; mRNA. DR EMBL; AF480891; AAL78041.1; -; Genomic_DNA. DR EMBL; BC001971; AAH01971.1; -; mRNA. DR IPI; IPI00006991; -. DR RefSeq; NP_004055.1; -. DR UniGene; Hs.238990; -. DR PDB; 1H27; X-ray; 2.20 A; E=25-35. DR PDB; 1JSU; X-ray; 2.30 A; C=23-106. DR PDB; 2AST; X-ray; 2.30 A; D=181-190. DR PDBsum; 1H27; -. DR PDBsum; 1JSU; -. DR PDBsum; 2AST; -. DR DisProt; DP00018; -. DR IntAct; P46527; 35. DR STRING; P46527; -. DR PhosphoSite; P46527; -. DR SWISS-2DPAGE; P46527; -. DR PRIDE; P46527; -. DR Ensembl; ENST00000228872; ENSP00000228872; ENSG00000111276; Homo sapiens. DR GeneID; 1027; -. DR KEGG; hsa:1027; -. DR UCSC; uc001rat.1; human. DR CTD; 1027; -. DR GeneCards; GC12P012761; -. DR H-InvDB; HIX0010441; -. DR HGNC; HGNC:1785; CDKN1B. DR HPA; CAB003691; -. DR HPA; CAB021888; -. DR MIM; 600778; gene. DR MIM; 610755; phenotype. DR Orphanet; 652; Multiple endocrine neoplasia type 1. DR PharmGKB; PA105; -. DR HOGENOM; P46527; -. DR HOVERGEN; P46527; -. DR OMA; VNHEELT; -. DR OrthoDB; EOG9WM7DW; -. DR Pathway_Interaction_DB; pi3kciaktpathway; Class I PI3K signaling events mediated by Akt. DR Pathway_Interaction_DB; hnf3apathway; FOXA1 transcription factor network. DR Pathway_Interaction_DB; foxopathway; FoxO family signaling. DR Pathway_Interaction_DB; avb3_integrin_pathway; Integrins in angiogenesis. DR Pathway_Interaction_DB; telomerasepathway; Regulation of Telomerase. DR Reactome; REACT_11061; Signalling by NGF. DR NextBio; 4315; -. DR PMAP-CutDB; P46527; -. DR ArrayExpress; P46527; -. DR Bgee; P46527; -. DR CleanEx; HS_CDKN1B; -. DR Genevestigator; P46527; -. DR GermOnline; ENSG00000111276; Homo sapiens. DR GO; GO:0005829; C:cytosol; EXP:Reactome. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0004861; F:cyclin-dependent protein kinase inhibitor a...; TAS:ProtInc. DR GO; GO:0005515; F:protein binding; IPI:UniProtKB. DR GO; GO:0005072; F:transforming growth factor beta receptor, c...; TAS:ProtInc. DR GO; GO:0048102; P:autophagic cell death; IDA:UniProtKB. DR GO; GO:0007050; P:cell cycle arrest; IMP:HGNC. DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; IDA:UniProtKB. DR GO; GO:0006917; P:induction of apoptosis; IDA:UniProtKB. DR GO; GO:0030308; P:negative regulation of cell growth; IDA:UniProtKB. DR GO; GO:0008285; P:negative regulation of cell proliferation; TAS:ProtInc. DR GO; GO:0032582; P:negative regulation of gene-specific transc...; IDA:UniProtKB. DR GO; GO:0033673; P:negative regulation of kinase activity; IDA:UniProtKB. DR GO; GO:0042326; P:negative regulation of phosphorylation; IDA:UniProtKB. DR GO; GO:0000079; P:regulation of cyclin-dependent protein kina...; TAS:ProtInc. DR InterPro; IPR003175; CDI. DR InterPro; IPR015456; Cyclin_inhib_p27. DR PANTHER; PTHR10265; CDI; 1. DR PANTHER; PTHR10265:SF4; p27_Kip1; 1. DR Pfam; PF02234; CDI; 1. PE 1: Evidence at protein level; KW 3D-structure; Cell cycle; Complete proteome; Cytoplasm; KW Direct protein sequencing; Nucleus; Phosphoprotein; Polymorphism; KW Protein kinase inhibitor; Proto-oncogene; Ubl conjugation. FT CHAIN 1 198 Cyclin-dependent kinase inhibitor 1B. FT /FTId=PRO_0000190084. FT MOTIF 153 169 Nuclear localization signal (Potential). FT MOD_RES 10 10 Phosphoserine; by UHMK1. FT MOD_RES 74 74 Phosphotyrosine; by SRC. FT MOD_RES 88 88 Phosphotyrosine; by ABL, LYN and SRC. FT MOD_RES 89 89 Phosphotyrosine. FT MOD_RES 140 140 Phosphoserine. FT MOD_RES 157 157 Phosphothreonine; by PKB/AKT1 and PIM1. FT MOD_RES 187 187 Phosphothreonine; by PKB/AKT1 and CDK2. FT MOD_RES 198 198 Phosphothreonine; by PKB/AKT1; RPS6KA4; FT RPS6KA5 and PIM1. FT VARIANT 15 15 R -> W (in dbSNP:rs2066828). FT /FTId=VAR_011871. FT VARIANT 109 109 V -> G (in dbSNP:rs2066827). FT /FTId=VAR_011872. FT MUTAGEN 10 10 S->A: Loss of phosphorylation by UHMK1. FT No translocation to the cytoplasm. FT Greater cell cycle arrest. FT MUTAGEN 10 10 S->D: Exported to the cytoplasm. Inhibits FT cell cycle arrest. FT MUTAGEN 10 10 S->E: Increased stability in vivo and in FT vitro. FT MUTAGEN 74 74 Y->F: No change in binding CDK4. FT Translocates to nucleus. FT MUTAGEN 88 88 Y->F: Abolishes LYN-mediated FT phosphorylation. Reduced CDK2 FT phosphorylation on T-187. Greater cell FT cycle arrest into S-phase. No effect on FT binding CDK2 complexes. Reduction of CDK4 FT binding. No nuclear translocation. FT Completely abolishes CDK4 binding; when FT associated with F-89. FT MUTAGEN 89 89 Y->F: No effect on binding CDK2 FT complexes. Reduction of CDK4 binding. No FT nuclear translocation. Completely FT abolishes CDK4 binding; when associated FT with F-88. FT MUTAGEN 157 157 T->A: Greatly reduced PKB/AKT1-mediated FT phosphorylation. Nuclear location. FT Inhibits cyclin E/CDK2 cell cycle FT progression. No effect on binding AKT1. FT Completely abolishes PKB/AKT1-mediated FT phosphorylation and no cytoplasmic FT translocation; when associated with A- FT 198. FT MUTAGEN 161 161 S->A: No change in PKB/AKT1-mediated FT phosphorylation. FT MUTAGEN 162 162 T->A: No change in PKB/AKT1-mediated FT phosphorylation. FT MUTAGEN 187 187 T->A,D: No change in PKB/AKT1- nor UHMK1- FT mediated phosphorylation. FT MUTAGEN 198 198 T->A,D: Abolishes PKB/AKT1-mediated FT phosphorylation. 46% cytoplasmic FT location. Greatly reduced binding to FT YWHAQ. Equally reduced binding; when FT associated with A-10 and A-187. No FT nuclear import; when associated with A- FT 157. Completely abolishes PKB/AKT1- FT mediated phosphorylation and no FT cytoplasmic translocation; when FT associated with A-157. FT CONFLICT 22 22 E -> D (in Ref. 2; AAD14244). FT HELIX 38 49 FT TURN 50 53 FT HELIX 54 60 FT TURN 64 67 FT STRAND 71 74 FT STRAND 77 80 FT HELIX 86 89 SQ SEQUENCE 198 AA; 22073 MW; 1118D58901CDF3FC CRC64; MSNVRVSNGS PSLERMDARQ AEHPKPSACR NLFGPVDHEE LTRDLEKHCR DMEEASQRKW NFDFQNHKPL EGKYEWQEVE KGSLPEFYYR PPRPPKGACK VPAQESQDVS GSRPAAPLIG APANSEDTHL VDPKTDPSDS QTGLAEQCAG IRKRPATDDS STQNKRANRT EENVSDGSPN AGSVEQTPKK PGLRRRQT //