CDN1B_HUMAN
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 03-AUG-2022, entry version 227.
DE RecName: Full=Cyclin-dependent kinase inhibitor 1B;
DE AltName: Full=Cyclin-dependent kinase inhibitor p27 {ECO:0000303|PubMed:28666995};
DE AltName: Full=p27Kip1 {ECO:0000303|PubMed:8033212};
GN Name=CDKN1B {ECO:0000303|PubMed:20824794};
GN Synonyms=KIP1 {ECO:0000303|PubMed:10831586},
GN p27 {ECO:0000303|PubMed:15509543};
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], PROTEIN SEQUENCE OF 28-79 AND 104-152, AND
RP TISSUE SPECIFICITY.
RC TISSUE=Kidney;
RX 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 potential
RT mediator of extracellular antimitogenic signals.";
RL Cell 78:59-66(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX 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 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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP UBIQUITINATION, AND PHOSPHORYLATION AT THR-187.
RX PubMed=10323868; DOI=10.1101/gad.13.9.1181;
RA Montagnoli A., Fiore F., Eytan E., Carrano A.C., Draetta G.F., Hershko A.,
RA Pagano M.;
RT "Ubiquitination of p27 is regulated by Cdk-dependent phosphorylation and
RT 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 p27(Kip1),
RT increases its protein stability.";
RL J. Biol. Chem. 275:25146-25154(2000).
RN [8]
RP INTERACTION WITH UHMK1, PHOSPHORYLATION AT SER-10, SUBCELLULAR LOCATION,
RP 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., Nabel G.J.,
RA 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 AND
RP YWHAQ, SUBCELLULAR LOCATION, AND MUTAGENESIS OF SER-10; THR-157; THR-187
RP 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 and
RT cytoplasmic localization.";
RL J. Biol. Chem. 277:28706-28713(2002).
RN [10]
RP PHOSPHORYLATION AT THR-157, SUBCELLULAR LOCATION, ASSOCIATION WITH BREAST
RP 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., Fusco A.,
RA Santoro M.;
RT "Cytoplasmic relocalization and inhibition of the cyclin-dependent kinase
RT inhibitor p27(Kip1) by PKB/Akt-mediated phosphorylation in breast cancer.";
RL Nat. Med. 8:1136-1144(2002).
RN [11]
RP PHOSPHORYLATION AT THR-157, INTERACTION WITH AKT1, SUBCELLULAR LOCATION,
RP 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 p27(Kip1) at
RT threonine 157 and modulation of its cellular localization.";
RL Nat. Med. 8:1145-1152(2002).
RN [12]
RP PHOSPHORYLATION AT SER-10 AND THR-198, INTERACTION WITH YWHAE; YWHAH; SFN;
RP YWHAQ; RPS6KA1 AND RPS6KA3, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP 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 S6
RT kinases promotes its binding to 14-3-3 and cytoplasmic 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 TISSUE SPECIFICITY.
RX PubMed=15509543; DOI=10.1016/s0002-9440(10)63430-x;
RA Gooch J.L., Toro J.J., Guler R.L., Barnes J.L.;
RT "Calcineurin A-alpha but not A-beta is required for normal kidney
RT development and function.";
RL Am. J. Pathol. 165:1755-1765(2004).
RN [15]
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 inhibitor
RT p27kip1 in breast cancer.";
RL Cell Cycle 3:1074-1080(2004).
RN [16]
RP INTERACTION WITH CDK1.
RX PubMed=16007079; DOI=10.1038/ncb1284;
RA Aleem E., Kiyokawa H., Kaldis P.;
RT "Cdc2-cyclin E complexes regulate the G1/S phase transition.";
RL Nat. Cell Biol. 7:831-836(2005).
RN [17]
RP PHOSPHORYLATION AT TYR-88 AND TYR-89, DEPHOSPHORYLATION, INTERACTION WITH
RP GRB2; CDK2 AND CDK4, SUBCELLULAR LOCATION, AND MUTAGENESIS OF TYR-74;
RP 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-dependent
RT kinases and subcellular localization of p27Kip1 in the acute promyelocytic
RT leukemia cell line NB4.";
RL Blood 107:1133-1140(2006).
RN [18]
RP INTERACTION WITH CDK4, AND FUNCTION.
RX PubMed=16782892; DOI=10.1128/mcb.02006-05;
RA Bockstaele L., Kooken H., Libert F., Paternot S., Dumont J.E.,
RA de Launoit Y., Roger P.P., Coulonval K.;
RT "Regulated activating Thr172 phosphorylation of cyclin-dependent kinase
RT 4(CDK4): its relationship with cyclins and CDK 'inhibitors'.";
RL Mol. Cell. Biol. 26:5070-5085(2006).
RN [19]
RP UBIQUITINATION, AND MUTAGENESIS OF THR-187.
RX PubMed=16880511; DOI=10.1128/mcb.01630-05;
RA Sabile A., Meyer A.M., Wirbelauer C., Hess D., Kogel U., Scheffner M.,
RA Krek W.;
RT "Regulation of p27 degradation and S-phase progression by Ro52 RING finger
RT protein.";
RL Mol. Cell. Biol. 26:5994-6004(2006).
RN [20]
RP INVOLVEMENT IN MEN4.
RX PubMed=17030811; DOI=10.1073/pnas.0603877103;
RA Pellegata N.S., Quintanilla-Martinez L., Siggelkow H., Samson E., Bink K.,
RA 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 [21]
RP PHOSPHORYLATION AT TYR-74 AND TYR-88 BY SRC.
RX PubMed=17254967; DOI=10.1016/j.cell.2006.11.049;
RA Chu I., Sun J., Arnaout A., Kahn H., Hanna W., Narod S., Sun P., Tan C.K.,
RA Hengst L., Slingerland J.;
RT "p27 phosphorylation by Src regulates inhibition of cyclin E-Cdk2.";
RL Cell 128:281-294(2007).
RN [22]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E.,
RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y.,
RA 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 [23]
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 down-
RT regulating p27Kip1 at the transcriptional and posttranscriptional levels.";
RL Cancer Res. 68:5076-5085(2008).
RN [24]
RP INTERACTION WITH CDK4, PHOSPHORYLATION, FUNCTION, AND MUTAGENESIS OF
RP TYR-74; TYR-88 AND TYR-89.
RX PubMed=19075005; DOI=10.1128/mcb.00898-08;
RA Ray A., James M.K., Larochelle S., Fisher R.P., Blain S.W.;
RT "p27Kip1 inhibits cyclin D-cyclin-dependent kinase 4 by two independent
RT modes.";
RL Mol. Cell. Biol. 29:986-999(2009).
RN [25]
RP DEPHOSPHORYLATION BY PPM1H AT THR-187.
RX PubMed=22586611; DOI=10.1158/2159-8290.cd-11-0062;
RA Lee-Hoeflich S.T., Pham T.Q., Dowbenko D., Munroe X., Lee J., Li L.,
RA Zhou W., Haverty P.M., Pujara K., Stinson J., Chan S.M.,
RA Eastham-Anderson J., Pandita A., Seshagiri S., Hoeflich K.P.,
RA Turashvili G., Gelmon K.A., Aparicio S.A., Davis D.P., Sliwkowski M.X.,
RA Stern H.M.;
RT "PPM1H is a p27 phosphatase implicated in trastuzumab resistance.";
RL Cancer Discov. 1:326-337(2011).
RN [26]
RP PHOSPHORYLATION AT TYR-88 BY JAK2.
RX PubMed=21423214; DOI=10.1038/onc.2011.68;
RA Jakel H., Weinl C., Hengst L.;
RT "Phosphorylation of p27Kip1 by JAK2 directly links cytokine receptor
RT signaling to cell cycle control.";
RL Oncogene 30:3502-3512(2011).
RN [27]
RP PHOSPHORYLATION AT THR-157 AND THR-198 BY CAMK1.
RX PubMed=23707388; DOI=10.1016/j.cellsig.2013.05.012;
RA Mallampalli R.K., Kaercher L., Snavely C., Pulijala R., Chen B.B., Coon T.,
RA Zhao J., Agassandian M.;
RT "Fbxl12 triggers G1 arrest by mediating degradation of calmodulin kinase
RT I.";
RL Cell. Signal. 25:2047-2059(2013).
RN [28]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-10, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [29]
RP PHOSPHORYLATION AT THR-187 BY CDK1 AND CDK2.
RX PubMed=23478441; DOI=10.1016/j.molcel.2013.02.004;
RA Rossi M., Duan S., Jeong Y.T., Horn M., Saraf A., Florens L.,
RA Washburn M.P., Antebi A., Pagano M.;
RT "Regulation of the CRL4(Cdt2) ubiquitin ligase and cell-cycle exit by the
RT SCF(Fbxo11) ubiquitin ligase.";
RL Mol. Cell 49:1159-1166(2013).
RN [30]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 23-106 IN COMPLEX WITH CCNA2 AND
RP CDK2.
RX 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 bound
RT to the cyclin A-Cdk2 complex.";
RL Nature 382:325-331(1996).
RN [31]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 181-190 IN COMPLEX WITH SKP1; SKP2
RP AND CKS1B, PHOSPHORYLATION AT THR-187, MUTAGENESIS OF GLU-185 AND THR-187,
RP AND UBIQUITINATION.
RX PubMed=16209941; DOI=10.1016/j.molcel.2005.09.003;
RA Hao B., Zheng N., Schulman B.A., Wu G., Miller J.J., Pagano M.,
RA Pavletich N.P.;
RT "Structural basis of the Cks1-dependent recognition of p27(Kip1) by the
RT SCF(Skp2) ubiquitin ligase.";
RL Mol. Cell 20:9-19(2005).
RN [32]
RP STRUCTURE BY NMR OF 22-104, PHOSPHORYLATION AT TYR-88, FUNCTION, INDUCTION,
RP INTERACTION WITH LYN, IDENTIFICATION BY MASS SPECTROMETRY, AND MUTAGENESIS
RP OF 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., Waddell M.B.,
RA Jaekel H., Kullmann M., Kriwacki R.W., Hengst L.;
RT "Cdk-inhibitory activity and stability of p27Kip1 are directly regulated by
RT oncogenic tyrosine kinases.";
RL Cell 128:269-280(2007).
RN [33] {ECO:0007744|PDB:5UQ3}
RP X-RAY CRYSTALLOGRAPHY (3.60 ANGSTROMS) IN COMPLEX WITH CDK2 AND SPDYA,
RP FUNCTION, AND SUBUNIT.
RX PubMed=28666995; DOI=10.15252/embj.201796905;
RA McGrath D.A., Fifield B.A., Marceau A.H., Tripathi S., Porter L.A.,
RA Rubin S.M.;
RT "Structural basis of divergent cyclin-dependent kinase activation by
RT Spy1/RINGO proteins.";
RL EMBO J. 36:2251-2262(2017).
RN [34]
RP VARIANT LEU-69, AND CHARACTERIZATION OF VARIANT LEU-69.
RX PubMed=20824794; DOI=10.1002/humu.21354;
RA Molatore S., Marinoni I., Lee M., Pulz E., Ambrosio M.R.,
RA degli Uberti E.C., Zatelli M.C., Pellegata N.S.;
RT "A novel germline CDKN1B mutation causing multiple endocrine tumors:
RT clinical, genetic and functional characterization.";
RL Hum. Mutat. 31:E1825-E1835(2010).
CC -!- FUNCTION: Important regulator of cell cycle progression. Inhibits the
CC kinase activity of CDK2 bound to cyclin A, but has little inhibitory
CC activity on CDK2 bound to SPDYA (PubMed:28666995). Involved in G1
CC arrest. Potent inhibitor of cyclin E- and cyclin A-CDK2 complexes.
CC Forms a complex with cyclin type D-CDK4 complexes and is involved in
CC the assembly, stability, and modulation of CCND1-CDK4 complex
CC activation. Acts either as an inhibitor or an activator of cyclin type
CC D-CDK4 complexes depending on its phosphorylation state and/or
CC stoichometry. {ECO:0000269|PubMed:10831586,
CC ECO:0000269|PubMed:12244301, ECO:0000269|PubMed:16782892,
CC ECO:0000269|PubMed:17254966, ECO:0000269|PubMed:19075005,
CC ECO:0000269|PubMed:28666995}.
CC -!- SUBUNIT: Forms a ternary complex composed of CCNE1, CDK2 and CDKN1B.
CC Interacts directly with CCNE1; the interaction is inhibited by CDK2-
CC dependent phosphorylation on Thr-187. Interacts with COPS5, subunit of
CC the COP9 signalosome complex; the interaction leads to CDKN1B
CC degradation. Interacts with NUP50; the interaction leads to nuclear
CC import and degradation of phosphorylated CDKN1B. Interacts with CCND1
CC and SNX6 (By similarity). Interacts (Thr-198-phosphorylated form) with
CC 14-3-3 proteins, binds strongly YWHAQ, weakly YWHAE and YWHAH, but not
CC YWHAB nor YWHAZ; the interaction with YWHAQ results in translocation to
CC the cytoplasm (PubMed:14504289). Interacts with AKT1 and LYN; the
CC interactions lead to cytoplasmic mislocation, phosphorylation of CDKN1B
CC and inhibition of cell cycle arrest (PubMed:12042314, PubMed:12244301,
CC PubMed:17254966). Forms a ternary complex with CCNA2 and CDK2; CDKN1B
CC inhibits the kinase activity of CDK2 through conformational
CC rearrangements. Interacts (unphosphorylated form) with CDK2. Forms a
CC complex with CDK2 and SPDYA, but does not directly interact with SPDYA
CC (PubMed:12972555, PubMed:28666995). Forms a ternary complex composed of
CC cyclin D, CDK4 and CDKN1B. Interacts (phosphorylated on Tyr-88 and Tyr-
CC 89) with CDK4; the interaction is required for cyclin D and CDK4
CC complex assembly, induces nuclear translocation and activates the CDK4
CC kinase activity. Interacts with GRB2 (PubMed:16195327). Interacts with
CC PIM1 (PubMed:18593906). Identified in a complex with SKP1, SKP2 and
CC CKS1B (PubMed:16209941). Interacts with UHMK1; the interaction leads to
CC cytoplasmic mislocation, phosphorylation of CDKN1B and inhibition of
CC cell cycle arrest (PubMed:12093740). Interacts also with CDK1
CC (PubMed:16007079). Dephosphorylated on Thr-187 by PPM1H, leading to
CC CDKN1B stability (PubMed:22586611). {ECO:0000250,
CC ECO:0000269|PubMed:12042314, ECO:0000269|PubMed:12093740,
CC ECO:0000269|PubMed:12244301, ECO:0000269|PubMed:12972555,
CC ECO:0000269|PubMed:14504289, ECO:0000269|PubMed:16007079,
CC ECO:0000269|PubMed:16195327, ECO:0000269|PubMed:16209941,
CC ECO:0000269|PubMed:16782892, ECO:0000269|PubMed:17254966,
CC ECO:0000269|PubMed:18593906, ECO:0000269|PubMed:19075005,
CC ECO:0000269|PubMed:22586611, ECO:0000269|PubMed:28666995,
CC ECO:0000269|PubMed:8684460}.
CC -!- INTERACTION:
CC P46527; Q8N9N5-2: BANP; NbExp=3; IntAct=EBI-519280, EBI-11524452;
CC P46527; P78396: CCNA1; NbExp=6; IntAct=EBI-519280, EBI-375065;
CC P46527; P20248: CCNA2; NbExp=17; IntAct=EBI-519280, EBI-457097;
CC P46527; P14635: CCNB1; NbExp=2; IntAct=EBI-519280, EBI-495332;
CC P46527; P24385: CCND1; NbExp=5; IntAct=EBI-519280, EBI-375001;
CC P46527; P30279: CCND2; NbExp=6; IntAct=EBI-519280, EBI-748789;
CC P46527; P24864: CCNE1; NbExp=8; IntAct=EBI-519280, EBI-519526;
CC P46527; O96020: CCNE2; NbExp=3; IntAct=EBI-519280, EBI-375033;
CC P46527; P06493: CDK1; NbExp=5; IntAct=EBI-519280, EBI-444308;
CC P46527; P24941: CDK2; NbExp=25; IntAct=EBI-519280, EBI-375096;
CC P46527; P11802: CDK4; NbExp=9; IntAct=EBI-519280, EBI-295644;
CC P46527; Q00535: CDK5; NbExp=9; IntAct=EBI-519280, EBI-1041567;
CC P46527; O15111: CHUK; NbExp=4; IntAct=EBI-519280, EBI-81249;
CC P46527; Q92905: COPS5; NbExp=3; IntAct=EBI-519280, EBI-594661;
CC P46527; Q13616: CUL1; NbExp=2; IntAct=EBI-519280, EBI-359390;
CC P46527; O00505: KPNA3; NbExp=4; IntAct=EBI-519280, EBI-358297;
CC P46527; O15131: KPNA5; NbExp=6; IntAct=EBI-519280, EBI-540602;
CC P46527; P07948: LYN; NbExp=2; IntAct=EBI-519280, EBI-79452;
CC P46527; P33993: MCM7; NbExp=2; IntAct=EBI-519280, EBI-355924;
CC P46527; Q5JR59-3: MTUS2; NbExp=3; IntAct=EBI-519280, EBI-11522433;
CC P46527; P11309-1: PIM1; NbExp=2; IntAct=EBI-519280, EBI-1018629;
CC P46527; P61586: RHOA; NbExp=3; IntAct=EBI-519280, EBI-446668;
CC P46527; Q15418: RPS6KA1; NbExp=2; IntAct=EBI-519280, EBI-963034;
CC P46527; Q9UQR0-1: SCML2; NbExp=2; IntAct=EBI-519280, EBI-16087037;
CC P46527; Q13309: SKP2; NbExp=4; IntAct=EBI-519280, EBI-456291;
CC P46527; Q5MJ70: SPDYA; NbExp=3; IntAct=EBI-519280, EBI-7125479;
CC P46527; P16949: STMN1; NbExp=3; IntAct=EBI-519280, EBI-445909;
CC P46527; Q9NVV9: THAP1; NbExp=3; IntAct=EBI-519280, EBI-741515;
CC P46527; Q12933: TRAF2; NbExp=6; IntAct=EBI-519280, EBI-355744;
CC P46527; P00520: Abl1; Xeno; NbExp=2; IntAct=EBI-519280, EBI-914519;
CC P46527; Q62120: Jak2; Xeno; NbExp=7; IntAct=EBI-519280, EBI-646604;
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Endosome {ECO:0000250}.
CC Note=Nuclear and cytoplasmic in quiescent cells. AKT- or RSK-mediated
CC phosphorylation on Thr-198, binds 14-3-3, translocates to the cytoplasm
CC and promotes cell cycle progression. Mitogen-activated UHMK1
CC phosphorylation on Ser-10 also results in translocation to the
CC cytoplasm and cell cycle progression. Phosphorylation on Ser-10
CC facilitates nuclear export. Translocates to the nucleus on
CC phosphorylation of Tyr-88 and Tyr-89. Colocalizes at the endosome with
CC SNX6; this leads to lysosomal degradation (By similarity).
CC {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in kidney (at protein level)
CC (PubMed:15509543). Expressed in all tissues tested (PubMed:8033212).
CC Highest levels in skeletal muscle, lowest in liver and kidney
CC (PubMed:8033212). {ECO:0000269|PubMed:15509543,
CC ECO:0000269|PubMed:8033212}.
CC -!- INDUCTION: Maximal levels in quiescence cells and early G(1). Levels
CC decrease after mitogen stimulation as cells progress toward S-phase.
CC {ECO:0000269|PubMed:17254966}.
CC -!- DOMAIN: A peptide sequence containing only AA 28-79 retains substantial
CC Kip1 cyclin A/CDK2 inhibitory activity.
CC -!- PTM: Phosphorylated; phosphorylation occurs on serine, threonine and
CC tyrosine residues. Phosphorylation on Ser-10 is the major site of
CC phosphorylation in resting cells, takes place at the G(0)-G(1) phase
CC and leads to protein stability. Phosphorylation on other sites is
CC greatly enhanced by mitogens, growth factors, cMYC and in certain
CC cancer cell lines. The phosphorylated form found in the cytoplasm is
CC inactivate. Phosphorylation on Thr-198 is required for interaction with
CC 14-3-3 proteins. Phosphorylation on Thr-187, by CDK1 and CDK2 leads to
CC protein ubiquitination and proteasomal degradation. Tyrosine
CC phosphorylation promotes this process. Phosphorylation by PKB/AKT1 can
CC be suppressed by LY294002, an inhibitor of the catalytic subunit of
CC PI3K. Phosphorylation on Tyr-88 and Tyr-89 has no effect on binding
CC CDK2, but is required for binding CDK4. Dephosphorylated on tyrosine
CC residues by G-CSF. {ECO:0000269|PubMed:10323868,
CC ECO:0000269|PubMed:10831586, ECO:0000269|PubMed:12042314,
CC ECO:0000269|PubMed:12093740, ECO:0000269|PubMed:14504289,
CC ECO:0000269|PubMed:15280662, ECO:0000269|PubMed:16195327,
CC ECO:0000269|PubMed:16209941, ECO:0000269|PubMed:17254966,
CC ECO:0000269|PubMed:17254967, ECO:0000269|PubMed:18593906,
CC ECO:0000269|PubMed:21423214, ECO:0000269|PubMed:23478441,
CC ECO:0000269|PubMed:23707388}.
CC -!- PTM: Ubiquitinated; in the cytoplasm by the KPC complex (composed of
CC RNF123/KPC1 and UBAC1/KPC2) and, in the nucleus, by SCF(SKP2). The
CC latter requires prior phosphorylation on Thr-187. Ubiquitinated; by a
CC TRIM21-containing SCF(SKP2)-like complex; leads to its degradation.
CC {ECO:0000269|PubMed:10323868, ECO:0000269|PubMed:12042314,
CC ECO:0000269|PubMed:16209941, ECO:0000269|PubMed:23478441}.
CC -!- PTM: Subject to degradation in the lysosome. Interaction with SNX6
CC promotes lysosomal degradation (By similarity). {ECO:0000250}.
CC -!- DISEASE: Multiple endocrine neoplasia 4 (MEN4) [MIM:610755]: Multiple
CC endocrine neoplasia (MEN) syndromes are inherited cancer syndromes of
CC the thyroid. MEN4 is a MEN-like syndrome with a phenotypic overlap of
CC both MEN1 and MEN2. {ECO:0000269|PubMed:17030811}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: Decreased levels of p27Kip1, mainly due to proteasomal
CC degradation, are found in various epithelial tumors originating from
CC lung, breast, colon, ovary, esophagus, thyroid and prostate.
CC -!- SIMILARITY: Belongs to the CDI family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/CDKN1BID116.html";
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/cdkn1b/";
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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 CCDS; CCDS8653.1; -.
DR RefSeq; NP_004055.1; NM_004064.4.
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 PDB; 5UQ3; X-ray; 3.60 A; C=1-198.
DR PDB; 6ATH; X-ray; 1.82 A; C=22-85.
DR PDB; 6P8E; X-ray; 2.30 A; C=25-93.
DR PDB; 6P8F; X-ray; 2.89 A; C=25-106.
DR PDB; 6P8G; X-ray; 2.80 A; C=25-93.
DR PDB; 7B5L; EM; 3.80 A; P=1-198.
DR PDB; 7B5M; EM; 3.91 A; P=1-198.
DR PDB; 7B5R; EM; 3.80 A; P=1-198.
DR PDBsum; 1H27; -.
DR PDBsum; 1JSU; -.
DR PDBsum; 2AST; -.
DR PDBsum; 5UQ3; -.
DR PDBsum; 6ATH; -.
DR PDBsum; 6P8E; -.
DR PDBsum; 6P8F; -.
DR PDBsum; 6P8G; -.
DR PDBsum; 7B5L; -.
DR PDBsum; 7B5M; -.
DR PDBsum; 7B5R; -.
DR AlphaFoldDB; P46527; -.
DR BMRB; P46527; -.
DR SMR; P46527; -.
DR BioGRID; 107461; 117.
DR CORUM; P46527; -.
DR DIP; DIP-33341N; -.
DR IntAct; P46527; 73.
DR MINT; P46527; -.
DR STRING; 9606.ENSP00000228872; -.
DR ChEMBL; CHEMBL3758070; -.
DR MoonDB; P46527; Predicted.
DR iPTMnet; P46527; -.
DR PhosphoSitePlus; P46527; -.
DR BioMuta; CDKN1B; -.
DR SWISS-2DPAGE; P46527; -.
DR CPTAC; CPTAC-1237; -.
DR CPTAC; CPTAC-1238; -.
DR EPD; P46527; -.
DR jPOST; P46527; -.
DR MassIVE; P46527; -.
DR PaxDb; P46527; -.
DR PeptideAtlas; P46527; -.
DR PRIDE; P46527; -.
DR ProteomicsDB; 55741; -.
DR TopDownProteomics; P46527; -.
DR Antibodypedia; 3295; 2716 antibodies from 48 providers.
DR DNASU; 1027; -.
DR Ensembl; ENST00000228872.9; ENSP00000228872.4; ENSG00000111276.12.
DR Ensembl; ENST00000614874.2; ENSP00000507272.1; ENSG00000111276.12.
DR GeneID; 1027; -.
DR KEGG; hsa:1027; -.
DR MANE-Select; ENST00000228872.9; ENSP00000228872.4; NM_004064.5; NP_004055.1.
DR CTD; 1027; -.
DR DisGeNET; 1027; -.
DR GeneCards; CDKN1B; -.
DR HGNC; HGNC:1785; CDKN1B.
DR HPA; ENSG00000111276; Low tissue specificity.
DR MalaCards; CDKN1B; -.
DR MIM; 600778; gene.
DR MIM; 610755; phenotype.
DR neXtProt; NX_P46527; -.
DR OpenTargets; ENSG00000111276; -.
DR Orphanet; 652; Multiple endocrine neoplasia type 1.
DR Orphanet; 276152; Multiple endocrine neoplasia type 4.
DR PharmGKB; PA105; -.
DR VEuPathDB; HostDB:ENSG00000111276; -.
DR eggNOG; KOG4743; Eukaryota.
DR GeneTree; ENSGT00940000159852; -.
DR HOGENOM; CLU_077692_2_0_1; -.
DR InParanoid; P46527; -.
DR OMA; QCAGMRK; -.
DR OrthoDB; 1595421at2759; -.
DR PhylomeDB; P46527; -.
DR TreeFam; TF101038; -.
DR PathwayCommons; P46527; -.
DR Reactome; R-HSA-187577; SCF(Skp2)-mediated degradation of p27/p21.
DR Reactome; R-HSA-198323; AKT phosphorylates targets in the cytosol.
DR Reactome; R-HSA-2559582; Senescence-Associated Secretory Phenotype (SASP).
DR Reactome; R-HSA-2559586; DNA Damage/Telomere Stress Induced Senescence.
DR Reactome; R-HSA-5625900; RHO GTPases activate CIT.
DR Reactome; R-HSA-5674400; Constitutive Signaling by AKT1 E17K in Cancer.
DR Reactome; R-HSA-6804116; TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest.
DR Reactome; R-HSA-69202; Cyclin E associated events during G1/S transition.
DR Reactome; R-HSA-69231; Cyclin D associated events in G1.
DR Reactome; R-HSA-69563; p53-Dependent G1 DNA Damage Response.
DR Reactome; R-HSA-69656; Cyclin A:Cdk2-associated events at S phase entry.
DR Reactome; R-HSA-8849470; PTK6 Regulates Cell Cycle.
DR Reactome; R-HSA-9607240; FLT3 Signaling.
DR Reactome; R-HSA-9617828; FOXO-mediated transcription of cell cycle genes.
DR Reactome; R-HSA-9634638; Estrogen-dependent nuclear events downstream of ESR-membrane signaling.
DR Reactome; R-HSA-9661069; Defective binding of RB1 mutants to E2F1,(E2F2, E2F3).
DR SignaLink; P46527; -.
DR SIGNOR; P46527; -.
DR BioGRID-ORCS; 1027; 20 hits in 1088 CRISPR screens.
DR ChiTaRS; CDKN1B; human.
DR EvolutionaryTrace; P46527; -.
DR GeneWiki; CDKN1B; -.
DR GenomeRNAi; 1027; -.
DR Pharos; P46527; Tbio.
DR PRO; PR:P46527; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; P46527; protein.
DR Bgee; ENSG00000111276; Expressed in pigmented layer of retina and 213 other tissues.
DR ExpressionAtlas; P46527; baseline and differential.
DR Genevisible; P46527; HS.
DR GO; GO:0031464; C:Cul4A-RING E3 ubiquitin ligase complex; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:HGNC-UCL.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005768; C:endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:BHF-UCL.
DR GO; GO:0051087; F:chaperone binding; IBA:GO_Central.
DR GO; GO:0030332; F:cyclin binding; IPI:CAFA.
DR GO; GO:0004861; F:cyclin-dependent protein serine/threonine kinase inhibitor activity; IDA:UniProtKB.
DR GO; GO:0030544; F:Hsp70 protein binding; IEA:Ensembl.
DR GO; GO:0019901; F:protein kinase binding; IPI:CAFA.
DR GO; GO:0004860; F:protein kinase inhibitor activity; IMP:CAFA.
DR GO; GO:0019903; F:protein phosphatase binding; IPI:BHF-UCL.
DR GO; GO:0044877; F:protein-containing complex binding; IPI:CAFA.
DR GO; GO:0048102; P:autophagic cell death; IDA:BHF-UCL.
DR GO; GO:0071236; P:cellular response to antibiotic; IEA:Ensembl.
DR GO; GO:0071285; P:cellular response to lithium ion; IDA:MGI.
DR GO; GO:0071407; P:cellular response to organic cyclic compound; IEA:Ensembl.
DR GO; GO:0090398; P:cellular senescence; TAS:Reactome.
DR GO; GO:0006977; P:DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest; TAS:Reactome.
DR GO; GO:1904019; P:epithelial cell apoptotic process; IEA:Ensembl.
DR GO; GO:0060767; P:epithelial cell proliferation involved in prostate gland development; IEA:Ensembl.
DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; IBA:GO_Central.
DR GO; GO:0007507; P:heart development; ISS:BHF-UCL.
DR GO; GO:0048839; P:inner ear development; IEA:Ensembl.
DR GO; GO:1905179; P:negative regulation of cardiac muscle tissue regeneration; ISS:BHF-UCL.
DR GO; GO:1902807; P:negative regulation of cell cycle G1/S phase transition; IDA:UniProtKB.
DR GO; GO:0030308; P:negative regulation of cell growth; IDA:BHF-UCL.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:UniProtKB.
DR GO; GO:1904030; P:negative regulation of cyclin-dependent protein kinase activity; IMP:CAFA.
DR GO; GO:0045736; P:negative regulation of cyclin-dependent protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:1904036; P:negative regulation of epithelial cell apoptotic process; IEA:Ensembl.
DR GO; GO:0060770; P:negative regulation of epithelial cell proliferation involved in prostate gland development; IEA:Ensembl.
DR GO; GO:0033673; P:negative regulation of kinase activity; IDA:UniProtKB.
DR GO; GO:0045930; P:negative regulation of mitotic cell cycle; IBA:GO_Central.
DR GO; GO:0042326; P:negative regulation of phosphorylation; IDA:BHF-UCL.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:1904706; P:negative regulation of vascular associated smooth muscle cell proliferation; IMP:BHF-UCL.
DR GO; GO:0007219; P:Notch signaling pathway; IEA:Ensembl.
DR GO; GO:0001890; P:placenta development; IEA:Ensembl.
DR GO; GO:0010942; P:positive regulation of cell death; IDA:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IEA:Ensembl.
DR GO; GO:0045737; P:positive regulation of cyclin-dependent protein serine/threonine kinase activity; IEA:Ensembl.
DR GO; GO:0031116; P:positive regulation of microtubule polymerization; IEA:Ensembl.
DR GO; GO:0045732; P:positive regulation of protein catabolic process; IDA:MGI.
DR GO; GO:0006813; P:potassium ion transport; IEA:Ensembl.
DR GO; GO:0051726; P:regulation of cell cycle; IMP:HGNC-UCL.
DR GO; GO:1902806; P:regulation of cell cycle G1/S phase transition; IMP:GO_Central.
DR GO; GO:0000079; P:regulation of cyclin-dependent protein serine/threonine kinase activity; IDA:GO_Central.
DR GO; GO:0007096; P:regulation of exit from mitosis; IEA:Ensembl.
DR GO; GO:2000045; P:regulation of G1/S transition of mitotic cell cycle; IDA:BHF-UCL.
DR GO; GO:1902746; P:regulation of lens fiber cell differentiation; IEA:Ensembl.
DR GO; GO:0043200; P:response to amino acid; IEA:Ensembl.
DR GO; GO:0046686; P:response to cadmium ion; IEA:Ensembl.
DR GO; GO:0032355; P:response to estradiol; IEA:Ensembl.
DR GO; GO:0009749; P:response to glucose; IEA:Ensembl.
DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl.
DR GO; GO:0043434; P:response to peptide hormone; IEA:Ensembl.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0007605; P:sensory perception of sound; IEA:Ensembl.
DR DisProt; DP00018; -.
DR Gene3D; 4.10.365.10; -; 1.
DR IDEAL; IID00049; -.
DR InterPro; IPR003175; CDI_dom.
DR InterPro; IPR044898; CDI_dom_sf.
DR InterPro; IPR029843; CDKN1B.
DR PANTHER; PTHR10265:SF9; PTHR10265:SF9; 1.
DR Pfam; PF02234; CDI; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell cycle; Cytoplasm; Direct protein sequencing; Endosome;
KW Nucleus; Phosphoprotein; Protein kinase inhibitor; Reference proteome;
KW Tumor suppressor; Ubl conjugation.
FT CHAIN 1..198
FT /note="Cyclin-dependent kinase inhibitor 1B"
FT /id="PRO_0000190084"
FT REGION 1..34
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 51..91
FT /note="Interaction with CDK2"
FT /evidence="ECO:0000269|PubMed:28666995"
FT REGION 85..198
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 153..169
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 158..172
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 10
FT /note="Phosphoserine; by UHMK1"
FT /evidence="ECO:0000269|PubMed:10831586,
FT ECO:0000269|PubMed:12042314, ECO:0000269|PubMed:12093740,
FT ECO:0000269|PubMed:14504289, ECO:0007744|PubMed:23186163"
FT MOD_RES 74
FT /note="Phosphotyrosine; by SRC"
FT /evidence="ECO:0000269|PubMed:17254967"
FT MOD_RES 88
FT /note="Phosphotyrosine; by ABL, LYN, SRC and JAK2"
FT /evidence="ECO:0000269|PubMed:16195327,
FT ECO:0000269|PubMed:17254966, ECO:0000269|PubMed:17254967,
FT ECO:0000269|PubMed:21423214"
FT MOD_RES 89
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:16195327"
FT MOD_RES 157
FT /note="Phosphothreonine; by CaMK1, PKB/AKT1 and PIM1"
FT /evidence="ECO:0000269|PubMed:12244301,
FT ECO:0000269|PubMed:12244303, ECO:0000269|PubMed:18593906,
FT ECO:0000269|PubMed:23707388"
FT MOD_RES 170
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P46414"
FT MOD_RES 187
FT /note="Phosphothreonine; by PKB/AKT1, CDK1 and CDK2"
FT /evidence="ECO:0000269|PubMed:10323868,
FT ECO:0000269|PubMed:12042314, ECO:0000269|PubMed:16209941,
FT ECO:0000269|PubMed:23478441"
FT MOD_RES 198
FT /note="Phosphothreonine; by CaMK1, PKB/AKT1, RPS6KA1,
FT RPS6KA3 and PIM1"
FT /evidence="ECO:0000269|PubMed:12042314,
FT ECO:0000269|PubMed:14504289, ECO:0000269|PubMed:15280662,
FT ECO:0000269|PubMed:18593906, ECO:0000269|PubMed:23707388"
FT VARIANT 15
FT /note="R -> W (in dbSNP:rs2066828)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_011871"
FT VARIANT 69
FT /note="P -> L (found in a patient with multiple endocrine
FT tumors; germline mutation; reduced expression levels; shows
FT impaired binding to CDK2; dbSNP:rs777354267)"
FT /evidence="ECO:0000269|PubMed:20824794"
FT /id="VAR_064429"
FT VARIANT 109
FT /note="V -> G (in dbSNP:rs2066827)"
FT /evidence="ECO:0000269|PubMed:15489334, ECO:0000269|Ref.3,
FT ECO:0000269|Ref.4"
FT /id="VAR_011872"
FT MUTAGEN 10
FT /note="S->A: Loss of phosphorylation by UHMK1. No
FT translocation to the cytoplasm. Greater cell cycle arrest."
FT /evidence="ECO:0000269|PubMed:12042314,
FT ECO:0000269|PubMed:12093740, ECO:0000269|PubMed:15280662"
FT MUTAGEN 10
FT /note="S->D: Exported to the cytoplasm. Inhibits cell cycle
FT arrest."
FT /evidence="ECO:0000269|PubMed:12042314,
FT ECO:0000269|PubMed:12093740, ECO:0000269|PubMed:15280662"
FT MUTAGEN 10
FT /note="S->E: Increased stability in vivo and in vitro."
FT /evidence="ECO:0000269|PubMed:12042314,
FT ECO:0000269|PubMed:12093740, ECO:0000269|PubMed:15280662"
FT MUTAGEN 74
FT /note="Y->F: No change in binding CDK4 and no inhibition of
FT CDK4 activity. Translocates to nucleus. No effect on in
FT vitro phosphorylation of CDK4 by CCNH-CDK7."
FT /evidence="ECO:0000269|PubMed:16195327,
FT ECO:0000269|PubMed:19075005"
FT MUTAGEN 88
FT /note="Y->F: Abolishes LYN-mediated phosphorylation,
FT reduces CDK2-mediated phosphorylation on T-187, has greater
FT cell cycle arrest into S-phase, no effect on binding CDK2
FT complexes, reduced CDK4 binding and inhibits CDK4 enzyme
FT activity. No nuclear translocation. No effect on in vitro
FT phosphorylation of CDK4 by CCNH-CDK7. Completely abolishes
FT CDK4 binding; when associated with F-89."
FT /evidence="ECO:0000269|PubMed:16195327,
FT ECO:0000269|PubMed:17254966, ECO:0000269|PubMed:19075005"
FT MUTAGEN 89
FT /note="Y->F: No effect on binding CDK2 complexes, reduced
FT CDK4 binding and greatly inhibits CDK4 enzyme activity. No
FT nuclear translocation. Inhibits in vitro phosphorylation of
FT CDK4 by CCNH-CDK7. Completely abolishes CDK4 binding; when
FT associated with F-88."
FT /evidence="ECO:0000269|PubMed:16195327,
FT ECO:0000269|PubMed:17254966, ECO:0000269|PubMed:19075005"
FT MUTAGEN 157
FT /note="T->A: Greatly reduced PKB/AKT1-mediated
FT phosphorylation. Nuclear location. Inhibits cyclin E/CDK2
FT cell cycle progression. No effect on binding AKT1.
FT Completely abolishes PKB/AKT1-mediated phosphorylation and
FT no cytoplasmic translocation; when associated with A-198."
FT /evidence="ECO:0000269|PubMed:12042314,
FT ECO:0000269|PubMed:12244301, ECO:0000269|PubMed:12244303,
FT ECO:0000269|PubMed:14504289, ECO:0000269|PubMed:15280662"
FT MUTAGEN 161
FT /note="S->A: No change in PKB/AKT1-mediated
FT phosphorylation."
FT /evidence="ECO:0000269|PubMed:12244301"
FT MUTAGEN 162
FT /note="T->A: No change in PKB/AKT1-mediated
FT phosphorylation."
FT /evidence="ECO:0000269|PubMed:12244301"
FT MUTAGEN 185
FT /note="E->A,D,Q: Strongly reduced ubiquitination by a
FT TRIM21-containing SCF(SKP2) complex."
FT /evidence="ECO:0000269|PubMed:16209941"
FT MUTAGEN 187
FT /note="T->A,D: No change in PKB/AKT1- nor UHMK1-mediated
FT phosphorylation."
FT /evidence="ECO:0000269|PubMed:12042314,
FT ECO:0000269|PubMed:12093740, ECO:0000269|PubMed:15280662,
FT ECO:0000269|PubMed:16209941, ECO:0000269|PubMed:16880511"
FT MUTAGEN 187
FT /note="T->A: Abolishes phosphorylation-dependent
FT ubiquitination."
FT /evidence="ECO:0000269|PubMed:12042314,
FT ECO:0000269|PubMed:12093740, ECO:0000269|PubMed:15280662,
FT ECO:0000269|PubMed:16209941, ECO:0000269|PubMed:16880511"
FT MUTAGEN 198
FT /note="T->A,D: Abolishes PKB/AKT1-mediated phosphorylation.
FT 46% cytoplasmic location. Greatly reduced binding to YWHAQ.
FT Equally reduced binding; when associated with A-10 and A-
FT 187. No nuclear import; when associated with A-157.
FT Completely abolishes PKB/AKT1-mediated phosphorylation and
FT no cytoplasmic translocation; when associated with A-157."
FT /evidence="ECO:0000269|PubMed:12042314,
FT ECO:0000269|PubMed:14504289, ECO:0000269|PubMed:15280662"
FT CONFLICT 22
FT /note="E -> D (in Ref. 2; AAD14244)"
FT /evidence="ECO:0000305"
FT HELIX 38..47
FT /evidence="ECO:0007829|PDB:6ATH"
FT TURN 50..53
FT /evidence="ECO:0007829|PDB:1JSU"
FT HELIX 55..60
FT /evidence="ECO:0007829|PDB:6ATH"
FT TURN 64..67
FT /evidence="ECO:0007829|PDB:6ATH"
FT STRAND 71..78
FT /evidence="ECO:0007829|PDB:6ATH"
FT HELIX 86..89
FT /evidence="ECO:0007829|PDB:1JSU"
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
