CDN1B_MOUSE
ID CDN1B_MOUSE Reviewed; 197 AA.
AC P46414; Q8BG74;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2012, sequence version 2.
DT 03-AUG-2022, entry version 177.
DE RecName: Full=Cyclin-dependent kinase inhibitor 1B;
DE AltName: Full=Cyclin-dependent kinase inhibitor p27 {ECO:0000303|PubMed:8033213};
DE AltName: Full=p27Kip1 {ECO:0000303|PubMed:8033212};
GN Name=Cdkn1b;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RX PubMed=8033213; DOI=10.1016/0092-8674(94)90573-8;
RA Toyoshima H., Hunter T.;
RT "p27, a novel inhibitor of G1 cyclin-Cdk protein kinase activity, is
RT related to p21.";
RL Cell 78:67-74(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Embryo;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Adipose tissue, Corpus striatum, and Liver;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Salivary gland;
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 INTERACTION WITH CCND1 IN THE CCND1-CDK4-CDKN1B COMPLEX.
RX PubMed=8534916; DOI=10.1091/mbc.6.9.1197;
RA Poon R.Y., Toyoshima H., Hunter T.;
RT "Redistribution of the CDK inhibitor p27 between different cyclin.CDK
RT complexes in the mouse fibroblast cell cycle and in cells arrested with
RT lovastatin or ultraviolet irradiation.";
RL Mol. Biol. Cell 6:1197-1213(1995).
RN [7]
RP PHOSPHORYLATION AT THR-187, INTERACTION WITH CCNE1 IN CCNE1/ CDK2/CDKN1B
RP COMPLEX, FUNCTION, AND MUTAGENESIS OF SER-10 AND THR-187.
RX PubMed=9399644; DOI=10.1038/sj.onc.1201440;
RA Mueller D., Bouchard C., Rudolph B., Steiner P., Stuckmann I., Saffrich R.,
RA Ansorge W., Huttner W., Eilers M.;
RT "Cdk2-dependent phosphorylation of p27 facilitates its Myc-induced release
RT from cyclin E/cdk2 complexes.";
RL Oncogene 15:2561-2576(1997).
RN [8]
RP INTERACTION WITH COPS5.
RX PubMed=10086358; DOI=10.1038/18230;
RA Tomoda K., Kubota Y., Kato J.-Y.;
RT "Degradation of the cyclin-dependent-kinase inhibitor p27Kip1 is instigated
RT by Jab1.";
RL Nature 398:160-165(1999).
RN [9]
RP INTERACTION WITH NUP50, AND MUTAGENESIS OF ARG-90.
RC STRAIN=BALB/cJ;
RX PubMed=10811608; DOI=10.1093/emboj/19.10.2168;
RA Mueller D., Thieke K., Buergin A., Dickmanns A., Eilers M.;
RT "Cyclin E-mediated elimination of p27 requires its interaction with the
RT nuclear pore-associated protein mNPAP60.";
RL EMBO J. 19:2168-2180(2000).
RN [10]
RP INTERACTION WITH UHMK1, FUNCTION, SUBCELLULAR LOCATION, AND PHOSPHORYLATION
RP AT SER-10.
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 [11]
RP INTERACTION WITH SPDYA, AND FUNCTION.
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 [12]
RP PHOSPHORYLATION AT SER-10, FUNCTION, AND MUTAGENESIS OF SER-10.
RX PubMed=15528185; DOI=10.1074/jbc.m406117200;
RA Kotake Y., Nakayama K., Ishida N., Nakayama K.I.;
RT "Role of serine 10 phosphorylation in p27 stabilization revealed by
RT analysis of p27 knock-in mice harboring a serine 10 mutation.";
RL J. Biol. Chem. 280:1095-1102(2005).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-10, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [14]
RP INTERACTION WITH CCND1.
RX PubMed=19767775; DOI=10.1038/onc.2009.287;
RA Barbash O., Egan E., Pontano L.L., Kosak J., Diehl J.A.;
RT "Lysine 269 is essential for cyclin D1 ubiquitylation by the
RT SCF(Fbx4/alphaB-crystallin) ligase and subsequent proteasome-dependent
RT degradation.";
RL Oncogene 28:4317-4325(2009).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Heart, Kidney, Liver, Lung, Pancreas, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [16]
RP FUNCTION, SUBCELLULAR LOCATION, DEGRADATION IN THE LYSOSOME, AND
RP INTERACTION WITH SNX6.
RX PubMed=20228253; DOI=10.1096/fj.09-138255;
RA Fuster J.J., Gonzalez J.M., Edo M.D., Viana R., Boya P., Cervera J.,
RA Verges M., Rivera J., Andres V.;
RT "Tumor suppressor p27(Kip1) undergoes endolysosomal degradation through its
RT interaction with sorting nexin 6.";
RL FASEB J. 24:2998-3009(2010).
RN [17]
RP PHOSPHORYLATION AT THR-170 AND THR-197 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).
CC -!- FUNCTION: Important regulator of cell cycle progression
CC (PubMed:8033213, PubMed:12972555). Inhibits the kinase activity of CDK2
CC bound to cyclin A, but has little inhibitory activity on CDK2 bound to
CC SPDYA (By similarity). Involved in G1 arrest. Potent inhibitor of
CC cyclin E- and cyclin A-CDK2 complexes (PubMed:8033213). Forms a complex
CC with cyclin type D-CDK4 complexes and is involved in the assembly,
CC stability, and modulation of CCND1-CDK4 complex activation. Acts either
CC as an inhibitor or an activator of cyclin type D-CDK4 complexes
CC depending on its phosphorylation state and/or stoichometry.
CC {ECO:0000250|UniProtKB:P46527, ECO:0000269|PubMed:12093740,
CC ECO:0000269|PubMed:12972555, ECO:0000269|PubMed:15528185,
CC ECO:0000269|PubMed:20228253, ECO:0000269|PubMed:8033213,
CC ECO:0000269|PubMed:9399644}.
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-197-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. Interacts with AKT1 and LYN; the interactions lead to
CC cytoplasmic mislocation, phosphorylation of CDKN1B and inhibition of
CC cell cycle arrest. 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 Forms a ternary complex composed of cyclin D, CDK4 and CDKN1B.
CC Interacts (phosphorylated on Tyr-88 and Tyr-89) with CDK4; the
CC interaction is required for cyclin D and CDK4 complex assembly, induces
CC nuclear translocation and activates the CDK4 kinase activity. Interacts
CC with GRB2. Interacts with PIM1. Identified in a complex with SKP1, SKP2
CC and CKS1B. Interacts with UHMK1; the interaction leads to cytoplasmic
CC mislocation, phosphorylation of CDKN1B and inhibition of cell cycle
CC arrest. Interacts also with CDK1. Dephosphorylated on Thr-187 by PPM1H,
CC leading to CDKN1B stability (By similarity).
CC {ECO:0000250|UniProtKB:P46527, ECO:0000269|PubMed:10086358,
CC ECO:0000269|PubMed:10811608, ECO:0000269|PubMed:12093740,
CC ECO:0000269|PubMed:12972555, ECO:0000269|PubMed:19767775,
CC ECO:0000269|PubMed:20228253, ECO:0000269|PubMed:8534916,
CC ECO:0000269|PubMed:9399644}.
CC -!- INTERACTION:
CC P46414; P30285: Cdk4; NbExp=2; IntAct=EBI-1005742, EBI-847225;
CC P46414; Q61881: Mcm7; NbExp=2; IntAct=EBI-1005742, EBI-457180;
CC P46414; P54227: Stmn1; NbExp=2; IntAct=EBI-1005742, EBI-1006438;
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Endosome
CC {ECO:0000269|PubMed:20228253}. Note=Nuclear and cytoplasmic in
CC quiescent cells. AKT- or RSK-mediated phosphorylation on Thr-197, binds
CC 14-3-3, translocates to the cytoplasm and promotes cell cycle
CC progression. Mitogen-activated UHMK1 phosphorylation on Ser-10 also
CC results in translocation to the cytoplasm and cell cycle progression.
CC Phosphorylation on Ser-10 facilitates nuclear export. Translocates to
CC the nucleus on phosphorylation of Tyr-88 and Tyr-89 (By similarity).
CC Colocalizes at the endosome with SNX6; this leads to lysosomal
CC degradation (PubMed:20228253). {ECO:0000250,
CC ECO:0000269|PubMed:20228253}.
CC -!- DOMAIN: A peptide sequence containing only AA 28-79 retains substantial
CC Kip1 cyclin A/CDK2 inhibitory activity. {ECO:0000250}.
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, MYC and in certain cancer
CC cell lines. The phosphorylated form found in the cytoplasm is
CC inactivate. Phosphorylation on Thr-197 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 (By similarity). Dephosphorylated on Thr-187 by
CC PPM1H, leading to CDKN1B stability (By similarity).
CC {ECO:0000250|UniProtKB:P46527}.
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 (By
CC similarity). {ECO:0000250}.
CC -!- PTM: Subject to degradation in the lysosome. Interaction with SNX6
CC promotes lysosomal degradation.
CC -!- SIMILARITY: Belongs to the CDI family. {ECO:0000305}.
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DR EMBL; U10440; AAA21149.1; -; mRNA.
DR EMBL; U09968; AAA20235.1; -; mRNA.
DR EMBL; AK046676; BAC32833.1; -; mRNA.
DR EMBL; AK047669; BAC33119.1; -; mRNA.
DR EMBL; AK050240; BAC34141.1; -; mRNA.
DR EMBL; AC122193; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC014296; AAH14296.1; -; mRNA.
DR CCDS; CCDS20642.1; -.
DR PIR; I49064; I49064.
DR RefSeq; NP_034005.2; NM_009875.4.
DR AlphaFoldDB; P46414; -.
DR SMR; P46414; -.
DR BioGRID; 198652; 38.
DR DIP; DIP-445N; -.
DR IntAct; P46414; 8.
DR MINT; P46414; -.
DR STRING; 10090.ENSMUSP00000003115; -.
DR iPTMnet; P46414; -.
DR PhosphoSitePlus; P46414; -.
DR EPD; P46414; -.
DR jPOST; P46414; -.
DR PaxDb; P46414; -.
DR PeptideAtlas; P46414; -.
DR PRIDE; P46414; -.
DR ProteomicsDB; 281520; -.
DR Antibodypedia; 3295; 2716 antibodies from 48 providers.
DR DNASU; 12576; -.
DR Ensembl; ENSMUST00000003115; ENSMUSP00000003115; ENSMUSG00000003031.
DR Ensembl; ENSMUST00000067327; ENSMUSP00000065832; ENSMUSG00000003031.
DR Ensembl; ENSMUST00000204807; ENSMUSP00000145056; ENSMUSG00000003031.
DR GeneID; 12576; -.
DR KEGG; mmu:12576; -.
DR UCSC; uc009ela.2; mouse.
DR CTD; 1027; -.
DR MGI; MGI:104565; Cdkn1b.
DR VEuPathDB; HostDB:ENSMUSG00000003031; -.
DR eggNOG; KOG4743; Eukaryota.
DR GeneTree; ENSGT00940000159852; -.
DR HOGENOM; CLU_077692_2_0_1; -.
DR InParanoid; P46414; -.
DR OMA; QCAGMRK; -.
DR OrthoDB; 1595421at2759; -.
DR PhylomeDB; P46414; -.
DR TreeFam; TF101038; -.
DR Reactome; R-MMU-187577; SCF(Skp2)-mediated degradation of p27/p21.
DR Reactome; R-MMU-198323; AKT phosphorylates targets in the cytosol.
DR Reactome; R-MMU-2559582; Senescence-Associated Secretory Phenotype (SASP).
DR Reactome; R-MMU-2559586; DNA Damage/Telomere Stress Induced Senescence.
DR Reactome; R-MMU-6804116; TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest.
DR Reactome; R-MMU-69202; Cyclin E associated events during G1/S transition.
DR Reactome; R-MMU-69231; Cyclin D associated events in G1.
DR Reactome; R-MMU-69563; p53-Dependent G1 DNA Damage Response.
DR Reactome; R-MMU-69656; Cyclin A:Cdk2-associated events at S phase entry.
DR Reactome; R-MMU-8849470; PTK6 Regulates Cell Cycle.
DR Reactome; R-MMU-9607240; FLT3 Signaling.
DR Reactome; R-MMU-9634638; Estrogen-dependent nuclear events downstream of ESR-membrane signaling.
DR BioGRID-ORCS; 12576; 2 hits in 75 CRISPR screens.
DR ChiTaRS; Cdkn1b; mouse.
DR PRO; PR:P46414; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; P46414; protein.
DR Bgee; ENSMUSG00000003031; Expressed in cerebellar vermis and 253 other tissues.
DR Genevisible; P46414; MM.
DR GO; GO:0031464; C:Cul4A-RING E3 ubiquitin ligase complex; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; IDA:MGI.
DR GO; GO:0005768; C:endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0051087; F:chaperone binding; ISO:MGI.
DR GO; GO:0030332; F:cyclin binding; IDA:BHF-UCL.
DR GO; GO:0004861; F:cyclin-dependent protein serine/threonine kinase inhibitor activity; IDA:MGI.
DR GO; GO:0030544; F:Hsp70 protein binding; ISO:MGI.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR GO; GO:0004860; F:protein kinase inhibitor activity; ISO:MGI.
DR GO; GO:0019903; F:protein phosphatase binding; ISO:MGI.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0006915; P:apoptotic process; IMP:MGI.
DR GO; GO:0048102; P:autophagic cell death; ISO:MGI.
DR GO; GO:0008219; P:cell death; ISO:MGI.
DR GO; GO:0071236; P:cellular response to antibiotic; IDA:MGI.
DR GO; GO:0071285; P:cellular response to lithium ion; ISO:MGI.
DR GO; GO:0071407; P:cellular response to organic cyclic compound; IDA:MGI.
DR GO; GO:1904019; P:epithelial cell apoptotic process; IMP:MGI.
DR GO; GO:0060767; P:epithelial cell proliferation involved in prostate gland development; IMP:MGI.
DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; IDA:UniProtKB.
DR GO; GO:0007507; P:heart development; IMP:BHF-UCL.
DR GO; GO:0048839; P:inner ear development; IMP:MGI.
DR GO; GO:1905179; P:negative regulation of cardiac muscle tissue regeneration; IMP:BHF-UCL.
DR GO; GO:1902807; P:negative regulation of cell cycle G1/S phase transition; ISO:MGI.
DR GO; GO:0030308; P:negative regulation of cell growth; ISO:MGI.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IMP:MGI.
DR GO; GO:1904030; P:negative regulation of cyclin-dependent protein kinase activity; ISO:MGI.
DR GO; GO:0045736; P:negative regulation of cyclin-dependent protein serine/threonine kinase activity; IDA:MGI.
DR GO; GO:1904036; P:negative regulation of epithelial cell apoptotic process; IMP:MGI.
DR GO; GO:0050680; P:negative regulation of epithelial cell proliferation; IMP:MGI.
DR GO; GO:0060770; P:negative regulation of epithelial cell proliferation involved in prostate gland development; IMP:MGI.
DR GO; GO:0033673; P:negative regulation of kinase activity; ISO:MGI.
DR GO; GO:0045930; P:negative regulation of mitotic cell cycle; IBA:GO_Central.
DR GO; GO:0042326; P:negative regulation of phosphorylation; ISO:MGI.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISO:MGI.
DR GO; GO:1904706; P:negative regulation of vascular associated smooth muscle cell proliferation; ISO:MGI.
DR GO; GO:0007219; P:Notch signaling pathway; IDA:MGI.
DR GO; GO:0001890; P:placenta development; IGI:MGI.
DR GO; GO:0010942; P:positive regulation of cell death; ISO:MGI.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:MGI.
DR GO; GO:0045737; P:positive regulation of cyclin-dependent protein serine/threonine kinase activity; ISO:MGI.
DR GO; GO:0031116; P:positive regulation of microtubule polymerization; IGI:MGI.
DR GO; GO:0045732; P:positive regulation of protein catabolic process; IEA:Ensembl.
DR GO; GO:0006813; P:potassium ion transport; IGI:MGI.
DR GO; GO:0051726; P:regulation of cell cycle; IMP:BHF-UCL.
DR GO; GO:1902806; P:regulation of cell cycle G1/S phase transition; ISO:MGI.
DR GO; GO:0000079; P:regulation of cyclin-dependent protein serine/threonine kinase activity; ISO:MGI.
DR GO; GO:0007096; P:regulation of exit from mitosis; IGI:MGI.
DR GO; GO:2000045; P:regulation of G1/S transition of mitotic cell cycle; ISO:MGI.
DR GO; GO:1902746; P:regulation of lens fiber cell differentiation; IGI:MGI.
DR GO; GO:0007346; P:regulation of mitotic cell cycle; IDA:MGI.
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; IMP:MGI.
DR Gene3D; 4.10.365.10; -; 1.
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 Cell cycle; Cytoplasm; Endosome; Nucleus; Phosphoprotein;
KW Protein kinase inhibitor; Reference proteome; Ubl conjugation.
FT CHAIN 1..197
FT /note="Cyclin-dependent kinase inhibitor 1B"
FT /id="PRO_0000190085"
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:0000250|UniProtKB:P46527"
FT REGION 86..197
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 103..121
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 158..172
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 90
FT /note="Required for interaction with NUP50"
FT MOD_RES 10
FT /note="Phosphoserine; by UHMK1"
FT /evidence="ECO:0000269|PubMed:12093740,
FT ECO:0000269|PubMed:15528185, ECO:0007744|PubMed:17242355"
FT MOD_RES 74
FT /note="Phosphotyrosine; by SRC"
FT /evidence="ECO:0000250|UniProtKB:P46527"
FT MOD_RES 88
FT /note="Phosphotyrosine; by ABL, LYN, SRC and JAK2"
FT /evidence="ECO:0000250|UniProtKB:P46527"
FT MOD_RES 89
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P46527"
FT MOD_RES 170
FT /note="Phosphothreonine; by CaMK1"
FT /evidence="ECO:0000269|PubMed:23707388"
FT MOD_RES 187
FT /note="Phosphothreonine; by PKB/AKT1, CDK1 and CDK2"
FT /evidence="ECO:0000269|PubMed:9399644"
FT MOD_RES 197
FT /note="Phosphothreonine; by CaMK1, PKB/AKT1, RPS6KA1,
FT RPS6KA3 and PIM1"
FT /evidence="ECO:0000250|UniProtKB:P46527"
FT MUTAGEN 10
FT /note="S->A: Loss of phosphorylation in G(0) phase. No
FT change in cMYC-induced CDK2-mediated phosphorylation. Rapid
FT dissociation from the cyclin E/CDK2 complex after induction
FT by cMYC. Loss of protein stability in G(0) phase. No change
FT in protein stability at S-phase."
FT /evidence="ECO:0000269|PubMed:15528185,
FT ECO:0000269|PubMed:9399644"
FT MUTAGEN 90
FT /note="R->G: Loss of interaction with NUP50. No cyclin E-
FT mediated degradation of phosphorylated p27KIP1."
FT /evidence="ECO:0000269|PubMed:10811608"
FT MUTAGEN 187
FT /note="T->E: Loss of cMyc-induced CDK2-mediated
FT phosphorylation. Rapid dissociation from the cyclin E/CDK2
FT complex after induction by c-Myc."
FT /evidence="ECO:0000269|PubMed:9399644"
FT MUTAGEN 187
FT /note="T->V: Loss of cMYC-induced CDK2-mediated
FT phosphorylation Dissociates very slowly from the cyclin
FT E/CDK2 complex after induction by cMYC. Cell cycle arrest."
FT /evidence="ECO:0000269|PubMed:9399644"
FT CONFLICT 22
FT /note="E -> D (in Ref. 1; AAA21149, 2; AAA20235 and 5;
FT AAH14296)"
FT /evidence="ECO:0000305"
FT CONFLICT 141
FT /note="P -> Q (in Ref. 1; AAA21149, 2; AAA20235 and 5;
FT AAH14296)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 197 AA; 22193 MW; BAC30D648B9BA3D6 CRC64;
MSNVRVSNGS PSLERMDARQ AEHPKPSACR NLFGPVNHEE LTRDLEKHCR DMEEASQRKW
NFDFQNHKPL EGRYEWQEVE RGSLPEFYYR PPRPPKSACK VLAQESQDVS GSRQAVPLIG
SQANSEDRHL VDQMPDSSDN PAGLAEQCPG MRKRPAAEDS SSQNKRANRT EENVSDGSPN
AGTVEQTPKK PGLRRQT
