Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Basket 0
(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

P46527

- CDN1B_HUMAN

UniProt

P46527 - CDN1B_HUMAN

Protein

Cyclin-dependent kinase inhibitor 1B

Gene

CDKN1B

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
    • BLAST
    • Align
    • Format
    • Add to basket
    • History
      Entry version 161 (01 Oct 2014)
      Sequence version 1 (01 Nov 1995)
      Previous versions | rss
    • Help video
    • Feedback
    • Comment

    Functioni

    Important regulator of cell cycle progression. Involved in G1 arrest. Potent inhibitor of cyclin E- and cyclin A-CDK2 complexes. Forms a complex with cyclin type D-CDK4 complexes and is involved in the assembly, stability, and modulation of CCND1-CDK4 complex activation. Acts either as an inhibitor or an activator of cyclin type D-CDK4 complexes depending on its phosphorylation state and/or stoichometry.5 Publications

    GO - Molecular functioni

    1. cyclin-dependent protein serine/threonine kinase inhibitor activity Source: ProtInc
    2. protein binding Source: UniProtKB
    3. protein phosphatase binding Source: BHF-UCL
    4. transforming growth factor beta receptor, cytoplasmic mediator activity Source: ProtInc

    GO - Biological processi

    1. activation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
    2. autophagic cell death Source: BHF-UCL
    3. cell cycle arrest Source: HGNC
    4. cellular response to antibiotic Source: Ensembl
    5. cellular response to lithium ion Source: MGI
    6. cellular response to organic cyclic compound Source: Ensembl
    7. DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest Source: Reactome
    8. epidermal growth factor receptor signaling pathway Source: Reactome
    9. Fc-epsilon receptor signaling pathway Source: Reactome
    10. fibroblast growth factor receptor signaling pathway Source: Reactome
    11. G1/S transition of mitotic cell cycle Source: BHF-UCL
    12. innate immune response Source: Reactome
    13. inner ear development Source: Ensembl
    14. mitotic cell cycle Source: Reactome
    15. mitotic cell cycle arrest Source: UniProtKB
    16. negative regulation of apoptotic process Source: Ensembl
    17. negative regulation of cell growth Source: BHF-UCL
    18. negative regulation of cell proliferation Source: UniProtKB
    19. negative regulation of cellular component movement Source: Ensembl
    20. negative regulation of cyclin-dependent protein serine/threonine kinase activity Source: Ensembl
    21. negative regulation of epithelial cell proliferation involved in prostate gland development Source: Ensembl
    22. negative regulation of kinase activity Source: UniProtKB
    23. negative regulation of mitotic cell cycle Source: UniProtKB
    24. negative regulation of phosphorylation Source: BHF-UCL
    25. negative regulation of transcription, DNA-templated Source: UniProtKB
    26. neurotrophin TRK receptor signaling pathway Source: Reactome
    27. phosphatidylinositol-mediated signaling Source: Reactome
    28. positive regulation of cell death Source: UniProtKB
    29. positive regulation of cell proliferation Source: Ensembl
    30. positive regulation of microtubule polymerization Source: Ensembl
    31. positive regulation of protein catabolic process Source: MGI
    32. potassium ion transport Source: Ensembl
    33. regulation of cyclin-dependent protein serine/threonine kinase activity Source: ProtInc
    34. response to amino acid Source: Ensembl
    35. response to cadmium ion Source: Ensembl
    36. response to drug Source: Ensembl
    37. response to estradiol Source: Ensembl
    38. response to glucose Source: Ensembl
    39. response to hypoxia Source: Ensembl
    40. response to peptide hormone Source: Ensembl
    41. sensory perception of sound Source: Ensembl

    Keywords - Molecular functioni

    Protein kinase inhibitor

    Keywords - Biological processi

    Cell cycle

    Enzyme and pathway databases

    ReactomeiREACT_1156. Orc1 removal from chromatin.
    REACT_12564. AKT phosphorylates targets in the cytosol.
    REACT_147727. Constitutive PI3K/AKT Signaling in Cancer.
    REACT_1625. p53-Dependent G1 DNA Damage Response.
    REACT_169168. Senescence-Associated Secretory Phenotype (SASP).
    REACT_169185. DNA Damage/Telomere Stress Induced Senescence.
    REACT_821. Cyclin D associated events in G1.
    REACT_9003. SCF(Skp2)-mediated degradation of p27/p21.
    REACT_9029. Cyclin A:Cdk2-associated events at S phase entry.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Cyclin-dependent kinase inhibitor 1B
    Alternative name(s):
    Cyclin-dependent kinase inhibitor p27
    p27Kip1
    Gene namesi
    Name:CDKN1B
    Synonyms:KIP1
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 12

    Organism-specific databases

    HGNCiHGNC:1785. CDKN1B.

    Subcellular locationi

    Nucleus. Cytoplasm. Endosome By similarity
    Note: Nuclear and cytoplasmic in quiescent cells. AKT- or RSK-mediated phosphorylation on Thr-198, binds 14-3-3, translocates to the cytoplasm and promotes cell cycle progression. Mitogen-activated UHMK1 phosphorylation on Ser-10 also results in translocation to the cytoplasm and cell cycle progression. Phosphorylation on Ser-10 facilitates nuclear export. Translocates to the nucleus on phosphorylation of Tyr-88 and Tyr-89. Colocalizes at the endosome with SNX6; this leads to lysosomal degradation By similarity.By similarity

    GO - Cellular componenti

    1. cytoplasm Source: HGNC
    2. cytosol Source: Reactome
    3. endosome Source: UniProtKB-SubCell
    4. nucleoplasm Source: Reactome
    5. nucleus Source: BHF-UCL
    6. protein complex Source: Ensembl

    Keywords - Cellular componenti

    Cytoplasm, Endosome, Nucleus

    Pathology & Biotechi

    Involvement in diseasei

    Multiple endocrine neoplasia 4 (MEN4) [MIM:610755]: Multiple endocrine neoplasia (MEN) syndromes are inherited cancer syndromes of the thyroid. MEN4 is a MEN-like syndrome with a phenotypic overlap of both MEN1 and MEN2.
    Note: The disease is caused by mutations affecting the gene represented in this entry.

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi10 – 101S → A: Loss of phosphorylation by UHMK1. No translocation to the cytoplasm. Greater cell cycle arrest. 3 Publications
    Mutagenesisi10 – 101S → D: Exported to the cytoplasm. Inhibits cell cycle arrest. 3 Publications
    Mutagenesisi10 – 101S → E: Increased stability in vivo and in vitro. 3 Publications
    Mutagenesisi74 – 741Y → F: No change in binding CDK4 and no inhibition of CDK4 activity. Translocates to nucleus. No effect on in vitro phosphorylation of CDK4 by CCNH-CDK7. 2 Publications
    Mutagenesisi88 – 881Y → F: Abolishes LYN-mediated phosphorylation, reduceS CDK2-mediated phosphorylation on T-187, has greater cell cycle arrest into S-phase, no effect on binding CDK2 complexes, reduced CDK4 binding and inhibits CDK4 enzyme activity. No nuclear translocation. No effect on in vitro phosphorylation of CDK4 by CCNH-CDK7. Completely abolishes CDK4 binding; when associated with F-89. 3 Publications
    Mutagenesisi89 – 891Y → F: No effect on binding CDK2 complexes, reduced CDK4 binding and greatly inhibits CDK4 enzyme activity. No nuclear translocation. Inhibits in vitro phosphorylation of CDK4 by CCNH-CDK7. Completely abolishes CDK4 binding; when associated with F-88. 3 Publications
    Mutagenesisi157 – 1571T → A: Greatly reduced PKB/AKT1-mediated phosphorylation. Nuclear location. Inhibits cyclin E/CDK2 cell cycle progression. No effect on binding AKT1. Completely abolishes PKB/AKT1-mediated phosphorylation and no cytoplasmic translocation; when associated with A-198. 5 Publications
    Mutagenesisi161 – 1611S → A: No change in PKB/AKT1-mediated phosphorylation. 1 Publication
    Mutagenesisi162 – 1621T → A: No change in PKB/AKT1-mediated phosphorylation. 1 Publication
    Mutagenesisi185 – 1851E → A, D or Q: Strongly reduced ubiquitination by a TRIM21-containing SCF(SKP2) complex. 1 Publication
    Mutagenesisi187 – 1871T → A or D: No change in PKB/AKT1- nor UHMK1-mediated phosphorylation. 5 Publications
    Mutagenesisi187 – 1871T → A: Abolishes phosphorylation-dependent ubiquitination. 5 Publications
    Mutagenesisi198 – 1981T → A or D: Abolishes PKB/AKT1-mediated phosphorylation. 46% cytoplasmic location. Greatly reduced binding to YWHAQ. Equally reduced binding; when associated with A-10 and A-187. No nuclear import; when associated with A-157. Completely abolishes PKB/AKT1-mediated phosphorylation and no cytoplasmic translocation; when associated with A-157. 3 Publications

    Keywords - Diseasei

    Proto-oncogene

    Organism-specific databases

    MIMi610755. phenotype.
    Orphaneti652. Multiple endocrine neoplasia type 1.
    276152. Multiple endocrine neoplasia type 4.
    PharmGKBiPA105.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 198198Cyclin-dependent kinase inhibitor 1BPRO_0000190084Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei10 – 101Phosphoserine; by UHMK15 Publications
    Modified residuei74 – 741Phosphotyrosine; by SRC2 Publications
    Modified residuei88 – 881Phosphotyrosine; by ABL, LYN, SRC and JAK25 Publications
    Modified residuei89 – 891Phosphotyrosine2 Publications
    Modified residuei157 – 1571Phosphothreonine; by CaMK1, PKB/AKT1 and PIM15 Publications
    Modified residuei170 – 1701PhosphothreonineBy similarity
    Modified residuei187 – 1871Phosphothreonine; by PKB/AKT1, CDK1 and CDK25 Publications
    Modified residuei198 – 1981Phosphothreonine; by CaMK1, PKB/AKT1, RPS6KA1, RPS6KA3 and PIM16 Publications

    Post-translational modificationi

    Phosphorylated; phosphorylation occurs on serine, threonine and tyrosine residues. Phosphorylation on Ser-10 is the major site of phosphorylation in resting cells, takes place at the G(0)-G1 phase and leads to protein stability. Phosphorylation on other sites is greatly enhanced by mitogens, growth factors, cMYC and in certain cancer cell lines. The phosphorylated form found in the cytoplasm is inactivate. Phosphorylation on Thr-198 is required for interaction with 14-3-3 proteins. Phosphorylation on Thr-187, by CDK1 and CDK2 leads to protein ubiquitination and proteasomal degradation. Tyrosine phosphorylation promotes this process. Phosphorylation by PKB/AKT1 can be suppressed by LY294002, an inhibitor of the catalytic subunit of PI3K. Phosphorylation on Tyr-88 and Tyr-89 has no effect on binding CDK2, but is required for binding CDK4. Dephosphorylated on tyrosine residues by G-CSF.14 Publications
    Ubiquitinated; in the cytoplasm by the KPC complex (composed of RNF123/KPC1 and UBAC1/KPC2) and, in the nucleus, by SCF(SKP2). The latter requires prior phosphorylation on Thr-187. Ubiquitinated; by a TRIM21-containing SCF(SKP2)-like complex; leads to its degradation.4 Publications
    Subject to degradation in the lysosome. Interaction with SNX6 promotes lysosomal degradation By similarity.By similarity

    Keywords - PTMi

    Phosphoprotein, Ubl conjugation

    Proteomic databases

    MaxQBiP46527.
    PaxDbiP46527.
    PRIDEiP46527.

    2D gel databases

    SWISS-2DPAGEP46527.

    PTM databases

    PhosphoSiteiP46527.

    Miscellaneous databases

    PMAP-CutDBP46527.

    Expressioni

    Tissue specificityi

    Expressed in all tissues tested. Highest levels in skeletal muscle, lowest in liver and kidney.

    Inductioni

    Maximal levels in quiescence cells and early G1. Levels decrease after mitogen stimulation as cells progress toward S-phase.1 Publication

    Gene expression databases

    ArrayExpressiP46527.
    BgeeiP46527.
    CleanExiHS_CDKN1B.
    GenevestigatoriP46527.

    Organism-specific databases

    HPAiCAB003691.
    CAB021888.

    Interactioni

    Subunit structurei

    Forms a ternary complex with CCNE1/CDK2/CDKN1B. Interacts directly with CCNE1; the interaction is inhibited by CDK2-dependent phosphorylation on Thr-187. Interacts with COPS5, subunit of the COP9 signalosome complex; the interaction leads to CDKN1B degradation. Interacts with NUP50; the interaction leads to nuclear import and degradation of phosphorylated CDKN1B. Interacts with CCND1 and SNX6 By similarity. Interacts (Thr-198-phosphorylated form) with 14-3-3 proteins, binds strongly YWHAQ, weakly YWHAE and YWHAH, but not YWHAB nor YWHAZ; the interaction with YWHAQ results in translocation to the cytoplasm. Interacts with AKT1 and LYN; the interactions lead to cytoplasmic mislocation, phosphorylation of CDKN1B and inhibition of cell cycle arrest. Interacts (unphosphorylated form) with CDK2. Forms a ternary complex, cyclin D/CDK4/CDKN1B. Interacts (phosphorylated on Tyr-88 and Tyr-89) with CDK4; the interaction is required for cyclin D/CDK4 complex assembly, induces nuclear translocation and activates the CDK4 kinase activity. Interacts with GRB2. Interacts with PIM1. Identified in a complex with SKP1, SKP2 and CKS1B. Interacts with UHMK1; the interaction leads to cytoplasmic mislocation, phosphorylation of CDKN1B and inhibition of cell cycle arrest. Interacts also with CDK1.By similarity13 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    Abl1P005202EBI-519280,EBI-914519From a different organism.
    CCNA2P2024813EBI-519280,EBI-457097
    CCND1P243852EBI-519280,EBI-375001
    CCNE1P248647EBI-519280,EBI-519526
    CCNE2O960202EBI-519280,EBI-375033
    CDK2P2494116EBI-519280,EBI-375096
    CDK4P118025EBI-519280,EBI-295644
    CDK5Q005356EBI-519280,EBI-1041567
    CHUKO151114EBI-519280,EBI-81249
    COPS5Q929053EBI-519280,EBI-594661
    Jak2Q621207EBI-519280,EBI-646604From a different organism.
    KPNA3O005054EBI-519280,EBI-358297
    KPNA5O151316EBI-519280,EBI-540602
    LYNP079482EBI-519280,EBI-79452
    MCM7P339932EBI-519280,EBI-355924
    SKP2Q133094EBI-519280,EBI-456291
    TRAF2Q129332EBI-519280,EBI-355744
    YWHAQP273484EBI-519280,EBI-359854

    Protein-protein interaction databases

    BioGridi107461. 68 interactions.
    DIPiDIP-33341N.
    IntActiP46527. 51 interactions.
    MINTiMINT-239177.
    STRINGi9606.ENSP00000228872.

    Structurei

    Secondary structure

    1
    198
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi38 – 4912
    Turni50 – 534
    Helixi54 – 607
    Turni64 – 674
    Beta strandi71 – 744
    Beta strandi77 – 804
    Helixi86 – 894

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1H27X-ray2.20E25-35[»]
    1JSUX-ray2.30C23-106[»]
    2ASTX-ray2.30D181-190[»]
    DisProtiDP00018.
    ProteinModelPortaliP46527.
    SMRiP46527. Positions 25-93.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP46527.

    Family & Domainsi

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi153 – 16917Nuclear localization signalSequence AnalysisAdd
    BLAST

    Domaini

    A peptide sequence containing only AA 28-79 retains substantial Kip1 cyclin A/CDK2 inhibitory activity.

    Sequence similaritiesi

    Belongs to the CDI family.Curated

    Phylogenomic databases

    eggNOGiNOG245842.
    HOGENOMiHOG000294081.
    HOVERGENiHBG073988.
    KOiK06624.
    OMAiFYFRPPR.
    OrthoDBiEOG7GJ6HD.
    PhylomeDBiP46527.
    TreeFamiTF101038.

    Family and domain databases

    InterProiIPR003175. CDI.
    [Graphical view]
    PANTHERiPTHR10265. PTHR10265. 1 hit.
    PfamiPF02234. CDI. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    P46527-1 [UniParc]FASTAAdd to Basket

    « Hide

    MSNVRVSNGS PSLERMDARQ AEHPKPSACR NLFGPVDHEE LTRDLEKHCR    50
    DMEEASQRKW NFDFQNHKPL EGKYEWQEVE KGSLPEFYYR PPRPPKGACK 100
    VPAQESQDVS GSRPAAPLIG APANSEDTHL VDPKTDPSDS QTGLAEQCAG 150
    IRKRPATDDS STQNKRANRT EENVSDGSPN AGSVEQTPKK PGLRRRQT 198
    Length:198
    Mass (Da):22,073
    Last modified:November 1, 1995 - v1
    Checksum:i1118D58901CDF3FC
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti22 – 221E → D in AAD14244. (PubMed:7882309)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti15 – 151R → W.1 Publication
    Corresponds to variant rs2066828 [ dbSNP | Ensembl ].
    VAR_011871
    Natural varianti69 – 691P → L Found in a patient with multiple endocrine tumors; germline mutation; reduced expression levels; shows impaired binding to CDK2. 1 Publication
    VAR_064429
    Natural varianti109 – 1091V → G.3 Publications
    Corresponds to variant rs2066827 [ dbSNP | Ensembl ].
    VAR_011872

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U10906 mRNA. Translation: AAA20240.1.
    S76988, S76986 Genomic DNA. Translation: AAD14244.1.
    BT019553 mRNA. Translation: AAV38360.1.
    BT019554 mRNA. Translation: AAV38361.1.
    AF480891 Genomic DNA. Translation: AAL78041.1.
    BC001971 mRNA. Translation: AAH01971.1.
    CCDSiCCDS8653.1.
    RefSeqiNP_004055.1. NM_004064.4.
    UniGeneiHs.238990.

    Genome annotation databases

    EnsembliENST00000228872; ENSP00000228872; ENSG00000111276.
    GeneIDi1027.
    KEGGihsa:1027.
    UCSCiuc001rat.2. human.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Web resourcesi

    Atlas of Genetics and Cytogenetics in Oncology and Haematology
    NIEHS-SNPs

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U10906 mRNA. Translation: AAA20240.1 .
    S76988 , S76986 Genomic DNA. Translation: AAD14244.1 .
    BT019553 mRNA. Translation: AAV38360.1 .
    BT019554 mRNA. Translation: AAV38361.1 .
    AF480891 Genomic DNA. Translation: AAL78041.1 .
    BC001971 mRNA. Translation: AAH01971.1 .
    CCDSi CCDS8653.1.
    RefSeqi NP_004055.1. NM_004064.4.
    UniGenei Hs.238990.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1H27 X-ray 2.20 E 25-35 [» ]
    1JSU X-ray 2.30 C 23-106 [» ]
    2AST X-ray 2.30 D 181-190 [» ]
    DisProti DP00018.
    ProteinModelPortali P46527.
    SMRi P46527. Positions 25-93.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 107461. 68 interactions.
    DIPi DIP-33341N.
    IntActi P46527. 51 interactions.
    MINTi MINT-239177.
    STRINGi 9606.ENSP00000228872.

    PTM databases

    PhosphoSitei P46527.

    2D gel databases

    SWISS-2DPAGE P46527.

    Proteomic databases

    MaxQBi P46527.
    PaxDbi P46527.
    PRIDEi P46527.

    Protocols and materials databases

    DNASUi 1027.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000228872 ; ENSP00000228872 ; ENSG00000111276 .
    GeneIDi 1027.
    KEGGi hsa:1027.
    UCSCi uc001rat.2. human.

    Organism-specific databases

    CTDi 1027.
    GeneCardsi GC12P012867.
    HGNCi HGNC:1785. CDKN1B.
    HPAi CAB003691.
    CAB021888.
    MIMi 600778. gene.
    610755. phenotype.
    neXtProti NX_P46527.
    Orphaneti 652. Multiple endocrine neoplasia type 1.
    276152. Multiple endocrine neoplasia type 4.
    PharmGKBi PA105.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG245842.
    HOGENOMi HOG000294081.
    HOVERGENi HBG073988.
    KOi K06624.
    OMAi FYFRPPR.
    OrthoDBi EOG7GJ6HD.
    PhylomeDBi P46527.
    TreeFami TF101038.

    Enzyme and pathway databases

    Reactomei REACT_1156. Orc1 removal from chromatin.
    REACT_12564. AKT phosphorylates targets in the cytosol.
    REACT_147727. Constitutive PI3K/AKT Signaling in Cancer.
    REACT_1625. p53-Dependent G1 DNA Damage Response.
    REACT_169168. Senescence-Associated Secretory Phenotype (SASP).
    REACT_169185. DNA Damage/Telomere Stress Induced Senescence.
    REACT_821. Cyclin D associated events in G1.
    REACT_9003. SCF(Skp2)-mediated degradation of p27/p21.
    REACT_9029. Cyclin A:Cdk2-associated events at S phase entry.

    Miscellaneous databases

    ChiTaRSi CDKN1B. human.
    EvolutionaryTracei P46527.
    GeneWikii CDKN1B.
    GenomeRNAii 1027.
    NextBioi 4315.
    PMAP-CutDB P46527.
    PROi P46527.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P46527.
    Bgeei P46527.
    CleanExi HS_CDKN1B.
    Genevestigatori P46527.

    Family and domain databases

    InterProi IPR003175. CDI.
    [Graphical view ]
    PANTHERi PTHR10265. PTHR10265. 1 hit.
    Pfami PF02234. CDI. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Cloning of p27Kip1, a cyclin-dependent kinase inhibitor and a potential mediator of extracellular antimitogenic signals."
      Polyak K., Lee M.-H., Erdjument-Bromage H., Koff A., Roberts J.M., Tempst P., Massague J.
      Cell 78:59-66(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 28-79 AND 104-152.
      Tissue: Kidney.
    2. "Assignment of the human p27Kip1 gene to 12p13 and its analysis in leukemias."
      Pietenpol J.A., Bohlander S.K., Sato Y., Papadopoulos N., Liu B., Friedman C., Trask B.J., Roberts J.M., Kinzler K.W., Rowley J.D.
      Cancer Res. 55:1206-1210(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    3. "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
      Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
      Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT GLY-109.
    4. NIEHS SNPs program
      Submitted (FEB-2002) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS TRP-15 AND GLY-109.
    5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT GLY-109.
      Tissue: Cervix.
    6. "Ubiquitination of p27 is regulated by Cdk-dependent phosphorylation and trimeric complex formation."
      Montagnoli A., Fiore F., Eytan E., Carrano A.C., Draetta G.F., Hershko A., Pagano M.
      Genes Dev. 13:1181-1189(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: UBIQUITINATION, PHOSPHORYLATION AT THR-187.
    7. "Phosphorylation at serine 10, a major phosphorylation site of p27(Kip1), increases its protein stability."
      Ishida N., Kitagawa M., Hatakeyama S., Nakayama K.
      J. Biol. Chem. 275:25146-25154(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT SER-10, FUNCTION.
    8. "A growth factor-dependent nuclear kinase phosphorylates p27(Kip1) and regulates cell cycle progression."
      Boehm M., Yoshimoto T., Crook M.F., Nallamshetty S., True A., Nabel G.J., Nabel E.G.
      EMBO J. 21:3390-3401(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH UHMK1, PHOSPHORYLATION AT SER-10, SUBCELLULAR LOCATION, MUTAGENESIS OF SER-10 AND THR-187.
    9. "Akt-dependent phosphorylation of p27Kip1 promotes binding to 14-3-3 and cytoplasmic localization."
      Fujita N., Sato S., Katayama K., Tsuruo T.
      J. Biol. Chem. 277:28706-28713(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT SER-10; THR-187 AND THR-198, INTERACTION WITH AKT1 AND YWHAQ, SUBCELLULAR LOCATION, MUTAGENESIS OF SER-10; THR-157; THR-187 AND THR-198.
    10. "Cytoplasmic relocalization and inhibition of the cyclin-dependent kinase inhibitor p27(Kip1) by PKB/Akt-mediated phosphorylation in breast cancer."
      Viglietto G., Motti M.L., Bruni P., Melillo R.M., D'Alessio A., Califano D., Vinci F., Chiappetta G., Tsichlis P., Bellacosa A., Fusco A., Santoro M.
      Nat. Med. 8:1136-1144(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT THR-157, SUBCELLULAR LOCATION, ASSOCIATION WITH BREAST CANCER, MUTAGENESIS OF THR-157.
    11. "PKB/Akt mediates cell-cycle progression by phosphorylation of p27(Kip1) at threonine 157 and modulation of its cellular localization."
      Shin I., Yakes F.M., Rojo F., Shin N.-Y., Bakin A.V., Baselga J., Arteaga C.L.
      Nat. Med. 8:1145-1152(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT THR-157, INTERACTION WITH AKT1, SUBCELLULAR LOCATION, FUNCTION, MUTAGENESIS OF THR-157; SER-161 AND THR-162.
    12. "Phosphorylation of p27Kip1 at threonine 198 by p90 ribosomal protein S6 kinases promotes its binding to 14-3-3 and cytoplasmic localization."
      Fujita N., Sato S., Tsuruo T.
      J. Biol. Chem. 278:49254-49260(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT SER-10 AND THR-198, INTERACTION WITH YWHAE; YWHAH; SFN; YWHAQ; RPS6KA1 AND RPS6KA3, SUBCELLULAR LOCATION, MUTAGENESIS OF THR-157 AND THR-198.
    13. "Spy1 interacts with p27Kip1 to allow G1/S progression."
      Porter L.A., Kong-Beltran M., Donoghue D.J.
      Mol. Biol. Cell 14:3664-3674(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH SPDYA.
    14. "Akt-dependent T198 phosphorylation of cyclin-dependent kinase inhibitor p27kip1 in breast cancer."
      Motti M.L., De Marco C., Califano D., Fusco A., Viglietto G.
      Cell Cycle 3:1074-1080(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT THR-198, SUBCELLULAR LOCATION, MUTAGENESIS OF SER-10; THR-157; THR-187 AND THR-198.
    15. "Cdc2-cyclin E complexes regulate the G1/S phase transition."
      Aleem E., Kiyokawa H., Kaldis P.
      Nat. Cell Biol. 7:831-836(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH CDK1.
    16. "Tyrosine phosphorylation modulates binding preference to cyclin-dependent kinases and subcellular localization of p27Kip1 in the acute promyelocytic leukemia cell line NB4."
      Kardinal C., Dangers M., Kardinal A., Koch A., Brandt D.T., Tamura T., Welte K.
      Blood 107:1133-1140(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT TYR-88 AND TYR-89, DEPHOSPHORYLATION, INTERACTION WITH GRB2; CDK2 AND CDK4, SUBCELLULAR LOCATION, MUTAGENESIS OF TYR-74; TYR-88 AND TYR-89.
    17. "Regulated activating Thr172 phosphorylation of cyclin-dependent kinase 4(CDK4): its relationship with cyclins and CDK 'inhibitors'."
      Bockstaele L., Kooken H., Libert F., Paternot S., Dumont J.E., de Launoit Y., Roger P.P., Coulonval K.
      Mol. Cell. Biol. 26:5070-5085(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH CDK4, FUNCTION.
    18. "Regulation of p27 degradation and S-phase progression by Ro52 RING finger protein."
      Sabile A., Meyer A.M., Wirbelauer C., Hess D., Kogel U., Scheffner M., Krek W.
      Mol. Cell. Biol. 26:5994-6004(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: UBIQUITINATION, MUTAGENESIS OF THR-187.
    19. "Germ-line mutations in p27(Kip1) cause a multiple endocrine neoplasia syndrome in rats and humans."
      Pellegata N.S., Quintanilla-Martinez L., Siggelkow H., Samson E., Bink K., Hoefler H., Fend F., Graw J., Atkinson M.J.
      Proc. Natl. Acad. Sci. U.S.A. 103:15558-15563(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: ASSOCIATION WITH MEN4.
    20. "p27 phosphorylation by Src regulates inhibition of cyclin E-Cdk2."
      Chu I., Sun J., Arnaout A., Kahn H., Hanna W., Narod S., Sun P., Tan C.K., Hengst L., Slingerland J.
      Cell 128:281-294(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT TYR-74 AND TYR-88 BY SRC.
    21. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Embryonic kidney.
    22. "Pim kinases promote cell cycle progression by phosphorylating and down-regulating p27Kip1 at the transcriptional and posttranscriptional levels."
      Morishita D., Katayama R., Sekimizu K., Tsuruo T., Fujita N.
      Cancer Res. 68:5076-5085(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH PIM1, PHOSPHORYLATION AT THR-157 AND THR-198.
    23. "p27Kip1 inhibits cyclin D-cyclin-dependent kinase 4 by two independent modes."
      Ray A., James M.K., Larochelle S., Fisher R.P., Blain S.W.
      Mol. Cell. Biol. 29:986-999(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH CDK4, PHOSPHORYLATION, FUNCTION, MUTAGENESIS OF TYR-74; TYR-88 AND TYR-89.
    24. "Phosphorylation of p27Kip1 by JAK2 directly links cytokine receptor signaling to cell cycle control."
      Jakel H., Weinl C., Hengst L.
      Oncogene 30:3502-3512(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT TYR-88 BY JAK2.
    25. "Fbxl12 triggers G1 arrest by mediating degradation of calmodulin kinase I."
      Mallampalli R.K., Kaercher L., Snavely C., Pulijala R., Chen B.B., Coon T., Zhao J., Agassandian M.
      Cell. Signal. 25:2047-2059(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT THR-157 AND THR-198 BY CAMK1.
    26. "Regulation of the CRL4(Cdt2) ubiquitin ligase and cell-cycle exit by the SCF(Fbxo11) ubiquitin ligase."
      Rossi M., Duan S., Jeong Y.T., Horn M., Saraf A., Florens L., Washburn M.P., Antebi A., Pagano M.
      Mol. Cell 49:1159-1166(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT THR-187 BY CDK1 AND CDK2.
    27. "Crystal structure of the p27Kip1 cyclin-dependent-kinase inhibitor bound to the cyclin A-Cdk2 complex."
      Russo A.A., Jeffrey P.D., Patten A.K., Massague J., Pavletich N.P.
      Nature 382:325-331(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 23-106 IN COMPLEX WITH CDK2 AND CG2A.
    28. "Structural basis of the Cks1-dependent recognition of p27(Kip1) by the SCF(Skp2) ubiquitin ligase."
      Hao B., Zheng N., Schulman B.A., Wu G., Miller J.J., Pagano M., Pavletich N.P.
      Mol. Cell 20:9-19(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 181-190 IN COMPLEX WITH SKP1; SKP2 AND CKS1B, PHOSPHORYLATION AT THR-187, MUTAGENESIS OF GLU-185 AND THR-187, UBIQUITINATION.
    29. "Cdk-inhibitory activity and stability of p27Kip1 are directly regulated by oncogenic tyrosine kinases."
      Grimmler M., Wang Y., Mund T., Cilensek Z., Keidel E.-M., Waddell M.B., Jaekel H., Kullmann M., Kriwacki R.W., Hengst L.
      Cell 128:269-280(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: STRUCTURE BY NMR OF 22-104, PHOSPHORYLATION AT TYR-88, FUNCTION, INDUCTION, INTERACTION WITH LYN, IDENTIFICATION BY MASS SPECTROMETRY, MUTAGENESIS OF TYR-88 AND TYR-89.
    30. "A novel germline CDKN1B mutation causing multiple endocrine tumors: clinical, genetic and functional characterization."
      Molatore S., Marinoni I., Lee M., Pulz E., Ambrosio M.R., degli Uberti E.C., Zatelli M.C., Pellegata N.S.
      Hum. Mutat. 31:E1825-E1835(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT LEU-69, CHARACTERIZATION OF VARIANT LEU-69.

    Entry informationi

    Entry nameiCDN1B_HUMAN
    AccessioniPrimary (citable) accession number: P46527
    Secondary accession number(s): Q16307, Q5U0H2, Q9BUS6
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 1, 1995
    Last sequence update: November 1, 1995
    Last modified: October 1, 2014
    This is version 161 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Miscellaneous

    Decreased levels of p27Kip1, mainly due to proteasomal degradation, are found in various epithelial tumors originating from lung, breast, colon, ovary, esophagus, thyroid and prostate.

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Human chromosome 12
      Human chromosome 12: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3