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P46527

- CDN1B_HUMAN

UniProt

P46527 - CDN1B_HUMAN

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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

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 phosphatase binding Source: BHF-UCL
  3. 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
Complete GO annotation...

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-KW
  4. nucleoplasm Source: Reactome
  5. nucleus Source: BHF-UCL
  6. protein complex Source: Ensembl
Complete GO annotation...

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 UHMK14 Publications
Modified residuei74 – 741Phosphotyrosine; by SRC1 Publication
Modified residuei88 – 881Phosphotyrosine; by ABL, LYN, SRC and JAK24 Publications
Modified residuei89 – 891Phosphotyrosine1 Publication
Modified residuei157 – 1571Phosphothreonine; by CaMK1, PKB/AKT1 and PIM14 Publications
Modified residuei170 – 1701PhosphothreonineBy similarity
Modified residuei187 – 1871Phosphothreonine; by PKB/AKT1, CDK1 and CDK24 Publications
Modified residuei198 – 1981Phosphothreonine; by CaMK1, PKB/AKT1, RPS6KA1, RPS6KA3 and PIM15 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

BgeeiP46527.
CleanExiHS_CDKN1B.
ExpressionAtlasiP46527. baseline and differential.
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. 69 interactions.
DIPiDIP-33341N.
IntActiP46527. 52 interactions.
MINTiMINT-239177.
STRINGi9606.ENSP00000228872.

Structurei

Secondary structure

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

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.
InParanoidiP46527.
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

        10         20         30         40         50
MSNVRVSNGS PSLERMDARQ AEHPKPSACR NLFGPVDHEE LTRDLEKHCR
60 70 80 90 100
DMEEASQRKW NFDFQNHKPL EGKYEWQEVE KGSLPEFYYR PPRPPKGACK
110 120 130 140 150
VPAQESQDVS GSRPAAPLIG APANSEDTHL VDPKTDPSDS QTGLAEQCAG
160 170 180 190
IRKRPATDDS STQNKRANRT EENVSDGSPN AGSVEQTPKK PGLRRRQT
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. 69 interactions.
DIPi DIP-33341N.
IntActi P46527. 52 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.
InParanoidi P46527.
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

Bgeei P46527.
CleanExi HS_CDKN1B.
ExpressionAtlasi P46527. baseline and differential.
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

« Hide 'large scale' publications
  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 29, 2014
This is version 162 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