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P46527 (CDN1B_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 156. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Cyclin-dependent kinase inhibitor 1B
Alternative name(s):
Cyclin-dependent kinase inhibitor p27
p27Kip1
Gene names
Name:CDKN1B
Synonyms:KIP1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length198 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.7 Ref.11 Ref.17 Ref.22 Ref.28

Subunit structure

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. Ref.8 Ref.9 Ref.11 Ref.12 Ref.13 Ref.15 Ref.16 Ref.17 Ref.21 Ref.22 Ref.28

Subcellular location

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. Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.14 Ref.16

Tissue specificity

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

Induction

Maximal levels in quiescence cells and early G1. Levels decrease after mitogen stimulation as cells progress toward S-phase. Ref.28

Domain

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

Post-translational modification

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. Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.14 Ref.16 Ref.21 Ref.22 Ref.23 Ref.24 Ref.25 Ref.27 Ref.28

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. Ref.6 Ref.18 Ref.27

Subject to degradation in the lysosome. Interaction with SNX6 promotes lysosomal degradation By similarity.

Involvement in disease

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. Ref.19

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.

Sequence similarities

Belongs to the CDI family.

Ontologies

Keywords
   Biological processCell cycle
   Cellular componentCytoplasm
Endosome
Nucleus
   Coding sequence diversityPolymorphism
   DiseaseProto-oncogene
   Molecular functionProtein kinase inhibitor
   PTMPhosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processDNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest

Traceable author statement. Source: Reactome

Fc-epsilon receptor signaling pathway

Traceable author statement. Source: Reactome

G1/S transition of mitotic cell cycle

Inferred from direct assay PubMed 10208428. Source: BHF-UCL

activation of cysteine-type endopeptidase activity involved in apoptotic process

Inferred from direct assay PubMed 19266349. Source: UniProtKB

autophagic cell death

Inferred from direct assay PubMed 12698196. Source: BHF-UCL

cell cycle arrest

Inferred from mutant phenotype Ref.8. Source: HGNC

cellular response to antibiotic

Inferred from electronic annotation. Source: Ensembl

cellular response to lithium ion

Inferred from direct assay PubMed 19056892. Source: MGI

cellular response to organic cyclic compound

Inferred from electronic annotation. Source: Ensembl

epidermal growth factor receptor signaling pathway

Traceable author statement. Source: Reactome

fibroblast growth factor receptor signaling pathway

Traceable author statement. Source: Reactome

innate immune response

Traceable author statement. Source: Reactome

inner ear development

Inferred from electronic annotation. Source: Ensembl

mitotic cell cycle

Traceable author statement. Source: Reactome

mitotic cell cycle arrest

Inferred from direct assay PubMed 19266349. Source: UniProtKB

negative regulation of apoptotic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of cell growth

Inferred from direct assay PubMed 10208428. Source: BHF-UCL

negative regulation of cell proliferation

Inferred from direct assay PubMed 19266349. Source: UniProtKB

negative regulation of cellular component movement

Inferred from electronic annotation. Source: Ensembl

negative regulation of cyclin-dependent protein serine/threonine kinase activity

Inferred from electronic annotation. Source: Ensembl

negative regulation of epithelial cell proliferation involved in prostate gland development

Inferred from electronic annotation. Source: Ensembl

negative regulation of kinase activity

Inferred from direct assay PubMed 19170105. Source: UniProtKB

negative regulation of mitotic cell cycle

Inferred from direct assay PubMed 19266349. Source: UniProtKB

negative regulation of phosphorylation

Inferred from direct assay PubMed 10208428. Source: BHF-UCL

negative regulation of transcription, DNA-templated

Inferred from direct assay PubMed 19170105. Source: UniProtKB

neurotrophin TRK receptor signaling pathway

Traceable author statement. Source: Reactome

phosphatidylinositol-mediated signaling

Traceable author statement. Source: Reactome

positive regulation of cell death

Inferred from direct assay PubMed 19266349. Source: UniProtKB

positive regulation of cell proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of microtubule polymerization

Inferred from electronic annotation. Source: Ensembl

positive regulation of protein catabolic process

Inferred from direct assay PubMed 19056892. Source: MGI

potassium ion transport

Inferred from electronic annotation. Source: Ensembl

regulation of cyclin-dependent protein serine/threonine kinase activity

Traceable author statement Ref.1. Source: ProtInc

response to amino acid

Inferred from electronic annotation. Source: Ensembl

response to cadmium ion

Inferred from electronic annotation. Source: Ensembl

response to drug

Inferred from electronic annotation. Source: Ensembl

response to estradiol

Inferred from electronic annotation. Source: Ensembl

response to glucose

Inferred from electronic annotation. Source: Ensembl

response to hypoxia

Inferred from electronic annotation. Source: Ensembl

response to peptide hormone

Inferred from electronic annotation. Source: Ensembl

sensory perception of sound

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcytoplasm

Inferred from direct assay Ref.8. Source: HGNC

cytosol

Traceable author statement. Source: Reactome

endosome

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay PubMed 11800646. Source: BHF-UCL

protein complex

Inferred from electronic annotation. Source: Ensembl

   Molecular_functioncyclin-dependent protein serine/threonine kinase inhibitor activity

Traceable author statement PubMed 10918569. Source: ProtInc

protein phosphatase binding

Inferred from physical interaction PubMed 19838216. Source: BHF-UCL

transforming growth factor beta receptor, cytoplasmic mediator activity

Traceable author statement Ref.1. Source: ProtInc

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 198198Cyclin-dependent kinase inhibitor 1B
PRO_0000190084

Regions

Motif153 – 16917Nuclear localization signal Potential

Amino acid modifications

Modified residue101Phosphoserine; by UHMK1 Ref.7 Ref.8 Ref.9 Ref.12
Modified residue741Phosphotyrosine; by SRC
Modified residue881Phosphotyrosine; by ABL, LYN, SRC and JAK2 Ref.16 Ref.28
Modified residue891Phosphotyrosine Ref.16
Modified residue1571Phosphothreonine; by CaMK1, PKB/AKT1 and PIM1 Ref.10 Ref.11 Ref.21 Ref.24
Modified residue1701Phosphothreonine By similarity
Modified residue1871Phosphothreonine; by PKB/AKT1, CDK1 and CDK2 Ref.6 Ref.9 Ref.25 Ref.27
Modified residue1981Phosphothreonine; by CaMK1, PKB/AKT1, RPS6KA1, RPS6KA3 and PIM1 Ref.9 Ref.12 Ref.14 Ref.21 Ref.24

Natural variations

Natural variant151R → W. Ref.4
Corresponds to variant rs2066828 [ dbSNP | Ensembl ].
VAR_011871
Natural variant691P → L Found in a patient with multiple endocrine tumors; germline mutation; reduced expression levels; shows impaired binding to CDK2. Ref.29
VAR_064429
Natural variant1091V → G. Ref.3 Ref.4 Ref.5
Corresponds to variant rs2066827 [ dbSNP | Ensembl ].
VAR_011872

Experimental info

Mutagenesis101S → A: Loss of phosphorylation by UHMK1. No translocation to the cytoplasm. Greater cell cycle arrest. Ref.8 Ref.9 Ref.14
Mutagenesis101S → D: Exported to the cytoplasm. Inhibits cell cycle arrest. Ref.8 Ref.9 Ref.14
Mutagenesis101S → E: Increased stability in vivo and in vitro. Ref.8 Ref.9 Ref.14
Mutagenesis741Y → 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. Ref.16 Ref.22
Mutagenesis881Y → 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. Ref.16 Ref.22 Ref.28
Mutagenesis891Y → 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. Ref.16 Ref.22 Ref.28
Mutagenesis1571T → 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. Ref.9 Ref.10 Ref.11 Ref.12 Ref.14
Mutagenesis1611S → A: No change in PKB/AKT1-mediated phosphorylation. Ref.11
Mutagenesis1621T → A: No change in PKB/AKT1-mediated phosphorylation. Ref.11
Mutagenesis1851E → A, D or Q: Strongly reduced ubiquitination by a TRIM21-containing SCF(SKP2) complex. Ref.27
Mutagenesis1871T → A or D: No change in PKB/AKT1- nor UHMK1-mediated phosphorylation. Ref.8 Ref.9 Ref.14 Ref.18 Ref.27
Mutagenesis1871T → A: Abolishes phosphorylation-dependent ubiquitination. Ref.8 Ref.9 Ref.14 Ref.18 Ref.27
Mutagenesis1981T → 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. Ref.9 Ref.12 Ref.14
Sequence conflict221E → D in AAD14244. Ref.2

Secondary structure

............. 198
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P46527 [UniParc].

Last modified November 1, 1995. Version 1.
Checksum: 1118D58901CDF3FC

FASTA19822,073
        10         20         30         40         50         60 
MSNVRVSNGS PSLERMDARQ AEHPKPSACR NLFGPVDHEE LTRDLEKHCR DMEEASQRKW 

        70         80         90        100        110        120 
NFDFQNHKPL EGKYEWQEVE KGSLPEFYYR PPRPPKGACK VPAQESQDVS GSRPAAPLIG 

       130        140        150        160        170        180 
APANSEDTHL VDPKTDPSDS QTGLAEQCAG IRKRPATDDS STQNKRANRT EENVSDGSPN 

       190 
AGSVEQTPKK PGLRRRQT 

« Hide

References

« Hide 'large scale' references
[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]"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage."
Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.
Science 316:1160-1166(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Embryonic kidney.
[21]"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.
[22]"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.
[23]"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 BY JAK2 AT TYR-88.
[24]"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.
[25]"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.
[26]"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.
[27]"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.
[28]"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.
[29]"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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_004055.1. NM_004064.4.
UniGeneHs.238990.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1H27X-ray2.20E25-35[»]
1JSUX-ray2.30C23-106[»]
2ASTX-ray2.30D181-190[»]
DisProtDP00018.
ProteinModelPortalP46527.
SMRP46527. Positions 25-93.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107461. 68 interactions.
DIPDIP-33341N.
IntActP46527. 48 interactions.
MINTMINT-239177.
STRING9606.ENSP00000228872.

PTM databases

PhosphoSiteP46527.

2D gel databases

SWISS-2DPAGEP46527.

Proteomic databases

PaxDbP46527.
PRIDEP46527.

Protocols and materials databases

DNASU1027.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000228872; ENSP00000228872; ENSG00000111276.
GeneID1027.
KEGGhsa:1027.
UCSCuc001rat.2. human.

Organism-specific databases

CTD1027.
GeneCardsGC12P012867.
HGNCHGNC:1785. CDKN1B.
HPACAB003691.
CAB021888.
MIM600778. gene.
610755. phenotype.
neXtProtNX_P46527.
Orphanet652. Multiple endocrine neoplasia type 1.
276152. Multiple endocrine neoplasia type 4.
PharmGKBPA105.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG245842.
HOGENOMHOG000294081.
HOVERGENHBG073988.
KOK06624.
OMARQAEYPK.
OrthoDBEOG7GJ6HD.
PhylomeDBP46527.
TreeFamTF101038.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_115566. Cell Cycle.
REACT_116125. Disease.
REACT_120956. Cellular responses to stress.
REACT_383. DNA Replication.
REACT_6900. Immune System.

Gene expression databases

ArrayExpressP46527.
BgeeP46527.
CleanExHS_CDKN1B.
GenevestigatorP46527.

Family and domain databases

InterProIPR003175. CDI.
[Graphical view]
PANTHERPTHR10265. PTHR10265. 1 hit.
PfamPF02234. CDI. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSCDKN1B. human.
EvolutionaryTraceP46527.
GeneWikiCDKN1B.
GenomeRNAi1027.
NextBio4315.
PMAP-CutDBP46527.
PROP46527.
SOURCESearch...

Entry information

Entry nameCDN1B_HUMAN
AccessionPrimary (citable) accession number: P46527
Secondary accession number(s): Q16307, Q5U0H2, Q9BUS6
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: April 16, 2014
This is version 156 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM