Tag Content
SG ID
SG00000465 
UniProt Accession
Theoretical PI
6.54  
Molecular Weight
22073 Da  
Genbank Nucleotide ID
Genbank Protein ID
Gene Name
CDKN1B 
Gene Synonyms/Alias
KIP1 
Protein Name
Cyclin-dependent kinase inhibitor 1B 
Protein Synonyms/Alias
Cyclin-dependent kinase inhibitor p27; p27Kip1; 
Organism
Homo sapiens (Human) 
NCBI Taxonomy ID
9606 
Chromosome Location
chr:12;12867992-12875305;1
View in Ensembl genome browser  
Function in Stage
Function in Cell Type
Description
The expression of p27kip1 transiently increases by a factor of 3 after x-irradiation in whole testicular lysates. Hence, p27kip1 seems to be involved in the cellular response after DNA damage. 
The information of related literatures
1. T. L. Beumer, H. Kiyokawa, H. L. Roepers-Gajadien, L. A. van den Bos, T. M. Lock, I. S. Gademan, D. H. Rutgers, A. Koff and D. G. de Rooij (1999) Regulatory role of p27kip1 in the mouse and human testis. Endocrinology 140(4): 1834-40. 

Abstract
p27kip1 is a cyclin-dependent kinase inhibitor that regulates the G1/S transition of the cell cycle. Immunohistochemical analysis showed that during mouse testicular development p27kip1 is induced when the fetal germ cells, gonocytes, become quiescent on day 16 postcoitum, suggesting that p27kip1 is an important factor for the G1/G0 arrest in gonocytes. In the adult mouse and human testis, in general, spermatogonia are proliferating actively, except for undifferentiated spermatogonia that also go through a long G1/G0 arrest. However, none of the different types of germ cells immunohistochemically stained for p27kip1. During development, Sertoli cells are proliferating actively and only occasionally were lightly p27kip1 stained Sertoli cells observed. In contrast, in the adult testis the terminally differentiated Sertoli cells heavily stain for p27kip1. Twenty to 30% of both fetal and adult type Leydig cells lightly stained for p27kip1, possibly indicating the proportion of terminally differentiated cells in the Leydig cell population. In p27kip1 knockout mice, aberrations in the spermatogenic process were observed. First, an increase in the numbers ofA spermatogonia was found, and second, abnormal (pre)leptotene spermatocytes were observed, some of which seemingly tried to enter a mitotic division instead of entering the meiotic prophase. These observations indicate that p27kip1 has a role in the regulation of spermatogonial proliferation, or apoptosis, and the onset of the meiotic prophase in preleptotene spermatocytes. However, as p27kip1 is only expressed in Sertoli cells, the role of p27kip1 in both spermatogonia and preleptotene spermatocytes must be indirect. Hence, part of the supportive and/or regulatory role of Sertoli cells in the spermatogenic process depends on the expression of p27kip1 in these cells. Finally, we show that the expression of p27kip1 transiently increases by a factor of 3 after x-irradiation in whole testicular lysates. Hence, p27kip1 seems to be involved in the cellular response after DNA damage. PMID: [10098522] 

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Figures for illustrating the function of this protein/gene
Ref: T. L. Beumer, H. Kiyokawa, H. L. Roepers-Gajadien, L. A. van den Bos, T. M. Lock, I. S. Gademan, D. H. Rutgers, A. Koff and D. G. de Rooij (1999) Regulatory role of p27kip1 in the mouse and human testis. Endocrinology 140(4): 1834-40. PMID: [10098522]
Ref: T. L. Beumer, H. Kiyokawa, H. L. Roepers-Gajadien, L. A. van den Bos, T. M. Lock, I. S. Gademan, D. H. Rutgers, A. Koff and D. G. de Rooij (1999) Regulatory role of p27kip1 in the mouse and human testis. Endocrinology 140(4): 1834-40. PMID: [10098522]
Function
Important regulator of cell cycle progression. Involvedin G1 arrest. Potent inhibitor of cyclin E- and cyclin A-CDK2complexes. Forms a complex with cyclin type D-CDK4 complexes andis involved in the assembly, stability, and modulation of CCND1-CDK4 complex activation. Acts either as an inhibitor or anactivator of cyclin type D-CDK4 complexes depending on itsphosphorylation state and/or stoichometry. 
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Subcellular Location
Nucleus. Cytoplasm. Endosome (Bysimilarity). 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 intranslocation to the cytoplasm and cell cycle progression.Phosphorylation on Ser-10 facilitates nuclear export. Translocatesto the nucleus on phosphorylation of Tyr-88 and Tyr-89.Colocalizes at the endosome with SNX6; this leads to lysosomaldegradation (By similarity). 
Tissue Specificity
Expressed in all tissues tested. Highestlevels in skeletal muscle, lowest in liver and kidney. 
Gene Ontology
GO IDGO termEvidence
GO:0005829 C:cytosol TAS:Reactome.
GO:0005768 C:endosome IEA:UniProtKB-SubCell.
GO:0005654 C:nucleoplasm TAS:Reactome.
GO:0004861 F:cyclin-dependent protein kinase inhibitor activity TAS:ProtInc.
GO:0005072 F:transforming growth factor beta receptor, cytoplasmic mediator activity TAS:ProtInc.
GO:0006919 P:activation of cysteine-type endopeptidase activity involved in apoptotic process IDA:UniProtKB.
GO:0048102 P:autophagic cell death IDA:BHF-UCL.
GO:0071236 P:cellular response to antibiotic IEA:Compara.
GO:0071285 P:cellular response to lithium ion IDA:MGI.
GO:0071407 P:cellular response to organic cyclic compound IEA:Compara.
GO:0006977 P:DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest TAS:Reactome.
GO:0007173 P:epidermal growth factor receptor signaling pathway TAS:Reactome.
GO:0008543 P:fibroblast growth factor receptor signaling pathway TAS:Reactome.
GO:0000080 P:G1 phase of mitotic cell cycle TAS:Reactome.
GO:0000082 P:G1/S transition of mitotic cell cycle IDA:BHF-UCL.
GO:0006917 P:induction of apoptosis IDA:BHF-UCL.
GO:0048839 P:inner ear development IEA:Compara.
GO:0071850 P:mitotic cell cycle arrest IDA:UniProtKB.
GO:0043066 P:negative regulation of apoptotic process IEA:Compara.
GO:0030308 P:negative regulation of cell growth IDA:BHF-UCL.
GO:0008285 P:negative regulation of cell proliferation IDA:UniProtKB.
GO:0051271 P:negative regulation of cellular component movement IEA:Compara.
GO:0045736 P:negative regulation of cyclin-dependent protein kinase activity IEA:Compara.
GO:0060770 P:negative regulation of epithelial cell proliferation involved in prostate gland development IEA:Compara.
GO:0045930 P:negative regulation of mitotic cell cycle IDA:UniProtKB.
GO:0045892 P:negative regulation of transcription, DNA-dependent IDA:UniProtKB.
GO:0048011 P:nerve growth factor receptor signaling pathway TAS:Reactome.
GO:0048015 P:phosphatidylinositol-mediated signaling TAS:Reactome.
GO:0008284 P:positive regulation of cell proliferation IEA:Compara.
GO:0031116 P:positive regulation of microtubule polymerization IEA:Compara.
GO:0045732 P:positive regulation of protein catabolic process IDA:MGI.
GO:0006813 P:potassium ion transport IEA:Compara.
GO:0000079 P:regulation of cyclin-dependent protein kinase activity TAS:ProtInc.
GO:0000084 P:S phase of mitotic cell cycle TAS:Reactome.
GO:0007605 P:sensory perception of sound IEA:Compara.
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Interpro
Pfam
PF02234;    CDI;    1.
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SMART
PROSITE
PRINTS
Created Date
18-Oct-2012 
Record Type
Experiment identified 
Protein sequence Annotation
CHAIN         1    198       Cyclin-dependent kinase inhibitor 1B.
                             /FTId=PRO_0000190084.
MOTIF       153    169       Nuclear localization signal (Potential).
MOD_RES      10     10       Phosphoserine; by UHMK1.
MOD_RES      74     74       Phosphotyrosine; by SRC.
MOD_RES      88     88       Phosphotyrosine; by ABL, LYN, SRC and
                             JAK2.
MOD_RES      89     89       Phosphotyrosine.
MOD_RES     140    140       Phosphoserine.
MOD_RES     157    157       Phosphothreonine; by PKB/AKT1 and PIM1.
MOD_RES     187    187       Phosphothreonine; by PKB/AKT1 and CDK2.
MOD_RES     198    198       Phosphothreonine; by PKB/AKT1, RPS6KA1,
                             RPS6KA3 and PIM1.
VARIANT      15     15       R -> W (in dbSNP:rs2066828).
                             /FTId=VAR_011871.
VARIANT      69     69       P -> L (found in a patient with multiple
                             endocrine tumors; germline mutation;
                             reduced expression levels; shows impaired
                             binding to CDK2).
                             /FTId=VAR_064429.
VARIANT     109    109       V -> G (in dbSNP:rs2066827).
                             /FTId=VAR_011872.
MUTAGEN      10     10       S->A: Loss of phosphorylation by UHMK1.
                             No translocation to the cytoplasm.
                             Greater cell cycle arrest.
MUTAGEN      10     10       S->D: Exported to the cytoplasm. Inhibits
                             cell cycle arrest.
MUTAGEN      10     10       S->E: Increased stability in vivo and in
                             vitro.
MUTAGEN      74     74       Y->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.
MUTAGEN      88     88       Y->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.
MUTAGEN      89     89       Y->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.
MUTAGEN     157    157       T->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.
MUTAGEN     161    161       S->A: No change in PKB/AKT1-mediated
                             phosphorylation.
MUTAGEN     162    162       T->A: No change in PKB/AKT1-mediated
                             phosphorylation.
MUTAGEN     185    185       E->A,D,Q: Strongly reduced ubiquitination
                             by a TRIM21-containing SCF(SKP2) complex.
MUTAGEN     187    187       T->A,D: No change in PKB/AKT1- nor UHMK1-
                             mediated phosphorylation.
MUTAGEN     187    187       T->A: Abolishes phosphorylation-dependent
                             ubiquitination.
MUTAGEN     198    198       T->A,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.
CONFLICT     22     22       E -> D (in Ref. 2; AAD14244).
HELIX        38     49
TURN         50     53
HELIX        54     60
TURN         64     67
STRAND       71     74
STRAND       77     80
HELIX        86     89
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Nucleotide Sequence
Length: 597 bp   Go to nucleotide: FASTA
Protein Sequence
Length: 198 bp   Go to amino acid: FASTA
The verified Protein-Protein interaction information
UniProt
Gene Symbol Ref Databases
YWHABIntAct 
YWHAEHPRD 
YWHAQMINT 
ABL1HPRD 
Abl1IntAct 
AKT1HPRD 
AKT1HPRD 
_BioGRID 
_HPRD 
_HPRD 
_BioGRID 
CASP8HPRD 
CCNA1HPRD 
CCNA2BioGRID 
CCNB1IntAct 
CCND1BioGRID 
CCND2HPRD 
CCND3BioGRID 
CCNE1BioGRID 
CCNE2HPRD 
CDIPTString 
Cdk1IntAct 
CDK2HPRD 
CDK4BioGRID 
CDK5IntAct 
YWHABHPRD 
YWHAEIntAct 
YWHAHHPRD 
YWHAGHPRD 
YWHAQHPRD 
CDK6BioGRID 
_MINT 
AKT1BioGRID 
AKT1BioGRID 
GRB2HPRD 
_HPRD 
_BioGRID 
_BioGRID 
_BioGRID 
_BioGRID 
_HPRD 
CCNA1BioGRID 
CCNA2HPRD 
CCNB1HPRD 
CCND1HPRD 
CCND2IntAct 
CCND3HPRD 
CCNE1BioGRID 
CCNE2IntAct 
CDIPTString 
CDK2BioGRID 
CDK3HPRD 
CDK4HPRD 
CDK5HPRD 
CDK6BioGRID 
CKS1BIntAct 
COPS5HPRD 
CUL1IntAct 
CUL4ABioGRID 
DDB1BioGRID 
CCND3BioGRID 
CCND3BioGRID 
ARHGDIAIntAct 
GRB2HPRD 
KPNA2MINT 
KPNA3HPRD 
KPNA5HPRD 
Kpnb1IntAct 
MCM7HPRD 
MLLIntAct 
NUTF2IntAct 
NUP50BioGRID 
CDK2deltaTBioGRID 
_IntAct 
_IntAct 
TSC1BioGRID 
UBBBioGRID 
CCND1HPRD 
TSC1BioGRID 
KPNA3HPRD 
_HPRD 
RANIntAct 
RBX1IntAct 
RHOADIP 
RNF123BioGRID 
SKP2BioGRID 
SPDYAHPRD 
STMN1IntAct 
TRAF2HPRD 
TSC1BioGRID 
TSC2BioGRID 
UBE2D2IntAct 
UBA1IntAct 
UBAC1BioGRID 
UBBBioGRID 
UBCBioGRID 
UCHL1HPRD 
XPO1BioGRID 
CKS1BHPRD 
COPS5BioGRID 
CUL4AHPRD 
CCND3BioGRID 
CCND3BioGRID 
ARHGDIAHPRD 
GRB2DIP 
KPNA3IntAct 
KPNA5IntAct 
RPS6KA1DIP 
LYNHPRD 
MCM7DIP 
NUP50HPRD 
CDK2deltaTBioGRID 
_HPRD 
CKS1BHPRD 
CCND3MINT 
UBBHPRD 
CCND1BioGRID 
LYNHPRD 
PUBC1BioGRID 
RNF123BioGRID 
TRIM21BioGRID 
SKP2HPRD 
SPDYABioGRID 
SRCHPRD 
TRAF2IntAct 
TSC2HPRD 
UBE2D2BioGRID 
CDC34BioGRID 
UBBHPRD 
UBE2BBioGRID 
XPO1HPRD 
YES1HPRD 
Other Protein-Protein interaction resources
String database  
View Microarray data
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