SpermatogenesisOnline 1.0
 

Tag Content
SG ID
SG00000772 
UniProt Accession
Theoretical PI
6.54  
Molecular Weight
22193 Da  
Genbank Nucleotide ID
Genbank Protein ID
Gene Name
Cdkn1b 
Gene Synonyms/Alias
 
Protein Name
Cyclin-dependent kinase inhibitor 1B 
Protein Synonyms/Alias
Cyclin-dependent kinase inhibitor p27; p27Kip1; 
Organism
Mus musculus (Mouse) 
NCBI Taxonomy ID
10090 
Chromosome Location
chr:6;134870419-134875531;1
View in Ensembl genome browser  
Function in Stage
Function in Cell Type
Description
p27kip1 is a cyclin-dependent kinase inhibitor that regulates the G1/S transition of the cell cycle. 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 cyclinD-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. Note=Nuclearand cytoplasmic in quiescent cells. AKT- or RSK-mediatedphosphorylation on Thr-197, binds 14-3-3, translocates to thecytoplasm and promotes cell cycle progression. Mitogen-activatedUHMK1 phosphorylation on Ser-10 also results in translocation tothe cytoplasm and cell cycle progression. Phosphorylation on Ser-10 facilitates nuclear export. Translocates to the nucleus onphosphorylation of Tyr-88 and Tyr-89 (By similarity). Colocalizesat the endosome with SNX6; this leads to lysosomal degradation. 
Tissue Specificity
 
Gene Ontology
GO IDGO termEvidence
GO:0005829 C:cytosol IDA:MGI.
GO:0005768 C:endosome IEA:UniProtKB-SubCell.
GO:0005634 C:nucleus IDA:MGI.
GO:0004861 F:cyclin-dependent protein kinase inhibitor activity IDA:MGI.
GO:0007050 P:cell cycle arrest IDA:MGI.
GO:0071236 P:cellular response to antibiotic IDA:MGI.
GO:0071285 P:cellular response to lithium ion ISO:MGI.
GO:0071407 P:cellular response to organic cyclic compound IDA:MGI.
GO:0000082 P:G1/S transition of mitotic cell cycle IDA:UniProtKB.
GO:0048839 P:inner ear development IMP:MGI.
GO:0043066 P:negative regulation of apoptotic process IMP:MGI.
GO:0051271 P:negative regulation of cellular component movement IDA:MGI.
GO:0045736 P:negative regulation of cyclin-dependent protein kinase activity IDA:MGI.
GO:0060770 P:negative regulation of epithelial cell proliferation involved in prostate gland development IMP:MGI.
GO:0008284 P:positive regulation of cell proliferation IMP:MGI.
GO:0031116 P:positive regulation of microtubule polymerization IGI:MGI.
GO:0006813 P:potassium ion transport IGI:MGI.
GO:0007605 P:sensory perception of sound IMP:MGI.
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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    197       Cyclin-dependent kinase inhibitor 1B.
                             /FTId=PRO_0000190085.
MOTIF       153    169       Nuclear localization signal (Potential).
SITE         90     90       Required for interaction with NUP50.
MOD_RES      10     10       Phosphoserine; by UHMK1.
MOD_RES      74     74       Phosphotyrosine; by SRC (By similarity).
MOD_RES      88     88       Phosphotyrosine; by ABL, LYN, SRC and
                             JAK2 (By similarity).
MOD_RES      89     89       Phosphotyrosine (By similarity).
MOD_RES     187    187       Phosphothreonine; by PKB/AKT1 and CDK2.
MOD_RES     197    197       Phosphothreonine; by PKB/AKT1, RPS6KA1,
                             RPS6KA3 and PIM1 (By similarity).
MUTAGEN      10     10       S->A: Loss of phosphorylation in G(0)
                             phase. No change in cMYC-induced CDK2-
                             mediated phosphorylation. Rapid
                             dissociation from the cyclin E/CDK2
                             complex after induction by cMYC. Loss of
                             protein stability in G(0) phase. No
                             change in protein stability at S-phase.
MUTAGEN      90     90       R->G: Loss of interaction with NUP50. No
                             cyclin E-mediated degradation of
                             phosphorylated p27KIP1.
MUTAGEN     187    187       T->E: Loss of cMyc-induced CDK2-mediated
                             phosphorylation. Rapid dissociation from
                             the cyclin E/CDK2 complex after induction
                             by c-Myc.
MUTAGEN     187    187       T->V: Loss of cMYC-induced CDK2-mediated
                             phosphorylation Dissociates very slowly
                             from the cyclin E/CDK2 complex after
                             induction by cMYC. Cell cycle arrest.
CONFLICT     22     22       E -> D (in Ref. 1; AAA21149, 2; AAA20235
                             and 5; AAH14296).
CONFLICT    141    141       P -> Q (in Ref. 1; AAA21149, 2; AAA20235
                             and 5; AAH14296).
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Nucleotide Sequence
Length: 889 bp   Go to nucleotide: FASTA
Protein Sequence
Length: 197 bp   Go to amino acid: FASTA
The verified Protein-Protein interaction information
Other Protein-Protein interaction resources
String database  
View Microarray data
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