SG ID

SG00001620 

UniProt Accession

CDN2D_MOUSE;Q60773;Q60794;Q91YV3;  

Theoretical PI

5.79  

Molecular Weight

17809 Da  

Genbank Nucleotide ID

U19597; U20497; AK132906; AC122525; CH466522; BC013898;  

Genbank Protein ID

AAC52194.1; AAA85437.1; BAE21414.1; EDL25176.1; AAH13898.1; 

Gene Name

Cdkn2d 

Gene Synonyms/Alias

 

Protein Name

Cyclin-dependent kinase 4 inhibitor D 

Protein Synonyms/Alias

p19-INK4d; 

Mus musculus (Mouse) 

10090 

Temporarily unavailable 

The information of related literatures

1. A. Gromley, M. L. Churchman, F. Zindy and C. J. Sherr (2009) Transient expression of the Arf tumor suppressor during male germ cell and eye development in Arf-Cre reporter mice. Proc Natl Acad Sci U S A 106(15): 6285-90. 

Abstract
The Arf tumor suppressor is expressed transiently during mouse male germ cell and eye development. Its inactivation compromises spermatogenesis as mice age and leads to aberrant postnatal proliferation of cells in the vitreous of the eye, resulting in blindness. In the testis, expression of p19(Arf) is limited to spermatogonia but is extinguished completely in spermatocytes, suggesting that Arf plays a physiologic role in setting the balance between mitotic and meiotic germ cell division. A knock-in allele encoding Cre recombinase regulated by the mouse cellular Arf promoter was used to trace Arf gene induction in vivo. Interbreeding to a reporter strain that expresses Cre-dependent YFP provided proof-of-principle that the Arf-Cre allele was appropriately expressed in the male germ cell lineage. However, Cre expression resulted in male sterility, limiting germ line transmission of the knock-in allele to females. Arf-null mice fail to resorb the hyaloid vasculature within the ocular vitreous where pericyte-like cells that express the PDGF-beta receptor (Pdgfrbeta) proliferate aberrantly and destroy the retina and lens. Interbreeding of Arf-Cre females to males containing "floxed" (FL) Arf alleles yielded Arf(Cre/FL) progeny that exhibited variably penetrant defects in visual acuity ranging to total blindness. Crossing the Arf(Cre/FL) alleles onto a Pdgfrbeta(FL/FL) background normalized all histopathology and restored vision fully. PMID: [19339492] 

2. F. Zindy, J. van Deursen, G. Grosveld, C. J. Sherr and M. F. Roussel (2000) INK4d-deficient mice are fertile despite testicular atrophy. Mol Cell Biol 20(1): 372-8. 

Abstract
The INK4 family of cyclin-dependent kinase (CDK) inhibitors includes four 15- to 19-kDa polypeptides (p16(INK4a), p15(INK4b), p18(INK4c), and p19(INK4d)) that bind to CDK4 and CDK6. By disrupting cyclin D-dependent holoenzymes, INK4 proteins prevent phosphorylation of the retinoblastoma protein and block entry into the DNA-synthetic phase of the cell division cycle. The founding family member, p16(INK4a), is a potent tumor suppressor in humans, whereas involvement, if any, of other INK4 proteins in tumor surveillance is less well documented. INK4c and INK4d are expressed during mouse embryogenesis in stereotypic tissue-specific patterns and are also detected, together with INK4b, in tissues of young mice. INK4a is expressed neither before birth nor at readily appreciable levels in young animals, but its increased expression later in life suggests that it plays some checkpoint function in response to cell stress, genotoxic damage, or aging per se. We used targeted gene disruption to generate mice lacking INK4d. These animals developed into adulthood, had a normal life span, and did not spontaneously develop tumors. Tumors did not arise at increased frequency in animals neonatally exposed to ionizing radiation or the carcinogen dimethylbenzanthrene. Mouse embryo fibroblasts, bone marrow-derived macrophages, and lymphoid T and B cells isolated from these animals proliferated normally and displayed typical lineage-specific differentiation markers. Males exhibited marked testicular atrophy associated with increased apoptosis of germ cells, although they remained fertile. The absence of tumors in INK4d-deficient animals demonstrates that, unlike INK4a, INK4d is not a tumor suppressor but is instead involved in spermatogenesis. PMID: [10594039] 

Figures for illustrating the function of this protein/gene

Function

Interacts strongly with CDK4 and CDK6 and inhibits them. 

Subcellular Location

Nucleus (By similarity). Cytoplasm (Bysimilarity). 

Tissue Specificity

 

Gene Ontology

GO ID	GO term	Evidence
GO:0005737	C:cytoplasm	IEA:UniProtKB-SubCell.
GO:0005634	C:nucleus	IEA:UniProtKB-SubCell.
GO:0007049	P:cell cycle	IEA:UniProtKB-KW.

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Interpro

IPR002110;    Ankyrin_rpt.
IPR020683;    Ankyrin_rpt-contain_dom.
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Pfam

PF12796;    Ank_2;    1.
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SMART

SM00248;    ANK;    3.
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PROSITE

PS50297;    ANK_REP_REGION;    1.
PS50088;    ANK_REPEAT;    1.
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PRINTS

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Created Date

18-Oct-2012 

Record Type

Experiment identified 

Protein sequence Annotation

Nucleotide Sequence

Length: 941 bp   Go to nucleotide: FASTA

Protein Sequence

Length: 166 bp   Go to amino acid: FASTA

The verified Protein-Protein interaction information

UniProt	Gene Symbol	Ref Databases
CDK6_HUMAN	CDK6	IntAct

Other Protein-Protein interaction resources

String database  

UniProt

Gene Symbol

Ref Databases

View Microarray data

Click to view expression 

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