Cdkn2c cyclin dependent kinase inhibitor 2C [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Cdkn2cprovided by MGI
Official Full Name: cyclin dependent kinase inhibitor 2Cprovided by MGI
Primary source: MGI:MGI:105388
See related: Ensembl:ENSMUSG00000028551 AllianceGenome:MGI:105388
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: p18; INK4c; p18-INK6; p18INK4c; p18-INK4c
Summary: The protein encoded by this gene is a member of the INK4 family of cyclin-dependent kinase (cdk) inhibitors, and contains five ankyrin repeats. This protein interacts with both Cdk4 and Cdk6 to inhibit their kinase activities, and prevent their interactions with D-type cyclins, thereby negatively regulating cell division. This gene is differentially expressed in a variety of tissues, and is cell cycle regulated. Deletion of this gene can lead to tumor growth. Maximal expression is observed at the G2/M phase. Alternative splicing and promoter usage results in multiple transript variants. [provided by RefSeq, Aug 2014]
Expression: Broad expression in testis adult (RPKM 24.9), subcutaneous fat pad adult (RPKM 21.7) and 24 other tissues See more
Orthologs: human all
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Genomic context

Location:: 4 C7; 4 51.32 cM

Exon count:: 3

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	4	NC_000070.7 (109518073..109523953, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	4	NC_000070.6 (109660876..109666756, complement)

Chromosome 4 - NC_000070.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

p18INK4C and BRCA1 inhibit follicular cell proliferation and dedifferentiation in thyroid cancer.
Title: p18INK4C and BRCA1 inhibit follicular cell proliferation and dedifferentiation in thyroid cancer.
Gata3 deficiency promotes B cell differentiation and proliferation, and cooperates with p18 loss to induce B cell lymphomas
Title: Gata3 restrains B cell proliferation and cooperates with p18INK4c to repress B cell lymphomagenesis.
These results indicate that p18 blocks reprogramming by targeting Cdk4/6-mediated cell cycle regulation.
Title: p18 inhibits reprogramming through inactivation of Cdk4/6.
Host Tumor Suppressor p18(INK4c) Functions as a Potent Cell-Intrinsic Inhibitor of Murine Gammaherpesvirus 68 Reactivation and Pathogenesis.
Title: Host Tumor Suppressor p18(INK4c) Functions as a Potent Cell-Intrinsic Inhibitor of Murine Gammaherpesvirus 68 Reactivation and Pathogenesis.
Specifically, the proteins p18INK4C, p21CIP1 and p27KIP1 seem to play an outstanding role in the maintenance of the differentiated state of adipocytes.
Title: Changes in the expression of cyclin dependent kinase inhibitors during differentiation of immortalized fibroblasts into adipocytes.
CD4+ T cells from mice genetically deficient for p18ink4c divide more rapidly than wild-type cells in response to antigenic, costimulatory and growth factor signals.
Title: Regulation of T cell differentiation and alloimmunity by the cyclin-dependent kinase inhibitor p18ink4c.
p18 represents a potent and specific target for enhancing the self-renewal property of HSC, as demonstrated the effect of inhibitors
Title: Small-molecule inhibitors targeting INK4 protein p18(INK4C) enhance ex vivo expansion of haematopoietic stem cells.
p18 may play protective roles and may be associated with or partially account for the cytoprotective effects of HO-1 in cisplatin-induced acute kidney injury.
Title: Cyclin-dependent kinase inhibitor p18INK4c is involved in protective roles of heme oxygenase-1 in cisplatin-induced acute kidney injury.
Cdk4 and Cdk6 cooperate in hematopoietic tumor development and suggest a role for Cdk6 in sequestering INK4 proteins away from Cdk4.
Title: Cdk4 and Cdk6 cooperate in counteracting the INK4 family of inhibitors during murine leukemogenesis.
Gata3/Ruvbl2 complex regulates T helper 2 cell proliferation via repression of Cdkn2c expression.
Title: Gata3/Ruvbl2 complex regulates T helper 2 cell proliferation via repression of Cdkn2c expression.

Submit: New GeneRIF Correction See all GeneRIFs (40)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Targeted (2) 1 citation
Endonuclease-mediated (5)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH126134 (e-PCR)
- UniSTS:162846

D5Lev19 (e-PCR)
- UniSTS:239712

PMC141153P1 (e-PCR)
- UniSTS:270994

PMC141153P2 (e-PCR)
- UniSTS:270995

Cdkn2c (e-PCR), detects polymorphism
- UniSTS:527282

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables cyclin-dependent protein serine/threonine kinase inhibitor activity	IDA Inferred from Direct Assay more info	PubMed
enables cyclin-dependent protein serine/threonine kinase inhibitor activity	ISO Inferred from Sequence Orthology more info
enables protein kinase binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase binding	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
acts_upstream_of_or_within cell cycle	IEA Inferred from Electronic Annotation more info
acts_upstream_of cell population proliferation	IGI Inferred from Genetic Interaction more info	PubMed
involved_in negative regulation of cell growth	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of cell population proliferation	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within negative regulation of cyclin-dependent protein serine/threonine kinase activity	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of phosphorylation	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within negative regulation of stem cell proliferation	IGI Inferred from Genetic Interaction more info	PubMed
involved_in regulation of G1/S transition of mitotic cell cycle	ISO Inferred from Sequence Orthology more info
involved_in regulation of cyclin-dependent protein serine/threonine kinase activity	ISO Inferred from Sequence Orthology more info
acts_upstream_of stem cell proliferation	IGI Inferred from Genetic Interaction more info	PubMed

Component	Evidence Code	Pubs
located_in cytoplasm	ISO Inferred from Sequence Orthology more info
located_in nucleus	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: cyclin-dependent kinase 4 inhibitor C

Names: cyclin-dependent kinase 6 inhibitor; cyclin-dependent kinase inhibitor 2C (p18, inhibits CDK4)

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001301368.1 → NP_001288297.1 cyclin-dependent kinase 4 inhibitor C

See identical proteins and their annotated locations for NP_001288297.1

Status: REVIEWED

Description

Transcript Variant: This variant (1, also known as p18(L)) represents the longer transcript. Variants 1 and 2 encode the same protein.

Source sequence(s)

AA189303, AK003933, AL627392, BG085472

Consensus CDS

CCDS18467.1

UniProtKB/Swiss-Prot

Q60772

UniProtKB/TrEMBL

Q3U054, Q9D153

Related

ENSMUSP00000095534.4, ENSMUST00000097921.10

Conserved Domains (2) summary

cd00204
Location:37 → 156

ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other ...

sd00045
Location:37 → 67

ANK; ANK repeat [structural motif]
NM_007671.3 → NP_031697.1 cyclin-dependent kinase 4 inhibitor C

See identical proteins and their annotated locations for NP_031697.1

Status: REVIEWED

Description

Transcript Variant: This variant (2, also known as p18(S)) differs in the 5' UTR and represents use of an alternate promoter, compared to variant 1. Both variants 1 and 2 encode the same protein.

Source sequence(s)

AA189303, AK003933, AL627392, BF657811

Consensus CDS

CCDS18467.1

UniProtKB/Swiss-Prot

Q60772

UniProtKB/TrEMBL

Q3U054, Q9D153

Related

ENSMUSP00000070313.5, ENSMUST00000063531.5

Conserved Domains (2) summary

cd00204
Location:37 → 156

ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other ...

sd00045
Location:37 → 67

ANK; ANK repeat [structural motif]