Cyclin-dependent kinase 4 inhibitor C (CDKN2C)
The protein contains 168 amino acids for an estimated molecular weight of 18127 Da.
Interacts strongly with CDK6, weakly with CDK4. Inhibits cell growth and proliferation with a correlated dependence on endogenous retinoblastoma protein RB. (updated: April 1, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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| Variant | Description |
|---|---|
| breast cancer | |
| dbSNP:rs17851380 |
Biological Process
Cell cycle arrest
G1/S transition of mitotic cell cycle
Mitotic cell cycle
Negative regulation of cell growth
Negative regulation of cell population proliferation
Negative regulation of cyclin-dependent protein serine/threonine kinase activity
Negative regulation of G1/S transition of mitotic cell cycle
Negative regulation of phosphorylation
Negative regulation of protein serine/threonine kinase activity
Obsolete negative regulation of cyclin-dependent protein serine/threonine kinase activity involved in G1/S transition of mitotic cell cycle
Oligodendrocyte differentiation
Regulation of cyclin-dependent protein serine/threonine kinase activity
The reference OMIM entry for this protein is 603369
Cyclin-dependent kinase inhibitor 2c; cdkn2c
P18(ink4c)
DESCRIPTION
Cyclin-dependent kinase inhibitors (CKIs) are a group of low molecular weight proteins that associate with cyclin-CDK complexes or CDKs alone and inhibit their activity. Members of the INK4 family of CKIs, which includes CDKN2C, specifically bind and inhibit CDK4 (123829) and CDK6 (603368), thereby preventing cyclin D-dependent phosphorylation of RB1 (614041). See INK4D (600947).CLONING
By using a yeast 2-hybrid screen to search for CDK6-interacting proteins, Guan et al. (1994) isolated a partial cDNA encoding a protein that they designated p18 based on its molecular mass of 18 kD. They used the partial cDNA to screen a HeLa cell library and recovered additional cDNAs corresponding to the entire p18 coding region. Sequence analysis revealed that the predicted 168-amino acid p18 protein shares 38% and 42% sequence identity with p16/INK4A (600160) and p14/INK4B (600431), respectively. Like p14 and p16, p18 contains an ankyrin repeat domain. Using Northern blot analysis, Guan et al. (1994) found that p18 is expressed as multiple transcripts in various human tissues, with the strongest expression in skeletal muscle.GENE FUNCTION
Guan et al. (1994) showed that, both in vivo and in vitro, p18 interacted strongly with CDK6 and weakly with CDK4, but not with the other CDKs tested. Recombinant p18 inhibited the kinase activity of cyclin D-CDK6 in vitro. Ectopic expression of either p16 or p18 suppressed the growth of human cells in a manner that appears to correlate with the presence of a wildtype RB1 function.GENE STRUCTURE
Blais et al. (1998) determined that the p18, or INK4C, gene contains 3 exons and spans more than 7.5 kb.MAPPING
By fluorescence in situ hybridization, Guan et al. (1994) mapped the p18 gene to 1p32, a chromosomal region associated with abnormalities in a variety of human tumors.MOLECULAR GENETICS
Lapointe et al. (1996) identified a single amino acid substitution (ala72 to pro; A72P) in BT-20 human breast cancer cells that abrogated the ability of p18 to interact with CDK6 and to suppress cell growth. These authors suggested that p18 inactivation by point mutations may contribute to deregulated growth control in certain cell lines and/or tumors. Blais et al. (1998) found this p18 variant in 3 of 35 breast tumors examined, and suggested that it may be a polymorphism.ANIMAL MODEL
Zindy et al. (2001) determined that both Ink4c and Ink4d were expressed in the seminiferous tubules of postnatal wildtype mice, being largely confined to postmitotic spermatocytes undergoing meiosis. Loss of either Ink4c or Ink4d alone was associated with male fertility, but double-knockout males were sterile. Spermatogonia did not differentiate properly and became apoptotic. Residual spermatozoa had reduced motility and decreased viability. Loss of Ink4c alone or in combination with loss of Ink4d was associated with impaired differentiation of Leydig cells and reduced testosterone levels, but there was no effect on the levels of luteinizing hormone produced by the anterior pituitary. Loss of Ink4c or Ink4d, either singly or in combination, had no effect on female reproductive function. Bai et al. (2003) noted that targeted disruption of Ink4c in mice leads to spontaneous pituitary tumors and lymphomas later in life. Treatment of Inc4c null and heterozygous mice with a chemical carcinogen resulted in tumor development at an accelerated rate. Bai et al. (2003) ... More on the omim web site
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 25, 2017: Additional information
No protein expression data in P. Mayeux work for CDKN2C
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 603369 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed