TP53RK

TP53-regulating kinase, also known as PRPK is an enzyme that in humans is encoded by the TP53RK gene.[5][6][7] This protein is a serine/threonine protein kinase that phosphorylates p53 at Ser15.

TP53RK
Identifiers
Aliases	TP53RK, BUD32, C20orf64, Nori-2, Nori-2p, PRPK, dJ101A2, TP53 regulating kinase, GAMOS4, TPRKB
External IDs	OMIM: 608679 MGI: 1914050 HomoloGene: 6042 GeneCards: TP53RK
EC number	3.6.-.-
Gene location (Human) Chr. Chromosome 20 (human)[1] Band 20q13.12 Start 46,684,365 bp[1] End 46,689,444 bp[1]
Gene location (Mouse) Chr. Chromosome 2 (mouse)[2] Band 2|2 H3 Start 166,792,531 bp[2] End 166,799,505 bp[2]
Gene ontology Molecular function • kinase activity • transferase activity • nucleotide binding • protein kinase activity • p53 binding • GO:0001948 protein binding • ATP binding • hydrolase activity • phosphotransferase activity, alcohol group as acceptor • protein serine/threonine kinase activity Cellular component • cytosol • membrane • cell nucleus • nucleoplasm • EKC/KEOPS complex • cytoplasm Biological process • protein phosphorylation • phosphorylation • tRNA threonylcarbamoyladenosine metabolic process • tRNA processing • regulation of signal transduction by p53 class mediator Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	112858	76367
Ensembl	ENSG00000172315	ENSMUSG00000042854
UniProt	Q96S44	Q99PW4
RefSeq (mRNA)	NM_033550	NM_023815
RefSeq (protein)	NP_291028	NP_076304.2
Location (UCSC)	Chr 20: 46.68 – 46.69 Mb	Chr 2: 166.79 – 166.8 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

PRPK is part of the KEOPS/EKC complex, which participates in transcription control,[8] telomere regulation [9] and tRNA modification.[10]

Model organisms

Model organisms have been used in the study of TP53RK function. A conditional knockout mouse line called Trp53rk^{tm1a(EUCOMM)Wtsi} was generated at the Wellcome Trust Sanger Institute.[11] Male and female animals underwent a standardized phenotypic screen[12] to determine the effects of deletion.[13][14][15][16] Additional screens performed: - In-depth immunological phenotyping[17]

Trp53rk knockout mouse phenotype

Characteristic	Phenotype
All data available at.[12][17]
Insulin	Normal
Homozygous viability at P14	Normal
Recessive lethal study	Normal
Homozygous Fertility	Normal
Body weight	Normal
Neurological assessment	Normal
Grip strength	Normal
Dysmorphology	Normal
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Normal
Radiography	Normal
Eye morphology	Normal
Clinical chemistry	Normal
Haematology 16 Weeks	Normal
Peripheral blood leukocytes 16 Weeks	Normal
Heart weight	Normal
Salmonella infection	Normal
Cytotoxic T Cell Function	Normal
Spleen Immunophenotyping	Normal
Mesenteric Lymph Node Immunophenotyping	Normal
Epidermal Immune Composition	Normal

References

1. GRCh38: Ensembl release 89: ENSG00000172315 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000042854 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Abe Y, Matsumoto S, Wei S, Nezu K, Miyoshi A, Kito K, Ueda N, Shigemoto K, Hitsumoto Y, Nikawa J, Enomoto Y (Nov 2001). "Cloning and characterization of a p53-related protein kinase expressed in interleukin-2-activated cytotoxic T-cells, epithelial tumor cell lines, and the testes". The Journal of Biological Chemistry. 276 (47): 44003–11. doi:10.1074/jbc.M105669200. PMID 11546806.
6. Facchin S, Lopreiato R, Ruzzene M, Marin O, Sartori G, Götz C, Montenarh M, Carignani G, Pinna LA (Aug 2003). "Functional homology between yeast piD261/Bud32 and human PRPK: both phosphorylate p53 and PRPK partially complements piD261/Bud32 deficiency". FEBS Letters. 549 (1–3): 63–6. doi:10.1016/S0014-5793(03)00770-1. PMID 12914926. S2CID 24581860.
7. "Entrez Gene: TP53RK TP53 regulating kinase".
8. Kisseleva-Romanova E, Lopreiato R, Baudin-Baillieu A, Rousselle JC, Ilan L, Hofmann K, Namane A, Mann C, Libri D (Aug 2006). "Yeast homolog of a cancer-testis antigen defines a new transcription complex". The EMBO Journal. 25 (15): 3576–85. doi:10.1038/sj.emboj.7601235. PMC 1538566. PMID 16874308.
9. Downey M, Houlsworth R, Maringele L, Rollie A, Brehme M, Galicia S, Guillard S, Partington M, Zubko MK, Krogan NJ, Emili A, Greenblatt JF, Harrington L, Lydall D, Durocher D (Mar 2006). "A genome-wide screen identifies the evolutionarily conserved KEOPS complex as a telomere regulator". Cell. 124 (6): 1155–68. doi:10.1016/j.cell.2005.12.044. PMID 16564010. S2CID 13928061.
10. Srinivasan M, Mehta P, Yu Y, Prugar E, Koonin EV, Karzai AW, Sternglanz R (Mar 2011). "The highly conserved KEOPS/EKC complex is essential for a universal tRNA modification, t6A". The EMBO Journal. 30 (5): 873–81. doi:10.1038/emboj.2010.343. PMC 3049205. PMID 21183954.
11. Gerdin AK (2010). "The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x. S2CID 85911512.
12. "International Mouse Phenotyping Consortium".
13. Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
14. Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
15. Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247. S2CID 18872015.
16. White JK, Gerdin AK, Karp NA, Ryder E, Buljan M, Bussell JN, Salisbury J, Clare S, Ingham NJ, Podrini C, Houghton R, Estabel J, Bottomley JR, Melvin DG, Sunter D, Adams NC, Tannahill D, Logan DW, Macarthur DG, Flint J, Mahajan VB, Tsang SH, Smyth I, Watt FM, Skarnes WC, Dougan G, Adams DJ, Ramirez-Solis R, Bradley A, Steel KP (Jul 2013). "Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes". Cell. 154 (2): 452–64. doi:10.1016/j.cell.2013.06.022. PMC 3717207. PMID 23870131.
17. "Infection and Immunity Immunophenotyping (3i) Consortium".

Further reading

• Bonaldo MF, Lennon G, Soares MB (Sep 1996). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Research. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
• Miyoshi A, Kito K, Aramoto T, Abe Y, Kobayashi N, Ueda N (Apr 2003). "Identification of CGI-121, a novel PRPK (p53-related protein kinase)-binding protein". Biochemical and Biophysical Research Communications. 303 (2): 399–405. doi:10.1016/S0006-291X(03)00333-4. PMID 12659830.
• Wang SC, Lien HC, Xia W, Chen IF, Lo HW, Wang Z, Ali-Seyed M, Lee DF, Bartholomeusz G, Ou-Yang F, Giri DK, Hung MC (Sep 2004). "Binding at and transactivation of the COX-2 promoter by nuclear tyrosine kinase receptor ErbB-2". Cancer Cell. 6 (3): 251–61. doi:10.1016/j.ccr.2004.07.012. PMID 15380516.
• Abe Y, Takeuchi T, Imai Y, Murase R, Kamei Y, Fujibuchi T, Matsumoto S, Ueda N, Ogasawara M, Shigemoto K, Kito K (May 2006). "A Small Ras-like protein Ray/Rab1c modulates the p53-regulating activity of PRPK". Biochemical and Biophysical Research Communications. 344 (1): 377–85. doi:10.1016/j.bbrc.2006.03.071. PMID 16600182.