PSPH
Phosphoserine phosphatase is an enzyme that in humans is encoded by the PSPH gene.[5][6][7]
Function[]
The protein encoded by this gene belongs to a subfamily of the phosphotransferases. This encoded enzyme is responsible for the third and last step in L-serine formation. It catalyzes magnesium-dependent hydrolysis of L-phosphoserine and is also involved in an exchange reaction between L-serine and L-phosphoserine. Deficiency of this protein is thought to be linked to Williams syndrome.[7]
Clinical significance[]
Homozygous or compound heterozygous mutations in PSPH cause Neu-Laxova syndrome[8] and Phosphoserine phosphatase deficiency.[9][10]
Model organisms[]
Model organisms have been used in the study of PSPH function. A conditional knockout mouse line called Psphtm1a(EUCOMM)Hmgu 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]
| Characteristic | Phenotype |
|---|---|
| All data available at.[12][17] | |
| Peripheral blood leukocytes 6 Weeks | Normal |
| Insulin | Normal |
| Haematology 6 Weeks | Normal |
| Homozygous viability at P14 | Abnormal |
| Recessive lethal study | Abnormal |
| Body weight | Normal |
| Neurological assessment | Normal |
| Grip strength | Normal |
| Dysmorphology | Normal |
| Indirect calorimetry | Normal |
| Glucose tolerance test | 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 |
| Bone Marrow Immunophenotyping | Normal |
| Epidermal Immune Composition | Normal |
| Influenza Challenge | Normal |
References[]
- ^ a b c GRCh38: Ensembl release 89: ENSG00000146733 - Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000029446 - Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Koch GA, Eddy RL, Haley LL, Byers MG, McAvoy M, Shows TB (Apr 1983). "Assignment of the human phosphoserine phosphatase gene (PSP) to the pter leads to q22 region of chromosome 7". Cytogenetics and Cell Genetics. 35 (1): 67–9. doi:10.1159/000131839. PMID 6297854.
- ^ Collet JF, Gerin I, Rider MH, Veiga-da-Cunha M, Van Schaftingen E (May 1997). "Human L-3-phosphoserine phosphatase: sequence, expression and evidence for a phosphoenzyme intermediate". FEBS Letters. 408 (3): 281–4. doi:10.1016/S0014-5793(97)00438-9. PMID 9188776. S2CID 6952728.
- ^ a b "Entrez Gene: PSPH phosphoserine phosphatase".
- ^ Acuna-Hidalgo R, Schanze D, Kariminejad A, Nordgren A, Kariminejad MH, Conner P, Grigelioniene G, Nilsson D, Nordenskjöld M, Wedell A, Freyer C, Wredenberg A, Wieczorek D, Gillessen-Kaesbach G, Kayserili H, Elcioglu N, Ghaderi-Sohi S, Goodarzi P, Setayesh H, van de Vorst M, Steehouwer M, Pfundt R, Krabichler B, Curry C, MacKenzie MG, Boycott KM, Gilissen C, Janecke AR, Hoischen A, Zenker M (Sep 2014). "Neu-Laxova syndrome is a heterogeneous metabolic disorder caused by defects in enzymes of the L-serine biosynthesis pathway". American Journal of Human Genetics. 95 (3): 285–93. doi:10.1016/j.ajhg.2014.07.012. PMC 4157144. PMID 25152457.
- ^ Veiga-da-Cunha M, Collet JF, Prieur B, Jaeken J, Peeraer Y, Rabbijns A, Van Schaftingen E (Feb 2004). "Mutations responsible for 3-phosphoserine phosphatase deficiency". European Journal of Human Genetics. 12 (2): 163–6. doi:10.1038/sj.ejhg.5201083. PMID 14673469.
- ^ Jaeken J, Detheux M, Fryns JP, Collet JF, Alliet P, Van Schaftingen E (Jul 1997). "Phosphoserine phosphatase deficiency in a patient with Williams syndrome". Journal of Medical Genetics. 34 (7): 594–6. doi:10.1136/jmg.34.7.594. PMC 1051004. PMID 9222972.
- ^ 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.
- ^ a b "International Mouse Phenotyping Consortium".
- ^ 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.
- ^ Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
- ^ 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.
- ^ 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.
- ^ a b "Infection and Immunity Immunophenotyping (3i) Consortium".
Further reading[]
- Minelli A, Piantanida M, Maserati E, Campagnoli E, Pasquali F, Danesino C (Jan 1990). "Gene dosage effect in acquired monosomy 7: distinct behaviour of beta-glucuronidase and phosphoserine phosphatase". Genes, Chromosomes & Cancer. 1 (3): 216–20. doi:10.1002/gcc.2870010305. PMID 1964582. S2CID 31576324.
- Shetty KT (Dec 1990). "Phosphoserine phosphatase of human brain: partial purification, characterization, regional distribution, and effect of certain modulators including psychoactive drugs". Neurochemical Research. 15 (12): 1203–10. doi:10.1007/BF01208581. PMID 1965857. S2CID 24831337.
- Novelli G, Dallapiccola B (1989). "Gene dosage studies regionally assign the phosphoserine phosphatase gene to 7p15.1 or 2". Annales de Génétique. 31 (3): 195–6. PMID 2851960.
- Moro-Furlani AM, Turner VS, Hopkinson DA (May 1980). "Genetical and biochemical studies on human phosphoserine phosphatase". Annals of Human Genetics. 43 (4): 323–33. doi:10.1111/j.1469-1809.1980.tb01566.x. PMID 6249179. S2CID 13270060.
- Sparkes RS, Mohandas T, Sparkes MC (1983). "The human phosphoserine phosphatase gene (PSP) is mapped to chromosome 7 by somatic cell genetic analysis". Cytogenetics and Cell Genetics. 35 (1): 70–1. doi:10.1159/000131840. PMID 6297855.
- Maruyama K, Sugano S (Jan 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
- Jaeken J, Detheux M, Fryns JP, Collet JF, Alliet P, Van Schaftingen E (Jul 1997). "Phosphoserine phosphatase deficiency in a patient with Williams syndrome". Journal of Medical Genetics. 34 (7): 594–6. doi:10.1136/jmg.34.7.594. PMC 1051004. PMID 9222972.
- Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (Oct 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
- Collet JF, Stroobant V, Pirard M, Delpierre G, Van Schaftingen E (Jun 1998). "A new class of phosphotransferases phosphorylated on an aspartate residue in an amino-terminal DXDX(T/V) motif". The Journal of Biological Chemistry. 273 (23): 14107–12. doi:10.1074/jbc.273.23.14107. PMID 9603909.
- Collet JF, Stroobant V, Van Schaftingen E (Nov 1999). "Mechanistic studies of phosphoserine phosphatase, an enzyme related to P-type ATPases". The Journal of Biological Chemistry. 274 (48): 33985–90. doi:10.1074/jbc.274.48.33985. PMID 10567362.
- Peeraer Y, Rabijns A, Verboven C, Collet JF, Van Schaftingen E, De Ranter C (Jan 2002). "Purification, crystallization and preliminary X-ray diffraction analysis of human phosphoserine phosphatase". Acta Crystallographica Section D. 58 (Pt 1): 133–4. doi:10.1107/S0907444901017310. PMID 11752790.
- Kim HY, Heo YS, Kim JH, Park MH, Moon J, Kim E, Kwon D, Yoon J, Shin D, Jeong EJ, Park SY, Lee TG, Jeon YH, Ro S, Cho JM, Hwang KY (Nov 2002). "Molecular basis for the local conformational rearrangement of human phosphoserine phosphatase". The Journal of Biological Chemistry. 277 (48): 46651–8. doi:10.1074/jbc.M204866200. PMID 12213811.
- Veiga-da-Cunha M, Collet JF, Prieur B, Jaeken J, Peeraer Y, Rabbijns A, Van Schaftingen E (Feb 2004). "Mutations responsible for 3-phosphoserine phosphatase deficiency". European Journal of Human Genetics. 12 (2): 163–6. doi:10.1038/sj.ejhg.5201083. PMID 14673469.
- Peeraer Y, Rabijns A, Collet JF, Van Schaftingen E, De Ranter C (Aug 2004). "How calcium inhibits the magnesium-dependent enzyme human phosphoserine phosphatase". European Journal of Biochemistry. 271 (16): 3421–7. doi:10.1111/j.0014-2956.2004.04277.x. PMID 15291819.
- Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Molecular Systems Biology. 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931.
External links[]
- Overview of all the structural information available in the PDB for UniProt: P78330 (Phosphoserine phosphatase) at the PDBe-KB.
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Categories:
- Genes on human chromosome 7