Biology:SPRED1
From HandWiki
Short description: Protein-coding gene in the species Homo sapiens
 Generic protein structure example |
Sprouty-related, EVH1 domain-containing protein 1 (Spread-1) is a protein that in humans is encoded by the SPRED1 gene located on chromosome 15q13.2 and has seven coding exons.[1]
Function
SPRED-1 is a member of the Sprouty family of proteins and is phosphorylated by tyrosine kinase in response to several growth factors. The encoded protein can act as a homodimer or as a heterodimer with SPRED2 to regulate activation of the MAP kinase cascade.[1]
Clinical associations
Defects in this gene are a cause of neurofibromatosis type 1-like syndrome (NFLS).[1]
Mutations in this gene are associated with
- Legius syndrome.[2][3]
- Childhood leukemia[4]
Mutations
The following mutations have been observed:
- An exon 3 c.46C>T mutation leading to p.Arg16Stop.[4] This mutation may result in a truncated nonfunctional protein. Blast cells analysis displayed the same abnormality as germline mutation with one mutated allele (no somatic SPRED1 single-point mutation or loss of heterozygosity was found). The M4/M5 phenotype of AML are most closely associated with Ras pathway mutations. Ras pathway mutations are also associated with monosomy 7.
- 3 Nonsense (R16X, E73X, R262X)[5]
- 2 Frameshift (c.1048_c1049 delGG, c.149_1152del 4 bp)[5]
- Missense (V44D)[5]
- p.R18X and p.Q194X with phenotype altered pigmentation without tumoriginesis.[6]
Disease Database
See also
- Neurofibromin 1
- Patients without Neurofibromin 1 or SPRED1 mutations may have SPRED2, SPRED3 or SPRY1, SPRY2, SPRY3 or SPRY4 mutations.[5]
References
- ↑ 1.0 1.1 1.2 "Entrez Gene: sprouty-related". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=161742.
- ↑ "Clinical and mutational spectrum of neurofibromatosis type 1-like syndrome". JAMA 302 (19): 2111–8. November 2009. doi:10.1001/jama.2009.1663. PMID 19920235.
- Allison Gandey (November 18, 2009). "Legius Syndrome Often Mistaken for Neurofibromatosis Type 1". http://www.medscape.com/viewarticle/712643.
- ↑ "Legius Syndrome (SPRED1) Sequencing & (NF1) Sequencing Exon 22 (Exon 17)". ARUP Laboratories. 2010. http://www.aruplab.com/Testing-Information/resources/TechnicalBulletins/Legius%20Syndrome%20%28SPRED1%29%20Sequencing%20%26%20%28NF1%29%20Sequencing%20Exon%2022%20%28Exon%2017%29.pdf.
- ↑ 4.0 4.1 "SPRED1 disorder and predisposition to leukemia in children". Blood 114 (5): 1131. July 2009. doi:10.1182/blood-2009-04-218503. PMID 19643996.
- ↑ 5.0 5.1 5.2 5.3 "SPRED1 mutations (Legius syndrome): another clinically useful genotype for dissecting the neurofibromatosis type 1 phenotype". Journal of Medical Genetics 46 (7): 431–7. July 2009. doi:10.1136/jmg.2008.065474. PMID 19443465.
- ↑ "SPRED 1 mutations in a neurofibromatosis clinic". Journal of Child Neurology 25 (10): 1203–9. October 2010. doi:10.1177/0883073809359540. PMID 20179001.
Further reading
- "Does SPRED1 contribute to leukemogenesis in juvenile myelomonocytic leukemia (JMML)?". Blood 115 (12): 2557–8. March 2010. doi:10.1182/blood-2009-12-260901. PMID 20339110. http://www.zora.uzh.ch/40092/1/Batz_et_al_Blood.pdf.
- "Spred-2 steady-state levels are regulated by phosphorylation and Cbl-mediated ubiquitination". Biochemical and Biophysical Research Communications 351 (4): 1018–23. December 2006. doi:10.1016/j.bbrc.2006.10.150. PMID 17094949.
- "SPRED1 germline mutations caused a neurofibromatosis type 1 overlapping phenotype". Journal of Medical Genetics 46 (7): 425–30. July 2009. doi:10.1136/jmg.2008.065243. PMID 19366998. https://hal.archives-ouvertes.fr/hal-00552683/file/PEER_stage2_10.1136%252Fjmg.2008.065243.pdf.
- "The Sprouty-related protein, Spred-1, localizes in a lipid raft/caveola and inhibits ERK activation in collaboration with caveolin-1". Genes to Cells 10 (9): 887–95. September 2005. doi:10.1111/j.1365-2443.2005.00886.x. PMID 16115197.
- "Violating the splicing rules: TG dinucleotides function as alternative 3' splice sites in U2-dependent introns". Genome Biology 8 (8): R154. 2007. doi:10.1186/gb-2007-8-8-r154. PMID 17672918.
- "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes". Genome Research 16 (1): 55–65. January 2006. doi:10.1101/gr.4039406. PMID 16344560.
- "Tesk1 interacts with Spry2 to abrogate its inhibition of ERK phosphorylation downstream of receptor tyrosine kinase signaling". The Journal of Biological Chemistry 283 (3): 1679–91. January 2008. doi:10.1074/jbc.M705457200. PMID 17974561.
- "Spred1 and TESK1--two new interaction partners of the kinase MARKK/TAO1 that link the microtubule and actin cytoskeleton". Molecular Biology of the Cell 19 (4): 1391–403. April 2008. doi:10.1091/mbc.E07-07-0730. PMID 18216281.
- "Spred-1 negatively regulates interleukin-3-mediated ERK/mitogen-activated protein (MAP) kinase activation in hematopoietic cells". The Journal of Biological Chemistry 279 (50): 52543–51. December 2004. doi:10.1074/jbc.M405189200. PMID 15465815.
- "Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip". American Journal of Human Genetics 85 (5): 628–42. November 2009. doi:10.1016/j.ajhg.2009.10.014. PMID 19913121.
- "Functional proteomics mapping of a human signaling pathway". Genome Research 14 (7): 1324–32. July 2004. doi:10.1101/gr.2334104. PMID 15231748.
- "Germline loss-of-function mutations in SPRED1 cause a neurofibromatosis 1-like phenotype". Nature Genetics 39 (9): 1120–6. September 2007. doi:10.1038/ng2113. PMID 17704776.
- "Spreds, inhibitors of the Ras/ERK signal transduction, are dysregulated in human hepatocellular carcinoma and linked to the malignant phenotype of tumors". Oncogene 25 (45): 6056–66. October 2006. doi:10.1038/sj.onc.1209635. PMID 16652141.
- "Distinct requirements for the Sprouty domain for functional activity of Spred proteins". The Biochemical Journal 388 (Pt 2): 445–54. June 2005. doi:10.1042/BJ20041284. PMID 15683364.
- "Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study". Diabetes Care 33 (10): 2250–3. October 2010. doi:10.2337/dc10-0452. PMID 20628086.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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