Protein-coding gene in the species Homo sapiens
| SPRED1 |
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| Available structures |
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| PDB | Ortholog search: PDBe RCSB |
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| Identifiers |
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| Aliases | SPRED1, NFLS, PPP1R147, hSpred1, spred-1, sprouty related EVH1 domain containing 1, LGSS |
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| External IDs | OMIM: 609291; MGI: 2150016; HomoloGene: 24919; GeneCards: SPRED1; OMA:SPRED1 - orthologs |
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| Gene location (Human) |
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 | | Chr. | Chromosome 15 (human)[1] |
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| | Band | 15q14 | Start | 38,252,836 bp[1] |
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| End | 38,357,249 bp[1] |
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| Gene location (Mouse) |
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 | | Chr. | Chromosome 2 (mouse)[2] |
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| | Band | 2|2 E5 | Start | 116,951,855 bp[2] |
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| End | 117,012,760 bp[2] |
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| RNA expression pattern |
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| Bgee | | Human | Mouse (ortholog) |
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| Top expressed in | - ventricular zone
- mucosa of sigmoid colon
- Achilles tendon
- entorhinal cortex
- lower lobe of lung
- germinal epithelium
- epithelium of colon
- pancreatic epithelial cell
- cartilage tissue
- Brodmann area 46
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| | Top expressed in | - condyle
- primitive streak
- fossa
- Region I of hippocampus proper
- dorsomedial hypothalamic nucleus
- substantia nigra
- primary motor cortex
- cingulate gyrus
- suprachiasmatic nucleus
- olfactory tubercle
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| | More reference expression data |
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| BioGPS | |
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| Gene ontology |
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| Molecular function | - protein serine/threonine kinase inhibitor activity
- phosphatase binding
- stem cell factor receptor binding
- protein binding
- protein kinase binding
| | Cellular component | - membrane
- plasma membrane
- caveola
- cytosol
- nucleus
- cytoplasmic vesicle
| | Biological process | - negative regulation of phosphatase activity
- negative regulation of peptidyl-threonine phosphorylation
- regulation of protein deacetylation
- MAPK cascade
- multicellular organism development
- fibroblast growth factor receptor signaling pathway
- regulation of signal transduction
- positive regulation of DNA damage response, signal transduction by p53 class mediator
- vasculogenesis involved in coronary vascular morphogenesis
- negative regulation of cell migration involved in sprouting angiogenesis
- negative regulation of MAPK cascade
- negative regulation of protein kinase activity
- negative regulation of angiogenesis
- regulation of MAPK cascade
- negative regulation of ERK1 and ERK2 cascade
| | Sources:Amigo / QuickGO |
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| Wikidata |
| View/Edit Human | View/Edit Mouse |
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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.[5]
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.[5]
Clinical associations
Defects in this gene are a cause of neurofibromatosis type 1-like syndrome (NFLS).[5]
Mutations in this gene are associated with
Mutations
The following mutations have been observed:
- An exon 3 c.46C>T mutation leading to p.Arg16Stop.[8] 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)[9]
- 2 Frameshift (c.1048_c1049 delGG, c.149_1152del 4 bp)[9]
- Missense (V44D)[9]
- p.R18X and p.Q194X with phenotype altered pigmentation without tumoriginesis.[10]
Disease Database
SPRED1 gene variant database
See also
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000166068 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000027351 – 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.
- ^ a b c "Entrez Gene: sprouty-related".
- ^ Messiaen L, Yao S, Brems H, Callens T, Sathienkijkanchai A, Denayer E, Spencer E, Arn P, Babovic-Vuksanovic D, Bay C, Bobele G, Cohen BH, Escobar L, Eunpu D, Grebe T, Greenstein R, Hachen R, Irons M, Kronn D, Lemire E, Leppig K, Lim C, McDonald M, Narayanan V, Pearn A, Pedersen R, Powell B, Shapiro LR, Skidmore D, Tegay D, Thiese H, Zackai EH, Vijzelaar R, Taniguchi K, Ayada T, Okamoto F, Yoshimura A, Parret A, Korf B, Legius E (November 2009). "Clinical and mutational spectrum of neurofibromatosis type 1-like syndrome". JAMA. 302 (19): 2111–8. doi:10.1001/jama.2009.1663. PMID 19920235.
- Allison Gandey (November 18, 2009). "Legius Syndrome Often Mistaken for Neurofibromatosis Type 1". Medscape.
- ^ "Legius Syndrome (SPRED1) Sequencing & (NF1) Sequencing Exon 22 (Exon 17)" (PDF). ARUP Laboratories. 2010. Archived from the original (PDF) on 2012-05-30. Retrieved 2011-06-07.
- ^ a b Pasmant E, Ballerini P, Lapillonne H, Perot C, Vidaud D, Leverger G, Landman-Parker J (July 2009). "SPRED1 disorder and predisposition to leukemia in children". Blood. 114 (5): 1131. doi:10.1182/blood-2009-04-218503. PMID 19643996.
- ^ a b c d Spurlock G, Bennett E, Chuzhanova N, Thomas N, Jim HP, Side L, Davies S, Haan E, Kerr B, Huson SM, Upadhyaya M (July 2009). "SPRED1 mutations (Legius syndrome): another clinically useful genotype for dissecting the neurofibromatosis type 1 phenotype". Journal of Medical Genetics. 46 (7): 431–7. doi:10.1136/jmg.2008.065474. PMID 19443465.
- ^ Muram-Zborovski TM, Stevenson DA, Viskochil DH, Dries DC, Wilson AR (October 2010). "SPRED 1 mutations in a neurofibromatosis clinic". Journal of Child Neurology. 25 (10): 1203–9. doi:10.1177/0883073809359540. PMC 3243064. PMID 20179001.
Further reading
- Batz C, Hasle H, Bergsträsser E, van den Heuvel-Eibrink MM, Zecca M, Niemeyer CM, Flotho C (March 2010). "Does SPRED1 contribute to leukemogenesis in juvenile myelomonocytic leukemia (JMML)?" (PDF). Blood. 115 (12): 2557–8. doi:10.1182/blood-2009-12-260901. PMID 20339110.
- Lock P, I ST, Straffon AF, Schieb H, Hovens CM, Stylli SS (December 2006). "Spred-2 steady-state levels are regulated by phosphorylation and Cbl-mediated ubiquitination". Biochemical and Biophysical Research Communications. 351 (4): 1018–23. doi:10.1016/j.bbrc.2006.10.150. PMID 17094949.
- Pasmant E, Sabbagh A, Hanna N, Masliah-Planchon J, Jolly E, Goussard P, Ballerini P, Cartault F, Barbarot S, Landman-Parker J, Soufir N, Parfait B, Vidaud M, Wolkenstein P, Vidaud D, France RN (July 2009). "SPRED1 germline mutations caused a neurofibromatosis type 1 overlapping phenotype" (PDF). Journal of Medical Genetics. 46 (7): 425–30. doi:10.1136/jmg.2008.065243. PMID 19366998. S2CID 21323989.
- Nonami A, Taketomi T, Kimura A, Saeki K, Takaki H, Sanada T, Taniguchi K, Harada M, Kato R, Yoshimura A (September 2005). "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. doi:10.1111/j.1365-2443.2005.00886.x. PMID 16115197.
- Szafranski K, Schindler S, Taudien S, Hiller M, Huse K, Jahn N, Schreiber S, Backofen R, Platzer M (2007). "Violating the splicing rules: TG dinucleotides function as alternative 3' splice sites in U2-dependent introns". Genome Biology. 8 (8): R154. doi:10.1186/gb-2007-8-8-r154. PMC 2374985. PMID 17672918.
- Kimura K, Wakamatsu A, Suzuki Y, Ota T, Nishikawa T, Yamashita R, Yamamoto J, Sekine M, Tsuritani K, Wakaguri H, Ishii S, Sugiyama T, Saito K, Isono Y, Irie R, Kushida N, Yoneyama T, Otsuka R, Kanda K, Yokoi T, Kondo H, Wagatsuma M, Murakawa K, Ishida S, Ishibashi T, Takahashi-Fujii A, Tanase T, Nagai K, Kikuchi H, Nakai K, Isogai T, Sugano S (January 2006). "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes". Genome Research. 16 (1): 55–65. doi:10.1101/gr.4039406. PMC 1356129. PMID 16344560.
- Chandramouli S, Yu CY, Yusoff P, Lao DH, Leong HF, Mizuno K, Guy GR (January 2008). "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. doi:10.1074/jbc.M705457200. PMID 17974561.
- Johne C, Matenia D, Li XY, Timm T, Balusamy K, Mandelkow EM (April 2008). "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. doi:10.1091/mbc.E07-07-0730. PMC 2291396. PMID 18216281.
- Nonami A, Kato R, Taniguchi K, Yoshiga D, Taketomi T, Fukuyama S, Harada M, Sasaki A, Yoshimura A (December 2004). "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. doi:10.1074/jbc.M405189200. PMID 15465815.
- Talmud PJ, Drenos F, Shah S, Shah T, Palmen J, Verzilli C, Gaunt TR, Pallas J, Lovering R, Li K, Casas JP, Sofat R, Kumari M, Rodriguez S, Johnson T, Newhouse SJ, Dominiczak A, Samani NJ, Caulfield M, Sever P, Stanton A, Shields DC, Padmanabhan S, Melander O, Hastie C, Delles C, Ebrahim S, Marmot MG, Smith GD, Lawlor DA, Munroe PB, Day IN, Kivimaki M, Whittaker J, Humphries SE, Hingorani AD (November 2009). "Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip". American Journal of Human Genetics. 85 (5): 628–42. doi:10.1016/j.ajhg.2009.10.014. PMC 2775832. PMID 19913121.
- Colland F, Jacq X, Trouplin V, Mougin C, Groizeleau C, Hamburger A, Meil A, Wojcik J, Legrain P, Gauthier JM (July 2004). "Functional proteomics mapping of a human signaling pathway". Genome Research. 14 (7): 1324–32. doi:10.1101/gr.2334104. PMC 442148. PMID 15231748.
- Brems H, Chmara M, Sahbatou M, Denayer E, Taniguchi K, Kato R, Somers R, Messiaen L, De Schepper S, Fryns JP, Cools J, Marynen P, Thomas G, Yoshimura A, Legius E (September 2007). "Germline loss-of-function mutations in SPRED1 cause a neurofibromatosis 1-like phenotype". Nature Genetics. 39 (9): 1120–6. doi:10.1038/ng2113. PMID 17704776. S2CID 35709088.
- Yoshida T, Hisamoto T, Akiba J, Koga H, Nakamura K, Tokunaga Y, Hanada S, Kumemura H, Maeyama M, Harada M, Ogata H, Yano H, Kojiro M, Ueno T, Yoshimura A, Sata M (October 2006). "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. doi:10.1038/sj.onc.1209635. PMID 16652141. S2CID 22188239.
- King JA, Straffon AF, D'Abaco GM, Poon CL, I ST, Smith CM, Buchert M, Corcoran NM, Hall NE, Callus BA, Sarcevic B, Martin D, Lock P, Hovens CM (June 2005). "Distinct requirements for the Sprouty domain for functional activity of Spred proteins". The Biochemical Journal. 388 (Pt 2): 445–54. doi:10.1042/BJ20041284. PMC 1138951. PMID 15683364.
- Bailey SD, Xie C, Do R, Montpetit A, Diaz R, Mohan V, Keavney B, Yusuf S, Gerstein HC, Engert JC, Anand S (October 2010). "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. doi:10.2337/dc10-0452. PMC 2945168. PMID 20628086.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
