SPRED1

SPRED1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3SYX
Identifiers
Aliases	SPRED1 , NFLS, PPP1R147, hSpred1, spred-1, sprouty related EVH1 domain containing 1, LGSS
External IDs	OMIM: 609291; MGI: 2150016; HomoloGene: 24919; GeneCards: SPRED1; OMA:SPRED1 - orthologs
Gene location (Human) Chr. Chromosome 15 (human) [1] Band 15q14 Start 38,252,836 bp [1] End 38,357,249 bp [1]
Gene location (Mouse) Chr. Chromosome 2 (mouse) [2] Band 2|2 E5 Start 116,951,855 bp [2] End 117,012,760 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) 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 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 More reference expression data BioGPS n/a
Gene ontology 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
Orthologs Species Human Mouse Entrez 161742 114715 Ensembl ENSG00000166068 ENSMUSG00000027351 UniProt Q7Z699 Q924S8 RefSeq (mRNA) NM_152594 NM_001277256 NM_033524 RefSeq (protein) NP_689807 NP_001264185 NP_277059 Location (UCSC) Chr 15: 38.25 – 38.36 Mb Chr 2: 116.95 – 117.01 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Sprouty-related, EVH1 domain-containing protein 1 (pronounced 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

• Legius syndrome. ^{[6] [7]}
• Childhood leukemia ^[8]

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

• Neurofibromin 1
• Patients without Neurofibromin 1 or SPRED1 mutations may have SPRED2, SPRED3 or SPRY1, SPRY2, SPRY3 or SPRY4 mutations. ^[9]

References

1. GRCh38: Ensembl release 89: ENSG00000166068 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000027351 – 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. "Entrez Gene: sprouty-related".
6. 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.
7. "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.
8. 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.
9. 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.
10. 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.^{[ permanent dead link ]}
• 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. Bibcode:2006BBRC..351.1018L. 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.