SPRED1

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]

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
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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]