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    SPRED2 sprouty related EVH1 domain containing 2 [ Homo sapiens (human) ]

    Gene ID: 200734, updated on 28-Oct-2024

    Summary

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    Official Symbol
    SPRED2provided by HGNC
    Official Full Name
    sprouty related EVH1 domain containing 2provided by HGNC
    Primary source
    HGNC:HGNC:17722
    See related
    Ensembl:ENSG00000198369 MIM:609292; AllianceGenome:HGNC:17722
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    NS14; Spred-2
    Summary
    SPRED2 is a member of the Sprouty (see SPRY1; MIM 602465)/SPRED family of proteins that regulate growth factor-induced activation of the MAP kinase cascade (see MAPK1; MIM 176948) (Nonami et al., 2004 [PubMed 15465815]).[supplied by OMIM, Mar 2008]
    Expression
    Ubiquitous expression in brain (RPKM 9.3), fat (RPKM 9.2) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See SPRED2 in Genome Data Viewer
    Location:
    2p14
    Exon count:
    11
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (65307175..65432599, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (65316846..65442268, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (65537985..65659733, complement)

    Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene H3K27ac hESC enhancer GRCh37_chr2:65454846-65455734 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15927 Neighboring gene actin related protein 2 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_58697 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr2:65502227-65502894 Neighboring gene uncharacterized LOC124907781 Neighboring gene ReSE screen-validated silencer GRCh37_chr2:65522924-65523106 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15928 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15929 Neighboring gene NANOG hESC enhancer GRCh37_chr2:65584660-65585161 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15930 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr2:65604858-65605439 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15931 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15932 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:65614878-65615414 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15933 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15934 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15935 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15936 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:65647515-65648016 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:65648017-65648516 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11579 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11580 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11581 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11582 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11583 Neighboring gene ReSE screen-validated silencer GRCh37_chr2:65663730-65663888 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr2:65664483-65665289 Neighboring gene uncharacterized LOC105374780 Neighboring gene uncharacterized LOC124907784

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Spred2 modulates the erythroid differentiation induced by imatinib in chronic myeloid leukemia cells. Yang Y, et al. PLoS One, 2015. PMID 25688862, Free PMC Article
    2. Negative impact of recipient SPRED2 deficiency on transplanted lung in a mouse model. Hashimoto K, et al. Transpl Immunol, 2019 Dec. PMID 31446154
    3. SPRED2 promotes autophagy and attenuates inflammatory response in IL-1β induced osteoarthritis chondrocytes via regulating the p38 MAPK signaling pathway. Wei J, et al. Tissue Cell, 2023 Jun. PMID 37058811
    4. SPRED2: A Novel Regulator of Epithelial-Mesenchymal Transition and Stemness in Hepatocellular Carcinoma Cells. Gao T, et al. Int J Mol Sci, 2023 Mar 5. PMID 36902429, Free PMC Article
    5. Autosomal recessive Noonan-like syndrome caused by homozygosity for a previously unreported variant in SPRED2. Markholt S, et al. Eur J Med Genet, 2023 Feb. PMID 36608738

    See all (69) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. SPRED2 Is a Novel Regulator of Autophagy in Hepatocellular Carcinoma Cells and Normal Hepatocytes.
      Title: SPRED2 Is a Novel Regulator of Autophagy in Hepatocellular Carcinoma Cells and Normal Hepatocytes.
    2. The ribosomal S6 kinase 2 (RSK2)-SPRED2 complex regulates the phosphorylation of RSK substrates and MAPK signaling.
      Title: The ribosomal S6 kinase 2 (RSK2)-SPRED2 complex regulates the phosphorylation of RSK substrates and MAPK signaling.
    3. SPRED2 promotes autophagy and attenuates inflammatory response in IL-1beta induced osteoarthritis chondrocytes via regulating the p38 MAPK signaling pathway.
      Title: SPRED2 promotes autophagy and attenuates inflammatory response in IL-1β induced osteoarthritis chondrocytes via regulating the p38 MAPK signaling pathway.
    4. SPRED2: A Novel Regulator of Epithelial-Mesenchymal Transition and Stemness in Hepatocellular Carcinoma Cells.
      Title: SPRED2: A Novel Regulator of Epithelial-Mesenchymal Transition and Stemness in Hepatocellular Carcinoma Cells.
    5. Autosomal recessive Noonan-like syndrome caused by homozygosity for a previously unreported variant in SPRED2.
      Title: Autosomal recessive Noonan-like syndrome caused by homozygosity for a previously unreported variant in SPRED2.
    6. SPRED2 loss-of-function causes a recessive Noonan syndrome-like phenotype.
      Title: SPRED2 loss-of-function causes a recessive Noonan syndrome-like phenotype.
    7. miR-19 Promotes Cell Proliferation, Invasion, Migration, and EMT by Inhibiting SPRED2-mediated Autophagy in Osteosarcoma Cells.
      Title: miR-19 Promotes Cell Proliferation, Invasion, Migration, and EMT by Inhibiting SPRED2-mediated Autophagy in Osteosarcoma Cells.
    8. Spred2 inhibits epithelialmesenchymal transition of colorectal cancer cells by impairing ERK signaling.
      Title: Spred2 inhibits epithelial‑mesenchymal transition of colorectal cancer cells by impairing ERK signaling.
    9. SPRED2 deficiency impairs autophagy, leading to cardiac dysfunction and life-threatening arrhythmias.
      Title: SPRED2 deficiency elicits cardiac arrhythmias and premature death via impaired autophagy.
    10. this study revealed more severe Ischemia-reperfusion injury in the lung grafts transplanted to Spred2-/- recipients
      Title: Negative impact of recipient SPRED2 deficiency on transplanted lung in a mouse model.
    Submit: New GeneRIF Correction See all GeneRIFs (31)

    Phenotypes

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    Review eQTL and phenotype association data in this region using PheGenI

    Associated conditions

    Description Tests
    Noonan syndrome 14
    MedGen: C5676916 OMIM: 619745 GeneReviews: Not available
    		not available

    EBI GWAS Catalog

    Description
    Genetics of rheumatoid arthritis contributes to biology and drug discovery.
    EBI GWAS Catalog
    Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci.
    EBI GWAS Catalog
    Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
    EBI GWAS Catalog
    Meta-analysis of genome-wide association studies in celiac disease and rheumatoid arthritis identifies fourteen non-HLA shared loci.
    EBI GWAS Catalog
    Novel risk loci for rheumatoid arthritis in Han Chinese and congruence with risk variants in Europeans.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • FLJ21897, FLJ31917, MGC163164

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein kinase binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables protein kinase binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein serine/threonine kinase inhibitor activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		 PubMed 
    enables stem cell factor receptor binding ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    Process Evidence Code Pubs
    involved_in negative regulation of ERK1 and ERK2 cascade IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in negative regulation of ERK1 and ERK2 cascade ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    acts_upstream_of_or_within negative regulation of MAPK cascade ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in negative regulation of epithelial to mesenchymal transition ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in negative regulation of lens fiber cell differentiation ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in negative regulation of peptidyl-threonine phosphorylation IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in negative regulation of transforming growth factor beta receptor signaling pathway ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in positive regulation of DNA damage response, signal transduction by p53 class mediator ISS
    Inferred from Sequence or Structural Similarity
    more info
    		 PubMed 
    involved_in regulation of protein deacetylation ISS
    Inferred from Sequence or Structural Similarity
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    is_active_in plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in plasma membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in transport vesicle membrane IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    sprouty-related, EVH1 domain-containing protein 2
    Names
    sprouty protein with EVH-1 domain 2, related sequence

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_001128210.2 → NP_001121682.1  sprouty-related, EVH1 domain-containing protein 2 isoform b

      See identical proteins and their annotated locations for NP_001121682.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (b) has a shorter and distinct N-terminus compared to isoform a.
      Source sequence(s)
      AK056479, AY299090, BC130292, DC335282
      Consensus CDS
      CCDS46308.1
      UniProtKB/TrEMBL
      B3KPL5
      Related
      ENSP00000393697.2, ENST00000443619.6
      Conserved Domains (3) summary
      cd10574
      Location:9 → 121
      EVH1_SPRED-like; Sprouty-related EVH1 domain-containing-like proteins EVH1 domain
      pfam05210
      Location:303 → 408
      Sprouty; Sprouty protein (Spry)
      pfam08633
      Location:226 → 298
      Rox3; Rox3 mediator complex subunit

    2. NM_181784.3 → NP_861449.2  sprouty-related, EVH1 domain-containing protein 2 isoform a

      See identical proteins and their annotated locations for NP_861449.2

      Status: VALIDATED

      Description
      Transcript Variant: This variant (1) encodes the longer isoform (a).
      Source sequence(s)
      AC012370, AK056479, AY299090, BC130292, DA102390
      Consensus CDS
      CCDS33211.1
      UniProtKB/Swiss-Prot
      A1L3V4, B7Z5K7, D6W5F7, E9PEP0, Q2NKX6, Q7Z698
      UniProtKB/TrEMBL
      B3KPL5
      Related
      ENSP00000348753.4, ENST00000356388.9
      Conserved Domains (3) summary
      cd10574
      Location:12 → 124
      EVH1_SPRED-like; Sprouty-related EVH1 domain-containing-like proteins EVH1 domain
      pfam05210
      Location:306 → 411
      Sprouty; Sprouty protein (Spry)
      pfam08633
      Location:229 → 301
      Rox3; Rox3 mediator complex subunit

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000002.12 Reference GRCh38.p14 Primary Assembly

      Range
      65307175..65432599 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_005264202.6 → XP_005264259.1  sprouty-related, EVH1 domain-containing protein 2 isoform X6

      Conserved Domains (1) summary
      cd10574
      Location:12 → 124
      EVH1_SPRED-like; Sprouty-related EVH1 domain-containing-like proteins EVH1 domain

    2. XM_005264200.6 → XP_005264257.2  sprouty-related, EVH1 domain-containing protein 2 isoform X3

      Conserved Domains (1) summary
      cd10574
      Location:12 → 124
      EVH1_SPRED-like; Sprouty-related EVH1 domain-containing-like proteins EVH1 domain

    3. XM_047443712.1 → XP_047299668.1  sprouty-related, EVH1 domain-containing protein 2 isoform X7

    4. XM_047443710.1 → XP_047299666.1  sprouty-related, EVH1 domain-containing protein 2 isoform X4

    5. XM_047443709.1 → XP_047299665.1  sprouty-related, EVH1 domain-containing protein 2 isoform X1

    6. XM_047443711.1 → XP_047299667.1  sprouty-related, EVH1 domain-containing protein 2 isoform X5

    7. XM_017003576.2 → XP_016859065.1  sprouty-related, EVH1 domain-containing protein 2 isoform X2

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060926.1 Alternate T2T-CHM13v2.0

      Range
      65316846..65442268 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054341012.1 → XP_054196987.1  sprouty-related, EVH1 domain-containing protein 2 isoform X6

    2. XM_054341009.1 → XP_054196984.1  sprouty-related, EVH1 domain-containing protein 2 isoform X3

    3. XM_054341013.1 → XP_054196988.1  sprouty-related, EVH1 domain-containing protein 2 isoform X7

    4. XM_054341010.1 → XP_054196985.1  sprouty-related, EVH1 domain-containing protein 2 isoform X4

    5. XM_054341007.1 → XP_054196982.1  sprouty-related, EVH1 domain-containing protein 2 isoform X1

    6. XM_054341011.1 → XP_054196986.1  sprouty-related, EVH1 domain-containing protein 2 isoform X5

    7. XM_054341008.1 → XP_054196983.1  sprouty-related, EVH1 domain-containing protein 2 isoform X2

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q7Z698.2 GenPept UniProtKB/Swiss-Prot:Q7Z698

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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