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    SPRY4 sprouty RTK signaling antagonist 4 [ Homo sapiens (human) ]

    Gene ID: 81848, updated on 2-Nov-2024

    Summary

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    Official Symbol
    SPRY4provided by HGNC
    Official Full Name
    sprouty RTK signaling antagonist 4provided by HGNC
    Primary source
    HGNC:HGNC:15533
    See related
    Ensembl:ENSG00000187678 MIM:607984; AllianceGenome:HGNC:15533
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    HH17
    Summary
    This gene encodes a member of a family of cysteine- and proline-rich proteins. The encoded protein is an inhibitor of the receptor-transduced mitogen-activated protein kinase (MAPK) signaling pathway. Activity of this protein impairs the formation of active GTP-RAS. Nucleotide variation in this gene has been associated with hypogonadotropic hypogonadism 17 with or without anosmia. Alternative splicing results in a multiple transcript variants. [provided by RefSeq, Jun 2014]
    Expression
    Broad expression in lung (RPKM 7.4), adrenal (RPKM 7.0) and 24 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See SPRY4 in Genome Data Viewer
    Location:
    5q31.3
    Exon count:
    5
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 5 NC_000005.10 (142310430..142325021, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 5 NC_060929.1 (142841037..142855632, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 5 NC_000005.9 (141689995..141704586, complement)

    Chromosome 5 - NC_000005.10Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16470 Neighboring gene H3K27ac hESC enhancer GRCh37_chr5:141488095-141488596 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23316 Neighboring gene Nedd4 family interacting protein 1 Neighboring gene uncharacterized LOC107986455 Neighboring gene uncharacterized LOC124901096 Neighboring gene Sharpr-MPRA regulatory region 837 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:141560390-141560908 Neighboring gene MPRA-validated peak5506 silencer Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:141563869-141564765 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:141564766-141565661 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:141566635-141567164 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr5:141580673-141581872 Neighboring gene H3K27ac hESC enhancer GRCh37_chr5:141585270-141585770 Neighboring gene ReSE screen-validated silencer GRCh37_chr5:141595973-141596142 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23317 Neighboring gene H3K27ac hESC enhancer GRCh37_chr5:141612188-141612688 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:141616039-141616767 Neighboring gene H3K27ac hESC enhancer GRCh37_chr5:141625205-141625997 Neighboring gene H3K27ac hESC enhancer GRCh37_chr5:141625998-141626789 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:141659038-141659604 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:141659605-141660171 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:141690483-141690984 Neighboring gene NANOG hESC enhancer GRCh37_chr5:141699157-141699901 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:141702584-141703548 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:141703549-141704511 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:141711019-141711518 Neighboring gene SPRY4 intronic transcript 1 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr5:141721844-141723043 Neighboring gene SPRY4 antisense RNA 1 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:141734625-141735426 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:141735427-141736228 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16471 Neighboring gene ReSE screen-validated silencer GRCh37_chr5:141740409-141740647 Neighboring gene Sharpr-MPRA regulatory region 738 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:141743173-141743894 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23319 Neighboring gene H3K27ac hESC enhancer GRCh37_chr5:141768171-141768672 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:141771555-141772234 Neighboring gene Sharpr-MPRA regulatory region 12170 Neighboring gene Sharpr-MPRA regulatory region 9292 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:141854065-141854633 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr5:141854634-141855201 Neighboring gene H3K27ac hESC enhancer GRCh37_chr5:141855756-141856266 Neighboring gene H3K27ac hESC enhancer GRCh37_chr5:141902675-141903176 Neighboring gene VISTA enhancer hs1640 Neighboring gene ribosomal protein S12 pseudogene 10

    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
    • 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. SPRY4 regulates trophoblast proliferation and apoptosis via regulating IFN-γ-induced STAT1 expression and activation in recurrent miscarriage. Qin S, et al. Am J Reprod Immunol, 2020 Jun. PMID 32196809
    2. Lower Expression of SPRY4 Predicts a Poor Prognosis and Regulates Cell Proliferation in Colorectal Cancer. Zhou X, et al. Cell Physiol Biochem, 2016. PMID 27997895
    3. SPRY4 Intronic Transcript 1 Promotes Epithelial-Mesenchymal Transition Through Association with Snail1 in Osteosarcoma. Ru N, et al. DNA Cell Biol, 2016 Jun. PMID 26982001
    4. Sprouty4 interferes with cell proliferation and migration of breast cancer-derived cell lines. Vanas V, et al. Tumour Biol, 2014 May. PMID 24402575
    5. Sprouty4 negatively regulates protein kinase C activation by inhibiting phosphatidylinositol 4,5-biphosphate hydrolysis. Ayada T, et al. Oncogene, 2009 Feb 26. PMID 19137008

    See all (98) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. PDK1-stabilized LncRNA SPRY4-IT1 promotes breast cancer progression via activating NF-kappaB signaling pathway.
      Title: PDK1-stabilized LncRNA SPRY4-IT1 promotes breast cancer progression via activating NF-κB signaling pathway.
    2. Sprouty4 is epigenetically upregulated in human colorectal cancer.
      Title: Sprouty4 is epigenetically upregulated in human colorectal cancer.
    3. Sprouty 4 suppresses glioblastoma invasion by inhibiting ERK phosphorylation and ETS-1-induced matrix metalloproteinase-9.
      Title: Sprouty 4 suppresses glioblastoma invasion by inhibiting ERK phosphorylation and ETS-1-induced matrix metalloproteinase-9.
    4. SPRY4 promotes adipogenic differentiation of human mesenchymal stem cells through the MEK-ERK1/2 signaling pathway.
      Title: SPRY4 promotes adipogenic differentiation of human mesenchymal stem cells through the MEK-ERK1/2 signaling pathway.
    5. Identification of SPRY4 as a Novel Candidate Susceptibility Gene for Familial Nonmedullary Thyroid Cancer.
      Title: Identification of SPRY4 as a Novel Candidate Susceptibility Gene for Familial Nonmedullary Thyroid Cancer.
    6. Coupling HDAC4 with transcriptional factor MEF2D abrogates SPRY4-mediated suppression of ERK activation and elicits hepatocellular carcinoma drug resistance.
      Title: Coupling HDAC4 with transcriptional factor MEF2D abrogates SPRY4-mediated suppression of ERK activation and elicits hepatocellular carcinoma drug resistance.
    7. Sprouty4 negatively regulates ERK/MAPK signaling and the transition from in situ to invasive breast ductal carcinoma.
      Title: Sprouty4 negatively regulates ERK/MAPK signaling and the transition from in situ to invasive breast ductal carcinoma.
    8. Prevalence and associated phenotypes of DUSP6, IL17RD and SPRY4 variants in a large Chinese cohort with isolated hypogonadotropic hypogonadism.
      Title: Prevalence and associated phenotypes of DUSP6, IL17RD and SPRY4 variants in a large Chinese cohort with isolated hypogonadotropic hypogonadism.
    9. SPRY4 suppresses proliferation and induces apoptosis of colorectal cancer cells by repressing oncogene EZH2.
      Title: SPRY4 suppresses proliferation and induces apoptosis of colorectal cancer cells by repressing oncogene EZH2.
    10. SPRY4 regulates trophoblast proliferation and apoptosis via regulating IFN-gamma-induced STAT1 expression and activation in recurrent miscarriage.
      Title: SPRY4 regulates trophoblast proliferation and apoptosis via regulating IFN-γ-induced STAT1 expression and activation in recurrent miscarriage.
    Submit: New GeneRIF Correction See all GeneRIFs (60)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    EBI GWAS Catalog

    Description
    A genome-wide association study of testicular germ cell tumor.
    EBI GWAS Catalog
    Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
    EBI GWAS Catalog
    Identification of nine new susceptibility loci for testicular cancer, including variants near DAZL and PRDM14.
    EBI GWAS Catalog
    Meta-analysis identifies four new loci associated with testicular germ cell tumor.
    EBI GWAS Catalog
    Variants near DMRT1, TERT and ATF7IP are associated with testicular germ cell cancer.
    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)

    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

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein kinase inhibitor activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in animal organ development IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in cellular response to leukemia inhibitory factor IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of ERK1 and ERK2 cascade IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in negative regulation of Ras protein signal transduction IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in negative regulation of fibroblast growth factor receptor signaling pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in negative regulation of substrate adhesion-dependent cell spreading IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    is_active_in cytosol IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in focal adhesion HDA PubMed 
    located_in ruffle membrane IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    protein sprouty homolog 4
    Names
    sprouty homolog 4

    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.

    Genomic

    1. NG_034148.1 RefSeqGene

      Range
      5035..19626
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001127496.3 → NP_001120968.1  protein sprouty homolog 4 isoform 2

      See identical proteins and their annotated locations for NP_001120968.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at a downstream in-frame start codon, compared to variant 1. The encoded isoform (2) has a shorter N-terminus than isoform 1. Variants 2, 3, and 4 encode the same isoform (2).
      Source sequence(s)
      AC091825, AK096464, AK226147, BP387943, T32786
      Consensus CDS
      CCDS47296.1
      UniProtKB/Swiss-Prot
      A4FVB2, A4FVB3, Q6QIX2, Q9C003, Q9C004
      Related
      ENSP00000399468.2, ENST00000434127.3
      Conserved Domains (1) summary
      pfam05210
      Location:165 → 262
      Sprouty; Sprouty protein (Spry)

    2. NM_001293289.3 → NP_001280218.1  protein sprouty homolog 4 isoform 2

      See identical proteins and their annotated locations for NP_001280218.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) contains multiple differences in the 5' region and initiates translation at a downstream in-frame start codon, compared to variant 1. The encoded isoform (2) has a shorter N-terminus than isoform 1. Variants 2, 3, and 4 encode the same isoform (2).
      Source sequence(s)
      AC091825
      Consensus CDS
      CCDS47296.1
      UniProtKB/Swiss-Prot
      A4FVB2, A4FVB3, Q6QIX2, Q9C003, Q9C004
      Conserved Domains (1) summary
      pfam05210
      Location:165 → 262
      Sprouty; Sprouty protein (Spry)

    3. NM_001293290.3 → NP_001280219.1  protein sprouty homolog 4 isoform 2

      See identical proteins and their annotated locations for NP_001280219.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at a downstream in-frame start codon, compared to variant 1. The encoded isoform (2) has a shorter N-terminus than isoform 1. Variants 2, 3, and 4 encode the same isoform (2).
      Source sequence(s)
      AC091825
      Consensus CDS
      CCDS47296.1
      UniProtKB/Swiss-Prot
      A4FVB2, A4FVB3, Q6QIX2, Q9C003, Q9C004
      Conserved Domains (1) summary
      pfam05210
      Location:165 → 262
      Sprouty; Sprouty protein (Spry)

    4. NM_030964.5 → NP_112226.2  protein sprouty homolog 4 isoform 1

      See identical proteins and their annotated locations for NP_112226.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longer isoform (1).
      Source sequence(s)
      AC091825, AF227516, AK226147, BP387943, DA183391, T32786
      Consensus CDS
      CCDS4274.1
      UniProtKB/TrEMBL
      A0A0C4DFS6
      Related
      ENSP00000344967.4, ENST00000344120.4
      Conserved Domains (1) summary
      pfam05210
      Location:188 → 285
      Sprouty; Sprouty protein (Spry)

    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_000005.10 Reference GRCh38.p14 Primary Assembly

      Range
      142310430..142325021 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011537685.4 → XP_011535987.1  protein sprouty homolog 4 isoform X1

      See identical proteins and their annotated locations for XP_011535987.1

      UniProtKB/TrEMBL
      A0A0C4DFS6
      Conserved Domains (1) summary
      pfam05210
      Location:188 → 285
      Sprouty; Sprouty protein (Spry)

    2. XM_017009910.3 → XP_016865399.1  protein sprouty homolog 4 isoform X2

      UniProtKB/Swiss-Prot
      A4FVB2, A4FVB3, Q6QIX2, Q9C003, Q9C004
      Conserved Domains (1) summary
      pfam05210
      Location:165 → 262
      Sprouty; Sprouty protein (Spry)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060929.1 Alternate T2T-CHM13v2.0

      Range
      142841037..142855632 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054353586.1 → XP_054209561.1  protein sprouty homolog 4 isoform X1

      UniProtKB/TrEMBL
      A0A0C4DFS6

    2. XM_054353587.1 → XP_054209562.1  protein sprouty homolog 4 isoform X2

      UniProtKB/Swiss-Prot
      A4FVB2, A4FVB3, Q6QIX2, Q9C003, Q9C004
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9C004.2 GenPept UniProtKB/Swiss-Prot:Q9C004

    Gene LinkOut

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

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