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    SIKE1 suppressor of IKBKE 1 [ Homo sapiens (human) ]

    Gene ID: 80143, updated on 3-Nov-2024

    Summary

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    Official Symbol
    SIKE1provided by HGNC
    Official Full Name
    suppressor of IKBKE 1provided by HGNC
    Primary source
    HGNC:HGNC:26119
    See related
    Ensembl:ENSG00000052723 MIM:611656; AllianceGenome:HGNC:26119
    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
    SIKE
    Summary
    SIKE interacts with IKK-epsilon (IKBKE; MIM 605048) and TBK1 (MIM 604834) and acts as a suppressor of TLR3 (MIM 603029) and virus-triggered interferon activation pathways (Huang et al., 2005 [PubMed 16281057]).[supplied by OMIM, Mar 2008]
    Expression
    Ubiquitous expression in thyroid (RPKM 7.5), lymph node (RPKM 7.0) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See SIKE1 in Genome Data Viewer
    Location:
    1p13.2
    Exon count:
    5
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (114769479..114780685, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (114780904..114792111, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (115312100..115323306, complement)

    Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1548 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1549 Neighboring gene NRAS proto-oncogene, GTPase Neighboring gene MPRA-validated peak382 silencer Neighboring gene MPRA-validated peak383 silencer Neighboring gene cold shock domain containing E1 Neighboring gene RNY1 pseudogene 13 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:115300157-115301150 Neighboring gene H3K27ac hESC enhancer GRCh37_chr1:115322492-115323058 Neighboring gene H3K27ac hESC enhancer GRCh37_chr1:115323059-115323624 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:115332573-115333482 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:115333483-115334390 Neighboring gene ReSE screen-validated silencer GRCh37_chr1:115337845-115338062 Neighboring gene MPRA-validated peak384 silencer Neighboring gene nuclear receptor subfamily 1 group H member 5, pseudogene Neighboring gene synaptonemal complex protein 1 Neighboring gene uncharacterized LOC105378915

    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. Prognostic values of inhibitory κB kinases mRNA expression in human gastric cancer. Gayed DT, et al. Biosci Rep, 2019 Jan 31. PMID 30487159, Free PMC Article
    2. SIKE is an IKK epsilon/TBK1-associated suppressor of TLR3- and virus-triggered IRF-3 activation pathways. Huang J, et al. EMBO J, 2005 Dec 7. PMID 16281057, Free PMC Article
    3. Architecture, substructures, and dynamic assembly of STRIPAK complexes in Hippo signaling. Tang Y, et al. Cell Discov, 2019. PMID 30622739, Free PMC Article
    4. Mechanism of endogenous regulation of the type I interferon response by suppressor of IκB kinase epsilon (SIKE), a novel substrate of TANK-binding kinase 1 (TBK1). Marion JD, et al. J Biol Chem, 2013 Jun 21. PMID 23649622, Free PMC Article
    5. Suppressor of IKKɛ is an essential negative regulator of pathological cardiac hypertrophy. Deng KQ, et al. Nat Commun, 2016 Jun 1. PMID 27249321, Free PMC Article

    See all (31) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. mRNA expression of individual inhibitory kappaB kinases and SIKE are associated with unique prognostic significance and may act as valuable prognostic biomarkers and potential targets for future therapeutic interventions in gastric cancer.
      Title: Prognostic values of inhibitory κB kinases mRNA expression in human gastric cancer.
    2. SIKE, a negative regulator of the interferon pathway, attenuates pathological cardiac hypertrophy.
      Title: Suppressor of IKKɛ is an essential negative regulator of pathological cardiac hypertrophy.
    3. Data indicate that suppressor of IKKepsilon (SIKE) inhibits TANK-binding kinase 1 (TBK1)-mediated phosphorylation of interferon regulatory factor 3 (IRF3), which is essential to type I interferon production.
      Title: Mechanism of endogenous regulation of the type I interferon response by suppressor of IκB kinase epsilon (SIKE), a novel substrate of TANK-binding kinase 1 (TBK1).
    4. Overexpression of SIKE inhibits virus- and Toll-like receptor 3-triggered interferon-stimulated response elements (ISRE) but not NF-kappa B activation.
      Title: SIKE is an IKK epsilon/TBK1-associated suppressor of TLR3- and virus-triggered IRF-3 activation pathways.
    Submit: New GeneRIF Correction

    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

    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

    Potential readthrough

    Included gene: CSDE1

    Homology

    Clone Names

    • FLJ21168, DKFZp686A0768

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein kinase binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein-macromolecule adaptor activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables small GTPase binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in negative regulation of hippo signaling IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    part_of FAR/SIN/STRIPAK complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  

    General protein information

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    Preferred Names
    suppressor of IKBKE 1
    Names
    suppressor of IKK epsilon

    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_001102396.2 → NP_001095866.1  suppressor of IKBKE 1 isoform 1

      See identical proteins and their annotated locations for NP_001095866.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (1) encodes the longer isoform (1).
      Source sequence(s)
      AI039175, AL096773, BC005934, CR749219, DA950119
      Consensus CDS
      CCDS41371.1
      UniProtKB/Swiss-Prot
      Q9BRV8
      Related
      ENSP00000358541.5, ENST00000369528.9
      Conserved Domains (1) summary
      pfam05769
      Location:2 → 191
      DUF837; Protein of unknown function (DUF837)

    2. NM_025073.3 → NP_079349.2  suppressor of IKBKE 1 isoform 2

      See identical proteins and their annotated locations for NP_079349.2

      Status: VALIDATED

      Description
      Transcript Variant: This variant (2) uses an alternate in-frame splice site in the 5' coding region, compared to variant 1, which results in a protein (isoform 2) with a shorter N-terminus, compared to isoform 1.
      Source sequence(s)
      AI039175, AL096773, BC005934, DA950119
      Consensus CDS
      CCDS878.1
      UniProtKB/Swiss-Prot
      Q5TEZ7, Q5TEZ9, Q68DZ4, Q9BRV8, Q9H778
      Related
      ENSP00000060969.6, ENST00000060969.6
      Conserved Domains (1) summary
      pfam05769
      Location:2 → 187
      SIKE; SIKE family

    RNA

    1. NR_049741.2 RNA Sequence

      Status: VALIDATED

      Description
      Transcript Variant: This variant (3) uses an alternate splice site in the 5' coding region, compared to variant 1, which results in a frameshift and an early stop codon. The transcript is sufficiently abundant to represent as a RefSeq record; however, the predicted protein is not represented because the product is significantly truncated and the transcript is a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AL096773, CR936771, DB459255

    2. NR_049742.2 RNA Sequence

      Status: VALIDATED

      Description
      Transcript Variant: This variant (4) has multiple differences in the 5' coding region, compared to variant 1, which result in a frameshift and an early stop codon. The transcript is sufficiently abundant to represent as a RefSeq record; however, the predicted protein is not represented because the product is significantly truncated and the transcript is a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AI221103, AL096773, CR936771

    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_000001.11 Reference GRCh38.p14 Primary Assembly

      Range
      114769479..114780685 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060925.1 Alternate T2T-CHM13v2.0

      Range
      114780904..114792111 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9BRV8.1 GenPept UniProtKB/Swiss-Prot:Q9BRV8

    Gene LinkOut

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

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