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    THEMIS thymocyte selection associated [ Homo sapiens (human) ]

    Gene ID: 387357, updated on 2-Nov-2024

    Summary

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    Official Symbol
    THEMISprovided by HGNC
    Official Full Name
    thymocyte selection associatedprovided by HGNC
    Primary source
    HGNC:HGNC:21569
    See related
    Ensembl:ENSG00000172673 MIM:613607; AllianceGenome:HGNC:21569
    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
    GASP; SPOT; TSEPA; THEMIS1; C6orf190; C6orf207
    Summary
    This gene encodes a protein that plays a regulatory role in both positive and negative T-cell selection during late thymocyte development. The protein functions through T-cell antigen receptor signaling, and is necessary for proper lineage commitment and maturation of T-cells. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2009]
    Expression
    Biased expression in lymph node (RPKM 2.2), appendix (RPKM 1.1) and 12 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See THEMIS in Genome Data Viewer
    Location:
    6q22.33
    Exon count:
    11
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 6 NC_000006.12 (127696628..127918595, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 6 NC_060930.1 (128897128..129107550, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (128029339..128239740, complement)

    Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC124901400 Neighboring gene long intergenic non-protein coding RNA 2536 Neighboring gene MPRA-validated peak6119 silencer Neighboring gene mitochondrial ribosomal protein S17 pseudogene 5 Neighboring gene NANOG hESC enhancer GRCh37_chr6:128343084-128343585 Neighboring gene protein tyrosine phosphatase receptor type K Neighboring gene PTPRK antisense RNA 1 Neighboring gene uncharacterized LOC124900216 Neighboring gene ReSE screen-validated silencer GRCh37_chr6:128446823-128447021

    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. Increased THEMIS First Exon Usage in CD4+ T-Cells Is Associated with a Genotype that Is Protective against Multiple Sclerosis. Davies JL, et al. PLoS One, 2016. PMID 27438997, Free PMC Article
    2. Themis imposes new law and order on positive selection. Allen PM. Nat Immunol, 2009 Aug. PMID 19621038
    3. Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer. Barbieri CE, et al. Nat Genet, 2012 May 20. PMID 22610119, Free PMC Article
    4. THEMIS and PTPRK in celiac intestinal mucosa: coexpression in disease and after in vitro gliadin challenge. Bondar C, et al. Eur J Hum Genet, 2014 Mar. PMID 23820479, Free PMC Article
    5. T cell receptor (TCR)-induced tyrosine phosphorylation dynamics identifies THEMIS as a new TCR signalosome component. Brockmeyer C, et al. J Biol Chem, 2011 Mar 4. PMID 21189249, Free PMC Article

    See all (32) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. THEMIS-SHP1 Recruitment by 4-1BB Tunes LCK-Mediated Priming of Chimeric Antigen Receptor-Redirected T Cells
      Title: THEMIS-SHP1 Recruitment by 4-1BB Tunes LCK-Mediated Priming of Chimeric Antigen Receptor-Redirected T Cells.
    2. we have demonstrated mutually exclusive use of exon 1 and 2 amongst 16 novel THEMIS isoforms. We also show inverse correlation between THEMIS expression in human CD4+ T-cells and dosage of the multiple sclerosis risk allele at rs13204742, driven by reduced expression of exon 1- containing isoforms
      Title: Increased THEMIS First Exon Usage in CD4+ T-Cells Is Associated with a Genotype that Is Protective against Multiple Sclerosis.
    3. we found that THEMIS directly regulated the catalytic activity of the tyrosine phosphatase SHP-1.
      Title: THEMIS enhances TCR signaling and enables positive selection by selective inhibition of the phosphatase SHP-1.
    4. the THEMIS:SHP complex dampens early TCR signalling by a previously unknown molecular mechanism that favours T-cell survival.
      Title: A THEMIS:SHP1 complex promotes T-cell survival.
    5. THEMIS showed higher mRNA expression in active celiac disease compared with treated patients and controls.
      Title: THEMIS and PTPRK in celiac intestinal mucosa: coexpression in disease and after in vitro gliadin challenge.
    6. THEMIS binding to GRB2 was required for thymocyte development.
      Title: GRB2-mediated recruitment of THEMIS to LAT is essential for thymocyte development.
    7. Themis1 exhibits the same potential to restore T cell development and T cell receptor-mediated signaling in Themis1-deficient mice.
      Title: Interchangeability of Themis1 and Themis2 in thymocyte development reveals two related proteins with conserved molecular function.
    8. SPOP mutations may define a new molecular subtype of prostate cancer.
      Title: Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer.
    9. specific role for THEMIS in early TCR signalosome function
      Title: T cell receptor (TCR)-induced tyrosine phosphorylation dynamics identifies THEMIS as a new TCR signalosome component.
    10. Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
      Title: Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
    Submit: New GeneRIF Correction See all GeneRIFs (14)

    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
    Generalization of variants identified by genome-wide association studies for electrocardiographic traits in African Americans.
    EBI GWAS Catalog
    Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.
    EBI GWAS Catalog
    Genome-wide analysis of polymorphisms associated with cytokine responses in smallpox vaccine recipients.
    EBI GWAS Catalog
    Multiple common variants for celiac disease influencing immune gene expression.
    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

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • FLJ40584, MGC163388

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in T cell receptor signaling pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in T cell receptor signaling pathway ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in adaptive immune response IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative T cell selection ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in positive T cell selection ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    Component Evidence Code Pubs
    part_of COP9 signalosome ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    located_in cell-cell junction IEA
    Inferred from Electronic Annotation
    more info
    		  
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytoplasm ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in nucleus ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  

    General protein information

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    Preferred Names
    protein THEMIS
    Names
    GRB2-associated protein
    signaling phosphoprotein specific for T cells
    thymocyte selection pathway associated
    thymocyte-expressed molecule involved in selection

    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_016226.2 RefSeqGene

      Range
      22537..215395
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001010923.3 → NP_001010923.1  protein THEMIS isoform 2

      See identical proteins and their annotated locations for NP_001010923.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks an alternate in-frame exon in the central coding region, compared to variant 1, resulting in an isoform (2) that is shorter than isoform 1.
      Source sequence(s)
      AL035470, AL356432, AL365224
      Consensus CDS
      CCDS34534.1
      UniProtKB/Swiss-Prot
      A1L4F0, A8K7N1, B3KT31, B3KW32, B3KY07, F5H1J9, Q5T3C4, Q5T3C5, Q6MZT7, Q8N1K5
      UniProtKB/TrEMBL
      A0A0D9SFD2
      Related
      ENSP00000357231.2, ENST00000368248.5
      Conserved Domains (1) summary
      pfam12736
      Location:17 → 265
      CABIT; Cell-cycle sustaining, positive selection,

    2. NM_001164685.2 → NP_001158157.1  protein THEMIS isoform 1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longest isoform (1).
      Source sequence(s)
      AL035470, AL356432, AL365224
      Consensus CDS
      CCDS55056.1
      UniProtKB/TrEMBL
      A0A0D9SFD2
      Related
      ENSP00000487358.1, ENST00000630369.2
      Conserved Domains (2) summary
      pfam12736
      Location:17 → 265
      CABIT; Cell-cycle sustaining, positive selection,
      pfam13900
      Location:586 → 608
      GVQW; Putative domain of unknown function

    3. NM_001164687.2 → NP_001158159.1  protein THEMIS isoform 3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) differs in the 5' UTR, lacks a portion of the 5' coding region, uses a downstream translational start codon, and lacks an alternate in-frame exon in the central coding region, compared to variant 1. The encoded isoform (3) is shorter than isoform 1.
      Source sequence(s)
      AK124031, BC043608, BC130516, DA818250
      Consensus CDS
      CCDS55055.1
      UniProtKB/TrEMBL
      A0A0D9SFD2
      Related
      ENSP00000439863.1, ENST00000537166.5
      Conserved Domains (1) summary
      pfam12736
      Location:3 → 230
      CABIT; Cell-cycle sustaining, positive selection,

    4. NM_001318531.1 → NP_001305460.1  protein THEMIS isoform 4

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) contains multiple differences in the 5' region, initiates translation at a downstream start codon, and lacks an alternate in-frame exon in the central coding region, compared to variant 1.. The encoded isoform (4) is shorter than isoform 1.
      Source sequence(s)
      AK128377, AL365224, BC043608, BC130516, BG461112
      UniProtKB/TrEMBL
      A0A0D9SFD2
      Conserved Domains (1) summary
      pfam12736
      Location:184 → 432
      CABIT; Cell-cycle sustaining, positive selection,

    5. NM_001394520.1 → NP_001381449.1  protein THEMIS isoform 5

      Status: REVIEWED

      Source sequence(s)
      AL035470, AL356432, AL365224
      UniProtKB/TrEMBL
      A0A0D9SFD2
      Conserved Domains (1) summary
      pfam12736
      Location:3 → 239
      CABIT; Cell-cycle sustaining, positive selection,

    6. NM_001394521.1 → NP_001381450.1  protein THEMIS isoform 6

      Status: REVIEWED

      Source sequence(s)
      AL035470, AL356432, AL365224
      Conserved Domains (1) summary
      pfam12736
      Location:128 → 376
      CABIT; Cell-cycle sustaining, positive selection,

    7. NM_001394522.1 → NP_001381451.1  protein THEMIS isoform 4

      Status: REVIEWED

      Source sequence(s)
      AL035470, AL356432, AL365224
      UniProtKB/TrEMBL
      A0A0D9SFD2
      Conserved Domains (1) summary
      pfam12736
      Location:184 → 432
      CABIT; Cell-cycle sustaining, positive selection,

    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_000006.12 Reference GRCh38.p14 Primary Assembly

      Range
      127696628..127918595 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047418766.1 → XP_047274722.1  protein THEMIS isoform X4

      UniProtKB/Swiss-Prot
      A1L4F0, A8K7N1, B3KT31, B3KW32, B3KY07, F5H1J9, Q5T3C4, Q5T3C5, Q6MZT7, Q8N1K5

    2. XM_047418764.1 → XP_047274720.1  protein THEMIS isoform X2

    3. XM_047418767.1 → XP_047274723.1  protein THEMIS isoform X5

    4. XM_047418765.1 → XP_047274721.1  protein THEMIS isoform X3

    5. XM_047418763.1 → XP_047274719.1  protein THEMIS isoform X1

    Reference GRCh38.p14 ALT_REF_LOCI_1

    Genomic

    1. NT_187556.1 Reference GRCh38.p14 ALT_REF_LOCI_1

      Range
      53392..263793 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054328693.1 → XP_054184668.1  protein THEMIS isoform X4

      UniProtKB/Swiss-Prot
      A1L4F0, A8K7N1, B3KT31, B3KW32, B3KY07, F5H1J9, Q5T3C4, Q5T3C5, Q6MZT7, Q8N1K5

    2. XM_054328691.1 → XP_054184666.1  protein THEMIS isoform X2

    3. XM_054328694.1 → XP_054184669.1  protein THEMIS isoform X5

    4. XM_054328692.1 → XP_054184667.1  protein THEMIS isoform X3

    5. XM_054328690.1 → XP_054184665.1  protein THEMIS isoform X1

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060930.1 Alternate T2T-CHM13v2.0

      Range
      128897128..129107550 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054355409.1 → XP_054211384.1  protein THEMIS isoform X4

    2. XM_054355407.1 → XP_054211382.1  protein THEMIS isoform X2

    3. XM_054355410.1 → XP_054211385.1  protein THEMIS isoform X8

    4. XM_054355408.1 → XP_054211383.1  protein THEMIS isoform X7

    5. XM_054355406.1 → XP_054211381.1  protein THEMIS isoform X6

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q8N1K5.3 GenPept UniProtKB/Swiss-Prot:Q8N1K5

    Gene LinkOut

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

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