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THEMIS thymocyte selection associated [ Homo sapiens (human) ]

Gene ID: 387357, updated on 3-Apr-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
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Genomic context

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Location:
6q22.33
Exon count:
11
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 6 NC_000006.12 (127696628..127918595, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 6 NC_060930.1 (128897128..129107550, complement)
105.20220307 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
  • 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. 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
  3. Themis imposes new law and order on positive selection. Allen PM. Nat Immunol, 2009 Aug. PMID 19621038
  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. Themis sets the signal threshold for positive and negative selection in T-cell development. Fu G, et al. Nature, 2013 Dec 19. PMID 24226767, 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_2023_10

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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