THEMIS thymocyte selection associated [Homo sapiens (human)] - Gene

Summary

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

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_000006.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
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.
THEMIS binding to GRB2 was required for thymocyte development.
Title: GRB2-mediated recruitment of THEMIS to LAT is essential for thymocyte development.
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.
SPOP mutations may define a new molecular subtype of prostate cancer.
Title: Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer.
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.
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 EBI GWAS CatalogPubMed
Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide analysis of polymorphisms associated with cytokine responses in smallpox vaccine recipients. EBI GWAS Catalog EBI GWAS CatalogPubMed
Multiple common variants for celiac disease influencing immune gene expression. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-144779 (e-PCR)
- UniSTS:184354

G59455 (e-PCR)
- UniSTS:136762

RH37468 (e-PCR)
- UniSTS:69540

RH93059 (e-PCR)
- UniSTS:89027

G54574 (e-PCR)
- UniSTS:117712

RH122986 (e-PCR)
- UniSTS:135378

WI-10674 (e-PCR)
- UniSTS:47354

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

NG_016226.2 RefSeqGene

Range

22537..215395

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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,
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
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,
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,
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,
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,
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,