TSHZ3

TSHZ3
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2DMI
Identifiers
Aliases	TSHZ3 , TSH3, ZNF537, teashirt zinc finger homeobox 3
External IDs	OMIM: 614119 MGI: 2442819 HomoloGene: 10835 GeneCards: TSHZ3
Gene location (Human) Chr. Chromosome 19 (human) [1] Band 19q12 Start 31,149,979 bp [1] End 31,349,436 bp [1]
Gene location (Mouse) Chr. Chromosome 7 (mouse) [2] Band 7|7 B2 Start 36,397,543 bp [2] End 36,472,978 bp [2]
RNA expression pattern Bgee Top expressed in cerebral cortex neocortex endometrium ovary lung More reference expression data BioGPS n/a
Gene ontology Molecular function metal ion binding DNA binding chromatin binding GO:0001948 protein binding GO:0001078, GO:0001214, GO:0001206 DNA-binding transcription repressor activity, RNA polymerase II-specific nucleic acid binding GO:0001200, GO:0001133, GO:0001201 DNA-binding transcription factor activity, RNA polymerase II-specific Cellular component cell projection growth cone nucleus nucleoplasm Biological process regulation of gene expression regulation of transcription, DNA-templated transcription, DNA-templated regulation of respiratory gaseous exchange by nervous system process negative regulation of transcription, DNA-templated multicellular organism development regulation of transcription by RNA polymerase II negative regulation of transcription by RNA polymerase II positive regulation of synaptic transmission, glutamatergic long-term synaptic potentiation Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	57616	243931
Ensembl	ENSG00000121297	ENSMUSG00000021217
UniProt	Q63HK5	Q8CGV9
RefSeq (mRNA)	NM_020856	NM_172298
RefSeq (protein)	NP_065907	NP_758502
Location (UCSC)	Chr 19: 31.15 – 31.35 Mb	Chr 7: 36.4 – 36.47 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Teashirt homolog 3 is a protein that in humans is encoded by the TSHZ3 gene. ^[5] In mice, it is a necessary part of the neural circuitry that controls breathing. The gene is also a homolog of the Drosophila melanogaster teashirt gene, which encodes a zinc finger transcription factor important for development of the trunk. ^[6]

Tshz3-knockout mice do not develop the respiratory rhythm generator (RRG) neural circuit, which is a pacemaker that produces an oscillating rhythm in the brainstem and controls autonomous breathing. The RRG neurons are present, but are abnormal. Those mice do not survive because they don't initiate breathing after birth. Tshz3 is being studied for its relationship to infant breathing defects in humans. ^[7]

TSHZ3 has been identified as a critical region for a syndrome associated with heterozygous deletions at 19q12-q13.11, which includes autism spectrum disorder (ASD) symptoms such autistic traits, speech disturbance and intellectual disability, as well as renal tract abnormalities. Mice with heterozygous Tshz3 deletion (Tshz3^lacZ/+) show enrichment of ASD-related gene orthologs in the cerebral cortex, functional alterations of corticostriatal circuitry and ASD-relevant behavioral abnormalities. ^[8]

Postnatal conditional deletion of Tshz3 in mouse induces behavioral deficits mimicking ASD, as well as abnormalities in synaptic transmission and plasticity in the corticostriatal circuit. These changes are associated to dysregulation of the cortical expression of more than 1000 genes, in particular coding for synaptic components, half of which has human orthologues involved in ASD. ^[9]

References

1. GRCh38: Ensembl release 89: ENSG00000121297 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000021217 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: TSHZ3 teashirt family zinc finger 3".
6. Fasano L, Röder L, Coré N, Alexandre E, Vola C, Jacq B, Kerridge S (January 1991). "The gene teashirt is required for the development of Drosophila embryonic trunk segments and encodes a protein with widely spaced zinc finger motifs". Cell. 64 (1): 63–79. doi:10.1016/0092-8674(91)90209-h. PMID   1846092. S2CID   39211509.
7. Caubit X, Thoby-Brisson M, Voituron N, Filippi P, Bévengut M, Faralli H, et al. (July 2010). "Teashirt 3 regulates development of neurons involved in both respiratory rhythm and airflow control". The Journal of Neuroscience. 30 (28): 9465–76. doi:10.1523/JNEUROSCI.1765-10.2010. PMC   6632443 . PMID   20631175.*Lay summary in: de Lange C (July 23, 2010). "Single gene could be key to a baby's first breath". New Scientist.
8. Caubit X, Gubellini P, Andrieux J, Roubertoux PL, Metwaly M, Jacq B, et al. (November 2016). "TSHZ3 deletion causes an autism syndrome and defects in cortical projection neurons". Nature Genetics. 48 (11): 1359–1369. doi:10.1038/ng.3681. PMC   5083212 . PMID   27668656.
9. Chabbert D, Caubit X, Roubertoux PL, Carlier M, Habermann B, Jacq B, et al. (August 2019). "Postnatal Tshz3 Deletion Drives Altered Corticostriatal Function and Autism Spectrum Disorder-like Behavior". Biological Psychiatry. 86 (4): 274–285. doi: 10.1016/j.biopsych.2019.03.974 . PMID   31060802. S2CID   85532974.

Further reading

• Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M (November 2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell. 127 (3): 635–48. doi: 10.1016/j.cell.2006.09.026 . PMID   17081983. S2CID   7827573.
• Mehrle A, Rosenfelder H, Schupp I, del Val C, Arlt D, Hahne F, et al. (January 2006). "The LIFEdb database in 2006". Nucleic Acids Research. 34 (Database issue): D415-8. doi:10.1093/nar/gkj139. PMC   1347501 . PMID   16381901.
• Wiemann S, Arlt D, Huber W, Wellenreuther R, Schleeger S, Mehrle A, et al. (October 2004). "From ORFeome to biology: a functional genomics pipeline". Genome Research. 14 (10B): 2136–44. doi:10.1101/gr.2576704. PMC   528930 . PMID   15489336.
• Brandenberger R, Wei H, Zhang S, Lei S, Murage J, Fisk GJ, et al. (June 2004). "Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation". Nature Biotechnology. 22 (6): 707–16. doi:10.1038/nbt971. PMID   15146197. S2CID   27764390.
• Wiemann S, Weil B, Wellenreuther R, Gassenhuber J, Glassl S, Ansorge W, et al. (March 2001). "Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs". Genome Research. 11 (3): 422–35. doi:10.1101/gr.GR1547R. PMC   311072 . PMID   11230166.
• Hartley JL, Temple GF, Brasch MA (November 2000). "DNA cloning using in vitro site-specific recombination". Genome Research. 10 (11): 1788–95. doi:10.1101/gr.143000. PMC   310948 . PMID   11076863.
• Nagase T, Kikuno R, Ishikawa K, Hirosawa M, Ohara O (April 2000). "Prediction of the coding sequences of unidentified human genes. XVII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Research. 7 (2): 143–50. doi: 10.1093/dnares/7.2.143 . PMID   10819331.

External links

• Overview of all the structural information available in the PDB for UniProt : Q63HK5 (Teashirt homolog 3) at the PDBe-KB .