THAP1, THAP-domaanin omaava mahdollinen Zf-proteiini

 https://www.genenames.org/data/genegroup/#!/group/65
THAP domeenin sisältävä tgranskriptiotekijä, Zf 

(Sinkkiä sitoneva ) THAP containing domain: 12 geeni ja 3 transkriptiotekijää.

THANATOS-associated protein, death associated protein.

LÄHDE:https://www.ncbi.nlm.nih.gov/gene/?term=THAP

THAP1(8p11.21), DYT6.

https://www.ncbi.nlm.nih.gov/gene/55145

Also known as DYT6 (dystonia 6)

Summary The protein encoded by this gene contains a THAP domain, a conserved DNA-binding domain. This protein colocalizes with the apoptosis response protein PAWR/PAR-4 in promyelocytic leukemia (PML) nuclear bodies, and functions as a proapoptotic factor that links PAWR to PML nuclear bodies. Alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2008]

Expression Ubiquitous expression in testis (RPKM 7.0), thyroid (RPKM 5.5) and 25 other tissues See more Orthologs mouse all

Preferred Names

THAP domain-containing protein 1

Names

4833431A01Rik

THAP domain containing, apoptosis associated protein 1

THAP domain protein 1

nuclear proapoptotic factor

https://www.ncbi.nlm.nih.gov/protein/NP_060575.1

ORIGIN      
        1 mvqscsaygc knrydkdkpv sfhkfpltrp slckeweaav rrknfkptky ssicsehftp
       61 dcfkrecnnk llkenavpti flctephdkk edllepqeql pppplpppvs qvdaaigllm
      121 pplqtpvnls vfcdhnytve dtmhqrkrih qleqqveklr kklktaqqrc rrqerqlekl
      181 kevvhfqkek ddvsergyvi lpndyfeive vpa

Conserved Domains (1) summary

smart00980
Location:4 → 82

THAP

The THAP domain is a putative DNA-binding domain (DBD) and probably also binds a zinc ion.

It features the conserved C2CH architecture (consensus sequence: Cys - 2-4 residues - Cys - 35-50 residues - Cys - 2 residues - His). Other universal features include the location of the domain at the N-termini of proteins, its size of about 90 residues, a C-terminal AVPTIF box and several other conserved residues. Orthologues of the human THAP domain have been identified in other vertebrates and probably worms and flies, but not in other eukaryotes or any prokaryotes.

Related articles in PubMed

1. Dystonia-causing mutations in the transcription factor THAP1 disrupt HCFC1 cofactor recruitment and alter gene expression. Hollstein R, et al. Hum Mol Genet, 2017 Aug 1. PMID 28486698
2. Genetic screening of THAP1 in primary dystonia patients of India. Giri S, et al. Neurosci Lett, 2017 Jan 10. PMID 27913194
3. New THAP1 mutation and role of putative modifier in TOR1A. Piovesana LG, et al. Acta Neurol Scand, 2017 Feb. PMID 26940431
4. Screening for THAP1 Mutations in Polish Patients with Dystonia Shows Known and Novel Substitutions. Golanska E, et al. PLoS One, 2015. PMID 26087139, Free PMC Article
5. High variability of clinical symptoms in a Polish family with a novel THAP1 mutation. Gajos A, et al. Int J Neurosci, 2015. PMID 25385508

See all (88) citations in PubMed

GeneRIFs: Gene References Into Functions

1. Dysfunction in similar pathways occurring with mutations in THAP1 as well as diverse dystonia genes highlight a point of convergence in the pathophysiology of several forms of inherited dystonia.
2. The region of amino acids 139-185 is involved in formation of THAP1 homodimers.
3. We functionally characterized for the first time three dystonia-causing missense variants (p.N136K, p.N136S and p.Y137C) within the HBM in the C-terminal region of THAP1. Dystonia-causing mutations affecting the residues N136 and Y137 in THAP1 significantly reduced HCFC1 recruitment to all four tested promoter regions.
4. that the THAP1 is likely to have a causative role in the pathogenesis of Indian primary pure dystonia patients
5. This study demonstrated that whole-exome sequencing show reveled THAP1 mutation with early-onset generalized dystonia.
6. Genetic screening targeted at currently known disease-causing mutations in TOR1A, THAP1, and TUBB4 appears to have low diagnostic yield in sporadic spasmodic dysphonia. In our cohort, only 2 patients tested positive for novel/rare variants in THAP1.
7. A deleterious THAP1 mutation was identified in patients with idiopathic isolated dystonia.
8. there might not be an association between TOR1A or THAP1 and patients with adult-onset primary focal dystonia
9. findings strongly suggest the role of other genetic factors or environmental triggers in the pathogenesis of dystonia related to mutations in THAP1 gene.
10. The aim of this study was to assess the presence of DYT6 mutations in Polish patients with isolated dystonia. It shows known and novel substitutions.

PLoS Genet. 2018 Jan 24;14(1):e1007169. doi: 10.1371/journal.pgen.1007169. eCollection 2018 Jan. Mutations in THAP1/DYT6 reveal that diverse dystonia genes disrupt similar neuronal pathways and functions.Zakirova Z¹, Fanutza T¹, Bonet J¹, Readhead B², Zhang W³, Yi Z³, Beauvais G⁴, Zwaka TP⁵, Ozelius LJ^6,7, Blitzer RD⁸, Gonzalez-Alegre P^4,9, Ehrlich ME^1,2.Abstract

Dystonia is characterized by involuntary muscle contractions. Its many forms are genetically, phenotypically and etiologically diverse and it is unknown whether their pathogenesis converges on shared pathways. Mutations in THAP1 [THAP (Thanatos-associated protein) domain containing, apoptosis associated protein 1], a ubiquitously expressed transcription factor with DNA binding and protein-interaction domains, cause dystonia, DYT6. There is a unique, neuronal 50-kDa Thap1-like immunoreactive species, and Thap1 levels are auto-regulated on the mRNA level. However, THAP1 downstream targets in neurons, and the mechanism via which it causes dystonia are largely unknown. We used RNA-Seq to assay the in vivo effect of a heterozygote Thap1 C54Y or ΔExon2 allele on the gene transcription signatures in neonatal mouse striatum and cerebellum. Enriched pathways and gene ontology terms include eIF2α Signaling, Mitochondrial Dysfunction, Neuron Projection Development, Axonal Guidance Signaling, and Synaptic LongTerm Depression, which are dysregulated in a genotype and tissue-dependent manner. Electrophysiological and neurite outgrowth assays were consistent with those enrichments, and the plasticity defects were partially corrected by salubrinal. Notably, several of these pathways were recently implicated in other forms of inherited dystonia, including DYT1. We conclude that dysfunction of these pathways may represent a point of convergence in the pathophysiology of several forms of inherited dystonia.

THAP2

THAP3

THAP4

THAP4

THAP5

THAP6

THAP7

THAP8

THAP9

THAP10

THAP11

THAP12

Pseudogeenejä useita:

THAP5P1,Kr.7.

THAP5P2, Kr.3.

THAP12P1, X-kromosomi.

THAP12P3, Kr.10, PRKRIRP3.

THAP12P4, Kr.11, PRKRIRP4.

THAP12P6, Kr.13, PRKRIRP6.

THAP12P7, Kr. 8, PRKRIRP7.

THAP12P8, Kr.1, PRKRIRP8.

THAP12P9, Kr.4, PRKRIRP9.

THAP12P10, Kr.13, PRKRIRP10.

Kaksi muuta THAP12P pseudogeeniä ( kromosomeissa 15 ja 12)

Name/Gene ID	Description	Location	Aliases
Select item 55145 THAP1 ID: 55145	THAP domain containing 1 [Homo sapiens (human)]	Chromosome 8, NC_000008.11 (42836674..42843331, complement)	DYT6
Select item 57215 THAP11 ID: 57215	THAP domain containing 11 [Homo sapiens (human)]	Chromosome 16, NC_000016.10 (67842310..67844195)	CTG-B43a, CTG-B45d, HRIHFB2206, RONIN
Select item 51078 THAP4 ID: 51078	THAP domain containing 4 [Homo sapiens (human)]	Chromosome 2, NC_000002.12 (241584405..241637543, complement)	CGI-36, Nb(III), PP238
Select item 80764 THAP7 ID: 80764	THAP domain containing 7 [Homo sapiens (human)]	Chromosome 22, NC_000022.11 (20999772..21002115, complement)
Select item 168451 THAP5 ID: 168451	THAP domain containing 5 [Homo sapiens (human)]	Chromosome 7, NC_000007.14 (108562144..108569768, complement)
Select item 5612 THAP12 ID: 5612	THAP domain containing 12 [Homo sapiens (human)]	Chromosome 11, NC_000011.10 (76349956..76380965, complement)	DAP4, P52rIPK, PRKRIR, THAP0
Select item 90326 THAP3 ID: 90326	THAP domain containing 3 [Homo sapiens (human)]	Chromosome 1, NC_000001.11 (6624616..6635586)
Select item 152815 THAP6 ID: 152815	THAP domain containing 6 [Homo sapiens (human)]	Chromosome 4, NC_000004.12 (75513944..75547334)
.
Select item 199745 THAP8 ID: 199745	THAP domain containing 8 [Homo sapiens (human)]	Chromosome 19, NC_000019.10 (36034985..36054762, complement)
Select item 79725 THAP9 ID: 79725	THAP domain containing 9 [Homo sapiens (human)]	Chromosome 4, NC_000004.12 (82900650..82920283)	hTh9
.
Select item 83591 THAP2 ID: 83591	THAP domain containing 2 [Homo sapiens (human)]	Chromosome 12, NC_000012.12 (71663897..71680648)
Select item 56906 THAP10 ID: 56906	THAP domain containing 10 [Homo sapiens (human)]	Chromosome 15, NC_000015.10 (70881342..70892433, complement)
..