https://www.genenames.org/data/genegroup/#!/group/65
THAP domeenin sisältävä transkriptiotekijöiden ryhmä sinkkisormiproteiineja
THAP11 (16q22.1), Hematopoieesitekijä, Cbl AV, Parkin vaimennus
- Also known as
- RONIN; CTG-B43a; CTG-B45d; HRIHFB2206
- Summary The protein encoded by this gene contains a THAP domain, which is a conserved DNA-binding domain that has striking similarity to the site-specific DNA-binding domain (DBD) of Drosophila P element transposases. [provided by RefSeq, Jul 2008] Orthologs mouse all
- Preferred Names
- THAP domain-containing protein 11
- THAP11 peptide https://www.ncbi.nlm.nih.gov/protein/NP_065190.2
- (Comment. Obs. Polyglutamine structure! Also some pq . “Wheaty” thing. )
ORIGIN 1 mpgftccvpg cynnshrdka lhfytfpkda elrrlwlknv sragvsgcfs tfqpttghrl 61 csvhfqggrk tytvrvptif plrgvnerkv arrpagaaaa rrrqqqqqqq qqqqqqqqqq 121 qqqqqqqqqq qqsspsasta qtaqlqpnlv sasaavlltl qatvdssqap gsvqpapitp 181 tgedvkpidl tvqvefaaae gaaaaaaase lqaataglea aecpmgpqlv vvgeegfpdt 241 gsdhsyslss gtteeellrk lneqrdilal mevkmkemkg sirhlrltea klreelrekd 301 rllamavirk khgm //
- The C-terminal region of the transcriptional regulator THAP11 forms a parallel coiled-coil domain involved in protein dimerization. Cukier CD, et al. J Struct Biol, 2016 Jun. PMID 26975212
- Effects of THAP11 on erythroid differentiation and megakaryocytic differentiation of K562 cells. Kong XZ, et al. PLoS One, 2014. PMID 24637716, Free PMC Article Abstract
Hematopoiesis is a complex process regulated by
sets of transcription factors in a stage-specific and
context-dependent manner. THAP11 is a transcription factor involved
in cell growth, ES cell pluripotency, and embryogenesis. Here we
showed that THAP11 was down-regulated during erythroid
differentiation but up-regulated during megakaryocytic
differentiation of cord blood CD34+ cells. Overexpression of THAP11
in K562 cells inhibited the erythroid differentiation induced by
hemin with decreased numbers of benzidine-positive cells and
decreased mRNA levels of α-globin (HBA) and glycophorin A (GPA), and
knockdown of THAP11 enhanced the erythroid differentiation.
Conversely, THAP11 overexpression accelerated the megakaryocytic
differentiation induced by phorbol myristate acetate (PMA) with
increased percentage of CD41+ cells, increased numbers of 4N cells,
and elevated CD61 mRNA levels, and THAP11 knockdown attenuated the
megakaryocytic differentiation. The expression levels of
transcription factors such as c-Myc, c-Myb, GATA-2, and Fli1 were
changed by THAP11 overexpression. In this way, our results suggested
that THAP11 reversibly regulated erythroid and megakaryocytic
differentiation.
- Genome-wide CRISPR screen for PARKIN regulators reveals transcriptional repression as a determinant of mitophagy. Potting C, et al. Proc Natl Acad Sci U S A, 2018 Jan 9. PMID 29269392, Free PMC Article Abstract
PARKIN, an E3 ligase (mutated in familial
Parkinson's disease), promotes mitophagy by ubiquitinating
mitochondrial proteins for efficient engagement of the autophagy
machinery. Specifically, PARKIN-synthesized ubiquitin chains
represent targets for the PINK1 kinase generating
phosphoS65-ubiquitin (pUb), which constitutes the mitophagy signal.
Physiological regulation of PARKIN abundance, however, and the impact
on pUb accumulation are poorly understood. Using cells designed to
discover physiological regulators of PARKIN abundance, we performed a
pooled genome-wide CRISPR/Cas9 knockout screen. Testing identified
genes individually resulted in a list of 53 positive and negative
regulators. A transcriptional repressor network including THAP11 was
identified and negatively regulates endogenous PARKIN abundance.
RNAseq analysis revealed the PARKIN-encoding locus as a prime THAP11
target, and THAP11 CRISPR knockout in multiple cell types
enhanced pUb accumulation. Thus, our work demonstrates the critical
role of PARKIN abundance, identifies regulating genes, and reveals a
link between transcriptional repression and mitophagy, which is also
apparent in human induced pluripotent stem cell-derived neurons, a
disease-relevant cell type. KEYWORDS: PARKIN; THAP11; genome-wide
screen; mitophagy; phosphoubiquitin
- Mutations in THAP11 cause an inborn error of cobalamin metabolism and developmental abnormalities. Quintana AM, et al. Hum Mol Genet, 2017 Aug 1. PMID 28449119, Free PMC Article Abstract
CblX (MIM309541) is an X-linked recessive disorder
characterized by defects in cobalamin (vitamin B12) metabolism and
other developmental defects. Mutations in HCFC1, a transcriptional
co-regulator which interacts with multiple transcription factors,
have been associated with cblX. HCFC1 regulates cobalamin metabolism
via the regulation of MMACHC expression
through its interaction with THAP11, a THAP
domain-containing transcription factor. The HCFC1/THAP11 complex
potentially regulates genes involved in diverse cellular functions
including cell cycle, proliferation, and transcription. Thus, it is
likely that mutation of THAP11 also results in biochemical and other
phenotypes similar to those observed in patients with cblX. We report
a patient who presented with clinical and biochemical phenotypic
features that overlap cblX, but who does not have any mutations in
either MMACHC or HCFC1. We sequenced THAP11 by Sanger sequencing and
discovered a potentially pathogenic, homozygous variant, c.240C > G
(p.Phe80Leu). Functional analysis in the developing zebrafish embryo
demonstrated that both THAP11 and HCFC1 regulate the proliferation
and differentiation of neural precursors, suggesting important roles
in normal brain development. The loss of THAP11 in zebrafish embryos
results in craniofacial abnormalities including the complete loss of
Meckel's cartilage, the ceratohyal, and all of the ceratobranchial
cartilages. These data are consistent with our previous work that
demonstrated a role for HCFC1 in vertebrate craniofacial development.
High throughput RNA-sequencing analysis reveals several overlapping
gene targets of HCFC1 and THAP11. Thus, both HCFC1 and THAP11 play
important roles in the regulation of cobalamin metabolism as well as
other pathways involved in early vertebrate development.
The MMACHC gene provides instructions for making
a protein that helps convert vitamin B12 (also called cobalamin)
into one of two molecules, adenosylcobalamin (AdoCbl) or
methylcobalamin (MeCbl). AdoCbl is required for the normal
function of an enzyme known as methylmalonyl CoA mutase. This
enzyme helps break down certain protein building blocks (amino
acids), fats (lipids), and cholesterol. AdoCbl is called a cofactor
because it helps methylmalonyl CoA mutase carry out its function.
MeCbl is also a cofactor, but for an enzyme known as
methionine synthase. This enzyme converts the amino acid
homocysteine to another amino acid, methionine. The body uses
methionine to make proteins and other important compounds.
Research indicates that the MMACHC protein
plays a role in processing different forms of vitamin B12
so that they can be converted to either of the cofactors, AdoCbl
or MeCbl. MMACHC also interacts with another protein called MMADHC
(produced from the MMADHC
gene). Together these proteins transport the processed vitamin
B12 to regions of the cell in which each cofactor is needed:
specialized structures that serve as energy-producing centers (the
mitochondria), where AdoCbl functions, or the fluid
inside the cell (the cytoplasm), where MeCbl
functions. Additional chemical reactions then convert vitamin B12
into AdoCbl or MeCbl.
- NMR studies of a new family of DNA binding proteins: the THAP proteins. Gervais V, et al. J Biomol NMR, 2013 May. PMID 23306615
Bcr-Abl activates various signaling pathways in
chronic myelogenous leukemia (CML) cells. The proliferation of
Bcr-Abl transformed cells is promoted by c-Myc through the activation
of Akt, JAK2 and NF-κB. However, the mechanism by which c-Myc
regulates CML cell proliferation is unclear. In our study, we
investigated the role of Thanatos-associated protein 11 (THAP11),
which inhibits c-Myc transcription, in CML cell lines and in
hematopoietic progenitor cells derived from CML patients. The
induction of THAP11 expression by Abl kinase inhibitors in CML cell
lines and in CML-derived hematopoietic progenitor cells resulted in
the suppression of c-Myc. In addition, over-expression of THAP11
inhibited CML cell proliferation. In colony forming cells derived
from CML-aldehyde dehydrogenase (ALDH)(hi) /CD34(+) cells, treatment
with Abl kinase inhibitors and siRNA depletion of Bcr-Abl induced
THAP11 expression and reduced c-Myc expression, resulting in
inhibited colony formation. Moreover, overexpression of THAP11
significantly decreased the colony numbers, and also inhibited the
expression of c-myc target genes such as Cyclin D1, ODC and induced
the expression of p21(Cip1) . The depletion of THAP11 inhibited JAK2
or STAT5 inactivation-mediated c-Myc reduction in ALDH(hi) /CD34(+)
CML cells. Thus, the induced THAP11 might be one of transcriptional
regulators of c-Myc expression in CML cell. Therefore, the induction
of THAP11 has a potential possibility as a target for the inhibition
of CML cell proliferation
