TYROSINE 3-MONOOXYGENASE/TRYPTOPHAN 5-MONOOXYGENASE ACTIVATION PROTEIN, THETA ISOFORM; YWHAQ

Alternative titles; symbols

• 14-3-3 PROTEIN, T-CELL
• 14-3-3-THETA
• 14-3-3-TAU
• HS1

HGNC Approved Gene Symbol: YWHAQ

Cytogenetic location: 2p25.1 Genomic coordinates (GRCh38): 2:9,583,966-9,630,996 (from NCBI)

▼ Description
YWHAQ is a member of the 14-3-3 family of signaling proteins involved in apoptosis and cell proliferation (Malaspina et al., 2000).

▼ Cloning and Expression
By screening a Jurkat human T-cell cDNA library with a probe coding for an uncharacterized nuclear protein, Nielsen (1991) cloned YWHAQ. The deduced 245-amino acid protein has a calculated molecular mass of 28 kD and shares 72% amino acid identity with bovine brain 14-3-3-eta (113508). Northern blot analysis of Jurkat and HeLa cells showed strong bands at 1.9 and 2.1 kb, and a weaker band at 1.7 kb. Strongest expression was in brain, followed by lung, kidney, liver, and spleen.

By sequencing cDNAs encoding related acidic human keratinocyte proteins, Leffers et al. (1993) cloned YWHAQ, which they designated HS1. The YWHAQ protein shares significant similarity with stratifin (601290). It showed an apparent molecular mass of 31.1 kD by 2-dimensional gel electrophoresis. Expression of YWHAQ was abundant in transformed amnion epithelia cells and fetal ear fibroblasts. Northern blot analysis detected high expression in all cell types and tissues analyzed. The authors identified 3 YWHAQ transcripts resulting from the utilization of different polyadenylation sites.

By screening a spinal cord cDNA library for cDNAs encoding trinucleotide- and tandem repeat-containing proteins, Malaspina et al. (2000) cloned YWHAQ. The 5-prime UTR immediately before the start codon of the YWHAQ transcript contains a homogeneous 6-bp (CCCCGG)3 tandem repeat. Northern blot analysis detected a 2-kb transcript abundantly expressed in brain, heart, and pancreas, with lower expression in kidney and placenta. Spinal cord mRNA showed transcripts of about 1.8 and 2.2 kb. Malaspina et al. (2000) found that YWHAQ was consistently upregulated in spinal cord of amyotrophic lateral sclerosis (105400) patients. Expression was highest in 2 individuals with the most consistent clinical picture of lower motor neuron involvement.

Watanabe et al. (1994) isolated the rat theta isoform of 14-3-3 from rat brain. The deduced 245-amino acid protein shares high sequence homology with other 14-3-3 subtypes. The theta mRNA was detected in gray matter of the cerebellar cortex and hippocampus and in white matter.

▼ Biochemical Features
Xiao et al. (1995) determined the crystal structure of the human T-cell YWHAQ dimer at 2.6-angstrom resolution. Each monomer is composed of an unusual arrangement of 9 antiparallel alpha helices organized as 2 structural domains. The dimer creates a large, negatively charged channel approximately 35 angstroms broad, 35 angstroms wide, and 20 angstroms deep. Overall, invariant residues line the interior of the channel, whereas more variable residues are distributed on the outer surface. At the base of the channel is a 16-residue segment implicated in the binding of 14-3-3 to protein kinase C (see 176960).

▼ Mapping
By analyzing human-rodent hybrids, Malaspina et al. (2000) mapped the YWHAQ gene to chromosome 2. They identified a pseudogene on chromosome 22.