14-3-3 protein theta (YWHAQ)

The protein contains 245 amino acids for an estimated molecular weight of 27764 Da.

 

Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. Negatively regulates the kinase activity of PDPK1. (updated: April 1, 2015)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
  3. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  4. Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
  5. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  6. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
  7. Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.

Interpro domains
Total structural coverage: 100%
Model score: 73

(right-click above to access to more options from the contextual menu)

The reference OMIM entry for this protein is 609009

Tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, theta isoform; ywhaq
14-3-3 protein, t-cell
14-3-3-theta
14-3-3-tau
Hs1

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

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. ... More on the omim web site

Subscribe to this protein entry history

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated

June 20, 2017: Protein entry updated
Automatic update: comparative model was added.

March 15, 2016: Protein entry updated
Automatic update: OMIM entry 609009 was added.

Jan. 27, 2016: Protein entry updated
Automatic update: model status changed

Jan. 24, 2016: Protein entry updated
Automatic update: model status changed