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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2008-6-2
pubmed:abstractText
To date, the literature concerning the HS1 (haematopoietic cell-specific protein 1)-associated protein X-1 (HAX1) protein has reported considerable variation regarding its function in mammalian cells, subcellular localisation and binding partners. We show here that HAX1 comprises a family of proteins. Murine tissues express three mRNA variants, encoded by two genes on chromosomes 2 and 3. The chromosome 2 gene is intronless and would encode a protein 100% identical with that encoded by chromosome 3. In humans, alternative splice variants, encoded by the chromosome 1 gene, produce a family of transcripts composed of up to eight members. Based on the sequences published in GenBank and Ensembl, we designed specific primers and detected by PCR three mRNA species in murine tissues and eight variants in human cells. We screened a panel of 19 human cell lines as well as primary fibroblasts, oral keratinocytes and freshly isolated peripheral blood mononuclear cells. All human cells studied expressed at least six of the possible HAX1 mRNA variants. In silico analysis of the variants revealed an open reading frame in all of them, suggesting that murine and human tissues can express two and eight HAX1 proteins, respectively. Analysis of human protein lysates by Western blotting with the use of a monoclonal anti-HAX1 antibody revealed multiple bands. These bands were decreased after treatment of cells with a single small interfering RNA duplex targeting a region common to six of the variants, confirming their identity as HAX1 proteins. Comparison of the human variants with the six HAX1 homologues described to date in the chimpanzee (Pan troglodytes) and the four homologues described in macaque (Macaca mulatta) revealed very high conservation with only one amino acid substitution between human and chimpanzee homologues. Moreover, a number of additional products were amplified and sequenced, which indicated that further human isoforms are likely to exist. These findings are likely to explain the current confusion concerning putative HAX1 function.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1089-8638
pubmed:author
pubmed:issnType
Electronic
pubmed:day
13
pubmed:volume
379
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
645-55
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:18472110-Adaptor Proteins, Signal Transducing, pubmed-meshheading:18472110-Alternative Splicing, pubmed-meshheading:18472110-Amino Acid Sequence, pubmed-meshheading:18472110-Animals, pubmed-meshheading:18472110-Base Sequence, pubmed-meshheading:18472110-Cell Line, pubmed-meshheading:18472110-Cells, Cultured, pubmed-meshheading:18472110-Chromosome Mapping, pubmed-meshheading:18472110-Conserved Sequence, pubmed-meshheading:18472110-DNA Primers, pubmed-meshheading:18472110-Genetic Variation, pubmed-meshheading:18472110-Humans, pubmed-meshheading:18472110-Macaca mulatta, pubmed-meshheading:18472110-Mice, pubmed-meshheading:18472110-Pan troglodytes, pubmed-meshheading:18472110-Protein Isoforms, pubmed-meshheading:18472110-Proteins, pubmed-meshheading:18472110-RNA, Messenger, pubmed-meshheading:18472110-Species Specificity, pubmed-meshheading:18472110-Tissue Distribution
pubmed:year
2008
pubmed:articleTitle
Existence of multiple isoforms of HS1-associated protein X-1 in murine and human tissues.
pubmed:affiliation
Centre for Tumour Biology, Institute of Cancer and Cancer Research UK Clinical Centre, Queen Mary's School of Medicine and Dentistry, Barts, UK. delphine.lees@cancer.org.uk
pubmed:publicationType
Journal Article