Disease relevance of HAX1

• HAX1 deficiency causes autosomal recessive severe congenital neutropenia (Kostmann disease) [1].
• HS1/HAX-1 association is confirmed by coimmunoprecipitation of these proteins in the lysates of B lymphoma cells and COS-7 cells transfected with the corresponding cDNA expression vectors [2].
• K15 protein of Kaposi's sarcoma-associated herpesvirus is latently expressed and binds to HAX-1, a protein with antiapoptotic function [3].
• In psoriasis, the epidermal differentiation could be disturbed due to the increased expression of HAX-1 and hence a prolonged resistance to terminal differentiation [4].
• In contrast to primary keratinocytes and melanocytes we found HAX-1 highly expressed in human immortalized keratinocytes (HaCaT) and different melanoma cell lines [4].

High impact information on HAX1

• Here, we show that HAX1 is critical for maintaining the inner mitochondrial membrane potential and protecting against apoptosis in myeloid cells [1].
• HAX1 encodes the mitochondrial protein HAX1, which has been assigned functions in signal transduction and cytoskeletal control [1].
• Using a positional cloning approach and candidate gene evaluation, we identified a recurrent homozygous germline mutation in HAX1 in three pedigrees [1].
• These findings reveal that nuclear localization of pre-IL-1alpha depends on the binding to HAX-1 and that biological activities might be elicited by the binding to both HAX-1 and IL-1RII in SSc fibroblasts [5].
• RNA interference of HAX-1 increased BSEP levels in the apical membrane of MDCK cells by 71% [6].

Biological context of HAX1

• Evidence that HAX-1 is an interleukin-1 alpha N-terminal binding protein [7].
• In vitro binding studies and transient transfection experiments confirmed that HAX-1 can associate with the IL-1 NTP [7].
• Pulse-chase studies indicated that HAX-1 depletion did not affect BSEP translation, post-translational modification, delivery to the plasma membrane, or half-life [6].
• HAX-1, identified by differential display reverse transcription polymerase chain reaction, is overexpressed in lesional psoriasis [4].
• Overexpression of Vpr in cells dislocates HAX-1 from its normal residence in mitochondria and creates mitochondrion instability and cell death [8].

Anatomical context of HAX1

• Our findings suggest that HAX1 is a major regulator of myeloid homeostasis and underline the significance of genetic control of apoptosis in neutrophil development [1].
• In sharp contrast to the human HAX1 which is highly expressed in skeletal muscle, the mouse ortholog was detected only at very low levels [9].
• On the basis of these identified interaction partners, HAX1 seems to play a role in apoptosis and the organization of the cytoskeleton [9].
• The HAX-1 gene is expressed ubiquitously among tissues, and its protein is localized mainly in mitochondria, but also in endoplasmic reticulum and nuclear envelope in the cell [2].
• BSEP and HAX-1 were over-represented in rat liver subcellular fractions enriched for canalicular membrane vesicles, microsomes, and clathrin-coated vesicles [6].

Associations of HAX1 with chemical compounds

• HAX-1 was first identified as a protein that associates with HS1, a target of non-receptor protein tyrosine kinases within haematopoietic cells [7].

Physical interactions of HAX1

• The 3' untranslated region of human vimentin mRNA interacts with protein complexes containing eEF-1gamma and HAX-1 [10].

Other interactions of HAX1

• During studies aimed at understanding the function of the N-terminal peptide of interleukin-1 alpha (IL-1 NTP, amino acids 1-112), which is liberated from the remainder of IL-1 alpha during intracellular processing, we identified by yeast two-hybrid analysis a putative interacting protein previously designated as HAX-1 [7].
• In contrast, two anti-apoptotic genes, hurpin and HAX-1, were downregulated [11].

Analytical, diagnostic and therapeutic context of HAX1

• Sequence analysis of different HAX-1 binding domains revealed a putative consensus binding motif that is present in various intracellular proteins [7].
• By mRNA differential display we found HAX-1 to be overexpressed in lesional psoriatic skin [4].
• The overexpression of HAX-1 was verified at the mRNA level by Northern blot and in situ hybridization, as well as at the protein level by Western blot and immunohistochemistry [4].

References