HCLS1 Associated Protein X-1 (HAX1) Human Recombinant Protein

The protein encoded by this gene is known to associate with hematopoietic cell-specific Lyn substrate 1, a substrate of Src family tyrosine kinases. It also interacts with the product of the polycystic kidney disease 2 gene, mutations in which are associated with autosomal-dominant polycystic kidney disease, and with the F-actin-binding protein, cortactin. It was earlier thought that this gene product is mainly localized in the mitochondria, however, recent studies indicate it to be localized in the cell body. Mutations in this gene result in autosomal recessive severe congenital neutropenia, also known as Kostmann disease. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

HAX1: Promotes cell survival. Potentiates GNA13-mediated cell migration. Involved in the clathrin-mediated endocytosis pathway. May be involved in internalization of ABC transporters such as ABCB11. May inhibit CASP9 and CASP3. May regulate intracellular calcium pools. Defects in HAX1 are the cause of neutropenia severe congenital autosomal recessive type 3 (SCN3); also known as Kostmann disease. A disorder of hematopoiesis characterized by maturation arrest of granulopoiesis at the level of promyelocytes with peripheral blood absolute neutrophil counts below 0.5 x 10(9)/l and early onset of severe bacterial infections. Some patients affected by severe congenital neutropenia type 3 have neurological manifestations such as psychomotor retardation and seizures. The clinical phenotype due to HAX1 deficiency appears to depend on the localization of the mutations and their influence on the transcript variants. Mutations affecting exclusively isoform 1 are associated with isolated congenital neutropenia, whereas mutations affecting both isoform 1 and isoform 5 are associated with additional neurologic symptoms. Belongs to the HAX1 family. 6 isoforms of the human protein are produced by alternative splicing.

Protein type: Endoplasmic reticulum; Mitochondrial; Apoptosis; Vesicle

Chromosomal Location of Human Ortholog: 1q21.3

Cellular Component: transcription factor complex; nuclear membrane; clathrin-coated vesicle; mitochondrion; sarcoplasmic reticulum; endoplasmic reticulum; lamellipodium; apical plasma membrane; nuclear envelope; actin cytoskeleton

Molecular Function: protein domain specific binding; protein binding; protein N-terminus binding; interleukin-1 binding

Biological Process: positive regulation of phosphoinositide 3-kinase cascade; regulation of apoptosis; positive regulation of protein kinase B signaling cascade; positive regulation of peptidyl-tyrosine phosphorylation; regulation of actin filament polymerization; positive regulation of granulocyte differentiation; positive regulation of transcription from RNA polymerase II promoter; positive regulation of peptidyl-serine phosphorylation

Disease: Neutropenia, Severe Congenital, 3, Autosomal Recessive