Stanford Home
Ovarian Kaleidoscope Database (OKdb)

Home

History

Transgenic Mouse Models

INFORGRAPHICS

Search
Submit
Update
Chroms
Browse
Admin

Hsueh lab

HPMR

Visits
since 01/2001:
176557

HCLS1 associated protein X-1 OKDB#: 4778
 Symbols: HAX1 Species: human
 Synonyms: SCN3, HS1BP1, HCLSBP1  Locus: 1q21.3 in Homo sapiens


For retrieval of Nucleotide and Amino Acid sequences please go to: OMIM Entrez Gene
Mammalian Reproductive Genetics   Endometrium Database Resource   Orthologous Genes   UCSC Genome Browser   GEO Profiles new!   Amazonia (transcriptome data) new!

R-L INTERACTIONS   MGI

DNA Microarrays
SHOW DATA ...
link to BioGPS
General Comment Hax-1 is required for Rac1-Cortactin interaction and ovarian carcinoma cell migration. Gomathinayagam R et al. (2014) Hax-1 is a multifunctional protein, which is involved in diverse cellular signaling pathways including tumor cell survival and migration. We have shown previously that cell migration stimulated by the oncogenic G protein, G13, requires Hax-1 for the formation of a functional complex involving Gα13, Rac1, and cortactin. However, the role of Hax-1 in cancer cell migration or its role in Rac1-cortactin complex formation, which is known to be required for such migration remains to be characterized. Results focused on resolving the role of Hax-1 in ovarian cancer pathophysiology indicate that Hax-1 is overexpressed in ovarian cancer cells and the silencing of Hax-1 inhibits lysophosphatidic acid (LPA)- or fetal bovine serum-stimulated migration of these cells. In addition, silencing of Hax-1 greatly reduces Rac1-cortactin interaction and their colocalization in SKOV3 cells. Mapping the structural domains of Hax-1 indicates that it interacts with cortactin via domains spanning amino acids 1 to 56 (Hax-D1) and amino acids 113 to 168 (Hax-D3). Much weaker interaction with cortactin was also observed with the region of Hax-1 spanning amino acids 169 - 224 (Hax-D4). Similar mapping of Hax-1 domains involved in Rac1 interaction indicates that it associates with Rac1 via two primary domains spanning amino acids 57 to 112 (Hax-D2) and 169 to 224 (Hax-D4). Furthermore, expression of either of these domains inhibits LPA-mediated migration of SKOV3 cells, possibly through their ability to exert competitive inhibition on endogenous Hax-1-Rac1 and/or Hax-1-cortactin interaction. More significantly, expression of Hax-D4 drastically reduces Rac1-cortactin colocalization in SKOV3 cells along with an attenuation of LPA-stimulated migration. Thus our results presented here describe for the first time that Hax-1 interaction is required for the association between Rac1 and cortactin and that these multiple interactions are required for the LPA-stimulated migration of SKOV3 ovarian cancer cells. //////////////////

NCBI Summary: 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]
General function Intracellular signaling cascade, Cytoskeleton
Comment
Cellular localization Cytoplasmic
Comment
Ovarian function
Comment
Expression regulated by
Comment
Ovarian localization Oocyte, Granulosa
Comment
Follicle stages
Comment
Phenotypes POF (premature ovarian failure)
Mutations 3 mutations

Species: human
Mutation name: None
type: naturally occurring
fertility: subfertile
Comment: Ovarian failure in HAX-1 deficient patients: is there a gender-specific difference in pubertal development in severe congenital neutropenia or Kostmann disease? Carlsson G et al. AIM: Severe congenital neutropenia (SCN) is a rare disorder of myelopoiesis characterized by neutropenia, recurrent bacterial infections, and a maturation arrest of the myelopoiesis in the bone marrow. Homozygous mutations in the HAX1 gene were described in patients with autosomal recessive SCN or Kostmann disease. Some of these patients display neurological disease. We noted, during the course of clinical management of patients with Kostmann disease, insufficient pubertal development in female patients, but not in our male patients. The study objective was to provide a detailed account of this phenotype and its possible relation to HAX1 mutations. METHODS: Detailed clinical histories and laboratory investigations of three patients with Kostmann disease belonging to the original kindred in northern Sweden described by Rolf Kostmann are reported. RESULTS: We report one male patient with normal puberty and two female patients with insufficient pubertal development. Elevated levels of LH and FSH were recorded in both patients. All three patients harbor the same p.Glu190X mutation in the HAX1 gene. CONCLUSIONS: We show for the first time that female patients with Kostmann disease display primary gonadal insufficiency. This suggests a possible role for HAX-1 in the development and/or function of the human ovary. 2012 The Author(s)/Acta Paediatrica 2012 Foundation Acta Paediatrica.

Species: human
Mutation name:
type: naturally occurring
fertility: subfertile
Comment: Delayed Puberty and Gonadal Failure in Patients with HAX1 Mutation. Cekic S et al. (2017) Homozygous mutations in the HAX1 gene cause an autosomal recessive form of severe congenital neutropenia (SCN). There are limited data on cases of gonadal insufficiency that involve the HAX1 gene mutation. We aimed to evaluate the pubertal development and gonadal functions of our patients with a p.Trp44X mutation in the HAX1 gene. Pubertal development, physical and laboratory findings of one male and seven female patients with HAX1 deficiency were evaluated. The age of the patients was between 13 and 25 years. All female patients were diagnosed with primary ovarian insufficiency (POI) based on amenorrhea and elevated gonadotropins. The ovary volumes in female patients were determined to be smaller than normal for their age through sonographic studies. Short stature associated with gonadal insufficiency was also observed in three patients. The HAX1 gene is important for ovarian development, in which a p.Trp44X mutation may cause POI in female patients. It is crucial to follow up and evaluate the gonadal functions of female patients in such cases.//////////////////

Species: mouse
Mutation name:
type: null mutation
fertility: None
Comment: behavior, endocrine/exocrine, growth/size/body, hematopoietic, immune, mortality/aging, skeleton////////////

Genomic Region show genomic region
Phenotypes and GWAS show phenotypes and GWAS
Links
OMIM (Online Mendelian Inheritance in Man: an excellent source of general gene description and genetic information.)
OMIM \ Animal Model
KEGG Pathways
Recent Publications
None
Search for Antibody


created: Oct. 17, 2012, 8:51 a.m. by: hsueh   email:
home page:
last update: April 27, 2020, 1 p.m. by: hsueh    email:



Use the back button of your browser to return to the Gene List.

Click here to return to gene search form