HAX1 explained

HCLS1-associated protein X-1 is a protein that in humans is encoded by the HAX1 gene.^{[1] [2] [3]}

The protein encoded by this gene is known to associate with HS1, a substrate of Src family tyrosine kinases. It also interacts with the product of PKD2 gene, mutations in which are associated with autosomal-dominant polycystic kidney disease, and with 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. Two transcript variants encoding different isoforms have been found for this gene.

In 2015, localization of the protein to P-bodies was demonstrated.^[4]

Severe congenital neutropenia

Homozygous mutations in HAX1 are associated with autosomal recessive severe congenital neutropenia.^[5]

Interactions

HAX1 has been shown to interact with IL1A.^[6] The protein has also been shown to interact with the 3' untranslated regions of vimentin and DNA polymerase B transcripts. The protein has been shown to interact with the mitochondrial protein disaggregase Skd3 and Skd3 has been shown to be essential for HAX1 solubility within mitochondria.^[7]

Further reading

• Modem S, Reddy TR . An anti-apoptotic protein, Hax-1, inhibits the HIV-1 rev function by altering its sub-cellular localization . J. Cell. Physiol. . 214 . 1 . 14–19 . 2007 . 17929250 . 10.1002/jcp.21305 . 36596625 .
• Klein C . HAX1 deficiency causes autosomal recessive severe congenital neutropenia (Kostmann disease) . Nat. Genet. . 39 . 1 . 86–92 . 2007 . 17187068 . 10.1038/ng1940 . Grudzien M . Appaswamy G . Germeshausen . Manuela . Sandrock . Inga . Schäffer . Alejandro A . Rathinam . Chozhavendan . Boztug . Kaan . Schwinzer . Beate . 22757727 .
• Kawaguchi Y . Intracellular IL-1α-binding proteins contribute to biological functions of endogenous IL-1α in systemic sclerosis fibroblasts . Proc. Natl. Acad. Sci. U.S.A. . 103 . 39 . 14501–06 . 2006 . 16971486 . 10.1073/pnas.0603545103 . 1599989 . Nishimagi E . Tochimoto A . Kawamoto . M . Katsumata . Y . Soejima . M . Kanno . T . Kamatani . N . Hara . M . 2006PNAS..10314501K. free .
• Han Y . Overexpression of HAX-1 protects cardiac myocytes from apoptosis through caspase-9 inhibition . Circ. Res. . 99 . 4 . 415–23 . 2006 . 16857965 . 10.1161/01.RES.0000237387.05259.a5 . Chen YS . Liu Z . Bodyak . N . Rigor . D . Bisping . E . Pu . WT . Kang . PM . free .
• Rual JF . Towards a proteome-scale map of the human protein-protein interaction network . Nature . 437 . 7062 . 1173–78 . 2005 . 16189514 . 10.1038/nature04209 . Venkatesan K . Hao T . Hirozane-Kishikawa . Tomoko . Dricot . Amélie . Li . Ning . Berriz . Gabriel F. . Gibbons . Francis D. . Dreze . Matija . 2005Natur.437.1173R. 4427026 .
• Gerhard DS . The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC) . Genome Res. . 14 . 10B . 2121–27 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 . Wagner L . Feingold EA . Shenmen . CM . Grouse . LH . Schuler . G . Klein . SL . Old . S . Rasooly . R .
• Ortiz DF . Identification of HAX-1 as a protein that binds bile salt export protein and regulates its abundance in the apical membrane of Madin-Darby canine kidney cells . J. Biol. Chem. . 279 . 31 . 32761–70 . 2004 . 15159385 . 10.1074/jbc.M404337200 . Moseley J . Calderon G . Swift . AL . Li . S . Arias . IM . free.
• Bouwmeester T . A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway . Nat. Cell Biol. . 6 . 2 . 97–105 . 2004 . 14743216 . 10.1038/ncb1086 . Bauch A . Ruffner H . Angrand . Pierre-Olivier . Bergamini . Giovanna . Croughton . Karen . Cruciat . Cristina . Eberhard . Dirk . Gagneur . Julien . 11683986 .
• Mirmohammadsadegh A . HAX-1, identified by differential display reverse transcription polymerase chain reaction, is overexpressed in lesional psoriasis . J. Invest. Dermatol. . 120 . 6 . 1045–51 . 2003 . 12787133 . 10.1046/j.1523-1747.2003.12247.x . Tartler U . Michel G . Baer . Annett . Walz . Markus . Wolf . Ronald . Ruzicka . Thomas . Hengge . Ulrich R . free .
• Strausberg RL . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . Feingold EA . Grouse LH . Derge . JG . Klausner . RD . Collins . FS . Wagner . L . Shenmen . CM . Schuler . GD . 2002PNAS...9916899M. free .
• Yin H . Evidence that HAX-1 is an interleukin-1 alpha N-terminal binding protein . Cytokine . 15 . 3 . 122–37 . 2001 . 11554782 . 10.1006/cyto.2001.0891 . Morioka H . Towle CA . Vidal . M . Watanabe . T . Weissbach . L .

Notes and References

1. Suzuki Y, Demoliere C, Kitamura D, Takeshita H, Deuschle U, Watanabe T . HAX-1, a novel intracellular protein, localized on mitochondria, directly associates with HS1, a substrate of Src family tyrosine kinases . J Immunol . 158 . 6 . 2736–44 . Apr 1997 . 10.4049/jimmunol.158.6.2736 . 9058808 .
2. Gallagher AR, Cedzich A, Gretz N, Somlo S, Witzgall R . The polycystic kidney disease protein PKD2 interacts with Hax-1, a protein associated with the actin cytoskeleton . Proc Natl Acad Sci U S A . 97 . 8 . 4017–22 . May 2000 . 10760273 . 18134 . 10.1073/pnas.97.8.4017 . 2000PNAS...97.4017G . free .
3. Web site: Entrez Gene: HAX1 HCLS1 associated protein X-1.
4. 1 January 2015. HAX-1: A Novel P-Body Protein. DNA and Cell Biology. 10.1089/dna.2014.2657. 25289648. Zayat V, Balcerak A, Korczynski J, Trebinska A, Wysocki J, Sarnowska E, Chmielarczyk M, Macech E, Konopiński R, Dziembowska M, Grzybowska EA. 34. 1. 4281894. 43–54.
5. Klein C . HAX1 deficiency causes autosomal recessive severe congenital neutropenia (Kostmann disease) . Nat. Genet. . 39 . 1 . 86–92 . January 2007 . 17187068 . 10.1038/ng1940 . Grudzien M . Appaswamy G . Germeshausen . Manuela . Sandrock . Inga . Schäffer . Alejandro A . Rathinam . Chozhavendan . Boztug . Kaan . Schwinzer . Beate. 22757727 .
6. Yin . H . Morioka H . Towle C A . Vidal M . Watanabe T . Weissbach L . Aug 2001 . Evidence that HAX-1 is an interleukin-1 alpha N-terminal binding protein . Cytokine . 15 . 3 . 122–37 . 1043-4666. 11554782 . 10.1006/cyto.2001.0891 .
7. Cupo. Ryan R. Shorter. James. 2020-06-23. Skd3 (human CLPB) is a potent mitochondrial protein disaggregase that is inactivated by 3-methylglutaconic aciduria-linked mutations. eLife. en. 9. e55279. 10.7554/eLife.55279. 32573439. 7343390. 2050-084X. free.