HAX1

HAX1
Identifiers
Aliases	HAX1, HCLSBP1, HS1BP1, SCN3, HCLS1 associated protein X-1
External IDs	OMIM: 605998; MGI: 1346319; HomoloGene: 4463; GeneCards: HAX1; OMA:HAX1 - orthologs
Gene location (Human)
Chr.	Chromosome 1 (human)
End	154,275,875 bp
Gene location (Mouse)
Chr.	Chromosome 3 (mouse)
End	89,906,087 bp
RNA expression pattern
	Top expressed in
	apex of heart; ; right ventricle; ; muscle of thigh; ; left ventricle; ; pituitary gland; ; body of tongue; ; anterior pituitary; ; beta cell; ; thoracic diaphragm; ; muscle of arm;
	Top expressed in
	morula; ; epiblast; ; pancreas; ; islet of Langerhans; ; primary oocyte; ; proximal tubule; ; adrenal gland; ; right kidney; ; yolk sac; ; embryo;
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	protein N-terminus binding; protein binding; interleukin-1 binding;
Cellular component	cytoplasm; nuclear membrane; nuclear envelope; membrane; transcription regulator complex; mitochondrial intermembrane space; sarcoplasmic reticulum; mitochondrial outer membrane; endoplasmic reticulum; mitochondrion; actin cytoskeleton; cytoplasmic vesicle; nucleus; lamellipodium; P-body; plasma membrane; cell cortex;
Biological process	regulation of apoptotic process; positive regulation of protein kinase B signaling; mitochondrion organization; negative regulation of apoptotic process; cellular response to cytokine stimulus; positive regulation of peptidyl-serine phosphorylation; regulation of actin filament polymerization; regulation of autophagy of mitochondrion; regulation of protein targeting to mitochondrion; positive regulation of peptidyl-tyrosine phosphorylation; positive regulation of granulocyte differentiation; positive regulation of phosphatidylinositol 3-kinase signaling; positive regulation of actin cytoskeleton reorganization; positive regulation of transcription by RNA polymerase II;
	Sources:Amigo / QuickGO
Orthologs
	10456
	23897
	ENSG00000143575
	ENSMUSG00000027944
	O00165; Q5VYD6
	O35387
	NM_006118; NM_001018837
	NM_001282032; NM_011826; NM_001310681
	NP_001018238; NP_006109
	NP_001268961; NP_001297610; NP_035956
	Wikidata
View/Edit Human	View/Edit Mouse

HCLS1-associated protein X-1 is a protein that in humans is encoded by the HAX1 gene.^[5]^[6]^[7]

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.^[7]

In 2015, localization of the protein to P-bodies was demonstrated.^[8]

Severe congenital neutropenia

Homozygous mutations in HAX1 are associated with autosomal recessive severe congenital neutropenia.^[9]

Interactions

HAX1 has been shown to interact with IL1A.^[10] The protein has also been shown to interact with the 3' untranslated regions of vimentin and DNA polymerase B transcripts.^[8] 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.^[11]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000143575 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000027944 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Suzuki Y, Demoliere C, Kitamura D, Takeshita H, Deuschle U, Watanabe T (Apr 1997). "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. PMID 9058808.
^ Gallagher AR, Cedzich A, Gretz N, Somlo S, Witzgall R (May 2000). "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. Bibcode:2000PNAS...97.4017G. doi:10.1073/pnas.97.8.4017. PMC 18134. PMID 10760273.
^ ^a ^b "Entrez Gene: HAX1 HCLS1 associated protein X-1".
^ ^a ^b Zayat V, Balcerak A, Korczynski J, Trebinska A, Wysocki J, Sarnowska E, Chmielarczyk M, Macech E, Konopiński R, Dziembowska M, Grzybowska EA (1 January 2015). "HAX-1: A Novel P-Body Protein". DNA and Cell Biology. 34 (1): 43–54. doi:10.1089/dna.2014.2657. PMC 4281894. PMID 25289648.
^ Klein C; Grudzien M; Appaswamy G; et al. (January 2007). "HAX1 deficiency causes autosomal recessive severe congenital neutropenia (Kostmann disease)". Nat. Genet. 39 (1): 86–92. doi:10.1038/ng1940. PMID 17187068. {{cite journal}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
^ 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. doi:10.1006/cyto.2001.0891. ISSN 1043-4666. PMID 11554782.
^ 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. 9: e55279. doi:10.7554/eLife.55279. ISSN 2050-084X.{{cite journal}}: CS1 maint: unflagged free DOI (link)

Modem S, Reddy TR (2007). "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. doi:10.1002/jcp.21305. PMID 17929250.
Klein C; Grudzien M; Appaswamy G; et al. (2007). "HAX1 deficiency causes autosomal recessive severe congenital neutropenia (Kostmann disease)". Nat. Genet. 39 (1): 86–92. doi:10.1038/ng1940. PMID 17187068. {{cite journal}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
Kawaguchi Y; Nishimagi E; Tochimoto A; et al. (2006). "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. Bibcode:2006PNAS..10314501K. doi:10.1073/pnas.0603545103. PMC 1599989. PMID 16971486. {{cite journal}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
Han Y; Chen YS; Liu Z; et al. (2006). "Overexpression of HAX-1 protects cardiac myocytes from apoptosis through caspase-9 inhibition". Circ. Res. 99 (4): 415–23. doi:10.1161/01.RES.0000237387.05259.a5. PMID 16857965. {{cite journal}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
Rual JF; Venkatesan K; Hao T; et al. (2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–78. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514. {{cite journal}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
Gerhard DS; Wagner L; Feingold EA; et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–27. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334. {{cite journal}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
Ortiz DF; Moseley J; Calderon G; et al. (2004). "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. doi:10.1074/jbc.M404337200. PMID 15159385. {{cite journal}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
Bouwmeester T; Bauch A; Ruffner H; et al. (2004). "A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway". Nat. Cell Biol. 6 (2): 97–105. doi:10.1038/ncb1086. PMID 14743216. {{cite journal}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
Mirmohammadsadegh A; Tartler U; Michel G; et al. (2003). "HAX-1, identified by differential display reverse transcription polymerase chain reaction, is overexpressed in lesional psoriasis". J. Invest. Dermatol. 120 (6): 1045–51. doi:10.1046/j.1523-1747.2003.12247.x. PMID 12787133. {{cite journal}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
Strausberg RL; Feingold EA; Grouse LH; et al. (2003). "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. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. {{cite journal}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
Yin H; Morioka H; Towle CA; et al. (2001). "Evidence that HAX-1 is an interleukin-1 alpha N-terminal binding protein". Cytokine. 15 (3): 122–37. doi:10.1006/cyto.2001.0891. PMID 11554782. {{cite journal}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)

This article on a gene on human chromosome 1 is a stub. You can help Wikipedia by expanding it.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000143575 – Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000027944 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid9058808-5] Suzuki Y, Demoliere C, Kitamura D, Takeshita H, Deuschle U, Watanabe T (Apr 1997). "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. PMID 9058808.

[pmid10760273-6] Gallagher AR, Cedzich A, Gretz N, Somlo S, Witzgall R (May 2000). "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. Bibcode:2000PNAS...97.4017G. doi:10.1073/pnas.97.8.4017. PMC 18134. PMID 10760273.

[entrez-7] "Entrez Gene: HAX1 HCLS1 associated protein X-1".

[:0-8] Zayat V, Balcerak A, Korczynski J, Trebinska A, Wysocki J, Sarnowska E, Chmielarczyk M, Macech E, Konopiński R, Dziembowska M, Grzybowska EA (1 January 2015). "HAX-1: A Novel P-Body Protein". DNA and Cell Biology. 34 (1): 43–54. doi:10.1089/dna.2014.2657. PMC 4281894. PMID 25289648.

[9] Klein C; Grudzien M; Appaswamy G; et al. (January 2007). "HAX1 deficiency causes autosomal recessive severe congenital neutropenia (Kostmann disease)". Nat. Genet. 39 (1): 86–92. doi:10.1038/ng1940. PMID 17187068. {{cite journal}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)

[pmid11554782-10] 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. doi:10.1006/cyto.2001.0891. ISSN 1043-4666. PMID 11554782.

[11] 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. 9: e55279. doi:10.7554/eLife.55279. ISSN 2050-084X.{{cite journal}}: CS1 maint: unflagged free DOI (link)

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Severe congenital neutropenia

Interactions

References

Further reading