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Hematopoietically expressed homeobox
Protein HHEX PDB 2e1o.png
PDB rendering based on 2e1o.
Available structures
PDB Ortholog search: PDBe, RCSB
External IDs OMIM604420 MGI96086 HomoloGene31110 GeneCards: HHEX Gene
RNA expression pattern
PBB GE HHEX 204689 at tn.png
PBB GE HHEX 215933 s at tn.png
More reference expression data
Species Human Mouse
Entrez 3087 15242
Ensembl ENSG00000152804 ENSMUSG00000024986
UniProt Q03014 P43120
RefSeq (mRNA) NM_002729 NM_008245
RefSeq (protein) NP_002720 NP_032271
Location (UCSC) Chr 10:
92.69 – 92.7 Mb
Chr 19:
37.43 – 37.44 Mb
PubMed search [1] [2]

Hematopoietically-expressed homeobox protein HHEX is a protein that in humans is encoded by the HHEX gene.[1][2][3]

This gene encodes a member of the homeobox family of transcription factors, many of which are involved in developmental processes. Expression in specific hematopoietic lineages suggests that this protein may play a role in hematopoietic differentiation.[3]


The HHEX transcription factor acts as a promoter in some instances and an inhibitor others.[4][5] It interacts with a number of other signaling molecules to play an important role in the development of multiple organs, such as the liver, thyroid and forebrain.[6] HHEX serves to repress VEGFA, another protein which is important in endothelial cell development.[7] SCL, a significant transcription factor for blood and endothelial cell differentiation, is shown to interact with HHEX to promote the correct development of the hematopoiesis process.[8] HHEX appears to work together with another molecule, β-catenin, for the development of the anterior organizer.[9] It also contributes to developmental remodeling and stabilization of endothelial cells in an unborn organism.[7] The importance of this transcription factor is illustrated by the inability of HHEX knockout mice embryos to survive gestation. Without the expression of HHEX, these mice embryos die in utero between Day 13 and Day 16.[7] HHEX knockout mice display a range of abnormalities including forebrain abnormalities in various levels of severity, as well as a number of other defects including heart, vasculature, liver, monocyte, and thyroid abnormalities.[6][7]


HHEX has been shown to interact with Promyelocytic leukemia protein.[10]


  1. ^ Bedford FK, Ashworth A, Enver T, Wiedemann LM (Mar 1993). "HEX: a novel homeobox gene expressed during haematopoiesis and conserved between mouse and human". Nucleic Acids Research 21 (5): 1245–9. doi:10.1093/nar/21.5.1245. PMC 309289. PMID 8096636. 
  2. ^ Hromas R, Radich J, Collins S (Sep 1993). "PCR cloning of an orphan homeobox gene (PRH) preferentially expressed in myeloid and liver cells". Biochemical and Biophysical Research Communications 195 (2): 976–83. doi:10.1006/bbrc.1993.2140. PMID 8103988. 
  3. ^ a b "Entrez Gene: HHEX hematopoietically expressed homeobox". 
  4. ^ Denson LA, Karpen SJ, Bogue CW, Jacobs HC (Aug 2000). "Divergent homeobox gene hex regulates promoter of the Na(+)-dependent bile acid cotransporter". American Journal of Physiology. Gastrointestinal and Liver Physiology 279 (2): G347–55. PMID 10915644. 
  5. ^ Brickman JM, Jones CM, Clements M, Smith JC, Beddington RS (Jun 2000). "Hex is a transcriptional repressor that contributes to anterior identity and suppresses Spemann organiser function". Development 127 (11): 2303–15. PMID 10804173. 
  6. ^ a b Martinez Barbera JP, Clements M, Thomas P, Rodriguez T, Meloy D, Kioussis D, Beddington RS (Jun 2000). "The homeobox gene Hex is required in definitive endodermal tissues for normal forebrain, liver and thyroid formation". Development 127 (11): 2433–45. PMID 10804184. 
  7. ^ a b c d Hallaq H, Pinter E, Enciso J, McGrath J, Zeiss C, Brueckner M, Madri J, Jacobs HC, Wilson CM, Vasavada H, Jiang X, Bogue CW (Oct 2004). "A null mutation of Hhex results in abnormal cardiac development, defective vasculogenesis and elevated Vegfa levels". Development 131 (20): 5197–209. doi:10.1242/dev.01393. PMID 15459110. 
  8. ^ Liao W, Ho CY, Yan YL, Postlethwait J, Stainier DY (Oct 2000). "Hhex and scl function in parallel to regulate early endothelial and blood differentiation in zebrafish". Development 127 (20): 4303–13. PMID 11003831. 
  9. ^ Zamparini AL, Watts T, Gardner CE, Tomlinson SR, Johnston GI, Brickman JM (Sep 2006). "Hex acts with beta-catenin to regulate anteroposterior patterning via a Groucho-related co-repressor and Nodal". Development 133 (18): 3709–22. doi:10.1242/dev.02516. PMID 16936074. 
  10. ^ Topcu Z, Mack DL, Hromas RA, Borden KL (Nov 1999). "The promyelocytic leukemia protein PML interacts with the proline-rich homeodomain protein PRH: a RING may link hematopoiesis and growth control". Oncogene 18 (50): 7091–100. doi:10.1038/sj.onc.1203201. PMID 10597310. 

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This article incorporates text from the United States National Library of Medicine, which is in the public domain.