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Hhex

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Hhex

Hematopoietically expressed homeobox

PDB rendering based on 2e1o.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols  ; HEX; HMPH; HOX11L-PEN; PRH; PRHX
External IDs GeneCards:
RNA expression pattern
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)
RefSeq (protein)
Location (UCSC)
PubMed search

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]

Interactions

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

References

  1. ^ Bedford FK, Ashworth A, Enver T, Wiedemann LM (May 1993). "HEX: a novel homeobox gene expressed during haematopoiesis and conserved between mouse and human". Nucleic Acids Res 21 (5): 1245–9.  
  2. ^ Hromas R, Radich J, Collins S (Oct 1993). "PCR cloning of an orphan homeobox gene (PRH) preferentially expressed in myeloid and liver cells". Biochem Biophys Res Commun 195 (2): 976–83.  
  3. ^ a b "Entrez Gene: HHEX hematopoietically expressed homeobox". 
  4. ^ Denson, Lee; Karpen, Saul; Bogue, Clifford; Jacobs, Harris (August 2000). "Divergent homeobox gene Hex regulates promoter of the Na+-dependent bile acid cotransporter". American Journal of Physiology – Gastrointestinal and Liver Physiology 279 (2): 347–355. 
  5. ^ Brickman, Joshua; Jones, C; Clements, Melanie; Smith, J; Beddington, Rosa (June 2000). "Hex is a transcriptional repressor that contributes to anterior identity and suppresses Spemann organiser function". Development 127: 2303–2315. 
  6. ^ a b Martinez Barbera, Juan; Clements, Melanie; Thomas, Paul; Rodriguez, Tristan; Meloy, Denise; Kioussis, Dimitris; Beddington, Rosa (May 2000). "The homeobox gene Hex is required in definitive endodermal tissues for normal forebrain, liver and thryoid formation". Development 127: 2433–2445. 
  7. ^ a b c d Hallaq, Haifa; Pinter, Emese; Enciso, Josephine; McGrath, James; Zeiss, Caroline; Brueckner, Martina; Madri, Joseph; Jacobs, Harris; Wilson, Christine; Vasavada, Hemaxi; Jiang, Xiaobing; Bogue, Clifford (October 2004). "A null mutation of Hhex results in abnormal cardiac development, defective vasculogenesis and elevated Vegfa levels". Development 131: 5197–5209.  
  8. ^ Liao, Wayne; Ho, Chi-Yip; Yi, Lin Yan; Postlewait, John; Stainier, Didier (September 2000). "Hhex and Scl function in parallel to regulate early endothelial and blood differentiation in zebrafish". Development 127: 4303–4313. 
  9. ^ Zamparini, Andrea; Watts, Tim; Gardner, Clare; Tomlinson, Simon; Johnston, Geoffrey; Brickman, Joshua (September 2006). "Hex acts with β-catenin to regulate anteroposterior patterning via a Groucho-related co-repressor and Nodal". Development 133: 3709–3722.  
  10. ^ Topcu, Z; Mack D L; Hromas R A; Borden K L (Nov 1999). "The promyelocytic leukemia protein PML interacts with the proline-rich homeodomain protein PRH: a RING may link hematopoiesis and growth control". Oncogene (ENGLAND) 18 (50): 7091–100.  

Further reading

External links

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