HHEX

Not to be confused with HEX.

Hematopoietically-expressed homeobox protein HHEX is a protein that in humans is encoded by the HHEX gene and also known as Proline Rich Homeodomain protein PRH.^[5][6][7]

HHEX
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2E1O
Identifiers
Aliases	HHEX, HEX, HMPH, HOX11L-PEN, PRH, PRHX, hematopoietically expressed homeobox
External IDs	OMIM: 604420; MGI: 96086; HomoloGene: 31110; GeneCards: HHEX; OMA:HHEX - orthologs
Gene location (Human) Chr. Chromosome 10 (human)[1] Band 10q23.33 Start 92,689,955 bp[1] End 92,695,647 bp[1]
Gene location (Mouse) Chr. Chromosome 19 (mouse)[2] Band 19 C2|19 32.28 cM Start 37,423,258 bp[2] End 37,429,179 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in secondary oocyte right lobe of thyroid gland left lobe of thyroid gland monocyte right lobe of liver granulocyte spleen body of pancreas gallbladder blood Top expressed in renal medulla primary oocyte outer renal medulla granulocyte adrenal gland zygote liver spleen inner renal medulla secondary oocyte More reference expression data BioGPS More reference expression data
Gene ontology Molecular function sequence-specific DNA binding DNA binding RNA polymerase II transcription regulatory region sequence-specific DNA binding protein homodimerization activity DNA-binding transcription factor activity HMG box domain binding transcription factor binding chromatin binding RNA polymerase II cis-regulatory region sequence-specific DNA binding DNA-binding transcription repressor activity, RNA polymerase II-specific protein binding eukaryotic initiation factor 4E binding TBP-class protein binding DNA binding, bending DNA-binding transcription factor activity, RNA polymerase II-specific Cellular component cytoplasm protein-DNA complex nucleus Biological process Notch signaling pathway myeloid leukocyte differentiation endoderm development DNA conformation change regulation of transcription, DNA-templated primary lung bud formation negative regulation of cyclin-dependent protein serine/threonine kinase activity multicellular organism growth embryonic organ development regulation of transcription by RNA polymerase II negative regulation of vascular endothelial growth factor receptor signaling pathway interkinetic nuclear migration negative regulation of transcription by competitive promoter binding hepatocyte differentiation in utero embryonic development negative regulation of transcription by RNA polymerase II Wnt signaling pathway tissue morphogenesis mRNA export from nucleus transcription, DNA-templated embryonic heart tube development vasculogenesis morphogenesis of an epithelium poly(A)+ mRNA export from nucleus positive regulation of Wnt signaling pathway forebrain morphogenesis multicellular organism development hepatoblast differentiation thyroid gland development common bile duct development regulation of cell population proliferation protein localization to nucleus gall bladder development negative regulation of angiogenesis pancreas development animal organ morphogenesis B cell differentiation hepatic duct development liver development negative regulation of transcription by transcription factor localization forebrain development cell population proliferation negative regulation of transcription, DNA-templated primitive streak formation anterior/posterior pattern specification positive regulation of transcription by RNA polymerase II signal transduction response to peptide hormone response to wounding cell differentiation hemopoiesis regulation of leukocyte proliferation Sources:Amigo / QuickGO
Orthologs 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: 37.42 – 37.43 Mb PubMed search [3] [4]
Wikidata
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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 but the expression of this protein is not limited to hematopoietic cells.^[7]

Function

The HHEX transcription factor acts as a activator of transcription in some instances and a repressor of transcription others.^[8][9] 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.^[10] HHEX serves to repress VEGFA, another protein which is important in endothelial cell development.^[11] 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.^[12] HHEX appears to work together with another molecule, β-catenin, for the development of the anterior organizer.^[13] It also contributes to developmental remodeling and stabilization of endothelial cells in an unborn organism.^[11] 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.^[11] 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.^[10][11] The HHEX protein is important in a variety of cancers and it can act as a tumour suppressor protein or as an oncoprotein depending on the cancer type.

Interactions

HHEX has been shown to interact with Promyelocytic leukemia protein.^[14]