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FLASH GENE

Symbol

HHEX

contributors: mct/npt/pgu - updated : 12-05-2010

HGNC name	hematopoietically expressed homeobox
HGNC id	4901

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	an Eh-1 (Engrailed homology) motif present within the N-terminal transcription repression domain of PRH mediates binding to Groucho/TLE proteins and enables co-repression
	an homeobox DNA-binding domain

HOMOLOGY

interspecies

homolog to murine Hhex

intraspecies

homolog to HOX11

Homologene

FAMILY

homeobox transcription factor family

CATEGORY

DNA associated , transcription factor

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,nucleus
text	when GPC3 binds to CD81, CD81-HHEX binding decreases, resulting in nuclear translocation of HHEX and transcriptional repression)

basic FUNCTION	may be playing a role in hematopoietic differentiation
	may play a role in differentiation of the epithelial breast cell
	regulates the nuclear retention of TLE proteins during cellular fractionation
	regulates transcription by binding to specific DNA sequences and regulates mRNA transport by binding to translation initiation factor EIF4E
	T lineage oncogene when misexpressed in hematopoietic precursor cells
	homeodomain factor expressed in multiple endoderm-derived tissues, like the liver, where it is essential for proper development
	recently implicated in pancreas development and the regulation of insulin secretion
	plays multiple roles in the control of gene expression during embryonic development and in the adult
	key regulator of the VEGF signaling pathway, playing an important role in tumorigenesis and leukemogenesis
	HHEX and CER1 mediate the SOX17 pathway for cardiac mesoderm formation in embryonic stem cells

CELLULAR PROCESS

nucleotide, transcription

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	interaction between HHEX (hematopoietically expressed homeobox) and SOX13 that modulates Wnt/TCF pathway activity (this interaction may contribute to control Wnt/TCF signaling in the early embryo)
	binds directly to the promoter regions of the VEGFA, FLT1, and KDR genes and that in each case, represses transcription
	interacts with the beta subunit of CK2 in cells (CK2 phosphorylates HHEX, and CK2 phosphorylation of the HHEX homeodomain functions as a reversible switch for DNA binding)
	CD81-HHEX binding (when GPC3 binds to CD81, CD81-HHEX binding decreases, resulting in nuclear translocation of HHEX and transcriptional repression)

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in T-cell-derived lymphomas

Susceptibility

to type 2 diabetes

Variant & Polymorphism other	poymorphisms increasing the risk of type 2 diabetes
	variant (rs5015480) near HHEX associated with the susceptibility of T2DM in females, but not in males (

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS