HHEX Human

Hematopoietically Expressed Homeobox Human Recombinant
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Cat. No.
BT21730
Source
Escherichia Coli.
Synonyms
Hematopoietically Expressed Homeobox, Hematopoietically-Expressed Homeobox Protein HHEX, Homeobox Hematopoietically Expressed, Proline-Rich Homeodomain-Containing Transcription Factor, Homeobox Protein PRH, Homeobox Protein HEX, HOX11L-PEN, PRHX, HMPH, PRH, HEX.
Appearance
Sterile filtered colorless solution.
Purity
Greater than 85% as determined by SDS-PAGE.
Usage

THE BioTek's products are furnished for LABORATORY RESEARCH USE ONLY. The product may not be used as drugs, agricultural or pesticidal products, food additives or household chemicals.

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Description

Overview of HHEX Human

The Hematopoietically Expressed Homeobox protein (HHEX), encoded by the HHEX gene (also known as PRH), is an evolutionarily conserved transcription factor critical for embryonic development, organogenesis, and hematopoiesis . It functions as both a transcriptional activator and repressor, depending on cellular context and interacting partners . HHEX is indispensable for survival, as knockout mice embryos die by gestational day 13–16 due to severe developmental defects in the liver, thyroid, forebrain, and hematopoietic systems .

2.1. Genetic Organization

The HHEX gene spans four exons on human chromosome 10 (chromosome 19 in mice) and encodes a 270-amino-acid protein containing a homeodomain for DNA binding .

Gene AttributeDetails
Gene SymbolHHEX
SynonymsHEX, PRH, HOX11L-PEN
Chromosomal Location10q23.33 (human)
Protein Size270 amino acids
Key DomainsN-terminal proline-rich domain, homeodomain, C-terminal activation domain
Expression SitesHematopoietic lineages, liver, pancreas, thyroid, endothelial cells
Data derived from Refs

3.1. Developmental Roles

  • Pancreas: HHEX drives pancreatic endoderm differentiation by regulating NKX6.1, PTF1A, ONECUT1, and ONECUT3. Knockdown reduces β-cell differentiation efficiency, linking it to type 2 diabetes risk .

  • Liver and Thyroid: Essential for hepatic bud formation and thyroid morphogenesis .

  • Vasculature: Represses VEGFA to stabilize endothelial cells during embryogenesis .

3.2. Hematopoiesis

HHEX maintains hematopoietic stem cell (HSC) self-renewal and lymphopoiesis:

  • B-cell Development: Deletion in mice abolishes B-cell progenitors (pre-pro-B, pro-B) but spares mature recirculating B cells .

  • Myeloid Regulation: Interacts with HOXA9 and eIF4E to balance myeloid proliferation and differentiation .

4.1. Mechanistic Insights

  • Transcriptional Regulation:

    • Binds GATA-1/2 and c-Myb at a hematopoietic-specific enhancer in its first intron .

    • Phosphorylation at S163/S177 by CK2β inhibits DNA binding, reversible by dephosphorylation .

  • Protein Interactions:

    • Forms oligomers to repress targets like Goosecoid and retains Groucho/TLE proteins in the nucleus for repression .

    • Competes with HOXA9 for eIF4E binding, influencing Cyclin D1 mRNA transport .

4.2. Functional Studies

Study ModelKey FindingsImplications
Human iPSCsHHEX knockdown reduces NKX6.1+/PDX1+ pancreatic endoderm cells by 50% .Links HHEX to diabetes susceptibility .
Murine HematopoiesisHhex deletion eliminates B-cell progenitors but preserves marginal zone B cells .Highlights stage-specific roles in lymphopoiesis .
Retinoic Acid (RA) SignalingRA inhibition in hESCs suppresses HHEX, disrupting pancreatic fate .RA-HHEX axis critical for human endoderm patterning .

Clinical and Pathological Relevance

  • Type 2 Diabetes: GWAS identifies HHEX locus variants (e.g., rs7923837) as risk factors .

  • Leukemia: Hypomethylation of HHEX occurs in trisomy 8 acute myeloid leukemia (AML), suggesting diagnostic utility 100.

  • Cancer Duality: Acts as a tumor suppressor in AML but as an oncogene in thyroid and colorectal cancers .

Future Directions

  • Elucidate HHEX’s post-translational modifications (e.g., proteasomal interactions) .

  • Develop HHEX-targeted therapies for diabetes and hematologic malignancies.

  • Validate findings in vivo, as current models rely heavily on iPSCs and cell lines .

Product Specs

Introduction
HHEX is a member of the homeobox protein family of transcription factors, which plays a crucial role in developmental processes. It is known to interact with the Promyelocytic leukemia protein. Its expression in specific hematopoietic cell lines suggests its involvement in hematopoietic differentiation.
Description
Recombinant HHEX protein, expressed in E.coli, is a single, non-glycosylated polypeptide chain. It consists of 293 amino acids (residues 1-270) and has a molecular weight of 32.4kDa. The protein includes a 23 amino acid His-tag fused at the N-terminus. Purification is achieved using proprietary chromatographic techniques.
Physical Appearance
A clear and colorless solution, sterilized by filtration.
Formulation
The HHEX solution is supplied in a buffer containing 20mM Tris-HCl (pH 8.0), 0.15M NaCl, 1mM DTT, and 40% glycerol.
Stability
For short-term storage (2-4 weeks), the product should be kept at 4°C. For extended storage, freeze the solution at -20°C. The addition of a carrier protein (0.1% HSA or BSA) is recommended for long-term storage. Repeated freezing and thawing cycles should be avoided.
Purity
The purity is determined to be greater than 85% using SDS-PAGE analysis.
Synonyms
Hematopoietically Expressed Homeobox, Hematopoietically-Expressed Homeobox Protein HHEX, Homeobox Hematopoietically Expressed, Proline-Rich Homeodomain-Containing Transcription Factor, Homeobox Protein PRH, Homeobox Protein HEX, HOX11L-PEN, PRHX, HMPH, PRH, HEX.
Source
Escherichia Coli.
Amino Acid Sequence
MGSSHHHHHH SSGLVPRGSH MGSMQYPHPG PAAGAVGVPL YAPTPLLQPA HPTPFYIEDI LGRGPAAPTP APTLPSPNSS FTSLVSPYRT PVYEPTPIHP AFSHHSAAAL AAAYGPGGFG GPLYPFPRTV NDYTHALLRH DPLGKPLLWS PFLQRPLHKR KGGQVRFSND QTIELEKKFE TQKYLSPPER KRLAKMLQLS ERQVKTWFQN RRAKWRRLKQ ENPQSNKKEE LESLDSSCDQ RQDLPSEQNK GASLDSSQCS PSPASQEDLE SEISEDSDQE VDIEGDKSYF NAG

Product Science Overview

Introduction

The Hematopoietically Expressed Homeobox (HHEX) gene, also known as HEX, PRH (Proline-Rich Homeodomain), or XHEX in Xenopus, is a non-clustered homeobox gene that plays a crucial role in various biological processes. This gene is evolutionarily conserved across species, including fish, amphibians, birds, mice, and humans .

Gene Structure and Location

The human HHEX gene is located on chromosome 10 and comprises four exons . In mice, it is located on chromosome 19 . The gene encodes a transcription factor that is essential for the regulation of embryogenesis and hematopoietic progenitor development .

Biological Functions

HHEX is a transcriptional repressor involved in several critical developmental processes:

  1. Embryogenesis: HHEX is vital for the development of the foregut endoderm, which gives rise to endocrine organs such as the pancreas . It is also necessary for the normal development of the bile duct and liver, the latter being the initial site of hematopoiesis .
  2. Hematopoiesis: HHEX governs the origins of hematopoietic cells and is crucial for the self-renewal of definitive hematopoietic stem cells (HSCs) and lymphopoiesis .
  3. Endocrine System: HHEX is required for the development of the forebrain and thyroid gland, and its dysfunction is linked to various endocrine disorders .
Clinical Significance

HHEX has been identified as a promising candidate gene for type 2 diabetes through genome-wide association studies . Polymorphisms in the HHEX gene, such as rs1111875, rs5015480, and rs7923837, have been associated with an increased risk of type 2 diabetes . Additionally, HHEX is implicated in various hematological malignancies and other diseases .

Research and Therapeutic Potential

The recombinant form of HHEX (Human Recombinant) is used in research to study its functions and potential therapeutic applications. Understanding the role of HHEX in various biological processes and diseases can lead to the development of targeted therapies for conditions such as diabetes, hematological malignancies, and endocrine disorders .

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