Hematopoietically-expressed homeobox protein HHEX

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functionⁱ

Regions

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functionⁱ

• DNA binding, bending Source: BHF-UCL <p>Inferred from Direct Assay</p> <p>Used to indicate a direct assay for the function, process or component indicated by the GO term.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#ida">GO evidence code guide</a></p> Inferred from direct assayⁱ
  • "DNA wrapping and distortion by an oligomeric homeodomain protein."
    Williams H., Jayaraman P.S., Gaston K.
    J Mol Biol 383:10-23(2008) [PubMed] [Europe PMC] [Abstract]
• DNA-binding transcription factor activity, RNA polymerase II-specific Source: NTNU_SB
• DNA-binding transcription repressor activity, RNA polymerase II-specific Source: NTNU_SBInferred from direct assayⁱ
  • "Interaction between hex and GATA transcription factors in vascular endothelial cells inhibits flk-1/KDR-mediated vascular endothelial growth factor signaling."
    Minami T., Murakami T., Horiuchi K., Miura M., Noguchi T., Miyazaki J., Hamakubo T., Aird W.C., Kodama T.
    J Biol Chem 279:20626-20635(2004) [PubMed] [Europe PMC] [Abstract]
• eukaryotic initiation factor 4E binding Source: BHF-UCLInferred from direct assayⁱ
  • "The proline-rich homeodomain protein, PRH, is a tissue-specific inhibitor of eIF4E-dependent cyclin D1 mRNA transport and growth."
    Topisirovic I., Culjkovic B., Cohen N., Perez J.M., Skrabanek L., Borden K.L.
    EMBO J 22:689-703(2003) [PubMed] [Europe PMC] [Abstract]
• protein homodimerization activity Source: BHF-UCL <p>Inferred from Physical Interaction</p> <p>Covers physical interactions between the gene product of interest and another molecule (or ion, or complex).</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#ipi">GO evidence code guide</a></p> Inferred from physical interactionⁱ
  • "Oligomerisation of the developmental regulator proline rich homeodomain (PRH/Hex) is mediated by a novel proline-rich dimerisation domain."
    Soufi A., Smith C., Clarke A.R., Gaston K., Jayaraman P.S.
    J Mol Biol 358:943-962(2006) [PubMed] [Europe PMC] [Abstract]
• repressing transcription factor binding Source: BHF-UCLInferred from direct assayⁱ
  • "The proline-rich homeodomain protein recruits members of the Groucho/Transducin-like enhancer of split protein family to co-repress transcription in hematopoietic cells."
    Swingler T.E., Bess K.L., Yao J., Stifani S., Jayaraman P.S.
    J Biol Chem 279:34938-34947(2004) [PubMed] [Europe PMC] [Abstract]
• RNA polymerase II cis-regulatory region sequence-specific DNA binding Source: NTNU_SBInferred from direct assayⁱ
  • "Interaction between hex and GATA transcription factors in vascular endothelial cells inhibits flk-1/KDR-mediated vascular endothelial growth factor signaling."
    Minami T., Murakami T., Horiuchi K., Miura M., Noguchi T., Miyazaki J., Hamakubo T., Aird W.C., Kodama T.
    J Biol Chem 279:20626-20635(2004) [PubMed] [Europe PMC] [Abstract]
• RNA polymerase II transcription regulatory region sequence-specific DNA binding Source: GO_Central <p>Inferred from Biological aspect of Ancestor</p> <p>A type of phylogenetic evidence whereby an aspect of a descendent is inferred through the characterization of an aspect of a ancestral gene.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#iba">GO evidence code guide</a></p> Inferred from biological aspect of ancestorⁱ
  • "Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium."
    Gaudet P., Livstone M.S., Lewis S.E., Thomas P.D.
    Brief Bioinform 12:449-462(2011) [PubMed] [Europe PMC] [Abstract]
• sequence-specific DNA binding Source: BHF-UCLInferred from direct assayⁱ
  • "Expression and function of the homeodomain-containing protein Hex in thyroid cells."
    Pellizzari L., D'Elia A., Rustighi A., Manfioletti G., Tell G., Damante G.
    Nucleic Acids Res 28:2503-2511(2000) [PubMed] [Europe PMC] [Abstract]
• TBP-class protein binding Source: BHF-UCL <p>Traceable Author Statement</p> <p>Used for information from review articles where the original experiments are traceable through that article and also for information from text books or dictionaries.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#tas">GO evidence code guide</a></p> Traceable author statementⁱ
  • "CK2 phosphorylation of the PRH/Hex homeodomain functions as a reversible switch for DNA binding."
    Soufi A., Noy P., Buckle M., Sawasdichai A., Gaston K., Jayaraman P.S.
    Nucleic Acids Res 37:3288-3300(2009) [PubMed] [Europe PMC] [Abstract]
• transcription factor binding Source: BHF-UCLInferred from physical interactionⁱ
  • "Interaction between hex and GATA transcription factors in vascular endothelial cells inhibits flk-1/KDR-mediated vascular endothelial growth factor signaling."
    Minami T., Murakami T., Horiuchi K., Miura M., Noguchi T., Miyazaki J., Hamakubo T., Aird W.C., Kodama T.
    J Biol Chem 279:20626-20635(2004) [PubMed] [Europe PMC] [Abstract]
• transcription regulatory region sequence-specific DNA binding Source: BHF-UCLInferred from direct assayⁱ
  • "DNA wrapping and distortion by an oligomeric homeodomain protein."
    Williams H., Jayaraman P.S., Gaston K.
    J Mol Biol 383:10-23(2008) [PubMed] [Europe PMC] [Abstract]

GO - Biological processⁱ

• anterior/posterior pattern specification Source: UniProtKB
• B cell differentiation Source: BHF-UCL
• cell differentiation Source: GO_CentralInferred from biological aspect of ancestorⁱ
  • "Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium."
    Gaudet P., Livstone M.S., Lewis S.E., Thomas P.D.
    Brief Bioinform 12:449-462(2011) [PubMed] [Europe PMC] [Abstract]
• DNA conformation change Source: BHF-UCLInferred from direct assayⁱ
  • "DNA wrapping and distortion by an oligomeric homeodomain protein."
    Williams H., Jayaraman P.S., Gaston K.
    J Mol Biol 383:10-23(2008) [PubMed] [Europe PMC] [Abstract]
• mRNA export from nucleus Source: BHF-UCLInferred from direct assayⁱ
  • "The proline-rich homeodomain protein, PRH, is a tissue-specific inhibitor of eIF4E-dependent cyclin D1 mRNA transport and growth."
    Topisirovic I., Culjkovic B., Cohen N., Perez J.M., Skrabanek L., Borden K.L.
    EMBO J 22:689-703(2003) [PubMed] [Europe PMC] [Abstract]
• negative regulation of angiogenesis Source: BHF-UCL <p>Inferred from Sequence or Structural Similarity<br />Used for any analysis based on sequence alignment, structure comparison, or evaluation of sequence features such as composition.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#iss">GO evidence code guide</a></p> Inferred from sequence or structural similarityⁱ
  • "Interaction between hex and GATA transcription factors in vascular endothelial cells inhibits flk-1/KDR-mediated vascular endothelial growth factor signaling."
    Minami T., Murakami T., Horiuchi K., Miura M., Noguchi T., Miyazaki J., Hamakubo T., Aird W.C., Kodama T.
    J Biol Chem 279:20626-20635(2004) [PubMed] [Europe PMC] [Abstract]
• negative regulation of cyclin-dependent protein serine/threonine kinase activity Source: BHF-UCLInferred from direct assayⁱ
  • "The proline-rich homeodomain protein, PRH, is a tissue-specific inhibitor of eIF4E-dependent cyclin D1 mRNA transport and growth."
    Topisirovic I., Culjkovic B., Cohen N., Perez J.M., Skrabanek L., Borden K.L.
    EMBO J 22:689-703(2003) [PubMed] [Europe PMC] [Abstract]
• negative regulation of transcription, DNA-templated Source: BHF-UCLInferred from direct assayⁱ
  • "Expression and function of the homeodomain-containing protein Hex in thyroid cells."
    Pellizzari L., D'Elia A., Rustighi A., Manfioletti G., Tell G., Damante G.
    Nucleic Acids Res 28:2503-2511(2000) [PubMed] [Europe PMC] [Abstract]
  • "Interaction between hex and GATA transcription factors in vascular endothelial cells inhibits flk-1/KDR-mediated vascular endothelial growth factor signaling."
    Minami T., Murakami T., Horiuchi K., Miura M., Noguchi T., Miyazaki J., Hamakubo T., Aird W.C., Kodama T.
    J Biol Chem 279:20626-20635(2004) [PubMed] [Europe PMC] [Abstract]
• negative regulation of transcription by competitive promoter binding Source: BHF-UCLTraceable author statementⁱ
  • "CK2 phosphorylation of the PRH/Hex homeodomain functions as a reversible switch for DNA binding."
    Soufi A., Noy P., Buckle M., Sawasdichai A., Gaston K., Jayaraman P.S.
    Nucleic Acids Res 37:3288-3300(2009) [PubMed] [Europe PMC] [Abstract]
• negative regulation of transcription by RNA polymerase II Source: BHF-UCLInferred from direct assayⁱ
  • "Expression and function of the homeodomain-containing protein Hex in thyroid cells."
    Pellizzari L., D'Elia A., Rustighi A., Manfioletti G., Tell G., Damante G.
    Nucleic Acids Res 28:2503-2511(2000) [PubMed] [Europe PMC] [Abstract]
  • "Interaction between hex and GATA transcription factors in vascular endothelial cells inhibits flk-1/KDR-mediated vascular endothelial growth factor signaling."
    Minami T., Murakami T., Horiuchi K., Miura M., Noguchi T., Miyazaki J., Hamakubo T., Aird W.C., Kodama T.
    J Biol Chem 279:20626-20635(2004) [PubMed] [Europe PMC] [Abstract]
• negative regulation of transcription by transcription factor localization Source: BHF-UCL <p>Inferred by Curator</p> <p>Used for cases where an annotation is not supported by any evidence but can be reasonably inferred by a curator from other GO annotations for which evidence<br />is available.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#ic">GO evidence code guide</a></p> Inferred by curatorⁱ
  • "The PRH/Hex repressor protein causes nuclear retention of Groucho/TLE co-repressors."
    Desjobert C., Noy P., Swingler T., Williams H., Gaston K., Jayaraman P.S.
    Biochem J 417:121-132(2009) [PubMed] [Europe PMC] [Abstract]
• negative regulation of vascular endothelial growth factor receptor signaling pathway Source: BHF-UCLInferred from sequence or structural similarityⁱ
  • "Interaction between hex and GATA transcription factors in vascular endothelial cells inhibits flk-1/KDR-mediated vascular endothelial growth factor signaling."
    Minami T., Murakami T., Horiuchi K., Miura M., Noguchi T., Miyazaki J., Hamakubo T., Aird W.C., Kodama T.
    J Biol Chem 279:20626-20635(2004) [PubMed] [Europe PMC] [Abstract]
• poly(A)+ mRNA export from nucleus Source: BHF-UCL <p>Inferred from Mutant Phenotype</p> <p>Describes annotations that are concluded from looking at variations or changes in a gene product such as mutations or abnormal levels and includes techniques such as knockouts, overexpression, anti-sense experiments and use of specific protein inhibitors.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#imp">GO evidence code guide</a></p> Inferred from mutant phenotypeⁱ
  • "The proline-rich homeodomain protein, PRH, is a tissue-specific inhibitor of eIF4E-dependent cyclin D1 mRNA transport and growth."
    Topisirovic I., Culjkovic B., Cohen N., Perez J.M., Skrabanek L., Borden K.L.
    EMBO J 22:689-703(2003) [PubMed] [Europe PMC] [Abstract]
• positive regulation of canonical Wnt signaling pathway Source: UniProtKBInferred from mutant phenotypeⁱ
  • Ref.8

    "Interaction between Hhex and SOX13 modulates Wnt/TCF activity."
    Marfil V., Moya M., Pierreux C.E., Castell J.V., Lemaigre F.P., Real F.X., Bort R.
    J. Biol. Chem. 285:5726-5737(2010) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, INTERACTION WITH SOX13.
• positive regulation of transcription by RNA polymerase II Source: BHF-UCLInferred from direct assayⁱ
  • "Thyroid-specific transcription factors control Hex promoter activity."
    Puppin C., D'Elia A.V., Pellizzari L., Russo D., Arturi F., Presta I., Filetti S., Bogue C.W., Denson L.A., Damante G.
    Nucleic Acids Res 31:1845-1852(2003) [PubMed] [Europe PMC] [Abstract]
• positive regulation of Wnt signaling pathway Source: UniProtKB
• protein localization to nucleus Source: BHF-UCLInferred from direct assayⁱ
  • "The PRH/Hex repressor protein causes nuclear retention of Groucho/TLE co-repressors."
    Desjobert C., Noy P., Swingler T., Williams H., Gaston K., Jayaraman P.S.
    Biochem J 417:121-132(2009) [PubMed] [Europe PMC] [Abstract]
• regulation of leukocyte proliferation Source: BHF-UCLInferred from direct assayⁱ
  • "The proline-rich homeodomain protein, PRH, is a tissue-specific inhibitor of eIF4E-dependent cyclin D1 mRNA transport and growth."
    Topisirovic I., Culjkovic B., Cohen N., Perez J.M., Skrabanek L., Borden K.L.
    EMBO J 22:689-703(2003) [PubMed] [Europe PMC] [Abstract]
• response to peptide hormone Source: Ensembl
• response to wounding Source: Ensembl
• Wnt signaling pathway Source: UniProtKB-KW

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsⁱ

Enzyme and pathway databases

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyⁱ

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationⁱ

Keywords - Cellular componentⁱ

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechⁱ

Organism-specific databases

Miscellaneous databases

Polymorphism and mutation databases

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingⁱ

Molecule processing

Amino acid modifications

Keywords - PTMⁱ

Proteomic databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressionⁱ

<p>This subsection of the 'Expression' section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified 'at protein level'.<br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityⁱ

<p>This subsection of the 'Expression' section provides information on the expression of the gene product at various stages of a cell, tissue or organism development. By default, the information is derived from experiments at the mRNA level, unless specified 'at the protein level'.<p><a href='/help/developmental_stage' target='_top'>More...</a></p>Developmental stageⁱ

Gene expression databases

Organism-specific databases

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactionⁱ

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction%5Fsection">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structureⁱ

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction%5Fsection">Interaction</a>' section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="https://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated at every <a href="http://www.uniprot.org/help/synchronization">UniProt release</a>.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsⁱ

GO - Molecular functionⁱ

• eukaryotic initiation factor 4E binding Source: BHF-UCLInferred from direct assayⁱ
  • "The proline-rich homeodomain protein, PRH, is a tissue-specific inhibitor of eIF4E-dependent cyclin D1 mRNA transport and growth."
    Topisirovic I., Culjkovic B., Cohen N., Perez J.M., Skrabanek L., Borden K.L.
    EMBO J 22:689-703(2003) [PubMed] [Europe PMC] [Abstract]
• protein homodimerization activity Source: BHF-UCLInferred from physical interactionⁱ
  • "Oligomerisation of the developmental regulator proline rich homeodomain (PRH/Hex) is mediated by a novel proline-rich dimerisation domain."
    Soufi A., Smith C., Clarke A.R., Gaston K., Jayaraman P.S.
    J Mol Biol 358:943-962(2006) [PubMed] [Europe PMC] [Abstract]
• repressing transcription factor binding Source: BHF-UCLInferred from direct assayⁱ
  • "The proline-rich homeodomain protein recruits members of the Groucho/Transducin-like enhancer of split protein family to co-repress transcription in hematopoietic cells."
    Swingler T.E., Bess K.L., Yao J., Stifani S., Jayaraman P.S.
    J Biol Chem 279:34938-34947(2004) [PubMed] [Europe PMC] [Abstract]
• TBP-class protein binding Source: BHF-UCLTraceable author statementⁱ
  • "CK2 phosphorylation of the PRH/Hex homeodomain functions as a reversible switch for DNA binding."
    Soufi A., Noy P., Buckle M., Sawasdichai A., Gaston K., Jayaraman P.S.
    Nucleic Acids Res 37:3288-3300(2009) [PubMed] [Europe PMC] [Abstract]
• transcription factor binding Source: BHF-UCLInferred from physical interactionⁱ
  • "Interaction between hex and GATA transcription factors in vascular endothelial cells inhibits flk-1/KDR-mediated vascular endothelial growth factor signaling."
    Minami T., Murakami T., Horiuchi K., Miura M., Noguchi T., Miyazaki J., Hamakubo T., Aird W.C., Kodama T.
    J Biol Chem 279:20626-20635(2004) [PubMed] [Europe PMC] [Abstract]

Protein-protein interaction databases

Miscellaneous databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structureⁱ

Secondary structure

3D structure databases

Miscellaneous databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsⁱ

Region

Compositional bias

Keywords - Domainⁱ

Phylogenomic databases

Family and domain databases

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequence (1+)ⁱ

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusⁱ: Complete.

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

        10         20         30         40         50
MQYPHPGPAA GAVGVPLYAP TPLLQPAHPT PFYIEDILGR GPAAPTPAPT 
        60         70         80         90        100
LPSPNSSFTS LVSPYRTPVY EPTPIHPAFS HHSAAALAAA YGPGGFGGPL 
       110        120        130        140        150
YPFPRTVNDY THALLRHDPL GKPLLWSPFL QRPLHKRKGG QVRFSNDQTI 
       160        170        180        190        200
ELEKKFETQK YLSPPERKRL AKMLQLSERQ VKTWFQNRRA KWRRLKQENP 
       210        220        230        240        250
QSNKKEELES LDSSCDQRQD LPSEQNKGAS LDSSQCSPSP ASQEDLESEI 
       260        270
SEDSDQEVDI EGDKSYFNAG                                  

Experimental Info

Sequence databases

Genome annotation databases

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsⁱ

• 100% Identity
• 90% Identity
• 50% Identity

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesⁱ

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Polymorphism and mutation databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Miscellaneous databases

Gene expression databases

Family and domain databases

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationⁱ

<p>This section contains any relevant information that doesn't fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousⁱ

Keywords - Technical termⁱ

Documents

1. MIM cross-references
   Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
2. PDB cross-references
   Index of Protein Data Bank (PDB) cross-references
3. Human chromosome 10
   Human chromosome 10: entries, gene names and cross-references to MIM