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    HEXIM1 HEXIM P-TEFb complex subunit 1 [ Homo sapiens (human) ]

    Gene ID: 10614, updated on 2-Nov-2024

    Summary

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    Official Symbol
    HEXIM1provided by HGNC
    Official Full Name
    HEXIM P-TEFb complex subunit 1provided by HGNC
    Primary source
    HGNC:HGNC:24953
    See related
    Ensembl:ENSG00000186834 MIM:607328; AllianceGenome:HGNC:24953
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    CLP1; EDG1; HIS1; MAQ1
    Summary
    Expression of this gene is induced by hexamethylene-bis-acetamide in vascular smooth muscle cells. This gene has no introns. [provided by RefSeq, Jul 2008]
    Orthologs
    mouse all
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    Genomic context

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    See HEXIM1 in Genome Data Viewer
    Location:
    17q21.31
    Exon count:
    1
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 17 NC_000017.11 (45148475..45152099)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 17 NC_060941.1 (46002353..46005981)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 17 NC_000017.10 (43225842..43229466)

    Chromosome 17 - NC_000017.11Genomic Context describing neighboring genes Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:43191895-43192759 Neighboring gene phospholipase C delta 3 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:43198136-43198673 Neighboring gene microRNA 6784 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8609 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8610 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12274 Neighboring gene acyl-CoA binding domain containing 4 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:43220320-43221042 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:43221043-43221764 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:43222487-43223207 Neighboring gene H3K27ac hESC enhancer GRCh37_chr17:43224945-43225827 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12275 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12276 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12277 Neighboring gene H3K27ac hESC enhancer GRCh37_chr17:43226945-43227500 Neighboring gene HEXIM2 antisense RNA 1 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:43237877-43238492 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:43238493-43239108 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:43239109-43239724 Neighboring gene uncharacterized LOC105371795 Neighboring gene HEXIM P-TEFb complex subunit 2 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:43247744-43248702 Neighboring gene Sharpr-MPRA regulatory region 8248 Neighboring gene Sharpr-MPRA regulatory region 499 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:43249661-43250619 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:43250620-43251577 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12282 Neighboring gene FMNL1 divergent transcript Neighboring gene ReSE screen-validated silencer GRCh37_chr17:43279930-43280114 Neighboring gene ReSE screen-validated silencer GRCh37_chr17:43281002-43281263 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8612

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Bibliography

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    Related articles in PubMed

    1. HMBA releases P-TEFb from HEXIM1 and 7SK snRNA via PI3K/Akt and activates HIV transcription. Contreras X, et al. PLoS Pathog, 2007 Oct 12. PMID 17937499, Free PMC Article
    2. HEXIM1 controls P-TEFb processing and regulates drug sensitivity in triple-negative breast cancer. Shao H, et al. Mol Biol Cell, 2020 Aug 1. PMID 32520633, Free PMC Article
    3. Increased HEXIM1 expression during erythroleukemia and neuroblastoma cell differentiation. Turano M, et al. J Cell Physiol, 2006 Mar. PMID 16222702
    4. Structural transitions in the RNA 7SK 5' hairpin and their effect on HEXIM binding. Röder K, et al. Nucleic Acids Res, 2020 Jan 10. PMID 31732748, Free PMC Article
    5. Hexim1, an RNA-controlled protein hub. Michels AA, et al. Transcription, 2018. PMID 29345523, Free PMC Article

    See all (157) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Rapid P-TEFb-dependent transcriptional reorganization underpins the glioma adaptive response to radiotherapy.
      Title: Rapid P-TEFb-dependent transcriptional reorganization underpins the glioma adaptive response to radiotherapy.
    2. HEXIM1 is an essential transcription regulator during human erythropoiesis.
      Title: HEXIM1 is an essential transcription regulator during human erythropoiesis.
    3. UHRF1 Suppresses HIV-1 Transcription and Promotes HIV-1 Latency by Competing with p-TEFb for Ubiquitination-Proteasomal Degradation of Tat.
      Title: UHRF1 Suppresses HIV-1 Transcription and Promotes HIV-1 Latency by Competing with p-TEFb for Ubiquitination-Proteasomal Degradation of Tat.
    4. Downregulation of Dihydrotestosterone and Estradiol Levels by HEXIM1.
      Title: Downregulation of Dihydrotestosterone and Estradiol Levels by HEXIM1.
    5. HEXIM1 controls P-TEFb processing and regulates drug sensitivity in triple-negative breast cancer.
      Title: HEXIM1 controls P-TEFb processing and regulates drug sensitivity in triple-negative breast cancer.
    6. Phosphorylation of the histone demethylase KDM5B and regulation of the phenotype of triple negative breast cancer.
      Title: Phosphorylation of the histone demethylase KDM5B and regulation of the phenotype of triple negative breast cancer.
    7. HEXIM1 Diffusion in the Nucleus Is Regulated by Its Interactions with Both 7SK and P-TEFb.
      Title: HEXIM1 Diffusion in the Nucleus Is Regulated by Its Interactions with Both 7SK and P-TEFb.
    8. HMBA and 4a1 induce HEXIM1 expression by inhibiting KDM5B. Upregulation of HEXIM1 expression levels plays a critical role in the inhibition of proliferation of breast cancer cells using KDM5B inhibitors.
      Title: Inhibition of the histone demethylase, KDM5B, directly induces re-expression of tumor suppressor protein HEXIM1 in cancer cells.
    9. Structural transitions in the RNA 7SK 5' hairpin and their effect on HEXIM binding have been reported.
      Title: Structural transitions in the RNA 7SK 5' hairpin and their effect on HEXIM binding.
    10. Both HEXIM1 and RAD51 promote BET inhibitor-induced fork slowing but also prevent a DNA damage response.
      Title: BET Inhibition Induces HEXIM1- and RAD51-Dependent Conflicts between Transcription and Replication.
    Submit: New GeneRIF Correction See all GeneRIFs (57)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    EBI GWAS Catalog

    Description
    Genome-wide association study identifies eight loci associated with blood pressure.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    HIV-1 interactions

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    Replication interactions

    Interaction Pubs
    HIV-1 infection increases HEXIM1 expression in monocyte derived macrophages PubMed

    Protein interactions

    Protein Gene Interaction Pubs
    Tat tat CDK9-CycT1-AFF1 is stimulated by HIV-1 Tat and transferred as a single complex unit to BRD4 upon stress-induced disruption of AFF1-containing 7SK snRNP (HEXIM1, MEPCE, LARP7, 7SK RNA, CDK9, CycT1, and AFF1) PubMed
    tat AFF1 enhances the affinity of HIV-1 Tat for CycT1, which competitively dissociates HEXIM1 and is responsible for AFF1's promotion of Tat's extraction of CDK9/CycT1 from 7SK snRNP PubMed
    tat HIV-1 Tat displaces HEXIM1 from Cyclin T1 in the context of the native 7SK snRNP by interacting with the Cyclin T1-binding domain (amino acid 255-359) of HEXIM1 PubMed
    tat CDK11 depletion reduces protein expression of CDK9 and HEXIM1 and Tat transactivation of HIV-1 provirus PubMed
    tat A La-related protein, LARP7, is associated with P-TEFb, HEXIM1/2, MEPCE, and 7SK RNA in a large stable complex form. Knockdown of LARP7 decreases the steady-state level of 7SK, but increases free P-TEFb and enhances Tat-mediated transcription PubMed
    tat HIV-1 Tat-mediated release of P-TEFb from the 7SK sn RNP results in a conformational change in 7SK RNA and release of HEXIM1 from the complex PubMed
    tat TAR binds Tat and P-TEFb as it emerges on the nascent transcript, competitively displacing the inhibitory 7SK snRNP (HEXIM1 and LARP7) and activating the P-TEFb kinase PubMed
    tat HIV-1 Tat competes with HEXIM1 for binding to 7SK RNA and inhibits the formation of the P-TEFb-HEXIM1-7SK complex. Tat binds to nucleotides 10-48 of 7SK RNA PubMed
    tat HIV-1 Tat directly interacts with human 7SK snRNA in living cells. The 5' hairpin of human 7SK snRNA carries a conserved Tat-binding element and two HEXIM1-binding sites. Tat competes with HEXIM1 for 7SK snRNA binding PubMed
    tat HIV-1 Tat transactivation is effectively inhibited by co-expression of HEXIM1 or its paralog HEXIM2; HEXIM1 expression specifically represses transcription mediated by the direct activation of P-TEFb through Tat recruitment of CycT1 PubMed
    tat MAQ1 complexes with 7SK RNA and cyclin T1 and competes with the binding of Tat to cyclin T1, suggesting the TAR RNA/Tat lentivirus system has evolved to subvert the cellular 7SK RNA/MAQ1 system PubMed
    tat HIV-1 Tat competes with Hexim1 (residues 255-359) for cyclin T1 binding, thus releasing P-TEFb from the inactive complex to stimulate the transcription of HIV-1 gene expression PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • FLJ13562

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables 7SK snRNA binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables 7SK snRNA binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables P-TEFb complex binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables cyclin-dependent protein serine/threonine kinase inhibitor activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables cyclin-dependent protein serine/threonine kinase inhibitor activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables identical protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein kinase inhibitor activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables snRNA binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables transcription regulator inhibitor activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in activation of innate immune response IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in heart development IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in innate immune response IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of transcription by RNA polymerase II IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in negative regulation of transcription by RNA polymerase II IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in negative regulation of transcription elongation by RNA polymerase II IC
    Inferred by Curator
    more info
    		 PubMed 
    involved_in negative regulation of transcription elongation by RNA polymerase II IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of viral transcription IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive regulation of signal transduction by p53 class mediator IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Component Evidence Code Pubs
    part_of 7SK snRNP IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in intracellular membrane-bounded organelle IDA
    Inferred from Direct Assay
    more info
    		  
    is_active_in nucleoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    protein HEXIM1
    Names
    HMBA-inducible
    cardiac lineage protein 1
    estrogen down-regulated gene 1 protein
    hexamethylene bis-acetamide inducible 1
    hexamethylene bis-acetamide-inducible protein 1
    hexamethylene bisacetamide inducible 1
    hexamethylene bisacetamide-inducible protein
    hexamethylene-bis-acetamide-inducible transcript 1
    hexamthylene bis-acetamide inducible 1
    menage a quatre 1
    menage a quatre protein 1

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_006460.3 → NP_006451.1  protein HEXIM1

      See identical proteins and their annotated locations for NP_006451.1

      Status: REVIEWED

      Source sequence(s)
      AC142472
      Consensus CDS
      CCDS11495.1
      UniProtKB/Swiss-Prot
      B2R8Y5, O94992
      UniProtKB/TrEMBL
      B3KN49
      Related
      ENSP00000328773.3, ENST00000332499.4
      Conserved Domains (2) summary
      TIGR04211
      Location:283 → 351
      SH3_and_anchor; SH3 domain protein
      pfam15313
      Location:200 → 298
      HEXIM; Hexamethylene bis-acetamide-inducible protein

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000017.11 Reference GRCh38.p14 Primary Assembly

      Range
      45148475..45152099
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060941.1 Alternate T2T-CHM13v2.0

      Range
      46002353..46005981
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O94992.1 GenPept UniProtKB/Swiss-Prot:O94992

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

    Chemical Information
    Molecular Biology Databases
    Research Materials
    Tools