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    HEXIM2 HEXIM P-TEFb complex subunit 2 [ Homo sapiens (human) ]

    Gene ID: 124790, updated on 5-Mar-2024

    Summary

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    Official Symbol
    HEXIM2provided by HGNC
    Official Full Name
    HEXIM P-TEFb complex subunit 2provided by HGNC
    Primary source
    HGNC:HGNC:28591
    See related
    Ensembl:ENSG00000168517 MIM:615695; AllianceGenome:HGNC:28591
    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
    L3
    Summary
    This gene encodes a member of the HEXIM family of proteins. This protein is a component of the 7SK small nuclear ribonucleoprotein. This protein has been found to negatively regulate the kinase activity of the cyclin-dependent kinase P-TEFb, which phosphorylates multiple target proteins to promote transcriptional elongation. This gene is located approximately 7 kb downstream from related family member HEXIM1 on chromosome 17. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]
    Expression
    Broad expression in testis (RPKM 8.0), kidney (RPKM 3.7) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    17q21.31
    Exon count:
    5
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 17 NC_000017.11 (45160174..45170040)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 17 NC_060941.1 (46014059..46023937)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 17 NC_000017.10 (43237541..43247407)

    Chromosome 17 - NC_000017.11Genomic Context describing neighboring genes Neighboring gene phospholipase C delta 3 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 H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:43220320-43221042 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:43221043-43221764 Neighboring gene acyl-CoA binding domain containing 4 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 HEXIM P-TEFb complex subunit 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 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 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8613 Neighboring gene Sharpr-MPRA regulatory region 174 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:43300291-43300791 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12283 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12284 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12285 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12286 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12287 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12288 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12289 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:43305824-43306459 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12291 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8615 Neighboring gene formin like 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:43318529-43319247 Neighboring gene FMNL1 antisense RNA 1

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. The transcription-dependent dissociation of P-TEFb-HEXIM1-7SK RNA relies upon formation of hnRNP-7SK RNA complexes. Barrandon C, et al. Mol Cell Biol, 2007 Oct. PMID 17709395, Free PMC Article
    2. Inhibition of Tat activity by the HEXIM1 protein. Fraldi A, et al. Retrovirology, 2005 Jul 2. PMID 15992410, Free PMC Article
    3. Analysis of the large inactive P-TEFb complex indicates that it contains one 7SK molecule, a dimer of HEXIM1 or HEXIM2, and two P-TEFb molecules containing Cdk9 phosphorylated at threonine 186. Li Q, et al. J Biol Chem, 2005 Aug 5. PMID 15965233
    4. [Misregulation of P-TEFb activity: pathological consequences]. Muniz L, et al. Med Sci (Paris), 2012 Feb. PMID 22377309
    5. Transcription-dependent association of multiple positive transcription elongation factor units to a HEXIM multimer. Dulac C, et al. J Biol Chem, 2005 Aug 26. PMID 15994294

    See all (48) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. The tripartite protein-RNA complex formation between Hexim, Cyclin T and 7SK snRNA, was analyzed.
      Title: Specificity of Hexim1 and Hexim2 complex formation with cyclin T1/T2, importin alpha and 7SK snRNA.
    2. utilization of HEXIM1 or HEXIM2 to bind and inhibit P-TEFb can be differentially regulated in vivo.
      Title: HEXIM2, a HEXIM1-related protein, regulates positive transcription elongation factor b through association with 7SK.
    3. HEXIM2 can functionally and quantitatively compensate for the loss of HEXIM1
      Title: Compensatory contributions of HEXIM1 and HEXIM2 in maintaining the balance of active and inactive positive transcription elongation factor b complexes for control of transcription.
    4. Positive transcription elongation factor b regulates eukaryotic gene expression at the level of elongation and is controlled by the reversible association with HEXIM2.
      Title: Analysis of the large inactive P-TEFb complex indicates that it contains one 7SK molecule, a dimer of HEXIM1 or HEXIM2, and two P-TEFb molecules containing Cdk9 phosphorylated at threonine 186.
    Submit: New GeneRIF Correction

    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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    Protein interactions

    Protein Gene Interaction Pubs
    Tat 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 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 the recruitment of CycT1 PubMed

    Go to the HIV-1, Human Interaction Database

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • FLJ32384, FLJ39466

    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 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 snRNA binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in negative regulation of DNA-templated transcription IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of cyclin-dependent protein serine/threonine kinase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in negative regulation of cyclin-dependent protein serine/threonine kinase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    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 IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytoplasm ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nuclear speck 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 ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  

    General protein information

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    Preferred Names
    protein HEXIM2
    Names
    MAQ1 paralog
    hexamethylene bis-acetamide inducible 2
    hexamethylene bis-acetamide-inducible protein 2
    hexamethylene bisacetamide inducible 2
    hexamethylene-bis-acetamide-inducible transcript 2

    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_001303436.1 → NP_001290365.1  protein HEXIM2 isoform 2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (10) uses an alternate splice site in the 5' terminal exon and initiates translation at an upstream start codon, compared to variant 1. This results in a protein (isoform 2) with a longer N-terminus compared to variant 1.
      Source sequence(s)
      AK056946, AW340131, BP398345, BU501076, CA312679
      UniProtKB/Swiss-Prot
      Q96MH2
      Conserved Domains (2) summary
      pfam15313
      Location:126 → 246
      HEXIM; Hexamethylene bis-acetamide-inducible protein
      pfam16559
      Location:236 → 291
      GIT_CC; GIT coiled-coil Rho guanine nucleotide exchange factor

    2. NM_001303437.1 → NP_001290366.1  protein HEXIM2 isoform 1

      See identical proteins and their annotated locations for NP_001290366.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) differs in the 5' UTR compared to variant 1. Variants 1-9 encode the same isoform (1).
      Source sequence(s)
      AK056946, AW340131, BP209696, BP398345, CA312679, DB160394, HY007091
      Consensus CDS
      CCDS11496.1
      UniProtKB/Swiss-Prot
      D3DX66, Q96MH2
      Conserved Domains (1) summary
      pfam15313
      Location:102 → 227
      HEXIM; Hexamethylene bis-acetamide-inducible protein

    3. NM_001303438.1 → NP_001290367.1  protein HEXIM2 isoform 1

      See identical proteins and their annotated locations for NP_001290367.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) differs in the 5' UTR compared to variant 1. Variants 1-9 encode the same isoform (1).
      Source sequence(s)
      AK056946, AW340131, BP209696, BP398345, CA312679, DB160394
      Consensus CDS
      CCDS11496.1
      UniProtKB/Swiss-Prot
      D3DX66, Q96MH2
      Related
      ENSP00000468773.2, ENST00000593138.6
      Conserved Domains (1) summary
      pfam15313
      Location:102 → 227
      HEXIM; Hexamethylene bis-acetamide-inducible protein

    4. NM_001303439.1 → NP_001290368.1  protein HEXIM2 isoform 1

      See identical proteins and their annotated locations for NP_001290368.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the shorter isoform (1). Variants 1-9 encode the same isoform (1).
      Source sequence(s)
      AK056946, AW340131, BI829228, BP398345, CA312679, DB160394
      Consensus CDS
      CCDS11496.1
      UniProtKB/Swiss-Prot
      D3DX66, Q96MH2
      Related
      ENSP00000465086.2, ENST00000586681.6
      Conserved Domains (1) summary
      pfam15313
      Location:102 → 227
      HEXIM; Hexamethylene bis-acetamide-inducible protein

    5. NM_001303440.2 → NP_001290369.1  protein HEXIM2 isoform 1

      See identical proteins and their annotated locations for NP_001290369.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (6) differs in the 5' UTR compared to variant 1. Variants 1-9 encode the same isoform (1).
      Source sequence(s)
      BC003531, BI829844
      Consensus CDS
      CCDS11496.1
      UniProtKB/Swiss-Prot
      D3DX66, Q96MH2
      Related
      ENSP00000467517.1, ENST00000592695.1
      Conserved Domains (1) summary
      pfam15313
      Location:102 → 227
      HEXIM; Hexamethylene bis-acetamide-inducible protein

    6. NM_001303441.2 → NP_001290370.1  protein HEXIM2 isoform 1

      See identical proteins and their annotated locations for NP_001290370.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (7) differs in the 5' UTR compared to variant 1. Variants 1-9 encode the same isoform (1).
      Source sequence(s)
      AA223138, AK056946, BI829844
      Consensus CDS
      CCDS11496.1
      UniProtKB/Swiss-Prot
      D3DX66, Q96MH2
      Related
      ENSP00000466200.2, ENST00000589230.6
      Conserved Domains (1) summary
      pfam15313
      Location:102 → 227
      HEXIM; Hexamethylene bis-acetamide-inducible protein

    7. NM_001303442.2 → NP_001290371.1  protein HEXIM2 isoform 1

      See identical proteins and their annotated locations for NP_001290371.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (8) differs in the 5' UTR compared to variant 1. Variants 1-9 encode the same isoform (1).
      Source sequence(s)
      BC025970, BI829844, CN425800
      Consensus CDS
      CCDS11496.1
      UniProtKB/Swiss-Prot
      D3DX66, Q96MH2
      Related
      ENSP00000465727.1, ENST00000591576.5
      Conserved Domains (1) summary
      pfam15313
      Location:102 → 227
      HEXIM; Hexamethylene bis-acetamide-inducible protein

    8. NM_001303443.2 → NP_001290372.1  protein HEXIM2 isoform 1

      See identical proteins and their annotated locations for NP_001290372.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (9) differs in the 5' UTR compared to variant 1. Variants 1-9 encode the same isoform (1).
      Source sequence(s)
      AK056946, BI829844, CN425800
      Consensus CDS
      CCDS11496.1
      UniProtKB/Swiss-Prot
      D3DX66, Q96MH2
      Related
      ENSP00000464807.2, ENST00000591070.6
      Conserved Domains (1) summary
      pfam15313
      Location:102 → 227
      HEXIM; Hexamethylene bis-acetamide-inducible protein

    9. NM_001303444.2 → NP_001290373.1  protein HEXIM2 isoform 1

      See identical proteins and their annotated locations for NP_001290373.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) differs in the 5' UTR compared to variant 1. Variants 1-9 encode the same isoform (1).
      Source sequence(s)
      AK056946, BG696988, BI829844, CN425800
      Consensus CDS
      CCDS11496.1
      UniProtKB/Swiss-Prot
      D3DX66, Q96MH2
      Conserved Domains (1) summary
      pfam15313
      Location:102 → 227
      HEXIM; Hexamethylene bis-acetamide-inducible protein

    10. NM_144608.2 → NP_653209.1  protein HEXIM2 isoform 1

      See identical proteins and their annotated locations for NP_653209.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Variants 1-9 encode the same isoform (1).
      Source sequence(s)
      AK056946, AW340131, BP398345, BU501076, CA312679
      Consensus CDS
      CCDS11496.1
      UniProtKB/Swiss-Prot
      D3DX66, Q96MH2
      Related
      ENSP00000302276.2, ENST00000307275.7
      Conserved Domains (1) summary
      pfam15313
      Location:102 → 227
      HEXIM; Hexamethylene bis-acetamide-inducible protein

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

    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
      45160174..45170040
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011524308.4 → XP_011522610.4  protein HEXIM2 isoform X1

    2. XM_011524307.4 → XP_011522609.4  protein HEXIM2 isoform X2

    3. XM_047435323.1 → XP_047291279.1  protein HEXIM2 isoform X4

      UniProtKB/Swiss-Prot
      D3DX66, Q96MH2

    4. XM_047435324.1 → XP_047291280.1  protein HEXIM2 isoform X4

      UniProtKB/Swiss-Prot
      D3DX66, Q96MH2

    5. XM_006721687.5 → XP_006721750.1  protein HEXIM2 isoform X3

      Conserved Domains (2) summary
      pfam15313
      Location:127 → 247
      HEXIM; Hexamethylene bis-acetamide-inducible protein
      pfam16559
      Location:237 → 292
      GIT_CC; GIT coiled-coil Rho guanine nucleotide exchange factor

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060941.1 Alternate T2T-CHM13v2.0

      Range
      46014059..46023937
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054315017.1 → XP_054170992.1  protein HEXIM2 isoform X1

    2. XM_054315018.1 → XP_054170993.1  protein HEXIM2 isoform X2

    3. XM_054315020.1 → XP_054170995.1  protein HEXIM2 isoform X4

      UniProtKB/Swiss-Prot
      D3DX66, Q96MH2

    4. XM_054315021.1 → XP_054170996.1  protein HEXIM2 isoform X4

      UniProtKB/Swiss-Prot
      D3DX66, Q96MH2

    5. XM_054315019.1 → XP_054170994.1  protein HEXIM2 isoform X3

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q96MH2.1 GenPept UniProtKB/Swiss-Prot:Q96MH2

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