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

Gene ID: 124790, updated on 2-Nov-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
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Genomic context

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See HEXIM2 in Genome Data Viewer
Location:
17q21.31
Exon count:
5
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 17 NC_000017.11 (45160174..45170040)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 17 NC_060941.1 (46014059..46023937)
RS_2024_09 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 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. Rapid P-TEFb-dependent transcriptional reorganization underpins the glioma adaptive response to radiotherapy. Walker FM, et al. Nat Commun, 2024 May 30. PMID 38816355, Free PMC Article
  2. 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
  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. Inhibition of Tat activity by the HEXIM1 protein. Fraldi A, et al. Retrovirology, 2005 Jul 2. PMID 15992410, Free PMC Article
  5. [Misregulation of P-TEFb activity: pathological consequences]. Muniz L, et al. Med Sci (Paris), 2012 Feb. PMID 22377309

See all (49) 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. 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.
  3. 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.
  4. 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.
  5. 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 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_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
    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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