HEXIM1

HEXIM1
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	2GD7, 3S9G
Identifiers
Aliases	HEXIM1 , CLP1, EDG1, HIS1, MAQ1, hexamethylene bis-acetamide inducible 1, hexamethylene bisacetamide inducible 1, HEXIM P-TEFb complex subunit 1
External IDs	OMIM: 607328 MGI: 2385923 HomoloGene: 31382 GeneCards: HEXIM1
Gene location (Human)
Chr.	Chromosome 17 (human)
End	45,152,099 bp
Gene location (Mouse)
Chr.	Chromosome 11 (mouse)
End	103,010,551 bp
RNA expression pattern
	Top expressed in
	middle temporal gyrus; ; germinal epithelium; ; kidney tubule; ; glomerulus; ; Brodmann area 23; ; placenta; ; metanephric glomerulus; ; amniotic fluid; ; parietal pleura; ; saphenous vein;
	Top expressed in
	median eminence; ; adrenal gland; ; lateral geniculate nucleus; ; ascending aorta; ; medial geniculate nucleus; ; ciliary body; ; subcutaneous adipose tissue; ; calvaria; ; Epithelium of stomach; ; trachea;
	More reference expression data
	; ;
	More reference expression data
Gene ontology
Molecular function	protein binding ; snRNA binding ; 7SK snRNA binding ; cyclin-dependent protein serine/threonine kinase inhibitor activity ;
Cellular component	nucleoplasm ; cytoplasm ; nucleus ;
Biological process	positive regulation of signal transduction by p53 class mediator ; heart development ; regulation of transcription, DNA-templated ; transcription, DNA-templated ; negative regulation of cyclin-dependent protein serine/threonine kinase activity ; negative regulation of transcription, DNA-templated ; negative regulation of transcription by RNA polymerase II ; activation of innate immune response ; immune system process ; innate immune response ;
	Sources:Amigo / QuickGO
Orthologs
	10614
	192231
	ENSG00000186834
	ENSMUSG00000048878
	O94992
	Q8R409
	NM_006460
	NM_138753
	NP_006451
	NP_620092
	Wikidata
View/Edit Human	View/Edit Mouse

Last updated October 14, 2022

Protein HEXIM1 is a protein that in humans is encoded by the HEXIM1 gene.^[5]^[6]^[7]

Interactions

HEXIM1 has been shown to interact with Cyclin T1 ^[6] and Cdk9 ^[8]

Related Research Articles

Cyclin-dependent kinase 4 also known as cell division protein kinase 4 is an enzyme that in humans is encoded by the CDK4 gene. CDK4 is a member of the cyclin-dependent kinase family.

The positive transcription elongation factor, P-TEFb, is a multiprotein complex that plays an essential role in the regulation of transcription by RNA polymerase II in eukaryotes. Immediately following initiation Pol II becomes trapped in promoter proximal paused positions on the majority of human genes. P-TEFb is a cyclin dependent kinase that can phosphorylate the DRB sensitivity inducing factor (DSIF) and negative elongation factor (NELF), as well as the carboxyl terminal domain of the large subunit of Pol II and this causes the transition into productive elongation leading to the synthesis of mRNAs. P-TEFb is regulated in part by a reversible association with the 7SK snRNP. Treatment of cells with the P-TEFb inhibitors DRB or flavopidirol leads to loss of mRNA production and ultimately cell death.

In molecular biology 7SK is an abundant small nuclear RNA found in metazoans. It plays a role in regulating transcription by controlling the positive transcription elongation factor P-TEFb. 7SK is found in a small nuclear ribonucleoprotein complex (snRNP) with a number of other proteins that regulate the stability and function of the complex.

Cyclin-dependent kinase 9 or CDK9 is a cyclin-dependent kinase associated with P-TEFb.

DNA-directed RNA polymerase II subunit RPB1, also known as RPB1, is an enzyme that in humans is encoded by the POLR2A gene.

Cyclin-T1 is a protein that in humans is encoded by the CCNT1 gene.

CDK-activating kinase assembly factor MAT1 is an enzyme that in humans is encoded by the MNAT1 gene.

Cyclin-A1 is a protein that in humans is encoded by the CCNA1 gene.

Transcription elongation factor SPT5 is a protein that in humans is encoded by the SUPT5H gene.

General transcription factor IIH subunit 4 is a protein that in humans is encoded by the GTF2H4 gene.

PITSLRE serine/threonine-protein kinase CDC2L1 is an enzyme that in humans is encoded by the CDC2L1 gene.

RNA polymerase II subunit A C-terminal domain phosphatase is an enzyme that in humans is encoded by the CTDP1 gene.

Transcription elongation factor SPT4 is a protein that in humans is encoded by the SUPT4H1 gene.

Cyclin-T2 is a protein that in humans is encoded by the CCNT2 gene.

General transcription factor IIH subunit 1 is a protein that in humans is encoded by the GTF2H1 gene.

CTD small phosphatase-like protein is an enzyme that in humans is encoded by the CTDSPL gene.

Cyclin-K is a protein that in humans is encoded by the CCNK gene.

Mediator of RNA polymerase II transcription subunit 26 is an enzyme that in humans is encoded by the MED26 gene. It forms part of the Mediator complex.

Protein HEXIM2 is a protein that in humans is encoded by the HEXIM2 gene.

In molecular biology, Tat is a protein that is encoded for by the tat gene in HIV-1. Tat is a regulatory protein that drastically enhances the efficiency of viral transcription. Tat stands for "Trans-Activator of Transcription". The protein consists of between 86 and 101 amino acids depending on the subtype. Tat vastly increases the level of transcription of the HIV dsDNA. Before Tat is present, a small number of RNA transcripts will be made, which allow the Tat protein to be produced. Tat then binds to cellular factors and mediates their phosphorylation, resulting in increased transcription of all HIV genes, providing a positive feedback cycle. This in turn allows HIV to have an explosive response once a threshold amount of Tat is produced, a useful tool for defeating the body's response.

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000186834 - Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000048878 - Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ Huang F, Wagner M, Siddiqui MA (Jul 2002). "Structure, expression, and functional characterization of the mouse CLP-1 gene". Gene. 292 (1–2): 245–59. doi:10.1016/S0378-1119(02)00596-6. PMID 12119119.
1 2 Michels AA, Nguyen VT, Fraldi A, Labas V, Edwards M, Bonnet F, Lania L, Bensaude O (Jun 2003). "MAQ1 and 7SK RNA Interact with CDK9/Cyclin T Complexes in a Transcription-Dependent Manner". Mol Cell Biol. 23 (14): 4859–69. doi:10.1128/MCB.23.14.4859-4869.2003. PMC 162212 . PMID 12832472.
↑ "Entrez Gene: HEXIM1 hexamethylene bis-acetamide inducible 1".
↑ Kobbi L, Demey-Thomas E, Braye F, Proux F, Kolesnikova O, Vinh J, Poterszman A, Bensaude O (October 2016). "An evolutionary conserved Hexim1 peptide binds to the Cdk9 catalytic site to inhibit P-TEFb". Proc Natl Acad Sci U S A. 113 (45): 12721–6. Bibcode:2016PNAS..11312721K. doi: 10.1073/pnas.1612331113 . PMC 5111705 . PMID 27791144.

Dias Neto E, Correa RG, Verjovski-Almeida S, Briones MR, Nagai MA, da Silva W, Zago MA, Bordin S, Costa FF, Goldman GH, Carvalho AF, Matsukuma A, Baia GS, Simpson DH, Brunstein A, de Oliveira PS, Bucher P, Jongeneel CV, O'Hare MJ, Soares F, Brentani RR, Reis LF, de Souza SJ, Simpson AJ (2000). "Shotgun sequencing of the human transcriptome with ORF expressed sequence tags". Proc. Natl. Acad. Sci. U.S.A. 97 (7): 3491–6. Bibcode:2000PNAS...97.3491D. doi: 10.1073/pnas.97.7.3491 . PMC 16267 . PMID 10737800.
Ouchida R, Kusuhara M, Shimizu N, Hisada T, Makino Y, Morimoto C, Handa H, Ohsuzu F, Tanaka H (2003). "Suppression of NF-kappaB-dependent gene expression by a hexamethylene bisacetamide-inducible protein HEXIM1 in human vascular smooth muscle cells". Genes Cells. 8 (2): 95–107. doi: 10.1046/j.1365-2443.2003.00618.x . PMID 12581153. S2CID 21478049.
Wittmann BM, Wang N, Montano MM (2003). "Identification of a novel inhibitor of breast cell growth that is down-regulated by estrogens and decreased in breast tumors". Cancer Res. 63 (16): 5151–8. PMID 12941847.
Yik JH, Chen R, Nishimura R, Jennings JL, Link AJ, Zhou Q (2003). "Inhibition of P-TEFb (CDK9/Cyclin T) kinase and RNA polymerase II transcription by the coordinated actions of HEXIM1 and 7SK snRNA". Mol. Cell. 12 (4): 971–82. doi: 10.1016/S1097-2765(03)00388-5 . PMID 14580347.
Paushkin SV, Patel M, Furia BS, Peltz SW, Trotta CR (2004). "Identification of a human endonuclease complex reveals a link between tRNA splicing and pre-mRNA 3' end formation". Cell. 117 (3): 311–21. doi: 10.1016/S0092-8674(04)00342-3 . PMID 15109492. S2CID 16049289.
Yik JH, Chen R, Pezda AC, Samford CS, Zhou Q (2004). "A Human Immunodeficiency Virus Type 1 Tat-Like Arginine-Rich RNA-Binding Domain Is Essential for HEXIM1 To Inhibit RNA Polymerase II Transcription through 7SK snRNA-Mediated Inactivation of P-TEFb". Mol. Cell. Biol. 24 (12): 5094–105. doi:10.1128/MCB.24.12.5094-5105.2004. PMC 419863 . PMID 15169877.
Michels AA, Fraldi A, Li Q, Adamson TE, Bonnet F, Nguyen VT, Sedore SC, Price JP, Price DH, Lania L, Bensaude O (2005). "Binding of the 7SK snRNA turns the HEXIM1 protein into a P-TEFb (CDK9/cyclin T) inhibitor". EMBO J. 23 (13): 2608–19. doi:10.1038/sj.emboj.7600275. PMC 449783 . PMID 15201869.
Yik JH, Chen R, Pezda AC, Zhou Q (2005). "Compensatory contributions of HEXIM1 and HEXIM2 in maintaining the balance of active and inactive positive transcription elongation factor b complexes for control of transcription". J. Biol. Chem. 280 (16): 16368–76. doi: 10.1074/jbc.M500912200 . PMID 15713661.
Byers SA, Price JP, Cooper JJ, Li Q, Price DH (2005). "HEXIM2, a HEXIM1-related protein, regulates positive transcription elongation factor b through association with 7SK". J. Biol. Chem. 280 (16): 16360–7. doi: 10.1074/jbc.M500424200 . PMID 15713662.
Schulte A, Czudnochowski N, Barboric M, Schönichen A, Blazek D, Peterlin BM, Geyer M (2005). "Identification of a cyclin T-binding domain in Hexim1 and biochemical analysis of its binding competition with HIV-1 Tat". J. Biol. Chem. 280 (26): 24968–77. doi: 10.1074/jbc.M501431200 . PMID 15855166.
Wittmann BM, Fujinaga K, Deng H, Ogba N, Montano MM (2005). "The breast cell growth inhibitor, estrogen down regulated gene 1, modulates a novel functional interaction between estrogen receptor alpha and transcriptional elongation factor cyclin T1". Oncogene. 24 (36): 5576–88. doi: 10.1038/sj.onc.1208728 . PMID 15940264.
Shimizu N, Ouchida R, Yoshikawa N, Hisada T, Watanabe H, Okamoto K, Kusuhara M, Handa H, Morimoto C, Tanaka H (2005). "HEXIM1 forms a transcriptionally abortive complex with glucocorticoid receptor without involving 7SK RNA and positive transcription elongation factor b". Proc. Natl. Acad. Sci. U.S.A. 102 (24): 8555–60. Bibcode:2005PNAS..102.8555S. doi: 10.1073/pnas.0409863102 . PMC 1150813 . PMID 15941832.
Li Q, Price JP, Byers SA, Cheng D, Peng J, Price DH (2005). "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". J. Biol. Chem. 280 (31): 28819–26. doi: 10.1074/jbc.M502712200 . PMID 15965233.
Fraldi A, Varrone F, Napolitano G, Michels AA, Majello B, Bensaude O, Lania L (2006). "Inhibition of Tat activity by the HEXIM1 protein". Retrovirology. 2: 42. doi:10.1186/1742-4690-2-42. PMC 1183248 . PMID 15992410.
Dulac C, Michels AA, Fraldi A, Bonnet F, Nguyen VT, Napolitano G, Lania L, Bensaude O (2005). "Transcription-dependent association of multiple positive transcription elongation factor units to a HEXIM multimer". J. Biol. Chem. 280 (34): 30619–29. doi: 10.1074/jbc.M502471200 . PMID 15994294.
Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514. S2CID 4427026.

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[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000186834 - Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000048878 - Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid12119119-5] Huang F, Wagner M, Siddiqui MA (Jul 2002). "Structure, expression, and functional characterization of the mouse CLP-1 gene". Gene. 292 (1–2): 245–59. doi:10.1016/S0378-1119(02)00596-6. PMID 12119119.

[pmid12832472-6] 1 2 Michels AA, Nguyen VT, Fraldi A, Labas V, Edwards M, Bonnet F, Lania L, Bensaude O (Jun 2003). "MAQ1 and 7SK RNA Interact with CDK9/Cyclin T Complexes in a Transcription-Dependent Manner". Mol Cell Biol. 23 (14): 4859–69. doi:10.1128/MCB.23.14.4859-4869.2003. PMC 162212 . PMID 12832472.

[entrez-7] "Entrez Gene: HEXIM1 hexamethylene bis-acetamide inducible 1".

[pmid27791144-8] Kobbi L, Demey-Thomas E, Braye F, Proux F, Kolesnikova O, Vinh J, Poterszman A, Bensaude O (October 2016). "An evolutionary conserved Hexim1 peptide binds to the Cdk9 catalytic site to inhibit P-TEFb". Proc Natl Acad Sci U S A. 113 (45): 12721–6. Bibcode:2016PNAS..11312721K. doi: 10.1073/pnas.1612331113 . PMC 5111705 . PMID 27791144.

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HEXIM1

Contents

Interactions

Related Research Articles

References

Further reading