Protein HEXIM1 (HEXIM1)
The protein contains 359 amino acids for an estimated molecular weight of 40623 Da.
Transcriptional regulator which functions as a general RNA polymerase II transcription inhibitor (PubMed:14580347, PubMed:15713661, PubMed:15201869). Core component of the 7SK RNP complex: in cooperation with 7SK snRNA sequesters P-TEFb in a large inactive 7SK snRNP complex preventing RNA polymerase II phosphorylation and subsequent transcriptional elongation (PubMed:12832472, PubMed:14580347, PubMed:15713661, PubMed:15201869). May also regulate NF-kappa-B, ESR1, NR3C1 and CIITA-dependent transcriptional activity (PubMed:15940264, PubMed:15941832, PubMed:17088550). Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway (PubMed:28712728). (updated: June 17, 2020)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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Biological Process
Activation of innate immune response
Heart development
Innate immune response
Negative regulation of cyclin-dependent protein serine/threonine kinase activity
Negative regulation of transcription by RNA polymerase II
Negative regulation of transcription elongation from RNA polymerase II promoter
Negative regulation of transcription, DNA-templated
Negative regulation of viral transcription
Positive regulation of signal transduction by p53 class mediator
Transcription, DNA-templated
The reference OMIM entry for this protein is 607328
Hexamethylene bis acetamide-inducible protein 1; hexim1
Cardiac lineage protein 1; clp1
His1
Menage a quatre 1; maq1
DESCRIPTION
RNA polymerase II is a multisubunit polymerase that is regulated by phosphorylation of serines in the C-terminal domain (CTD) of the largest subunit (POLR2A; 180660). The CTD is phosphorylated by positive transcription factor b (P-TEFb), a complex containing CDK9 (603251) and either cyclin T1 (CCNT1; 143055) or T2 (CCNT2; 603862). HEXIM1 or HEXIM2 (615695), along with 7SK small nuclear RNA (RN7SK; 606515), interacts with P-TEFb in a reversible manner and inhibits CDK9 kinase activity, thereby inhibiting activation of RNA polymerase II (summary by Byers et al., 2005).CLONING
Huang et al. (2002) cloned mouse Clp1. The deduced 41-kD protein is 85.3% homologous to human HIS1. Northern and Western blot analyses revealed wide expression during postnatal development, with highest levels in heart, skeletal muscle, and brain. Immunofluorescence localization of endogenous Clp1 in rat vascular smooth muscle and rat primary cardiac cells indicated nuclear localization. By mass spectrometric analysis of tryptic peptides that copurified with inactive P-TEFb/7SK complexes from HeLa cell lysates, Michels et al. (2003) identified HEXIM1, which they designated MAQ1. The deduced 359-amino acid protein has a central bipartite nuclear localization sequence. Database analysis revealed a paralog, HEXIM2, in mammals, but only a single MAQ1 ortholog was found in frogs, fish, and possibly insects. No orthologs were detected in worm or yeast. Immunofluorescence analysis detected MAQ1 in HeLa cell nuclei. Byers et al. (2005) stated that human HEXIM1 has a calculated molecular mass of 41 kD. However, they found by SDS-PAGE that the HEXIM1 expressed in E. coli had an apparent molecular mass of 67 kD. By Northern blot analysis, Yik et al. (2005) found HEXIM1 transcripts of approximately 4.0 and 2.4 kb in all 10 human tissues examined, with a particularly high level of the short form in placenta. The 2 forms differed in alternate usage of poly(A) signals.GENE FUNCTION
By coimmunoprecipitation of HeLa cell lysates, Michels et al. (2003) found that MAQ1 associated with inactive P-TEFb/7SK complexes, but not with active P-TEFb complexes. 7SK RNA appeared to be required to maintain stable association between MAQ1 and P-TEFb. MAQ1 interacted directly with cyclins T1 and T2, but not with CDK9, in yeast 2-hybrid assays. Domain analysis revealed that the C-terminal region of MAQ1 interacted with the N terminus of cyclin T1 or T2. Byers et al. (2005) stated that the PYNT motif of HEXIM1 is required for high-affinity binding of HEXIM1 to the P-TEFb complex. Western blot analysis of fractions of human cell lines separated by gradient sedimentation revealed a portion of HEXIM1 that cosedimented with CDK9 and cyclin T1 and another portion in the free form. A similar pattern was found for HEXIM2. The 2 proteins had similar affinity for 7SK RNA and P-TEFb, and both inhibited the in vitro kinase activity of P-TEFb. P-TEFb phosphorylated threonine within the PYNT motif of HEXIM1 or HEXIM2, and the HEXIM proteins required this motif for inhibition of P-TEFb. Inhibition of transcription elongation increased the amount of free HEXIM proteins, in addition to causing dissociation of the P-TEFb complex from RNA polymerase II. Knockdown of HEXIM1 in HeLa cells via small interfering RNA caused upregulation of HEXIM2. Using epitope-tagged proteins expressed in HeLa cells, Yik et al. (2005) found that HEXIM1 and HEXIM2 formed stable homo- and heter ... More on the omim web site
June 29, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 607328 was added.
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed