HEXI1_HUMAN
ID HEXI1_HUMAN Reviewed; 359 AA.
AC O94992; B2R8Y5;
DT 02-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=Protein HEXIM1;
DE AltName: Full=Cardiac lineage protein 1;
DE AltName: Full=Estrogen down-regulated gene 1 protein;
DE AltName: Full=Hexamethylene bis-acetamide-inducible protein 1;
DE AltName: Full=Menage a quatre protein 1;
GN Name=HEXIM1; Synonyms=CLP1, EDG1, HIS1, MAQ1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Vascular smooth muscle;
RA Kusuhara M., Nagasaki K., Kimura K., Maass N., Manabe T., Ishikawa S.,
RA Aikawa M., Miyazaki K., Yamaguchi K.;
RT "Cloning of hexamethylene-bis-acetamide-inducible transcript, HEXIM1, in
RT human vascular smooth muscle cells.";
RL Biomed. Res. 20:273-279(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Pericardium;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INDUCTION BY ESTROGEN.
RX PubMed=12941847;
RA Wittmann B.M., Wang N., Montano M.M.;
RT "Identification of a novel inhibitor of breast cell growth that is down-
RT regulated by estrogens and decreased in breast tumors.";
RL Cancer Res. 63:5151-5158(2003).
RN [5]
RP FUNCTION, INTERACTION WITH RELA, SUBCELLULAR LOCATION, AND INDUCTION BY
RP HMBA.
RX PubMed=12581153; DOI=10.1046/j.1365-2443.2003.00618.x;
RA Ouchida R., Kusuhara M., Shimizu N., Hisada T., Makino Y., Morimoto C.,
RA Handa H., Ohsuzu F., Tanaka H.;
RT "Suppression of NF-kappaB-dependent gene expression by a hexamethylene
RT bisacetamide-inducible protein HEXIM1 in human vascular smooth muscle
RT cells.";
RL Genes Cells 8:95-107(2003).
RN [6]
RP FUNCTION.
RX PubMed=14580347; DOI=10.1016/s1097-2765(03)00388-5;
RA Yik J.H.N., Chen R., Nishimura R., Jennings J.L., Link A.J., Zhou Q.;
RT "Inhibition of P-TEFb (CDK9/Cyclin T) kinase and RNA polymerase II
RT transcription by the coordinated actions of HEXIM1 and 7SK snRNA.";
RL Mol. Cell 12:971-982(2003).
RN [7]
RP FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE 7SK
RP RNP COMPLEX, INTERACTION WITH CCNT1, AND SUBCELLULAR LOCATION.
RX PubMed=12832472; DOI=10.1128/mcb.23.14.4859-4869.2003;
RA Michels A.A., Nguyen V.T., Fraldi A., Labas V., Edwards M., Bonnet F.,
RA Lania L., Bensaude O.;
RT "MAQ1 and 7SK RNA interact with CDK9/cyclin T complexes in a transcription-
RT dependent manner.";
RL Mol. Cell. Biol. 23:4859-4869(2003).
RN [8]
RP FUNCTION, MUTAGENESIS OF 152-LYS--ARG-155; TYR-203 AND THR-205, AND
RP INTERACTION WITH P-TEFB.
RX PubMed=15201869; DOI=10.1038/sj.emboj.7600275;
RA Michels A.A., Fraldi A., Li Q., Adamson T.E., Bonnet F., Nguyen V.T.,
RA Sedore S.C., Price J.P., Price D.H., Lania L., Bensaude O.;
RT "Binding of the 7SK snRNA turns the HEXIM1 protein into a P-TEFb
RT (CDK9/cyclin T) inhibitor.";
RL EMBO J. 23:2608-2619(2004).
RN [9]
RP INTERACTION WITH P-TEFB.
RX PubMed=15169877; DOI=10.1128/mcb.24.12.5094-5105.2004;
RA Yik J.H.N., Chen R., Pezda A.C., Samford C.S., Zhou Q.;
RT "A human immunodeficiency virus type 1 Tat-like arginine-rich RNA-binding
RT domain is essential for HEXIM1 to inhibit RNA polymerase II transcription
RT through 7SK snRNA-mediated inactivation of P-TEFb.";
RL Mol. Cell. Biol. 24:5094-5105(2004).
RN [10]
RP SUBCELLULAR LOCATION, INTERACTION WITH THE 7SK SNRNA AND P-TEFB, AND
RP MUTAGENESIS OF 154-ARG--ARG-156.
RX PubMed=16362050; DOI=10.1038/sj.emboj.7600883;
RA Barboric M., Kohoutek J., Price J.P., Blazek D., Price D.H., Peterlin B.M.;
RT "Interplay between 7SK snRNA and oppositely charged regions in HEXIM1
RT direct the inhibition of P-TEFb.";
RL EMBO J. 24:4291-4303(2005).
RN [11]
RP FUNCTION, INTERACTION WITH HEXIM2, OLIGOMERIZATION, TISSUE SPECIFICITY, AND
RP INDUCTION.
RX PubMed=15713661; DOI=10.1074/jbc.m500912200;
RA Yik J.H.N., Chen R., Pezda A.C., Zhou Q.;
RT "Compensatory contributions of HEXIM1 and HEXIM2 in maintaining the balance
RT of active and inactive positive transcription elongation factor b complexes
RT for control of transcription.";
RL J. Biol. Chem. 280:16368-16376(2005).
RN [12]
RP INTERACTION WITH CCNT1.
RX PubMed=15855166; DOI=10.1074/jbc.m501431200;
RA Schulte A., Czudnochowski N., Barboric M., Schoenichen A., Blazek D.,
RA Peterlin B.M., Geyer M.;
RT "Identification of a cyclin T-binding domain in Hexim1 and biochemical
RT analysis of its binding competition with HIV-1 Tat.";
RL J. Biol. Chem. 280:24968-24977(2005).
RN [13]
RP OLIGOMERIZATION, AND MUTAGENESIS OF PHE-208 AND TYR-271.
RX PubMed=15965233; DOI=10.1074/jbc.m502712200;
RA Li Q., Price J.P., Byers S.A., Cheng D., Peng J., Price D.H.;
RT "Analysis of the large inactive P-TEFb complex indicates that it contains
RT one 7SK molecule, a dimer of HEXIM1 or HEXIM2, and two P-TEFb molecules
RT containing Cdk9 phosphorylated at threonine 186.";
RL J. Biol. Chem. 280:28819-28826(2005).
RN [14]
RP INTERACTION WITH P-TEFB, OLIGOMERIZATION, AND MUTAGENESIS OF LEU-287;
RP LEU-294; LEU-332 AND LEU-339.
RX PubMed=16377779; DOI=10.1093/nar/gki997;
RA Blazek D., Barboric M., Kohoutek J., Oven I., Peterlin B.M.;
RT "Oligomerization of HEXIM1 via 7SK snRNA and coiled-coil region directs the
RT inhibition of P-TEFb.";
RL Nucleic Acids Res. 33:7000-7010(2005).
RN [15]
RP FUNCTION IN ESR1-DEPENDENT TRANSCRIPTION, AND INTERACTION WITH ESR1.
RX PubMed=15940264; DOI=10.1038/sj.onc.1208728;
RA Wittmann B.M., Fujinaga K., Deng H., Ogba N., Montano M.M.;
RT "The breast cell growth inhibitor, estrogen down regulated gene 1,
RT modulates a novel functional interaction between estrogen receptor alpha
RT and transcriptional elongation factor cyclin T1.";
RL Oncogene 24:5576-5588(2005).
RN [16]
RP FUNCTION IN NR3C1-DEPENDENT TRANSCRIPTION, AND INTERACTION WITH NR3C1.
RX PubMed=15941832; DOI=10.1073/pnas.0409863102;
RA Shimizu N., Ouchida R., Yoshikawa N., Hisada T., Watanabe H., Okamoto K.,
RA Kusuhara M., Handa H., Morimoto C., Tanaka H.;
RT "HEXIM1 forms a transcriptionally abortive complex with glucocorticoid
RT receptor without involving 7SK RNA and positive transcription elongation
RT factor b.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:8555-8560(2005).
RN [17]
RP FUNCTION IN CIITA-DEPENDENT TRANSCRIPTION.
RX PubMed=17088550; DOI=10.1073/pnas.0603079103;
RA Kohoutek J., Blazek D., Peterlin B.M.;
RT "Hexim1 sequesters positive transcription elongation factor b from the
RT class II transactivator on MHC class II promoters.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:17349-17354(2006).
RN [18]
RP IDENTIFICATION IN THE 7SK RNP COMPLEX.
RX PubMed=17643375; DOI=10.1016/j.molcel.2007.06.027;
RA Jeronimo C., Forget D., Bouchard A., Li Q., Chua G., Poitras C.,
RA Therien C., Bergeron D., Bourassa S., Greenblatt J., Chabot B.,
RA Poirier G.G., Hughes T.R., Blanchette M., Price D.H., Coulombe B.;
RT "Systematic analysis of the protein interaction network for the human
RT transcription machinery reveals the identity of the 7SK capping enzyme.";
RL Mol. Cell 27:262-274(2007).
RN [19]
RP INTERACTION WITH NCOR1.
RX PubMed=17452463; DOI=10.1128/mcb.00857-06;
RA Fu J., Yoon H.-G., Qin J., Wong J.;
RT "Regulation of P-TEFb elongation complex activity by CDK9 acetylation.";
RL Mol. Cell. Biol. 27:4641-4651(2007).
RN [20]
RP SUBCELLULAR LOCATION.
RX PubMed=17395637; DOI=10.1093/nar/gkm150;
RA Li Q., Cooper J.J., Altwerger G.H., Feldkamp M.D., Shea M.A., Price D.H.;
RT "HEXIM1 is a promiscuous double-stranded RNA-binding protein and interacts
RT with RNAs in addition to 7SK in cultured cells.";
RL Nucleic Acids Res. 35:2503-2512(2007).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-97; SER-98; SER-233; THR-236;
RP SER-237 AND SER-252, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-233; THR-236; SER-237 AND
RP SER-252, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [23]
RP INTERACTION WITH CCNT2.
RX PubMed=19883659; DOI=10.1016/j.jmb.2009.10.055;
RA Czudnochowski N., Vollmuth F., Baumann S., Vogel-Bachmayr K., Geyer M.;
RT "Specificity of Hexim1 and Hexim2 complex formation with cyclin T1/T2,
RT importin alpha and 7SK snRNA.";
RL J. Mol. Biol. 395:28-41(2010).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-233; THR-236; SER-237 AND
RP SER-252, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [25]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [26]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-252, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [27]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [28]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH PRKDC; XRCC5; XRCC6;
RP SFPQ; NONO; PSPC1; RBM14 AND MATR3.
RX PubMed=28712728; DOI=10.1016/j.molcel.2017.06.020;
RA Morchikh M., Cribier A., Raffel R., Amraoui S., Cau J., Severac D.,
RA Dubois E., Schwartz O., Bennasser Y., Benkirane M.;
RT "HEXIM1 and NEAT1 Long non-coding RNA form a multi-subunit complex that
RT regulates DNA-mediated innate immune response.";
RL Mol. Cell 67:387-399(2017).
RN [29]
RP STRUCTURE BY NMR OF 255-359, SUBUNIT, AND INTERACTION WITH CCNT1.
RX PubMed=17724342; DOI=10.1073/pnas.0701848104;
RA Dames S.A., Schoenichen A., Schulte A., Barboric M., Peterlin B.M.,
RA Grzesiek S., Geyer M.;
RT "Structure of the Cyclin T binding domain of Hexim1 and molecular basis for
RT its recognition of P-TEFb.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:14312-14317(2007).
CC -!- FUNCTION: Transcriptional regulator which functions as a general RNA
CC polymerase II transcription inhibitor (PubMed:14580347,
CC PubMed:15713661, PubMed:15201869). Core component of the 7SK RNP
CC complex: in cooperation with 7SK snRNA sequesters P-TEFb in a large
CC inactive 7SK snRNP complex preventing RNA polymerase II phosphorylation
CC and subsequent transcriptional elongation (PubMed:12832472,
CC PubMed:14580347, PubMed:15713661, PubMed:15201869). May also regulate
CC NF-kappa-B, ESR1, NR3C1 and CIITA-dependent transcriptional activity
CC (PubMed:15940264, PubMed:15941832, PubMed:17088550). Plays a role in
CC the regulation of DNA virus-mediated innate immune response by
CC assembling into the HDP-RNP complex, a complex that serves as a
CC platform for IRF3 phosphorylation and subsequent innate immune response
CC activation through the cGAS-STING pathway (PubMed:28712728).
CC {ECO:0000269|PubMed:12581153, ECO:0000269|PubMed:12832472,
CC ECO:0000269|PubMed:14580347, ECO:0000269|PubMed:15201869,
CC ECO:0000269|PubMed:15713661, ECO:0000269|PubMed:15940264,
CC ECO:0000269|PubMed:15941832, ECO:0000269|PubMed:17088550,
CC ECO:0000269|PubMed:28712728}.
CC -!- SUBUNIT: Homooligomer and heterooligomer with HEXIM2; probably dimeric
CC (PubMed:15713661, PubMed:15965233, PubMed:16377779). Core component of
CC the 7SK RNP complex, at least composed of 7SK RNA, LARP7, MEPCE, HEXIM1
CC (or HEXIM2) and P-TEFb (composed of CDK9 and CCNT1/cyclin-T1)
CC (PubMed:12832472, PubMed:15201869, PubMed:15169877, PubMed:16362050,
CC PubMed:15713661, PubMed:15855166, PubMed:16377779, PubMed:17643375,
CC PubMed:17724342). Interacts with the N-CoR complex through NCOR1
CC (PubMed:17452463). Interacts with ESR1 and NR3C1 (PubMed:15940264,
CC PubMed:15941832). May interact with NF-kappa-B through RELA
CC (PubMed:12581153). Interacts with CCNT2; mediates formation of a
CC tripartite complex with KPNA2 (PubMed:19883659). Part of the HDP-RNP
CC complex composed of at least HEXIM1, PRKDC, XRCC5, XRCC6, paraspeckle
CC proteins (SFPQ, NONO, PSPC1, RBM14, and MATR3) and NEAT1 non-coding RNA
CC (PubMed:28712728). {ECO:0000269|PubMed:12581153,
CC ECO:0000269|PubMed:12832472, ECO:0000269|PubMed:15169877,
CC ECO:0000269|PubMed:15201869, ECO:0000269|PubMed:15713661,
CC ECO:0000269|PubMed:15855166, ECO:0000269|PubMed:15940264,
CC ECO:0000269|PubMed:15941832, ECO:0000269|PubMed:15965233,
CC ECO:0000269|PubMed:16362050, ECO:0000269|PubMed:16377779,
CC ECO:0000269|PubMed:17452463, ECO:0000269|PubMed:17643375,
CC ECO:0000269|PubMed:17724342, ECO:0000269|PubMed:19883659,
CC ECO:0000269|PubMed:28712728}.
CC -!- INTERACTION:
CC O94992; O60563: CCNT1; NbExp=10; IntAct=EBI-2832510, EBI-2479671;
CC O94992; P50750: CDK9; NbExp=12; IntAct=EBI-2832510, EBI-1383449;
CC O94992; O94992: HEXIM1; NbExp=2; IntAct=EBI-2832510, EBI-2832510;
CC O94992; Q96MH2: HEXIM2; NbExp=4; IntAct=EBI-2832510, EBI-5460660;
CC O94992; Q4G0J3: LARP7; NbExp=10; IntAct=EBI-2832510, EBI-2371923;
CC O94992; Q15554: TERF2; NbExp=2; IntAct=EBI-2832510, EBI-706637;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:12581153,
CC ECO:0000269|PubMed:12832472, ECO:0000269|PubMed:12941847,
CC ECO:0000269|PubMed:16362050, ECO:0000269|PubMed:17395637}. Cytoplasm
CC {ECO:0000269|PubMed:12581153, ECO:0000269|PubMed:17395637}. Note=Binds
CC alpha-importin and is mostly nuclear (PubMed:16362050).
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed with higher expression in
CC placenta. HEXIM1 and HEXIM2 are differentially expressed. Expressed in
CC endocrine tissues. {ECO:0000269|PubMed:12941847,
CC ECO:0000269|PubMed:15713661}.
CC -!- INDUCTION: Up-regulated by HMBA (hexamethylene bisacetamide) (at
CC protein level). Down-regulated by estrogen.
CC {ECO:0000269|PubMed:12581153, ECO:0000269|PubMed:12941847,
CC ECO:0000269|PubMed:15713661}.
CC -!- DOMAIN: The coiled-coil domain mediates oligomerization.
CC -!- MISCELLANEOUS: Inhibits Tat activity which is required for HIV-1
CC transcription.
CC -!- SIMILARITY: Belongs to the HEXIM family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AB021179; BAA36166.1; -; mRNA.
DR EMBL; AK313557; BAG36332.1; -; mRNA.
DR EMBL; BC006460; AAH06460.1; -; mRNA.
DR CCDS; CCDS11495.1; -.
DR RefSeq; NP_006451.1; NM_006460.2.
DR PDB; 2GD7; NMR; -; A/B=255-359.
DR PDB; 3S9G; X-ray; 2.10 A; A/B=255-359.
DR PDBsum; 2GD7; -.
DR PDBsum; 3S9G; -.
DR AlphaFoldDB; O94992; -.
DR BMRB; O94992; -.
DR SMR; O94992; -.
DR BioGRID; 115860; 899.
DR CORUM; O94992; -.
DR DIP; DIP-46463N; -.
DR IntAct; O94992; 70.
DR MINT; O94992; -.
DR STRING; 9606.ENSP00000328773; -.
DR ChEMBL; CHEMBL3120044; -.
DR GlyGen; O94992; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O94992; -.
DR PhosphoSitePlus; O94992; -.
DR BioMuta; HEXIM1; -.
DR EPD; O94992; -.
DR jPOST; O94992; -.
DR MassIVE; O94992; -.
DR MaxQB; O94992; -.
DR PaxDb; O94992; -.
DR PeptideAtlas; O94992; -.
DR PRIDE; O94992; -.
DR ProteomicsDB; 50620; -.
DR Antibodypedia; 1837; 465 antibodies from 40 providers.
DR DNASU; 10614; -.
DR Ensembl; ENST00000332499.4; ENSP00000328773.3; ENSG00000186834.4.
DR GeneID; 10614; -.
DR KEGG; hsa:10614; -.
DR MANE-Select; ENST00000332499.4; ENSP00000328773.3; NM_006460.3; NP_006451.1.
DR UCSC; uc002iig.4; human.
DR CTD; 10614; -.
DR DisGeNET; 10614; -.
DR GeneCards; HEXIM1; -.
DR HGNC; HGNC:24953; HEXIM1.
DR HPA; ENSG00000186834; Low tissue specificity.
DR MIM; 607328; gene.
DR neXtProt; NX_O94992; -.
DR OpenTargets; ENSG00000186834; -.
DR PharmGKB; PA142671694; -.
DR VEuPathDB; HostDB:ENSG00000186834; -.
DR eggNOG; ENOG502QQP8; Eukaryota.
DR GeneTree; ENSGT00390000002808; -.
DR HOGENOM; CLU_066028_0_0_1; -.
DR InParanoid; O94992; -.
DR OMA; CHDSEAN; -.
DR OrthoDB; 1055089at2759; -.
DR PhylomeDB; O94992; -.
DR TreeFam; TF336851; -.
DR PathwayCommons; O94992; -.
DR SignaLink; O94992; -.
DR SIGNOR; O94992; -.
DR BioGRID-ORCS; 10614; 96 hits in 1075 CRISPR screens.
DR ChiTaRS; HEXIM1; human.
DR EvolutionaryTrace; O94992; -.
DR GeneWiki; HEXIM1; -.
DR GenomeRNAi; 10614; -.
DR Pharos; O94992; Tbio.
DR PRO; PR:O94992; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; O94992; protein.
DR Bgee; ENSG00000186834; Expressed in esophagus squamous epithelium and 205 other tissues.
DR Genevisible; O94992; HS.
DR GO; GO:0120259; C:7SK snRNP; IDA:FlyBase.
DR GO; GO:0005737; C:cytoplasm; IDA:HGNC-UCL.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0097322; F:7SK snRNA binding; IDA:UniProtKB.
DR GO; GO:0004861; F:cyclin-dependent protein serine/threonine kinase inhibitor activity; IDA:HGNC-UCL.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0106140; F:P-TEFb complex binding; IDA:FlyBase.
DR GO; GO:0004860; F:protein kinase inhibitor activity; IDA:FlyBase.
DR GO; GO:0017069; F:snRNA binding; IDA:HGNC-UCL.
DR GO; GO:0002218; P:activation of innate immune response; IDA:UniProtKB.
DR GO; GO:0007507; P:heart development; IEA:Ensembl.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0045736; P:negative regulation of cyclin-dependent protein serine/threonine kinase activity; IDA:HGNC-UCL.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:HGNC-UCL.
DR GO; GO:0034244; P:negative regulation of transcription elongation from RNA polymerase II promoter; IC:FlyBase.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:HGNC-UCL.
DR GO; GO:0032897; P:negative regulation of viral transcription; IMP:FlyBase.
DR GO; GO:1901798; P:positive regulation of signal transduction by p53 class mediator; IMP:CACAO.
DR InterPro; IPR024872; HEXIM.
DR PANTHER; PTHR13469; PTHR13469; 1.
DR Pfam; PF15313; HEXIM; 1.
DR PRINTS; PR02094; HEXIMFAMILY.
PE 1: Evidence at protein level;
KW 3D-structure; Coiled coil; Cytoplasm; Immunity; Innate immunity; Nucleus;
KW Phosphoprotein; Reference proteome; Repressor; Transcription;
KW Transcription regulation.
FT CHAIN 1..359
FT /note="Protein HEXIM1"
FT /id="PRO_0000305263"
FT REGION 1..163
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 150..177
FT /note="Basic region; mediates nuclear localization and
FT interaction with 7SK snRNA and NR3C1"
FT /evidence="ECO:0000269|PubMed:15941832"
FT REGION 202..205
FT /note="Interaction with P-TEFb"
FT REGION 210..250
FT /note="Autoinhibitory acidic region; in absence of 7SK
FT snRNA interacts with the basic region preventing
FT interaction with P-TEFb and modulating subcellular
FT localization"
FT REGION 213..262
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 286..314
FT /note="Mediates interaction with CCNT1"
FT REGION 310..355
FT /note="Required for inhibition of ESR1-dependent
FT transcription"
FT COILED 283..349
FT /evidence="ECO:0000255"
FT COMPBIAS 8..23
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 31..46
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 148..163
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 237..251
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 97
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 98
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 233
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231"
FT MOD_RES 236
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231"
FT MOD_RES 237
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231"
FT MOD_RES 252
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692"
FT MOD_RES 260
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8R409"
FT MUTAGEN 152..155
FT /note="KHRR->ILAA: Abolishes interaction with 7SK snRNA."
FT /evidence="ECO:0000269|PubMed:15201869"
FT MUTAGEN 154..156
FT /note="RRR->AAA: Abolishes interaction with 7SK snRNA."
FT /evidence="ECO:0000269|PubMed:16362050"
FT MUTAGEN 203
FT /note="Y->D: Abolishes interaction with P-TEFb; when
FT associated with D-205."
FT /evidence="ECO:0000269|PubMed:15201869"
FT MUTAGEN 205
FT /note="T->D: Abolishes interaction with P-TEFb. Same
FT effect; when associated with D-203."
FT /evidence="ECO:0000269|PubMed:15201869"
FT MUTAGEN 208
FT /note="F->A,D,K: Partial loss of function."
FT /evidence="ECO:0000269|PubMed:15965233"
FT MUTAGEN 271
FT /note="Y->A,E: Loss of function."
FT /evidence="ECO:0000269|PubMed:15965233"
FT MUTAGEN 287
FT /note="L->A: Loss of oligomerization; when associated with
FT A-294; A-332 and A-339. Loss of function and interaction
FT with P-TEFb; when associated with A-294."
FT /evidence="ECO:0000269|PubMed:16377779"
FT MUTAGEN 294
FT /note="L->A: Loss of oligomerization; when associated with
FT A-287; A-332 and A-339. Loss of function and interaction
FT with P-TEFb; when associated with A-287."
FT /evidence="ECO:0000269|PubMed:16377779"
FT MUTAGEN 332
FT /note="L->A: Loss of oligomerization; when associated with
FT A-287; A-294 and A-339."
FT /evidence="ECO:0000269|PubMed:16377779"
FT MUTAGEN 339
FT /note="L->A: Loss of oligomerization; when associated with
FT A-287; A-294 and A-332."
FT /evidence="ECO:0000269|PubMed:16377779"
FT HELIX 268..280
FT /evidence="ECO:0007829|PDB:3S9G"
FT HELIX 284..315
FT /evidence="ECO:0007829|PDB:3S9G"
FT HELIX 319..348
FT /evidence="ECO:0007829|PDB:3S9G"
SQ SEQUENCE 359 AA; 40623 MW; B12845C4E2595FF0 CRC64;
MAEPFLSEYQ HQPQTSNCTG AAAVQEELNP ERPPGAEERV PEEDSRWQSR AFPQLGGRPG
PEGEGSLESQ PPPLQTQACP ESSCLREGEK GQNGDDSSAG GDFPPPAEVE PTPEAELLAQ
PCHDSEASKL GAPAAGGEEE WGQQQRQLGK KKHRRRPSKK KRHWKPYYKL TWEEKKKFDE
KQSLRASRIR AEMFAKGQPV APYNTTQFLM DDHDQEEPDL KTGLYSKRAA AKSDDTSDDD
FMEEGGEEDG GSDGMGGDGS EFLQRDFSET YERYHTESLQ NMSKQELIKE YLELEKCLSR
MEDENNRLRL ESKRLGGDDA RVRELELELD RLRAENLQLL TENELHRQQE RAPLSKFGD
