Full text data of HEXIM1
HEXIM1
(CLP1, EDG1, HIS1, MAQ1)
[Confidence: low (only semi-automatic identification from reviews)]
Protein HEXIM1 (Cardiac lineage protein 1; Estrogen down-regulated gene 1 protein; Hexamethylene bis-acetamide-inducible protein 1; Menage a quatre protein 1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Protein HEXIM1 (Cardiac lineage protein 1; Estrogen down-regulated gene 1 protein; Hexamethylene bis-acetamide-inducible protein 1; Menage a quatre protein 1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
O94992
ID HEXI1_HUMAN Reviewed; 359 AA.
AC O94992; B2R8Y5;
DT 02-OCT-2007, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-MAY-1999, sequence version 1.
DT 22-JAN-2014, entry version 97.
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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,
RT in 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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INDUCTION BY
RP 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
RT down-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
RP BY HMBA.
RX PubMed=12581153; DOI=10.1046/j.1365-2443.2003.00618.x;
RA Ouchida R., Kusuhara M., Shimizu N., Hisada T., Makino Y.,
RA Morimoto C., 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
RP 7SK SNRNP 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
RT transcription-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-
RT binding domain is essential for HEXIM1 to inhibit RNA polymerase II
RT transcription 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.,
RA 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
RP SPECIFICITY, AND 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
RT balance of active and inactive positive transcription elongation
RT factor b complexes 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
RT contains one 7SK molecule, a dimer of HEXIM1 or HEXIM2, and two P-TEFb
RT molecules 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
RT directs the 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
RT alpha 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.,
RA Okamoto K., 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
RT elongation 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 SNRNP 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
RT 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
RT 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.,
RA Price D.H.;
RT "HEXIM1 is a promiscuous double-stranded RNA-binding protein and
RT interacts 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;
RP THR-236; SER-237 AND SER-252, AND MASS SPECTROMETRY.
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
RP AND SER-252, AND MASS SPECTROMETRY.
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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-233; THR-236; SER-237
RP AND SER-252, AND MASS SPECTROMETRY.
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.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [24]
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.,
RA Buerckstuemmer T., 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 [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-252, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [26]
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
RT basis for 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
CC RNA polymerase II transcription inhibitor. In cooperation with 7SK
CC snRNA sequesters P-TEFb in a large inactive 7SK snRNP complex
CC preventing RNA polymerase II phosphorylation and subsequent
CC transcriptional elongation. May also regulate NF-kappa-B, ESR1,
CC NR3C1 and CIITA-dependent transcriptional activity.
CC -!- SUBUNIT: Homooligomer and heterooligomer with HEXIM2; probably
CC dimeric. Component of the 7SK snRNP complex at least composed of
CC P-TEFb (composed of CDK9 and CCNT1/cyclin-T1), HEXIM1, HEXIM2,
CC BCDIN3, SART3 proteins and 7SK and U6 snRNAs. Interacts with the
CC N-CoR complex through NCOR1. Interacts with ESR1 and NR3C1. May
CC interact with NF-kappa-B through RELA.
CC -!- INTERACTION:
CC P50750:CDK9; NbExp=6; IntAct=EBI-2832510, EBI-1383449;
CC Q4G0J3:LARP7; NbExp=5; IntAct=EBI-2832510, EBI-2371923;
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=Binds alpha-
CC importin and is mostly nuclear.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed with higher expression
CC in placenta. HEXIM1 and HEXIM2 are differentially expressed.
CC Expressed in endocrine tissues.
CC -!- INDUCTION: Up-regulated by HMBA (hexamethylene bisacetamide) (at
CC protein level). Down-regulated by estrogen.
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.
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DR EMBL; AB021179; BAA36166.1; -; mRNA.
DR EMBL; AK313557; BAG36332.1; -; mRNA.
DR EMBL; BC006460; AAH06460.1; -; mRNA.
DR RefSeq; NP_006451.1; NM_006460.2.
DR UniGene; Hs.586945; -.
DR UniGene; Hs.741758; -.
DR UniGene; Hs.745252; -.
DR PDB; 2GD7; NMR; -; A/B=257-359.
DR PDB; 3S9G; X-ray; 2.10 A; A/B=255-359.
DR PDBsum; 2GD7; -.
DR PDBsum; 3S9G; -.
DR ProteinModelPortal; O94992; -.
DR SMR; O94992; 254-359.
DR DIP; DIP-46463N; -.
DR IntAct; O94992; 5.
DR STRING; 9606.ENSP00000328773; -.
DR PhosphoSite; O94992; -.
DR PaxDb; O94992; -.
DR PeptideAtlas; O94992; -.
DR PRIDE; O94992; -.
DR DNASU; 10614; -.
DR Ensembl; ENST00000332499; ENSP00000328773; ENSG00000186834.
DR GeneID; 10614; -.
DR KEGG; hsa:10614; -.
DR UCSC; uc002iig.3; human.
DR CTD; 10614; -.
DR GeneCards; GC17P043224; -.
DR HGNC; HGNC:24953; HEXIM1.
DR HPA; CAB011625; -.
DR HPA; HPA008926; -.
DR MIM; 607328; gene.
DR neXtProt; NX_O94992; -.
DR PharmGKB; PA142671694; -.
DR eggNOG; NOG72325; -.
DR HOGENOM; HOG000060338; -.
DR HOVERGEN; HBG053249; -.
DR InParanoid; O94992; -.
DR KO; K15189; -.
DR OMA; EDSRWQS; -.
DR OrthoDB; EOG771281; -.
DR PhylomeDB; O94992; -.
DR ChiTaRS; HEXIM1; human.
DR EvolutionaryTrace; O94992; -.
DR GeneWiki; HEXIM1; -.
DR GenomeRNAi; 10614; -.
DR NextBio; 40326; -.
DR PRO; PR:O94992; -.
DR Bgee; O94992; -.
DR CleanEx; HS_CLP1; -.
DR CleanEx; HS_HEXIM1; -.
DR Genevestigator; O94992; -.
DR GO; GO:0005737; C:cytoplasm; IDA:HGNC.
DR GO; GO:0005634; C:nucleus; IDA:HGNC.
DR GO; GO:0004861; F:cyclin-dependent protein serine/threonine kinase inhibitor activity; IDA:HGNC.
DR GO; GO:0017069; F:snRNA binding; IDA:HGNC.
DR GO; GO:0007507; P:heart development; IEA:Ensembl.
DR GO; GO:0045736; P:negative regulation of cyclin-dependent protein serine/threonine kinase activity; IDA:HGNC.
DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IDA:HGNC.
DR GO; GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
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; Complete proteome; Cytoplasm; Nucleus;
KW Phosphoprotein; Reference proteome; Repressor; Transcription;
KW Transcription regulation.
FT CHAIN 1 359 Protein HEXIM1.
FT /FTId=PRO_0000305263.
FT REGION 150 177 Basic region; mediates nuclear
FT localization and interaction with 7SK
FT snRNA and NR3C1.
FT REGION 202 205 Interaction with P-TEFb.
FT REGION 210 250 Autoinhibitory acidic region; in absence
FT of 7SK snRNA interacts with the basic
FT region preventing interaction with P-TEFb
FT and modulating subcellular localization.
FT REGION 286 314 Mediates interaction with CCNT1.
FT REGION 310 355 Required for inhibition of ESR1-dependent
FT transcription.
FT COILED 283 349 Potential.
FT MOD_RES 97 97 Phosphoserine.
FT MOD_RES 98 98 Phosphoserine.
FT MOD_RES 233 233 Phosphoserine.
FT MOD_RES 236 236 Phosphothreonine.
FT MOD_RES 237 237 Phosphoserine.
FT MOD_RES 252 252 Phosphoserine.
FT MUTAGEN 152 155 KHRR->ILAA: Abolishes interaction with
FT 7SK snRNA.
FT MUTAGEN 154 156 RRR->AAA: Abolishes interaction with 7SK
FT snRNA.
FT MUTAGEN 203 203 Y->D: Abolishes interaction with P-TEFb;
FT when associated with D-205.
FT MUTAGEN 205 205 T->D: Abolishes interaction with P-TEFb.
FT Same effect; when associated with D-203.
FT MUTAGEN 208 208 F->A,D,K: Partial loss of function.
FT MUTAGEN 271 271 Y->A,E: Loss of function.
FT MUTAGEN 287 287 L->A: Loss of oligomerization; when
FT associated with A-294; A-332 and A-339.
FT Loss of function and interaction with P-
FT TEFb; when associated with A-294.
FT MUTAGEN 294 294 L->A: Loss of oligomerization; when
FT associated with A-287; A-332 and A-339.
FT Loss of function and interaction with P-
FT TEFb; when associated with A-287.
FT MUTAGEN 332 332 L->A: Loss of oligomerization; when
FT associated with A-287; A-294 and A-339.
FT MUTAGEN 339 339 L->A: Loss of oligomerization; when
FT associated with A-287; A-294 and A-332.
FT HELIX 268 280
FT HELIX 284 315
FT HELIX 319 348
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
//
ID HEXI1_HUMAN Reviewed; 359 AA.
AC O94992; B2R8Y5;
DT 02-OCT-2007, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-MAY-1999, sequence version 1.
DT 22-JAN-2014, entry version 97.
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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,
RT in 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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INDUCTION BY
RP 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
RT down-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
RP BY HMBA.
RX PubMed=12581153; DOI=10.1046/j.1365-2443.2003.00618.x;
RA Ouchida R., Kusuhara M., Shimizu N., Hisada T., Makino Y.,
RA Morimoto C., 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
RP 7SK SNRNP 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
RT transcription-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-
RT binding domain is essential for HEXIM1 to inhibit RNA polymerase II
RT transcription 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.,
RA 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
RP SPECIFICITY, AND 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
RT balance of active and inactive positive transcription elongation
RT factor b complexes 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
RT contains one 7SK molecule, a dimer of HEXIM1 or HEXIM2, and two P-TEFb
RT molecules 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
RT directs the 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
RT alpha 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.,
RA Okamoto K., 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
RT elongation 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 SNRNP 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
RT 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
RT 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.,
RA Price D.H.;
RT "HEXIM1 is a promiscuous double-stranded RNA-binding protein and
RT interacts 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;
RP THR-236; SER-237 AND SER-252, AND MASS SPECTROMETRY.
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
RP AND SER-252, AND MASS SPECTROMETRY.
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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-233; THR-236; SER-237
RP AND SER-252, AND MASS SPECTROMETRY.
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.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [24]
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.,
RA Buerckstuemmer T., 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 [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-252, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [26]
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
RT basis for 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
CC RNA polymerase II transcription inhibitor. In cooperation with 7SK
CC snRNA sequesters P-TEFb in a large inactive 7SK snRNP complex
CC preventing RNA polymerase II phosphorylation and subsequent
CC transcriptional elongation. May also regulate NF-kappa-B, ESR1,
CC NR3C1 and CIITA-dependent transcriptional activity.
CC -!- SUBUNIT: Homooligomer and heterooligomer with HEXIM2; probably
CC dimeric. Component of the 7SK snRNP complex at least composed of
CC P-TEFb (composed of CDK9 and CCNT1/cyclin-T1), HEXIM1, HEXIM2,
CC BCDIN3, SART3 proteins and 7SK and U6 snRNAs. Interacts with the
CC N-CoR complex through NCOR1. Interacts with ESR1 and NR3C1. May
CC interact with NF-kappa-B through RELA.
CC -!- INTERACTION:
CC P50750:CDK9; NbExp=6; IntAct=EBI-2832510, EBI-1383449;
CC Q4G0J3:LARP7; NbExp=5; IntAct=EBI-2832510, EBI-2371923;
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=Binds alpha-
CC importin and is mostly nuclear.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed with higher expression
CC in placenta. HEXIM1 and HEXIM2 are differentially expressed.
CC Expressed in endocrine tissues.
CC -!- INDUCTION: Up-regulated by HMBA (hexamethylene bisacetamide) (at
CC protein level). Down-regulated by estrogen.
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.
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DR EMBL; AB021179; BAA36166.1; -; mRNA.
DR EMBL; AK313557; BAG36332.1; -; mRNA.
DR EMBL; BC006460; AAH06460.1; -; mRNA.
DR RefSeq; NP_006451.1; NM_006460.2.
DR UniGene; Hs.586945; -.
DR UniGene; Hs.741758; -.
DR UniGene; Hs.745252; -.
DR PDB; 2GD7; NMR; -; A/B=257-359.
DR PDB; 3S9G; X-ray; 2.10 A; A/B=255-359.
DR PDBsum; 2GD7; -.
DR PDBsum; 3S9G; -.
DR ProteinModelPortal; O94992; -.
DR SMR; O94992; 254-359.
DR DIP; DIP-46463N; -.
DR IntAct; O94992; 5.
DR STRING; 9606.ENSP00000328773; -.
DR PhosphoSite; O94992; -.
DR PaxDb; O94992; -.
DR PeptideAtlas; O94992; -.
DR PRIDE; O94992; -.
DR DNASU; 10614; -.
DR Ensembl; ENST00000332499; ENSP00000328773; ENSG00000186834.
DR GeneID; 10614; -.
DR KEGG; hsa:10614; -.
DR UCSC; uc002iig.3; human.
DR CTD; 10614; -.
DR GeneCards; GC17P043224; -.
DR HGNC; HGNC:24953; HEXIM1.
DR HPA; CAB011625; -.
DR HPA; HPA008926; -.
DR MIM; 607328; gene.
DR neXtProt; NX_O94992; -.
DR PharmGKB; PA142671694; -.
DR eggNOG; NOG72325; -.
DR HOGENOM; HOG000060338; -.
DR HOVERGEN; HBG053249; -.
DR InParanoid; O94992; -.
DR KO; K15189; -.
DR OMA; EDSRWQS; -.
DR OrthoDB; EOG771281; -.
DR PhylomeDB; O94992; -.
DR ChiTaRS; HEXIM1; human.
DR EvolutionaryTrace; O94992; -.
DR GeneWiki; HEXIM1; -.
DR GenomeRNAi; 10614; -.
DR NextBio; 40326; -.
DR PRO; PR:O94992; -.
DR Bgee; O94992; -.
DR CleanEx; HS_CLP1; -.
DR CleanEx; HS_HEXIM1; -.
DR Genevestigator; O94992; -.
DR GO; GO:0005737; C:cytoplasm; IDA:HGNC.
DR GO; GO:0005634; C:nucleus; IDA:HGNC.
DR GO; GO:0004861; F:cyclin-dependent protein serine/threonine kinase inhibitor activity; IDA:HGNC.
DR GO; GO:0017069; F:snRNA binding; IDA:HGNC.
DR GO; GO:0007507; P:heart development; IEA:Ensembl.
DR GO; GO:0045736; P:negative regulation of cyclin-dependent protein serine/threonine kinase activity; IDA:HGNC.
DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IDA:HGNC.
DR GO; GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
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; Complete proteome; Cytoplasm; Nucleus;
KW Phosphoprotein; Reference proteome; Repressor; Transcription;
KW Transcription regulation.
FT CHAIN 1 359 Protein HEXIM1.
FT /FTId=PRO_0000305263.
FT REGION 150 177 Basic region; mediates nuclear
FT localization and interaction with 7SK
FT snRNA and NR3C1.
FT REGION 202 205 Interaction with P-TEFb.
FT REGION 210 250 Autoinhibitory acidic region; in absence
FT of 7SK snRNA interacts with the basic
FT region preventing interaction with P-TEFb
FT and modulating subcellular localization.
FT REGION 286 314 Mediates interaction with CCNT1.
FT REGION 310 355 Required for inhibition of ESR1-dependent
FT transcription.
FT COILED 283 349 Potential.
FT MOD_RES 97 97 Phosphoserine.
FT MOD_RES 98 98 Phosphoserine.
FT MOD_RES 233 233 Phosphoserine.
FT MOD_RES 236 236 Phosphothreonine.
FT MOD_RES 237 237 Phosphoserine.
FT MOD_RES 252 252 Phosphoserine.
FT MUTAGEN 152 155 KHRR->ILAA: Abolishes interaction with
FT 7SK snRNA.
FT MUTAGEN 154 156 RRR->AAA: Abolishes interaction with 7SK
FT snRNA.
FT MUTAGEN 203 203 Y->D: Abolishes interaction with P-TEFb;
FT when associated with D-205.
FT MUTAGEN 205 205 T->D: Abolishes interaction with P-TEFb.
FT Same effect; when associated with D-203.
FT MUTAGEN 208 208 F->A,D,K: Partial loss of function.
FT MUTAGEN 271 271 Y->A,E: Loss of function.
FT MUTAGEN 287 287 L->A: Loss of oligomerization; when
FT associated with A-294; A-332 and A-339.
FT Loss of function and interaction with P-
FT TEFb; when associated with A-294.
FT MUTAGEN 294 294 L->A: Loss of oligomerization; when
FT associated with A-287; A-332 and A-339.
FT Loss of function and interaction with P-
FT TEFb; when associated with A-287.
FT MUTAGEN 332 332 L->A: Loss of oligomerization; when
FT associated with A-287; A-294 and A-339.
FT MUTAGEN 339 339 L->A: Loss of oligomerization; when
FT associated with A-287; A-294 and A-332.
FT HELIX 268 280
FT HELIX 284 315
FT HELIX 319 348
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
//
MIM
607328
*RECORD*
*FIELD* NO
607328
*FIELD* TI
*607328 HEXAMETHYLENE BIS ACETAMIDE-INDUCIBLE PROTEIN 1; HEXIM1
;;CARDIAC LINEAGE PROTEIN 1; CLP1;;
read moreHIS1;;
MAQ1
*FIELD* TX
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.
GENE FUNCTION
Kohoutek et al. (2006) found that HEXIM1 inhibited the ability of C2TA
(MHC2TA; 600005) to activate transcription of MHC class II genes in HeLa
cells. This inhibition depended on the cyclin T1 (CCNT1; 143055)-binding
domain of HEXIM1. In vitro binding experiments and chromatin
immunoprecipitation analyses showed that HEXIM1 competed with C2TA for
binding to CCNT1, which together with CDK9 (603251) forms the positive
transcription elongation factor B (PTEFB), and sequestered PTEFB from
C2TA. HeLa cells depleted of HEXIM1 by small interfering RNA displayed
increased C2TA activity and induction of C2TA-dependent genes.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the HEXIM1
gene to chromosome 17 (TMAP BCD3293).
*FIELD* RF
1. Huang, F.; Wagner, M.; Siddiqui, M. A. Q.: Structure, expression,
and functional characterization of the mouse CLP-1 gene. Gene 292:
245-259, 2002.
2. Kohoutek, J.; Blazek, D.; Peterlin, B. M.: Hexim1 sequesters positive
transcription elongation factor b from the class II transactivator
on MHC class II promoters. Proc. Nat. Acad. Sci. 103: 17349-17354,
2006.
*FIELD* CN
Paul J. Converse - updated: 12/14/2006
Patricia A. Hartz - updated: 9/22/2005
*FIELD* CD
Patricia A. Hartz: 10/30/2002
*FIELD* ED
mgross: 02/20/2009
mgross: 1/2/2007
terry: 12/14/2006
wwang: 9/26/2005
wwang: 9/22/2005
mgross: 10/30/2002
*RECORD*
*FIELD* NO
607328
*FIELD* TI
*607328 HEXAMETHYLENE BIS ACETAMIDE-INDUCIBLE PROTEIN 1; HEXIM1
;;CARDIAC LINEAGE PROTEIN 1; CLP1;;
read moreHIS1;;
MAQ1
*FIELD* TX
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.
GENE FUNCTION
Kohoutek et al. (2006) found that HEXIM1 inhibited the ability of C2TA
(MHC2TA; 600005) to activate transcription of MHC class II genes in HeLa
cells. This inhibition depended on the cyclin T1 (CCNT1; 143055)-binding
domain of HEXIM1. In vitro binding experiments and chromatin
immunoprecipitation analyses showed that HEXIM1 competed with C2TA for
binding to CCNT1, which together with CDK9 (603251) forms the positive
transcription elongation factor B (PTEFB), and sequestered PTEFB from
C2TA. HeLa cells depleted of HEXIM1 by small interfering RNA displayed
increased C2TA activity and induction of C2TA-dependent genes.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the HEXIM1
gene to chromosome 17 (TMAP BCD3293).
*FIELD* RF
1. Huang, F.; Wagner, M.; Siddiqui, M. A. Q.: Structure, expression,
and functional characterization of the mouse CLP-1 gene. Gene 292:
245-259, 2002.
2. Kohoutek, J.; Blazek, D.; Peterlin, B. M.: Hexim1 sequesters positive
transcription elongation factor b from the class II transactivator
on MHC class II promoters. Proc. Nat. Acad. Sci. 103: 17349-17354,
2006.
*FIELD* CN
Paul J. Converse - updated: 12/14/2006
Patricia A. Hartz - updated: 9/22/2005
*FIELD* CD
Patricia A. Hartz: 10/30/2002
*FIELD* ED
mgross: 02/20/2009
mgross: 1/2/2007
terry: 12/14/2006
wwang: 9/26/2005
wwang: 9/22/2005
mgross: 10/30/2002