HEXI1_MOUSE
ID HEXI1_MOUSE Reviewed; 356 AA.
AC Q8R409;
DT 02-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=Protein HEXIM1;
DE AltName: Full=Cardiac lineage protein 1 {ECO:0000303|PubMed:12119119};
GN Name=Hexim1; Synonyms=Clp1 {ECO:0000303|PubMed:12119119};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND INDUCTION.
RC STRAIN=129/SvJ; TISSUE=Embryonic heart;
RX PubMed=12119119; DOI=10.1016/s0378-1119(02)00596-6;
RA Huang F., Wagner M., Siddiqui M.A.Q.;
RT "Structure, expression, and functional characterization of the mouse CLP-1
RT gene.";
RL Gene 292:245-259(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Medulla oblongata;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-103; SER-230; THR-233;
RP SER-234; SER-249 AND SER-257, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Kidney, Liver, Lung, Pancreas, Spleen, and
RC Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Transcriptional regulator which functions as a general RNA
CC polymerase II transcription inhibitor. 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. May also regulate NF-kappa-
CC B, ESR1, NR3C1 and CIITA-dependent transcriptional activity. Plays a
CC role in 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.
CC {ECO:0000250|UniProtKB:O94992}.
CC -!- SUBUNIT: Homooligomer and heterooligomer with HEXIM2; probably dimeric.
CC Core component of the 7SK RNP complex, at least composed of 7SK RNA,
CC LARP7, MEPCE, HEXIM1 (or HEXIM2) and P-TEFb (composed of CDK9 and
CC CCNT1/cyclin-T1). Interacts with the N-CoR complex through NCOR1.
CC Interacts with ESR1 and NR3C1. May interact with NF-kappa-B through
CC RELA. Interacts with CCNT2; mediates formation of a tripartite complex
CC with KPNA2. Part of the HDP-RNP complex composed of at least HEXIM1,
CC PRKDC, XRCC5, XRCC6, paraspeckle proteins (SFPQ, NONO, PSPC1, RBM14,
CC and MATR3) and NEAT1 non-coding RNA. {ECO:0000250|UniProtKB:O94992}.
CC -!- INTERACTION:
CC Q8R409; Q6PDM2: Srsf1; NbExp=4; IntAct=EBI-6261031, EBI-2550360;
CC Q8R409; Q62093: Srsf2; NbExp=4; IntAct=EBI-6261031, EBI-2550402;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:O94992}. Cytoplasm
CC {ECO:0000250|UniProtKB:O94992}. Note=Binds alpha-importin and is mostly
CC nuclear. {ECO:0000250|UniProtKB:O94992}.
CC -!- TISSUE SPECIFICITY: Widely expressed with higher expression in heart,
CC skeletal muscle and brain (at protein level).
CC {ECO:0000269|PubMed:12119119}.
CC -!- INDUCTION: Up-regulated by HMBA (hexamethylene bisacetamide).
CC {ECO:0000269|PubMed:12119119}.
CC -!- DOMAIN: The coiled-coil domain mediates oligomerization. {ECO:0000250}.
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; AY090614; AAM09026.1; -; mRNA.
DR EMBL; AK134535; BAE22173.1; -; mRNA.
DR EMBL; AL731805; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS25513.1; -.
DR RefSeq; NP_620092.1; NM_138753.2.
DR AlphaFoldDB; Q8R409; -.
DR SMR; Q8R409; -.
DR BioGRID; 228682; 2.
DR IntAct; Q8R409; 3.
DR STRING; 10090.ENSMUSP00000057339; -.
DR iPTMnet; Q8R409; -.
DR PhosphoSitePlus; Q8R409; -.
DR EPD; Q8R409; -.
DR jPOST; Q8R409; -.
DR MaxQB; Q8R409; -.
DR PaxDb; Q8R409; -.
DR PeptideAtlas; Q8R409; -.
DR PRIDE; Q8R409; -.
DR ProteomicsDB; 269704; -.
DR Antibodypedia; 1837; 465 antibodies from 40 providers.
DR Ensembl; ENSMUST00000053063; ENSMUSP00000057339; ENSMUSG00000048878.
DR GeneID; 192231; -.
DR KEGG; mmu:192231; -.
DR UCSC; uc007lto.1; mouse.
DR CTD; 10614; -.
DR MGI; MGI:2385923; Hexim1.
DR VEuPathDB; HostDB:ENSMUSG00000048878; -.
DR eggNOG; ENOG502QQP8; Eukaryota.
DR GeneTree; ENSGT00390000002808; -.
DR HOGENOM; CLU_066028_0_0_1; -.
DR InParanoid; Q8R409; -.
DR OMA; CHDSEAN; -.
DR OrthoDB; 1055089at2759; -.
DR PhylomeDB; Q8R409; -.
DR TreeFam; TF336851; -.
DR BioGRID-ORCS; 192231; 16 hits in 74 CRISPR screens.
DR ChiTaRS; Hexim1; mouse.
DR PRO; PR:Q8R409; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q8R409; protein.
DR Bgee; ENSMUSG00000048878; Expressed in dorsal pancreas and 241 other tissues.
DR Genevisible; Q8R409; MM.
DR GO; GO:0120259; C:7SK snRNP; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0097322; F:7SK snRNA binding; ISS:UniProtKB.
DR GO; GO:0004861; F:cyclin-dependent protein serine/threonine kinase inhibitor activity; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0106140; F:P-TEFb complex binding; ISO:MGI.
DR GO; GO:0004860; F:protein kinase inhibitor activity; ISO:MGI.
DR GO; GO:0017069; F:snRNA binding; ISS:UniProtKB.
DR GO; GO:0002218; P:activation of innate immune response; ISO:MGI.
DR GO; GO:0007507; P:heart development; IMP:MGI.
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; ISS:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:MGI.
DR GO; GO:0032897; P:negative regulation of viral transcription; ISO:MGI.
DR GO; GO:1901798; P:positive regulation of signal transduction by p53 class mediator; ISO:MGI.
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 Coiled coil; Cytoplasm; Immunity; Innate immunity; Nucleus; Phosphoprotein;
KW Reference proteome; Repressor; Transcription; Transcription regulation.
FT CHAIN 1..356
FT /note="Protein HEXIM1"
FT /id="PRO_0000305264"
FT REGION 1..162
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 147..174
FT /note="Basic region; mediates nuclear localization and
FT interaction with 7SK snRNA and NR3C1"
FT /evidence="ECO:0000250"
FT REGION 199..202
FT /note="Interaction with P-TEFb"
FT /evidence="ECO:0000250"
FT REGION 207..247
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 /evidence="ECO:0000250"
FT REGION 210..259
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 283..311
FT /note="Mediates interaction with CCNT1"
FT /evidence="ECO:0000250"
FT REGION 307..352
FT /note="Required for inhibition of ESR1-dependent
FT transcription"
FT /evidence="ECO:0000250"
FT COILED 280..346
FT /evidence="ECO:0000255"
FT COMPBIAS 8..23
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 25..46
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 144..162
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 234..248
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 98
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O94992"
FT MOD_RES 103
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 230
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 233
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 234
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 249
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 257
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
SQ SEQUENCE 356 AA; 40243 MW; 242DE7EE66BA293B CRC64;
MAEPLLTEHQ HQPQTSNCTG AAVVHEEHTS ERPPSAEERV PKEDSRWQSR ASLQSGSRPG
QEGEGGLKHQ LPPLQTNACP ELSSLEKGEK GQNGEDLSTG GASPSAEGEP MSESLVQPGH
DSEATKQEAP AAGGEEPWGQ QQRQLGKKKH RRRPSKKKRH WKPYYKLTWE EKKKFDEKQS
LRASRVRAEM FAKGQPVAPY NTTQFLMDDH DQEEPDLKTG LYPKRAAAKS DDTSDEDFVE
EAGEEDGGSD GMGGDGSEFL QRDFSETYER YHAESLQNMS KQELIKEYLE LEKCLSRKED
ENNRLRLESK RLGGVDARVR ELELELDRLR AENLQLLTEN ELHRQQERAP LSKFGD
