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Protein

Protein HEXIM1

Gene

HEXIM1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Transcriptional regulator which functions as a general RNA polymerase II transcription inhibitor (PubMed:14580347, PubMed:15713661, PubMed:15201869). 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).9 Publications

Miscellaneous

Inhibits Tat activity which is required for HIV-1 transcription.

GO - Molecular functioni

  • 7SK snRNA binding Source: UniProtKB
  • cyclin-dependent protein serine/threonine kinase inhibitor activity Source: HGNC
  • snRNA binding Source: HGNC

GO - Biological processi

  • activation of innate immune response Source: UniProtKB
  • heart development Source: Ensembl
  • innate immune response Source: UniProtKB-KW
  • negative regulation of cyclin-dependent protein serine/threonine kinase activity Source: HGNC
  • negative regulation of transcription, DNA-templated Source: HGNC
  • negative regulation of transcription by RNA polymerase II Source: HGNC
  • positive regulation of signal transduction by p53 class mediator Source: CACAO
  • transcription, DNA-templated Source: UniProtKB-KW

Keywordsi

Molecular functionRepressor
Biological processImmunity, Innate immunity, Transcription, Transcription regulation

Names & Taxonomyi

Protein namesi
Recommended name:
Protein HEXIM1
Alternative name(s):
Cardiac lineage protein 1
Estrogen down-regulated gene 1 protein
Hexamethylene bis-acetamide-inducible protein 1
Menage a quatre protein 1
Gene namesi
Name:HEXIM1
Synonyms:CLP1, EDG1, HIS1, MAQ1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

EuPathDBiHostDB:ENSG00000186834.3
HGNCiHGNC:24953 HEXIM1
MIMi607328 gene
neXtProtiNX_O94992

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi152 – 155KHRR → ILAA: Abolishes interaction with 7SK snRNA. 1 Publication4
Mutagenesisi154 – 156RRR → AAA: Abolishes interaction with 7SK snRNA. 1 Publication3
Mutagenesisi203Y → D: Abolishes interaction with P-TEFb; when associated with D-205. 1 Publication1
Mutagenesisi205T → D: Abolishes interaction with P-TEFb. Same effect; when associated with D-203. 1 Publication1
Mutagenesisi208F → A, D or K: Partial loss of function. 1 Publication1
Mutagenesisi271Y → A or E: Loss of function. 1 Publication1
Mutagenesisi287L → A: Loss of oligomerization; when associated with A-294; A-332 and A-339. Loss of function and interaction with P-TEFb; when associated with A-294. 1 Publication1
Mutagenesisi294L → A: Loss of oligomerization; when associated with A-287; A-332 and A-339. Loss of function and interaction with P-TEFb; when associated with A-287. 1 Publication1
Mutagenesisi332L → A: Loss of oligomerization; when associated with A-287; A-294 and A-339. 1 Publication1
Mutagenesisi339L → A: Loss of oligomerization; when associated with A-287; A-294 and A-332. 1 Publication1

Organism-specific databases

DisGeNETi10614
OpenTargetsiENSG00000186834
PharmGKBiPA142671694

Chemistry databases

ChEMBLiCHEMBL3120044

Polymorphism and mutation databases

BioMutaiHEXIM1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003052631 – 359Protein HEXIM1Add BLAST359

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei97PhosphoserineCombined sources1
Modified residuei98PhosphoserineCombined sources1
Modified residuei233PhosphoserineCombined sources1
Modified residuei236PhosphothreonineCombined sources1
Modified residuei237PhosphoserineCombined sources1
Modified residuei252PhosphoserineCombined sources1
Modified residuei260PhosphoserineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiO94992
MaxQBiO94992
PaxDbiO94992
PeptideAtlasiO94992
PRIDEiO94992
ProteomicsDBi50620

PTM databases

iPTMnetiO94992
PhosphoSitePlusiO94992

Expressioni

Tissue specificityi

Ubiquitously expressed with higher expression in placenta. HEXIM1 and HEXIM2 are differentially expressed. Expressed in endocrine tissues.2 Publications

Inductioni

Up-regulated by HMBA (hexamethylene bisacetamide) (at protein level). Down-regulated by estrogen.3 Publications

Gene expression databases

BgeeiENSG00000186834
CleanExiHS_CLP1
HS_HEXIM1
GenevisibleiO94992 HS

Organism-specific databases

HPAiCAB011625
HPA008926

Interactioni

Subunit structurei

Homooligomer and heterooligomer with HEXIM2; probably dimeric (PubMed:15713661, PubMed:15965233, PubMed:16377779). Component of the 7SK snRNP complex at least composed of P-TEFb (composed of CDK9 and CCNT1/cyclin-T1), HEXIM1, HEXIM2, BCDIN3, SART3 proteins and 7SK and U6 snRNAs (PubMed:12832472, PubMed:15201869, PubMed:15169877, PubMed:16362050, PubMed:15713661, PubMed:15855166, PubMed:16377779, PubMed:17643375, PubMed:17724342). Interacts with the N-CoR complex through NCOR1 (PubMed:17452463). Interacts with ESR1 and NR3C1 (PubMed:15940264, PubMed:15941832). May interact with NF-kappa-B through RELA (PubMed:12581153). Interacts with CCNT2; mediates formation of a tripartite complex with KPNA2 (PubMed:19883659). Part of the HDP-RNP complex composed of at least HEXIM1, PRKDC, XRCC5, XRCC6, paraspeckle proteins (SFPQ, NONO, PSPC1, RBM14, and MATR3) and NEAT1 non-coding RNA (PubMed:28712728).16 Publications

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi115860, 57 interactors
CORUMiO94992
DIPiDIP-46463N
IntActiO94992, 17 interactors
MINTiO94992
STRINGi9606.ENSP00000328773

Structurei

Secondary structure

1359
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi268 – 280Combined sources13
Helixi284 – 315Combined sources32
Helixi319 – 348Combined sources30

3D structure databases

ProteinModelPortaliO94992
SMRiO94992
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO94992

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni150 – 177Basic region; mediates nuclear localization and interaction with 7SK snRNA and NR3C11 PublicationAdd BLAST28
Regioni202 – 205Interaction with P-TEFb4
Regioni210 – 250Autoinhibitory acidic region; in absence of 7SK snRNA interacts with the basic region preventing interaction with P-TEFb and modulating subcellular localizationAdd BLAST41
Regioni286 – 314Mediates interaction with CCNT1Add BLAST29
Regioni310 – 355Required for inhibition of ESR1-dependent transcriptionAdd BLAST46

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili283 – 349Sequence analysisAdd BLAST67

Domaini

The coiled-coil domain mediates oligomerization.

Sequence similaritiesi

Belongs to the HEXIM family.Curated

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiENOG410IH8I Eukaryota
ENOG4111K9Z LUCA
GeneTreeiENSGT00390000002808
HOGENOMiHOG000060338
HOVERGENiHBG053249
InParanoidiO94992
KOiK15189
OMAiEAWGQQQ
OrthoDBiEOG091G0Y9A
PhylomeDBiO94992
TreeFamiTF336851

Family and domain databases

InterProiView protein in InterPro
IPR024872 HEXIM
PANTHERiPTHR13469 PTHR13469, 1 hit
PfamiView protein in Pfam
PF15313 HEXIM, 1 hit
PRINTSiPR02094 HEXIMFAMILY

Sequencei

Sequence statusi: Complete.

O94992-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAEPFLSEYQ HQPQTSNCTG AAAVQEELNP ERPPGAEERV PEEDSRWQSR
60 70 80 90 100
AFPQLGGRPG PEGEGSLESQ PPPLQTQACP ESSCLREGEK GQNGDDSSAG
110 120 130 140 150
GDFPPPAEVE PTPEAELLAQ PCHDSEASKL GAPAAGGEEE WGQQQRQLGK
160 170 180 190 200
KKHRRRPSKK KRHWKPYYKL TWEEKKKFDE KQSLRASRIR AEMFAKGQPV
210 220 230 240 250
APYNTTQFLM DDHDQEEPDL KTGLYSKRAA AKSDDTSDDD FMEEGGEEDG
260 270 280 290 300
GSDGMGGDGS EFLQRDFSET YERYHTESLQ NMSKQELIKE YLELEKCLSR
310 320 330 340 350
MEDENNRLRL ESKRLGGDDA RVRELELELD RLRAENLQLL TENELHRQQE

RAPLSKFGD
Length:359
Mass (Da):40,623
Last modified:May 1, 1999 - v1
Checksum:iB12845C4E2595FF0
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB021179 mRNA Translation: BAA36166.1
AK313557 mRNA Translation: BAG36332.1
BC006460 mRNA Translation: AAH06460.1
CCDSiCCDS11495.1
RefSeqiNP_006451.1, NM_006460.2
UniGeneiHs.586945
Hs.741758
Hs.745252

Genome annotation databases

EnsembliENST00000332499; ENSP00000328773; ENSG00000186834
GeneIDi10614
KEGGihsa:10614
UCSCiuc002iig.4 human

Similar proteinsi

Entry informationi

Entry nameiHEXI1_HUMAN
AccessioniPrimary (citable) accession number: O94992
Secondary accession number(s): B2R8Y5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 2, 2007
Last sequence update: May 1, 1999
Last modified: July 18, 2018
This is version 135 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

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