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Integrator complex subunit 1 (INTS1)
- Target
- INTS1
- Molecular classification
- Other (Integrator complex subunit), Transcription regulation co-factor, Scaffold protein (within Integrator complex)
01
Overview
Integrator complex subunit 1 (INTS1) is the largest and core scaffold protein of the Integrator complex, which associates with the C-terminal domain (CTD) of RNA Polymerase II and is critical for 3’-end processing of U-rich small nuclear RNAs and promoter-proximal termination of transcription by RNA Polymerase II[1][3][4]. The Integrator complex, and specifically INTS1, mediates transcriptional quality control, premature termination of improperly configured transcripts, chromatin remodeling activities, and participates in complex interactions with other transcription regulatory factors such as PP2A and STAT5[2][4]. INTS1 levels correlate with Integrator complex occupancy and function, especially during dynamic processes such as erythroid maturation[2]. Mutations or disruptions of INTS1 are implicated in rare neurodevelopmental disorders and developmental diseases[1][2].
- Other names
- INTS1Int1NET28Integrator complex subunit 1KIAA1440UNQ1821/PRO3434DKFZp586J0619INT1NDCAGF
02
Mechanism of action
Not applicable; no drugs directly targeting INTS1 are described
03
Biological functions
3'-end processing of small nuclear RNAs (snRNAs), specifically U1 and U2 RNAsTermination of RNA Polymerase II transcription, particularly promoter-proximal terminationQuality control checkpoint during transcription elongationRecruitment of cytoplasmic dynein to the nuclear envelopeRegulation of erythroid maturation and gene expression during erythropoiesis
04
Disease associations
Neurodevelopmental disorder with cataracts, poor growth, and dysmorphic faciesAutism spectrum disorderOther: Mutations can disrupt erythroid maturation and viability
05
Safety considerations
No direct safety concerns are known for targeting INTS1, as it is not an established drug target.Disruption of INTS1 or Integrator complex function can result in severe transcriptional dysregulation and impaired development, especially in erythroid cells and neurodevelopment
06
Biomarkers
INTS1 can be used as a molecular marker for Integrator complex levels and occupancy in specific transcriptional studies, especially as assessed by protein abundance or genomic occupancy in erythroid cells
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