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SUPT5H

Function

Component of the DRB sensitivity-inducing factor complex (DSIF complex), which regulates mRNA processing and transcription elongation by RNA polymerase II. DSIF positively regulates mRNA capping by stimulating the mRNA guanylyltransferase activity of RNGTT/CAP1A. DSIF also acts cooperatively with the negative elongation factor complex (NELF complex) to enhance transcriptional pausing at sites proximal to the promoter. Transcriptional pausing may facilitate the assembly of an elongation competent RNA polymerase II complex. DSIF and NELF promote pausing by inhibition of the transcription elongation factor TFIIS/S-II. TFIIS/S-II binds to RNA polymerase II at transcription pause sites and stimulates the weak intrinsic nuclease activity of the enzyme. Cleavage of blocked transcripts by RNA polymerase II promotes the resumption of transcription from the new 3' terminus and may allow repeated attempts at transcription through natural pause sites. DSIF can also positively regulate transcriptional elongation and is required for the efficient activation of transcriptional elongation by the HIV-1 nuclear transcriptional activator, Tat. DSIF acts to suppress transcriptional pausing in transcripts derived from the HIV-1 LTR and blocks premature release of HIV-1 transcripts at terminator sequences.

Post-translational modifications

Methylated by PRMT1/HRMT1L2 and PRMT5/SKB1. Methylation negatively regulates interaction with P-TEFb and RNA polymerase II.

Phosphorylated by CDK7 and CDK9. Phosphorylation by P-TEFb alleviates transcriptional pausing and can stimulate transcriptional elongation from the HIV-1 LTR. P-TEFb dependent phosphorylation is stimulated by the HIV-1 Tat protein. Phosphorylation may also stimulate interaction with PIN1. Bulk phosphorylation occurs predominantly in mitosis.

Ubiquitinated by UBR5 when not assembled in the DSIF complex, leading to its degradation: UBR5 recognizes and binds a degron that is not accessible when SUPT5H is part of the DSIF complex.

Sequence Similarities

Belongs to the SPT5 family.

Tissue Specificity

Ubiquitously expressed.

Cellular localization

Alternative names

SPT5, SPT5H, SUPT5H, Transcription elongation factor SPT5, hSPT5, DRB sensitivity-inducing factor 160 kDa subunit, DRB sensitivity-inducing factor large subunit, Tat-cotransactivator 1 protein, DSIF p160, DSIF large subunit, Tat-CT1 protein

swissprot:O00267 omim:602102 entrezGene:6829 swissprot:Q99639