UniProt functional annotation for O00267



	UniProt functional annotation for O00267

UniProt code: O00267.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

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. {ECO:0000269|PubMed:10075709, ECO:0000269|PubMed:10199401, ECO:0000269|PubMed:10393184, ECO:0000269|PubMed:10421630, ECO:0000269|PubMed:10454543, ECO:0000269|PubMed:10757782, ECO:0000269|PubMed:10912001, ECO:0000269|PubMed:11112772, ECO:0000269|PubMed:11553615, ECO:0000269|PubMed:11809800, ECO:0000269|PubMed:12653964, ECO:0000269|PubMed:12718890, ECO:0000269|PubMed:14701750, ECO:0000269|PubMed:15136722, ECO:0000269|PubMed:15380072, ECO:0000269|PubMed:16214896, ECO:0000269|PubMed:9450929, ECO:0000269|PubMed:9514752, ECO:0000269|PubMed:9857195}.

Subunit: Interacts with SUPT4H1 to form DSIF. DSIF interacts with the positive transcription elongation factor b complex (P-TEFb complex), which is composed of CDK9 and cyclin-T (CCNT1 or CCNT2). DSIF interacts with RNA polymerase II, and this interaction is reduced by phosphorylation of the C-terminal domain (CTD) of POLR2A by P-TEFb. DSIF also interacts with the NELF complex, which is composed of NELFA, NELFB, NELFD and NELFE, and this interaction occurs following prior binding of DSIF to RNA polymerase II. DSIF also interacts with PRMT1/HRMT1L2, HTATSF1/TATSF1, RNGTT/CAP1A, PRMT5/SKB1, SUPT6H, and can interact with PIN1. Component of a complex which is at least composed of HTATSF1/Tat-SF1, the P-TEFb complex components CDK9 and CCNT1, RNA polymerase II, SUPT5H, and NCL/nucleolin. Interacts with MCM3AP isoform GANP (PubMed:23652018). {ECO:0000269|PubMed:10075709, ECO:0000269|PubMed:10199401, ECO:0000269|PubMed:10393184, ECO:0000269|PubMed:10421630, ECO:0000269|PubMed:10454543, ECO:0000269|PubMed:10757782, ECO:0000269|PubMed:11575923, ECO:0000269|PubMed:11940650, ECO:0000269|PubMed:12612062, ECO:0000269|PubMed:12653964, ECO:0000269|PubMed:12718890, ECO:0000269|PubMed:15060154, ECO:0000269|PubMed:19860741, ECO:0000269|PubMed:23652018, ECO:0000269|PubMed:9450929, ECO:0000269|PubMed:9857195}.

Subcellular location: Nucleus {ECO:0000269|PubMed:10075709}.

Tissue specificity: Ubiquitously expressed. {ECO:0000269|PubMed:10075709, ECO:0000269|PubMed:8975720}.

Ptm: Methylated by PRMT1/HRMT1L2 and PRMT5/SKB1. Methylation negatively regulates interaction with P-TEFb and RNA polymerase II. {ECO:0000269|PubMed:12718890}.

Ptm: 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. {ECO:0000269|PubMed:10757782, ECO:0000269|PubMed:11112772, ECO:0000269|PubMed:11145967, ECO:0000269|PubMed:11575923, ECO:0000269|PubMed:11809800, ECO:0000269|PubMed:15564463, ECO:0000269|PubMed:16327805, ECO:0000269|PubMed:9199507}.

Similarity: Belongs to the SPT5 family. {ECO:0000305}.

Sequence caution: Sequence=BAD92494.1; Type=Erroneous initiation; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



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. {ECO:0000269\|PubMed:10075709, ECO:0000269\|PubMed:10199401, ECO:0000269\|PubMed:10393184, ECO:0000269\|PubMed:10421630, ECO:0000269\|PubMed:10454543, ECO:0000269\|PubMed:10757782, ECO:0000269\|PubMed:10912001, ECO:0000269\|PubMed:11112772, ECO:0000269\|PubMed:11553615, ECO:0000269\|PubMed:11809800, ECO:0000269\|PubMed:12653964, ECO:0000269\|PubMed:12718890, ECO:0000269\|PubMed:14701750, ECO:0000269\|PubMed:15136722, ECO:0000269\|PubMed:15380072, ECO:0000269\|PubMed:16214896, ECO:0000269\|PubMed:9450929, ECO:0000269\|PubMed:9514752, ECO:0000269\|PubMed:9857195}.


Subunit:		Interacts with SUPT4H1 to form DSIF. DSIF interacts with the positive transcription elongation factor b complex (P-TEFb complex), which is composed of CDK9 and cyclin-T (CCNT1 or CCNT2). DSIF interacts with RNA polymerase II, and this interaction is reduced by phosphorylation of the C-terminal domain (CTD) of POLR2A by P-TEFb. DSIF also interacts with the NELF complex, which is composed of NELFA, NELFB, NELFD and NELFE, and this interaction occurs following prior binding of DSIF to RNA polymerase II. DSIF also interacts with PRMT1/HRMT1L2, HTATSF1/TATSF1, RNGTT/CAP1A, PRMT5/SKB1, SUPT6H, and can interact with PIN1. Component of a complex which is at least composed of HTATSF1/Tat-SF1, the P-TEFb complex components CDK9 and CCNT1, RNA polymerase II, SUPT5H, and NCL/nucleolin. Interacts with MCM3AP isoform GANP (PubMed:23652018). {ECO:0000269\|PubMed:10075709, ECO:0000269\|PubMed:10199401, ECO:0000269\|PubMed:10393184, ECO:0000269\|PubMed:10421630, ECO:0000269\|PubMed:10454543, ECO:0000269\|PubMed:10757782, ECO:0000269\|PubMed:11575923, ECO:0000269\|PubMed:11940650, ECO:0000269\|PubMed:12612062, ECO:0000269\|PubMed:12653964, ECO:0000269\|PubMed:12718890, ECO:0000269\|PubMed:15060154, ECO:0000269\|PubMed:19860741, ECO:0000269\|PubMed:23652018, ECO:0000269\|PubMed:9450929, ECO:0000269\|PubMed:9857195}.
Subcellular location:		Nucleus {ECO:0000269\|PubMed:10075709}.
Tissue specificity:		Ubiquitously expressed. {ECO:0000269\|PubMed:10075709, ECO:0000269\|PubMed:8975720}.
Ptm:		Methylated by PRMT1/HRMT1L2 and PRMT5/SKB1. Methylation negatively regulates interaction with P-TEFb and RNA polymerase II. {ECO:0000269\|PubMed:12718890}.
Ptm:		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. {ECO:0000269\|PubMed:10757782, ECO:0000269\|PubMed:11112772, ECO:0000269\|PubMed:11145967, ECO:0000269\|PubMed:11575923, ECO:0000269\|PubMed:11809800, ECO:0000269\|PubMed:15564463, ECO:0000269\|PubMed:16327805, ECO:0000269\|PubMed:9199507}.
Similarity:		Belongs to the SPT5 family. {ECO:0000305}.
Sequence caution:		Sequence=BAD92494.1; Type=Erroneous initiation; Evidence={ECO:0000305};