UniProt Accession

 SPT5H_HUMAN; O00267; O43279; Q59G52; Q99639 

Genbank Protein ID

 U56402; Y12790; AB000516; AF040253; AB209257; BC024203 

Genbank Nucleotide ID

 AAC51102.1; CAA73326.1; BAA24075.1; AAD02179.1; BAD92494.1; AAH24203.1 

Protein Name

 Transcription elongation factor SPT5 

Protein Synonyms/Alias

 hSPT5; DRB sensitivity-inducing factor 160 kDa subunit; DSIF p160; DRB sensitivity-inducing factor large subunit; DSIF large subunit; Tat-cotransactivator 1 protein; Tat-CT1 protein 

Gene Name

 SUPT5H 

Gene Synonyms/Alias

 SPT5; SPT5H 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
143	ELGEYYMKKYAKSSV	ubiquitination	[1]
144	LGEYYMKKYAKSSVG	ubiquitination	[2]
199	TAISLMRKFIAYQFT	ubiquitination	[3, 4, 5]
213	TDTPLQIKSVVAPEH	ubiquitination	[2, 3, 5]
231	YIYVEAYKQTHVKQA	ubiquitination	[3, 5]
258	NQQMVPIKEMTDVLK	ubiquitination	[1]
306	SQNTISLKMIPRIDY	ubiquitination	[6, 7]
323	IKARMSLKDWFAKRK	ubiquitination	[2, 3, 4, 5]
328	SLKDWFAKRKKFKRP	acetylation	[8]
650	LVLAGGSKPRDVTNF	ubiquitination	[4, 9]
718	RISQGPYKGYIGVVK	ubiquitination	[3, 4, 5]
1037	LEPITPTKNNKVKVI	ubiquitination	[1, 2]
1040	ITPTKNNKVKVILGE	ubiquitination	[2]

Reference

 [1] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [2] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [3] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [4] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
 [5] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [6] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
 [7] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [8] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
 [9] A data set of human endogenous protein ubiquitination sites.
 Shi Y, Chan DW, Jung SY, Malovannaya A, Wang Y, Qin J.
 Mol Cell Proteomics. 2011 May;10(5):M110.002089. [PMID: 20972266] 

Functional Description

 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. 

Sequence Annotation

 DOMAIN 273 306 KOW 1.
 DOMAIN 420 451 KOW 2.
 DOMAIN 472 503 KOW 3.
 DOMAIN 594 627 KOW 4.
 DOMAIN 704 737 KOW 5.
 REPEAT 754 759 CTR1-1; approximate.
 REPEAT 760 765 CTR1-2.
 REPEAT 766 771 CTR1-3.
 REPEAT 772 778 CTR1-4.
 REPEAT 781 787 CTR1-5.
 REPEAT 788 794 CTR1-6.
 REPEAT 796 802 CTR1-7.
 REPEAT 803 809 CTR1-8.
 REPEAT 811 817 CTR1-9.
 REPEAT 844 851 CTR2-1.
 REPEAT 854 862 CTR2-2; approximate.
 REPEAT 863 869 CTR2-3; approximate.
 REPEAT 881 885 CTR2-4; half-length.
 REPEAT 896 902 CTR2-5; approximate.
 REPEAT 904 911 CTR2-6.
 REPEAT 916 921 CTR2-7; approximate.
 REPEAT 924 930 CTR2-8.
 REPEAT 932 939 CTR2-9.
 REPEAT 943 950 CTR2-10.
 REGION 176 270 Interaction with SUPT4H1.
 REGION 313 420 Interaction with RNA polymerase II.
 REGION 754 817 9 X 7 AA approximate tandem repeats of G-
 REGION 844 950 10 X 8 AA approximate tandem repeats of
 MOD_RES 666 666 Phosphoserine.
 MOD_RES 681 681 Asymmetric dimethylarginine; by PRMT1;
 MOD_RES 681 681 Omega-N-methylarginine; by PRMT1;
 MOD_RES 696 696 Asymmetric dimethylarginine; by PRMT1;
 MOD_RES 696 696 Omega-N-methylarginine; by PRMT1;
 MOD_RES 698 698 Asymmetric dimethylarginine; by PRMT1;
 MOD_RES 698 698 Omega-N-methylarginine; by PRMT1 and
 MOD_RES 698 698 Symmetric dimethylarginine; by PRMT5;
 MOD_RES 775 775 Phosphothreonine; by CDK9.
 MOD_RES 784 784 Phosphothreonine; by CDK9.
 MOD_RES 799 799 Phosphothreonine (By similarity).
 MOD_RES 1034 1034 Phosphothreonine.  

Keyword

 3D-structure; Activator; Alternative splicing; Complete proteome; Direct protein sequencing; Methylation; Nucleus; Phosphoprotein; Reference proteome; Repeat; Repressor; Transcription; Transcription regulation. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 1087 AA 

Protein Sequence

Gene Ontology

 GO:0032044; C:DSIF complex; IDA:UniProtKB.
 GO:0006370; P:7-methylguanosine mRNA capping; TAS:Reactome.
 GO:0007049; P:cell cycle; NAS:UniProtKB.
 GO:0006338; P:chromatin remodeling; NAS:UniProtKB.
 GO:0032785; P:negative regulation of DNA-dependent transcription, elongation; IDA:UniProtKB.
 GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IDA:UniProtKB.
 GO:0032786; P:positive regulation of DNA-dependent transcription, elongation; IDA:UniProtKB.
 GO:0016239; P:positive regulation of macroautophagy; IMP:BHF-UCL.
 GO:0032968; P:positive regulation of transcription elongation from RNA polymerase II promoter; IEA:InterPro.
 GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:UniProtKB.
 GO:0050434; P:positive regulation of viral transcription; TAS:Reactome.
 GO:0010033; P:response to organic substance; TAS:UniProtKB.
 GO:0045090; P:retroviral genome replication; NAS:UniProtKB.
 GO:0006368; P:transcription elongation from RNA polymerase II promoter; IDA:UniProtKB. 

Interpro

 IPR005824; KOW.
 IPR024945; Spt5_C_dom.
 IPR022581; Spt5_N.
 IPR017071; TF_Spt5.
 IPR005100; TF_Spt5_NGN-domain.
 IPR006645; Transcrpt_antiterm_NusG_N.
 IPR008991; Translation_prot_SH3-like. 

Pfam

 PF00467; KOW
 PF03439; Spt5-NGN
 PF11942; Spt5_N 

SMART

 SM01104; CTD
 SM00739; KOW
 SM00738; NGN 

PROSITE

  

PRINTS