Summary

Transcription factor S-II (TFIIS)

No Pfam abstract.

InterPro entry IPR001222

Zinc finger (Znf) domains are relatively small protein motifs which contain multiple finger-like protrusions that make tandem contacts with their target molecule. Some of these domains bind zinc, but many do not; instead binding other metals such as iron, or no metal at all. For example, some family members form salt bridges to stabilise the finger-like folds. They were first identified as a DNA-binding motif in transcription factor TFIIIA from Xenopus laevis (African clawed frog), however they are now recognised to bind DNA, RNA, protein and/or lipid substrates PUBMED:10529348, PUBMED:15963892, PUBMED:15718139, PUBMED:17210253, PUBMED:12665246. Their binding properties depend on the amino acid sequence of the finger domains and of the linker between fingers, as well as on the higher-order structures and the number of fingers. Znf domains are often found in clusters, where fingers can have different binding specificities. There are many superfamilies of Znf motifs, varying in both sequence and structure. They display considerable versatility in binding modes, even between members of the same class (e.g. some bind DNA, others protein), suggesting that Znf motifs are stable scaffolds that have evolved specialised functions. For example, Znf-containing proteins function in gene transcription, translation, mRNA trafficking, cytoskeleton organisation, epithelial development, cell adhesion, protein folding, chromatin remodelling and zinc sensing, to name but a few PUBMED:11179890. Zinc-binding motifs are stable structures, and they rarely undergo conformational changes upon binding their target.

This entry represents a zinc finger motif found in transcription factor IIs (TFIIS). In eukaryotes the initiation of transcription of protein encoding genes by polymerase II (Pol II) is modulated by general and specific transcription factors. The general transcription factors operate through common promoters elements (such as the TATA box). At least eight different proteins associate to form the general transcription factors: TFIIA, -IIB, -IID, -IIE, -IIF, -IIG, -IIH and -IIS PUBMED:3346229. During mRNA elongation, Pol II can encounter DNA sequences that cause reverse movement of the enzyme. Such backtracking involves extrusion of the RNA 3'-end into the pore, and can lead to transcriptional arrest. Escape from arrest requires cleavage of the extruded RNA with the help of TFIIS, which induces mRNA cleavage by enhancing the intrinsic nuclease activity of RNA polymerase (Pol) II, past template-encoded pause sites PUBMED:10723030. TFIIS extends from the polymerase surface via a pore to the internal active site. Two essential and invariant acidic residues in a TFIIS loop complement the Pol II active site and could position a metal ion and a water molecule for hydrolytic RNA cleavage. TFIIS also induces extensive structural changes in Pol II that would realign nucleic acids in the active centre.

TFIIS is a protein of about 300 amino acids. It contains three regions: a variable N-terminal domain not required for TFIIS activity; a conserved central domain required for Pol II binding; and a conserved C-terminal C4-type zinc finger essential for RNA cleavage. The zinc finger folds in a conformation termed a zinc ribbon PUBMED:7626141 characterised by a three-stranded antiparallel beta-sheet and two beta-hairpins. A backbone model for Pol II-TFIIS complex was obtained from X-ray analysis. It shows that a beta hairpin protrudes from the zinc finger and complements the pol II active site PUBMED:12914699.

Some viral proteins also contain the TFIIS zinc ribbon C-terminal domain. The Vaccinia virus protein, unlike its eukaryotic homologue, is an integral RNA polymerase subunit rather than a readily separable transcription factor PUBMED:2398897.

More information about these proteins can be found at Protein of the Month: Zinc Fingers PUBMED:.

Clan

This family is a member of clan Zn_Beta_Ribbon (CL0167), which contains the following 30 members:

A2L_zn_ribbon Auto_anti-p27 Baculo_LEF5_C CxxC_CxxC_SSSS DNA_RNApol_7kD DUF1407 DUF1610 DUF1936 DUF2387 Elf1 GATA Ogr_Delta PhnA_Zn_Ribbon Prim_Zn_Ribbon Ribosomal_S27 Ribosomal_S27e RNA_POL_M_15KD RRN7 Spt4 TF_Zn_Ribbon TFIIS_C Topo_Zn_Ribbon Transposase_35 Trm112p UPF0547 zf-C4_Topoisom zf-CHC2 zf-dskA_traR zf-GRF zf-NADH-PPase

Gene Ontology

Molecular function	transcription regulator activity (GO:0030528)
	zinc ion binding (GO:0008270)
	nucleic acid binding (GO:0003676)
Biological process	regulation of transcription (GO:0045449)

Internal database links

SCOOP:

zf-AN1 zf-C4_Topoisom zf-DNL Desulfoferrod_N Transposase_35 zf-HYPF DUF1610 C1_4 PADR1 TF_Zn_Ribbon PhnA_Zn_Ribbon Rubredoxin NOB1_Zn_bind zf-LYAR A2L_zn_ribbon zf-DNA_Pol Opy2 DUF2387 FYDLN_acid CxxC_CxxC_SSSS DUF2072 DUF2082 DUF2296 DUF2318 XPA_N

External database links

HOMSTRAD:	TFIIS
PANDIT:	PF01096
PROSITE:	PDOC00383
SCOP:	1tfi
SYSTERS:	TFIIS_C

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Alignments

There are various ways to view or download the sequence alignments that we store. You can use a sequence viewer to look at either the seed or full alignment for the family, or you can look at a plain text version of the sequence in a variety of different formats. More...

View options

Alignment:	Seed (110) Full (833) NCBI (1328) Metagenomics (290)
Viewer:

Formatting options

Alignment:	Seed (110) Full (833)
Format:
Order:	Tree Alphabetical
Sequence:	Inserts lower case All upper case
Gaps:
Download/view:	Download View

Download options

Very large alignments can often cause problems for the formatting tool above. If you find that downloading or viewing a large alignment is problematic, you can also download a gzip-compressed, Stockholm-format file containing the seed or full alignment for this family.

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

The main seed and full alignments are generated using sequences from the UniProt sequence database. However, we also generate alignments using sequences from the NCBI sequence database and the "metaseq" metagenomics dataset.

You can view alignments from these two additional datasets using the form above, or you can download alignments of NCBI or metagenomics sequences, as gzip-compressed files.

Pfam alignments:	Seed (110) Full (833) NCBI (1328) Metagenomics (290)
Full length sequences	Full-sequences (833)

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER2.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed or full alignments.

Note: You can also download the data files for the seed, full, NCBI or metagenomics trees.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation

Seed source:

Prosite

Previous IDs:

TFIIS;

Type:

Domain

Author:

Finn RD, Bateman A

Number in seed:

110

Number in full:

833

Average length of the domain:

39.10 aa

Average identity of full alignment:

41 %

Average coverage of the sequence by the domain:

20.58 %

HMM information

HMM build commands:

build method: hmmbuild -o /dev/null HMM SEED

search method: hmmsearch -Z 9421015 -E 1000 HMM pfamseq

Model details:

Parameter	Sequence	Domain
Gathering cut-off	20.7	20.7
Trusted cut-off	20.7	21.3
Noise cut-off	20.6	20.6

Model length:

39

Family (HMM) version:

11

Download:

download the raw HMM for this family

Species distribution

Tree controls

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The tree shows the occurrence of this domain across different species. More...

Species trees

We show the species tree in one of two ways. For smaller trees we try to show an interactive representation, which allows you to select specific nodes in the tree and view them as an alignment or as a set of Pfam domain graphics.

Unfortunately we have found that there are problems viewing the interactive tree when the it becomes larger than a certain limit. Furthermore, we have found that Internet Explorer can become unresponsive when viewing some trees, regardless of their size. We therefore show a text representation of the species tree when the size is above a certain limit or if you are using Internet Explorer to view the site.

If you are using IE you can still load the interactive tree by clicking the "Generate interactive tree" button, but please be aware of the potential problems that the interactive species tree can cause.

Interactive tree

For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.

We also count the number of unique sequences on which each domain is found, which is shown in green. Note that a domain may appear multiple times on the same sequence, leading to the difference between these two numbers.

Finally, we group sequences from the same organism according to the NCBI code that is assigned by UniProt, allowing us to count the number of distinct sequences on which the domain is found. This value is shown in the pink boxes.

We use the NCBI species tree to group organisms according to their taxonomy and this forms the structure of the displayed tree. Note that in some cases the trees are too large (have too many nodes) to allow us to build an interactive tree, but in most cases you can still view the tree in a plain text, non-interactive representation. Those species which are represented in the seed alignment for this domain are highlighted.

You can use the tree controls to manipulate how the interactive tree is displayed:

show/hide the summary boxes
highlight species that are represented in the seed alignment
expand/collapse the tree or expand it to a given depth
select a sub-tree or a set of species within the tree and view them graphically or as an alignment
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Interactions

There are 11 interactions for this family. More...

RNA_pol_Rpb1_6 RNA_pol_Rpb1_5 RNA_POL_M_15KD RNA_pol_Rpb2_6 RNA_pol_Rpb2_2 RNA_pol_Rpb2_1 RNA_pol_Rpb1_2 RNA_pol_Rpb2_4 RNA_pol_Rpb1_4 RNA_pol_Rpb2_3 RNA_pol_Rpb1_3

Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the TFIIS_C domain has been found.

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Family: TFIIS_C (PF01096)

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