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2  structures 149  species 0  interactions 572  sequences 13  architectures

Family: zf_C2HC_14 (PF18574)

Summary: C2HC Zing finger domain

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This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

C2HC Zing finger domain Provide feedback

This is a zinc finger domain together with a linker region found in RNF125, a small protein (25kD) that contains a RING domain, three zinc fingers (ZnFs) and a ubiquitin interacting motif (UIM). The C2HC ZnF plays an essential role in the interaction of RNF125 with the E2 UbcH5a, which originates from the requirement of the C2HC-ZnF for the structural stability of the RING domain. A mutation at one of the contact residues in the C2HC-ZnF, a highly conserved M112, resulted in the loss of ubiquitin ligase activity. Furthermore, mutations at the Zn2+ chelating cysteine residues, C100 and C103 of this domain resulted in a loss of activity [1].

Literature references

  1. Bijlmakers MJ, Teixeira JM, Boer R, Mayzel M, Puig-Sarries P, Karlsson G, Coll M, Pons M, Crosas B;, Sci Rep. 2016;6:29232.: A C2HC zinc finger is essential for the RING-E2 interaction of the ubiquitin ligase RNF125. PUBMED:27411375 EPMC:27411375


This tab holds annotation information from the InterPro database.

InterPro entry IPR034734

This entry includes the C2HC RNF-type zinc finger.

Ubiquitination is a post-translational modification that mediates the covalent attachment of ubiquitin (Ub), a small, highly conserved, cytoplasmic protein of 76 amino acid residues, to target proteins. This conjugation is catalyzed by the sequential action of three enzymes: Ub-activating (E1) enzyme, Ub-conjugating (E2) enzyme and Ub ligase (E3). A large number of RING finger (RNF) proteins are present in eukaryotic cells and the majority of them are believed to act as E3 ubiquitin ligases. The closely related proteins RNF125/TRAC-1, RNF114 (also known as Zpf313), RNF138 (or NARF) and RNF166 contain, apart from the RING domain, a C2HC (Cys2-His-Cys)- and two C2H2 (Cys2-His2)-type zinc fingers, as well as an ubiquitin interacting motif (UIM) [PUBMED:17990982, PUBMED:25165885, PUBMED:27195665, PUBMED:26456228].

Some proteins known to contain a C2HC RNF-type zinc finger are listed below:

  • Mammalian RNF125/T-cell RING protein in activation 1 (TRAC-1)/, a positive regulator of T-cell activation. It negatively regulates RIG-1 mediated antiviral activity via conjugating ubiquitin chains to RIG-1 and MDA5, leading to their degradation by the proteasome.
  • Vertebrate RNF114, acts as negative regulator of NF-kappaB-dependent transcription. It interacts with A20 in T cells and modulates A20 ubiquitylation.
  • Vertebrate RNF138, likely involved in regulating homologous recombination repair pathway.
  • Vertebrate RNF166, potentiates the RNA virus-induced production of IFN-beta via enhancing the ubiquitination of TRAF3 and TRAF6.

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

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the UniProtKB sequence database, the NCBI sequence database, and our metagenomics sequence database. More...

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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

  Seed
(19)
Full
(572)
Representative proteomes UniProt
(870)
NCBI
(1471)
Meta
(0)
RP15
(32)
RP35
(119)
RP55
(336)
RP75
(574)
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PP/heatmap 1 View               

1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(19)
Full
(572)
Representative proteomes UniProt
(870)
NCBI
(1471)
Meta
(0)
RP15
(32)
RP35
(119)
RP55
(336)
RP75
(574)
Alignment:
Format:
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Sequence:
Gaps:
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Download options

We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(19)
Full
(572)
Representative proteomes UniProt
(870)
NCBI
(1471)
Meta
(0)
RP15
(32)
RP35
(119)
RP55
(336)
RP75
(574)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download    
Gzipped Download   Download   Download   Download   Download   Download   Download   Download    

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

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's seed alignment. 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 alignment.

Note: You can also download the data file for the tree.

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 View help on the curation process

Seed source: ECOD:EUF08696
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: El-Gebali S
Number in seed: 19
Number in full: 572
Average length of the domain: 32.70 aa
Average identity of full alignment: 46 %
Average coverage of the sequence by the domain: 14.33 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 47079205 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 25.0 25.0
Trusted cut-off 25.2 26.5
Noise cut-off 24.6 24.6
Model length: 33
Family (HMM) version: 2
Download: download the raw HMM for this family

Species distribution

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Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence

Selections

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This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

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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 zf_C2HC_14 domain has been found. There are 2 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.

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