Summary: C2HC Zing finger domain
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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
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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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Pfam Clan
This family is a member of clan C2H2-zf (CL0361), which has the following description:
Superfamily of classical and closely related C2H2 or beta-beta-alpha zinc finger DNA-binding domains.
The clan contains the following 52 members:
ARS2 DUF3449 GAGA Hat1_N Integrase_H2C2 KN17_SH3 Nairovirus_M ROS_MUCR Sgf11 UBZ_FAAP20 Zap1_zf2 zf-AD zf-BED zf-C2H2 zf-C2H2_10 zf-C2H2_11 zf-C2H2_2 zf-C2H2_3 zf-C2H2_3rep zf-C2H2_4 zf-C2H2_6 zf-C2H2_7 zf-C2H2_8 zf-C2H2_9 zf-C2H2_aberr zf-C2H2_jaz zf-C2HC_2 zf-C2HE zf-CRD zf-DBF zf-Di19 zf-H2C2 zf-H2C2_2 zf-H2C2_5 zf-H3C2 zf-LYAR zf-met zf-met2 zf-MYST zf-RAG1 zf-U1 zf-U11-48K zf-WRNIP1_ubi zf_C2H2_10 zf_C2H2_13 zf_C2H2_6 zf_C2H2_ZHX zf_C2HC_14 zf_Hakai zf_UBZ zf_ZIC Zn-C2H2_12Alignments
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) |
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RP15 (32) |
RP35 (119) |
RP55 (336) |
RP75 (574) |
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PP/heatmap | 1 |
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key:
available,
not generated,
— not available.
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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) |
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RP15 (32) |
RP35 (119) |
RP55 (336) |
RP75 (574) |
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Raw Stockholm | |||||||||
Gzipped |
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
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
HMM build commands: |
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 47079205 -E 1000 --cpu 4 HMM pfamseq
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Model details: |
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Model length: | 33 | ||||||||||||
Family (HMM) version: | 2 | ||||||||||||
Download: | download the raw HMM for this family |
Species distribution
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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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