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1  structure 3377  species 1  interaction 4732  sequences 15  architectures

Family: zf-RAG1 (PF10426)

Summary: Recombination-activating protein 1 zinc-finger domain

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Recombination-activating protein 1 zinc-finger domain Provide feedback

This is a C2-H2 zinc-finger domain closely resembling the classical TFIIIA-type zinc-finger, CX3FX5LX2-3H, despite having a valine and a tyrosine at the core instead of a phenylalanine and a leucine, hence CX3VX1LX2YX2H. The structure, nevertheless, contains the characteristic two-stranded beta-sheet and alpha-helix of a classical zinc-finger. The domain binds one zinc and, in complex with the zinc-RING-finger domain, helps to stabilise the whole of the dimerisation region of recombination activating protein 1 (RAG1) [1]. The function of the whole is to bind double-stranded DNA.

Literature references

  1. Bellon SF, Rodgers KK, Schatz DG, Coleman JE, Steitz TA; , Nat Struct Biol. 1997;4:586-591.: Crystal structure of the RAG1 dimerization domain reveals multiple zinc-binding motifs including a novel zinc binuclear cluster. PUBMED:9228952 EPMC:9228952


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR019485

During lymphocyte development, the genes encoding immunoglobulins and T-cell receptors are assembled from variable (V), diversity (D), and joining (J) gene segments. This combinatorial process, known as V(D)J recombination, allows the generation of an enormous range of binding specificities from a limited amount of genetic information. The V(D)J recombination-activating proteins 1 and 2 (RAG1 and RAG2) form a complex that initiates this process by binding to the conserved recombination signal sequences (RSS) and introducing a double-strand break between the RSS and the adjacent coding segment. These breaks are generated in two steps, nicking of one strand (hydrolysis), followed by hairpin formation (transesterification). RAG1/2 has also been shown to function as a transposase in vitro, and to possess RSS-independent endonuclease activity (end processing) and hairpin opening. RAG1 alone can bind to RSS but stable, efficient binding requires RAG2. All known catalytic activities require the presence of both proteins. For more information see [PUBMED:18066091].

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.

C2H2-type (classical) zinc fingers (Znf) were the first class to be characterised. They contain a short beta hairpin and an alpha helix (beta/beta/alpha structure), where a single zinc atom is held in place by Cys(2)His(2) (C2H2) residues in a tetrahedral array. C2H2 Znf's can be divided into three groups based on the number and pattern of fingers: triple-C2H2 (binds single ligand), multiple-adjacent-C2H2 (binds multiple ligands), and separated paired-C2H2 [PUBMED:11361095]. C2H2 Znf's are the most common DNA-binding motifs found in eukaryotic transcription factors, and have also been identified in prokaryotes [PUBMED:10664601]. Transcription factors usually contain several Znf's (each with a conserved beta/beta/alpha structure) capable of making multiple contacts along the DNA, where the C2H2 Znf motifs recognise DNA sequences by binding to the major groove of DNA via a short alpha-helix in the Znf, the Znf spanning 3-4 bases of the DNA [PUBMED:10940247]. C2H2 Znf's can also bind to RNA and protein targets [PUBMED:18253864].

This entry represents a C2H2-type zinc-finger domain found in the RAG1 protein. The structure contains the characteristic two-stranded beta-sheet and alpha-helix of a classical zinc-finger. The domain binds one zinc and, in complex with an adjacent RING-type zinc finger domain, helps to stabilise the whole of the dimerisation region of recombination activating protein 1 (RAG1) [PUBMED:9228952]. The function of the whole is to bind double-stranded DNA.

Gene Ontology

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Domain organisation

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Alignments

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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.

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(53)
Full
(4732)
Representative proteomes NCBI
(4638)
Meta
(0)
RP15
(1)
RP35
(2)
RP55
(4)
RP75
(20)
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Format an alignment

  Seed
(53)
Full
(4732)
Representative proteomes NCBI
(4638)
Meta
(0)
RP15
(1)
RP35
(2)
RP55
(4)
RP75
(20)
Alignment:
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Sequence:
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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
(53)
Full
(4732)
Representative proteomes NCBI
(4638)
Meta
(0)
RP15
(1)
RP35
(2)
RP55
(4)
RP75
(20)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download    
Gzipped 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.

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 HMMER3.

Pfam alignments:

HMM logo

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Trees

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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: Gene3D, pdb_1rmd
Previous IDs: none
Type: Domain
Author: Finn RD, Coggill PC
Number in seed: 53
Number in full: 4732
Average length of the domain: 29.20 aa
Average identity of full alignment: 66 %
Average coverage of the sequence by the domain: 5.20 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 20.7 20.7
Trusted cut-off 21.0 21.0
Noise cut-off 20.4 20.6
Model length: 30
Family (HMM) version: 4
Download: download the raw HMM for this family

Species distribution

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Interactions

There is 1 interaction for this family. More...

zf-C3HC4

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-RAG1 domain has been found. There are 1 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 seqence.

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