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V(D)J recombinase-1 (V(D)J recombination-activating protein-1, RING finger protein 74, RAG1)
Function:
- role in V(D)J recombination
- RAG1/RAG2 complex initiates V(D)J recombination by binding to conserved recombination signal sequences (RSS) & introducing a double-strand break between the RSS & the adjacent coding segment
- breaks are generated in 2 steps, nicking of one strand (hydrolysis), followed by hairpin formation (transesterification)
- RAG1/RAG2 complex functions as a transposase in vitro, & possesses RSS-independent endonuclease activity (end processing) & hairpin opening.
- RAG1 alone can bind to RSS but stable, efficient binding requires RAG2
- all known catalytic activities require the presence of both proteins
- established hallmarks of the Ig or TCR recombinase system include site specificity organized around signal sequences, N-region addition, & nibbling at the coding sequence junctions
- in connection with RAG2, RAG1 confers V(D)J recombinase activity on virtually any cell type [2]
Cofactor: binds 1 Mg+2 or Mn+2 per subunit
Structure:
- specific binding to the nonamer RSS motif is mediated by the nonamer binding domain (NBD)
- contains 1 NBD (nonamer binding) DNA-binding domain
- contains 1 RING-type Zn+2 finger
Compartment: nucleus
Expression: maturing lymphoid cells
Pathology:
- defects in RAG1 are a cause of:
a) severe combined immunodeficiency, B-cell-negative
b) Omenn syndrome
Related
recombination-activating gene-1
General
recombinase
ring finger protein
Properties
SIZE: entity length = 1043 aa
MW = 119 kD
COMPARTMENT: cell nucleus
CELL: lymphocyte
MOTIF: importin alpha-1 interaction {1-288}
RING-finger {293-332}
EFFECTOR-BOUND: Zn+2
FOR-BINDING-OF: DNA motif
DNA-binding motif
SITE: 392-447
glutamate residue {E965}
MISC-INFO: CONSENSUS-SIGNAL
:SEQUENCE CACTGTC
CACAGTC
RECOMBINASE-SIGNAL
:SEQUENCE TTTTCCTTA
Database Correlations
OMIM correlations
MORBIDMAP 179615
UniProt P15918
Pfam PF00097
Kegg hsa:5896
References
- Aplan PD, Lombardi DP, Ginsberg AM, Cossman J, Bertness VL,
Kirsch IR.
Disruption of the human SCL locus by "illegitimate" V-(D)-J
recombinase activity.
Science. 1990 Dec 7;250(4986):1426-9.
PMID: 2255914
- Jackson SP, Jeggo PA.
DNA double-strand break repair and V(D)J recombination:
involvement of DNA-PK.
Trends Biochem Sci. 1995 Oct;20(10):412-5. Review.
PMID: 8533154
- RAG1base; Note: RAG1 deficiency database
http://bioinf.uta.fi/RAG1base/
- GeneReviews
https://www.genecards.org/cgi-bin/carddisp.pl?gene=RAG1
- UniProt :accession P15918
Component-of
RAG1/RAG2 complex