RAG1_MOUSE
ID RAG1_MOUSE Reviewed; 1040 AA.
AC P15919; A2AVN8;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 195.
DE RecName: Full=V(D)J recombination-activating protein 1;
DE Short=RAG-1;
DE Includes:
DE RecName: Full=Endonuclease RAG1;
DE EC=3.1.-.-;
DE Includes:
DE RecName: Full=E3 ubiquitin-protein ligase RAG1;
DE EC=2.3.2.27;
DE AltName: Full=RING-type E3 ubiquitin transferase RAG1 {ECO:0000305};
GN Name=Rag1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RX PubMed=2598259; DOI=10.1016/0092-8674(89)90760-5;
RA Schatz D.G., Oettinger M.A., Baltimore D.;
RT "The V(D)J recombination activating gene, RAG-1.";
RL Cell 59:1035-1048(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP DISRUPTION PHENOTYPE.
RX PubMed=1547488; DOI=10.1016/0092-8674(92)90030-g;
RA Mombaerts P., Iacomini J., Johnson R.S., Herrup K., Tonegawa S.,
RA Papaioannou V.E.;
RT "RAG-1-deficient mice have no mature B and T lymphocytes.";
RL Cell 68:869-877(1992).
RN [6]
RP SUBCELLULAR LOCATION.
RX PubMed=8284210; DOI=10.1093/nar/21.24.5644;
RA Sadofsky M.J., Hesse J.E., McBlane J.F., Gellert M.;
RT "Expression and V(D)J recombination activity of mutated RAG-1 proteins.";
RL Nucleic Acids Res. 21:5644-5650(1993).
RN [7]
RP FUNCTION, AND INTERACTION WITH RAG2.
RX PubMed=8521468; DOI=10.1016/0092-8674(95)90116-7;
RA McBlane J.F., van Gent D.C., Ramsden D.A., Romeo C., Cuomo C.A.,
RA Gellert M., Oettinger M.A.;
RT "Cleavage at a V(D)J recombination signal requires only RAG1 and RAG2
RT proteins and occurs in two steps.";
RL Cell 83:387-395(1995).
RN [8]
RP FUNCTION, AND IDENTIFICATION IN THE RAG COMPLEX.
RX PubMed=9094713; DOI=10.1016/s0092-8674(00)80181-6;
RA Agrawal A., Schatz D.G.;
RT "RAG1 and RAG2 form a stable postcleavage synaptic complex with DNA
RT containing signal ends in V(D)J recombination.";
RL Cell 89:43-53(1997).
RN [9]
RP IDENTIFICATION IN THE RAG COMPLEX.
RX PubMed=9184213; DOI=10.1093/emboj/16.10.2665;
RA van Gent D.C., Hiom K., Paull T.T., Gellert M.;
RT "Stimulation of V(D)J cleavage by high mobility group proteins.";
RL EMBO J. 16:2665-2670(1997).
RN [10]
RP FUNCTION AS ENDONUCLEASE, DNA-BINDING, COFACTOR, AND MUTAGENESIS OF
RP GLU-597; ASP-600; ASP-708; GLU-709; GLU-719; ASP-792; GLU-811; GLU-959;
RP GLU-962 AND ASP-986.
RX PubMed=10601032; DOI=10.1101/gad.13.23.3059;
RA Landree M.A., Wibbenmeyer J.A., Roth D.B.;
RT "Mutational analysis of RAG1 and RAG2 identifies three catalytic amino
RT acids in RAG1 critical for both cleavage steps of V(D)J recombination.";
RL Genes Dev. 13:3059-3069(1999).
RN [11]
RP MUTAGENESIS OF ASP-600; ASP-708 AND GLU-962.
RX PubMed=10601033; DOI=10.1101/gad.13.23.3070;
RA Kim D.R., Dai Y., Mundy C.L., Yang W., Oettinger M.A.;
RT "Mutations of acidic residues in RAG1 define the active site of the V(D)J
RT recombinase.";
RL Genes Dev. 13:3070-3080(1999).
RN [12]
RP FUNCTION, AND MUTAGENESIS OF ASP-600 AND ASP-708.
RX PubMed=10678172; DOI=10.1016/s1097-2765(00)80406-2;
RA Fugmann S.D., Villey I.J., Ptaszek L.M., Schatz D.G.;
RT "Identification of two catalytic residues in RAG1 that define a single
RT active site within the RAG1/RAG2 protein complex.";
RL Mol. Cell 5:97-107(2000).
RN [13]
RP FUNCTION AS AN E3 UBIQUITIN LIGASE.
RX PubMed=12629039; DOI=10.1101/gad.1058103;
RA Yurchenko V., Xue Z., Sadofsky M.;
RT "The RAG1 N-terminal domain is an E3 ubiquitin ligase.";
RL Genes Dev. 17:581-585(2003).
RN [14]
RP FUNCTION, AUTOUBIQUITINATION, UBIQUITINATION AT LYS-233, RING-TYPE
RP ZINC-FINGER, AND MUTAGENESIS OF LYS-233 AND CYS-325.
RX PubMed=14671314; DOI=10.1073/pnas.2637012100;
RA Jones J.M., Gellert M.;
RT "Autoubiquitylation of the V(D)J recombinase protein RAG1.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:15446-15451(2003).
RN [15]
RP FUNCTION, AND MUTAGENESIS OF TYR-707; TYR-725; TRP-760; TRP-893; TYR-935;
RP TRP-956; GLU-962; PHE-971; ARG-972 AND LYS-973.
RX PubMed=17028591; DOI=10.1038/nsmb1154;
RA Lu C.P., Sandoval H., Brandt V.L., Rice P.A., Roth D.B.;
RT "Amino acid residues in Rag1 crucial for DNA hairpin formation.";
RL Nat. Struct. Mol. Biol. 13:1010-1015(2006).
RN [16]
RP FUNCTION.
RX PubMed=19524534; DOI=10.1016/j.molcel.2009.05.011;
RA Shimazaki N., Tsai A.G., Lieber M.R.;
RT "H3K4me3 stimulates the V(D)J RAG complex for both nicking and hairpinning
RT in trans in addition to tethering in cis: implications for
RT translocations.";
RL Mol. Cell 34:535-544(2009).
RN [17]
RP FUNCTION, AND AUTOUBIQUITINATION.
RX PubMed=19118899; DOI=10.1016/j.molimm.2008.11.009;
RA Simkus C., Makiya M., Jones J.M.;
RT "Karyopherin alpha 1 is a putative substrate of the RAG1 ubiquitin
RT ligase.";
RL Mol. Immunol. 46:1319-1325(2009).
RN [18]
RP FUNCTION, AND MUTAGENESIS OF ASP-708.
RX PubMed=19448632; DOI=10.1038/ni.1735;
RA Hewitt S.L., Yin B., Ji Y., Chaumeil J., Marszalek K., Tenthorey J.,
RA Salvagiotto G., Steinel N., Ramsey L.B., Ghysdael J., Farrar M.A.,
RA Sleckman B.P., Schatz D.G., Busslinger M., Bassing C.H., Skok J.A.;
RT "RAG-1 and ATM coordinate monoallelic recombination and nuclear positioning
RT of immunoglobulin loci.";
RL Nat. Immunol. 10:655-664(2009).
RN [19]
RP FUNCTION AS AN E3 UBIQUITIN LIGASE, AND MUTAGENESIS OF HIS-307 AND CYS-325.
RX PubMed=20122409; DOI=10.1016/j.molcel.2009.12.035;
RA Grazini U., Zanardi F., Citterio E., Casola S., Goding C.R., McBlane F.;
RT "The RING domain of RAG1 ubiquitylates histone H3: a novel activity in
RT chromatin-mediated regulation of V(D)J joining.";
RL Mol. Cell 37:282-293(2010).
RN [20]
RP FUNCTION, AND INTERACTION WITH DCAF1.
RX PubMed=22157821; DOI=10.1038/emboj.2011.455;
RA Kassmeier M.D., Mondal K., Palmer V.L., Raval P., Kumar S., Perry G.A.,
RA Anderson D.K., Ciborowski P., Jackson S., Xiong Y., Swanson P.C.;
RT "VprBP binds full-length RAG1 and is required for B-cell development and
RT V(D)J recombination fidelity.";
RL EMBO J. 31:945-958(2012).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 265-380 IN COMPLEX WITH ZINC, AND
RP SUBUNIT.
RX PubMed=9228952; DOI=10.1038/nsb0797-586;
RA Bellon S.F., Rodgers K.K., Schatz D.G., Coleman J.E., Steitz T.A.;
RT "Crystal structure of the RAG1 dimerization domain reveals multiple zinc-
RT binding motifs including a novel zinc binuclear cluster.";
RL Nat. Struct. Biol. 4:586-591(1997).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 389-464 IN COMPLEX WITH DNA
RP NONAMER, FUNCTION AS ENDONUCLEASE, DNA-BINDING, DOMAIN NBD, INTERACTION
RP WITH RAG2, AND MUTAGENESIS OF ARG-391; ARG-393; ARG-401; ARG-402; LYS-405;
RP HIS-406; ARG-407; ASN-443 AND HIS-445.
RX PubMed=19396172; DOI=10.1038/nsmb.1593;
RA Yin F.F., Bailey S., Innis C.A., Ciubotaru M., Kamtekar S., Steitz T.A.,
RA Schatz D.G.;
RT "Structure of the RAG1 nonamer binding domain with DNA reveals a dimer that
RT mediates DNA synapsis.";
RL Nat. Struct. Mol. Biol. 16:499-508(2009).
CC -!- FUNCTION: Catalytic component of the RAG complex, a multiprotein
CC complex that mediates the DNA cleavage phase during V(D)J
CC recombination. V(D)J recombination assembles a diverse repertoire of
CC immunoglobulin and T-cell receptor genes in developing B and T-
CC lymphocytes through rearrangement of different V (variable), in some
CC cases D (diversity), and J (joining) gene segments. In the RAG complex,
CC RAG1 mediates the DNA-binding to the conserved recombination signal
CC sequences (RSS) and catalyzes the DNA cleavage activities by
CC introducing a double-strand break between the RSS and the adjacent
CC coding segment. RAG2 is not a catalytic component but is required for
CC all known catalytic activities. DNA cleavage occurs in 2 steps: a first
CC nick is introduced in the top strand immediately upstream of the
CC heptamer, generating a 3'-hydroxyl group that can attack the
CC phosphodiester bond on the opposite strand in a direct
CC transesterification reaction, thereby creating 4 DNA ends: 2 hairpin
CC coding ends and 2 blunt, 5'-phosphorylated ends. The chromatin
CC structure plays an essential role in the V(D)J recombination reactions
CC and the presence of histone H3 trimethylated at 'Lys-4' (H3K4me3)
CC stimulates both the nicking and haipinning steps. The RAG complex also
CC plays a role in pre-B cell allelic exclusion, a process leading to
CC expression of a single immunoglobulin heavy chain allele to enforce
CC clonality and monospecific recognition by the B-cell antigen receptor
CC (BCR) expressed on individual B-lymphocytes. The introduction of DNA
CC breaks by the RAG complex on one immunoglobulin allele induces ATM-
CC dependent repositioning of the other allele to pericentromeric
CC heterochromatin, preventing accessibility to the RAG complex and
CC recombination of the second allele. In addition to its endonuclease
CC activity, RAG1 also acts as an E3 ubiquitin-protein ligase that
CC mediates monoubiquitination of histone H3. Histone H3
CC monoubiquitination is required for the joining step of V(D)J
CC recombination. Mediates polyubiquitination of KPNA1.
CC {ECO:0000269|PubMed:10601032, ECO:0000269|PubMed:10678172,
CC ECO:0000269|PubMed:12629039, ECO:0000269|PubMed:14671314,
CC ECO:0000269|PubMed:17028591, ECO:0000269|PubMed:19118899,
CC ECO:0000269|PubMed:19396172, ECO:0000269|PubMed:19448632,
CC ECO:0000269|PubMed:19524534, ECO:0000269|PubMed:20122409,
CC ECO:0000269|PubMed:22157821, ECO:0000269|PubMed:2598259,
CC ECO:0000269|PubMed:8521468, ECO:0000269|PubMed:9094713}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.27;
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:10601032};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:10601032};
CC Note=Binds 1 divalent metal cation per subunit. Mg(2+) or Mn(2+).
CC {ECO:0000269|PubMed:10601032};
CC -!- SUBUNIT: Homodimer. Component of the RAG complex composed of core
CC components RAG1 and RAG2, and associated component HMGB1 or HMGB2.
CC Interacts with DCAF1, leading to recruitment of the CUL4A-RBX1-DDB1-
CC DCAF1/VPRBP complex to ubiquitinate proteins and limit error-prone
CC repair during V(D)J recombination. {ECO:0000269|PubMed:19396172,
CC ECO:0000269|PubMed:22157821, ECO:0000269|PubMed:8521468,
CC ECO:0000269|PubMed:9094713, ECO:0000269|PubMed:9184213,
CC ECO:0000269|PubMed:9228952}.
CC -!- INTERACTION:
CC P15919; P15919: Rag1; NbExp=4; IntAct=EBI-7602168, EBI-7602168;
CC P15919; P21784: Rag2; NbExp=4; IntAct=EBI-7602168, EBI-7602123;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00820,
CC ECO:0000269|PubMed:8284210}.
CC -!- TISSUE SPECIFICITY: Maturing lymphoid cells and central nervous system.
CC -!- DOMAIN: The RING-type zinc finger mediates the E3 ubiquitin-protein
CC ligase activity. {ECO:0000269|PubMed:19396172}.
CC -!- DOMAIN: The NBD (nonamer binding) DNA-binding domain mediates the
CC specific binding to the nonamer RSS motif by forming a tightly
CC interwoven homodimer that binds and synapses 2 nonamer elements, with
CC each NBD making contact with both DNA molecules. Each RSS is composed
CC of well-conserved heptamer (consensus 5'-CACAGTG-3') and nonamer
CC (consensus 5'-ACAAAAACC-3') sequences separated by a spacer of either
CC 12 bp or 23 bp. {ECO:0000255|PROSITE-ProRule:PRU00820,
CC ECO:0000269|PubMed:19396172}.
CC -!- PTM: Autoubiquitinated in the presence of CDC34/UBCH3.
CC {ECO:0000269|PubMed:14671314, ECO:0000269|PubMed:19118899}.
CC -!- DISRUPTION PHENOTYPE: Mice display a severe combined immunodeficiency
CC phenotype. The have a small lymphoid organs that do not contain mature
CC B and T-lymphocytes. The arrest of B- and T-cell differentiation occurs
CC at an early stage and correlates with the inability to perform V(D)J
CC recombination. The frequency of homologous immunoglobulin pairing is
CC much lower. No obvious neuroanatomical or behavioral abnormalities have
CC been observed. {ECO:0000269|PubMed:1547488}.
CC -!- SIMILARITY: Belongs to the RAG1 family. {ECO:0000255|PROSITE-
CC ProRule:PRU00820}.
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DR EMBL; M29475; AAA40028.1; -; mRNA.
DR EMBL; AL929569; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466519; EDL27655.1; -; Genomic_DNA.
DR EMBL; BC138342; AAI38343.1; -; mRNA.
DR CCDS; CCDS16463.1; -.
DR PIR; B33754; B33754.
DR RefSeq; NP_033045.2; NM_009019.2.
DR RefSeq; XP_006499075.1; XM_006499012.1.
DR PDB; 1RMD; X-ray; 2.10 A; A=265-380.
DR PDB; 3GNA; X-ray; 2.40 A; A=389-464.
DR PDB; 3GNB; X-ray; 3.00 A; A=389-464.
DR PDB; 4WWX; X-ray; 3.20 A; B/E=392-1008.
DR PDB; 5ZDZ; X-ray; 2.80 A; A/C=384-1008.
DR PDB; 5ZE0; X-ray; 2.75 A; A/C=384-1008.
DR PDB; 5ZE1; X-ray; 3.00 A; A/C=384-1008.
DR PDB; 5ZE2; X-ray; 3.30 A; A/C=384-1008.
DR PDB; 6CG0; EM; 3.17 A; A/C=265-1039.
DR PDB; 6CIJ; EM; 3.90 A; A/C=265-1040.
DR PDB; 6CIK; X-ray; 3.15 A; A/C=384-1008.
DR PDB; 6CIL; X-ray; 4.15 A; A/C=384-1008.
DR PDB; 6CIM; X-ray; 3.60 A; A/C=384-1008.
DR PDB; 6OEM; EM; 3.60 A; A/C=1-1040.
DR PDB; 6OEN; EM; 4.30 A; A/C=1-1040.
DR PDB; 6OEO; EM; 3.69 A; A/C=1-1040.
DR PDB; 6OEP; EM; 3.70 A; A/C=1-1040.
DR PDB; 6OEQ; EM; 4.30 A; A/C=1-1040.
DR PDB; 6OER; EM; 3.29 A; A/C=1-1040.
DR PDB; 6OES; EM; 3.06 A; A/C=1-1040.
DR PDB; 6OET; EM; 3.40 A; A/C=1-1040.
DR PDB; 6V0V; EM; 3.61 A; A=265-1039.
DR PDB; 6XNX; EM; 2.70 A; A/C=261-1008.
DR PDB; 6XNY; EM; 2.90 A; A/C=261-1008.
DR PDB; 6XNZ; EM; 3.80 A; A/C=261-1008.
DR PDBsum; 1RMD; -.
DR PDBsum; 3GNA; -.
DR PDBsum; 3GNB; -.
DR PDBsum; 4WWX; -.
DR PDBsum; 5ZDZ; -.
DR PDBsum; 5ZE0; -.
DR PDBsum; 5ZE1; -.
DR PDBsum; 5ZE2; -.
DR PDBsum; 6CG0; -.
DR PDBsum; 6CIJ; -.
DR PDBsum; 6CIK; -.
DR PDBsum; 6CIL; -.
DR PDBsum; 6CIM; -.
DR PDBsum; 6OEM; -.
DR PDBsum; 6OEN; -.
DR PDBsum; 6OEO; -.
DR PDBsum; 6OEP; -.
DR PDBsum; 6OEQ; -.
DR PDBsum; 6OER; -.
DR PDBsum; 6OES; -.
DR PDBsum; 6OET; -.
DR PDBsum; 6V0V; -.
DR PDBsum; 6XNX; -.
DR PDBsum; 6XNY; -.
DR PDBsum; 6XNZ; -.
DR AlphaFoldDB; P15919; -.
DR SMR; P15919; -.
DR BioGRID; 202574; 13.
DR CORUM; P15919; -.
DR DIP; DIP-48518N; -.
DR IntAct; P15919; 4.
DR MINT; P15919; -.
DR STRING; 10090.ENSMUSP00000077584; -.
DR iPTMnet; P15919; -.
DR PhosphoSitePlus; P15919; -.
DR MaxQB; P15919; -.
DR PaxDb; P15919; -.
DR PRIDE; P15919; -.
DR ProteomicsDB; 254894; -.
DR Antibodypedia; 42779; 122 antibodies from 26 providers.
DR DNASU; 19373; -.
DR Ensembl; ENSMUST00000078494; ENSMUSP00000077584; ENSMUSG00000061311.
DR GeneID; 19373; -.
DR KEGG; mmu:19373; -.
DR UCSC; uc008lhk.2; mouse.
DR CTD; 5896; -.
DR MGI; MGI:97848; Rag1.
DR VEuPathDB; HostDB:ENSMUSG00000061311; -.
DR eggNOG; ENOG502QSFV; Eukaryota.
DR GeneTree; ENSGT00390000008679; -.
DR HOGENOM; CLU_010909_0_0_1; -.
DR InParanoid; P15919; -.
DR OMA; WKFKLFK; -.
DR OrthoDB; 85196at2759; -.
DR PhylomeDB; P15919; -.
DR TreeFam; TF331926; -.
DR BioGRID-ORCS; 19373; 0 hits in 74 CRISPR screens.
DR EvolutionaryTrace; P15919; -.
DR PRO; PR:P15919; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; P15919; protein.
DR Bgee; ENSMUSG00000061311; Expressed in thymus and 46 other tissues.
DR Genevisible; P15919; MM.
DR GO; GO:0097519; C:DNA recombinase complex; IBA:GO_Central.
DR GO; GO:1905347; C:endodeoxyribonuclease complex; IBA:GO_Central.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0004519; F:endonuclease activity; IMP:UniProtKB.
DR GO; GO:0042393; F:histone binding; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0046872; F:metal ion binding; IMP:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:MGI.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR GO; GO:0002250; P:adaptive immune response; IMP:MGI.
DR GO; GO:0030183; P:B cell differentiation; IDA:MGI.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0006310; P:DNA recombination; TAS:MGI.
DR GO; GO:0010390; P:histone monoubiquitination; IDA:UniProtKB.
DR GO; GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; IMP:MGI.
DR GO; GO:0070233; P:negative regulation of T cell apoptotic process; IGI:MGI.
DR GO; GO:0070244; P:negative regulation of thymocyte apoptotic process; IMP:MGI.
DR GO; GO:0045582; P:positive regulation of T cell differentiation; IMP:CACAO.
DR GO; GO:0002331; P:pre-B cell allelic exclusion; IMP:UniProtKB.
DR GO; GO:0051865; P:protein autoubiquitination; IDA:UniProtKB.
DR GO; GO:2000822; P:regulation of behavioral fear response; ISO:MGI.
DR GO; GO:0045580; P:regulation of T cell differentiation; IGI:MGI.
DR GO; GO:0033077; P:T cell differentiation in thymus; IMP:UniProtKB.
DR GO; GO:0043029; P:T cell homeostasis; IGI:MGI.
DR GO; GO:0048538; P:thymus development; IGI:MGI.
DR GO; GO:0033151; P:V(D)J recombination; IMP:UniProtKB.
DR GO; GO:0008542; P:visual learning; ISO:MGI.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR024627; RAG1.
DR InterPro; IPR035714; RAG1_imp-bd.
DR InterPro; IPR019485; RAG1_Znf.
DR InterPro; IPR023336; RAG_nonamer-bd_dom.
DR InterPro; IPR036236; Znf_C2H2_sf.
DR InterPro; IPR018957; Znf_C3HC4_RING-type.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR017907; Znf_RING_CS.
DR PANTHER; PTHR11539; PTHR11539; 1.
DR Pfam; PF12940; RAG1; 1.
DR Pfam; PF12560; RAG1_imp_bd; 1.
DR Pfam; PF00097; zf-C3HC4; 1.
DR Pfam; PF10426; zf-RAG1; 1.
DR SMART; SM00184; RING; 1.
DR SUPFAM; SSF57667; SSF57667; 1.
DR PROSITE; PS51487; NBD; 1.
DR PROSITE; PS51765; ZF_RAG1; 1.
DR PROSITE; PS00518; ZF_RING_1; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Chromatin regulator; DNA recombination; DNA-binding;
KW Endonuclease; Hydrolase; Isopeptide bond; Metal-binding;
KW Multifunctional enzyme; Nuclease; Nucleus; Reference proteome; Transferase;
KW Ubl conjugation; Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..1040
FT /note="V(D)J recombination-activating protein 1"
FT /id="PRO_0000056005"
FT ZN_FING 290..329
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT ZN_FING 351..380
FT /note="RAG1-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01101"
FT DNA_BIND 389..456
FT /note="NBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00820"
FT REGION 39..71
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 39..55
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 266
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:9228952"
FT BINDING 270
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:9228952"
FT BINDING 290
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:9228952"
FT BINDING 293
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:9228952"
FT BINDING 293
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:9228952"
FT BINDING 295
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:9228952"
FT BINDING 305
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000269|PubMed:9228952"
FT BINDING 307
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000269|PubMed:9228952"
FT BINDING 310
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:9228952"
FT BINDING 313
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:9228952"
FT BINDING 325
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000269|PubMed:9228952"
FT BINDING 328
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000269|PubMed:9228952"
FT BINDING 355
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01101,
FT ECO:0000269|PubMed:9228952"
FT BINDING 360
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01101,
FT ECO:0000269|PubMed:9228952"
FT BINDING 372
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01101,
FT ECO:0000269|PubMed:9228952"
FT BINDING 376
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01101,
FT ECO:0000269|PubMed:9228952"
FT BINDING 600
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000305"
FT BINDING 708
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000305"
FT BINDING 962
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000305"
FT SITE 893
FT /note="Essential for DNA hairpin formation, participates in
FT base-stacking interactions near the cleavage site"
FT CROSSLNK 233
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:14671314"
FT MUTAGEN 233
FT /note="K->M: Abolishes autoubiquitination."
FT /evidence="ECO:0000269|PubMed:14671314"
FT MUTAGEN 307
FT /note="H->A: Displays lower E3 ligase activity and affects
FT the joining step of V(D)J recombination."
FT /evidence="ECO:0000269|PubMed:20122409"
FT MUTAGEN 325
FT /note="C->G: Loss of E3 ligase activity and affects the
FT joining step of V(D)J recombination."
FT /evidence="ECO:0000269|PubMed:14671314,
FT ECO:0000269|PubMed:20122409"
FT MUTAGEN 391
FT /note="R->A: Defects in converting nicked products to
FT hairpins."
FT /evidence="ECO:0000269|PubMed:19396172"
FT MUTAGEN 391
FT /note="R->L: Impairs DNA-binding and hairpin formation
FT while maintaining some nicking activity."
FT /evidence="ECO:0000269|PubMed:19396172"
FT MUTAGEN 393
FT /note="R->A: Impairs DNA-binding and hairpin formation
FT while maintaining some nicking activity."
FT /evidence="ECO:0000269|PubMed:19396172"
FT MUTAGEN 401
FT /note="R->A: Allows robust hairpin activity."
FT /evidence="ECO:0000269|PubMed:19396172"
FT MUTAGEN 402
FT /note="R->A: Defects in converting nicked products to
FT hairpins."
FT /evidence="ECO:0000269|PubMed:19396172"
FT MUTAGEN 405
FT /note="K->A: Reduced hairpin activity."
FT /evidence="ECO:0000269|PubMed:19396172"
FT MUTAGEN 406
FT /note="H->A: Allows robust hairpin activity."
FT /evidence="ECO:0000269|PubMed:19396172"
FT MUTAGEN 407
FT /note="R->A: Impairs DNA-binding and reduces hairpin
FT formation without affecting nicking activity."
FT /evidence="ECO:0000269|PubMed:19396172"
FT MUTAGEN 443
FT /note="N->A: Impairs DNA-binding; when associated with A-
FT 445."
FT /evidence="ECO:0000269|PubMed:19396172"
FT MUTAGEN 445
FT /note="H->A: Impairs DNA-binding; when associated with A-
FT 443."
FT /evidence="ECO:0000269|PubMed:19396172"
FT MUTAGEN 546
FT /note="D->A: Loss of DNA-binding."
FT MUTAGEN 560
FT /note="D->A: Loss of DNA-binding."
FT MUTAGEN 597
FT /note="E->Q: Impaired cleavage."
FT /evidence="ECO:0000269|PubMed:10601032"
FT MUTAGEN 600
FT /note="D->A: Loss of cleavage and strand transfer
FT activities."
FT /evidence="ECO:0000269|PubMed:10601032,
FT ECO:0000269|PubMed:10601033, ECO:0000269|PubMed:10678172"
FT MUTAGEN 600
FT /note="D->N: Loss of cleavage (both nicking and hairpin
FT formation)."
FT /evidence="ECO:0000269|PubMed:10601032,
FT ECO:0000269|PubMed:10601033, ECO:0000269|PubMed:10678172"
FT MUTAGEN 707
FT /note="Y->A: Deficient in both nicking and hairpin
FT formation."
FT /evidence="ECO:0000269|PubMed:17028591"
FT MUTAGEN 708
FT /note="D->A: Loss of cleavage and strand transfer
FT activities without affecting allelic exclusion."
FT /evidence="ECO:0000269|PubMed:10601032,
FT ECO:0000269|PubMed:10601033, ECO:0000269|PubMed:10678172,
FT ECO:0000269|PubMed:19448632"
FT MUTAGEN 708
FT /note="D->N: Loss of cleavage (both nicking and hairpin
FT formation)."
FT /evidence="ECO:0000269|PubMed:10601032,
FT ECO:0000269|PubMed:10601033, ECO:0000269|PubMed:10678172,
FT ECO:0000269|PubMed:19448632"
FT MUTAGEN 709
FT /note="E->A: Impaired cleavage (defective in hairpin
FT formation)."
FT /evidence="ECO:0000269|PubMed:10601032"
FT MUTAGEN 709
FT /note="E->Q: Impaired cleavage."
FT /evidence="ECO:0000269|PubMed:10601032"
FT MUTAGEN 713
FT /note="R->A,C: Impaired cleavage (both nicking and hairpin
FT formation)."
FT MUTAGEN 719
FT /note="E->Q: Impaired cleavage."
FT /evidence="ECO:0000269|PubMed:10601032"
FT MUTAGEN 725
FT /note="Y->A: Deficient in both nicking and hairpin
FT formation."
FT /evidence="ECO:0000269|PubMed:17028591"
FT MUTAGEN 760
FT /note="W->A: Deficient in both nicking and hairpin
FT formation."
FT /evidence="ECO:0000269|PubMed:17028591"
FT MUTAGEN 792
FT /note="D->N: Impaired cleavage."
FT /evidence="ECO:0000269|PubMed:10601032"
FT MUTAGEN 811
FT /note="E->A: Impaired cleavage."
FT /evidence="ECO:0000269|PubMed:10601032"
FT MUTAGEN 811
FT /note="E->Q: Loss of DNA-binding."
FT /evidence="ECO:0000269|PubMed:10601032"
FT MUTAGEN 893
FT /note="W->A: Capable of nicking but defective for
FT hairpinning."
FT /evidence="ECO:0000269|PubMed:17028591"
FT MUTAGEN 893
FT /note="W->F: Capable of nicking and retains some
FT hairpinning."
FT /evidence="ECO:0000269|PubMed:17028591"
FT MUTAGEN 935
FT /note="Y->A,L,F: Capable of nicking but defective for
FT hairpinning."
FT /evidence="ECO:0000269|PubMed:17028591"
FT MUTAGEN 935
FT /note="Y->S,T: Capable of both nicking and hairpinning."
FT /evidence="ECO:0000269|PubMed:17028591"
FT MUTAGEN 938
FT /note="K->A: Capable of nicking but defective for
FT hairpinning."
FT MUTAGEN 956
FT /note="W->A: Deficient in both nicking and hairpin
FT formation."
FT /evidence="ECO:0000269|PubMed:17028591"
FT MUTAGEN 959
FT /note="E->Q: Impaired cleavage."
FT /evidence="ECO:0000269|PubMed:10601032"
FT MUTAGEN 962
FT /note="E->A,Q: Loss of cleavage (both nicking and hairpin
FT formation)."
FT /evidence="ECO:0000269|PubMed:10601032,
FT ECO:0000269|PubMed:10601033, ECO:0000269|PubMed:17028591"
FT MUTAGEN 971
FT /note="F->A,W: Capable of nicking but defective for
FT hairpinning."
FT /evidence="ECO:0000269|PubMed:17028591"
FT MUTAGEN 972
FT /note="R->A: Capable of nicking but defective for
FT hairpinning."
FT /evidence="ECO:0000269|PubMed:17028591"
FT MUTAGEN 973
FT /note="K->A: Moderately defective with 56% of activity."
FT /evidence="ECO:0000269|PubMed:17028591"
FT MUTAGEN 986
FT /note="D->N: Impaired cleavage."
FT /evidence="ECO:0000269|PubMed:10601032"
FT CONFLICT 609
FT /note="H -> L (in Ref. 1; AAA40028)"
FT /evidence="ECO:0000305"
FT HELIX 266..268
FT /evidence="ECO:0007829|PDB:1RMD"
FT HELIX 273..275
FT /evidence="ECO:0007829|PDB:1RMD"
FT STRAND 276..278
FT /evidence="ECO:0007829|PDB:1RMD"
FT HELIX 282..287
FT /evidence="ECO:0007829|PDB:1RMD"
FT TURN 291..293
FT /evidence="ECO:0007829|PDB:1RMD"
FT STRAND 298..302
FT /evidence="ECO:0007829|PDB:1RMD"
FT STRAND 308..310
FT /evidence="ECO:0007829|PDB:1RMD"
FT HELIX 311..320
FT /evidence="ECO:0007829|PDB:1RMD"
FT TURN 326..328
FT /evidence="ECO:0007829|PDB:1RMD"
FT HELIX 334..336
FT /evidence="ECO:0007829|PDB:1RMD"
FT HELIX 342..350
FT /evidence="ECO:0007829|PDB:1RMD"
FT STRAND 352..354
FT /evidence="ECO:0007829|PDB:1RMD"
FT STRAND 363..365
FT /evidence="ECO:0007829|PDB:1RMD"
FT HELIX 366..374
FT /evidence="ECO:0007829|PDB:1RMD"
FT HELIX 396..398
FT /evidence="ECO:0007829|PDB:3GNA"
FT HELIX 401..422
FT /evidence="ECO:0007829|PDB:3GNA"
FT HELIX 427..441
FT /evidence="ECO:0007829|PDB:3GNA"
FT HELIX 445..454
FT /evidence="ECO:0007829|PDB:3GNA"
FT HELIX 464..473
FT /evidence="ECO:0007829|PDB:6XNX"
FT HELIX 478..491
FT /evidence="ECO:0007829|PDB:6XNX"
FT STRAND 492..494
FT /evidence="ECO:0007829|PDB:6XNX"
FT HELIX 500..510
FT /evidence="ECO:0007829|PDB:6XNX"
FT STRAND 511..515
FT /evidence="ECO:0007829|PDB:6XNX"
FT STRAND 517..521
FT /evidence="ECO:0007829|PDB:6XNX"
FT STRAND 534..536
FT /evidence="ECO:0007829|PDB:6XNX"
FT TURN 537..540
FT /evidence="ECO:0007829|PDB:6XNX"
FT STRAND 545..547
FT /evidence="ECO:0007829|PDB:6XNY"
FT STRAND 554..557
FT /evidence="ECO:0007829|PDB:6XNX"
FT HELIX 559..569
FT /evidence="ECO:0007829|PDB:6XNX"
FT HELIX 571..580
FT /evidence="ECO:0007829|PDB:6XNX"
FT STRAND 590..602
FT /evidence="ECO:0007829|PDB:6XNX"
FT STRAND 610..612
FT /evidence="ECO:0007829|PDB:6XNX"
FT STRAND 619..631
FT /evidence="ECO:0007829|PDB:6XNX"
FT STRAND 639..642
FT /evidence="ECO:0007829|PDB:6XNX"
FT TURN 649..651
FT /evidence="ECO:0007829|PDB:6XNX"
FT STRAND 652..658
FT /evidence="ECO:0007829|PDB:6XNX"
FT HELIX 665..682
FT /evidence="ECO:0007829|PDB:6XNX"
FT STRAND 687..691
FT /evidence="ECO:0007829|PDB:6XNX"
FT STRAND 694..702
FT /evidence="ECO:0007829|PDB:6XNX"
FT HELIX 709..715
FT /evidence="ECO:0007829|PDB:6XNX"
FT STRAND 721..725
FT /evidence="ECO:0007829|PDB:6XNX"
FT STRAND 728..730
FT /evidence="ECO:0007829|PDB:6XNX"
FT HELIX 734..739
FT /evidence="ECO:0007829|PDB:6XNX"
FT HELIX 750..762
FT /evidence="ECO:0007829|PDB:6XNX"
FT HELIX 769..775
FT /evidence="ECO:0007829|PDB:6XNX"
FT TURN 776..778
FT /evidence="ECO:0007829|PDB:6XNX"
FT HELIX 793..812
FT /evidence="ECO:0007829|PDB:6XNX"
FT TURN 813..817
FT /evidence="ECO:0007829|PDB:6XNX"
FT HELIX 825..839
FT /evidence="ECO:0007829|PDB:6XNX"
FT HELIX 851..857
FT /evidence="ECO:0007829|PDB:6XNX"
FT HELIX 860..867
FT /evidence="ECO:0007829|PDB:6XNX"
FT HELIX 873..894
FT /evidence="ECO:0007829|PDB:6XNX"
FT HELIX 898..901
FT /evidence="ECO:0007829|PDB:6XNX"
FT HELIX 903..907
FT /evidence="ECO:0007829|PDB:6XNX"
FT HELIX 909..922
FT /evidence="ECO:0007829|PDB:6XNX"
FT TURN 926..928
FT /evidence="ECO:0007829|PDB:6XNX"
FT HELIX 934..941
FT /evidence="ECO:0007829|PDB:6XNX"
FT HELIX 943..950
FT /evidence="ECO:0007829|PDB:6XNX"
FT HELIX 954..956
FT /evidence="ECO:0007829|PDB:6XNX"
FT HELIX 959..974
FT /evidence="ECO:0007829|PDB:6XNX"
FT TURN 980..982
FT /evidence="ECO:0007829|PDB:6XNX"
FT HELIX 983..994
FT /evidence="ECO:0007829|PDB:6XNX"
FT HELIX 997..1002
FT /evidence="ECO:0007829|PDB:6XNX"
FT TURN 1003..1007
FT /evidence="ECO:0007829|PDB:6XNX"
SQ SEQUENCE 1040 AA; 119185 MW; 7C2E6AD68DCBA081 CRC64;
MAASLPSTLS FSSAPDEIQH PQIKFSEWKF KLFRVRSFEK APEEAQKEKD SSEGKPYLEQ
SPVVPEKPGG QNSILTQRAL KLHPKFSKKF HADGKSSDKA VHQARLRHFC RICGNRFKSD
GHSRRYPVHG PVDAKTQSLF RKKEKRVTSW PDLIARIFRI DVKADVDSIH PTEFCHDCWS
IMHRKFSSSH SQVYFPRKVT VEWHPHTPSC DICFTAHRGL KRKRHQPNVQ LSKKLKTVLN
HARRDRRKRT QARVSSKEVL KKISNCSKIH LSTKLLAVDF PAHFVKSISC QICEHILADP
VETSCKHLFC RICILRCLKV MGSYCPSCRY PCFPTDLESP VKSFLNILNS LMVKCPAQDC
NEEVSLEKYN HHVSSHKESK ETLVHINKGG RPRQHLLSLT RRAQKHRLRE LKIQVKEFAD
KEEGGDVKAV CLTLFLLALR ARNEHRQADE LEAIMQGRGS GLQPAVCLAI RVNTFLSCSQ
YHKMYRTVKA ITGRQIFQPL HALRNAEKVL LPGYHPFEWQ PPLKNVSSRT DVGIIDGLSG
LASSVDEYPV DTIAKRFRYD SALVSALMDM EEDILEGMRS QDLDDYLNGP FTVVVKESCD
GMGDVSEKHG SGPAVPEKAV RFSFTVMRIT IEHGSQNVKV FEEPKPNSEL CCKPLCLMLA
DESDHETLTA ILSPLIAERE AMKSSELTLE MGGIPRTFKF IFRGTGYDEK LVREVEGLEA
SGSVYICTLC DTTRLEASQN LVFHSITRSH AENLQRYEVW RSNPYHESVE ELRDRVKGVS
AKPFIETVPS IDALHCDIGN AAEFYKIFQL EIGEVYKHPN ASKEERKRWQ ATLDKHLRKR
MNLKPIMRMN GNFARKLMTQ ETVDAVCELI PSEERHEALR ELMDLYLKMK PVWRSSCPAK
ECPESLCQYS FNSQRFAELL STKFKYRYEG KITNYFHKTL AHVPEIIERD GSIGAWASEG
NESGNKLFRR FRKMNARQSK CYEMEDVLKH HWLYTSKYLQ KFMNAHNALK SSGFTMNSKE
TLGDPLGIED SLESQDSMEF
