ID RAG1_XENLA Reviewed; 1045 AA.
AC Q91829;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 27-MAR-2024, entry version 121.
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 Xenopus laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=HD-1;
RX PubMed=8376769;
RA Greenhalgh P.H., Olesen C.E., Steiner L.A.;
RT "Characterization and expression of recombination activating genes (RAG-1
RT and RAG-2) in Xenopus laevis.";
RL J. Immunol. 151:3100-3110(1993).
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. In addition to its
CC endonuclease activity, RAG1 also acts as an E3 ubiquitin-protein ligase
CC that mediates monoubiquitination of histone H3. Histone H3
CC monoubiquitination is required for the joining step of V(D)J
CC recombination (By similarity). {ECO:0000250}.
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; Evidence={ECO:0000250};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250};
CC Note=Binds 1 divalent metal cation per subunit. Mg(2+) or Mn(2+).
CC {ECO:0000250};
CC -!- SUBUNIT: Homodimer. Component of the RAG complex composed of core
CC components rag1 and rag2 (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00820}.
CC -!- TISSUE SPECIFICITY: Expressed within the thymus, liver and spleen in
CC juvenile frogs, and within the thymus and bone marrow of adults.
CC -!- DOMAIN: The RING-type zinc finger mediates the E3 ubiquitin-protein
CC ligase activity. {ECO:0000250}.
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 -!- SIMILARITY: Belongs to the RAG1 family. {ECO:0000255|PROSITE-
CC ProRule:PRU00820}.
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DR EMBL; L19324; AAA03068.1; -; Genomic_DNA.
DR PIR; I51555; I51555.
DR RefSeq; NP_001165554.1; NM_001172083.1.
DR AlphaFoldDB; Q91829; -.
DR SMR; Q91829; -.
DR GeneID; 100337558; -.
DR KEGG; xla:100337558; -.
DR AGR; Xenbase:XB-GENE-17346869; -.
DR Xenbase; XB-GENE-17346869; rag1.S.
DR OrthoDB; 4577803at2759; -.
DR Proteomes; UP000186698; Chromosome 4S.
DR Bgee; 100337558; Expressed in spleen.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0004519; F:endonuclease activity; ISS:UniProtKB.
DR GO; GO:0042393; F:histone binding; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0043565; F:sequence-specific DNA binding; ISS:UniProtKB.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IEA:InterPro.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; ISS:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR GO; GO:0030183; P:B cell differentiation; ISS:UniProtKB.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0033077; P:T cell differentiation in thymus; ISS:UniProtKB.
DR GO; GO:0033151; P:V(D)J recombination; ISS:UniProtKB.
DR CDD; cd16530; RING-HC_RAG1; 1.
DR Gene3D; 6.10.140.510; -; 1.
DR Gene3D; 3.30.160.60; Classic Zinc Finger; 1.
DR Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 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:SF0; V(D)J RECOMBINATION-ACTIVATING PROTEIN 1; 1.
DR PANTHER; PTHR11539; VDJ RECOMBINATION ACTIVATING PROTEIN 1 RAG1; 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 SUPFAM; SSF57667; beta-beta-alpha zinc fingers; 1.
DR SUPFAM; SSF57850; RING/U-box; 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 2: Evidence at transcript level;
KW Chromatin regulator; DNA recombination; DNA-binding; Endonuclease;
KW Hydrolase; Metal-binding; Multifunctional enzyme; Nuclease; Nucleus;
KW Reference proteome; Transferase; Ubl conjugation pathway; Zinc;
KW Zinc-finger.
FT CHAIN 1..1045
FT /note="V(D)J recombination-activating protein 1"
FT /id="PRO_0000056012"
FT ZN_FING 294..333
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT ZN_FING 355..384
FT /note="RAG1-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01101"
FT DNA_BIND 395..462
FT /note="NBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00820"
FT REGION 33..55
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 67..87
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 222..253
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 67..84
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 228..243
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 270
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 274
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 294
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 297
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 297
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 299
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 309
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 311
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 314
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 317
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 329
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 332
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 359
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01101"
FT BINDING 364
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01101"
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 BINDING 380
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01101"
FT BINDING 606
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 714
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 968
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT SITE 899
FT /note="Essential for DNA hairpin formation, participates in
FT base-stacking interactions near the cleavage site"
FT /evidence="ECO:0000250"
SQ SEQUENCE 1045 AA; 119893 MW; 93F45B5E77590153 CRC64;
MEVALPNVPT KMQHPFTKYS EWKFKLFRVK SLERRPSEEE TEGSEVSYNS SQETYPKSTV
VLEDLSLGSA PQSPTNFKPQ QSEKSNVVDN HETDLKRLEE EAHITVIQQL CRICGASFKM
DQQNRSYPVH GPVDSETHDI LRRREKKVTS WPELISKVFK TDVRADVDTI HPTQFCHNCW
TIMNQKFSNI SSEVYFPHNQ AVEWTPHSAN CYVCHSSKPW GKRKSAPQLN PHKMKKRKRG
PEFVKKSKTS SGNSIQWKNM KAFNQMKDSC KKIHLDNNLL VLDYPSDFVK SVSCLVCEHI
LSDPVQTSCK HLFCRICILK YIKLMGCYCP SCKYPCFPTD LTVPVKSYLN VLNALLLKCT
VSGCDEEISL GKYSHHISKH KETKGKEVYA HINKGGRPRQ HLLTLTRRAQ KHRLRELKMQ
VKAFADKEEE GDVKSVCLTL FLLALRARNE HRQADELEAI MEGRGAGLHP AVCLAIRVNT
FLSCSQYHKM YRTVKATTGR QIFQPLHALR NAEKALIPGY HTFEWRPPLK NVSTRTDVGI
IDGLSGLNQS LDEYPVDTIS KRFRYDAALV SALKDMEEDI LEGLKAQDLD DYVSGPFTVV
VKESCDGMGD VSEKHGSGPP VPEKAVRFSF TVMNISVPNK NGPVRIFEET KPNSELCCKP
LCLMLADESD HETLTAILSP LIAEREAMKT AELLLEMGGI LRNFKFSFRG TGYDEKLVRE
VEGLEASGSL YICTLCDATR LEAAQNLVNH SITRSHCENL QRYEMWRSNP HHESPDELRD
RVKGVSAKPF IETLPSIDAL HCDIGNAAEF YRIFQLEIGE LYKNLSATKE EKKRWQATLD
NHIRKRMNLK PIMRMNGNFA RKLMSKETVE AVCELVPCEE RQAALTELMD LYLKMKPVWR
SSCPAKECPE LLCQYSFHSQ RFAELLSTKF KYRYEGKITN YFHKTLAHVP EIIERDGSIG
AWASEGNESG NKLFRRFRKM NARQSKFYEM EDVLKHHWLY TSKYLQKFMN AHNNLKNQGF
TVDLDNPDLE QRLESSMESL ESMEF
//
