RAG1_RABIT
ID RAG1_RABIT Reviewed; 1042 AA.
AC P34088;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1994, sequence version 1.
DT 03-AUG-2022, entry version 125.
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 Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8350872; DOI=10.1016/0161-5890(93)90127-w;
RA Fuschiotti P., Harindranath N., Mage R.G., McCormack W.T., Dhanarajan P.,
RA Roux K.H.;
RT "Recombination activating genes-1 and -2 of the rabbit: cloning and
RT characterization of germline and expressed genes.";
RL Mol. Immunol. 30:1021-1032(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. 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 (By similarity).
CC {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, 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 (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00820}.
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 -!- PTM: Autoubiquitinated in the presence of CDC34/UBCH3. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the RAG1 family. {ECO:0000255|PROSITE-
CC ProRule:PRU00820}.
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DR EMBL; M77666; AAA03025.1; -; Genomic_DNA.
DR PIR; S42511; S42511.
DR RefSeq; NP_001164611.1; NM_001171140.1.
DR AlphaFoldDB; P34088; -.
DR SMR; P34088; -.
DR STRING; 9986.ENSOCUP00000020586; -.
DR PRIDE; P34088; -.
DR GeneID; 100328950; -.
DR KEGG; ocu:100328950; -.
DR CTD; 5896; -.
DR eggNOG; ENOG502QSFV; Eukaryota.
DR InParanoid; P34088; -.
DR OrthoDB; 85196at2759; -.
DR Proteomes; UP000001811; Unplaced.
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:0010390; P:histone monoubiquitination; ISS:UniProtKB.
DR GO; GO:0002331; P:pre-B cell allelic exclusion; ISS:UniProtKB.
DR GO; GO:0051865; P:protein autoubiquitination; ISS:UniProtKB.
DR GO; GO:0033077; P:T cell differentiation in thymus; ISS:UniProtKB.
DR GO; GO:0033151; P:V(D)J recombination; ISS:UniProtKB.
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; 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; 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 3: Inferred from homology;
KW Chromatin regulator; DNA recombination; DNA-binding; Endonuclease;
KW Hydrolase; Isopeptide bond; Metal-binding; Multifunctional enzyme;
KW Nuclease; Nucleus; Reference proteome; Transferase; Ubl conjugation;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..1042
FT /note="V(D)J recombination-activating protein 1"
FT /id="PRO_0000056007"
FT ZN_FING 292..331
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT ZN_FING 353..382
FT /note="RAG1-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01101"
FT DNA_BIND 391..458
FT /note="NBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00820"
FT REGION 40..80
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 40..54
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 268
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 272
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 292
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 295
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 295
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 307
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
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 312
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 315
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 327
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 330
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 357
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01101"
FT BINDING 362
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01101"
FT BINDING 374
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01101"
FT BINDING 378
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01101"
FT BINDING 602
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 710
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 964
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT SITE 895
FT /note="Essential for DNA hairpin formation, participates in
FT base-stacking interactions near the cleavage site"
FT /evidence="ECO:0000250"
FT CROSSLNK 233
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P15919"
SQ SEQUENCE 1042 AA; 119007 MW; 136C6286C6E22FAE CRC64;
MAVSCTPTLG LSSAPDEIQH PHIKFSEWKF KLFRVRSFEK TTEENQKEKN SSEGKPSLEQ
SPAVLDKASG QKPEVAPPAF KVHPKFSKKF HDDGKARDKA IHQANLRHLC RICGNSLKTD
EHNRRYPVHG PVDSKTQGLL RKKEKKATSW PDLIAKVFRI DVKTDVDSIH PTEFCHNCWR
IMHRKFSGAP CEVYFPRNAT MEWHPHAPSC DICYTARRGL KRRNHQPNVQ LSKKLKTVLD
QARQARQRKR RVQARITSKE VMKMIANCSK IHLSTKLLAV DFPAHFVKSI SCQICEHILA
DPVETSCKHV FCRICILRCL KVMGSYCPSC QYPCFPTDLE SPVKSFLCIL NSLIVKCSAP
ECNEEVSLEK YNHHVSSHKE SRDTFVHINK GGRPRQHLLS LTRRAQKHRL RELKLQVKAF
ADKEEGGDVK SVCLTLFLLA LRARNEHRQA DELEAIMQGR GSGLQPAVCL AIRVNTFLSC
SQYHKMYRTV KAITGRQIFQ PLHALRNAEK VLLPGYHPFE WQPPLKNVSS STDVGIIDGL
SGLSSSVDDY PVDTIAKRFR YDSALVSALM DMEEDILEGM RSQDLEDYLN GPFTVVVKES
CDGMGDVTEK HGSGPAVPEK AVRFSFTVMK ITIAHGSQNV KVFEEAKPNS ELCCKPLCLM
LADESDHETL TAILSPLIAE REAMKSSELM LEMGGILRTF KFIFRGTGYD EKLVREVEGL
EASGSVYICT LCDATRLEAS QNLVFHSITR SHAENLERYE VWRSNPYHES VEELRDRVKG
VSAKPFIETV PSIDALHCDI GNAAEFYKIF QLEIGEVYKN PSASKEERKR WQATLDKHLR
KKMNLKPIMR MNGNFARKLM TIETVEAVCE LIPSKERHEA LRELMELYLK MKPVWRSSCP
AKECPESLCQ YSFNSQRFAE LLSTKFKYRY EGKITNYFHK TLAHVPEIIE RDGSIGAWAS
EGNESGNKLF RRFRKMNARQ SKCYEMEDVL KHHWLYTSKY LQKFMNAHNA VKNSGFTMNS
QVSLEDPLGI EDSLESQYSM EF
