RAG1_PIG
ID RAG1_PIG Reviewed; 1043 AA.
AC Q867B5;
DT 24-JAN-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 106.
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 Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=Large white; TISSUE=Liver;
RA Hatsuse H., Homma D., Hiraiwa H., Yasue H., Takagaki Y.;
RT "Porcine RAG-1 gene promoter and coding region.";
RL Submitted (SEP-2002) to the EMBL/GenBank/DDBJ databases.
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; AB091392; BAC54968.1; -; Genomic_DNA.
DR RefSeq; NP_001116656.1; NM_001123184.1.
DR AlphaFoldDB; Q867B5; -.
DR SMR; Q867B5; -.
DR STRING; 9823.ENSSSCP00000029411; -.
DR PaxDb; Q867B5; -.
DR PRIDE; Q867B5; -.
DR Ensembl; ENSSSCT00035084210; ENSSSCP00035035015; ENSSSCG00035062658.
DR Ensembl; ENSSSCT00035084211; ENSSSCP00035035016; ENSSSCG00035062658.
DR GeneID; 397506; -.
DR KEGG; ssc:397506; -.
DR CTD; 5896; -.
DR eggNOG; ENOG502QSFV; Eukaryota.
DR InParanoid; Q867B5; -.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; 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..1043
FT /note="V(D)J recombination-activating protein 1"
FT /id="PRO_0000056006"
FT ZN_FING 293..332
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT ZN_FING 354..383
FT /note="RAG1-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01101"
FT DNA_BIND 392..459
FT /note="NBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00820"
FT REGION 39..98
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 269
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 273
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 293
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 296
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 296
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 298
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 308
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 310
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 313
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 316
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 328
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 331
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 358
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01101"
FT BINDING 363
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01101"
FT BINDING 375
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01101"
FT BINDING 379
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01101"
FT BINDING 603
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 711
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 965
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT SITE 896
FT /note="Essential for DNA hairpin formation, participates in
FT base-stacking interactions near the cleavage site"
FT /evidence="ECO:0000250"
FT CROSSLNK 234
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P15919"
SQ SEQUENCE 1043 AA; 119068 MW; D0E75CD5488690AC CRC64;
MAVSLPPTLG LSSAPDEIQH PHIKFSEWKF KLFRVRSFEK APEKAQTEKQ DSSEGKPSLE
QSPAVLDKPG GQKSALPQPA FKPHPKFLKE SHEDGKARDK AIHQANLRRL CRICGNSFNT
TGHKRRYPVH GPVDGKTQVL LRKKEKRATS WPDLIAKVFR IDVKADVDSI HPTEFCHNCW
SFMHRKFSST PCEVYSPRNA AMEWHPHTLN CDICHIARRG LKRKSQQPNM QLSKKLKTVI
DRARQARQRK RRAQARISSK ELMKKIANCG QIHLSPKLLA VDFPAHFVKS ISCQICEHIL
ADPVETSCKH VFCRICILRC LKVMGSSCPS CHYPCFPTDL ESPVKSFLSI LNTLMVKCPA
KECNEEISLE KYNHHISSHK ESKETFVHIN KGGRPRQHLL SLTRRAQKHR LRELKLQVKA
FADKEEGGDV KSVCLTLFLL VLRARNEHRQ ADELEAIMRG QGSGLQPAVC LAIRVNTFLS
CSQYHKMYRT VKAITGRQIF QPLHALRNAE KVLLPGYHPF EWQPPLKNVS SSTDVGIIDG
LSGLSSSVDD YPVDTIAKRF RYDSALVSAL MDMEEDILEG MRAQDLDDYL NGPFTVVVKE
SCDGMGDVSE KHGSGPVVPE KAVRFSFTVM KITIAHGSQN VKVFEEAKPN SELCCKPLCL
MLADESDHET LTAILSPLIA EREAMKSSQL MLEMGGILRT FKFIFRGTGY DEKLVREVEG
LEASGSVYIC TLCDATRLEA SQNLVFHSIT RSHAENLERY EVWRSNPYHE TVDELRDRVK
GVSAKPFIET VPSIDALHCD IGNAAEFYKI FQLEIGEAYK NPHASKEERK RWQATLDKHL
RKKMNLKPIM RMNGNFARKL MTKETVEAVC ELIPSEERHE ALRELMDLYL KMKPVWRSSC
PAKECPESLC QYSFNSQRFA ELLSTKFKYR YEGKITNYFH KTLAHVPEII ERDGSIGAWA
SEGNESGNKL FRRFRKMNAR QSKYYEMEDV LKHHWLYTSK YLQKFMNAHK AFKNSGFTIN
LQRSSGDTLD LENSPESQDL MEF
