RAG2_RABIT
ID RAG2_RABIT Reviewed; 527 AA.
AC P34089;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1994, sequence version 1.
DT 03-AUG-2022, entry version 106.
DE RecName: Full=V(D)J recombination-activating protein 2;
DE Short=RAG-2;
GN Name=RAG2;
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: Core component of the RAG complex, a multiprotein complex
CC that mediates the DNA cleavage phase during V(D)J recombination. V(D)J
CC recombination assembles a diverse repertoire of immunoglobulin and T-
CC cell receptor genes in developing B and T-lymphocytes through
CC rearrangement of different V (variable), in some cases D (diversity),
CC and J (joining) gene segments. DNA cleavage by the RAG complex occurs
CC in 2 steps: a first nick is introduced in the top strand immediately
CC upstream of the heptamer, generating a 3'-hydroxyl group that can
CC attack the 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 the RAG complex, RAG2 is not the
CC catalytic component but is required for all known catalytic activities
CC mediated by RAG1. It probably acts as a sensor of chromatin state that
CC recruits the RAG complex to H3K4me3 (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Component of the RAG complex composed of core components RAG1
CC and RAG2, and associated component HMGB1 or HMGB2. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Thymus.
CC -!- DOMAIN: The atypical PHD-type zinc finger recognizes and binds histone
CC H3 trimethylated on 'Lys-4' (H3K4me3). The presence Tyr-445 instead of
CC a carboxylate in classical PHD-type zinc fingers results in an enhanced
CC binding to H3K4me3 in presence of dimethylated on 'Arg-2' (H3R2me2)
CC rather than inhibited. The atypical PHD-type zinc finger also binds
CC various phosphoinositides, such as phosphatidylinositol 3,4-
CC bisphosphate binding (PtdIns(3,4)P2), phosphatidylinositol 3,5-
CC bisphosphate binding (PtdIns(3,5)P2), phosphatidylinositol 4,5-
CC bisphosphate (PtdIns(4,5)P2) and phosphatidylinositol 3,4,5-
CC trisphosphate binding (PtdIns(3,4,5)P3) (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the RAG2 family. {ECO:0000305}.
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DR EMBL; M77667; AAA03029.1; -; Genomic_DNA.
DR PIR; S42512; S42512.
DR RefSeq; NP_001164612.1; NM_001171141.1.
DR AlphaFoldDB; P34089; -.
DR SMR; P34089; -.
DR STRING; 9986.ENSOCUP00000020912; -.
DR Ensembl; ENSOCUT00000006991; ENSOCUP00000020912; ENSOCUG00000006995.
DR GeneID; 100328951; -.
DR KEGG; ocu:100328951; -.
DR CTD; 5897; -.
DR eggNOG; ENOG502QVKU; Eukaryota.
DR GeneTree; ENSGT00390000012559; -.
DR HOGENOM; CLU_516740_0_0_1; -.
DR InParanoid; P34089; -.
DR OMA; WNSVVDC; -.
DR OrthoDB; 687724at2759; -.
DR TreeFam; TF331236; -.
DR Proteomes; UP000001811; Chromosome 1.
DR Bgee; ENSOCUG00000006995; Expressed in lung and 1 other tissue.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0003682; F:chromatin binding; ISS:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IEA:InterPro.
DR GO; GO:0035064; F:methylated histone binding; ISS:UniProtKB.
DR GO; GO:0035091; F:phosphatidylinositol binding; ISS:UniProtKB.
DR GO; GO:0005547; F:phosphatidylinositol-3,4,5-trisphosphate binding; ISS:UniProtKB.
DR GO; GO:0043325; F:phosphatidylinositol-3,4-bisphosphate binding; ISS:UniProtKB.
DR GO; GO:0080025; F:phosphatidylinositol-3,5-bisphosphate binding; ISS:UniProtKB.
DR GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; ISS:UniProtKB.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IEA:Ensembl.
DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR GO; GO:0030183; P:B cell differentiation; ISS:UniProtKB.
DR GO; GO:0002358; P:B cell homeostatic proliferation; IEA:Ensembl.
DR GO; GO:0002326; P:B cell lineage commitment; IEA:Ensembl.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0042742; P:defense response to bacterium; IEA:Ensembl.
DR GO; GO:1904155; P:DN2 thymocyte differentiation; IEA:Ensembl.
DR GO; GO:0035265; P:organ growth; IEA:Ensembl.
DR GO; GO:0046622; P:positive regulation of organ growth; IEA:Ensembl.
DR GO; GO:0002331; P:pre-B cell allelic exclusion; ISS:UniProtKB.
DR GO; GO:0033077; P:T cell differentiation in thymus; ISS:UniProtKB.
DR GO; GO:0002360; P:T cell lineage commitment; IEA:Ensembl.
DR GO; GO:0033151; P:V(D)J recombination; ISS:UniProtKB.
DR CDD; cd15569; PHD_RAG2; 1.
DR Gene3D; 2.120.10.80; -; 1.
DR InterPro; IPR011043; Gal_Oxase/kelch_b-propeller.
DR InterPro; IPR015915; Kelch-typ_b-propeller.
DR InterPro; IPR004321; RAG2.
DR InterPro; IPR025162; RAG2_PHD.
DR InterPro; IPR011011; Znf_FYVE_PHD.
DR PANTHER; PTHR10960; PTHR10960; 1.
DR Pfam; PF03089; RAG2; 1.
DR Pfam; PF13341; RAG2_PHD; 1.
DR SUPFAM; SSF50965; SSF50965; 1.
DR SUPFAM; SSF57903; SSF57903; 1.
PE 2: Evidence at transcript level;
KW Chromatin regulator; DNA recombination; Metal-binding; Nucleus;
KW Reference proteome; Zinc; Zinc-finger.
FT CHAIN 1..527
FT /note="V(D)J recombination-activating protein 2"
FT /id="PRO_0000167139"
FT ZN_FING 416..484
FT /note="PHD-type; atypical"
FT REGION 359..380
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 419
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 423
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 446
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 452
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 455
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 458
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 478
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 481
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
SQ SEQUENCE 527 AA; 59491 MW; B8BDC0BD709AE7ED CRC64;
MSLQMITVRN NTALIQPGFS LMNFDGQIFF FGQKGWPKRS CPTGVFHFDI KQNHLKLKPA
VFSKDSCYLP PLRYPATCTF QGSSESEKQQ YIIHGGKTPN NELSDKIYVM SVVCKNNKKV
TFRCTERDLV GDVPEARYGH SLDVVYSRGK SMGVLFGGRS YMPSNQRTTE KWNSVADCLP
HVFLVDFEFG CATSYILPEL QDGLSFHVSI ARNDTVYILG GHSLANNIRP ANLYRIRVDL
PLGSPAINCT VLPGGISVSS AILTQTNNDE FVIVGGYQLE NQKRMVCNIV SLEDNKIEIQ
EMETPDWTPD IKHSKIWFGS NMGNGSVFLG IPGDNKQIVS EAFYFYMLKC TEDDVHEDQR
TFTNSQTSTE DPGDSTPFED SEEFCFSAEA NSFDGDDEFD TYNEDDEDDE SETGYWITCC
PTCDVDINTW VPFYSTELNK PAMIYCSHGD GHWVHAKCMD LAERTLIHLS EGSNKYYCNE
HVEIARALQT PKRTIPLRKP PMKSLHKKGS GKILTPAKKS FLRRLFD
