Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Basket 0
(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

P21784

- RAG2_MOUSE

UniProt

P21784 - RAG2_MOUSE

Protein

V(D)J recombination-activating protein 2

Gene

Rag2

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
    • BLAST
    • Align
    • Format
    • Add to basket
    • History
      Entry version 122 (01 Oct 2014)
      Sequence version 2 (15 Jul 1998)
      Previous versions | rss
    • Help video
    • Feedback
    • Comment

    Functioni

    Core component of the RAG complex, a multiprotein complex that mediates the DNA cleavage phase during V(D)J recombination. V(D)J recombination assembles a diverse repertoire of immunoglobulin and T-cell receptor genes in developing B and T-lymphocytes through rearrangement of different V (variable), in some cases D (diversity), and J (joining) gene segments. DNA cleavage by the RAG complex occurs in 2 steps: a first nick is introduced in the top strand immediately upstream of the heptamer, generating a 3'-hydroxyl group that can attack the phosphodiester bond on the opposite strand in a direct transesterification reaction, thereby creating 4 DNA ends: 2 hairpin coding ends and 2 blunt, 5'-phosphorylated ends. The chromatin structure plays an essential role in the V(D)J recombination reactions and the presence of histone H3 trimethylated at 'Lys-4' (H3K4me3) stimulates both the nicking and haipinning steps. The RAG complex also plays a role in pre-B cell allelic exclusion, a process leading to expression of a single immunoglobulin heavy chain allele to enforce clonality and monospecific recognition by the B-cell antigen receptor (BCR) expressed on individual B-lymphocytes. The introduction of DNA breaks by the RAG complex on one immunoglobulin allele induces ATM-dependent repositioning of the other allele to pericentromeric heterochromatin, preventing accessibility to the RAG complex and recombination of the second allele. In the RAG complex, RAG2 is not the catalytic component but is required for all known catalytic activities mediated by RAG1. It probably acts as a sensor of chromatin state that recruits the RAG complex to H3K4me3.6 Publications

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi419 – 4191Zinc 12 Publications
    Metal bindingi423 – 4231Zinc 12 Publications
    Metal bindingi446 – 4461Zinc 22 Publications
    Metal bindingi452 – 4521Zinc 22 Publications
    Metal bindingi455 – 4551Zinc 12 Publications
    Metal bindingi458 – 4581Zinc 12 Publications
    Metal bindingi478 – 4781Zinc 22 Publications
    Metal bindingi481 – 4811Zinc 22 Publications

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri416 – 48469PHD-type; atypicalAdd
    BLAST

    GO - Molecular functioni

    1. chromatin binding Source: UniProtKB
    2. DNA binding Source: InterPro
    3. methylated histone binding Source: UniProtKB
    4. phosphatidylinositol-3,4,5-trisphosphate binding Source: UniProtKB
    5. phosphatidylinositol-3,4-bisphosphate binding Source: UniProtKB
    6. phosphatidylinositol-3,5-bisphosphate binding Source: UniProtKB
    7. phosphatidylinositol-4,5-bisphosphate binding Source: UniProtKB
    8. phosphatidylinositol binding Source: UniProtKB
    9. protein binding Source: UniProtKB
    10. zinc ion binding Source: UniProtKB

    GO - Biological processi

    1. B cell differentiation Source: UniProtKB
    2. B cell homeostatic proliferation Source: MGI
    3. B cell lineage commitment Source: MGI
    4. chromatin modification Source: UniProtKB-KW
    5. DNA recombination Source: MGI
    6. positive regulation of organ growth Source: MGI
    7. pre-B cell allelic exclusion Source: UniProtKB
    8. T cell differentiation Source: MGI
    9. T cell differentiation in thymus Source: UniProtKB
    10. T cell lineage commitment Source: MGI
    11. V(D)J recombination Source: UniProtKB

    Keywords - Molecular functioni

    Chromatin regulator

    Keywords - Biological processi

    DNA recombination

    Keywords - Ligandi

    Metal-binding, Zinc

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    V(D)J recombination-activating protein 2
    Short name:
    RAG-2
    Gene namesi
    Name:Rag2
    Synonyms:Rag-2
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 2

    Organism-specific databases

    MGIiMGI:97849. Rag2.

    Subcellular locationi

    GO - Cellular componenti

    1. nucleus Source: UniProtKB

    Keywords - Cellular componenti

    Nucleus

    Pathology & Biotechi

    Disruption phenotypei

    Mice are viable but fail to produce mature B or T-lymphocytes. Very immature lymphoid cells are present in primary lymphoid organs. These cells do not rearrange their immunoglobulin or T-cell receptor loci. Double knockout with TREX1 does not show a visible phenotype.2 Publications

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi128 – 1281D → N: Does not affect the endonuclease activity of the RAG complex. 1 Publication
    Mutagenesisi199 – 1991E → Q: Does not affect the endonuclease activity of the RAG complex. 1 Publication
    Mutagenesisi202 – 2021D → N: Does not affect the endonuclease activity of the RAG complex. 1 Publication
    Mutagenesisi280 – 2801E → Q: Does not affect the endonuclease activity of the RAG complex. 1 Publication
    Mutagenesisi310 – 3101D → N: Does not affect the endonuclease activity of the RAG complex. 1 Publication
    Mutagenesisi358 – 3581D → N: Does not affect the endonuclease activity of the RAG complex. 1 Publication
    Mutagenesisi374 – 3741D → N: Does not affect the endonuclease activity of the RAG complex. 1 Publication
    Mutagenesisi402 – 4021Y → A: Reduced interaction with histones. 1 Publication
    Mutagenesisi403 – 4031N → A: Reduced interaction with histones. 1 Publication
    Mutagenesisi406 – 4061D → A: Reduced interaction with histones. 1 Publication
    Mutagenesisi407 – 4071E → A: Reduced interaction with histones. 1 Publication
    Mutagenesisi408 – 4081D → A: Induces a slight reduction in V(D)J recombination without affecting interaction with histones.
    Mutagenesisi415 – 4151Y → A: Abolishes binding to H3K4me3 without affecting phosphoinositide-binding. 1 Publication
    Mutagenesisi440 – 4401K → A: Binds PtdIns(4,5)P2 at wild-type level. 1 Publication
    Mutagenesisi443 – 4431M → A: Abolishes binding to H3K4me3 without affecting phosphoinositide-binding. 1 Publication
    Mutagenesisi445 – 4451Y → A or D: Still binds H3K4me3 and H3R2me2 but with reduced affinity. 1 Publication
    Mutagenesisi453 – 4531W → R: Abolishes binding to H3K4me3 without affecting phosphoinositide-binding. Impairs enzymatic activity of the RAG complex. 2 Publications
    Mutagenesisi464 – 4641R → A: Leads to a strong reduction in PtdIns(4,5)P2-binding. 1 Publication
    Mutagenesisi468 – 4681H → A: Leads to a strong reduction in PtdIns(4,5)P2-binding. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 527527V(D)J recombination-activating protein 2PRO_0000167138Add
    BLAST

    Proteomic databases

    PRIDEiP21784.

    PTM databases

    PhosphoSiteiP21784.

    Expressioni

    Tissue specificityi

    Maturing lymphoid cells.

    Gene expression databases

    BgeeiP21784.
    CleanExiMM_RAG2.
    GenevestigatoriP21784.

    Interactioni

    Subunit structurei

    Component of the RAG complex composed of core components RAG1 and RAG2, and associated component HMGB1 or HMGB2.4 Publications

    Protein-protein interaction databases

    BioGridi202575. 1 interaction.
    DIPiDIP-46179N.
    IntActiP21784. 3 interactions.
    MINTiMINT-8384500.

    Structurei

    Secondary structure

    1
    527
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi414 – 4174
    Turni427 – 4293
    Beta strandi434 – 4363
    Beta strandi438 – 4403
    Beta strandi443 – 4464
    Beta strandi448 – 4503
    Beta strandi452 – 4554
    Helixi457 – 4593
    Helixi463 – 4719
    Turni479 – 4835

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2JWONMR-A414-487[»]
    2V83X-ray2.40A/B/C414-487[»]
    2V85X-ray2.00A/B414-487[»]
    2V86X-ray2.05A/B414-487[»]
    2V87X-ray1.80A/B414-487[»]
    2V88X-ray2.00A/B414-487[»]
    2V89X-ray1.10A/B414-487[»]
    ProteinModelPortaliP21784.
    SMRiP21784. Positions 414-487.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP21784.

    Family & Domainsi

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi352 – 41059Asp/Glu-rich (acidic)Add
    BLAST

    Domaini

    The atypical PHD-type zinc finger recognizes and binds histone H3 trimethylated on 'Lys-4' (H3K4me3). The presence Tyr-445 instead of a carboxylate in classical PHD-type zinc fingers results in an enhanced binding to H3K4me3 in presence of dimethylated on 'Arg-2' (H3R2me2) rather than inhibited. The atypical PHD-type zinc finger also binds various phosphoinositides, such as phosphatidylinositol 3,4-bisphosphate binding (PtdIns(3,4)P2), phosphatidylinositol 3,5-bisphosphate binding (PtdIns(3,5)P2), phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) and phosphatidylinositol 3,4,5-trisphosphate binding (PtdIns(3,4,5)P3).2 Publications

    Sequence similaritiesi

    Belongs to the RAG2 family.Curated
    Contains 1 PHD-type zinc finger.Curated

    Zinc finger

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri416 – 48469PHD-type; atypicalAdd
    BLAST

    Keywords - Domaini

    Zinc-finger

    Phylogenomic databases

    eggNOGiNOG39310.
    HOGENOMiHOG000237346.
    HOVERGENiHBG006694.
    InParanoidiP21784.
    KOiK10988.
    OMAiFGQKGWP.
    OrthoDBiEOG73804B.
    PhylomeDBiP21784.
    TreeFamiTF331236.

    Family and domain databases

    Gene3Di2.120.10.80. 1 hit.
    InterProiIPR011043. Gal_Oxase/kelch_b-propeller.
    IPR015915. Kelch-typ_b-propeller.
    IPR004321. RAG2.
    IPR025162. RAG2_PHD.
    IPR011011. Znf_FYVE_PHD.
    [Graphical view]
    PANTHERiPTHR10960. PTHR10960. 1 hit.
    PfamiPF03089. RAG2. 1 hit.
    PF13341. RAG2_PHD. 1 hit.
    [Graphical view]
    SUPFAMiSSF50965. SSF50965. 1 hit.
    SSF57903. SSF57903. 1 hit.

    Sequencei

    Sequence statusi: Complete.

    P21784-1 [UniParc]FASTAAdd to Basket

    « Hide

    MSLQMVTVGH NIALIQPGFS LMNFDGQVFF FGQKGWPKRS CPTGVFHFDI    50
    KQNHLKLKPA IFSKDSCYLP PLRYPATCSY KGSIDSDKHQ YIIHGGKTPN 100
    NELSDKIYIM SVACKNNKKV TFRCTEKDLV GDVPEPRYGH SIDVVYSRGK 150
    SMGVLFGGRS YMPSTQRTTE KWNSVADCLP HVFLIDFEFG CATSYILPEL 200
    QDGLSFHVSI ARNDTVYILG GHSLASNIRP ANLYRIRVDL PLGTPAVNCT 250
    VLPGGISVSS AILTQTNNDE FVIVGGYQLE NQKRMVCSLV SLGDNTIEIS 300
    EMETPDWTSD IKHSKIWFGS NMGNGTIFLG IPGDNKQAMS EAFYFYTLRC 350
    SEEDLSEDQK IVSNSQTSTE DPGDSTPFED SEEFCFSAEA TSFDGDDEFD 400
    TYNEDDEDDE SVTGYWITCC PTCDVDINTW VPFYSTELNK PAMIYCSHGD 450
    GHWVHAQCMD LEERTLIHLS EGSNKYYCNE HVQIARALQT PKRNPPLQKP 500
    PMKSLHKKGS GKVLTPAKKS FLRRLFD 527
    Length:527
    Mass (Da):59,074
    Last modified:July 15, 1998 - v2
    Checksum:i51086F95A4A664A7
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M64796 mRNA. Translation: AAB82302.1.
    CCDSiCCDS16462.1.
    PIRiA34852.
    RefSeqiNP_033046.1. NM_009020.3.
    UniGeneiMm.4988.

    Genome annotation databases

    EnsembliENSMUST00000044031; ENSMUSP00000038204; ENSMUSG00000032864.
    ENSMUST00000111227; ENSMUSP00000106858; ENSMUSG00000032864.
    GeneIDi19374.
    KEGGimmu:19374.
    UCSCiuc008lhj.1. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M64796 mRNA. Translation: AAB82302.1 .
    CCDSi CCDS16462.1.
    PIRi A34852.
    RefSeqi NP_033046.1. NM_009020.3.
    UniGenei Mm.4988.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    2JWO NMR - A 414-487 [» ]
    2V83 X-ray 2.40 A/B/C 414-487 [» ]
    2V85 X-ray 2.00 A/B 414-487 [» ]
    2V86 X-ray 2.05 A/B 414-487 [» ]
    2V87 X-ray 1.80 A/B 414-487 [» ]
    2V88 X-ray 2.00 A/B 414-487 [» ]
    2V89 X-ray 1.10 A/B 414-487 [» ]
    ProteinModelPortali P21784.
    SMRi P21784. Positions 414-487.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 202575. 1 interaction.
    DIPi DIP-46179N.
    IntActi P21784. 3 interactions.
    MINTi MINT-8384500.

    PTM databases

    PhosphoSitei P21784.

    Proteomic databases

    PRIDEi P21784.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000044031 ; ENSMUSP00000038204 ; ENSMUSG00000032864 .
    ENSMUST00000111227 ; ENSMUSP00000106858 ; ENSMUSG00000032864 .
    GeneIDi 19374.
    KEGGi mmu:19374.
    UCSCi uc008lhj.1. mouse.

    Organism-specific databases

    CTDi 5897.
    MGIi MGI:97849. Rag2.

    Phylogenomic databases

    eggNOGi NOG39310.
    HOGENOMi HOG000237346.
    HOVERGENi HBG006694.
    InParanoidi P21784.
    KOi K10988.
    OMAi FGQKGWP.
    OrthoDBi EOG73804B.
    PhylomeDBi P21784.
    TreeFami TF331236.

    Miscellaneous databases

    EvolutionaryTracei P21784.
    NextBioi 296467.
    PROi P21784.
    SOURCEi Search...

    Gene expression databases

    Bgeei P21784.
    CleanExi MM_RAG2.
    Genevestigatori P21784.

    Family and domain databases

    Gene3Di 2.120.10.80. 1 hit.
    InterProi IPR011043. Gal_Oxase/kelch_b-propeller.
    IPR015915. Kelch-typ_b-propeller.
    IPR004321. RAG2.
    IPR025162. RAG2_PHD.
    IPR011011. Znf_FYVE_PHD.
    [Graphical view ]
    PANTHERi PTHR10960. PTHR10960. 1 hit.
    Pfami PF03089. RAG2. 1 hit.
    PF13341. RAG2_PHD. 1 hit.
    [Graphical view ]
    SUPFAMi SSF50965. SSF50965. 1 hit.
    SSF57903. SSF57903. 1 hit.
    ProtoNeti Search...

    Publicationsi

    1. "RAG-1 and RAG-2, adjacent genes that synergistically activate V(D)J recombination."
      Oettinger M.A., Schatz D.G., Gorka C., Baltimore D.
      Science 248:1517-1523(1990) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION.
    2. Oettinger M.A., Schatz D.G., Gorka C., Baltimore D.
      Submitted (NOV-1997) to the EMBL/GenBank/DDBJ databases
      Cited for: SEQUENCE REVISION TO 458.
    3. "RAG-2-deficient mice lack mature lymphocytes owing to inability to initiate V(D)J rearrangement."
      Shinkai Y., Rathbun G., Lam K.P., Oltz E.M., Stewart V., Mendelsohn M., Charron J., Datta M., Young F., Stall A.M., Alt F.W.
      Cell 68:855-867(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE.
    4. "Cleavage at a V(D)J recombination signal requires only RAG1 and RAG2 proteins and occurs in two steps."
      McBlane J.F., van Gent D.C., Ramsden D.A., Romeo C., Cuomo C.A., Gellert M., Oettinger M.A.
      Cell 83:387-395(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH RAG1.
    5. "RAG1 and RAG2 form a stable postcleavage synaptic complex with DNA containing signal ends in V(D)J recombination."
      Agrawal A., Schatz D.G.
      Cell 89:43-53(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, IDENTIFICATION IN THE RAG COMPLEX.
    6. "Stimulation of V(D)J cleavage by high mobility group proteins."
      van Gent D.C., Hiom K., Paull T.T., Gellert M.
      EMBO J. 16:2665-2670(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION IN THE RAG COMPLEX.
    7. "Mutational analysis of RAG1 and RAG2 identifies three catalytic amino acids in RAG1 critical for both cleavage steps of V(D)J recombination."
      Landree M.A., Wibbenmeyer J.A., Roth D.B.
      Genes Dev. 13:3059-3069(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: MUTAGENESIS OF ASP-128; GLU-199; ASP-202; GLU-280; ASP-310; ASP-358 AND ASP-374.
    8. "A direct interaction between the RAG2 C terminus and the core histones is required for efficient V(D)J recombination."
      West K.L., Singha N.C., De Ioannes P., Lacomis L., Erdjument-Bromage H., Tempst P., Cortes P.
      Immunity 23:203-212(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, HISTONE-BINDING, MUTAGENESIS OF TYR-402; ASN-403; ASP-406 AND GLU-407.
    9. Cited for: DOMAIN PHD-TYPE ZINC-FINGER, ZINC-BINDING, HISTONE-BINDING, MUTAGENESIS OF TYR-415; MET-443 AND TRP-453.
    10. "Trex1 prevents cell-intrinsic initiation of autoimmunity."
      Stetson D.B., Ko J.S., Heidmann T., Medzhitov R.
      Cell 134:587-598(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE.
    11. "H3K4me3 stimulates the V(D)J RAG complex for both nicking and hairpinning in trans in addition to tethering in cis: implications for translocations."
      Shimazaki N., Tsai A.G., Lieber M.R.
      Mol. Cell 34:535-544(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, MUTAGENESIS OF TRP-453.
    12. Cited for: FUNCTION.
    13. "Structure of the RAG1 nonamer binding domain with DNA reveals a dimer that mediates DNA synapsis."
      Yin F.F., Bailey S., Innis C.A., Ciubotaru M., Kamtekar S., Steitz T.A., Schatz D.G.
      Nat. Struct. Mol. Biol. 16:499-508(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH RAG1.
    14. Cited for: STRUCTURE BY NMR OF 414-487 IN COMPLEX WITH ZINC, ZINC-BINDING, PHOSPHOINOSITIDE-BINDING, MUTAGENESIS OF LYS-440; ARG-464 AND HIS-468.
    15. "The plant homeodomain finger of RAG2 recognizes histone H3 methylated at both lysine-4 and arginine-2."
      Ramon-Maiques S., Kuo A.J., Carney D., Matthews A.G., Oettinger M.A., Gozani O., Yang W.
      Proc. Natl. Acad. Sci. U.S.A. 104:18993-18998(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 414-487 IN COMPLEX WITH ZINC AND H3 PEPTIDE, DOMAIN PHD-TYPE ZINC-FINGER, ZINC-BINDING, HISTONE-BINDING, MUTAGENESIS OF TYR-445.

    Entry informationi

    Entry nameiRAG2_MOUSE
    AccessioniPrimary (citable) accession number: P21784
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 1, 1991
    Last sequence update: July 15, 1998
    Last modified: October 1, 2014
    This is version 122 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3