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P55895

- RAG2_HUMAN

UniProt

P55895 - RAG2_HUMAN

Protein

V(D)J recombination-activating protein 2

Gene

RAG2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 124 (01 Oct 2014)
      Sequence version 1 (01 Nov 1997)
      Previous versions | rss
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    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 By similarity.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi419 – 4191Zinc 1By similarity
    Metal bindingi423 – 4231Zinc 1By similarity
    Metal bindingi446 – 4461Zinc 2By similarity
    Metal bindingi452 – 4521Zinc 2By similarity
    Metal bindingi455 – 4551Zinc 1By similarity
    Metal bindingi458 – 4581Zinc 1By similarity
    Metal bindingi478 – 4781Zinc 2By similarity
    Metal bindingi481 – 4811Zinc 2By similarity

    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. zinc ion binding Source: UniProtKB

    GO - Biological processi

    1. B cell differentiation Source: UniProtKB
    2. B cell homeostatic proliferation Source: Ensembl
    3. B cell lineage commitment Source: Ensembl
    4. chromatin modification Source: UniProtKB-KW
    5. positive regulation of organ growth Source: Ensembl
    6. pre-B cell allelic exclusion Source: UniProtKB
    7. T cell differentiation in thymus Source: UniProtKB
    8. T cell lineage commitment Source: Ensembl
    9. 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
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 11

    Organism-specific databases

    HGNCiHGNC:9832. RAG2.

    Subcellular locationi

    Nucleus By similarity

    GO - Cellular componenti

    1. nucleus Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Nucleus

    Pathology & Biotechi

    Involvement in diseasei

    Combined cellular and humoral immune defects with granulomas (CHIDG) [MIM:233650]: Immunodeficiency disease with granulomas in the skin, mucous membranes, and internal organs. Other characteristics include hypogammaglobulinemia, a diminished number of T and B-cells, and sparse thymic tissue on ultrasonography.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti77 – 771T → N in CHIDG; reduced recombination activity. 1 Publication
    VAR_045960
    Natural varianti451 – 4511G → A in CHIDG; reduced recombination activity. 1 Publication
    VAR_045962
    Severe combined immunodeficiency autosomal recessive T-cell-negative/B-cell-negative/NK-cell-positive (T(-)B(-)NK(+) SCID) [MIM:601457]: A form of severe combined immunodeficiency (SCID), a genetically and clinically heterogeneous group of rare congenital disorders characterized by impairment of both humoral and cell-mediated immunity, leukopenia, and low or absent antibody levels. Patients present in infancy recurrent, persistent infections by opportunistic organisms. The common characteristic of all types of SCID is absence of T-cell-mediated cellular immunity due to a defect in T-cell development.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti229 – 2291R → Q in T(-)B(-)NK(+) SCID. 1 Publication
    VAR_005570
    Natural varianti478 – 4781C → Y in T(-)B(-)NK(+) SCID. 1 Publication
    VAR_005571
    Omenn syndrome (OS) [MIM:603554]: Severe immunodeficiency characterized by the presence of activated, anergic, oligoclonal T-cells, hypereosinophilia, and high IgE levels.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti41 – 411C → W in OS. 1 Publication
    VAR_008895
    Natural varianti285 – 2851M → R in OS. 1 Publication
    VAR_008896

    Keywords - Diseasei

    Disease mutation, SCID

    Organism-specific databases

    MIMi233650. phenotype.
    601457. phenotype.
    603554. phenotype.
    Orphaneti157949. Combined immunodeficiency with skin granulomas.
    39041. Omenn syndrome.
    331206. Severe combined immunodeficiency due to complete RAG1/2 deficiency.
    PharmGKBiPA34186.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 527527V(D)J recombination-activating protein 2PRO_0000167137Add
    BLAST

    Proteomic databases

    PaxDbiP55895.
    PRIDEiP55895.

    PTM databases

    PhosphoSiteiP55895.

    Expressioni

    Tissue specificityi

    Cells of the B- and T-lymphocyte lineages.

    Gene expression databases

    BgeeiP55895.
    CleanExiHS_RAG2.
    GenevestigatoriP55895.

    Interactioni

    Subunit structurei

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

    Protein-protein interaction databases

    BioGridi111833. 6 interactions.
    STRINGi9606.ENSP00000308620.

    Structurei

    3D structure databases

    ProteinModelPortaliP55895.
    SMRiP55895. Positions 414-486.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    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) By similarity.By similarity

    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.
    InParanoidiP55895.
    KOiK10988.
    OMAiFGQKGWP.
    OrthoDBiEOG73804B.
    PhylomeDBiP55895.
    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.

    P55895-1 [UniParc]FASTAAdd to Basket

    « Hide

    MSLQMVTVSN NIALIQPGFS LMNFDGQVFF FGQKGWPKRS CPTGVFHLDV    50
    KHNHVKLKPT IFSKDSCYLP PLRYPATCTF KGSLESEKHQ YIIHGGKTPN 100
    NEVSDKIYVM SIVCKNNKKV TFRCTEKDLV GDVPEARYGH SINVVYSRGK 150
    SMGVLFGGRS YMPSTHRTTE KWNSVADCLP CVFLVDFEFG CATSYILPEL 200
    QDGLSFHVSI AKNDTIYILG GHSLANNIRP ANLYRIRVDL PLGSPAVNCT 250
    VLPGGISVSS AILTQTNNDE FVIVGGYQLE NQKRMICNII SLEDNKIEIR 300
    EMETPDWTPD IKHSKIWFGS NMGNGTVFLG IPGDNKQVVS EGFYFYMLKC 350
    AEDDTNEEQT TFTNSQTSTE DPGDSTPFED SEEFCFSAEA NSFDGDDEFD 400
    TYNEDDEEDE SETGYWITCC PTCDVDINTW VPFYSTELNK PAMIYCSHGD 450
    GHWVHAQCMD LAERTLIHLS AGSNKYYCNE HVEIARALHT PQRVLPLKKP 500
    PMKSLRKKGS GKILTPAKKS FLRRLFD 527
    Length:527
    Mass (Da):59,241
    Last modified:November 1, 1997 - v1
    Checksum:i1CC4D0F88635BA87
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti154 – 1541V → A in AAH22397. (PubMed:15489334)Curated
    Sequence conflicti322 – 3221M → T in AAH22397. (PubMed:15489334)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti41 – 411C → W in OS. 1 Publication
    VAR_008895
    Natural varianti77 – 771T → N in CHIDG; reduced recombination activity. 1 Publication
    VAR_045960
    Natural varianti229 – 2291R → Q in T(-)B(-)NK(+) SCID. 1 Publication
    VAR_005570
    Natural varianti285 – 2851M → R in OS. 1 Publication
    VAR_008896
    Natural varianti293 – 2931E → G.
    Corresponds to variant rs16929093 [ dbSNP | Ensembl ].
    VAR_045961
    Natural varianti451 – 4511G → A in CHIDG; reduced recombination activity. 1 Publication
    VAR_045962
    Natural varianti478 – 4781C → Y in T(-)B(-)NK(+) SCID. 1 Publication
    VAR_005571

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M94633 Genomic DNA. No translation available.
    AK292664 mRNA. Translation: BAF85353.1.
    CH471064 Genomic DNA. Translation: EAW68117.1.
    BC022397 mRNA. Translation: AAH22397.1.
    CCDSiCCDS7903.1.
    RefSeqiNP_000527.2. NM_000536.3.
    NP_001230714.1. NM_001243785.1.
    NP_001230715.1. NM_001243786.1.
    UniGeneiHs.714519.

    Genome annotation databases

    EnsembliENST00000311485; ENSP00000308620; ENSG00000175097.
    GeneIDi5897.
    KEGGihsa:5897.
    UCSCiuc001mwv.4. human.

    Polymorphism databases

    DMDMi2498830.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Web resourcesi

    RAG2base

    RAG2 deficiency database

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M94633 Genomic DNA. No translation available.
    AK292664 mRNA. Translation: BAF85353.1 .
    CH471064 Genomic DNA. Translation: EAW68117.1 .
    BC022397 mRNA. Translation: AAH22397.1 .
    CCDSi CCDS7903.1.
    RefSeqi NP_000527.2. NM_000536.3.
    NP_001230714.1. NM_001243785.1.
    NP_001230715.1. NM_001243786.1.
    UniGenei Hs.714519.

    3D structure databases

    ProteinModelPortali P55895.
    SMRi P55895. Positions 414-486.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 111833. 6 interactions.
    STRINGi 9606.ENSP00000308620.

    PTM databases

    PhosphoSitei P55895.

    Polymorphism databases

    DMDMi 2498830.

    Proteomic databases

    PaxDbi P55895.
    PRIDEi P55895.

    Protocols and materials databases

    DNASUi 5897.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000311485 ; ENSP00000308620 ; ENSG00000175097 .
    GeneIDi 5897.
    KEGGi hsa:5897.
    UCSCi uc001mwv.4. human.

    Organism-specific databases

    CTDi 5897.
    GeneCardsi GC11M036613.
    H-InvDB HIX0009568.
    HGNCi HGNC:9832. RAG2.
    MIMi 179616. gene.
    233650. phenotype.
    601457. phenotype.
    603554. phenotype.
    neXtProti NX_P55895.
    Orphaneti 157949. Combined immunodeficiency with skin granulomas.
    39041. Omenn syndrome.
    331206. Severe combined immunodeficiency due to complete RAG1/2 deficiency.
    PharmGKBi PA34186.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG39310.
    HOGENOMi HOG000237346.
    HOVERGENi HBG006694.
    InParanoidi P55895.
    KOi K10988.
    OMAi FGQKGWP.
    OrthoDBi EOG73804B.
    PhylomeDBi P55895.
    TreeFami TF331236.

    Miscellaneous databases

    GenomeRNAii 5897.
    NextBioi 22938.
    PROi P55895.
    SOURCEi Search...

    Gene expression databases

    Bgeei P55895.
    CleanExi HS_RAG2.
    Genevestigatori P55895.

    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. "Sequence and chromosome assignment to 11p13-p12 of human RAG genes."
      Ichihara Y., Hirai M., Kurosawa Y.
      Immunol. Lett. 33:277-284(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
      Tissue: Placenta.
    2. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Thymus.
    3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Testis.
    5. "Expression of human recombination activating genes (RAG1 and RAG2) in neoplastic lymphoid cells: correlation with cell differentiation and antigen receptor expression."
      Bories J.C., Cayuela J.-M., Loiseau P., Sigaux F.
      Blood 78:2053-2061(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 318-411.
    6. Cited for: VARIANTS T(-)B(-)NK(+) SCID GLN-229 AND TYR-478.
    7. Cited for: VARIANTS OS TRP-41 AND ARG-285.
    8. Cited for: VARIANTS CHIDG ASN-77 AND ALA-451, CHARACTERIZATION OF VARIANTS CHIDG ASN-77 AND ALA-451.

    Entry informationi

    Entry nameiRAG2_HUMAN
    AccessioniPrimary (citable) accession number: P55895
    Secondary accession number(s): A8K9E9, Q8TBL4
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 1, 1997
    Last sequence update: November 1, 1997
    Last modified: October 1, 2014
    This is version 124 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 11
      Human chromosome 11: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3