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P15918

- RAG1_HUMAN

UniProt

P15918 - RAG1_HUMAN

Protein

V(D)J recombination-activating protein 1

Gene

RAG1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 166 (01 Oct 2014)
      Sequence version 2 (30 Nov 2010)
      Previous versions | rss
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    Functioni

    Catalytic 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. In the RAG complex, RAG1 mediates the DNA-binding to the conserved recombination signal sequences (RSS) and catalyzes the DNA cleavage activities by introducing a double-strand break between the RSS and the adjacent coding segment. RAG2 is not a catalytic component but is required for all known catalytic activities. DNA cleavage 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 addition to its endonuclease activity, RAG1 also acts as a E3 ubiquitin-protein ligase that mediates monoubiquitination of histone H3. Histone H3 monoubiquitination is required for the joining step of V(D)J recombination. Mediates polyubiquitination of KPNA1 By similarity.By similarity

    Cofactori

    Binds 1 divalent metal cation per subunit. Magnesium or manganese By similarity.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi269 – 2691Zinc 1By similarity
    Metal bindingi273 – 2731Zinc 1By similarity
    Metal bindingi293 – 2931Zinc 2By similarity
    Metal bindingi296 – 2961Zinc 1By similarity
    Metal bindingi296 – 2961Zinc 2By similarity
    Metal bindingi298 – 2981Zinc 1By similarity
    Metal bindingi308 – 3081Zinc 3By similarity
    Metal bindingi310 – 3101Zinc 3By similarity
    Metal bindingi313 – 3131Zinc 2By similarity
    Metal bindingi316 – 3161Zinc 2By similarity
    Metal bindingi328 – 3281Zinc 3By similarity
    Metal bindingi331 – 3311Zinc 3By similarity
    Metal bindingi358 – 3581Zinc 4By similarity
    Metal bindingi363 – 3631Zinc 4By similarity
    Metal bindingi375 – 3751Zinc 4By similarity
    Metal bindingi379 – 3791Zinc 4By similarity
    Metal bindingi603 – 6031Divalent metal cation; catalyticBy similarity
    Metal bindingi711 – 7111Divalent metal cation; catalyticBy similarity
    Sitei896 – 8961Essential for DNA hairpin formation, participates in base-stacking interactions near the cleavage siteBy similarity
    Metal bindingi965 – 9651Divalent metal cation; catalyticBy similarity

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri293 – 33240RING-typePROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri354 – 38330RAG1-typeAdd
    BLAST
    DNA bindingi392 – 45968NBDPROSITE-ProRule annotationAdd
    BLAST

    GO - Molecular functioni

    1. acid-amino acid ligase activity Source: InterPro
    2. DNA binding Source: ProtInc
    3. endonuclease activity Source: UniProtKB
    4. histone binding Source: UniProtKB
    5. hydrolase activity, acting on ester bonds Source: InterPro
    6. metal ion binding Source: UniProtKB
    7. protein binding Source: IntAct
    8. protein homodimerization activity Source: UniProtKB
    9. sequence-specific DNA binding Source: UniProtKB
    10. ubiquitin-protein transferase activity Source: UniProtKB
    11. zinc ion binding Source: UniProtKB

    GO - Biological processi

    1. adaptive immune response Source: Ensembl
    2. B cell differentiation Source: UniProtKB
    3. DNA recombination Source: ProtInc
    4. histone monoubiquitination Source: UniProtKB
    5. immune response Source: ProtInc
    6. negative regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: Ensembl
    7. negative regulation of thymocyte apoptotic process Source: Ensembl
    8. nucleic acid phosphodiester bond hydrolysis Source: GOC
    9. pre-B cell allelic exclusion Source: UniProtKB
    10. protein autoubiquitination Source: UniProtKB
    11. regulation of T cell differentiation Source: Ensembl
    12. T cell differentiation in thymus Source: UniProtKB
    13. T cell homeostasis Source: Ensembl
    14. thymus development Source: Ensembl
    15. V(D)J recombination Source: UniProtKB

    Keywords - Molecular functioni

    Chromatin regulator, Endonuclease, Hydrolase, Ligase, Nuclease

    Keywords - Biological processi

    DNA recombination, Ubl conjugation pathway

    Keywords - Ligandi

    DNA-binding, Metal-binding, Zinc

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    V(D)J recombination-activating protein 1
    Short name:
    RAG-1
    Alternative name(s):
    RING finger protein 74
    Including the following 2 domains:
    Endonuclease RAG1 (EC:3.1.-.-)
    E3 ubiquitin-protein ligase RAG1 (EC:6.3.2.-)
    Gene namesi
    Name:RAG1
    Synonyms:RNF74
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 11

    Organism-specific databases

    HGNCiHGNC:9831. RAG1.

    Subcellular locationi

    Nucleus PROSITE-ProRule annotation

    GO - Cellular componenti

    1. nucleus Source: UniProtKB

    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 varianti314 – 3141R → W in CHIDG; reduced recombination activity. 1 Publication
    Corresponds to variant rs121918568 [ dbSNP | Ensembl ].
    VAR_045957
    Natural varianti507 – 5071R → W in OS/T(-)B(-)NK(+) SCID and CHIDG; atypical; reduced recombination activity when associated with H-737. 2 Publications
    Corresponds to variant rs104894298 [ dbSNP | Ensembl ].
    VAR_025979
    Natural varianti737 – 7371R → H in OS and CHIDG; reduced recombination activity when associated with T-507. 2 Publications
    Corresponds to variant rs104894286 [ dbSNP | Ensembl ].
    VAR_008891
    Natural varianti778 – 7781R → Q in CHIDG; reduced recombination activity. 1 Publication
    Corresponds to variant rs121918569 [ dbSNP | Ensembl ].
    VAR_045958
    Natural varianti975 – 9751R → W in CHIDG; reduced recombination activity. 1 Publication
    Corresponds to variant rs121918570 [ dbSNP | Ensembl ].
    VAR_045959
    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.2 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti410 – 4101R → Q in OS/T(-)B(-)NK(+) SCID; atypical. 1 Publication
    Corresponds to variant rs199474684 [ dbSNP | Ensembl ].
    VAR_025974
    Natural varianti433 – 4331V → M in T(-)B(-)NK(+) SCID and OS/T(-)B(-)NK(+) SCID; atypical. 2 Publications
    Corresponds to variant rs199474679 [ dbSNP | Ensembl ].
    VAR_025975
    Natural varianti444 – 4441A → V in OS/T(-)B(-)NK(+) SCID; atypical. 1 Publication
    Corresponds to variant rs199474685 [ dbSNP | Ensembl ].
    VAR_025977
    Natural varianti474 – 4741R → H in OS/T(-)B(-)NK(+) SCID; atypical. 1 Publication
    Corresponds to variant rs199474686 [ dbSNP | Ensembl ].
    VAR_025978
    Natural varianti507 – 5071R → W in OS/T(-)B(-)NK(+) SCID and CHIDG; atypical; reduced recombination activity when associated with H-737. 2 Publications
    Corresponds to variant rs104894298 [ dbSNP | Ensembl ].
    VAR_025979
    Natural varianti522 – 5221W → C in OS/T(-)B(-)NK(+) SCID; atypical. 1 Publication
    Corresponds to variant rs193922461 [ dbSNP | Ensembl ].
    VAR_025980
    Natural varianti559 – 5591R → S in T(-)B(-)NK(+) SCID and OS. 2 Publications
    Corresponds to variant rs199474681 [ dbSNP | Ensembl ].
    VAR_025981
    Natural varianti624 – 6241R → H in T(-)B(-)NK(+) SCID. 2 Publications
    Corresponds to variant rs199474680 [ dbSNP | Ensembl ].
    VAR_007803
    Natural varianti722 – 7221E → K in T(-)B(-)NK(+) SCID. 1 Publication
    Corresponds to variant rs28933392 [ dbSNP | Ensembl ].
    VAR_007804
    Natural varianti753 – 7531H → L in OS/T(-)B(-)NK(+) SCID; atypical. 1 Publication
    Corresponds to variant rs199474687 [ dbSNP | Ensembl ].
    VAR_025984
    Omenn syndrome (OS) [MIM:603554]: Severe immunodeficiency characterized by the presence of activated, anergic, oligoclonal T-cells, hypereosinophilia, and high IgE levels.6 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti328 – 3281C → Y in OS. 1 Publication
    Corresponds to variant rs121918571 [ dbSNP | Ensembl ].
    VAR_025971
    Natural varianti396 – 3961R → C in OS. 2 Publications
    Corresponds to variant rs104894289 [ dbSNP | Ensembl ].
    VAR_008886
    Natural varianti396 – 3961R → H in OS. 2 Publications
    Corresponds to variant rs104894291 [ dbSNP | Ensembl ].
    VAR_008887
    Natural varianti396 – 3961R → L in OS. 1 Publication
    Corresponds to variant rs104894291 [ dbSNP | Ensembl ].
    VAR_025972
    Natural varianti401 – 4011S → P in OS. 2 Publications
    Corresponds to variant rs199474682 [ dbSNP | Ensembl ].
    VAR_025973
    Natural varianti410 – 4101R → Q in OS/T(-)B(-)NK(+) SCID; atypical. 1 Publication
    Corresponds to variant rs199474684 [ dbSNP | Ensembl ].
    VAR_025974
    Natural varianti429 – 4291D → G in OS. 1 Publication
    Corresponds to variant rs104894292 [ dbSNP | Ensembl ].
    VAR_008888
    Natural varianti433 – 4331V → M in T(-)B(-)NK(+) SCID and OS/T(-)B(-)NK(+) SCID; atypical. 2 Publications
    Corresponds to variant rs199474679 [ dbSNP | Ensembl ].
    VAR_025975
    Natural varianti435 – 4351M → V in OS. 1 Publication
    Corresponds to variant rs141524540 [ dbSNP | Ensembl ].
    VAR_025976
    Natural varianti444 – 4441A → V in OS/T(-)B(-)NK(+) SCID; atypical. 1 Publication
    Corresponds to variant rs199474685 [ dbSNP | Ensembl ].
    VAR_025977
    Natural varianti454 – 4541L → Q in OS. 1 Publication
    Corresponds to variant rs199474677 [ dbSNP | Ensembl ].
    VAR_067274
    Natural varianti474 – 4741R → H in OS/T(-)B(-)NK(+) SCID; atypical. 1 Publication
    Corresponds to variant rs199474686 [ dbSNP | Ensembl ].
    VAR_025978
    Natural varianti507 – 5071R → W in OS/T(-)B(-)NK(+) SCID and CHIDG; atypical; reduced recombination activity when associated with H-737. 2 Publications
    Corresponds to variant rs104894298 [ dbSNP | Ensembl ].
    VAR_025979
    Natural varianti522 – 5221W → C in OS/T(-)B(-)NK(+) SCID; atypical. 1 Publication
    Corresponds to variant rs193922461 [ dbSNP | Ensembl ].
    VAR_025980
    Natural varianti559 – 5591R → S in T(-)B(-)NK(+) SCID and OS. 2 Publications
    Corresponds to variant rs199474681 [ dbSNP | Ensembl ].
    VAR_025981
    Natural varianti561 – 5611R → C in OS. 1 Publication
    Corresponds to variant rs104894285 [ dbSNP | Ensembl ].
    VAR_008890
    Natural varianti561 – 5611R → H in OS. 1 Publication
    Corresponds to variant rs104894284 [ dbSNP | Ensembl ].
    VAR_008889
    Natural varianti624 – 6241R → C in OS. 1 Publication
    Corresponds to variant rs199474688 [ dbSNP | Ensembl ].
    VAR_025982
    Natural varianti669 – 6691E → G in OS. 1 Publication
    Corresponds to variant rs199474689 [ dbSNP | Ensembl ].
    VAR_025983
    Natural varianti699 – 6991R → W in OS; also in a patient with multiple autoimmune disorders. 1 Publication
    Corresponds to variant rs199474676 [ dbSNP | Ensembl ].
    VAR_067276
    Natural varianti737 – 7371R → H in OS and CHIDG; reduced recombination activity when associated with T-507. 2 Publications
    Corresponds to variant rs104894286 [ dbSNP | Ensembl ].
    VAR_008891
    Natural varianti753 – 7531H → L in OS/T(-)B(-)NK(+) SCID; atypical. 1 Publication
    Corresponds to variant rs199474687 [ dbSNP | Ensembl ].
    VAR_025984
    Natural varianti885 – 8851L → R in OS. 1 Publication
    Corresponds to variant rs199474691 [ dbSNP | Ensembl ].
    VAR_008893
    Natural varianti912 – 9121Y → C in OS. 1 Publication
    Corresponds to variant rs104894290 [ dbSNP | Ensembl ].
    VAR_008894
    Natural varianti975 – 9751R → Q in OS. 1 Publication
    Corresponds to variant rs150739647 [ dbSNP | Ensembl ].
    VAR_025987
    Alpha/beta T-cell lymphopenia, with gamma/delta T-cell expansion, severe cytomegalovirus infection and autoimmunity (T-CMVA) [MIM:609889]: An immunological disorder characterized by oligoclonal expansion of TCR gamma/delta T-cells, TCR alpha/beta T-cell lymphopenia, severe, disseminated cytomegalovirus infection and autoimmune cytopenia.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti841 – 8411R → W in T-CMVA; also found in a patient with an atypical form of severe combined immunodeficiency /Omenn syndrome. 1 Publication
    Corresponds to variant rs104894287 [ dbSNP | Ensembl ].
    VAR_025985
    Natural varianti981 – 9811Q → P in T-CMVA. 1 Publication
    Corresponds to variant rs104894288 [ dbSNP | Ensembl ].
    VAR_025988

    Keywords - Diseasei

    Disease mutation, SCID

    Organism-specific databases

    MIMi233650. phenotype.
    601457. phenotype.
    603554. phenotype.
    609889. phenotype.
    Orphaneti231154. Combined immunodeficiency T+ B+ due to partial RAG1 deficiency.
    157949. Combined immunodeficiency with skin granulomas.
    39041. Omenn syndrome.
    331206. Severe combined immunodeficiency due to complete RAG1/2 deficiency.
    PharmGKBiPA34185.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 10431043V(D)J recombination-activating protein 1PRO_0000056004Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Cross-linki234 – 234Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity

    Post-translational modificationi

    Autoubiquitinated in the presence of CDC34/UBCH3.By similarity

    Keywords - PTMi

    Isopeptide bond, Ubl conjugation

    Proteomic databases

    PaxDbiP15918.
    PRIDEiP15918.

    PTM databases

    PhosphoSiteiP15918.

    Expressioni

    Tissue specificityi

    Maturing lymphoid cells.

    Gene expression databases

    ArrayExpressiP15918.
    BgeeiP15918.
    CleanExiHS_RAG1.
    GenevestigatoriP15918.

    Interactioni

    Subunit structurei

    Homodimer. Component of the RAG complex composed of core components RAG1 and RAG2, and associated component HMGB1 or HMGB2. Interacts with VPRBP, leading to recruitment of the CUL4A-RBX1-DDB1-DCAF1/VPRBP complex to ubiquitinate proteins and limit error-prone repair during V(D)J recombination By similarity.By similarity

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    NCK1P163332EBI-1755109,EBI-389883

    Protein-protein interaction databases

    BioGridi111832. 18 interactions.
    IntActiP15918. 14 interactions.
    MINTiMINT-1511469.
    STRINGi9606.ENSP00000299440.

    Structurei

    3D structure databases

    ProteinModelPortaliP15918.
    SMRiP15918. Positions 268-383, 392-459.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni1 – 288288Interaction with importin alpha-1Add
    BLAST

    Domaini

    The RING-type zinc finger mediates the E3 ubiquitin-protein ligase activity.By similarity
    The NBD (nonamer binding) DNA-binding domain mediates the specific binding to the nonamer RSS motif by forming a tightly interwoven homodimer that binds and synapses 2 nonamer elements, with each NBD making contact with both DNA molecules. Each RSS is composed of well-conserved heptamer (consensus 5'-CACAGTG-3') and nonamer (consensus 5'-ACAAAAACC-3') sequences separated by a spacer of either 12 bp or 23 bp.PROSITE-ProRule annotation

    Sequence similaritiesi

    Belongs to the RAG1 family.PROSITE-ProRule annotation
    Contains 1 NBD (nonamer binding) DNA-binding domain.PROSITE-ProRule annotation
    Contains 1 RAG1-type zinc finger.Curated
    Contains 1 RING-type zinc finger.PROSITE-ProRule annotation

    Zinc finger

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri293 – 33240RING-typePROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri354 – 38330RAG1-typeAdd
    BLAST

    Keywords - Domaini

    Zinc-finger

    Phylogenomic databases

    eggNOGiNOG45367.
    HOGENOMiHOG000232009.
    HOVERGENiHBG003861.
    InParanoidiP15918.
    KOiK10628.
    OMAiIAKRFRY.
    PhylomeDBiP15918.
    TreeFamiTF331926.

    Family and domain databases

    Gene3Di3.30.160.60. 1 hit.
    3.30.40.10. 1 hit.
    InterProiIPR024627. RAG1.
    IPR023336. RAG_nonamer-bd_dom.
    IPR015880. Znf_C2H2-like.
    IPR013087. Znf_C2H2/integrase_DNA-bd.
    IPR018957. Znf_C3HC4_RING-type.
    IPR001841. Znf_RING.
    IPR013083. Znf_RING/FYVE/PHD.
    IPR017907. Znf_RING_CS.
    IPR019485. Znf_VDJ_recomb-activ_1.
    [Graphical view]
    PANTHERiPTHR11539. PTHR11539. 1 hit.
    PfamiPF12940. RAG1. 1 hit.
    PF00097. zf-C3HC4. 1 hit.
    PF10426. zf-RAG1. 1 hit.
    [Graphical view]
    SMARTiSM00184. RING. 1 hit.
    SM00355. ZnF_C2H2. 2 hits.
    [Graphical view]
    PROSITEiPS51487. NBD. 1 hit.
    PS00518. ZF_RING_1. 1 hit.
    PS50089. ZF_RING_2. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: P15918-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MAASFPPTLG LSSAPDEIQH PHIKFSEWKF KLFRVRSFEK TPEEAQKEKK     50
    DSFEGKPSLE QSPAVLDKAD GQKPVPTQPL LKAHPKFSKK FHDNEKARGK 100
    AIHQANLRHL CRICGNSFRA DEHNRRYPVH GPVDGKTLGL LRKKEKRATS 150
    WPDLIAKVFR IDVKADVDSI HPTEFCHNCW SIMHRKFSSA PCEVYFPRNV 200
    TMEWHPHTPS CDICNTARRG LKRKSLQPNL QLSKKLKTVL DQARQARQHK 250
    RRAQARISSK DVMKKIANCS KIHLSTKLLA VDFPEHFVKS ISCQICEHIL 300
    ADPVETNCKH VFCRVCILRC LKVMGSYCPS CRYPCFPTDL ESPVKSFLSV 350
    LNSLMVKCPA KECNEEVSLE KYNHHISSHK ESKEIFVHIN KGGRPRQHLL 400
    SLTRRAQKHR LRELKLQVKA FADKEEGGDV KSVCMTLFLL ALRARNEHRQ 450
    ADELEAIMQG KGSGLQPAVC LAIRVNTFLS CSQYHKMYRT VKAITGRQIF 500
    QPLHALRNAE KVLLPGYHHF EWQPPLKNVS SSTDVGIIDG LSGLSSSVDD 550
    YPVDTIAKRF RYDSALVSAL MDMEEDILEG MRSQDLDDYL NGPFTVVVKE 600
    SCDGMGDVSE KHGSGPVVPE KAVRFSFTIM KITIAHSSQN VKVFEEAKPN 650
    SELCCKPLCL MLADESDHET LTAILSPLIA EREAMKSSEL MLELGGILRT 700
    FKFIFRGTGY DEKLVREVEG LEASGSVYIC TLCDATRLEA SQNLVFHSIT 750
    RSHAENLERY EVWRSNPYHE SVEELRDRVK GVSAKPFIET VPSIDALHCD 800
    IGNAAEFYKI FQLEIGEVYK NPNASKEERK RWQATLDKHL RKKMNLKPIM 850
    RMNGNFARKL MTKETVDAVC ELIPSEERHE ALRELMDLYL KMKPVWRSSC 900
    PAKECPESLC QYSFNSQRFA ELLSTKFKYR YEGKITNYFH KTLAHVPEII 950
    ERDGSIGAWA SEGNESGNKL FRRFRKMNAR QSKCYEMEDV LKHHWLYTSK 1000
    YLQKFMNAHN ALKTSGFTMN PQASLGDPLG IEDSLESQDS MEF 1043
    Length:1,043
    Mass (Da):119,097
    Last modified:November 30, 2010 - v2
    Checksum:i5417A7413DA8CB65
    GO
    Isoform 2 (identifier: P15918-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         931-1043: YEGKITNYFH...SLESQDSMEF → N

    Note: No experimental confirmation available.

    Show »
    Length:931
    Mass (Da):106,179
    Checksum:iB69216D4F28FE756
    GO

    Sequence cautioni

    The sequence AAM77798.1 differs from that shown. Reason: Erroneous gene model prediction.

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti156 – 1561A → V.1 Publication
    Corresponds to variant rs1801203 [ dbSNP | Ensembl ].
    VAR_007800
    Natural varianti169 – 1691S → L.
    Corresponds to variant rs4151027 [ dbSNP | Ensembl ].
    VAR_029260
    Natural varianti244 – 2441R → G.1 Publication
    Corresponds to variant rs199474683 [ dbSNP | Ensembl ].
    VAR_007801
    Natural varianti247 – 2471R → H.
    Corresponds to variant rs4151029 [ dbSNP | Ensembl ].
    VAR_029261
    Natural varianti249 – 2491H → R.3 Publications
    Corresponds to variant rs3740955 [ dbSNP | Ensembl ].
    VAR_007802
    Natural varianti302 – 3021D → E.
    Corresponds to variant rs4151030 [ dbSNP | Ensembl ].
    VAR_020113
    Natural varianti314 – 3141R → W in CHIDG; reduced recombination activity. 1 Publication
    Corresponds to variant rs121918568 [ dbSNP | Ensembl ].
    VAR_045957
    Natural varianti328 – 3281C → Y in OS. 1 Publication
    Corresponds to variant rs121918571 [ dbSNP | Ensembl ].
    VAR_025971
    Natural varianti396 – 3961R → C in OS. 2 Publications
    Corresponds to variant rs104894289 [ dbSNP | Ensembl ].
    VAR_008886
    Natural varianti396 – 3961R → H in OS. 2 Publications
    Corresponds to variant rs104894291 [ dbSNP | Ensembl ].
    VAR_008887
    Natural varianti396 – 3961R → L in OS. 1 Publication
    Corresponds to variant rs104894291 [ dbSNP | Ensembl ].
    VAR_025972
    Natural varianti401 – 4011S → P in OS. 2 Publications
    Corresponds to variant rs199474682 [ dbSNP | Ensembl ].
    VAR_025973
    Natural varianti410 – 4101R → Q in OS/T(-)B(-)NK(+) SCID; atypical. 1 Publication
    Corresponds to variant rs199474684 [ dbSNP | Ensembl ].
    VAR_025974
    Natural varianti429 – 4291D → G in OS. 1 Publication
    Corresponds to variant rs104894292 [ dbSNP | Ensembl ].
    VAR_008888
    Natural varianti433 – 4331V → M in T(-)B(-)NK(+) SCID and OS/T(-)B(-)NK(+) SCID; atypical. 2 Publications
    Corresponds to variant rs199474679 [ dbSNP | Ensembl ].
    VAR_025975
    Natural varianti435 – 4351M → V in OS. 1 Publication
    Corresponds to variant rs141524540 [ dbSNP | Ensembl ].
    VAR_025976
    Natural varianti444 – 4441A → V in OS/T(-)B(-)NK(+) SCID; atypical. 1 Publication
    Corresponds to variant rs199474685 [ dbSNP | Ensembl ].
    VAR_025977
    Natural varianti449 – 4491R → K.
    Corresponds to variant rs4151031 [ dbSNP | Ensembl ].
    VAR_029262
    Natural varianti454 – 4541L → Q in OS. 1 Publication
    Corresponds to variant rs199474677 [ dbSNP | Ensembl ].
    VAR_067274
    Natural varianti474 – 4741R → C Probable disease-associated mutation found in a patient with relatively late onset of infections and isolated T-cell lymphopenia. 1 Publication
    Corresponds to variant rs199474678 [ dbSNP | Ensembl ].
    VAR_067275
    Natural varianti474 – 4741R → H in OS/T(-)B(-)NK(+) SCID; atypical. 1 Publication
    Corresponds to variant rs199474686 [ dbSNP | Ensembl ].
    VAR_025978
    Natural varianti507 – 5071R → W in OS/T(-)B(-)NK(+) SCID and CHIDG; atypical; reduced recombination activity when associated with H-737. 2 Publications
    Corresponds to variant rs104894298 [ dbSNP | Ensembl ].
    VAR_025979
    Natural varianti522 – 5221W → C in OS/T(-)B(-)NK(+) SCID; atypical. 1 Publication
    Corresponds to variant rs193922461 [ dbSNP | Ensembl ].
    VAR_025980
    Natural varianti525 – 5251P → S.
    Corresponds to variant rs4151032 [ dbSNP | Ensembl ].
    VAR_029263
    Natural varianti559 – 5591R → S in T(-)B(-)NK(+) SCID and OS. 2 Publications
    Corresponds to variant rs199474681 [ dbSNP | Ensembl ].
    VAR_025981
    Natural varianti561 – 5611R → C in OS. 1 Publication
    Corresponds to variant rs104894285 [ dbSNP | Ensembl ].
    VAR_008890
    Natural varianti561 – 5611R → H in OS. 1 Publication
    Corresponds to variant rs104894284 [ dbSNP | Ensembl ].
    VAR_008889
    Natural varianti624 – 6241R → C in OS. 1 Publication
    Corresponds to variant rs199474688 [ dbSNP | Ensembl ].
    VAR_025982
    Natural varianti624 – 6241R → H in T(-)B(-)NK(+) SCID. 2 Publications
    Corresponds to variant rs199474680 [ dbSNP | Ensembl ].
    VAR_007803
    Natural varianti669 – 6691E → G in OS. 1 Publication
    Corresponds to variant rs199474689 [ dbSNP | Ensembl ].
    VAR_025983
    Natural varianti699 – 6991R → W in OS; also in a patient with multiple autoimmune disorders. 1 Publication
    Corresponds to variant rs199474676 [ dbSNP | Ensembl ].
    VAR_067276
    Natural varianti722 – 7221E → K in T(-)B(-)NK(+) SCID. 1 Publication
    Corresponds to variant rs28933392 [ dbSNP | Ensembl ].
    VAR_007804
    Natural varianti737 – 7371R → H in OS and CHIDG; reduced recombination activity when associated with T-507. 2 Publications
    Corresponds to variant rs104894286 [ dbSNP | Ensembl ].
    VAR_008891
    Natural varianti753 – 7531H → L in OS/T(-)B(-)NK(+) SCID; atypical. 1 Publication
    Corresponds to variant rs199474687 [ dbSNP | Ensembl ].
    VAR_025984
    Natural varianti778 – 7781R → Q in CHIDG; reduced recombination activity. 1 Publication
    Corresponds to variant rs121918569 [ dbSNP | Ensembl ].
    VAR_045958
    Natural varianti820 – 8201K → R.
    Corresponds to variant rs2227973 [ dbSNP | Ensembl ].
    VAR_008892
    Natural varianti841 – 8411R → W in T-CMVA; also found in a patient with an atypical form of severe combined immunodeficiency /Omenn syndrome. 1 Publication
    Corresponds to variant rs104894287 [ dbSNP | Ensembl ].
    VAR_025985
    Natural varianti855 – 8551N → I in immunodeficiency; severe combined. 1 Publication
    Corresponds to variant rs199474690 [ dbSNP | Ensembl ].
    VAR_025986
    Natural varianti880 – 8801E → K.
    Corresponds to variant rs4151033 [ dbSNP | Ensembl ].
    VAR_020114
    Natural varianti885 – 8851L → R in OS. 1 Publication
    Corresponds to variant rs199474691 [ dbSNP | Ensembl ].
    VAR_008893
    Natural varianti887 – 8871D → N.
    Corresponds to variant rs4151034 [ dbSNP | Ensembl ].
    VAR_029264
    Natural varianti912 – 9121Y → C in OS. 1 Publication
    Corresponds to variant rs104894290 [ dbSNP | Ensembl ].
    VAR_008894
    Natural varianti975 – 9751R → Q in OS. 1 Publication
    Corresponds to variant rs150739647 [ dbSNP | Ensembl ].
    VAR_025987
    Natural varianti975 – 9751R → W in CHIDG; reduced recombination activity. 1 Publication
    Corresponds to variant rs121918570 [ dbSNP | Ensembl ].
    VAR_045959
    Natural varianti981 – 9811Q → P in T-CMVA. 1 Publication
    Corresponds to variant rs104894288 [ dbSNP | Ensembl ].
    VAR_025988

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei931 – 1043113YEGKI…DSMEF → N in isoform 2. 1 PublicationVSP_055883Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M29474 mRNA. Translation: AAA60248.1.
    AY130302 Genomic DNA. Translation: AAM77798.1. Sequence problems.
    AC061999 Genomic DNA. No translation available.
    AC139427 Genomic DNA. No translation available.
    BC037344 mRNA. Translation: AAH37344.1.
    CCDSiCCDS7902.1.
    PIRiA33754.
    RefSeqiNP_000439.1. NM_000448.2.
    XP_005253098.1. XM_005253041.2.
    UniGeneiHs.677010.
    Hs.73958.

    Genome annotation databases

    EnsembliENST00000299440; ENSP00000299440; ENSG00000166349. [P15918-1]
    ENST00000534663; ENSP00000434610; ENSG00000166349. [P15918-2]
    GeneIDi5896.
    KEGGihsa:5896.
    UCSCiuc001mwu.4. human.

    Polymorphism databases

    DMDMi313104166.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    NIEHS-SNPs
    RAG1base

    RAG1 deficiency database

    Mendelian genes recombination activating gene 1 (RAG1)

    Leiden Open Variation Database (LOVD)

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M29474 mRNA. Translation: AAA60248.1 .
    AY130302 Genomic DNA. Translation: AAM77798.1 . Sequence problems.
    AC061999 Genomic DNA. No translation available.
    AC139427 Genomic DNA. No translation available.
    BC037344 mRNA. Translation: AAH37344.1 .
    CCDSi CCDS7902.1.
    PIRi A33754.
    RefSeqi NP_000439.1. NM_000448.2.
    XP_005253098.1. XM_005253041.2.
    UniGenei Hs.677010.
    Hs.73958.

    3D structure databases

    ProteinModelPortali P15918.
    SMRi P15918. Positions 268-383, 392-459.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 111832. 18 interactions.
    IntActi P15918. 14 interactions.
    MINTi MINT-1511469.
    STRINGi 9606.ENSP00000299440.

    PTM databases

    PhosphoSitei P15918.

    Polymorphism databases

    DMDMi 313104166.

    Proteomic databases

    PaxDbi P15918.
    PRIDEi P15918.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000299440 ; ENSP00000299440 ; ENSG00000166349 . [P15918-1 ]
    ENST00000534663 ; ENSP00000434610 ; ENSG00000166349 . [P15918-2 ]
    GeneIDi 5896.
    KEGGi hsa:5896.
    UCSCi uc001mwu.4. human.

    Organism-specific databases

    CTDi 5896.
    GeneCardsi GC11P036546.
    HGNCi HGNC:9831. RAG1.
    MIMi 179615. gene.
    233650. phenotype.
    601457. phenotype.
    603554. phenotype.
    609889. phenotype.
    neXtProti NX_P15918.
    Orphaneti 231154. Combined immunodeficiency T+ B+ due to partial RAG1 deficiency.
    157949. Combined immunodeficiency with skin granulomas.
    39041. Omenn syndrome.
    331206. Severe combined immunodeficiency due to complete RAG1/2 deficiency.
    PharmGKBi PA34185.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG45367.
    HOGENOMi HOG000232009.
    HOVERGENi HBG003861.
    InParanoidi P15918.
    KOi K10628.
    OMAi IAKRFRY.
    PhylomeDBi P15918.
    TreeFami TF331926.

    Miscellaneous databases

    GenomeRNAii 5896.
    NextBioi 22934.
    PROi P15918.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P15918.
    Bgeei P15918.
    CleanExi HS_RAG1.
    Genevestigatori P15918.

    Family and domain databases

    Gene3Di 3.30.160.60. 1 hit.
    3.30.40.10. 1 hit.
    InterProi IPR024627. RAG1.
    IPR023336. RAG_nonamer-bd_dom.
    IPR015880. Znf_C2H2-like.
    IPR013087. Znf_C2H2/integrase_DNA-bd.
    IPR018957. Znf_C3HC4_RING-type.
    IPR001841. Znf_RING.
    IPR013083. Znf_RING/FYVE/PHD.
    IPR017907. Znf_RING_CS.
    IPR019485. Znf_VDJ_recomb-activ_1.
    [Graphical view ]
    PANTHERi PTHR11539. PTHR11539. 1 hit.
    Pfami PF12940. RAG1. 1 hit.
    PF00097. zf-C3HC4. 1 hit.
    PF10426. zf-RAG1. 1 hit.
    [Graphical view ]
    SMARTi SM00184. RING. 1 hit.
    SM00355. ZnF_C2H2. 2 hits.
    [Graphical view ]
    PROSITEi PS51487. NBD. 1 hit.
    PS00518. ZF_RING_1. 1 hit.
    PS50089. ZF_RING_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "The V(D)J recombination activating gene, RAG-1."
      Schatz D.G., Oettinger M.A., Baltimore D.
      Cell 59:1035-1048(1989) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT ARG-249.
    2. NIEHS SNPs program
      Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    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] (ISOFORM 2), VARIANT ARG-249.
      Tissue: Testis.
    5. "RAG-1 interacts with the repeated amino acid motif of the human homologue of the yeast protein SRP1."
      Cortes P., Ye Z.-S., Baltimore D.
      Proc. Natl. Acad. Sci. U.S.A. 91:7633-7637(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION OF IMPORTIN ALPHA-1 BINDING DOMAIN.
    6. "Two new variants of RAG-1 protein predicted by SSCP."
      Nomdedeu J.F., Lasa A., Seminago R., Rubiol E., Baiget M., Soler J.
      Hum. Mutat. 8:191-192(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS GLY-244 AND ARG-249.
    7. Cited for: VARIANTS T(-)B(-)NK(+) SCID HIS-624 AND LYS-722, VARIANT VAL-156.
    8. Cited for: VARIANTS OS CYS-396; HIS-396; GLY-429; HIS-561; CYS-561; HIS-737 AND CYS-912.
    9. "Characterization of immune function and analysis of RAG gene mutations in Omenn syndrome and related disorders."
      Wada T., Takei K., Kudo M., Shimura S., Kasahara Y., Koizumi S., Kawa-Ha K., Ishida Y., Imashuku S., Seki H., Yachie A.
      Clin. Exp. Immunol. 119:148-155(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS OS CYS-396 AND ARG-885.
    10. Cited for: VARIANTS OS TYR-328; LEU-396; PRO-401; VAL-435; SER-559; CYS-624; GLY-669 AND GLN-975, VARIANTS OS/T(-)B(-)NK(+) SCID GLN-410; MET-433; VAL-444; HIS-474; TRP-507; CYS-522 AND LEU-753, VARIANT IMMUNODEFICIENCY ILE-855.
    11. Cited for: VARIANTS T-CMVA TRP-841 AND PRO-981.
    12. Cited for: VARIANTS CHIDG TRP-314; TRP-507; HIS-737; GLN-778 AND TRP-975, CHARACTERIZATION OF VARIANTS CHIDG TRP-314; TRP-507; HIS-737; GLN-778 AND TRP-975.
    13. "Molecular analysis of T-B-NK+ severe combined immunodeficiency and Omenn syndrome cases in Saudi Arabia."
      Alsmadi O., Al-Ghonaium A., Al-Muhsen S., Arnaout R., Al-Dhekri H., Al-Saud B., Al-Kayal F., Al-Saud H., Al-Mousa H.
      BMC Med. Genet. 10:116-116(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS T(-)B(-)NK(+) SCID MET-433; SER-559 AND HIS-624, VARIANTS OS HIS-396 AND PRO-401.
    14. Cited for: VARIANT CYS-474.
    15. "Novel mutations in RAG1/2 and ADA genes in Israeli patients presenting with T-B-SCID or Omenn syndrome."
      Dalal I., Tasher D., Somech R., Etzioni A., Garti B.Z., Lev D., Cohen S., Somekh E., Leshinsky-Silver E.
      Clin. Immunol. 140:284-290(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT OS GLN-454.
    16. "Clinical characteristics and molecular analysis of three Chinese children with Omenn syndrome."
      Zhang Z.Y., Zhao X.D., Jiang L.P., Liu E.M., Cui Y.X., Wang M., Wei H., Yu J., An Y.F., Yang X.Q.
      Pediatr. Allergy Immunol. 22:482-487(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT OS TRP-699.

    Entry informationi

    Entry nameiRAG1_HUMAN
    AccessioniPrimary (citable) accession number: P15918
    Secondary accession number(s): E9PPC4, Q8IY72, Q8NER2
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 1, 1990
    Last sequence update: November 30, 2010
    Last modified: October 1, 2014
    This is version 166 of the entry and version 2 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, Multifunctional enzyme, 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