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Protein

V(D)J recombination-activating protein 1

Gene

RAG1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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 an 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

Mg2+By similarity, Mn2+By similarityNote: Binds 1 divalent metal cation per subunit. Mg2+ or Mn2+.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi269Zinc 1By similarity1
Metal bindingi273Zinc 1By similarity1
Metal bindingi293Zinc 2By similarity1
Metal bindingi296Zinc 1By similarity1
Metal bindingi296Zinc 2By similarity1
Metal bindingi298Zinc 1By similarity1
Metal bindingi308Zinc 3By similarity1
Metal bindingi310Zinc 3By similarity1
Metal bindingi313Zinc 2By similarity1
Metal bindingi316Zinc 2By similarity1
Metal bindingi328Zinc 3By similarity1
Metal bindingi331Zinc 3By similarity1
Metal bindingi358Zinc 4By similarity1
Metal bindingi363Zinc 4By similarity1
Metal bindingi375Zinc 4By similarity1
Metal bindingi379Zinc 4By similarity1
Metal bindingi603Divalent metal cation; catalyticBy similarity1
Metal bindingi711Divalent metal cation; catalyticBy similarity1
Sitei896Essential for DNA hairpin formation, participates in base-stacking interactions near the cleavage siteBy similarity1
Metal bindingi965Divalent metal cation; catalyticBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri293 – 332RING-typePROSITE-ProRule annotationAdd BLAST40
Zinc fingeri354 – 383RAG1-typePROSITE-ProRule annotationAdd BLAST30
DNA bindingi392 – 459NBDPROSITE-ProRule annotationAdd BLAST68

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Chromatin regulator, Endonuclease, Hydrolase, Ligase, Nuclease

Keywords - Biological processi

DNA recombination, Ubl conjugation pathway

Keywords - Ligandi

DNA-binding, Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:ENSG00000166349-MONOMER.
ReactomeiR-HSA-1266695. Interleukin-7 signaling.
R-HSA-5687128. MAPK6/MAPK4 signaling.
SIGNORiP15918.

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
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:9831. RAG1.

Subcellular locationi

  • Nucleus PROSITE-ProRule annotation

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

Combined cellular and humoral immune defects with granulomas (CHIDG)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionImmunodeficiency 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.
See also OMIM:233650
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_045957314R → W in CHIDG; reduced recombination activity. 1 PublicationCorresponds to variant rs121918568dbSNPEnsembl.1
Natural variantiVAR_025979507R → W in CHIDG and OS; found in patients with an atypical form of severe combined immunodeficiency/Omenn syndrome; reduced recombination activity when associated with H-737. 2 PublicationsCorresponds to variant rs104894298dbSNPEnsembl.1
Natural variantiVAR_008891737R → H in OS and CHIDG; reduced recombination activity when associated with T-507. 2 PublicationsCorresponds to variant rs104894286dbSNPEnsembl.1
Natural variantiVAR_045958778R → Q in CHIDG; reduced recombination activity. 1 PublicationCorresponds to variant rs121918569dbSNPEnsembl.1
Natural variantiVAR_045959975R → W in CHIDG; reduced recombination activity. 1 PublicationCorresponds to variant rs121918570dbSNPEnsembl.1
Severe combined immunodeficiency autosomal recessive T-cell-negative/B-cell-negative/NK-cell-positive (T(-)B(-)NK(+) SCID)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:601457
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_025975433V → M in OS and T(-)B(-)NK(+) SCID; found in a patient with an atypical form of severe combined immunodeficiency/Omenn syndrome. 2 PublicationsCorresponds to variant rs199474679dbSNPEnsembl.1
Natural variantiVAR_025981559R → S in T(-)B(-)NK(+) SCID and OS. 2 PublicationsCorresponds to variant rs199474681dbSNPEnsembl.1
Natural variantiVAR_007803624R → H in T(-)B(-)NK(+) SCID. 2 PublicationsCorresponds to variant rs199474680dbSNPEnsembl.1
Natural variantiVAR_007804722E → K in T(-)B(-)NK(+) SCID. 1 PublicationCorresponds to variant rs28933392dbSNPEnsembl.1
Omenn syndrome (OS)6 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionSevere immunodeficiency characterized by the presence of activated, anergic, oligoclonal T-cells, hypereosinophilia, and high IgE levels.
See also OMIM:603554
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_025971328C → Y in OS. 1 PublicationCorresponds to variant rs121918571dbSNPEnsembl.1
Natural variantiVAR_008886396R → C in OS. 2 PublicationsCorresponds to variant rs104894289dbSNPEnsembl.1
Natural variantiVAR_008887396R → H in OS. 2 PublicationsCorresponds to variant rs104894291dbSNPEnsembl.1
Natural variantiVAR_025972396R → L in OS. 1 PublicationCorresponds to variant rs104894291dbSNPEnsembl.1
Natural variantiVAR_025973401S → P in OS. 2 PublicationsCorresponds to variant rs199474682dbSNPEnsembl.1
Natural variantiVAR_025974410R → Q in OS; found in patients with an atypical form of severe combined immunodeficiency/Omenn syndrome. 1 PublicationCorresponds to variant rs199474684dbSNPEnsembl.1
Natural variantiVAR_008888429D → G in OS. 1 PublicationCorresponds to variant rs104894292dbSNPEnsembl.1
Natural variantiVAR_025975433V → M in OS and T(-)B(-)NK(+) SCID; found in a patient with an atypical form of severe combined immunodeficiency/Omenn syndrome. 2 PublicationsCorresponds to variant rs199474679dbSNPEnsembl.1
Natural variantiVAR_025976435M → V in OS. 1 PublicationCorresponds to variant rs141524540dbSNPEnsembl.1
Natural variantiVAR_025977444A → V in OS; found in patients with an atypical form of severe combined immunodeficiency/Omenn syndrome. 1 PublicationCorresponds to variant rs199474685dbSNPEnsembl.1
Natural variantiVAR_067274454L → Q in OS. 1 PublicationCorresponds to variant rs199474677dbSNPEnsembl.1
Natural variantiVAR_025978474R → H in OS; found in patients with an atypical form of severe combined immunodeficiency/Omenn syndrome. 1 PublicationCorresponds to variant rs199474686dbSNPEnsembl.1
Natural variantiVAR_025979507R → W in CHIDG and OS; found in patients with an atypical form of severe combined immunodeficiency/Omenn syndrome; reduced recombination activity when associated with H-737. 2 PublicationsCorresponds to variant rs104894298dbSNPEnsembl.1
Natural variantiVAR_025980522W → C in OS; found in patients with an atypical form of severe combined immunodeficiency/Omenn syndrome. 1 PublicationCorresponds to variant rs193922461dbSNPEnsembl.1
Natural variantiVAR_025981559R → S in T(-)B(-)NK(+) SCID and OS. 2 PublicationsCorresponds to variant rs199474681dbSNPEnsembl.1
Natural variantiVAR_008890561R → C in OS. 1 PublicationCorresponds to variant rs104894285dbSNPEnsembl.1
Natural variantiVAR_008889561R → H in OS. 1 PublicationCorresponds to variant rs104894284dbSNPEnsembl.1
Natural variantiVAR_025982624R → C in OS. 1 PublicationCorresponds to variant rs199474688dbSNPEnsembl.1
Natural variantiVAR_025983669E → G in OS. 1 PublicationCorresponds to variant rs199474689dbSNPEnsembl.1
Natural variantiVAR_067276699R → W in OS; also in a patient with multiple autoimmune disorders. 1 PublicationCorresponds to variant rs199474676dbSNPEnsembl.1
Natural variantiVAR_008891737R → H in OS and CHIDG; reduced recombination activity when associated with T-507. 2 PublicationsCorresponds to variant rs104894286dbSNPEnsembl.1
Natural variantiVAR_025984753H → L in OS; found in patients with an atypical form of severe combined immunodeficiency/Omenn syndrome. 1 PublicationCorresponds to variant rs199474687dbSNPEnsembl.1
Natural variantiVAR_008893885L → R in OS. 1 PublicationCorresponds to variant rs199474691dbSNPEnsembl.1
Natural variantiVAR_008894912Y → C in OS. 1 PublicationCorresponds to variant rs104894290dbSNPEnsembl.1
Natural variantiVAR_025987975R → Q in OS. 1 PublicationCorresponds to variant rs150739647dbSNPEnsembl.1
Alpha/beta T-cell lymphopenia, with gamma/delta T-cell expansion, severe cytomegalovirus infection and autoimmunity (T-CMVA)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn 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.
See also OMIM:609889
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_025985841R → W in T-CMVA; also found in a patient with an atypical form of severe combined immunodeficiency /Omenn syndrome. 1 PublicationCorresponds to variant rs104894287dbSNPEnsembl.1
Natural variantiVAR_025988981Q → P in T-CMVA. 1 PublicationCorresponds to variant rs104894288dbSNPEnsembl.1

Keywords - Diseasei

Disease mutation, SCID

Organism-specific databases

DisGeNETi5896.
MalaCardsiRAG1.
MIMi233650. phenotype.
601457. phenotype.
603554. phenotype.
609889. phenotype.
OpenTargetsiENSG00000166349.
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.

Polymorphism and mutation databases

BioMutaiRAG1.
DMDMi313104166.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000560041 – 1043V(D)J recombination-activating protein 1Add BLAST1043

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki234Glycyl 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

iPTMnetiP15918.
PhosphoSitePlusiP15918.

Expressioni

Tissue specificityi

Maturing lymphoid cells.

Gene expression databases

BgeeiENSG00000166349.
CleanExiHS_RAG1.
GenevisibleiP15918. HS.

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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi111832. 25 interactors.
IntActiP15918. 14 interactors.
MINTiMINT-1511469.
STRINGi9606.ENSP00000299440.

Structurei

3D structure databases

ProteinModelPortaliP15918.
SMRiP15918.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 288Interaction with importin alpha-1Add BLAST288

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.PROSITE-ProRule annotationCurated
Contains 1 RING-type zinc finger.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri293 – 332RING-typePROSITE-ProRule annotationAdd BLAST40
Zinc fingeri354 – 383RAG1-typePROSITE-ProRule annotationAdd BLAST30

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiENOG410IKNG. Eukaryota.
ENOG4110KH0. LUCA.
GeneTreeiENSGT00390000008679.
HOGENOMiHOG000232009.
HOVERGENiHBG003861.
InParanoidiP15918.
KOiK10628.
OMAiIAKRFRY.
OrthoDBiEOG091G00XO.
PhylomeDBiP15918.
TreeFamiTF331926.

Family and domain databases

Gene3Di3.30.160.60. 1 hit.
3.30.40.10. 1 hit.
InterProiIPR024627. RAG1.
IPR019485. RAG1_Znf.
IPR023336. RAG_nonamer-bd_dom.
IPR013087. Znf_C2H2/integrase_DNA-bd.
IPR018957. Znf_C3HC4_RING-type.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
[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.
[Graphical view]
PROSITEiPS51487. NBD. 1 hit.
PS51765. ZF_RAG1. 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. AlignAdd to basket

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

        10         20         30         40         50
MAASFPPTLG LSSAPDEIQH PHIKFSEWKF KLFRVRSFEK TPEEAQKEKK
60 70 80 90 100
DSFEGKPSLE QSPAVLDKAD GQKPVPTQPL LKAHPKFSKK FHDNEKARGK
110 120 130 140 150
AIHQANLRHL CRICGNSFRA DEHNRRYPVH GPVDGKTLGL LRKKEKRATS
160 170 180 190 200
WPDLIAKVFR IDVKADVDSI HPTEFCHNCW SIMHRKFSSA PCEVYFPRNV
210 220 230 240 250
TMEWHPHTPS CDICNTARRG LKRKSLQPNL QLSKKLKTVL DQARQARQHK
260 270 280 290 300
RRAQARISSK DVMKKIANCS KIHLSTKLLA VDFPEHFVKS ISCQICEHIL
310 320 330 340 350
ADPVETNCKH VFCRVCILRC LKVMGSYCPS CRYPCFPTDL ESPVKSFLSV
360 370 380 390 400
LNSLMVKCPA KECNEEVSLE KYNHHISSHK ESKEIFVHIN KGGRPRQHLL
410 420 430 440 450
SLTRRAQKHR LRELKLQVKA FADKEEGGDV KSVCMTLFLL ALRARNEHRQ
460 470 480 490 500
ADELEAIMQG KGSGLQPAVC LAIRVNTFLS CSQYHKMYRT VKAITGRQIF
510 520 530 540 550
QPLHALRNAE KVLLPGYHHF EWQPPLKNVS SSTDVGIIDG LSGLSSSVDD
560 570 580 590 600
YPVDTIAKRF RYDSALVSAL MDMEEDILEG MRSQDLDDYL NGPFTVVVKE
610 620 630 640 650
SCDGMGDVSE KHGSGPVVPE KAVRFSFTIM KITIAHSSQN VKVFEEAKPN
660 670 680 690 700
SELCCKPLCL MLADESDHET LTAILSPLIA EREAMKSSEL MLELGGILRT
710 720 730 740 750
FKFIFRGTGY DEKLVREVEG LEASGSVYIC TLCDATRLEA SQNLVFHSIT
760 770 780 790 800
RSHAENLERY EVWRSNPYHE SVEELRDRVK GVSAKPFIET VPSIDALHCD
810 820 830 840 850
IGNAAEFYKI FQLEIGEVYK NPNASKEERK RWQATLDKHL RKKMNLKPIM
860 870 880 890 900
RMNGNFARKL MTKETVDAVC ELIPSEERHE ALRELMDLYL KMKPVWRSSC
910 920 930 940 950
PAKECPESLC QYSFNSQRFA ELLSTKFKYR YEGKITNYFH KTLAHVPEII
960 970 980 990 1000
ERDGSIGAWA SEGNESGNKL FRRFRKMNAR QSKCYEMEDV LKHHWLYTSK
1010 1020 1030 1040
YLQKFMNAHN ALKTSGFTMN PQASLGDPLG IEDSLESQDS MEF
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 differs from that shown. Reason: Erroneous gene model prediction.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_007800156A → V.1 PublicationCorresponds to variant rs1801203dbSNPEnsembl.1
Natural variantiVAR_029260169S → L.Corresponds to variant rs4151027dbSNPEnsembl.1
Natural variantiVAR_007801244R → G.1 PublicationCorresponds to variant rs199474683dbSNPEnsembl.1
Natural variantiVAR_029261247R → H.Corresponds to variant rs4151029dbSNPEnsembl.1
Natural variantiVAR_007802249H → R.3 PublicationsCorresponds to variant rs3740955dbSNPEnsembl.1
Natural variantiVAR_020113302D → E.Corresponds to variant rs4151030dbSNPEnsembl.1
Natural variantiVAR_045957314R → W in CHIDG; reduced recombination activity. 1 PublicationCorresponds to variant rs121918568dbSNPEnsembl.1
Natural variantiVAR_025971328C → Y in OS. 1 PublicationCorresponds to variant rs121918571dbSNPEnsembl.1
Natural variantiVAR_008886396R → C in OS. 2 PublicationsCorresponds to variant rs104894289dbSNPEnsembl.1
Natural variantiVAR_008887396R → H in OS. 2 PublicationsCorresponds to variant rs104894291dbSNPEnsembl.1
Natural variantiVAR_025972396R → L in OS. 1 PublicationCorresponds to variant rs104894291dbSNPEnsembl.1
Natural variantiVAR_025973401S → P in OS. 2 PublicationsCorresponds to variant rs199474682dbSNPEnsembl.1
Natural variantiVAR_025974410R → Q in OS; found in patients with an atypical form of severe combined immunodeficiency/Omenn syndrome. 1 PublicationCorresponds to variant rs199474684dbSNPEnsembl.1
Natural variantiVAR_008888429D → G in OS. 1 PublicationCorresponds to variant rs104894292dbSNPEnsembl.1
Natural variantiVAR_025975433V → M in OS and T(-)B(-)NK(+) SCID; found in a patient with an atypical form of severe combined immunodeficiency/Omenn syndrome. 2 PublicationsCorresponds to variant rs199474679dbSNPEnsembl.1
Natural variantiVAR_025976435M → V in OS. 1 PublicationCorresponds to variant rs141524540dbSNPEnsembl.1
Natural variantiVAR_025977444A → V in OS; found in patients with an atypical form of severe combined immunodeficiency/Omenn syndrome. 1 PublicationCorresponds to variant rs199474685dbSNPEnsembl.1
Natural variantiVAR_029262449R → K.Corresponds to variant rs4151031dbSNPEnsembl.1
Natural variantiVAR_067274454L → Q in OS. 1 PublicationCorresponds to variant rs199474677dbSNPEnsembl.1
Natural variantiVAR_067275474R → C Probable disease-associated mutation found in a patient with relatively late onset of infections and isolated T-cell lymphopenia. 1 PublicationCorresponds to variant rs199474678dbSNPEnsembl.1
Natural variantiVAR_025978474R → H in OS; found in patients with an atypical form of severe combined immunodeficiency/Omenn syndrome. 1 PublicationCorresponds to variant rs199474686dbSNPEnsembl.1
Natural variantiVAR_025979507R → W in CHIDG and OS; found in patients with an atypical form of severe combined immunodeficiency/Omenn syndrome; reduced recombination activity when associated with H-737. 2 PublicationsCorresponds to variant rs104894298dbSNPEnsembl.1
Natural variantiVAR_025980522W → C in OS; found in patients with an atypical form of severe combined immunodeficiency/Omenn syndrome. 1 PublicationCorresponds to variant rs193922461dbSNPEnsembl.1
Natural variantiVAR_029263525P → S.Corresponds to variant rs4151032dbSNPEnsembl.1
Natural variantiVAR_025981559R → S in T(-)B(-)NK(+) SCID and OS. 2 PublicationsCorresponds to variant rs199474681dbSNPEnsembl.1
Natural variantiVAR_008890561R → C in OS. 1 PublicationCorresponds to variant rs104894285dbSNPEnsembl.1
Natural variantiVAR_008889561R → H in OS. 1 PublicationCorresponds to variant rs104894284dbSNPEnsembl.1
Natural variantiVAR_025982624R → C in OS. 1 PublicationCorresponds to variant rs199474688dbSNPEnsembl.1
Natural variantiVAR_007803624R → H in T(-)B(-)NK(+) SCID. 2 PublicationsCorresponds to variant rs199474680dbSNPEnsembl.1
Natural variantiVAR_025983669E → G in OS. 1 PublicationCorresponds to variant rs199474689dbSNPEnsembl.1
Natural variantiVAR_067276699R → W in OS; also in a patient with multiple autoimmune disorders. 1 PublicationCorresponds to variant rs199474676dbSNPEnsembl.1
Natural variantiVAR_007804722E → K in T(-)B(-)NK(+) SCID. 1 PublicationCorresponds to variant rs28933392dbSNPEnsembl.1
Natural variantiVAR_008891737R → H in OS and CHIDG; reduced recombination activity when associated with T-507. 2 PublicationsCorresponds to variant rs104894286dbSNPEnsembl.1
Natural variantiVAR_025984753H → L in OS; found in patients with an atypical form of severe combined immunodeficiency/Omenn syndrome. 1 PublicationCorresponds to variant rs199474687dbSNPEnsembl.1
Natural variantiVAR_045958778R → Q in CHIDG; reduced recombination activity. 1 PublicationCorresponds to variant rs121918569dbSNPEnsembl.1
Natural variantiVAR_008892820K → R.Corresponds to variant rs2227973dbSNPEnsembl.1
Natural variantiVAR_025985841R → W in T-CMVA; also found in a patient with an atypical form of severe combined immunodeficiency /Omenn syndrome. 1 PublicationCorresponds to variant rs104894287dbSNPEnsembl.1
Natural variantiVAR_025986855N → I Probable disease-associated mutation found in a patient with severe combined immunodeficiency with maternal fetal engraftment. 1 PublicationCorresponds to variant rs199474690dbSNPEnsembl.1
Natural variantiVAR_020114880E → K.Corresponds to variant rs4151033dbSNPEnsembl.1
Natural variantiVAR_008893885L → R in OS. 1 PublicationCorresponds to variant rs199474691dbSNPEnsembl.1
Natural variantiVAR_029264887D → N.Corresponds to variant rs4151034dbSNPEnsembl.1
Natural variantiVAR_008894912Y → C in OS. 1 PublicationCorresponds to variant rs104894290dbSNPEnsembl.1
Natural variantiVAR_025987975R → Q in OS. 1 PublicationCorresponds to variant rs150739647dbSNPEnsembl.1
Natural variantiVAR_045959975R → W in CHIDG; reduced recombination activity. 1 PublicationCorresponds to variant rs121918570dbSNPEnsembl.1
Natural variantiVAR_025988981Q → P in T-CMVA. 1 PublicationCorresponds to variant rs104894288dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_055883931 – 1043YEGKI…DSMEF → N in isoform 2. 1 PublicationAdd BLAST113

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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. [P15918-1]
PIRiA33754.
RefSeqiNP_000439.1. NM_000448.2.
XP_005253098.1. XM_005253041.4. [P15918-1]
XP_011518552.1. XM_011520250.2. [P15918-1]
UniGeneiHs.538979.
Hs.677010.
Hs.73958.

Genome annotation databases

EnsembliENST00000299440; ENSP00000299440; ENSG00000166349. [P15918-1]
ENST00000534663; ENSP00000434610; ENSG00000166349. [P15918-2]
GeneIDi5896.
KEGGihsa:5896.
UCSCiuc001mwt.4. human. [P15918-1]

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:
EMBLi
GenBanki
DDBJi
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. [P15918-1]
PIRiA33754.
RefSeqiNP_000439.1. NM_000448.2.
XP_005253098.1. XM_005253041.4. [P15918-1]
XP_011518552.1. XM_011520250.2. [P15918-1]
UniGeneiHs.538979.
Hs.677010.
Hs.73958.

3D structure databases

ProteinModelPortaliP15918.
SMRiP15918.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111832. 25 interactors.
IntActiP15918. 14 interactors.
MINTiMINT-1511469.
STRINGi9606.ENSP00000299440.

PTM databases

iPTMnetiP15918.
PhosphoSitePlusiP15918.

Polymorphism and mutation databases

BioMutaiRAG1.
DMDMi313104166.

Proteomic databases

PaxDbiP15918.
PRIDEiP15918.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000299440; ENSP00000299440; ENSG00000166349. [P15918-1]
ENST00000534663; ENSP00000434610; ENSG00000166349. [P15918-2]
GeneIDi5896.
KEGGihsa:5896.
UCSCiuc001mwt.4. human. [P15918-1]

Organism-specific databases

CTDi5896.
DisGeNETi5896.
GeneCardsiRAG1.
HGNCiHGNC:9831. RAG1.
MalaCardsiRAG1.
MIMi179615. gene.
233650. phenotype.
601457. phenotype.
603554. phenotype.
609889. phenotype.
neXtProtiNX_P15918.
OpenTargetsiENSG00000166349.
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.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IKNG. Eukaryota.
ENOG4110KH0. LUCA.
GeneTreeiENSGT00390000008679.
HOGENOMiHOG000232009.
HOVERGENiHBG003861.
InParanoidiP15918.
KOiK10628.
OMAiIAKRFRY.
OrthoDBiEOG091G00XO.
PhylomeDBiP15918.
TreeFamiTF331926.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000166349-MONOMER.
ReactomeiR-HSA-1266695. Interleukin-7 signaling.
R-HSA-5687128. MAPK6/MAPK4 signaling.
SIGNORiP15918.

Miscellaneous databases

GenomeRNAii5896.
PROiP15918.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000166349.
CleanExiHS_RAG1.
GenevisibleiP15918. HS.

Family and domain databases

Gene3Di3.30.160.60. 1 hit.
3.30.40.10. 1 hit.
InterProiIPR024627. RAG1.
IPR019485. RAG1_Znf.
IPR023336. RAG_nonamer-bd_dom.
IPR013087. Znf_C2H2/integrase_DNA-bd.
IPR018957. Znf_C3HC4_RING-type.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
[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.
[Graphical view]
PROSITEiPS51487. NBD. 1 hit.
PS51765. ZF_RAG1. 1 hit.
PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

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: November 30, 2016
This is version 188 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.