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P15918

- RAG1_HUMAN

UniProt

P15918 - RAG1_HUMAN

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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

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

Mg2+By similarity, Mn2+By similarityNote: Binds 1 divalent metal cation per subunit. Mg(2+) or Mn(2+).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. metal ion binding Source: UniProtKB
  6. protein homodimerization activity Source: UniProtKB
  7. sequence-specific DNA binding Source: UniProtKB
  8. ubiquitin-protein transferase activity Source: UniProtKB
  9. 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
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

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
Complete GO annotation...

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

BgeeiP15918.
CleanExiHS_RAG1.
ExpressionAtlasiP15918. baseline and differential.
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. 13 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.
GeneTreeiENSGT00390000008679.
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

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

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:
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_005253041.2. [P15918-1]
UniGeneiHs.677010.
Hs.73958.

Genome annotation databases

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

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:
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 .
CCDSi CCDS7902.1. [P15918-1 ]
PIRi A33754.
RefSeqi NP_000439.1. NM_000448.2.
XP_005253098.1. XM_005253041.2. [P15918-1 ]
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. 13 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. [P15918-1 ]

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.
GeneTreei ENSGT00390000008679.
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

Bgeei P15918.
CleanExi HS_RAG1.
ExpressionAtlasi P15918. baseline and differential.
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

« Hide 'large scale' publications
  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: November 26, 2014
This is version 168 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