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Protein

V(D)J recombination-activating protein 1

Gene

Rag1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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 KPNA1.14 Publications

Catalytic activityi

S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N6-ubiquitinyl-[acceptor protein]-L-lysine.

Cofactori

Mg2+1 Publication, Mn2+1 PublicationNote: Binds 1 divalent metal cation per subunit. Mg2+ or Mn2+.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi266Zinc 11 Publication1
Metal bindingi270Zinc 11 Publication1
Metal bindingi290Zinc 21 Publication1
Metal bindingi293Zinc 11 Publication1
Metal bindingi293Zinc 21 Publication1
Metal bindingi295Zinc 11 Publication1
Metal bindingi305Zinc 31 Publication1
Metal bindingi307Zinc 31 Publication1
Metal bindingi310Zinc 21 Publication1
Metal bindingi313Zinc 21 Publication1
Metal bindingi325Zinc 31 Publication1
Metal bindingi328Zinc 31 Publication1
Metal bindingi355Zinc 41 Publication1
Metal bindingi360Zinc 41 Publication1
Metal bindingi372Zinc 41 Publication1
Metal bindingi376Zinc 41 Publication1
Metal bindingi600Divalent metal cation; catalyticCurated1
Metal bindingi708Divalent metal cation; catalyticCurated1
Sitei893Essential for DNA hairpin formation, participates in base-stacking interactions near the cleavage site1
Metal bindingi962Divalent metal cation; catalyticCurated1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri290 – 329RING-typePROSITE-ProRule annotationAdd BLAST40
Zinc fingeri351 – 380RAG1-typePROSITE-ProRule annotationAdd BLAST30
DNA bindingi389 – 456NBDPROSITE-ProRule annotationAdd BLAST68

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionChromatin regulator, DNA-binding, Endonuclease, Hydrolase, Multifunctional enzyme, Nuclease, Transferase
Biological processDNA recombination, Ubl conjugation pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

BRENDAi6.3.2.19 3474

Names & Taxonomyi

Protein namesi
Recommended name:
V(D)J recombination-activating protein 1
Short name:
RAG-1
Including the following 2 domains:
Endonuclease RAG1 (EC:3.1.-.-)
E3 ubiquitin-protein ligase RAG1 (EC:2.3.2.27)
Alternative name(s):
RING-type E3 ubiquitin transferase RAG1Curated
Gene namesi
Name:Rag1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:97848 Rag1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Disruption phenotypei

Mice display a severe combined immunodeficiency phenotype. The have a small lymphoid organs that do not contain mature B and T-lymphocytes. The arrest of B- and T-cell differentiation occurs at an early stage and correlates with the inability to perform V(D)J recombination. The frequency of homologous immunoglobulin pairing is much lower. No obvious neuroanatomical or behavioral abnormalities have been observed.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi233K → M: Abolishes autoubiquitination. 1 Publication1
Mutagenesisi307H → A: Displays lower E3 ligase activity and affects the joining step of V(D)J recombination. 1 Publication1
Mutagenesisi325C → G: Loss of E3 ligase activity and affects the joining step of V(D)J recombination. 2 Publications1
Mutagenesisi391R → A: Defects in converting nicked products to hairpins. 1 Publication1
Mutagenesisi391R → L: Impairs DNA-binding and hairpin formation while maintaining some nicking activity. 1 Publication1
Mutagenesisi393R → A: Impairs DNA-binding and hairpin formation while maintaining some nicking activity. 1 Publication1
Mutagenesisi401R → A: Allows robust hairpin activity. 1 Publication1
Mutagenesisi402R → A: Defects in converting nicked products to hairpins. 1 Publication1
Mutagenesisi405K → A: Reduced hairpin activity. 1 Publication1
Mutagenesisi406H → A: Allows robust hairpin activity. 1 Publication1
Mutagenesisi407R → A: Impairs DNA-binding and reduces hairpin formation without affecting nicking activity. 1 Publication1
Mutagenesisi443N → A: Impairs DNA-binding; when associated with A-445. 1 Publication1
Mutagenesisi445H → A: Impairs DNA-binding; when associated with A-443. 1 Publication1
Mutagenesisi546D → A: Loss of DNA-binding. 1
Mutagenesisi560D → A: Loss of DNA-binding. 1
Mutagenesisi597E → Q: Impaired cleavage. 1 Publication1
Mutagenesisi600D → A: Loss of cleavage and strand transfer activities. 3 Publications1
Mutagenesisi600D → N: Loss of cleavage (both nicking and hairpin formation). 3 Publications1
Mutagenesisi707Y → A: Deficient in both nicking and hairpin formation. 1 Publication1
Mutagenesisi708D → A: Loss of cleavage and strand transfer activities without affecting allelic exclusion. 4 Publications1
Mutagenesisi708D → N: Loss of cleavage (both nicking and hairpin formation). 4 Publications1
Mutagenesisi709E → A: Impaired cleavage (defective in hairpin formation). 1 Publication1
Mutagenesisi709E → Q: Impaired cleavage. 1 Publication1
Mutagenesisi713R → A or C: Impaired cleavage (both nicking and hairpin formation). 1
Mutagenesisi719E → Q: Impaired cleavage. 1 Publication1
Mutagenesisi725Y → A: Deficient in both nicking and hairpin formation. 1 Publication1
Mutagenesisi760W → A: Deficient in both nicking and hairpin formation. 1 Publication1
Mutagenesisi792D → N: Impaired cleavage. 1 Publication1
Mutagenesisi811E → A: Impaired cleavage. 1 Publication1
Mutagenesisi811E → Q: Loss of DNA-binding. 1 Publication1
Mutagenesisi893W → A: Capable of nicking but defective for hairpinning. 1 Publication1
Mutagenesisi893W → F: Capable of nicking and retains some hairpinning. 1 Publication1
Mutagenesisi935Y → A, L or F: Capable of nicking but defective for hairpinning. 1 Publication1
Mutagenesisi935Y → S or T: Capable of both nicking and hairpinning. 1 Publication1
Mutagenesisi938K → A: Capable of nicking but defective for hairpinning. 1
Mutagenesisi956W → A: Deficient in both nicking and hairpin formation. 1 Publication1
Mutagenesisi959E → Q: Impaired cleavage. 1 Publication1
Mutagenesisi962E → A or Q: Loss of cleavage (both nicking and hairpin formation). 3 Publications1
Mutagenesisi971F → A or W: Capable of nicking but defective for hairpinning. 1 Publication1
Mutagenesisi972R → A: Capable of nicking but defective for hairpinning. 1 Publication1
Mutagenesisi973K → A: Moderately defective with 56% of activity. 1 Publication1
Mutagenesisi986D → N: Impaired cleavage. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000560051 – 1040V(D)J recombination-activating protein 1Add BLAST1040

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki233Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication

Post-translational modificationi

Autoubiquitinated in the presence of CDC34/UBCH3.2 Publications

Keywords - PTMi

Isopeptide bond, Ubl conjugation

Proteomic databases

MaxQBiP15919
PaxDbiP15919
PRIDEiP15919

PTM databases

iPTMnetiP15919
PhosphoSitePlusiP15919

Expressioni

Tissue specificityi

Maturing lymphoid cells and central nervous system.

Gene expression databases

BgeeiENSMUSG00000061311 Expressed in 41 organ(s), highest expression level in thymus
CleanExiMM_RAG1
GenevisibleiP15919 MM

Interactioni

Subunit structurei

Homodimer. Component of the RAG complex composed of core components RAG1 and RAG2, and associated component HMGB1 or HMGB2. Interacts with DCAF1, leading to recruitment of the CUL4A-RBX1-DDB1-DCAF1/VPRBP complex to ubiquitinate proteins and limit error-prone repair during V(D)J recombination.6 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi202574, 12 interactors
CORUMiP15919
DIPiDIP-48518N
IntActiP15919, 5 interactors
MINTiP15919
STRINGi10090.ENSMUSP00000077584

Structurei

Secondary structure

11040
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP15919
SMRiP15919
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP15919

Family & Domainsi

Domaini

The RING-type zinc finger mediates the E3 ubiquitin-protein ligase activity.1 Publication
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 annotation1 Publication

Sequence similaritiesi

Belongs to the RAG1 family.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri290 – 329RING-typePROSITE-ProRule annotationAdd BLAST40
Zinc fingeri351 – 380RAG1-typePROSITE-ProRule annotationAdd BLAST30

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiENOG410IKNG Eukaryota
ENOG4110KH0 LUCA
GeneTreeiENSGT00390000008679
HOGENOMiHOG000232009
HOVERGENiHBG003861
InParanoidiP15919
KOiK10628
OMAiGYHPFEW
OrthoDBiEOG091G00XO
TreeFamiTF331926

Family and domain databases

Gene3Di3.30.40.10, 1 hit
InterProiView protein in InterPro
IPR024627 RAG1
IPR035714 RAG1_imp-bd
IPR019485 RAG1_Znf
IPR023336 RAG_nonamer-bd_dom
IPR036236 Znf_C2H2_sf
IPR018957 Znf_C3HC4_RING-type
IPR001841 Znf_RING
IPR013083 Znf_RING/FYVE/PHD
IPR017907 Znf_RING_CS
PANTHERiPTHR11539 PTHR11539, 1 hit
PfamiView protein in Pfam
PF12940 RAG1, 1 hit
PF12560 RAG1_imp_bd, 1 hit
PF00097 zf-C3HC4, 1 hit
PF10426 zf-RAG1, 1 hit
SMARTiView protein in SMART
SM00184 RING, 1 hit
SUPFAMiSSF57667 SSF57667, 1 hit
PROSITEiView protein in PROSITE
PS51487 NBD, 1 hit
PS51765 ZF_RAG1, 1 hit
PS00518 ZF_RING_1, 1 hit
PS50089 ZF_RING_2, 1 hit

Sequencei

Sequence statusi: Complete.

P15919-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MAASLPSTLS FSSAPDEIQH PQIKFSEWKF KLFRVRSFEK APEEAQKEKD
60 70 80 90 100
SSEGKPYLEQ SPVVPEKPGG QNSILTQRAL KLHPKFSKKF HADGKSSDKA
110 120 130 140 150
VHQARLRHFC RICGNRFKSD GHSRRYPVHG PVDAKTQSLF RKKEKRVTSW
160 170 180 190 200
PDLIARIFRI DVKADVDSIH PTEFCHDCWS IMHRKFSSSH SQVYFPRKVT
210 220 230 240 250
VEWHPHTPSC DICFTAHRGL KRKRHQPNVQ LSKKLKTVLN HARRDRRKRT
260 270 280 290 300
QARVSSKEVL KKISNCSKIH LSTKLLAVDF PAHFVKSISC QICEHILADP
310 320 330 340 350
VETSCKHLFC RICILRCLKV MGSYCPSCRY PCFPTDLESP VKSFLNILNS
360 370 380 390 400
LMVKCPAQDC NEEVSLEKYN HHVSSHKESK ETLVHINKGG RPRQHLLSLT
410 420 430 440 450
RRAQKHRLRE LKIQVKEFAD KEEGGDVKAV CLTLFLLALR ARNEHRQADE
460 470 480 490 500
LEAIMQGRGS GLQPAVCLAI RVNTFLSCSQ YHKMYRTVKA ITGRQIFQPL
510 520 530 540 550
HALRNAEKVL LPGYHPFEWQ PPLKNVSSRT DVGIIDGLSG LASSVDEYPV
560 570 580 590 600
DTIAKRFRYD SALVSALMDM EEDILEGMRS QDLDDYLNGP FTVVVKESCD
610 620 630 640 650
GMGDVSEKHG SGPAVPEKAV RFSFTVMRIT IEHGSQNVKV FEEPKPNSEL
660 670 680 690 700
CCKPLCLMLA DESDHETLTA ILSPLIAERE AMKSSELTLE MGGIPRTFKF
710 720 730 740 750
IFRGTGYDEK LVREVEGLEA SGSVYICTLC DTTRLEASQN LVFHSITRSH
760 770 780 790 800
AENLQRYEVW RSNPYHESVE ELRDRVKGVS AKPFIETVPS IDALHCDIGN
810 820 830 840 850
AAEFYKIFQL EIGEVYKHPN ASKEERKRWQ ATLDKHLRKR MNLKPIMRMN
860 870 880 890 900
GNFARKLMTQ ETVDAVCELI PSEERHEALR ELMDLYLKMK PVWRSSCPAK
910 920 930 940 950
ECPESLCQYS FNSQRFAELL STKFKYRYEG KITNYFHKTL AHVPEIIERD
960 970 980 990 1000
GSIGAWASEG NESGNKLFRR FRKMNARQSK CYEMEDVLKH HWLYTSKYLQ
1010 1020 1030 1040
KFMNAHNALK SSGFTMNSKE TLGDPLGIED SLESQDSMEF
Length:1,040
Mass (Da):119,185
Last modified:July 27, 2011 - v2
Checksum:i7C2E6AD68DCBA081
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti609H → L in AAA40028 (PubMed:2598259).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M29475 mRNA Translation: AAA40028.1
AL929569 Genomic DNA Translation: CAM20888.1
CH466519 Genomic DNA Translation: EDL27655.1
BC138342 mRNA Translation: AAI38343.1
CCDSiCCDS16463.1
PIRiB33754
RefSeqiNP_033045.2, NM_009019.2
XP_006499075.1, XM_006499012.1
UniGeneiMm.828

Genome annotation databases

EnsembliENSMUST00000078494; ENSMUSP00000077584; ENSMUSG00000061311
GeneIDi19373
KEGGimmu:19373
UCSCiuc008lhk.2 mouse

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M29475 mRNA Translation: AAA40028.1
AL929569 Genomic DNA Translation: CAM20888.1
CH466519 Genomic DNA Translation: EDL27655.1
BC138342 mRNA Translation: AAI38343.1
CCDSiCCDS16463.1
PIRiB33754
RefSeqiNP_033045.2, NM_009019.2
XP_006499075.1, XM_006499012.1
UniGeneiMm.828

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1RMDX-ray2.10A265-380[»]
3GNAX-ray2.40A389-464[»]
3GNBX-ray3.00A389-464[»]
4WWXX-ray3.20B/E392-1008[»]
5ZDZX-ray2.80A/C384-1008[»]
5ZE0X-ray2.75A/C384-1008[»]
5ZE1X-ray3.00A/C384-1008[»]
5ZE2X-ray3.30A/C384-1008[»]
6CG0electron microscopy3.17A/C265-1039[»]
6CIJelectron microscopy3.90A/C265-1040[»]
6CIKX-ray3.15A/C384-1008[»]
6CILX-ray4.15A/C384-1008[»]
6CIMX-ray3.60A/C384-1008[»]
ProteinModelPortaliP15919
SMRiP15919
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi202574, 12 interactors
CORUMiP15919
DIPiDIP-48518N
IntActiP15919, 5 interactors
MINTiP15919
STRINGi10090.ENSMUSP00000077584

PTM databases

iPTMnetiP15919
PhosphoSitePlusiP15919

Proteomic databases

MaxQBiP15919
PaxDbiP15919
PRIDEiP15919

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000078494; ENSMUSP00000077584; ENSMUSG00000061311
GeneIDi19373
KEGGimmu:19373
UCSCiuc008lhk.2 mouse

Organism-specific databases

CTDi5896
MGIiMGI:97848 Rag1

Phylogenomic databases

eggNOGiENOG410IKNG Eukaryota
ENOG4110KH0 LUCA
GeneTreeiENSGT00390000008679
HOGENOMiHOG000232009
HOVERGENiHBG003861
InParanoidiP15919
KOiK10628
OMAiGYHPFEW
OrthoDBiEOG091G00XO
TreeFamiTF331926

Enzyme and pathway databases

BRENDAi6.3.2.19 3474

Miscellaneous databases

EvolutionaryTraceiP15919
PROiPR:P15919
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000061311 Expressed in 41 organ(s), highest expression level in thymus
CleanExiMM_RAG1
GenevisibleiP15919 MM

Family and domain databases

Gene3Di3.30.40.10, 1 hit
InterProiView protein in InterPro
IPR024627 RAG1
IPR035714 RAG1_imp-bd
IPR019485 RAG1_Znf
IPR023336 RAG_nonamer-bd_dom
IPR036236 Znf_C2H2_sf
IPR018957 Znf_C3HC4_RING-type
IPR001841 Znf_RING
IPR013083 Znf_RING/FYVE/PHD
IPR017907 Znf_RING_CS
PANTHERiPTHR11539 PTHR11539, 1 hit
PfamiView protein in Pfam
PF12940 RAG1, 1 hit
PF12560 RAG1_imp_bd, 1 hit
PF00097 zf-C3HC4, 1 hit
PF10426 zf-RAG1, 1 hit
SMARTiView protein in SMART
SM00184 RING, 1 hit
SUPFAMiSSF57667 SSF57667, 1 hit
PROSITEiView protein in PROSITE
PS51487 NBD, 1 hit
PS51765 ZF_RAG1, 1 hit
PS00518 ZF_RING_1, 1 hit
PS50089 ZF_RING_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiRAG1_MOUSE
AccessioniPrimary (citable) accession number: P15919
Secondary accession number(s): A2AVN8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: July 27, 2011
Last modified: November 7, 2018
This is version 176 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

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

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