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Protein

V(D)J recombination-activating protein 2

Gene

Rag2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Core component of the RAG complex, a multiprotein complex that mediates the DNA cleavage phase during V(D)J recombination. V(D)J recombination assembles a diverse repertoire of immunoglobulin and T-cell receptor genes in developing B and T-lymphocytes through rearrangement of different V (variable), in some cases D (diversity), and J (joining) gene segments. DNA cleavage by the RAG complex occurs in 2 steps: a first nick is introduced in the top strand immediately upstream of the heptamer, generating a 3'-hydroxyl group that can attack the phosphodiester bond on the opposite strand in a direct transesterification reaction, thereby creating 4 DNA ends: 2 hairpin coding ends and 2 blunt, 5'-phosphorylated ends. The chromatin structure plays an essential role in the V(D)J recombination reactions and the presence of histone H3 trimethylated at 'Lys-4' (H3K4me3) stimulates both the nicking and haipinning steps. The RAG complex also plays a role in pre-B cell allelic exclusion, a process leading to expression of a single immunoglobulin heavy chain allele to enforce clonality and monospecific recognition by the B-cell antigen receptor (BCR) expressed on individual B-lymphocytes. The introduction of DNA breaks by the RAG complex on one immunoglobulin allele induces ATM-dependent repositioning of the other allele to pericentromeric heterochromatin, preventing accessibility to the RAG complex and recombination of the second allele. In the RAG complex, RAG2 is not the catalytic component but is required for all known catalytic activities mediated by RAG1. It probably acts as a sensor of chromatin state that recruits the RAG complex to H3K4me3.6 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi419Zinc 12 Publications1
Metal bindingi423Zinc 12 Publications1
Metal bindingi446Zinc 22 Publications1
Metal bindingi452Zinc 22 Publications1
Metal bindingi455Zinc 12 Publications1
Metal bindingi458Zinc 12 Publications1
Metal bindingi478Zinc 22 Publications1
Metal bindingi481Zinc 22 Publications1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri416 – 484PHD-type; atypicalAdd BLAST69

GO - Molecular functioni

  • chromatin binding Source: UniProtKB
  • DNA binding Source: InterPro
  • methylated histone binding Source: UniProtKB
  • phosphatidylinositol-3,4,5-trisphosphate binding Source: UniProtKB
  • phosphatidylinositol-3,4-bisphosphate binding Source: UniProtKB
  • phosphatidylinositol-3,5-bisphosphate binding Source: UniProtKB
  • phosphatidylinositol-4,5-bisphosphate binding Source: UniProtKB
  • phosphatidylinositol binding Source: UniProtKB
  • ubiquitin protein ligase activity Source: MGI
  • zinc ion binding Source: UniProtKB

GO - Biological processi

  • B cell differentiation Source: UniProtKB
  • B cell homeostatic proliferation Source: MGI
  • B cell lineage commitment Source: MGI
  • chromatin modification Source: UniProtKB-KW
  • DNA recombination Source: MGI
  • positive regulation of organ growth Source: MGI
  • pre-B cell allelic exclusion Source: UniProtKB
  • T cell differentiation Source: MGI
  • T cell differentiation in thymus Source: UniProtKB
  • T cell lineage commitment Source: MGI
  • V(D)J recombination Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Chromatin regulator

Keywords - Biological processi

DNA recombination

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-MMU-1266695. Interleukin-7 signaling.

Names & Taxonomyi

Protein namesi
Recommended name:
V(D)J recombination-activating protein 2
Short name:
RAG-2
Gene namesi
Name:Rag2
Synonyms:Rag-2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:97849. Rag2.

Subcellular locationi

GO - Cellular componenti

  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Disruption phenotypei

Mice are viable but fail to produce mature B or T-lymphocytes. Very immature lymphoid cells are present in primary lymphoid organs. These cells do not rearrange their immunoglobulin or T-cell receptor loci. Double knockout with TREX1 does not show a visible phenotype.2 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi128D → N: Does not affect the endonuclease activity of the RAG complex. 1 Publication1
Mutagenesisi199E → Q: Does not affect the endonuclease activity of the RAG complex. 1 Publication1
Mutagenesisi202D → N: Does not affect the endonuclease activity of the RAG complex. 1 Publication1
Mutagenesisi280E → Q: Does not affect the endonuclease activity of the RAG complex. 1 Publication1
Mutagenesisi310D → N: Does not affect the endonuclease activity of the RAG complex. 1 Publication1
Mutagenesisi358D → N: Does not affect the endonuclease activity of the RAG complex. 1 Publication1
Mutagenesisi374D → N: Does not affect the endonuclease activity of the RAG complex. 1 Publication1
Mutagenesisi402Y → A: Reduced interaction with histones. 1 Publication1
Mutagenesisi403N → A: Reduced interaction with histones. 1 Publication1
Mutagenesisi406D → A: Reduced interaction with histones. 1 Publication1
Mutagenesisi407E → A: Reduced interaction with histones. 1 Publication1
Mutagenesisi408D → A: Induces a slight reduction in V(D)J recombination without affecting interaction with histones. 1
Mutagenesisi415Y → A: Abolishes binding to H3K4me3 without affecting phosphoinositide-binding. 1 Publication1
Mutagenesisi440K → A: Binds PtdIns(4,5)P2 at wild-type level. 1 Publication1
Mutagenesisi443M → A: Abolishes binding to H3K4me3 without affecting phosphoinositide-binding. 1 Publication1
Mutagenesisi445Y → A or D: Still binds H3K4me3 and H3R2me2 but with reduced affinity. 1 Publication1
Mutagenesisi453W → R: Abolishes binding to H3K4me3 without affecting phosphoinositide-binding. Impairs enzymatic activity of the RAG complex. 2 Publications1
Mutagenesisi464R → A: Leads to a strong reduction in PtdIns(4,5)P2-binding. 1 Publication1
Mutagenesisi468H → A: Leads to a strong reduction in PtdIns(4,5)P2-binding. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001671381 – 527V(D)J recombination-activating protein 2Add BLAST527

Proteomic databases

PaxDbiP21784.
PRIDEiP21784.

PTM databases

iPTMnetiP21784.
PhosphoSitePlusiP21784.

Expressioni

Tissue specificityi

Maturing lymphoid cells.

Gene expression databases

BgeeiENSMUSG00000032864.
CleanExiMM_RAG2.
ExpressionAtlasiP21784. baseline and differential.
GenevisibleiP21784. MM.

Interactioni

Subunit structurei

Component of the RAG complex composed of core components RAG1 and RAG2, and associated component HMGB1 or HMGB2.4 Publications

GO - Molecular functioni

  • methylated histone binding Source: UniProtKB

Protein-protein interaction databases

BioGridi202575. 1 interactor.
DIPiDIP-46179N.
IntActiP21784. 3 interactors.
MINTiMINT-8384500.
STRINGi10090.ENSMUSP00000038204.

Structurei

Secondary structure

1527
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi3 – 8Combined sources6
Helixi12 – 14Combined sources3
Beta strandi20 – 24Combined sources5
Beta strandi27 – 31Combined sources5
Beta strandi34 – 36Combined sources3
Beta strandi45 – 51Combined sources7
Beta strandi54 – 59Combined sources6
Beta strandi76 – 80Combined sources5
Beta strandi90 – 94Combined sources5
Beta strandi107 – 115Combined sources9
Beta strandi120 – 127Combined sources8
Beta strandi130 – 132Combined sources3
Beta strandi141 – 145Combined sources5
Beta strandi148 – 150Combined sources3
Beta strandi152 – 156Combined sources5
Beta strandi159 – 161Combined sources3
Turni164 – 166Combined sources3
Helixi169 – 171Combined sources3
Beta strandi175 – 177Combined sources3
Beta strandi182 – 186Combined sources5
Turni187 – 190Combined sources4
Beta strandi191 – 195Combined sources5
Beta strandi208 – 212Combined sources5
Beta strandi215 – 219Combined sources5
Beta strandi224 – 226Combined sources3
Beta strandi233 – 237Combined sources5
Beta strandi249 – 252Combined sources4
Beta strandi262 – 267Combined sources6
Beta strandi270 – 274Combined sources5
Beta strandi277 – 279Combined sources3
Beta strandi288 – 291Combined sources4
Beta strandi298 – 300Combined sources3
Helixi309 – 312Combined sources4
Beta strandi318 – 321Combined sources4
Beta strandi323 – 325Combined sources3
Beta strandi327 – 331Combined sources5
Beta strandi344 – 348Combined sources5
Beta strandi414 – 417Combined sources4
Turni427 – 429Combined sources3
Beta strandi434 – 436Combined sources3
Beta strandi438 – 440Combined sources3
Beta strandi443 – 446Combined sources4
Beta strandi448 – 450Combined sources3
Beta strandi452 – 455Combined sources4
Helixi457 – 459Combined sources3
Helixi463 – 471Combined sources9
Turni479 – 483Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2JWONMR-A414-487[»]
2V83X-ray2.40A/B/C414-487[»]
2V85X-ray2.00A/B414-487[»]
2V86X-ray2.05A/B414-487[»]
2V87X-ray1.80A/B414-487[»]
2V88X-ray2.00A/B414-487[»]
2V89X-ray1.10A/B414-487[»]
4WWXX-ray3.20X/Y2-350[»]
ProteinModelPortaliP21784.
SMRiP21784.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP21784.

Family & Domainsi

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi352 – 410Asp/Glu-rich (acidic)Add BLAST59

Domaini

The atypical PHD-type zinc finger recognizes and binds histone H3 trimethylated on 'Lys-4' (H3K4me3). The presence Tyr-445 instead of a carboxylate in classical PHD-type zinc fingers results in an enhanced binding to H3K4me3 in presence of dimethylated on 'Arg-2' (H3R2me2) rather than inhibited. The atypical PHD-type zinc finger also binds various phosphoinositides, such as phosphatidylinositol 3,4-bisphosphate binding (PtdIns(3,4)P2), phosphatidylinositol 3,5-bisphosphate binding (PtdIns(3,5)P2), phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) and phosphatidylinositol 3,4,5-trisphosphate binding (PtdIns(3,4,5)P3).2 Publications

Sequence similaritiesi

Belongs to the RAG2 family.Curated
Contains 1 PHD-type zinc finger.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri416 – 484PHD-type; atypicalAdd BLAST69

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiENOG410IJ5S. Eukaryota.
ENOG4110081. LUCA.
GeneTreeiENSGT00390000012559.
HOGENOMiHOG000237346.
HOVERGENiHBG006694.
InParanoidiP21784.
KOiK10988.
OMAiFGQKGWP.
OrthoDBiEOG091G052K.
PhylomeDBiP21784.
TreeFamiTF331236.

Family and domain databases

CDDicd15569. PHD_RAG2. 1 hit.
Gene3Di2.120.10.80. 1 hit.
InterProiIPR011043. Gal_Oxase/kelch_b-propeller.
IPR015915. Kelch-typ_b-propeller.
IPR004321. RAG2.
IPR025162. RAG2_PHD.
IPR011011. Znf_FYVE_PHD.
[Graphical view]
PANTHERiPTHR10960. PTHR10960. 1 hit.
PfamiPF03089. RAG2. 1 hit.
PF13341. RAG2_PHD. 1 hit.
[Graphical view]
SUPFAMiSSF50965. SSF50965. 1 hit.
SSF57903. SSF57903. 1 hit.

Sequencei

Sequence statusi: Complete.

P21784-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSLQMVTVGH NIALIQPGFS LMNFDGQVFF FGQKGWPKRS CPTGVFHFDI
60 70 80 90 100
KQNHLKLKPA IFSKDSCYLP PLRYPATCSY KGSIDSDKHQ YIIHGGKTPN
110 120 130 140 150
NELSDKIYIM SVACKNNKKV TFRCTEKDLV GDVPEPRYGH SIDVVYSRGK
160 170 180 190 200
SMGVLFGGRS YMPSTQRTTE KWNSVADCLP HVFLIDFEFG CATSYILPEL
210 220 230 240 250
QDGLSFHVSI ARNDTVYILG GHSLASNIRP ANLYRIRVDL PLGTPAVNCT
260 270 280 290 300
VLPGGISVSS AILTQTNNDE FVIVGGYQLE NQKRMVCSLV SLGDNTIEIS
310 320 330 340 350
EMETPDWTSD IKHSKIWFGS NMGNGTIFLG IPGDNKQAMS EAFYFYTLRC
360 370 380 390 400
SEEDLSEDQK IVSNSQTSTE DPGDSTPFED SEEFCFSAEA TSFDGDDEFD
410 420 430 440 450
TYNEDDEDDE SVTGYWITCC PTCDVDINTW VPFYSTELNK PAMIYCSHGD
460 470 480 490 500
GHWVHAQCMD LEERTLIHLS EGSNKYYCNE HVQIARALQT PKRNPPLQKP
510 520
PMKSLHKKGS GKVLTPAKKS FLRRLFD
Length:527
Mass (Da):59,074
Last modified:July 15, 1998 - v2
Checksum:i51086F95A4A664A7
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M64796 mRNA. Translation: AAB82302.1.
CCDSiCCDS16462.1.
PIRiA34852.
RefSeqiNP_033046.1. NM_009020.3.
XP_017172095.1. XM_017316606.1.
UniGeneiMm.4988.

Genome annotation databases

EnsembliENSMUST00000044031; ENSMUSP00000038204; ENSMUSG00000032864.
ENSMUST00000111227; ENSMUSP00000106858; ENSMUSG00000032864.
GeneIDi19374.
KEGGimmu:19374.
UCSCiuc008lhj.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M64796 mRNA. Translation: AAB82302.1.
CCDSiCCDS16462.1.
PIRiA34852.
RefSeqiNP_033046.1. NM_009020.3.
XP_017172095.1. XM_017316606.1.
UniGeneiMm.4988.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2JWONMR-A414-487[»]
2V83X-ray2.40A/B/C414-487[»]
2V85X-ray2.00A/B414-487[»]
2V86X-ray2.05A/B414-487[»]
2V87X-ray1.80A/B414-487[»]
2V88X-ray2.00A/B414-487[»]
2V89X-ray1.10A/B414-487[»]
4WWXX-ray3.20X/Y2-350[»]
ProteinModelPortaliP21784.
SMRiP21784.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi202575. 1 interactor.
DIPiDIP-46179N.
IntActiP21784. 3 interactors.
MINTiMINT-8384500.
STRINGi10090.ENSMUSP00000038204.

PTM databases

iPTMnetiP21784.
PhosphoSitePlusiP21784.

Proteomic databases

PaxDbiP21784.
PRIDEiP21784.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000044031; ENSMUSP00000038204; ENSMUSG00000032864.
ENSMUST00000111227; ENSMUSP00000106858; ENSMUSG00000032864.
GeneIDi19374.
KEGGimmu:19374.
UCSCiuc008lhj.1. mouse.

Organism-specific databases

CTDi5897.
MGIiMGI:97849. Rag2.

Phylogenomic databases

eggNOGiENOG410IJ5S. Eukaryota.
ENOG4110081. LUCA.
GeneTreeiENSGT00390000012559.
HOGENOMiHOG000237346.
HOVERGENiHBG006694.
InParanoidiP21784.
KOiK10988.
OMAiFGQKGWP.
OrthoDBiEOG091G052K.
PhylomeDBiP21784.
TreeFamiTF331236.

Enzyme and pathway databases

ReactomeiR-MMU-1266695. Interleukin-7 signaling.

Miscellaneous databases

EvolutionaryTraceiP21784.
PROiP21784.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000032864.
CleanExiMM_RAG2.
ExpressionAtlasiP21784. baseline and differential.
GenevisibleiP21784. MM.

Family and domain databases

CDDicd15569. PHD_RAG2. 1 hit.
Gene3Di2.120.10.80. 1 hit.
InterProiIPR011043. Gal_Oxase/kelch_b-propeller.
IPR015915. Kelch-typ_b-propeller.
IPR004321. RAG2.
IPR025162. RAG2_PHD.
IPR011011. Znf_FYVE_PHD.
[Graphical view]
PANTHERiPTHR10960. PTHR10960. 1 hit.
PfamiPF03089. RAG2. 1 hit.
PF13341. RAG2_PHD. 1 hit.
[Graphical view]
SUPFAMiSSF50965. SSF50965. 1 hit.
SSF57903. SSF57903. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiRAG2_MOUSE
AccessioniPrimary (citable) accession number: P21784
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 1, 1991
Last sequence update: July 15, 1998
Last modified: November 2, 2016
This is version 141 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. 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.