UniProtKB - P55895 (RAG2_HUMAN)
V(D)J recombination-activating protein 2
RAG2
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 (By similarity).
By similaritySites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 419 | Zinc 1By similarity | 1 | |
Metal bindingi | 423 | Zinc 1By similarity | 1 | |
Metal bindingi | 446 | Zinc 2By similarity | 1 | |
Metal bindingi | 452 | Zinc 2By similarity | 1 | |
Metal bindingi | 455 | Zinc 1By similarity | 1 | |
Metal bindingi | 458 | Zinc 1By similarity | 1 | |
Metal bindingi | 478 | Zinc 2By similarity | 1 | |
Metal bindingi | 481 | Zinc 2By similarity | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 416 – 484 | PHD-type; atypicalAdd BLAST | 69 |
GO - Molecular functioni
- chromatin binding Source: UniProtKB
- 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
- sequence-specific DNA binding Source: GO_Central
- ubiquitin protein ligase activity Source: Ensembl
- zinc ion binding Source: UniProtKB
GO - Biological processi
- B cell differentiation Source: UniProtKB
- B cell homeostatic proliferation Source: Ensembl
- B cell lineage commitment Source: Ensembl
- chromatin organization Source: UniProtKB-KW
- defense response to bacterium Source: Ensembl
- mature B cell differentiation involved in immune response Source: Ensembl
- negative regulation of T cell differentiation in thymus Source: Ensembl
- positive regulation of organ growth Source: Ensembl
- pre-B cell allelic exclusion Source: UniProtKB
- T cell differentiation in thymus Source: UniProtKB
- T cell lineage commitment Source: Ensembl
- V(D)J recombination Source: UniProtKB
Keywordsi
Molecular function | Chromatin regulator |
Biological process | DNA recombination |
Ligand | Metal-binding, Zinc |
Enzyme and pathway databases
PathwayCommonsi | P55895 |
Reactomei | R-HSA-1266695, Interleukin-7 signaling R-HSA-5687128, MAPK6/MAPK4 signaling |
SignaLinki | P55895 |
SIGNORi | P55895 |
Names & Taxonomyi
Protein namesi | Recommended name: V(D)J recombination-activating protein 2Short name: RAG-2 |
Gene namesi | Name:RAG2 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:9832, RAG2 |
MIMi | 179616, gene |
neXtProti | NX_P55895 |
VEuPathDBi | HostDB:ENSG00000175097 |
Subcellular locationi
Nucleus
- Nucleus By similarity
Nucleus
- nucleoplasm Source: Reactome
Other locations
- DNA recombinase complex Source: GO_Central
Keywords - Cellular componenti
NucleusPathology & Biotechi
Involvement in diseasei
Combined cellular and humoral immune defects with granulomas (CHIDG)1 Publication
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_045960 | 77 | T → N in CHIDG; reduced recombination activity. 1 PublicationCorresponds to variant dbSNP:rs121918574EnsemblClinVar. | 1 | |
Natural variantiVAR_045962 | 451 | G → A in CHIDG; reduced recombination activity. 1 PublicationCorresponds to variant dbSNP:rs121918575EnsemblClinVar. | 1 |
Severe combined immunodeficiency autosomal recessive T-cell-negative/B-cell-negative/NK-cell-positive (T(-)B(-)NK(+) SCID)1 Publication
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_005570 | 229 | R → Q in T(-)B(-)NK(+) SCID. 1 PublicationCorresponds to variant dbSNP:rs121917894EnsemblClinVar. | 1 | |
Natural variantiVAR_005571 | 478 | C → Y in T(-)B(-)NK(+) SCID. 1 PublicationCorresponds to variant dbSNP:rs121918573EnsemblClinVar. | 1 |
Omenn syndrome (OS)1 Publication
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_008895 | 41 | C → W in OS. 1 PublicationCorresponds to variant dbSNP:rs121917895EnsemblClinVar. | 1 | |
Natural variantiVAR_008896 | 285 | M → R in OS. 1 PublicationCorresponds to variant dbSNP:rs121917896EnsemblClinVar. | 1 |
Keywords - Diseasei
Disease variant, SCIDOrganism-specific databases
DisGeNETi | 5897 |
MalaCardsi | RAG2 |
MIMi | 233650, phenotype 601457, phenotype 603554, phenotype |
OpenTargetsi | ENSG00000175097 |
Orphaneti | 157949, Combined immunodeficiency with granulomatosis 39041, Omenn syndrome 331206, Severe combined immunodeficiency due to complete RAG1/2 deficiency |
PharmGKBi | PA34186 |
Miscellaneous databases
Pharosi | P55895, Tbio |
Genetic variation databases
BioMutai | RAG2 |
DMDMi | 2498830 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000167137 | 1 – 527 | V(D)J recombination-activating protein 2Add BLAST | 527 |
Proteomic databases
jPOSTi | P55895 |
PaxDbi | P55895 |
PRIDEi | P55895 |
PTM databases
iPTMneti | P55895 |
PhosphoSitePlusi | P55895 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000175097, Expressed in bone marrow and 101 other tissues |
ExpressionAtlasi | P55895, baseline and differential |
Genevisiblei | P55895, HS |
Organism-specific databases
HPAi | ENSG00000175097, Tissue enriched (lymphoid) |
Interactioni
Subunit structurei
Component of the RAG complex composed of core components RAG1 and RAG2, and associated component HMGB1 or HMGB2.
By similarityGO - Molecular functioni
- methylated histone binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 111833, 7 interactors |
CORUMi | P55895 |
STRINGi | 9606.ENSP00000478672 |
Miscellaneous databases
RNActi | P55895, protein |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 357 – 380 | DisorderedSequence analysisAdd BLAST | 24 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 357 – 374 | Polar residuesSequence analysisAdd BLAST | 18 |
Domaini
Sequence similaritiesi
Zinc finger
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 416 – 484 | PHD-type; atypicalAdd BLAST | 69 |
Keywords - Domaini
Zinc-fingerPhylogenomic databases
eggNOGi | ENOG502QVKU, Eukaryota |
GeneTreei | ENSGT00390000012559 |
HOGENOMi | CLU_516740_0_0_1 |
InParanoidi | P55895 |
OMAi | WNSVVDC |
OrthoDBi | 687724at2759 |
PhylomeDBi | P55895 |
TreeFami | TF331236 |
Family and domain databases
CDDi | cd15569, PHD_RAG2, 1 hit |
Gene3Di | 2.120.10.80, 1 hit |
InterProi | View protein in InterPro IPR011043, Gal_Oxase/kelch_b-propeller IPR015915, Kelch-typ_b-propeller IPR004321, RAG2 IPR025162, RAG2_PHD IPR011011, Znf_FYVE_PHD |
PANTHERi | PTHR10960, PTHR10960, 1 hit |
Pfami | View protein in Pfam PF03089, RAG2, 1 hit PF13341, RAG2_PHD, 1 hit |
SUPFAMi | SSF50965, SSF50965, 1 hit SSF57903, SSF57903, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All
10 20 30 40 50
MSLQMVTVSN NIALIQPGFS LMNFDGQVFF FGQKGWPKRS CPTGVFHLDV
60 70 80 90 100
KHNHVKLKPT IFSKDSCYLP PLRYPATCTF KGSLESEKHQ YIIHGGKTPN
110 120 130 140 150
NEVSDKIYVM SIVCKNNKKV TFRCTEKDLV GDVPEARYGH SINVVYSRGK
160 170 180 190 200
SMGVLFGGRS YMPSTHRTTE KWNSVADCLP CVFLVDFEFG CATSYILPEL
210 220 230 240 250
QDGLSFHVSI AKNDTIYILG GHSLANNIRP ANLYRIRVDL PLGSPAVNCT
260 270 280 290 300
VLPGGISVSS AILTQTNNDE FVIVGGYQLE NQKRMICNII SLEDNKIEIR
310 320 330 340 350
EMETPDWTPD IKHSKIWFGS NMGNGTVFLG IPGDNKQVVS EGFYFYMLKC
360 370 380 390 400
AEDDTNEEQT TFTNSQTSTE DPGDSTPFED SEEFCFSAEA NSFDGDDEFD
410 420 430 440 450
TYNEDDEEDE SETGYWITCC PTCDVDINTW VPFYSTELNK PAMIYCSHGD
460 470 480 490 500
GHWVHAQCMD LAERTLIHLS AGSNKYYCNE HVEIARALHT PQRVLPLKKP
510 520
PMKSLRKKGS GKILTPAKKS FLRRLFD
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketE9PPU5 | E9PPU5_HUMAN | V(D)J recombination-activating prot... | RAG2 | 150 | Annotation score: | ||
E9PQB9 | E9PQB9_HUMAN | V(D)J recombination-activating prot... | RAG2 | 70 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 154 | V → A in AAH22397 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 322 | M → T in AAH22397 (PubMed:15489334).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_008895 | 41 | C → W in OS. 1 PublicationCorresponds to variant dbSNP:rs121917895EnsemblClinVar. | 1 | |
Natural variantiVAR_045960 | 77 | T → N in CHIDG; reduced recombination activity. 1 PublicationCorresponds to variant dbSNP:rs121918574EnsemblClinVar. | 1 | |
Natural variantiVAR_005570 | 229 | R → Q in T(-)B(-)NK(+) SCID. 1 PublicationCorresponds to variant dbSNP:rs121917894EnsemblClinVar. | 1 | |
Natural variantiVAR_008896 | 285 | M → R in OS. 1 PublicationCorresponds to variant dbSNP:rs121917896EnsemblClinVar. | 1 | |
Natural variantiVAR_045961 | 293 | E → G. Corresponds to variant dbSNP:rs16929093EnsemblClinVar. | 1 | |
Natural variantiVAR_045962 | 451 | G → A in CHIDG; reduced recombination activity. 1 PublicationCorresponds to variant dbSNP:rs121918575EnsemblClinVar. | 1 | |
Natural variantiVAR_005571 | 478 | C → Y in T(-)B(-)NK(+) SCID. 1 PublicationCorresponds to variant dbSNP:rs121918573EnsemblClinVar. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M94633 Genomic DNA No translation available. AK292664 mRNA Translation: BAF85353.1 CH471064 Genomic DNA Translation: EAW68117.1 BC022397 mRNA Translation: AAH22397.1 |
CCDSi | CCDS7903.1 |
RefSeqi | NP_000527.2, NM_000536.3 NP_001230714.1, NM_001243785.1 NP_001230715.1, NM_001243786.1 |
Genome annotation databases
Ensembli | ENST00000311485; ENSP00000308620; ENSG00000175097 ENST00000618712; ENSP00000478672; ENSG00000175097 |
GeneIDi | 5897 |
KEGGi | hsa:5897 |
MANE-Selecti | ENST00000311485.8; ENSP00000308620.4; NM_000536.4; NP_000527.2 |
UCSCi | uc001mwv.5, human |
Similar proteinsi
Cross-referencesi
Web resourcesi
RAG2base RAG2 deficiency database |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M94633 Genomic DNA No translation available. AK292664 mRNA Translation: BAF85353.1 CH471064 Genomic DNA Translation: EAW68117.1 BC022397 mRNA Translation: AAH22397.1 |
CCDSi | CCDS7903.1 |
RefSeqi | NP_000527.2, NM_000536.3 NP_001230714.1, NM_001243785.1 NP_001230715.1, NM_001243786.1 |
3D structure databases
SMRi | P55895 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 111833, 7 interactors |
CORUMi | P55895 |
STRINGi | 9606.ENSP00000478672 |
PTM databases
iPTMneti | P55895 |
PhosphoSitePlusi | P55895 |
Genetic variation databases
BioMutai | RAG2 |
DMDMi | 2498830 |
Proteomic databases
jPOSTi | P55895 |
PaxDbi | P55895 |
PRIDEi | P55895 |
Protocols and materials databases
Antibodypediai | 26023, 274 antibodies from 33 providers |
DNASUi | 5897 |
Genome annotation databases
Ensembli | ENST00000311485; ENSP00000308620; ENSG00000175097 ENST00000618712; ENSP00000478672; ENSG00000175097 |
GeneIDi | 5897 |
KEGGi | hsa:5897 |
MANE-Selecti | ENST00000311485.8; ENSP00000308620.4; NM_000536.4; NP_000527.2 |
UCSCi | uc001mwv.5, human |
Organism-specific databases
CTDi | 5897 |
DisGeNETi | 5897 |
GeneCardsi | RAG2 |
HGNCi | HGNC:9832, RAG2 |
HPAi | ENSG00000175097, Tissue enriched (lymphoid) |
MalaCardsi | RAG2 |
MIMi | 179616, gene 233650, phenotype 601457, phenotype 603554, phenotype |
neXtProti | NX_P55895 |
OpenTargetsi | ENSG00000175097 |
Orphaneti | 157949, Combined immunodeficiency with granulomatosis 39041, Omenn syndrome 331206, Severe combined immunodeficiency due to complete RAG1/2 deficiency |
PharmGKBi | PA34186 |
VEuPathDBi | HostDB:ENSG00000175097 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502QVKU, Eukaryota |
GeneTreei | ENSGT00390000012559 |
HOGENOMi | CLU_516740_0_0_1 |
InParanoidi | P55895 |
OMAi | WNSVVDC |
OrthoDBi | 687724at2759 |
PhylomeDBi | P55895 |
TreeFami | TF331236 |
Enzyme and pathway databases
PathwayCommonsi | P55895 |
Reactomei | R-HSA-1266695, Interleukin-7 signaling R-HSA-5687128, MAPK6/MAPK4 signaling |
SignaLinki | P55895 |
SIGNORi | P55895 |
Miscellaneous databases
BioGRID-ORCSi | 5897, 6 hits in 1042 CRISPR screens |
ChiTaRSi | RAG2, human |
GenomeRNAii | 5897 |
Pharosi | P55895, Tbio |
PROi | PR:P55895 |
RNActi | P55895, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000175097, Expressed in bone marrow and 101 other tissues |
ExpressionAtlasi | P55895, baseline and differential |
Genevisiblei | P55895, HS |
Family and domain databases
CDDi | cd15569, PHD_RAG2, 1 hit |
Gene3Di | 2.120.10.80, 1 hit |
InterProi | View protein in InterPro IPR011043, Gal_Oxase/kelch_b-propeller IPR015915, Kelch-typ_b-propeller IPR004321, RAG2 IPR025162, RAG2_PHD IPR011011, Znf_FYVE_PHD |
PANTHERi | PTHR10960, PTHR10960, 1 hit |
Pfami | View protein in Pfam PF03089, RAG2, 1 hit PF13341, RAG2_PHD, 1 hit |
SUPFAMi | SSF50965, SSF50965, 1 hit SSF57903, SSF57903, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | RAG2_HUMAN | |
Accessioni | P55895Primary (citable) accession number: P55895 Secondary accession number(s): A8K9E9, Q8TBL4 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 1, 1997 |
Last sequence update: | November 1, 1997 | |
Last modified: | February 23, 2022 | |
This is version 169 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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
Reference proteomeDocuments
- Human chromosome 11
Human chromosome 11: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families